Suddenly we heard cannon fire, he wrote. Moments later shells were landing in the street outside our quarters. More shells and the windows were blown into our room. Grabbing our medical pouches, we headed down the stairway at the end of the hall.

Amid the confusion, my father was ordered in one direction and his two roommates were sent elsewhere. One of them Staff Sergeant John Winter, his best friend in the Army was killed, as was their company commander. They were among tens of thousands of Allied casualties during the last big Nazi offensive of World War II, which became known as the Battle of the Bulge.

Before that attack on Dec. 16, 1944, our own unit had been dormant for weeks, my father wrote. A degree of complacency existed amongst us.

In the days afterward, we were literally in panic. Convoys moved in all directions. Equipment and personal belongings were left behind. We moved from one town to the next, further and further backward ... back and forth. Sometimes returning again to the same town and a new location every few hours.

My father was a sergeant in the Army Medical Corps, and as he and others in his unit raced from town to town, somewhere we had a dead German soldier on our hands. Perhaps he died after we picked him up. I dont remember. We buried him in a shallow ditch in case we were captured and still had him in the ambulance.

For a day or two, he was assigned to a hospital in Huy, Belgium: My job, give injections of penicillin. So many casualties, by the time I finished one round, it was time to start again.

Those memories, rekindled decades later, found their way into the book he wrote a memoir that could easily have never existed.

Born in 1921, Donald S. Marquard was a prolific recorder of lifes events, large and small. He began writing diaries at age 9 and kept them on and off until several days before dying of a brain tumor, at 76.

He also was a lifelong dedicated letter writer, and while in the Army in basic training and Europe he sent hundreds home to family and friends.

In the mid-1970s, after his father had died and his mother was in a nursing home, he was cleaning out his boyhood home in a Connecticut town along Long Island Sound. In one box, he was surprised to find some 400 of his wartime letters that his mother had saved.

Taking them to our familys home in Vermont, he let a decade pass before opening the envelopes one day to find that some letters were beginning to fade.

To preserve the text, he copied them all out in longhand. In his memoirs prologue, he said he probably wouldnt have summoned the courage to start had he realized the task before me.

During those hand-cramping months, he found that re-reading what he wrote long ago revived long-forgotten memories he had never mentioned in letters that were subject to Army censors.

In his late 60s, having retired and joined a writers group, he began to fill in the gaps including his memoir passages about the early days of the Battle of the Bulge.

By contrast, he had been far more circumspect on Dec. 20, 1944, in his first letter home after the battle had begun.

Dear Ma, he wrote under his handwritten dateline Somewhere in Belgium, a purposefully vague location he listed in every letter, always in quotes.

Everything is going alright, he told his mother, and Im well but have been rather busy the last few days so that explains why I havent written.

Busy not getting killed, to be precise.

Offering reassurances was a common theme in the letters home after his unit left England the night of June 12, 1944, and headed across the English Channel during the invasion of Normandy.

In his first letter to his mother after landing on the Sugar Red section of Utah Beach early on June 13, he noted that he was now writing from Somewhere in France.

Am doing alright and feeling fine, he wrote. At last I feel that Im really helping out in my small way.

That last phrase, in my small way, provided the title for his memoir.

History books often celebrate the exploits of generals and heroes, but wars are largely won or lost by those whose days and nights are rarely recorded. My father wrote about the ordinary experiences of ordinary troops.

In the military, you wait in line a lot. He wrote about boredom, too.

Believe today is Sunday if Im not mistaken, he wrote home in late June 1944. Its rather easy to get mixed up on the dates and days now for one day is just like another.

Like soldiers throughout history, he traipsed through countries he had never expected to visit, complaining about rain and welcoming sunny days. The weather was a safe topic for letters reviewed by censors, but he summoned more pointed images in his memoir.

With much debris everywhere, it was sometimes difficult to drive through with a vehicle, he wrote of his time in France. Dead farm animals, bloated to enormous size by the heat and sun, lay in the fields and farm yards. Yet among all this, people survived and were attempting to put their lives back in order.

As he and other soldiers pushed on through Normandy, a German reconnaissance plane would fly over our area. Bed Check Charlie as we came to call him. Ack, Ack guns would cut loose as the dull thud of the shells bursting echoed high above us. One morning when I awoke, I found a piece of shell lying in my bedroll.

My father probably owes his survival in part to serving in the medical corps. Though not a doctor, he had trained to be a funeral director before the war, studying anatomy and physiology at a junior college. That was enough to earn a medical corps assignment.

He treated all manner of ailments. Some paratroopers who landed in Normandy before the ground troops were emotionally unable to adjust to the demands placed upon them, he wrote, adding that in later years they probably would have been diagnosed with PTSD.

My father also treated Nazi soldiers captured during the invasion. Using rudimentary German language skills, he struggled to communicate.

I still recall a German whom I endeavored to help, he wrote in his memoir. He kept pointing to his ear. I thought he had an injury and shaved a portion of his head. His only problem was that he couldnt understand me!

This year, the 75th anniversary of the action he saw in 1944, Ive been paging through his memoir and letters, reading about his wartime experiences on present times corresponding days.

He had inscribed for me a Xeroxed copy of his memoir as a Christmas present in 1993, less than four years before he died. I was in my 30s then and distracted in the way of children-turned-adults who are busy building careers.

Ill always regret not reading his memoir immediately and asking questions, even ones he might not have answered.

What had it been like for him to know that, at 23, he lived and his best friend died because they went separate ways leaving a stairwell? Did he feel some sense of duty the rest of his life to live up to the quirk of fate that gave him another half-century?

But in one sense, reading what my father wrote about World War II in letters as it unfolded and in memoir looking back when he was older is a way of having the conversation we never had when he was alive.

He speaks to me and others through his writing, excerpts of which I post occasionally on Facebook and Instagram with his wartime photos introducing his first-person accounts to an audience he surely sought by writing a memoir.

On the day the Battle of the Bulge began, my father was a sergeant, and Staff Sergeant Winter was his immediate superior. Since training stateside, they had spent nearly all their days together, including killing time with a 12-hour card game during a train ride through England, rowing on the River Thames while awaiting the Normandy invasion, and rooming together on Winters last night alive.

Yet whenever my father mentioned his friend, in person or on paper, he always called him Sergeant Winter, not John. Military respect never faded.

In the mid-1980s, I was a copy editor at Newsday, on Long Island, N.Y., where the headquarters was across the street from an enormous national cemetery. After the war, my father had visited that very cemetery to join his friends family for the burial, after Sergeant Winters remains were brought home from Europe.

The first time my parents visited me on Long Island, my father asked to visit the cemetery, where after some searching we found his friends grave.

His memoir was not yet written, and he had talked little about the war, so I had no sense of the enormity of the moment. My father was someone who laughed easily and cried never, but on that morning his voice broke as he and I stood by a grave he had last seen decades ago.

My friend Sergeant Winter, he said softly. I miss him.

Bryan Marquard can be reached at bryan.marquard@globe.com.

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Through one soldiers eyes, World War IIs Battle of the Bulge - The Boston Globe

New research highlights the importance of getting out and staying active during the winter months. Susan Chiang/Istock via AFP

LONDON, Dec 13 New UK research has shown that although it might be difficult to get out and about on cold, dark winter days, its important we all try to keep moving to preserve muscle mass and avoid weight gain, particularly for seniors.

Carried out by researchers at the University of Liverpool, the new study looked at 47 participants who were all walking over 10,000 steps per day, but did not do any vigorous exercise.

The participants were split into two groups depending on their age, with 26 subjects in their 20s and 30s placed in the younger group, and 21 subjects in their 50s and 60s places in the older group.

At the start of the study, the researchers carried out tests to assess various physiological measures such as participants lean mass, bone mineral density (BMD), muscle function and strength.

The participants were then asked to reduce their physical activity to just 1,500 steps a day for a period of 14 days, before going back to their usual 10,000 steps a day for another 14 days.

The findings, presented at The Physiological Societys conference Future Physiology 2019, showed that after just two weeks of reduced physical activity, muscle size, muscle strength and bone mass was equally reduced in both the younger and older groups. The two groups also gained a similar amount of fat around their waist and in their muscle tissue, which reduces its quality, leading to significant reductions in muscle strength.

However, as the older adults had less muscle and more fat to begin with, these changes are likely to have a bigger negative effect on this population, compared with younger adults.

Moreover, the researchers found that there were two physiological measures that decreased substantially in the older group but not among the younger participants cardiorespiratory fitness (CRF) and mitochondrial function. CRF is how efficiently oxygen is supplied to muscles during sustained physical activity, with low CRF usually found in those with poor physical health and linked with developing diseases at a younger age, while mitochondrial function, which is the energy production of our cells, is important for muscle and metabolic health. The declines in both CRF and mitochondrial function may also be linked to the loss of muscle mass and strength and the gains in muscle and body fat during the period of physical inactivity.

Researchers Juliette Norman commented on the findings saying, The severe impact of short-term inactivity on our health is hugely important to communicate to people. If the gym is hard to get to, people should be encouraged to just meet 10,000 steps as even this can guard against reductions in muscle and bone health, as well as maintaining healthy levels of body fat. AFP-Relaxnews

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Just two weeks of reduced activity decreases muscle strength, particularly among seniors - Malay Mail

Maria A Risso,1 Sofa Sallustio,1 Valentin Sueiro,1 Victoria Bertoni,1 Henry Gonzalez-Torres,2,3 Carlos G Musso1,2

1Human Physiology Department, Instituto Universitario del Hospital Italiano de Buenos Aires, Buenos Aires, Argentina; 2Facultad de Ciencias de la Salud, Universidad Simon Bolivar, Barranquilla, Colombia; 3Ciencias Biomdicas, Universidad del Valle, Cali, Colombia

Correspondence: Carlos G MussoHuman Physiology Department, Instituto Universitario del Hospital Italiano de Buenos Aires, Buenos Aires, ArgentinaEmail carlos.musso@hospitalitaliano.org.ar

Abstract: Glomerular filtration rate (GFR) and proteinuria-albuminuria are the renal functional parameters currently used to evaluate chronic kidney disease (CKD) severity. However, tubular secretion is another important renal functional parameter to be taken into accountsince proximal tubule (PT) secretion, in particular, is a crucial renal mechanism for endogenous organic cations, anions and drug elimination. The residual diuresis is a relevant survival predictor in patients on dialysis, since their urine is produced by the glomerular and tubular functions. It has been hypothesized that drugs which up-regulate some renal tubular transporters could contribute to uremic toxin excretion, and nephroprevention. However, if tubular transporters down-regulation observed in CKD patients and experimental models is a PT adaptation to avoid intracellular accumulation and damage from uremic toxins, consequently the increase of toxin removal by inducing tubular transporters up-regulation could be deleterious to the kidney. Therefore, a deeper understanding of this phenomenon is currently needed. In conclusion, tubular function has an important role for endogenous organic cations, anions and drug excretion in CKD patients, and a deeper understanding of its multiple mechanisms could provide new therapeutic alternatives in this population.

Keywords: tubular function, chronic kidney disease, drugs

This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License.By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

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The Importance of Tubular Function in Chronic Kidney Disease | IJNRD - Dove Medical Press

A review of more than 130 studies explains how sleep helps people learn new information and plays an important role in storing learned content for future use. The review is published in the January 2020 issue of Physiology.

Forming memories consists of learning new information, consolidating it in areas of the brain for long-term storage and the ability to recall the learned content later. The reviewers looked at studies in humans and animals that suggested that sleep helps the brain consolidate information stored in long-term memory. Earlier findings were based on the concept that different stages of sleep strengthened different types of memory retention. While brain activity during certain sleep states, such as slow wave activity, may be more beneficial for storing specific types of memory, it is now clear that consolidation in sleep has many facets.

Examining electrical activity in the brain can define various stages of sleep and the patterns of sleep architecture (structural organization of sleep). Looking at research that explores these patterns helps scientists understand how the brain consolidates memories during sleep and while awake. Several studies in the review found that learning a task increases subsequent slow-wave activity and sleep spindles-;neural movements (oscillations) that are abundant during sleep-;in the brain. The increase in these activities has been associated with improved performance of the task after sleeping. Other studies showed that enhancing slow-wave activity and spindles during sleep boosted retention of certain types of memories.

More recent research also investigates processes of forming false memories and generalizing previously learned content. "Overall, the specific modulation of brain oscillations of sleep to impact memory consolidation is a relatively new area, but provides substantial potential in unraveling the role of neural oscillations in the process of memory consolidation," the review's authors wrote.

Scientific research continues to develop tools that link neural activity to sleep behavior, the authors explained. "Future research should utilize these tools to scrutinize present and newly evolving concepts of memory consolidation," they wrote.

Source:

Journal reference:

Marshall, L., et al. (2019) Brain Rhythms During Sleep and Memory Consolidation: Neurobiological Insights. Physiology. doi.org/10.1152/physiol.00004.2019.

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Sleep helps the brain consolidate information stored in long-term memory - News-Medical.net

Abstract

Intrinsic water use efficiency (iWUE), defined as the ratio of photosynthesis to stomatal conductance, is a key variable in plant physiology and ecology. Yet, how rising atmospheric CO2 concentration affects iWUE at broad species and ecosystem scales is poorly understood. In a field-based study of 244 woody angiosperm species across eight biomes over the past 25 years of increasing atmospheric CO2 (~45 ppm), we show that iWUE in evergreen species has increased more rapidly than in deciduous species. Specifically, the difference in iWUE gain between evergreen and deciduous taxa diverges along a mean annual temperature gradient from tropical to boreal forests and follows similar observed trends in leaf functional traits such as leaf mass per area. Synthesis of multiple lines of evidence supports our findings. This study provides timely insights into the impact of Anthropocene climate change on forest ecosystems and will aid the development of next-generation trait-based vegetation models.

Climate change will likely alter future carbon and hydrologic cycles (1). These cycles are closely tied to plant assimilation of atmospheric CO2 through photosynthesis by the regulation of CO2 and water vapor exchange via small pores on the leaf surface, called stomata. CO2 uptake is necessarily accompanied by water loss through stomata, and this carbon gain to water loss metric is generally referred to as water use efficiency (2). At the leaf level, variation in the photosynthesis (A)tostomatal conductance (gs) ratio over a leaf life span represents a time-integrative or averaged estimate of the intrinsic water use efficiency (iWUE), operating at a common evaporative demand (2). Thus, iWUE, a form of water use efficiency, is an important measure of the potential water cost of maintaining a given rate of carbon assimilation per unit leaf area.

A primary response of plants to increasing CO2 is to increase A and is often accompanied by reducing diffusive gs to minimize transpirational water loss (3). As a result, iWUE is generally known to increase with rising atmospheric CO2 (4). However, the magnitude and direction of iWUE responses to elevated CO2 at broad ecosystem and species ranges in natural ecosystems are poorly understood. Specifically, the decadal responses of two key plant functional groups, evergreen and deciduous, are not clear; this is important given that these functional groups occur across many taxonomic groups, and their relative proportions largely define global ecosystems and ecosystem functions and services (5, 6). It is hypothesized that evergreen plants are more sensitive in their iWUE response to elevated atmospheric CO2 than deciduous plants (7). However, to date, experimental CO2 enrichment studies, which were based on limited species and ecosystem type, are equivocal (7).

Here, we assessed the impact of human-driven increases in atmospheric CO2 [~45 parts per million (ppm)] over the past ~25 years on the iWUE of deciduous versus evergreen plants (244 species; table S1). We focus on iWUE responses of woody taxa from 20 field sites spanning eight biomes between two time periods: 19881991 and 20132015 (Fig. 1A and table S2). To compare the iWUE response of contemporary (20132015) to historical plants (19881991), we used a unique georeferenced herbarium collection of C3 woody flowering species, known as Climate-Leaf Analysis Multivariate Programme (CLAMP) (8), to represent historical samples. We compared these to contemporary leaves collected 25 years later by our team from the same species at the same sites (which we will refer to as species sites) and biomes (which we will refer to as species biomes). We inferred iWUE using leaf stable carbon isotopes (13C). To minimize variability in leaf 13C between historical and contemporary samplesdue to possible differences in phenology, seasonality, and field protocolswe operated the same field sampling protocol as CLAMP (8) and sampled during approximately the same collection season or month as the historical leaves.

(A) Major study areas. (B) Historical and contemporary iWUE at 355 and 400 ppm atmospheric CO2 concentration respectively arranged by increasing averaged iWUE values. Boxplots show median (center line), mean (red dot), interquartile range (IQR), 1.5 times of IQR (whiskers), and outliers (black dots). Numbers in brackets are the number of leaves. All iWUE gains are likely to be larger than zero.

A total of 2031 historical and contemporary leaves were analyzed for leaf 13C, leaf mass per area (LMA), carbon per mass (Cmass), and nitrogen per mass (Nmass). There is no likely difference in average total LMA and Nmass between the historical and contemporary samples [LMA = 0.4 g m2; 95% credible interval (CI95%), 1.4 to 0.6; Nmass = 0.06%; CI95%, 0.12 to 0.27] and the slopes of regression between the two time periods through the origin are close to 1 (LMA slope = 0.97; CI95%, 0.96 to 0.98; r2 = 0.92; Nmass slope = 0.97; CI95%, 0.94 to 1.00; r2 = 0.93) (fig. S1). Average evergreen LMA is likely higher than deciduous within each biome in both the historical and contemporary samples (table S3).

An unequivocal increase in average iWUE (iWUE) was observed in all eight biomes investigated, ranging from highest in the tropical seasonal moist forest [TSF(M)] (17.2 mol mol1; CI95%, 14.3 to 20.0) to lowest in the tropical rainforest (TF) (5.2 mol mol1; CI95%, 1.6 to 8.3) (Fig. 1B and table S4). Among the seven biomes with both evergreen and deciduous groups, evergreen species generally demonstrated a greater iWUE in response to ~45 ppm rise in CO2 than deciduous plants, within cooler biomes (Fig. 2A and table S5): this trend also prevailed when data were further grouped into growth habit (tree versus shrub) or high- and low-light habitat (understory subcanopy versus open canopy) (figs. S2 and S3 and tables S6 and S7). A substantial decrease in the ratio of leaf intercellular CO2 (ci) to ambient atmospheric CO2 (ca), ci/ca, in evergreens compared with deciduous taxa resulted in a higher calculated iWUE gain (fig. S4). Our results agree well with published studies that have reported either a decrease in ci/ca (9, 10) or a near constant ci/ca (11, 12) for tree species. Differences between average iWUE gain in evergreen and deciduous taxa (iWUEe-d) widened, however, with decreasing mean annual temperature (MAT) from the tropical toward the boreal biomes (slope = 0.395; CI95%, 0.770 to 0.004; r2 = 0.70; Fig. 2B).

Dotplots represent mean of posterior distributions (n = 6000 samples), CI95%. Red line is the fitted regression. (A) iWUE of deciduous and evergreen plants in biomes arranged by increasing MAT. (B) Differences between evergreen and deciduous iWUE (iWUEe-d) versus MAT, iWUEe-d = 11 0.4MAT, r2 = 0.70. (C) iWUEe-d versus average difference of evergreen and deciduous LMA (LMAe-d), iWUEe-d = 2.0 + 0.14 LMAe-d, r2 = 0.80. (D) Boxplots of deciduous and evergreen LMA across biomes for combined historical and contemporary samples arranged by increasing MAT. All P(LMAevergreen > LMAdeciduous) 0.95. (E) Comparison of the rate of iWUE gain per unit of CO2 concentration (iWUE/CO2) for total deciduous and evergreen samples [P(iWUE/CO2 evergreen > iWUE/CO2 deciduous) = 0.87]. (F) Scatter plot of LMA versus MAT of evergreen and deciduous plants for combined historical and contemporary samples, n = 2031 leaves.

In this study, atmospheric CO2 is likely a dominant factor for iWUE gain because of the likely difference in atmospheric CO2 concentration between the two time periods (Mauna Loa station; CI95%, 43.60 to 45.89 ppm). In contrast with this, other influential climatic variables, such as air temperature and vapor pressure deficit (VPD) showed only small changes with no likely difference statistically within biomes at CI95% (table S8). Furthermore, our result demonstrated that the small changes in MAT (MAT) and VPD (VPD) between historical and contemporary periods in this study were unlikely to affect iWUEe-d, as the differences in iWUE between evergreen and deciduous within the same biome were not highly influenced by MAT or VPD (fig. S5).

In relation to leaf functional traits, iWUEe-d also varied increasing tightly (r2 = 0.80) with the biome average difference between LMA in evergreen and in deciduous species (LMAe-d; slope = 0.14; CI95%, 0.05 to 0.23; Fig. 2, C and D). The total average iWUE value for each deciduous and evergreen group, with all biomes combined, was quantified by normalizing iWUE with VPD, temperature, precipitation, and altitude using models developed in this study (table S9). We found that average iWUE was higher in evergreen than in deciduous species [P(iWUEevergreen > iWUEdeciduous) = 1] with gains of ~39% (17.1 mol mol1; CI95%, 13.8 to 20.5) and ~15% (7.8 mol mol1; CI95%, 5.0 to 10.4), respectively. These correspond to an iWUE gain of 0.39 mol mol1 ppm1 (CI95%, 0.30 to 0.46) in evergreen and 0.18 mol mol1 ppm1 (CI95%, 0.12 to 0.25) in deciduous species [P(iWUE/CO2evergreen > iWUE/CO2deciduous) = 0.99] (Fig. 2E).

The divergence of evergreen and deciduous iWUE along a MAT gradient (1.4 to 26.7C) parallels those observed for LMA (Fig. 2F) and Nmass (fig. S6). The LMA divergence in functional groups from warmer to colder sites (27.5 to 16C) was observed in a previous study (13) and was associated with LMA increment with leaf life span; this divergent trend is related to the requirement of leaves with longer life spans to maximize carbon gain in shorter growing seasons, i.e., in colder biomes (14). Our results demonstrated how this well-studied trend (13, 14), in LMA divergence from warmer to colder biomes, also manifests in the differential response of evergreen and deciduous taxa to anthropogenic CO2 rise. The smaller differences in LMA between the leaf habit classes in the warmer biomes compared with the colder biomes contributed to the observed trend. High LMA generally occurs in woody evergreens because of their robust leaf structure, which can incur resistance to CO2 diffusion and, hence, lower mesophyll conductance (gm) (7, 15, 16). Therefore, evergreen leaves, in general, are likely to operate at lower gm values than deciduous leaves (16, 17).

Under elevated CO2, leaves with low gm may show a higher increase in A than high gm taxa, and their A is less sensitive to reduction in gsthis, in turn, leads to strong iWUE gain (iWUE = A/gs) (7). At a given gs, A of leaves with low gm (i.e., evergreens) is more limited by lower chloroplast CO2 concentration (cc) and, thus, responds more strongly to rising CO2. The reason for this is that the higher cc gets, the less CO2 affects photosynthesis because of the saturation of the A versus cc relationship (7). We did not measure gm, but we did observe greater average LMA and iWUE responses in evergreens than in deciduous species, suggesting increased CO2 diffusion limitations in the former. LMA and gm are inversely correlated, but the relationship is confounded by mesophyll cell wall thickness and chloroplast surface area that can vary across environmental gradients and species (15, 18). Therefore, in this study, high LMA was associated with greater iWUE response to a ~45-ppm rise in atmospheric CO2 concentration in evergreen compared with deciduous leaves (Fig. 2, C and E).

To validate our results from the two time periods, we used published tree ring 13C datasets (19702013) and leaf 13C datasets (19812005) (1921) containing continuous recent sampling points to track iWUE trends along a rising atmospheric CO2 gradient (iWUE/CO2). The meta-analysis of tree ring iWUE data showed higher average iWUE response in evergreen (0.29 mol mol1 ppm1; CI95%, 0.27 to 0.33) than deciduous (0.21 mol mol1 ppm1; CI95%, 0.18 to 0.24) trees (Fig. 3A, fig. S7, and table S10). Evergreen trees in the boreal-temperate region(s), which were all gymnosperms in the published datasets (seven species), showed a greater average rate of iWUE gain (0.33 mol mol1 ppm1; CI95%, 0.30 to 0.36) than their angiosperm and gymnosperm deciduous counterparts (four species) (0.14 mol mol1 ppm1; CI95%, 0.11 to 0.17), but in the tropics, this disparity was not observed (Fig. 3B). This result corroborated with published studies that showed the average gm of temperate evergreen gymnosperm was onefold lower than temperate deciduous angiosperms (15, 16). Furthermore, a tree ring study at 23 sites across Europe showed that evergreen gymnosperm trees (four species) increased their iWUE substantially more than deciduous angiosperm trees (two species) in the last c. 100 years at ~22 and ~14%, respectively (10). Our meta-analysis of published leaf 13C data from woody angiosperm species showed the same trend of higher collective iWUE increase (iWUEc/CO2) in evergreen (0.76 mol mol1 ppm1; CI95%, 0.62 to 0.91) than in deciduous (0.51 mol mol1 ppm1; CI95%, 0.32 to 0.70) leaves (Fig. 3C and fig. S8). These results confirm our original observations from the two time periods: There is an overall stronger iWUE gain in evergreen compared with deciduous species (Fig. 2, A and E) in response to rising atmospheric CO2.

Dotplots represent mean of posterior distributions (n = 6000 samples), CI95%. (A) iWUE/CO2 from published tree ring 13C data for the various time intervals between 1970 and 2013 for evergreen (n = 29 trees) and deciduous trees (n = 23 trees). (B) Result from (A) separated into bioclimatic zones showing higher average iWUE gain in evergreen (n = 24 trees) than in deciduous trees (14 trees) in the boreal-temperate zone, but the opposite in the tropical zone (deciduous n = 9 trees; evergreen n = 5 trees) [P(iWUE/CO2 deciduous > iWUE/CO2 evergreen) = 0.95]. (C) iWUEc/CO2 calculated from published leaf 13C data collected between 1981 and 2005 for deciduous (n = 470 species sites) and evergreen (n = 1053 species sites) species.

To further test this differential evergreen/deciduous response to ~45-ppm rise in CO2, we used data from a field infrared gas exchange analysis (IRGA) experiment conducted in situ on a subset of the same leaves used for this 13C study. Leaf A and gs responses to ~355- and ~400-ppm cuvette CO2 concentration were measured, referencing values for the historical and contemporary period, respectively. The responses measured with the gas analyzer were instantaneous responses to CO2 concentration rather than long-term responses (decadal) that are most likely influenced by acclimation. This experiment showed that average gain in leaf iWUE in evergreen leaves (0.22 mol mol1 ppm1; CI95%, 0.20 to 0.25) was likely higher than that in deciduous leaves (0.20 mol mol1 ppm1; CI95%, 0.17 to 0.23) [P(iWUE/CO2evergreen > iWUE/CO2deciduous) = 0.92] (Fig. 4A). Results from our in situ gas exchange study showed that an increase in A can largely contribute to an increase in iWUE under a ~45-ppm CO2 rise with higher average A gain in evergreen (22.4%; CI95%, 19.1 to 25.7) than in deciduous leaves (16.7%; CI95%, 13.4 to 20.1) (Fig. 4B). However, gs instantaneous responses showed no likely change in both groups (evergreen: 0.2%; CI95%, 2.3 to 1.8; deciduous: 1.0%; CI95%, 1.1 to 3.2) (Fig. 4C). Evergreen ci/ca showed a likely decrease, but no change was observed in deciduous leaves (evergreen: 0.015 Pa; CI95%, 0.019 to 0.010; deciduous: 0.001 Pa; CI95%, 0.003 to 0.006).

Dotplots represent means of posterior distributions (n = 6000 samples), CI95%. Evergreen n = 135 leaf samples (33 species); deciduous n = 119 leaf samples (31 species). (A) Dotplots of iWUE in evergreen and deciduous leaves. (B) Dotplots of A in evergreen and deciduous leaves. (C) Dotplots showing average gs in evergreen and deciduous are unlikely to be higher than zero at CI95%.

Currently, these experimental results (Fig. 4C) do not account for possible anatomical adaptions in stomatal density and/or size that could influence gs. Stomatal density in most plant species is well known to decrease with increasing atmospheric CO2 concentration that could lead to a general decrease in maximum stomatal conductance (22). Work is therefore ongoing to assess anatomical adaptations at the species and functional group level to test these conclusions further. Results from the in situ IRGA measurements, which estimate the instantaneous responses to CO2, lend support to the long-term observations from our extensive biome-level field-based 13C study and suggest that the magnitude of iWUE change observed here is due to a substantial increase in A coupled with little or no change in gs. Together, these results suggest that notable adjustment of photosynthetic biochemistry has occurred in woody vegetation with ~45-ppm CO2 rise.

Our biome-wide field study of iWUE responses to a mere 45-ppm CO2 rise between 1988 and 2015 suggests greater average iWUE gain in evergreen than in deciduous species, particularly in the cooler climate biomes. The diverging trend in iWUE gain highlights a strong link between LMA, MAT, and plant-CO2 responses in woody evergreen and deciduous taxa: This is strongly associated with the more distinct differences in LMA and leaf phenological traits observed between evergreen and deciduous taxa in colder biomes than in warmer biomes. This knowledge has the potential to enhance development of new-generation trait-based vegetation models, of which temperature, photosynthetic water use, and LMA are important components. That the differential response of evergreen and deciduous leaf habits in natural ecosystems has been given little attention to date is unexpected given that such a profound physiological response occurring at a continental scale could incur a substantial shift in natural forest and woodland ecology (e.g., forest fraction of evergreeness and deciduousness) and alter seasonal energy, water, and carbon balance and dynamics. Our results indicate that future increases in atmospheric CO2 may confer a competitive advantage to woody angiosperm evergreens over their deciduous neighbors to a greater extent in cooler biomes than in warmer biomes. Therefore, understanding of the differential physiological response induced by climate change in evergreen and deciduous taxa will improve our ability to build more mechanistic and predictive models on vegetation response to future climate change. While our field study covered a substantial number of woody angiosperm species, and was supported by published tree ring 13C data that included gymnosperm species (seven evergreen and two deciduous species), future research may benefit by including more gymnosperm species to confirm the differential response of leaf habits within this group to rising atmospheric CO2, particularly in the conifer-dominated boreal biome. Further profound increases in atmospheric CO2 are projected by the year 2050 under all representative concentration pathway (RCP) scenarios [RCP 2.5 = 443 ppm; RCP 4.5 = 487 ppm; RCP 6.0 = 478 ppm; RCP 8.5 = 541 ppm (23, 24)]. In this context, higher iWUE under elevated CO2 atmospheres may have contributed to evergreen expansion in past greenhouse intervals such as the Eocene (ca. 55 million years ago), particularly in seasonally dry areas of the mid latitudes (25), rather than to elevated temperatures alone, which is the current paradigm (26).

Historical herbarium samples from the CLAMP collected using the same protocol and person (Wolfe) (8) in 19881991 were recollected in 20132015 by our team (W.K.S., M.M., and J.C.M.). This yielded contemporary leaf samples of the same species from the same sites/biomes. The same standard collection protocol was used for both historical and contemporary samples. This approach was used to minimize variability of leaf 13C. To our knowledge, CLAMP, a unique georeferenced global inventory of C3 woody angiosperm leaf physiognomic data (8, 27), is the only herbarium archive that was collected by the same person (Wolfe) using the same protocol over several biomes with each including many species (average, 25 species per site). In this study, field sites in each biome were selected from the CLAMP archive. Of the original 173 sites sampled by Wolfe (8), we selected 20 to represent eight of Whittakers vegetation biomes (28): boreal forest (BF), temperate rainforest, temperate deciduous forest (TDF), Mediterranean (MED), subtropical desert, tropical seasonal dry forest [TSF(D)], TSF(M), and TF (table S2). We restricted selection to sites below 700 m above sea level to limit the influence of lower CO2 partial pressure and atmospheric pressure on leaf traits and carbon isotope composition (13C) at higher altitudes. Site selection was based on individual site accessibility within the planned data gathering schedule and acquisition of the required scientific collection permits. Where possible, we selected three sampling sites in each biome, except in the TF of Fiji (two sites) and TSF(D) in Puerto Rico (one site). As a result of using CLAMP herbarium samples, sites in the boreal and temperate biomes are restricted to Northern America, with tropical biomes in Puerto Rico [TSF(D) and TSF(M)] and Fiji (TF). Although all the tropical biome sites are situated on islands, the plants species sampled here are from areas that experience tropical climate. We are confident that our tropical sites are representative tropical biomes as there is no evidence to suggest that the physiology of tropical island vegetation differs from that on a tropical mainland, especially at the leaf level. For instance, one of the best studied tropical forests in the world is Barro Colorado Island in Panama. Only evergreen plants were sampled in Fiji, and therefore, this biome was not used to quantify iWUEe-d. To obtain a representative sample of C3 woody angiosperm species within the BF, which is usually dominated by conifers, our sampling was conducted within the interior BF zone of Alaska, which has extensive areas of open and closed deciduous forests (29). Regarding our BF sites, deciduous trees make up virtually all of the native angiosperm tree population, while the gymnosperms are mostly evergreen trees. Since we are making a direct comparison of the historical CLAMP samples with contemporary samples of exactly the same species from the same locations, we were prohibited from including gymnosperms. As a result, our fieldwork study on BF only covered angiosperms of three leaf habit and growth habit groups without evergreen trees. These included deciduous trees, deciduous shrubs, and evergreen shrubs.

Contemporary leaf samples were collected in the field between 2013 and 2015 from the same species as those in the historical CLAMP herbarium collected between 1988 and 1991 from the same sites or biomes. All fieldwork was carried out in the growing season (table S2), corresponding as closely as possible to the collection month of historical samples. Tree and shrub growth habits were sampled in all biomes and were largely represented in both evergreen and deciduous plant groups. Our sampling focused on outer-canopy leaves, meaning sun leaves for plants growing in relatively open environments, and leaves exposed to sun flecks when sampling naturally shade-dwelling species. We sampled fully expanded leaves, the developmental stage at which many leaf traits are relatively stable. In one aspect of the statistical analyses in this study (see section on Statistical analysis), we divided our dataset into two broadly defined habitat groups based on our field observations to reflect high- and low-light habitat: open canopy and understory subcanopy. For this study, open canopy refers to plants that are located either in open areas or at the forest canopy edge and receiving direct sunlight. By contrast, understory subcanopy refers to plants occurring within the forest canopy, in shade but receiving sun flecks. In all biomes, we sampled both the open-canopy and understory-subcanopy habitats for evergreen and deciduous plants, except for the BF and TDF biomes, there were no evergreen plant samples in the open-canopy habitat, and in the subtropical desert biome, all habitats were classified as open canopy. In the historical CLAMP samples, sun-exposed twigs were collected that may be directly exposed to the sun or sun fleck subjected to a species natural habitat. On each herbarium specimen, we had carefully selected leaves that were fully expanded (i.e., visually mature) and thick to increase the chance of including mature sun-exposed leaves.

To minimize the potentially confounding influence of height on leaf 13C and LMA, leaves from tall trees were collected at basal-exterior canopy level within arms reach, up to 3 m in line with CLAMP historical collection methods. This protocol standardized collection height with historical samples. Before collection, the leaves gathered for trait analysis were also used for physiological measurements (see section on In situ field IRGA experiments). Our sampling protocol is in accordance with the collection methods used by Wolfe (8) following the CLAMP protocol. That is, our protocol standardizes historical and contemporary sampling methods, with the aim of reducing trait variability caused by sampling method and relevant biotic and abiotic factors that may have differed between contemporary and historical sampling periods.

Only broadleaf woody C3 angiosperm species were sampled for this study (gymnosperms, grasses, and crops were not included). A total of 1550 contemporary leaf samples, each from individual plants, were collected in the contemporary fieldwork. A total of 481 historical leaf samples were subsampled from the CLAMP herbarium collection. The entire dataset used in this study comprises 244 matching historical and contemporary woody angiosperm species from 64 families (table S1). All specimens were identified to species level. Taxonomic nomenclature was updated using the online Taxonomic Name Resolution Service v 4.0.

Mean monthly precipitation, mean monthly air temperature, maximum monthly air temperature, and vapor pressure over time periods (19881991 and 20132015) for each study site were obtained from 0.5 0.5 resolution Climate Research Unit data (CRU TS v.4.0) (30) gridded dataset via The Royal Netherlands Meteorological Institute (KNMI) Climate Explorer. Monthly saturated vapor pressure was calculated from maximum monthly air temperature. These were then subtracted with monthly vapor pressure to obtain monthly VPD (31) and used to infer leaf-to-air VPD. MAT and mean annual precipitation (MAP) were calculated from the monthly data.

Leaf samples were oven dried at 50 to 60C for 2 days. One half of each dried leaf blade was used for LMA analysis and the other half for 13C, carbon (C), and nitrogen (N) elemental analyses. To standardize LMA data collection from both historical and contemporary leaves, all leaves were rehydrated. Leaf area shrinkage from drying can be reversed by rehydration (32). LMA was determined by dividing the dry leaf mass by the rehydrated leaf area. For the 13C, N, and C elemental analyses, dried leaf fragments were placed with a tungsten bead in Eppendorf tubes and finely ground in a mixer mill (Tissue Lyser, Qiagen Inc., Valencia, CA, USA). Each sample (~3 mg) was then enclosed in a tin capsule using a crimper plate. Samples were analyzed for 13C, C, and N using a PDZ Europa ANCA-GSL elemental analyzer interfaced with a PDZ Europa 20-20 isotope ratio mass spectrometer (Sercon Ltd., Cheshire, UK) at UC Davis Stable Isotope Facility, University of California, Davis, USA. Instrumental error was 0.18 (per mil) for 13C (SD). Carbon isotope composition was calculated as13C()=(RsampleRstandard)/Rstandard1000(Eq. 1)where Rsample and Rstandard are the 13C/12C ratio of the sample and the international standards Vienna Pee Dee Belemnite, respectively. Carbon isotopic discrimination (plant) is given asplant=(13Cair13Cplant)/1+(13Cplant/1000)(Eq. 2)

In relation to the intercellular CO2 (ci) and ambient CO2 (ca) partial pressures, plant in C3 leaves is given as follows (33)plant=a+(ba)(ci/ca)(Eq. 3)where a is the fractionation due to diffusion in air (4.4) and b is the net fractionation caused by carboxylation (27). Equation 3 is widely used and assumes that the effects of boundary layer, internal conductance, photorespiration, day respiration, and allocation are negligible. Atmospheric CO2 concentration (ca) and 13Cair information were taken from a published instrumental dataset (19802015) from the Mauna Loa station (3436) corresponding to the historical and contemporary collection months (table S2). The full equation of plant includes several elements such as photorespiration, day respiration, and the CO2 mole fractions in the ambient air, at the leaf surface, in the intercellular air spaces, and at the chloroplast (cc) (37, 38). Photorespiration and cc are known to influence plant (38), and therefore, it is desirable to include these traits. However, we did not measure photorespiration and gm; the latter is required for estimating cc. In this study, we were interested in quantifying the differences between evergreen and deciduous iWUE (iWUEe-d) rather than their absolute values. On the basis of this reasoning, the use of the simplified linear model of Farquhar et al. (33) (Eq. 3) as an approximation to plant is appropriate for the purpose of this study.

iWUE can be expressed as the ratio of photosynthesis (A) and leaf conductance to water vapor transfer (g) in Eq. 4 below (33) using ci/ca calculated from Eq. 3 and caiWUE=A/g=ca(1ci/ca)/1.6=ca(1(a)/(ba))/1.6(Eq. 4)

iWUE inferred from 13C is an average estimate of iWUE over a leaf life span, i.e., time integrated.

All statistical analysis was undertaken using JAGS 4.1.0. (39) and R statistical software (40). Bayesian models using JAGS, through the R package rjags (41) interface, were used: Inference of each parameter was made from Markov Chain Monte Carlo (MCMC) sampling from 6000 samples of the posterior distribution from three chains, each with 10,000 iterations with a burn-in of 2000 and a thin rate of 4 (42). Normal distribution priors with mean zero and variance 100 were used for intercept and slope parameters, while a uniform (0, 10) prior was used for the SD on the variance terms. Convergence was checked by visual assessment of MCMC chains and using the Gelman-Rubin statistic (42). Mean of trait or group was calculated from posterior distributions. CI95%s of parameter estimates were calculated as the 2.5 and 97.5% quantile of posterior distributions. The 50% credible interval (CI50%) of parameter estimates were calculated as 25 and 75% quantile of posterior distributions. The CI95% represents the interval that captures 95% of the posterior distribution, e.g., when the CI95% for a statistics score is between a and b, this means that we have a 95% chance of having a score between a and b (note that credible interval is different from confidence interval). A CI50% statistics score between a and b implies a 50% chance of having a score between these two values. Therefore, the extent of CI overlapping with zero determines how likely a value is close to zero. Statistical comparisons between groups were made by examining value of CI95% and/or by probability of group differences bigger than or smaller than zero, e.g., P(x > y) = z denotes that the probability of variable x being bigger than variable y, given the data, is z.

To evaluate the robustness of our sampling method in minimizing the variability between the historical and contemporary samples, we first statistically test the difference in the mean of LMA and Nmass in the two time points. Second, we plotted historical and contemporary samples through the origin each for LMA and Nmass. A regression slope that is close to 1 would indicate a general level of uniformity between the historical and contemporary samples. LMA and Nmass are well known to vary with plant height, sun and shade leaf morphotypes, and age (43, 44).

We aggregate across biomes the iWUE at each time point (historical versus contemporary) to calculate the total gain in iWUE (iWUE) for the deciduous and evergreen species groups, using statistical models incorporating environmental variables (environment-normalized model) (Fig. 2E). However, samples from the TF biome (Fiji) were excluded because of the absence of deciduous plant samples. The environment-normalized model standardizes the aggregated iWUE values when calculating the total gain in iWUE: Leaf 13C or its derived variables (e.g., iWUE and ci/ca) are widely known to be confounded by latitude (20), altitude (19, 20), and site climatic variables such as VPD (45), temperature (1921, 45), and precipitation (1921). Using our own dataset, we examined the relationship between iWUE and environmental variables such as altitude, latitude, and bioclimatic variables (precipitation, temperature, and VPD). Our aim was to generate an equation that could be used to normalize iWUE values against environmental variables when aggregating data across biomes (see Fig. 2E).

For evergreen species, we averaged site monthly precipitation, temperature, VPD, and atmospheric CO2 concentration by 12 months up to and including the collection month to match the average period of photosynthetic opportunities. One meta-analysis study showed that mean annual climate parameters were more likely to match evergreen photosynthetic windows for carbon isotope discrimination of C3 plants (21). Although photosynthesis of evergreens is reduced during winter time with small winter carbon gain (46, 47), this may still influence the average carbon isotope discrimination in a leaf life span. The leaf life span of evergreen angiosperms in the boreal-temperate and tropical biomes each showed a skewed distribution with central tendencies (median) of approximately 18 and 15 months (48), respectively (fig. S9). Therefore, our approach of averaging site climatic data by a period of 12 months up to and including the collection month was a reasonable approximation of evergreen leaf life span collected at the time. This approximation took into consideration the fact that we sampled only fully expanded leaves that were neither young nor too old (i.e., visibly unhealthy). For deciduous species, we averaged these climate variables from the start of growing months up to and including the collection month.

The correlation matrix between iWUE and the foregoing environmental variables are presented in table S11. VPD shows the strongest correlation with iWUE (r2 = 0.26) followed by precipitation (r2 = 0.24), altitude (r2 = 0.20), and absolute latitude (r2 = 0.10). Temperature shows the weakest correlation with iWUE (r2 = 0.05) but is instead strongly correlated with absolute latitude (r2 = 0.93), precipitation (r2 = 0.65), and VPD (r2 = 0.53), and weakly correlated with altitude (r2 = 0.10). Therefore, temperature was not included in our model because of the extreme collinearity between covariates, which could lead to high correlation in some of the posterior parameter estimates. Last, our statistical model consists of iWUE as the dependent variable, while time (factor), altitude, averaged site VPD, and precipitation are the independent variables (Model 1). Latitude was excluded from the model because its coefficient was subsequently shown to likely contain zero at CI95% when included in the regression. To calculate the rate of iWUE change in relation to atmospheric CO2 concentration, the same model was used with time factor replaced by CO2 concentration (Model 2). In the following models, each i represents one leaf. See table S9 for coefficient values.iWUEi=j(i)+j(i)Timei+1VPDi+2PREPi+3ALTi+i(Model 1)where iWUEi is the iWUE of individual i; Timei is the categorical time variable (historic and contemporary) corresponding to individual i; VPDi is the VPD corresponding to individual i; PREPi is the precipitation corresponding to individual i; ALTi is the altitude corresponding to individual i; j(i) is the intercept of the iWUE-time relationship in categorical leaf habit j (deciduous and evergreen); j(i) is the slope of the iWUE-time relationship in categorical leaf habit j (deciduous and evergreen), this is iWUE; 1 is the slope of the iWUE-VPD relationship; 2 is the slope of the iWUE-PREP relationship; 3 is the slope of the iWUE-ALT relationship; and i is the residual of individual i.iWUEi=j(i)+j(i)(CO2)i+1VPDi+2PREPi+3ALTi+i(Model 2)where, iWUEi is the iWUE of individual i; (CO2)i is the atmospheric carbon dioxide concentration corresponding to individual i; VPDi is the atmospheric VPD corresponding to individual i; PREPi is the precipitation corresponding to individual i; ALTi is the altitude corresponding to individual i; j(i) is the intercept of the iWUE-CO2 relationship in categorical leaf habit j (deciduous and evergreen); j(i) is the slope of the iWUE-CO2 relationship in categorical leaf habit j (deciduous and evergreen), this is iWUE/CO2; 1 is the slope of the iWUE-VPD relationship; 2 is the slope of the iWUE-PREP relationship; 3 is the slope of the iWUE-ALT relationship; and i is the residual of individual i.

For j(i), the slope of the iWUE-CO2 relationship, the actual full unit of WUEi/CO2 is mol CO2 mol1 H2O/mol CO2 mol1 air: For simplicity and readability, we prefer to use mol mol1 ppm1. We further investigate iWUE in evergreen and deciduous plants in each biome by dividing the dataset into growth habit (shrub versus tree) or habitat (understory-subcanopy versus open-canopy) categories. In each category, the probability of evergreen iWUE higher than deciduous iWUE was calculated.

Photosynthesis and photosynthetic water use were measured on 254 leaf samples from 64 of our 13C study species. Measurements were made with a CIRAS-2 gas analyzer (PP Systems, Amesbury, MA, USA) attached to a PLC6 (U) cuvette fitted with a 1.7-cm2 measurement window and a red/white-light light-emitting diode unit. Measurements were carried out between June and August 2014 at two BF sites (16 species, Bird Creek and Kenai, Alaska, USA), one TDF site (11 species, Smithsonian Environmental Research Center, Maryland, USA), two TSF(M) sites (15 species, Cambalache and Guajataca, Puerto Rico), and one TSF(D) site (9 species, Borinquen, Puerto Rico), all from a subset of the contemporary samples. Photosynthesis (A) and stomatal conductance (gs) were assessed on an average of four individual plants per species between 9:00 am and 13:00 pm. A sun-exposed branch was sampled from each plant using a pruner and was immediately recut under water (49). Following this, a fully expanded leaf from each branch was enclosed in the cuvette of the gas analyzer, which was running at a subambient 19881991 averaged reference CO2 concentration of 355 ppm. Stomatal conductance at subambient CO2 concentration was recorded upon stabilization of its value, which typically took less than 15 min. Subsequently, reference CO2 was established at 400 ppm (year 2016 values), and the leaf was left to equilibrate for at least 15 min before gs at contemporary ambient atmospheric CO2 was recorded. Randomization of the sequence of the two treatments was ensured; overall, about 65% of the measurements started at 400 ppm and were reduced to 355 ppm, while the rest of measurements (35%) started at 355 ppm and were increased to 400 ppm. On several occasions, the reversibility of the CO2 effects on A and gs was tested. This was done by measuring gs at a starting CO2 concentration of 400 ppm, after which CO2 was reduced to 355 ppm for several minutes before it was returned to the initial concentration of 400 ppm. The final A and gs values at 400 ppm were the same as those initially recorded.

iWUE data calculated from tree ring 13C were used to quantify the iWUE-CO2 response of individual deciduous and evergreen trees along a decadal time series of various time intervals between 1970 and 2013. Data were compiled from 17 published studies (5066) consisting of 52 trees from 22 species, of which 23 trees were deciduous (12 species) and 29 evergreen (10 species). Atmospheric CO2 concentration data were acquired from the Mauna Loa station data (3436). Annual 13Cair information was obtained from published ice-core data. iWUE values were calculated from 13C by using Eq. 3. For each study site, we obtained mean monthly precipitation, mean monthly air temperature, maximum monthly air temperature, and vapor pressure from 0.5 0.5 resolution CRU TS v.4.0 (30) gridded dataset for the period of 13C for each individual tree. VPD values were calculated as per the method described in the section Climate data. Regression slopes (iWUE/CO2) for individual trees were determined by fitting a simple linear model (using the Bayesian linear regression approach, see section on Statistical analysis) with iWUE as the dependent variable, and atmospheric CO2 concentration, VPD, and MAP as the independent variables. In the following model, each i represents a value from a growth ring as determined in a study, from a tree, jiWUEi=j(i)+j(i)(CO2)i+1VPDi+2PREPi+3ALTi+i(Model 3)where, iWUEi is the iWUE of individual i; (CO2)i is the atmospheric carbon dioxide concentration corresponding to individual i; VPDi is the atmospheric VPD corresponding to individual i; MAPi is the MAP corresponding to individual i; j(i) is the intercept of the iWUE-CO2 relationship in categorical individual tree j; j(i) is the slope of the iWUE-CO2 relationship in categorical individual tree j; 1 is the slope of the iWUE-VPD relationship; 2 is the slope of the iWUE-PREP relationship; and i is the residual of individual i.

By including VPD and MAP in the regression, we normalized the response slope of each tree with climatic variables, VPD and MAP. MAT is excluded from the model because of the strong collinearity with VPD (r2 = 0.72). The values for 1 and 2 are 5.47 (CI95%, 4.01 to 6.97) and 0.08 (CI95%, 0.09 to 0.06), respectively. On a centennial scale, a long-term iWUE fluctuation along the atmospheric CO2 gradient generally follows an exponential increase. However, we can reasonably approximate the iWUE trend with a linear model at a shorter decadal time scale. This shorter decadal time scale varies between 10 and 40 years from 1970 to 2013 depending on studies. Last, iWUE/CO2 values from posterior distributions of trees (6000 samples for each tree) were aggregated into deciduous and evergreen plant groups by averaging iWUE/CO2 values from posterior distributions. This approach therefore takes account of the uncertainty of iWUE/CO2 values of each tree. Further, we also aggregated deciduous and evergreen plant groups for two climatic zones: boreal-temperate and tropical.

Published (1921) and unpublished angiosperm leaf 13C data collected between 1981 and 2005 were used for meta-analysis. Year of data collection was added to the collated dataset based on original publications. Any data source without collection dates was assumed to be 2 years before the date of paper submission (~5% of datasets). Atmospheric CO2 concentration and 13Cair information corresponding to collection year were obtained from a published instrumental dataset (19802015) at the Mauna Loa station (3436). For 13C values without environmental data, we obtained MAT and MAP data from 0.5 0.5 resolution CRU TS v. 4.0 (30) gridded dataset. The final dataset includes 1523 species site points from 76 studies of 1000 species across eight biomes. To quantify the response of deciduous and evergreen leaves to elevated CO2, we used a linear model with iWUE as the dependent variable and atmospheric CO2 with interaction between deciduous and evergreen groups. The iWUE trend along rising atmospheric CO2 gradient across collective leaf samples from different studies in various localities may be influenced by environmental conditions of the location. To investigate the likely influential environment factor that may have contributed to the observed iWUE trend, we quantified the amount of variation contributed by atmospheric CO2 concentration, MAT, MAP, altitude, and latitude across time. We first regressed collection year against all the foregoing environmental variables and then used R package relaimpo (67) to quantify the amount of variation contributed by each environmental factor. The proportion of variance explained by the model was 99.3%, of which 98% was contributed by CO2 followed by MAT at ~1%. Therefore, we can be confident that CO2 was influential in driving iWUE trends across collection time compared with other environmental variables. We designated the iWUE gain across collective leaf samples of different species and environmental conditions/locations as iWUEc to differentiate it from iWUE. The latter is derived from iWUE gain of the same species composition and locality.

Supplementary material for this article is available at http://advances.sciencemag.org/cgi/content/full/5/12/eaax7906/DC1

Fig. S1. Historical and contemporary leaf functional trait plots through the origin.

Fig. S2. iWUE gain (iWUE) of deciduous and evergreen plants in biomes for growth habit, arranged by increasing MAT.

Fig. S3. iWUE gain (iWUE) of deciduous and evergreen plants in biomes for habitat group, arranged by increasing MAT.

Fig. S4. The changes in the ratio of leaf intercellular (ci) to ambient CO2 (ca), ci/ca, in evergreens and deciduous species in biomes, arranged by increasing MAT.

Fig. S5. iWUE change (iWUE) of deciduous and evergreen plants versus MAT change (MAT) and VPD change (VPD) in biome growth habit and habitat group.

Fig. S6. Scatter plot of Nmass versus MAT for combined historical and contemporary samples of evergreen and deciduous plants.

Fig. S7. Trend of iWUE from tree ring data along increasing atmospheric CO2 concentration between the years 1970 and 2013.

Fig. S8. Evergreen and deciduous iWUE plotted against atmospheric CO2 concentration showing slope of response.

Fig. S9. Kernel density plots of leaf life span (month) of deciduous and evergreen plants in the boreal-temperate and tropical biomes.

Table S1. List of species studied, their leaf habit (evergreen, deciduous), habitat (understory subcanopy and open canopy), and growth habit (shrub and tree).

Table S2. Summary of historical and contemporary site location, vegetation type, and collection date in alphabetical order by biome and site name.

Table S3. Historical and contemporary samples showing average LMA in evergreen and deciduous group within biome and probability of evergreen LMA larger than deciduous LMA, P* = P(LMAevergreen > LMAdeciduous).

Table S4. Average iWUE change (iWUE) in biome between two time points 19881991 and 20132015 with CI95% from posterior distributions in Bayesian analysis.

Table S5. Average iWUE gain (iWUE) in evergreen and deciduous plants within biome with CI95% from posterior distributions in Bayesian analysis.

Table S6. Shrub and tree, average iWUE gain (iWUE) in evergreen and deciduous plants within biome, with CI95% from posterior distributions in Bayesian analysis.

Table S7. Understory-subcanopy and open-canopy habitat, average iWUE gain (iWUE) in evergreen and deciduous plants within biome, with CI95% from posterior distributions in Bayesian analysis.

Table S8. Average annual air temperature change and average annual VPD change of biomes between two time periods 19881991 and 20132015 with CI95% from posterior distributions in Bayesian analysis.

Table S9. Average of coefficients of Model 1 and Model 2 with CI95% from posterior distributions in Bayesian analysis.

Table S10. Slope of iWUE response to atmospheric CO2 concentration (iWUE/CO2) for individual trees arranged by leaf habit, species, and references.

Table S11. Pearson correlation matrix (lower half panel in gray) and significance (upper half panel) between iWUE, VPD, precipitation, temperature, altitude, and latitude.

This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license, which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.

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Acknowledgments: We are grateful to S. Wing and staff at Smithsonian NMNH for the hospitality and for access to herbarium specimens and the loan of leaves from the CLAMP collection. We are also grateful to the following people and institutions for permissions and field assistance: Smithsonian Environmental Research Center, Maryland, USA (P. Megonigal, S. McMahon, and J. Shue), Jasper Ridge Biological Preserve, California, USA (N. Chiariello and T. Corelli); The University of the South Pacific, Fiji (M. Tuiwawa, A. Naikatini, and S. Pene), Tonto National Forest (E. Hoskins and C. Denton), California State Parks (T. Hyland and J. Kerbavaz), Alaska State Parks (P. Russell and L. Ess), and Oregon State Parks (N. Bacheller). Many thanks to S. Culhane, E. Doyle, and C. Egan for field assistance. Funding: We gratefully acknowledge funding from a Science Foundation Ireland (SFI) Principal Investigator Award (PI) 11/PI/1103. A.P. was supported by SFI Career Development Award grant 17/CDA/4695 and SFI center grant SFI/12/RC/2289_P2. R.A.S. was supported by a Natural Environment Research Council grant (no. NE/P013805/1) and an XTBG International Fellowship for Visiting Scientists. Author contributions: W.K.S. led the writing, with input from J.C.M., C.Y., and M.M. J.C.M., C.Y., M.M., I.J.W., A.P., R.A.S., T.L., and R.C. discussed and commented on the manuscript. W.K.S., M.M., C.Y., and J.C.M. designed the study and organized and conducted fieldworks. W.K.S. and M.M. sampled CLAMP historical herbarium samples and curated all leaf samples. W.K.S. contributed to the LMA, Nmass, and 13C data. C.Y. and W.K.S. contributed to the IRGA experiment data. C.Y. processed the IRGA experiment data. W.K.S. and A.P. performed the statistical analysis. W.K.S. conducted meta-analysis for published tree ring and leaf 13C data. I.J.W. contributed leaf 13C data for meta-analysis. Competing interests: The authors declare that they have no competing interests. Data and materials availability: All data needed to evaluate the conclusions in the paper are present in the paper and/or the Supplementary Materials. Additional data related to this paper may be requested from the authors.

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Rising CO2 drives divergence in water use efficiency of evergreen and deciduous plants - Science Advances

KEY POINTS

Overeating has been an issue for most of us at some time or the other. Some people have been able to control it, but others who havent been able to do it suffer from issues such as weight gain and obesity.

A new study has looked into how food craving affects the brain. Food craving leads to loss of self-control and eating even when your brain tells you that the foodstuff may be harmful to your health. Impulsivity is one of the reasons behind overeating, binge eating, weight gain, obesity and many psychological disorders such as drug addiction and gambling addiction.

The researchers have found that a specific circuit in the brain causes impulsivity. Because the researchers have identified this circuit, this holds hope that future medical therapies to treat overeating.

"There's underlying physiology in your brain that is regulating your capacity to say no to (impulsive eating), in experimental models, you can activate that circuitry and get a specific behavioural respons." Emily Noble, an assistant professor in the UGA College of Family and Consumer Sciences who served as lead author on the paper, stated in the findings, which were published in a paper titled Hypothalamus-hippocampus circuitry regulates impulsivity via melanin-concentrating hormone, published in the Nature journal.

The experiment was done on rats and the researchers focused on a subset of brain cells, which produce a transmitter called the melanin concentrating hormone (MCH). The researchers trained the rats so that they could press a lever to receive a high-sugar, high fat pellet and kept a timer at 20 seconds for every press. If the rat would press the lever before 20 seconds were up, the delivery of the pellet would be delayed another 20 seconds.

The researchers confirmed the findings of previous studies, which stated that MCH was responsible for increasedfood intake but also showed for the first time that it was responsible for impulsivity. They then used advanced techniques to activate MCH neural pathways between the hippocampus and hypothalamus in these mice parts of the brain responsible for learning and memory.

MCH did not interfere with the liking for the food, but rather it acted on the inhibitory control in the rats the ability to control themselves from reaching out for the pellet before 20 seconds were up. Activating the pathway increased impulsive behavior regardless of whether their body needed the calories or not.

Activating this specific pathway of MCH neurons increased impulsive behavior without affecting normal eating for caloric need or motivation to consume delicious food. Understanding that this circuit, which selectively affectsfoodimpulsivity, exists opens the door to the possibility that one day we might be able to develop therapeutics for overeating that help people stick to a diet without reducing normal appetite or making delicious foods less delicious," Noble stated.

s According to the World Population Review, Micronesian country Nauru holds the position as the most obese country in the world. Pictured: A physiotherapist (L) assists obese patients with exercises in an obesity unit at the CHU Angers teaching hospital. Photo: Getty Images/Jean-Sebastien Evrard

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Brain Circuitry Holds Key To Treating Obesity: Study - International Business Times

A 2019 study by the University of Colorado Boulder, published in the Journalof Experimental Physiology, proposed a new potential mechanism through which one can trace howsleepinfluences an individualshearthealthand overall physiology.The study states that people who do not get 7 hours ofsleepat night often suffer from lower blood levels of microRNAs that play a key role in maintaining vascularhealth.Through time, while such studies have led to the discovery that people who do not get enoughsleepare at a greater risk of experiencing a stroke orheartattack. There is an increased risk of cardiovascular disease and death in persons whosleepless than 6 hours every day than those whosleepmore.Dr Santosh Kumar Dora, Senior Cardiologist, Asian Heart Institute, Mumbai lists effects of sleep deprivation and tips to sleep well.

ALSO READ|Easy And Healthy Drinks To Keep You Warm And Healthy This Winter Season

The effect of acutesleepdeprivation results in cognitive impairment, which includes deficits in behavioural alertness and vigilant attention, lack of logical reasoning, errors in simple tasks, accidents, poor work performance, poor mood, irritability, low energy, decreased libido and poor judgement.On the other hand, chronicsleepdeprivation (CSD) results in accidents, workplace errors, inappropriate drowsiness and unplanned naps with consequences both at home and at the workplace.

One must thus cultivate healthysleepinghabits for a healthyheart, never underestimating the importance of a good nightssleep. The prescribed duration ofsleepis nothing less than 7 to 9 hrs. The depth ofsleepis as important as its duration as this happens to be the time when the body undergoes repair, restoration and rest.

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The following are a few tips to help yousleepwell:

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Disclaimer: The content provided above is for information purposes. This is no way intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health providers with any questions you may have regarding a medical condition.

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Effects of sleep deprivation and tips to follow to sleep well - Republic World - Republic World

Female cyclists are at a lower risk of suffering Sudden Cardiac Death than male athletes, but women should still learn about ways to screen for heart problems before engaging in endurance sports.

Dr. Mehreen Quhreshi is a cardiologist with advanced training in stress testing and cardiac imaging from Columbia University Medical Center in New York. She practices in Harrisburg, Pennsylvania and serves as the director of the Preventative Cardiology Program and the Nuclear Stress Lab at UPMC Pinnacle Heart and Vascular Institute. Dr. Bill Apollo, an amateur bike racer, runner, and duathlete is a Harrisburg, Pennsylvania-based cardiologist, who directs the UPMC Pinnacle Sports and Exercise Cardiology Clinic.

At the Paris Olympics in 1900, endurance sports were exclusively dominated by men; a mere 22 women participated, competing in the five gentrified events of croquet, equestrian, golf, tennis, and sailing. It took until the latter half of the twentieth century for the world to witness women competing in major Olympic endurance sports such as cycling (Los Angeles, 1984) and triathlon (Sydney, 2000).

Wider womens participation in the Olympics roughly coincided with the establishment of Title IX of the United States Educational Amendments of 1972, which mandated equal access for women in any program that received Federal funding including sports in public schools and universities. These two major developments fueled an explosion of female participation in a variety of events at all skill levels. The percentage of women finishers in marathons in the U.S. rose from only 10% in 1980 to a robust 45% by 2015. Women set a new record for Olympic participation at the 2016 Rio Olympics, with nearly equal numbers (5,176 athletes, or 45% of total), and with representation in all events included in the games.

Paradoxically, women have generally been under-represented in medical research studies looking at cardiac health, adaptation to endurance training and its potential consequences. Despite this surge of female athletic participation, we still havent achieved gender equality when it comes to understanding and caring for the female athletes heart. And recent small-scale studies suggest that there are in fact important cardiac differences between the sexes.

Some of the key questions are: to what extent do underlying genetic and hormonal factors impact normal changes in a womans heart related to exercise? How do these influences alter her risk for developing chronic heart problems or sudden cardiac death during competition? Are women better equipped to handle endurance training by design? Some recent research suggests that pregnancy subjects the female body to cardiac stresses similar to those that male athletes experience in even the most competitive events, including events like the Tour de France.

Below we examine the current understanding of cardiac development and risks in women endurance athletes, how and why women may differ from men in this regard, and recommended precautions that should be taken in training and competition by elite female endurance athletes.

Sudden cardiac death (SCD) during athletic competition is fortunately a rare occurrence, and it tends to affect men more commonly than women. In fact, a womans risk of SCD during endurance sports is estimated to be some 10 times lower than for her male colleagues. Professional cycling, during the past 3 seasons, has seen a total of 6 elite men tragically die directly from heart problems during races (5 in road racing, 1 on the track), with the most recent being Robbert de Greef in March 2019. During the same time period, there were zero incidents involving women, and indeed there are no known reports of SCD during elite womens cycling events for the past 20 years. Professional female cyclists are far more likely to die from training accidents (usually involving automobile collisions) than from heart problems.

Interestingly, these observations regarding SCD in cycling seem not to be true for other endurance sports. Marathon running has a huge participant base much larger than the womens pro peloton with nearly a half million participants in 2019 alone. This huge statistical sampling clarifies the measure of SCD risk: 1 incident per 150,000 participants overall, but more commonly occurring in men (1/ 100,000), and much less likely to occur in women (1/243,000).

Despite this fairly low risk of SCD in women, the sheer volume of running participants makes it easier to find reports of SCD. For example, Taylor Ceepo, age 22, died in May 2019 less than 1 mile from the finish line at the Rite-Aid Cleveland Marathon. The medical examiners report indicated that Ceepo experienced sudden cardiac death in association with physical exertion, pseudoephedrine use (a fairly benign over-the-counter decongestant) and cardiomyopathy. Her tragedy should remind us that even in very young and apparently healthy women, undiagnosed heart disease is still a common killer (3rd behind unintentional injuries and cancer in her age group), and her autopsy findings highlight the importance of screening women for underlying heart problems.

The most common causes of SCD are generally driven by age rather than sex. Athletes under age 35 both men and women alike are susceptible to genetically inherited structural heart problems including hypertrophic cardiomyopathy (HCM) and arrhythmogenic right ventricular cardiomyopathy (ARVC), as well as potentially lethal heart rhythm problems called channelopathies. Above age 35, coronary artery disease predominates, with women being preferentially protected by their higher estrogen levels, until they reach menopause. Initially, the ten-fold higher incidence of SCD in men was thought to be simply due to the much larger numbers of men participating in endurance sports. But now that participation rates are becoming nearly equal, womens risk of SCD is still not as high as that experienced in the male population.

Several theories exist that might explain why women appear to be more protected from SCD during intense competition. One explanation may lie in the sympathetic nervous system, which is responsible for the bodys fight or flight response. Male physiology is observed to be wound more tightly, meaning that their arteries and blood vessels tend to constrict more during intense activity than women. The increased blood pressure adds resistance to blood the heart is pumping out. When this increased pressure load is coupled with an outpouring of adrenaline during competition, the strains placed on the heart may trigger lethal rhythm problems in susceptible individuals generally those with underlying inherited cardiac problems or acquired fibrosis (scarring) from long-term training. For unclear reasons, even in the context of equal training volumes, men more commonly develop potentially lethal fibrosis substrate, placing them at higher risk of SCD than women.

Another possible explanation relates to obvious hormonal differences between men and women. In some animal models, testosterone has been shown to affect the way the heart conducts impulses making men, at least in theory more susceptible than women to developing electrical instability resulting in malignant heart arrhythmias. Clinically, testosterone promotes thickening of the heart muscle, which may explain why men are more susceptible than women in developing complications from diseases like HCM and ARVC. Estrogens, on the other hand, are protective in this regard, and delay that same process of heart muscle thickening. Despite equal patterns of genetic transmission of HCM and ARVC between both sexes, hormonal differences may explain why these maladies tend to remain latent for a longer period of time in women, presumably translating to a survival advantage and lower risk of SCD.

Sports medicine screening programs are designed to identify potential cardiac risks in individuals who exhibit no outward symptoms of heart problems. Such programs aim to increase participation but to do so with a reasonable level of caution, to ensure the safety of the athlete. Despite the lower risk of SCD in women, screening is still important.

Pre-participation screening typically involves a comprehensive medical history review, focused physical examination, and in some cases an electrocardiogram (EKG). EKG tests are proven to be more sensitive than history and physical examination alone in detecting pathology, especially regarding heart rhythm issues. EKG interpretation should always be completed by a skilled reader able to distinguish the fine line between normal adaptation to exercise and pathology. Guidelines like the International Recommendations for EKG Interpretation in Athletes will increase reading accuracy and reduce the number of false findings, which often lead to expensive and unnecessary longitudinal testing. Men exhibit changes in their EKG patterns more often than women, and these variations in many instances are considered normal purely as the result of physiologic adaptation to training. On the other hand, women are less likely to stray from normal parameters, so most EKG changes are concerning and more likely represent a real problem.

Consistent endurance training induces physiologic remodeling, or normal adaptations to the heart resulting in improved efficiency of an athletes engine. Cyclists are unique because they typically perform the most prolonged exercise pattern more hours per day and more days per year than nearly any other athletes. Cyclists often sustain markedly elevated heart rates for extended periods of time during two distinct types of high cardiac output workouts. First, high intensity aerobic workouts at near peak efficiency, coupled with sustained elevations in heart rate, create a dynamic stress, or a volume load on the heart. And second, long tempo efforts punctuated by intense anaerobic dashes create static stress, exposing the heart to a pressure load because of sustained increases in blood pressure.

Cyclists therefore typically exhibit prominent changes in heart structure due to a combination of dynamic stress (volume overload) and static stress (pressure overload) resulting in generally increased cardiac mass, with mildly enlarged hearts and mildly increased heart wall thickness at least in men. Statistically, women are generally smaller than men with lower lean body mass. Due to their higher estrogen levels, women tend to adapt to exercise in a qualitatively similar manner, but quantitatively different than men showing only minimal heart enlargement and virtually no heart wall thickening. In fact, only about 7% of healthy women show any significant increase in their heart size due to habitual exercise, whereas 47% of men show cardiac enlargement.

Symptoms of heart problems in women are often different to those reported by men. For example, women are less likely to experience classic chest pain due to a heart problem, but may report more subtle symptoms like indigestion, heartburn, fatigue, or poor exercise performance. Misinterpretation of these sometimes confusing symptoms often leads to a delay in diagnosis and poorer long-term outcomes for women. An unexplained decline in athletic performance is obviously concerning to any elite athlete whether male or female because this may be the only clue to a serious underlying heart problem.

However, in young women, such nonspecific symptoms are often incorrectly blamed on things like menstrual problems, eating disorders, iron deficiency anemia, pregnancy, or thyroid disease. In many cases it is the womans primary care provider who must be savvy enough to exclude these other diagnoses, realizing there is a potential heart problem and then making an appropriate referral to a cardiologist.

Estrogen generally protects women from developing CAD at young ages, but the risk rises as they reach menopause. And paradoxically, some young women may actually be at increased risk for CAD because of a syndrome called Relative Energy Deficiency in Sports (RED-S). Sports which favor lean body mass are often associated with heavy training loads and dieting to achieve optimal body weight. In some women this results in the Female Athlete Triad of menstrual dysfunction, unexplained decline in performance (with or without an eating disorder), and decreased bone density, leading to increased probability of fractures.

Prolonged endurance training in young women can lead to menstrual irregularities resulting in the same kind of reduced estrogen levels typically seen in older postmenopausal women. These athletes should be evaluated for the more traditional cardiac risk factors such as high blood pressure, cholesterol problems, and diabetes, with appropriate intervention to modify their risk. Treatment of the Female Athlete Triad is challenging and may require a multidisciplinary approach to improve an athletes overall energy balance. Strategies include decreasing training volume, modifying dietary habits, medically replacing estrogen levels, promoting bone health with dietary supplements, and seeking appropriate professional help to correct eating disorders if present. Due to the focused and highly competitive nature of many endurance athletes, this is often a tall order to fill since they may resist decreasing their training volume.

Regular exercise is the cornerstone of prevention and treatment of many cardiac and non-cardiac diseases. But some researchers suggest that the benefits of exercise are like a drug the benefits of moderate training reach a plateau and exceeding that plateau, or overdosing, may be detrimental to the athletes health. Several studies have reported unexpected abnormalities in endurance athletes primarily in men suggesting either transient or permanent heart damage which puts them at risk for chronic heart issues. Findings have included a five-fold increased risk of atrial fibrillation (AFIB), increased coronary artery calcium deposits (which indicate clinically silent CAD), and scarring of the heart muscle. However, there are several general guidelines that all athletes should be aware of:

The biological adaptation to handle the stress of pregnancy may be a key reason for the apparently better female adaptation to endurance training. Recent research has highlighted that during pregnancy, the body functions at a basal metabolic rate of 2.2 times the normal burning up to 4000 calories a day. Extended over a period of 40 weeks, pregnancy can essentially be considered the ultimate endurance event a true test on the limits of human performance. Under typical circumstances, a body functioning above 2.5 times the normal metabolic rate over a prolonged period will begin to break down. But most women emerge from pregnancy and go on to live healthy lives, having tolerated a level of metabolic strain considered by some to be similar to that experienced by athletes participating in some of the most competitive endurance events.

There are also massive changes in the amount of fluid in a womans body during pregnancy, creating cardiac stresses similar to endurance training. In order to support the developing fetus, she must increase her blood volume by a massive 50%, and her cardiac output by 40-50% constituting the ultimate dynamic stress on the heart. The female body appears to require less adaptation by the heart muscle and chambers to accommodate these changes.

More overlap in research examining the similarities between the effects of endurance training in women and the cardiac demands placed on them during pregnancy may help to explain these gender-based differences in adaptation to exercise and related cardiac risk. Additional research specifically devoted to women is critical to a better understanding of how gender influences normal cardiac adaptation to exercise, as well as to more accurately identify pathologic conditions which sometimes seem to overlap with normal physiology.

Despite the substantially lower risk of SCD in women, cardiac risk screening of female endurance athletes and at-risk pregnant women is still important, and should be carried out by clinicians familiar with the differences in adaptive physiology between men and women. Women often experience challenging and atypical cardiac symptoms, requiring a high index of suspicion on the part of their doctors often at the primary care level to identify these underlying problems. As the current generation of elite female athletes matures into tomorrows Masters champions, we will undoubtedly learn a great deal more about the long-term cardiac implications of endurance training in women.

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The Outer Line: The impact of endurance training on the cardiac health of women - VeloNews

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Every year, members of the Swedish royal family gather for Nobel Prize Award Ceremony and banquet, honoring the 2019 Nobel laureates awarded the prizes in physics, chemistry, physiology or medicine, and literature in Stockholm, Sweden. (The Nobel Peace Prize is awarded in Oslo, Norway, and the Norwegian royal family hosts that ceremony).

The Swedish royal family goes all-out for the occasion with King Carl XVI Gustaf and Queen Silvia in attendance, along with Crown Princess Victoria and her husband Prince Daniel, Princess Madeleine, and Prince Carl Philip with Princess Sofia. The royal ladies traditionally wear sparkling tiaras and formal gowns fo the event, for added dazzle.

Last year, Silvia wore one of her favorite tiaras, the stunning Queen Sophia tiara, with a diamond and emerald necklace that perfectly coordinated with her green gown. Crown Princess Victoria, who is the heir to the Swedish throne, made a statement in the Connaught 'Forget-me-not" tiara, a diamond topper with circular detailing. Sofia went with pearls for her jewelry look, wearing the diamond and pearl Palmette tiara with a matching pearl choker.

Here, we've rounded up the standout tiaras as seen at the Nobel Prize Award Ceremony in Stockholm today:

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Queen Silvia and Crown Princess Victoria

Silvia chose a gown with intricate gold detailing, while Victoria opted for a black off-the-shoulder style. Both royals wore tiaras.

Queen Silvia

Silvia wore one of her favorite tiaras, the Queen Sophia tiara, which is also called the Nine Prong tiara,. Silvia also wore it to last year's Nobel Prize ceremony.

Crown Princess Victoria

Victoria wore the sparkling Baden fringe diamond tiara, paired with a diamond necklace and the Braganza Rose diamond brooch.

Princess Sofia and Princess Madeleine

Princess Sofia arrives at the ceremony with Princess Madeleine. Madeleine, who did not attend the Nobel Prize ceremony last year, wore a pink gown and an aquamarine tiara.

Princess Sofia

Sofia went for an all-blue ensemble, wearing a blue off-the-shoulder gown with her diamond wedding tiara, which was accented by new blue stones. The stones appear to be turquoises.

Princess Sofia

On her wedding day, Sofia's tiara was set with emeralds, but she has swapped out those stones on a few occasions. The Princess has replaced the stones with pearls in the past, like at the Nobel Prize ceremony in 2017 and 2018.

Princess Sofia

Another look at Sofia's tiara.

Princess Madeleine

Madeleine chose the Swedish Aquamarine Kokoshnik tiara, which once belonged to Princess Margaretha. The stunning diamond piece has been worn by Madeleine before, and by Crown Princess Victoria wore the tiara to the 2017 Nobel Prize Awards, per the Court Jeweller.

Princess Madeleine

A full look at her pink ensemble.

Princess Madeleine

Madeleine also wore dazzling diamond earrings and a matching bracelet with her tiara and sash.

Princess Madeleine

Another view of Madeleine's tiara at the Nobel Prize banquet.

Queen Silvia

Silvia's stunning brooch is on display as she arrives at the Nobel Prize banquet.

Princess Sofia

A look at Sofia's coordinating turquoise earrings, which perfectly match her tiara.

Princess Sofia

The new blue stones on the top of Sofia's diamond tiara were front and center as the royal sat during the Nobel Prize banquet.

Princess Madeleine

Another look at Madeleine's tiara.

Crown Princess Victoria

Victoria dazzled in the Baden fringe tiara.

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The Swedish Royal Family Wore Dazzling Tiaras to the Nobel Prize Ceremony - TownandCountrymag.com

Images of monkeys undergoing experiments in a German laboratory stirred a wave of public outrage recently, prompting questions whether such barbaric procedures are necessary in the 21st century. Technology exists today that could replace animal testing in the future, but how far is it from practical use?

In 2018, a team of Oxford University researchers announced that their computer models of human heart cells were able to predict side effects of various medications on the heart more accurately than animal studies.

While studies done on animals assessed the risk of arrythmias in human users with the accuracy of 75-85 per cent, the computer model of actual human heart cells made a correct prediction in 89-96 per cent of cases. That means that drugs could pass the animal tests but still later cause dangerous heart problems in patients, while this risk is lower when using computer models.

We took 62 drugs such as painkillers, antihistamines or antibiotics, many of which are on the market, and we looked for biomarkers indicating the risk of arrhythmias in our simulations, says Elisa Passini, a senior researcher in the Computational Cardiovascular Science team at the University of Oxford and the lead author of the paper published in the journal Frontiers in Physiology. Then we compared our results with what is known about these drugs. For example, there are reports of patients who have had a cardiac episode while taking these drugs. We compared our results with these reports and thats how we calculated the accuracy.

Passini says the difference in favour of the human heart cells computer model might arise because animal cells and organs, while having been widely used in drug development for decades, are in many ways similar to but by no means identical to human organs and cells.

Sometimes you dont see an effect in animals and then, if you give the drug to a human being, you will see an adverse effect on the heart, she adds.

In fact, according to a 2009 paper by Yale University epidemiologist Michael B Bracken, which was published in the Journal of the Royal Society of Medicine, there have been many cases in the past when drugs deemed safe in animal studies in fact caused serious harm once introduced to humans.

For example, thalidomide, a drug sold in the late 1950s and early 1960s as a sedative and treatment for morning sickness for pregnant women caused the foetuses to develop serious defects. Such side effects were not observed in animal studies.

A 2006 UK-based phase I clinical study of am immunomodulatory drug called TGN1412 (theralizumab), designed to alleviate symptoms of autoimmune diseases, caused life-threatening side-effects to all of the six previously healthy human volunteers enrolled in the study who were given the drug. Although they received doses 500 times lower than what had been found safe in animal studies, the human subjects quickly developed multi-organ failures and required lengthy hospitalisation. The drug had previously successfully passed tests not only in mice but also in rhesus monkeys, which up until then had been considered very similar to humans in their physiology.

Hazel Screen, a professor of biomedical engineering at Queen Mary University of London (QMUL), says that despite decades of use and refinement, the success rate in drug development based on the current animal models is extremely low.

Today, if something goes into clinical trials because it worked in animal models, the likelihood of it coming off is terrible, says Screen, who co-leads a project developing organ-on-a-chip technology another alternative that could replace animal tests in the future.

It currently takes approximately 14 years to develop a drug and only about 5 per cent of drugs actually end up being used to treat patients, she says.

Screen agrees with Passinis statement that one of the reasons for such a poor outcome is the fact that the cells, bodies and physiological processes of animals, while in many ways similar, simply do not perfectly match those of humans.

Screens colleague Professor Martin Knight says big pharma companies, hoping to improve this abysmal success rate, are looking for alternative technologies to at least partially replace animal tests.

Big pharma companies are primarily interested in increasing profits by getting better benefits for patients, rather than reducing animal testing per se, Knight says. They want to be able to predict more accurately whether these drugs are going to work and make sure that they progress more efficiently through the development pipeline.

According to the UK Home Office, 3.52 million scientific procedures were carried out in 2018 in the UK involving living animals, with mice, rats and fish making up 93 per cent of the total number.

The amount, the Home Office said, decreased by 7 per cent compared to 2017. Of the total amount, 1.80 million procedures were for experimental purposes, focusing on basic research, the development of new treatments, safety testing of pharmaceuticals, surgical training and education. The rest focused on the creation and breeding of genetically altered animals.

The cost of these experiments is substantial, especially since regulators, pressured by the 21st-century animal-rights-conscious public, require the scientists to improve conditions and minimise pain and suffering of the creatures used.

Many pharma companies are interested in the in-silico simulations of the Oxford University team, according to Passini. The team, which is part of the EU-funded Compbiomed initiative, has developed a software called Virtual Assay, which can run on a regular laptop and complete a simulation of 100 human heart cells interacting with a certain drug in about five minutes.

Our models are built on data from human patients, says Passini. Its usually patients that have gone through some surgery during which the doctors removed some cells, which were further studied. We also use data from healthy hearts that were not suitable for transplantations. The models are based on a large number of equations that represent what we know about the cardiac cells, their behaviour, their membranes, and the transport of ions in and out of cells.

These models, Passini says, are now quite ready to replace the early stage so-called in-vitro experiments experiments conducted on animal cells or small tissue samples.

We hope that our technology could in the not so distant future replace most of the in-vitro experiments, she adds. That would already make a huge difference because very large numbers of animals are used for these early stage experiments. The scientists kill the animals and take their cells. A much smaller number of animals is used for the later-stage in-vivo experiments.

The Oxford team can already run 3D simulations of an entire human heart. The availability of computational power, or lack thereof, is, however, the major stumbling block for this type of complex simulation.

We have access to some of the most powerful supercomputers in Europe, but it still takes hours to simulate a single heartbeat in 3D, Passini adds. We can afford to do this for scientific purposes, but the availability of such computer power is still limiting the use of these simulations by the industry. We are exploring alternatives, such as GPUs, which might make it more affordable in the future.

The Compbiomed project, which has recently concluded its first stage, has the ultimate goal of creating the entire human organism in silico that could be used for drug testing and simulations of various health conditions.

QMULs Knight says that the organ-on-a-chip technology could in the future reduce the number of mice, the most commonly used animal species in medical research, needed at certain stages of the drug development process. But for that to happen, the alternative technologies have to be validated and proved as reliable (if not more) as the currently used animal models.

The regulatory authorities are understandably going to be nervous about accepting results entirely from a completely new technology compared to using a set of well-established, if not always very accurate, animal models, Knight declares.

For them to accept new technologies, such as organ-on-a-chip, you have to prove that your liver, lung or gut model works in every imaginable set-up. Thats a lot of science and validation and confirmation before you reach that point.

Organ-on-a-chip systems use living human cells in a 3D device to mimic how human organs function. These devices can be used to test both the safety and efficacy of new medicines and other products, reducing the dependency on animal experiments. Usually the size of a 50-pence coin, chips already exist simulating human liver, lung and intestine.

Creating an environment that would simulate, as closely as possible, the environment in which the cells exist in the human body is the greatest engineering challenge facing the researchers.

Its become clear recently that mechanical forces have a huge impact on cell biology and therefore on how drugs behave, says Knight. Therefore, we need to make sure that the model systems that are being developed incorporate the right mechanical forces that the different tissues experience. For example, a model of the lung has to incorporate stretching as you inflate your lung; it has to incorporate the flow of air over the surface of the cells of the lung and the flow of blood in the blood vessels. And only by incorporating these key mechanical stimuli can we hope to generate a model that is truly predictive of how a drug is to behave in a body.

Last year, QMUL received a grant from Research Councils UK to lead a network that aims to bring together the UK research community in order to advance organ-on-a-chip development and cooperate with regulators and industry on validating the technology so that it can be rolled out on a larger scale.

While the complete end of animal experiments in medical science may be decades away, the researchers are positive that with the introduction of already existing technologies, their validation and further improvement, the numbers of animals required for the advancement of science will be gradually but significantly reduced over the coming decades.

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Is the end of animal testing in sight? - E&T Magazine