Physics-informed machine learning: case studies for weather and climate modelling.

Machine learning (ML) provides novel and powerful ways of accurately and efficiently recognizing complex patterns, emulating nonlinear dynamics, and predicting the spatio-temporal evolution of weather and climate processes. Off-the-shelf ML models, however, do not necessarily obey the fundamental governing laws of physical systems, nor do they generalize well to scenarios on which they have not been trained. We survey systematic approaches to incorporating physics and domain knowledge into ML models and distill these approaches into broad categories. Through 10 case studies, we show how these approaches have been used successfully for emulating, downscaling, and forecasting weather and climate processes. The accomplishments of these studies include greater physical consistency, reduced training time, improved data efficiency, and better generalization. Finally, we synthesize the lessons learned and identify scientific, diagnostic, computational, and resource challenges for developing truly robust and reliable physics-informed ML models for weather and climate processes. This article is part of the theme issue 'Machine learning for weather and climate modelling'.

Genetic influences on eight psychiatric disorders based on family data of 4 408 646 full and half-siblings, and genetic data of 333 748 cases and controls.

BACKGROUND: Most studies underline the contribution of heritable factors for psychiatric disorders. However, heritability estimates depend on the population under study, diagnostic instruments, and study designs that each has its inherent assumptions, strengths, and biases. We aim to test the homogeneity in heritability estimates between two powerful, and state of the art study designs for eight psychiatric disorders. METHODS: We assessed heritability based on data of Swedish siblings (N = 4 408 646 full and maternal half-siblings), and based on summary data of eight samples with measured genotypes (N = 125 533 cases and 208 215 controls). All data were based on standard diagnostic criteria. Eight psychiatric disorders were studied: (1) alcohol dependence (AD), (2) anorexia nervosa, (3) attention deficit/hyperactivity disorder (ADHD), (4) autism spectrum disorder, (5) bipolar disorder, (6) major depressive disorder, (7) obsessive-compulsive disorder (OCD), and (8) schizophrenia. RESULTS: Heritability estimates from sibling data varied from 0.30 for Major Depression to 0.80 for ADHD. The estimates based on the measured genotypes were lower, ranging from 0.10 for AD to 0.28 for OCD, but were significant, and correlated positively (0.19) with national sibling-based estimates. When removing OCD from the data the correlation increased to 0.50. CONCLUSIONS: Given the unique character of each study design, the convergent findings for these eight psychiatric conditions suggest that heritability estimates are robust across different methods. The findings also highlight large differences in genetic and environmental influences between psychiatric disorders, providing future directions for etiological psychiatric research.

Hydrogen-poor superluminous stellar explosions.

Supernovae are stellar explosions driven by gravitational or thermonuclear energy that is observed as electromagnetic radiation emitted over weeks or more. In all known supernovae, this radiation comes from internal energy deposited in the outflowing ejecta by one or more of the following processes: radioactive decay of freshly synthesized elements (typically (56)Ni), the explosion shock in the envelope of a supergiant star, and interaction between the debris and slowly moving, hydrogen-rich circumstellar material. Here we report observations of a class of luminous supernovae whose properties cannot be explained by any of these processes. The class includes four new supernovae that we have discovered and two previously unexplained events (SN 2005ap and SCP 06F6) that we can now identify as members of the same class. These supernovae are all about ten times brighter than most type Ia supernova, do not show any trace of hydrogen, emit significant ultraviolet flux for extended periods of time and have late-time decay rates that are inconsistent with radioactivity. Our data require that the observed radiation be emitted by hydrogen-free material distributed over a large radius (∼10(15) centimetres) and expanding at high speeds (>10(4) kilometres per second). These long-lived, ultraviolet-luminous events can be observed out to redshifts z > 4.

Plastic and evolutionary responses to heat stress in a temperate dung fly: negative correlation between basal and induced heat tolerance?

Extreme weather events such as heat waves are becoming more frequent and intense. Populations can cope with elevated heat stress by evolving higher basal heat tolerance (evolutionary response) and/or stronger induced heat tolerance (plastic response). However, there is ongoing debate about whether basal and induced heat tolerance are negatively correlated and whether adaptive potential in heat tolerance is sufficient under ongoing climate warming. To evaluate the evolutionary potential of basal and induced heat tolerance, we performed experimental evolution on a temperate source population of the dung fly Sepsis punctum. Offspring of flies adapted to three thermal selection regimes (Hot, Cold and Reference) were subjected to acute heat stress after having been exposed to either a hot-acclimation or non-acclimation pretreatment. As different traits may respond differently to temperature stress, several physiological and life history traits were assessed. Condition dependence of the response was evaluated by exposing juveniles to different levels of developmental (food restriction/rearing density) stress. Heat knockdown times were highest, whereas acclimation effects were lowest in the Hot selection regime, indicating a negative association between basal and induced heat tolerance. However, survival, adult longevity, fecundity and fertility did not show such a pattern. Acclimation had positive effects in heat-shocked flies, but in the absence of heat stress hot-acclimated flies had reduced life spans relative to non-acclimated ones, thereby revealing a potential cost of acclimation. Moreover, body size positively affected heat tolerance and unstressed individuals were less prone to heat stress than stressed flies, offering support for energetic costs associated with heat tolerance. Overall, our results indicate that heat tolerance of temperate insects can evolve under rising temperatures, but this response could be limited by a negative relationship between basal and induced thermotolerance, and may involve some but not other fitness-related traits.

Atom-scale compositional distribution in InAlAsSb-based triple junction solar cells by atom probe tomography.

The analysis by atom probe tomography (APT) of InAlAsSb layers with applications in triple junction solar cells (TJSCs) has shown the existence of In- and Sb-rich regions in the material. The composition variation found is not evident from the direct observation of the 3D atomic distribution and because of this a statistical analysis has been required. From previous analysis of these samples, it is shown that the small compositional fluctuations determined have a strong effect on the optical properties of the material and ultimately on the performance of TJSCs.

A new highly penetrant form of obesity due to deletions on chromosome 16p11.2.

Obesity has become a major worldwide challenge to public health, owing to an interaction between the Western 'obesogenic' environment and a strong genetic contribution. Recent extensive genome-wide association studies (GWASs) have identified numerous single nucleotide polymorphisms associated with obesity, but these loci together account for only a small fraction of the known heritable component. Thus, the 'common disease, common variant' hypothesis is increasingly coming under challenge. Here we report a highly penetrant form of obesity, initially observed in 31 subjects who were heterozygous for deletions of at least 593 kilobases at 16p11.2 and whose ascertainment included cognitive deficits. Nineteen similar deletions were identified from GWAS data in 16,053 individuals from eight European cohorts. These deletions were absent from healthy non-obese controls and accounted for 0.7% of our morbid obesity cases (body mass index (BMI) >or= 40 kg m(-2) or BMI standard deviation score >or= 4; P = 6.4 x 10(-8), odds ratio 43.0), demonstrating the potential importance in common disease of rare variants with strong effects. This highlights a promising strategy for identifying missing heritability in obesity and other complex traits: cohorts with extreme phenotypes are likely to be enriched for rare variants, thereby improving power for their discovery. Subsequent analysis of the loci so identified may well reveal additional rare variants that further contribute to the missing heritability, as recently reported for SIM1 (ref. 3). The most productive approach may therefore be to combine the 'power of the extreme' in small, well-phenotyped cohorts, with targeted follow-up in case-control and population cohorts.

Effect of commercial cleansers on skin barrier permeability.

BACKGROUND: Addition of hydrophobically modified polymers (HMPs) to cleansers can reduce the negative impact of surfactant-based cleansers. In this study, the effects of a cleanser containing HMPs, a gentle lotion cleanser (GLC), water, and 1% sodium lauryl sulfate (SLS) on barrier permeability, were evaluated in vitro in pig skin and in vivo in humans. METHODS: Skin stratum corneum (SC) barrier function was quantitated by imaging fluorescence intensity of the sulforhodamine B (SRB) in a pig skin model system using 2-photon and conventional fluorescence confocal microscopy. Solutions containing SRB were applied to pig skin in Franz diffusion cells over a period of 2 h. Penetration of SRB into the skin was monitored from 2 µm to 38 µm. In vivo surfactant/cleanser penetration in human skin was determined using tape stripping. RESULTS: After 2 h, water, 1% SLS, and GLC, significantly increased SRB intensity at all depths measured. SRB intensity was reduced in the HMP-cleanser group compared with other groups at each depth. In vivo, the presence of HMP reduced SLS penetration as measured by tape stripping. CONCLUSION: The cleanser containing HMP prevented changes in SC permeability and surfactant penetration, indicating a protective effect on skin barrier properties.

Contractures and muscle disease.

Contractures are one of a handful of signs in muscle disease, besides weakness and its distribution, whose presence can help guide us diagnostically, a welcome star on the horizon. Contractures are associated with several myopathies, some with important cardiac manifestations, and consequently are important to recognise; their presence may also provide us with a potential satisfying 'penny dropping' diagnostic moment.

Experimental evolution for generalists and specialists reveals multivariate genetic constraints on thermal reaction norms.

Theory predicts the emergence of generalists in variable environments and antagonistic pleiotropy to favour specialists in constant environments, but empirical data seldom support such generalist-specialist trade-offs. We selected for generalists and specialists in the dung fly Sepsis punctum (Diptera: Sepsidae) under conditions that we predicted would reveal antagonistic pleiotropy and multivariate trade-offs underlying thermal reaction norms for juvenile development. We performed replicated laboratory evolution using four treatments: adaptation at a hot (31 °C) or a cold (15 °C) temperature, or under regimes fluctuating between these temperatures, either within or between generations. After 20 generations, we assessed parental effects and genetic responses of thermal reaction norms for three correlated life-history traits: size at maturity, juvenile growth rate and juvenile survival. We find evidence for antagonistic pleiotropy for performance at hot and cold temperatures, and a temperature-mediated trade-off between juvenile survival and size at maturity, suggesting that trade-offs associated with environmental tolerance can arise via intensified evolutionary compromises between genetically correlated traits. However, despite this antagonistic pleiotropy, we found no support for the evolution of increased thermal tolerance breadth at the expense of reduced maximal performance, suggesting low genetic variance in the generalist-specialist dimension.

Associations of blood glucose and prevalent diabetes with risk of cardiovascular disease in 500 000 adult Chinese: the China Kadoorie Biobank.

AIMS: To examine the relationship of self-reported diabetes, and of random blood glucose levels among individuals without known diabetes, with the prevalence of cardiovascular disease in Chinese adults. METHODS: We examined cross-sectional data from the China Kadoorie Biobank of 0.5 million people aged 30-79 years recruited from 10 diverse regions of China in the period 2004-2008. Logistic regression was used to estimate the odds ratios of prevalent cardiovascular disease associated with self-reported diabetes, and with measured random blood glucose levels among participants with no history of diabetes, adjusting simultaneously for age, sex, area, education, smoking, alcohol, blood pressure and physical activity. RESULTS: A total of 3.2% of participants had self-reported diabetes (men 2.9%; women 3.3%) and 2.8% had screen-detected diabetes (men 2.6%; women 2.8%), i.e. they had no self-reported history of diabetes but a blood glucose level suggestive of a diagnosis of diabetes. Compared with individuals without a history of diabetes, the odds ratios associated with self-reported diabetes were 2.18 (95% CI 2.06-2.30) and 1.88 (95% CI 1.75-2.01) for prevalent ischaemic heart disease and stroke/transient ischaemic attack, respectively. Among participants without self-reported diabetes there was a positive association between random blood glucose and ischaemic heart disease and stroke/transient ischaemic attack prevalence (P for trend <0.0001). Below the diabetic threshold (<11.1 mmol/l) each additional 1 mmol/l of random blood glucose was associated with 4% (95% CI 2-5%) and 5% (95% CI 3-7%) higher odds of prevalent ischaemic heart disease and stroke/transient ischaemic attack, respectively. CONCLUSIONS: In this adult Chinese population, self-reported diabetes was associated with a doubling of the odds of prevalent cardiovascular disease. Below the threshold for diabetes there was still a modest, positive association between random blood glucose and prevalent cardiovascular disease.

Muscle diseases: mimics and chameleons.

Muscle diseases are not as common as headaches and funny turns in our general neurology clinics, but most of us will encounter them. We all pride ourselves on a methodical approach to clinical problems-discovering the where and what in neurological parlance-but any diagnostic process can unravel, particularly if one condition resembles another. Before we settle on a diagnosis, we need to ask ourselves, whether the 'ducks all line up' to avoid cases of mistaken identity.

Distinct and shared genetic architectures of Gestational diabetes mellitus and Type 2 Diabetes Mellitus.

Gestational diabetes mellitus (GDM) affects more than 16 million pregnancies annually worldwide and is related to an increased lifetime risk of Type 2 diabetes (T2D). The diseases are hypothesized to share a genetic predisposition, but there are few GWAS studies of GDM and none of them is sufficiently powered to assess whether any variants or biological pathways are specific to GDM. We conducted the largest genome-wide association study of GDM to date in 12,332 cases and 131,109 parous female controls in the FinnGen Study and identified 13 GDM-associated loci including 8 novel loci. Genetic features distinct from T2D were identified both at the locus and genomic scale. Our results suggest that the genetics of GDM risk falls into two distinct categories - one part conventional T2D polygenic risk and one part predominantly influencing mechanisms disrupted in pregnancy. Loci with GDM-predominant effects map to genes related to islet cells, central glucose homeostasis, steroidogenesis, and placental expression. These results pave the way for an improved biological understanding of GDM pathophysiology and its role in the development and course of T2D.

Quality of life and control of allergic rhinitis in patients from regions beyond western Europe and the United States.

There is comparatively little information on health-related quality of life (HRQoL) in subjects with allergic rhinitis (AR) or allergic rhinoconjunctivitis (AR/C) in countries beyond western Europe and North America. The primary aim of this investigation was therefore to review and assess the information in the public domain on HRQoL in AR/C patients from diverse regions of the world, represented by different countries, including Argentina, Australia, Brazil, Russia, Singapore, South Africa and Turkey. Second, in view of the absence of a standardized definition for 'AR control', the review aimed to determine whether a working definition of AR/C can be inferred from validated tests or other instruments documented to date. Despite the comparatively low number of studies, this review demonstrated that overall the symptoms of AR/C impair the HRQoL of patients in these regions by adversely impacting sleep, daily activities, physical and mental status and social functioning, similar to that demonstrated in much larger numbers of studies of AR/C patients in Europe and the United States. Furthermore, the findings of the review suggest that 'overall' control of the disease should encompass reduction of nasal and ocular symptoms, as well as improvements in HRQoL, comorbid conditions and cognition. Although some instruments are currently available for measuring control of AR, none are capable of assessing all these aspects, emphasizing the need to develop appropriate new instruments.

Prevalence and diversity of allergic rhinitis in regions of the world beyond Europe and North America.

BACKGROUND: There is comparatively little information in the public domain on the diversity in prevalence and triggers/factors associated with allergic rhinitis (AR) or allergic rhinoconjunctivitis (AR/C) in countries beyond western-Europe and North America. OBJECTIVE: To review the prevalence and the sensitizing agents/triggers and factors associated with AR/C in several countries in Africa, the Asia-Pacific region, Australia, Eastern Europe, Latin America, Middle East and Turkey. METHODS: Articles published in English in peer-reviewed journals were assessed and selected for further review, following an extensive literature search using the Medline database. RESULTS: This review demonstrated that prevalence of AR and AR/C in these regions has predominantly been investigated in children; with studies indicating wide inter- and intra-regional variations ranging from 2.9% AR and 3.8% AR/C in 10-18-years-old children from one region in Turkey to 54.1% AR and 39.2% AR/C in 13-14-years-old children in one region in Nigeria. Moreover, the prevalence of AR and AR/C has increased markedly over the last decade particularly in some of the more affluent African countries, China-Taiwan and several Middle East countries, likely as a consequence of improved living standards leading to increased exposure to multiple traditional and non-traditional sensitizing agents and risk factors similar to those noted in western-Europe and North America. CONCLUSIONS AND CLINICAL RELEVANCE: Our findings suggest that the greater diversity in prevalence of AR or AR/C in populations in these regions is in contrast to the lower diversity of AR or AR/C in the 'western populations (USA and Europe), which tend to be more uniform. This review provides a comprehensive database of the important allergens and triggers which are likely to influence the prevalence of allergic rhinitis in these diverse regions, where the prevalence of allergic rhinitis is increasing and its adverse impact on the quality of life of affected individuals is increasingly recognised.

Lower prevalence of varicoceles in obese patients found on routine scrotal ultrasound.

PURPOSE: Research shows that obese patients have a lower incidence of varicoceles. Increased adipose tissue, which makes physical examination difficult, was hypothesized to be the cause. We evaluated the varicocele incidence on routine scrotal ultrasound to see whether difficult physical examination was causative. MATERIALS AND METHODS: We reviewed all scrotal ultrasounds from the last 2 years for men 18 to 40 years old who had a recorded body mass index. Physical examination findings and the indication for ultrasound were included. We used standard criteria for ultrasound detected varicoceles. National Institutes of Health criteria was used to classify patients as normal-body mass index less than 25 kg/m(2), overweight-25 to 30 or obese-greater than 30. RESULTS: Of the 1,079 patients 330 (30.6%) had an ultrasound detected varicocele. Mean ± SD body mass index in those with vs without a varicocele was 26.7 ± 3.8 vs 26.0 ± 3.7 kg/m(2) (p = 0.04). On physical examination 171 patients (16.0%) had a varicocele. Mean body mass index in those with vs without a varicocele on physical examination was 26.6 ± 3.7 vs 26.4 ± 3.9 kg/m(2) (p = 0.09). We calculated varicocele frequency by body mass index for ultrasound detected varicoceles only. Of 374 normal weight patients 129 (34.5%) had a varicocele while in the overweight and obese groups 163 of 535 (30.6%) and 43 of 170 (25.6%), respectively, had a varicocele. The difference between normal and obese patients was statistically significant (p = 0.04). CONCLUSIONS: Obese patients have a lower prevalence of varicoceles detected by ultrasound. The lower prevalence is independent of physical examination and more likely due to another factor.

The relationship between anogenital distance and reproductive hormone levels in adult men.

PURPOSE: Anogenital distance is a marker for endocrine disruption in animal studies in which decreased distance has been associated with testicular dysfunction. In this study we investigated whether anogenital distance was associated with reproductive hormone levels in adult men. MATERIALS AND METHODS: A total of 116 men (mean age 36.1 ± 8.0 years) were evaluated at an andrology clinic in Houston. Anogenital distance (the distance from the posterior aspect of the scrotum to the anal verge) and penile length were measured using digital calipers. Testis size was estimated by physical examination. Linear regression was used to determine correlations between genital measurements and hormone levels. RESULTS: Anogenital distance (r = 0.20, p = 0.03) and penile length (r = 0.20, p = 0.03) were significantly associated with serum testosterone levels while total testis size was not (r = 0.17, p = 0.07). No relationship between genital length and luteinizing hormone, follicle-stimulating hormone or estradiol was identified. After adjusting for age the serum testosterone increased by 20.1 ng/dl (95% CI 1.8, 38.4; p = 0.03) for each 1 cm increase in anogenital distance. On multivariable models no statistically significant relationship existed between penile length and testosterone levels. Moreover men with hypogonadal testosterone levels (less than 300 ng/dl) had a significantly shorter anogenital distance compared to men with higher testosterone levels (31.6 vs 37.3 mm, p = 0.02). CONCLUSIONS: Anogenital distance may provide a novel metric to assess testicular function in men. Assuming that anogenital distance at birth predicts adult anogenital distance, our findings suggest a fetal origin for adult testicular function.

The relationship between anogenital distance and azoospermia in adult men.

Anogenital distance (AGD) is a marker for endocrine disruption in animal studies in which decreased male AGD has been associated with testicular dysfunction. The objective of the study was to investigate whether anogenital distance could distinguish men with obstructive azoospermia (OA) from those with nonobstructive azoospermia (NOA). To accomplish this, azoospermic men were recruited and evaluated at a men's reproductive health clinic in Houston, TX. Anogenital distance (the distance from the posterior aspect of the scrotum to the anal verge) and penile length (PL) were measured using digital calipers. Testis size was estimated by physical examination. Logistic regression was used to compare AGD lengths in men with OA and men with NOA. A total of 69 OA men (mean age: 44.2 ± 9.2) and 29 NOA men (mean age: 32.8 ± 4.8) were recruited. The NOA men possessed significantly shorter mean AGD than the men with OA (AGD: 36.3 vs. 41.9 mm, p = 0.01). An AGD of less than 30 mm, had a 91% specificity in accurately classifying NOA. Moreover, after adjustment for age, race, and BMI, an AGD of less than 30 mm yielded a significantly increased odds of NOA compared to OA (OR 5.6, 95% CI 1.0, 30.7). In summary, AGD may provide a novel metric for assessing testicular function in men and in distinguishing OA from NOA.

The relationship between anogenital distance and the efficacy of varicocele repair.

UNLABELLED: Study Type--Therapy (case series) Level of Evidence 4. What's known on the subject? and What does the study add? Anogenital distance (AGD) is a marker of genital development and adult testicular function. To date, there is no data on the clinical utility of using such an anthropomorphic variable. About 30% of men will have no improvement in semen parameters after varicocele repair. It is currently difficult to assess which patients are most likely to benefit from surgical repair. The present study showed that men with a longer AGD had a higher likelihood of improvement after varicocelectomy. As such, AGD may allow clinicians to better counsel men on the efficacy of varicocele repair. OBJECTIVE: • To investigate whether anogenital distance (AGD) can identify men most likely to show improved semen parameters after varicocele ligation, as AGD has been shown to correlate with intrinsic adult testicular function. PATIENTS AND METHODS: • Men with varicoceles who were evaluated at a men's reproductive health clinic in Houston were recruited. • AGD (the distance from the posterior aspect of the scrotum to the anal verge) was measured using digital callipers. • Logistic regression was used to compare outcomes after stratifying men based on AGD. RESULTS: • In all, 46 men with a mean (sd) age of 33.1 (6.3) years with postoperative semen data were recruited. • Semen concentration, motility, and total motile sperm count all showed significant improvement postoperatively (P < 0.01). • While 48% of men with a shorter AGD had improvements in sperm concentration postoperatively, 84% of men with a longer AGD improved (P = 0.01). • There was a trend toward a lower percentage of men (62% vs 84%) with shorter AGDs showing improvements in total motile sperm count (P = 0.09). CONCLUSION: • AGD may provide a novel metric to assess intrinsic testicular function and predict efficacy of varicocele repair.

Imaging the distribution of sodium dodecyl sulfate in skin by confocal Raman and infrared microspectroscopy.

PURPOSE: To image SDS distribution across different skin regions, to compare the permeability difference between porcine and human skin, and to evaluate the interaction between SDS and skin. METHODS: Full thickness porcine and human skin was treated with acyl chain perdeuterated SDS (SDS-d(25)) at room temperature and at 34 °C for 3, 24 and 40 h. SDS distribution in skin was monitored by confocal Raman and IR microspectroscopic imaging. Permeation profiles of SDS-d(25) in skin were derived from the band intensities of the CD(2) stretching vibrations. The interaction between SDS and skin was monitored through the CH(2) and CD(2) stretching frequencies and the Amide I and II spectral region. RESULTS: SDS-d(25) penetrates both porcine and human skin in a time and temperature-dependent manner, with slightly higher permeability through the stratum corneum (SC) in porcine skin. When SDS permeates into the SC, its chains are more ordered compared to SDS micelles. The secondary structure of keratin in the SC is not affected by SDS-d(25). CONCLUSION: The spatial distribution of SDS-d(25) in skin was obtained for the first time. Infrared microscopic imaging provides unique opportunities to measure concentration profiles of exogenous materials in skin and offers insights to interaction between permeants and skin.