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Identification and characterization of soybean germplasm and gene(s)/allele(s) for salt tolerance is an effective way to develop improved varieties for saline soils. Previous studies identified GmCHX1 (Glyma03g32900) as a major salt tolerance gene in soybean, and two main functional variations were found in the promoter region (148/150 bp insertion) and the third exon with a retrotransposon insertion (3.78 kb). In the current study, we identified four salt-tolerant soybean lines, including PI 483460B (Glycine soja), carrying the previously identified salt-sensitive variations at GmCHX1 , suggesting new gene(s) or new functional allele(s) of GmCHX1 in these soybean lines. Subsequently, we conducted quantitative trait locus (QTL) mapping in a recombinant-inbred line population (Williams 82 (salt-sensitive) × PI 483460B) to identify the new salt tolerance loci/alleles. A new locus, qSalt_Gm18 , was mapped on chromosome 18 associated with leaf scorch score. Another major QTL, qSalt_Gm03 , was identified to be associated with chlorophyll content ratio and leaf scorch score in the same chromosomal region of GmCHX1 on chromosome 3. Novel variations in a STRE (stress response element) cis -element in the promoter region of GmCHX1 were found to regulate the salt-inducible expression of the gene in these four newly identified salt-tolerant lines including PI 483460B. This new allele of GmCHX1 with salt-inducible expression pattern provides an energy cost efficient (conditional gene expression) strategy to protect soybean yield in saline soils without yield penalty under non-stress conditions. Our results suggest that there might be no other major salt tolerance locus similar to GmCHX1 in soybean germplasm, and further improvement of salt tolerance in soybean may rely on gene-editing techniques instead of looking for natural variations. [ABSTRACT FROM AUTHOR]

We present a catalogue of 507 cataclysmic variables (CVs) observed in SDSS I to IV including 70 new classifications collated from multiple archival data sets. This represents the largest sample of CVs with high-quality and homogeneous optical spectroscopy. We have used this sample to derive unbiased space densities and period distributions for the major sub-types of CVs. We also report on some peculiar CVs, period bouncers and also CVs exhibiting large changes in accretion rates. We report 70 new CVs, 59 new periods, 178 unpublished spectra, and 262 new or updated classifications. From the SDSS spectroscopy, we also identified 18 systems incorrectly identified as CVs in the literature. We discuss the observed properties of 13 peculiar CVS, and we identify a small set of eight CVs that defy the standard classification scheme. We use this sample to investigate the distribution of different CV sub-types, and we estimate their individual space densities, as well as that of the entire CV population. The SDSS I to IV sample includes 14 period bounce CVs or candidates. We discuss the variability of CVs across the Hertzsprung–Russell diagram, highlighting selection biases of variability-based CV detection. Finally, we searched for, and found eight tertiary companions to the SDSS CVs. We anticipate that this catalogue and the extensive material included in the Supplementary Data will be useful for a range of observational population studies of CVs. [ABSTRACT FROM AUTHOR]

Context: The presence of islet autoimmunity identifies individuals likely to progress to clinical type 1 diabetes (T1D). In clinical research studies, autoantibody screening followed by regular metabolic monitoring every 6 months reduces incidence of diabetic ketoacidosis (DKA) at diagnosis. Objective: We hypothesized that DKA reduction can be achieved on a population basis with a reduced frequency of metabolic monitoring visits. We reasoned that prolonged time between the development of T1D and the time of clinical diagnosis ("undiagnosed time") would more commonly result in DKA and thus that limiting undiagnosed time would decrease DKA. Methods: An analysis was conducted of data from TrialNet's Pathway to Prevention (PTP), a cross-sectional longitudinal study that identifies and follows at-risk relatives of people with T1D. PTP is a population-based study enrolling across multiple countries. A total of 6193 autoantibody (AAB)-positive individuals participated in PTP from March 2004 to April 2019. We developed models of progression to clinical diagnosis for pediatric and adult populations with single or multiple AAB, and summarized results using estimated hazard rate. An optimal monitoring visit schedule was determined for each model to achieve a minimum average level of undiagnosed time for each population. Results: Halving the number of monitoring visits usually conducted in research studies is likely to substantially lower the population incidence of DKA at diagnosis of T1D. Conclusion: Our study has clinical implications for the metabolic monitoring of at-risk individuals. Fewer monitoring visits would reduce the clinical burden, suggesting a path toward transitioning monitoring beyond the research setting. [ABSTRACT FROM AUTHOR]

Feeding rumen-protected choline (RPC) to late gestation dairy cows has potential to affect growth in offspring. The objective of this study was to evaluate the effects of in utero choline exposure on the growth, feed efficiency (FE), metabolism, and carcass quality of Angus × Holstein cattle. Multiparous Holstein cows pregnant with male (N = 17) or female (N = 30) Angus-sired calves were enrolled 21 d prepartum and randomly assigned to one of four dietary treatments varying in quantity and formulation of RPC. The treatments included a control with 0 g/d supplemental RPC (CTL), supplemental RPC fed at the recommended dose (RD) of 15 g/d from either an established RPC product (RPC1RD; ReaShure; Balchem Corp.) or choline ion from a concentrated RPC prototype (RPC2RD; Balchem Corp.), or a high dose (HD) of RPC2 fed at 22 g/d (RPC2HD). From 2 to 6 mo of age, calves were group housed and offered 2.3 kg grain/hd/d (42% CP) with ad libitum grass hay, and stepped up to a complete finishing diet by 7 mo (12.0% CP; 1.34 Mcal/kg NEg). Weight and height were measured monthly. Animal FE was measured in individual pens for 35 d at 8 mo. Feed intake was measured daily, and blood was obtained on day 18 during the FE period. Afterwards, cattle were group housed and offered a free-choice finishing diet until slaughter, where carcass yield and quality characteristics were measured. Mixed models were used in PROC MIXED (SAS, 9.4) with the fixed effects of treatment, sex, time, their interactions, and the random effect of calf. Month was the repeated measure, and preplanned contrasts were used. Blood and FE data were analyzed with the fixed effect of dam choline treatment, calf sex, and the interaction. Increasing dose of RPC tended to increase weight over the entire study period. Feeding any RPC increased hip and wither height compared with CTL, and increasing RPC dose linearly increased hip and wither height. Treatment and sex interacted on DMI whereby increasing RPC intake linearly increased DMI for males but not females. Compared with control, feeding any RPC decreased plasma insulin, glucose, and an insulin sensitivity index (RQUICKI). In utero choline exposure increased kidney–pelvic–heart fat and marbling score. Mechanisms of action for intrauterine choline exposure on offspring growth, metabolism, and carcass characteristics should be explored as they have direct implications for profitability for cattle growers and feeders. [ABSTRACT FROM AUTHOR]

This Clinical Practice Guideline addresses early mobilization and rehabilitation (EMR) of critically ill adult burn patients in an intensive care unit (ICU) setting. We defined EMR as any systematic or protocolized intervention that could include muscle activation, active exercises in bed, active resistance exercises, active side-to-side turning, or mobilization to sitting at the bedside, standing, or walking, including mobilization using assistance with hoists or tilt tables, which was initiated within at least 14 days of injury, while the patient was still in an ICU setting. After developing relevant PICO (Population, Intervention, Comparator, Outcomes) questions, a comprehensive literature search was conducted with the help of a professional medical librarian. Available literature was reviewed and systematically evaluated. Recommendations were formulated through the consensus of a multidisciplinary committee, which included burn nurses, physicians, and rehabilitation therapists, based on the available scientific evidence. No recommendation could be formed on the use of EMR to reduce the duration of mechanical ventilation in the burn ICU, but we conditionally recommend the use of EMR to reduce ICU-acquired weakness in critically ill burn patients. No recommendation could be made regarding EMR's effects on the development of hospital-acquired pressure injuries or disruption or damage to the skin grafts and skin substitutes. We conditionally recommend the use of EMR to reduce delirium in critically ill burn patients in the ICU. [ABSTRACT FROM AUTHOR]

Background: Programmed cell death receptor‐1 (PD‐1) monotherapy is a standard treatment for advanced cutaneous melanoma, but its efficacy and toxicity are defined in white populations and remain poorly characterized in other ethnic groups, such as East Asian, Hispanic and African. Objectives: To determine the efficacy and toxicity of PD‐1 monotherapy in different ethnic groups. Methods: Clinical data for patients with unresectable or advanced melanoma treated with anti‐PD‐1 monotherapy between 2009 and 2019 were collected retrospectively from five independent institutions in the USA, Australia and China. Tumour response, survival and immune‐related adverse events (irAEs) were compared by ethnicity (white vs. East Asian/Hispanic/African) across different melanoma subtypes: nonacral cutaneous (NAC)/unknown primary (UP) and acral/mucosal/uveal. Results: In total, 1135 patients were included. White patients had significantly higher objective response rate (ORR) [54%, 95% confidence interval (CI) 50–57% vs. 20%, 95% CI 13–28%; adjusted P < 0·001] and longer progression‐free survival (14·2 months, 95% CI 10·7–20·3 vs. 5·4 months, 95% CI 4·5–7·0; adjusted P < 0·001) than East Asian, Hispanic and African patients in the NAC and UP subtypes. White ethnicity remained independently associated with a higher ORR (odds ratio 4·10, 95% CI 2·48–6·81; adjusted P < 0·001) and longer PFS (hazard ratio 0·58, 95% CI 0·46–0·74; adjusted P < 0·001) in multivariate analyses after adjustment for age, sex, primary anatomical location, metastasis stage, baseline lactate dehydrogenase level, mutational status and prior systemic treatment. White and East Asian/Hispanic/African patients shared similar ORR and progression‐free survival in acral/mucosal/uveal melanomas. Similar melanoma‐subtype‐specific ethnic discrepancies were observed in complete response rate and overall survival. White patients had higher rates of gastrointestinal irAEs but lower rates of endocrine, liver and other rare types of irAEs. These differences in irAEs by ethnicity were not attributable to varying melanoma subtypes. Conclusions: Ethnic discrepancy in clinical benefit is specific to melanoma subtype, and East Asian, Hispanic and African patients with NAC and UP melanomas have poorer clinical benefits than previously recognized. The ethnic discrepancy in toxicity observed across different melanoma subtypes warrants an ethnicity‐based irAE surveillance strategy. More research is needed to elucidate the molecular and immunological determinants of these differences. What is already known about this topic?There is a great difference in response to immunotherapy between different subtypes of melanoma (cutaneous, mucosal, acral and uveal) in patients with advanced disease. What does this study add?Our data show for the first time that there are differences between different ethnic groups in terms of both response and toxicity to immunotherapy beyond the well‐appreciated discrepancies due to melanoma subtype. [ABSTRACT FROM AUTHOR]

This article examines the possible effects of the end of a federal constitutional right to abortion on clinical practice and research involving ex vivo human embryos. It first analyzes the likely outcomes of Dobbs v. Mississippi , concluding the Supreme Court will either overrule the federal constitutional abortion right or restrict it in a way that leads to its rapid disappearance. Next, the article discusses a possible increase in use of preimplantation genetic testing as one result. It then forecasts the likely ramifications of such a court decision on state legislation affecting ex vivo human embryos in two ways. It examines the possibility that victory over Roe will inspire embryo support groups to push for limitations on in vitro fertilization, perhaps on its destruction of embryos and more likely on permissible grounds for prospective parents to use in choosing embryos for transfer. It ends by discussing the prospects of new laws in some states banning or limiting research with human embryos. [ABSTRACT FROM AUTHOR]

"Dawn Songs: A Birdwatcher's Field Guide to the Poetics of Migration" is a diverse anthology edited by Jamie K. Reaser and J. Drew Lanham. The book features 114 entries by 62 contemporary writers, including 88 poems and numerous poetic essays, exploring the theme of migration in relation to birds. The poems in the anthology vary in structure and style, with only 10 of them incorporating rhyme. The entries focus on specific bird species, as well as broader topics such as seasons, climate change, and personal experiences. The book also includes a section with discussion questions and citations to the sources of the writings. Overall, "Dawn Songs" offers a unique perspective on the intersection of birds, migration, and poetry. [Extracted from the article]

The study was designed to investigate the association of Insulin-like growth factor 1 (IGF1) gene polymorphism with the reproductive performance of FUNAAB-Alpha, Sasso, and Kuroiler dual-purpose chicken breeds. To achieve this, a total of 250 healthy hens were selected at 12 wk of age and were intensively managed in cages for 52 wk. Blood sample was taken from each chicken at the 34th week and genomic DNA was extracted using Qiagentm DNA extraction kit, PCR was used to amplify the DNA fragments, and the PCR products were electrophoresed. Amplicons obtained were digested with restriction enzyme hinf1, and were further electrophoresed on 1.5% agarose gel. Data obtained were analyzed using the General linear model of SAS (2002) version 9.0 to determine the effect of IGF1 gene polymorphism and the distribution of alleles within the breeds. Results show polymorphism of the IGF1 gene and the restriction analysis indicated two alleles; A 58% and C 42% with the identification of genotypes AA, AC, and CC, and genotypic frequency of 22%, 43%, and 35%, respectively. Significant associations were observed between the polymorphism of the IGF1 gene, age of the bird at first lay, and weight of the hen at first lay. Chickens with haplotype CC came earlier into lay compared to those with the other two haplotypes (AA and AC). Therefore, the study suggests that haplotype CC could be used as a genetic marker to select for an improved laying performance in chickens. [ABSTRACT FROM AUTHOR]

The U.S. Centers for Disease Control and Prevention (CDC), state, tribal, and local health departments assess available and promising interventions and individual and population health outcomes when crafting public health recommendations. This supplement provides a snapshot of some of the science, experience, and expertise supporting the COVID-19 response. [ABSTRACT FROM AUTHOR]

Aluminium (Al) toxicity inhibits soybean root growth, leading to insufficient water and nutrient uptake. Two soybean lines ('Magellan' and PI 567731) were identified differing in Al tolerance, as determined by primary root length ratio, total root length ratio, and root tip number ratio under Al stress. Serious root necrosis was observed in PI 567731, but not in Magellan under Al stress. An F8 recombinant inbred line population derived from a cross between Magellan and PI 567731 was used to map the quantitative trait loci (QTL) for Al tolerance. Three QTL on chromosomes 3, 13, and 20, with tolerant alleles from Magellan, were identified. qAl_Gm13 and qAl_Gm20 explained large phenotypic variations (13–27%) and helped maintain root elongation and initiation under Al stress. In addition, qAl_Gm13 and qAl_Gm20 were confirmed in near-isogenic backgrounds and were identified to epistatically regulate Al tolerance via internal detoxification instead of Al3+ exclusion. Phylogenetic and pedigree analysis identified the tolerant alleles of both loci derived from the US ancestral line, A.K.[FC30761], originally from China. Our results provide novel genetic resources for breeding Al-tolerant soybean and suggest that internal detoxification contributes to soybean tolerance to excessive soil Al. [ABSTRACT FROM AUTHOR]

Introduction: Canadian Armed Forces adopted fibrinogen concentrate (RiaSTAP) for hemostatic resuscitation in the far-forward combat setting, given its potential benefits of reducing blood loss, blood transfusion and mortality, and its long storage stability and high portability. The current guidance recommends that RiaSTAP should be administered within 8 hours after reconstitution when stored at room temperature. However, little information about its stability is available. There is also a need to investigate the stability and efficacy of RiaSTAP after reconstitution and exposure to extreme temperatures in which our forces may operate.Materials and Methods: RiaSTAP was reconstituted as per manufacturer's instruction and stored at specific temperatures (-20°C, 4°C, 22°C, 35°C, 42°C, or 50°C) for up to 6 months. Reconstituted RiaSTAP was also oscillated on a rocker at 18 rpm under 22°C and 50°C. Its hemostatic function was measured using rotational thromboelastometry performed with RiaSTAP-spiked whole blood. Fibrinogen concentrations were measured by a commercial enzyme-linked immunosorbent assay (ELISA) kit. Gel electrophoresis was also conducted for initial and stored samples.Results: We found no change to the hemostatic function of reconstituted RiaSTAP after storage at -20°C for 6 months. At 4°C, no obvious changes to the hemostatic effect of reconstituted RiaSTAP relative to 0 hours were seen until 1,680 hours. At 22°C, a remarkable decrease began after storage for 168 hours. Storage at 35°C significantly decreased the hemostatic effect after 144 hours, while the storage at 42°C resulted in decreased hemostatic function after 72 hours. Finally, storage at 50°C for 8 hours resulted in complete loss of hemostatic function. Compared to the hemostatic activity, the fibrinogen concentration for reconstituted RiaSTAP showed less change over time. No apparent decline in fibrinogen concentration was seen after storage at -20°C for 6 months and at 4°C for 1,680 hours. At 22°C, there were no clear alterations until 792 hours. There was a decline in fibrinogen concentration at 35°C and 42°C after 672 and 600 hours of storage, respectively. At 50°C, little amount of fibrinogen was detected by ELISA at 8 hours. Similar changes in the hemostatic effect and fibrinogen concentration over time were observed under the rocking condition in comparison with the static condition at the same temperature. The gel electrophoresis confirmed fibrinogen degradation which increased with storage temperature and time.Conclusions: The stability of reconstituted RiaSTAP decreases with increasing storage temperature. The hemostatic function deteriorated before fibrinogen concentration and integrity were significantly altered at all temperatures for the study period except at 50°C where there was a rapid decline in both hemostatic function and fibrinogen concentration. Sample oscillation did not significantly affect its stability. The shelf life of reconstituted RiaSTAP may, therefore, be recommended accordingly when stored at different temperatures and extended to 6 days at room temperature provided that sterility is maintained. [ABSTRACT FROM AUTHOR]

Objective: To apply natural language processing (NLP) techniques to identify individual events and modes of communication between healthcare professionals and families of critically ill patients from electronic medical records (EMR).Materials and Methods: Retrospective cohort study of 280 randomly selected adult patients admitted to 1 of 15 intensive care units (ICU) in Alberta, Canada from June 19, 2012 to June 11, 2018. Individual events and modes of communication were independently abstracted using NLP and manual chart review (reference standard). Preprocessing techniques and 2 NLP approaches (rule-based and machine learning) were evaluated using sensitivity, specificity, and area under the receiver operating characteristic curves (AUROC).Results: Over 2700 combinations of NLP methods and hyperparameters were evaluated for each mode of communication using a holdout subset. The rule-based approach had the highest AUROC in 65 datasets compared to the machine learning approach in 21 datasets. Both approaches had similar performance in 17 datasets. The rule-based AUROC for the grouped categories of patient documented to have family or friends (0.972, 95% CI 0.934-1.000), visit by family/friend (0.882 95% CI 0.820-0.943) and phone call with family/friend (0.975, 95% CI: 0.952-0.998) were high.Discussion: We report an automated method to quantify communication between healthcare professionals and family members of adult patients from free-text EMRs. A rule-based NLP approach had better overall operating characteristics than a machine learning approach.Conclusion: NLP can automatically and accurately measure frequency and mode of documented family visitation and communication from unstructured free-text EMRs, to support patient- and family-centered care initiatives. [ABSTRACT FROM AUTHOR]

We present general theoretical limits on the possible accuracy (mean squared error or MSE) of occupancy estimates for a large range of occupancy study designs with imperfect detection and confirm our theoretical results via a simulation study. In particular, we show that for a given total survey effort, the best possible MSE is driven by two design‐related factors: the fraction of visits made at occupied sites (regardless of whether that occupancy status is known or not) and the number of visits made to each site with unknown occupancy status (ie, sites with no detections). The limits reveal that there is very little room for improvement over optimal implementations of the three existing occupancy design paradigms: standard design (visit S sites K times each), removal design (visit S sites up to K times each, halting visits to each site following a positive detection), and conditional design (visit S sites once, then resurvey sites with a positive detection an additional K−1 times). For the small portion of the occupancy‐detection parameter space where improvement can be achieved, we introduce a new hybrid survey design with accuracy closer to the theoretical limit, which we illustrate by reanalyzing an existing coyote (Canis latrans) camera trap dataset. Our results provide new clarity and intuition regarding key factors of occupancy study design. [ABSTRACT FROM AUTHOR]

Background delirium is an acute state of confusion that affects >20% of hospitalised patients. Recent literature indicates that more severe delirium may lead to worse patient outcomes and health system outcomes, such as increased mortality, cognitive impairment and length of stay (LOS). Methods using systematic review methodology, we summarised associations between delirium severity and patient or health system outcomes in hospitalised adults. We searched MEDLINE, EMBASE, PsycINFO, CINAHL and Scopus databases with no restrictions, from inception to 25 October 2018. We included original observational research conducted in hospitalised adults that reported on associations between delirium severity and patient or health system outcomes. Quality of included articles was assessed using the Newcastle–Ottawa Scale. The level of evidence was quantified based on the consistency of findings and quality of studies reporting on each outcome. Results we included 20 articles evaluating associations that reported: mortality (n  = 11), cognitive ability (n  = 3), functional ability (n  = 3), patient distress (n  = 1), quality of life (n  = 1), hospital LOS (n  = 4), intensive care unit (ICU) LOS (n  = 2) and discharge home (n  = 2). There was strong-level evidence that delirium severity was associated with increased ICU LOS and a lower proportion of patients discharged home. There was inconclusive evidence for associations between delirium severity and mortality, hospital LOS, functional ability, cognitive ability, patient distress and quality of life. Conclusion delirium severity is associated with increased ICU LOS and a lower proportion of patients discharged home. Delirium severity may be a useful adjunct to existing delirium screening to determine the burden to health care system resources. [ABSTRACT FROM AUTHOR]

To ensure the food security of future generations and to address the challenge of the 'no hunger zone' proposed by the FAO (Food and Agriculture Organization), crop production must be doubled by 2050, but environmental stresses are counteracting this goal. Heat stress in particular is affecting agricultural crops more frequently and more severely. Since the discovery of the physiological, molecular, and genetic bases of heat stress responses, cultivated plants have become the subject of intense research on how they may avoid or tolerate heat stress by either using natural genetic variation or creating new variation with DNA technologies, mutational breeding, or genome editing. This review reports current understanding of the genetic and molecular bases of heat stress in crops together with recent approaches to creating heat-tolerant varieties. Research is close to a breakthrough of global relevance, breeding plants fitter to face the biggest challenge of our time. [ABSTRACT FROM AUTHOR]

Slow canopy wilting (SW) is a water conservation trait controlled by quantitative trait loci (QTLs) in late maturity group soybeans [ Glycine max (L.) Merr.]. Recently, two exotic (landraces) plant introductions (PI 567690 and PI 567731) were identified as new SW lines in early maturity groups. Here, we show that the two PIs share the same water conservation strategy of limited maximum transpiration rates as PI 416937. However, in contrast to PI 416937, the transpiration rates of these PIs were sensitive to an aquaporin inhibitor, indicating an independence between limited maximum transpiration and the lack of silver-sensitive aquaporins. Yield tests of selected recombinant inbred lines from two elite/exotic crosses provide direct evidence to support the benefit of SW in drought tolerance. Four SW QTLs mapped in a Pana×PI 567690 cross at multiple environments were found to be co-located with previous reports. Moreover, two new SW QTLs were mapped on chromosomes 6 and 10 from a Magellan×PI 567731 cross. These two QTLs explain the observed relatively large contributions of 20–30% and were confirmed in a near-isogenic background. These findings demonstrate the importance of SW in yield protection under drought and provide genetic resources for improving drought tolerance in early maturity group soybeans. [ABSTRACT FROM AUTHOR]

There is much discussion of adopting COVID-19 immunity certificates to allow those proven to have antibodies to the SARS-CoV-2 virus that causes COVID-19 to resume normal life and help restart the economy. This article points out issues that must be considered before adopting any such program. These issues fall into six categories: the uncertain science of COVID-19 immunity; the questionable quality of COVID-19 antibody tests; practical problems with issuing such certificates; deciding how the certificates might be used; ethical and social issues they would raise, especially fairness and self-infection; and potential legal barriers. It does not ultimately take a position on whether some narrow COVID-19 immunity plans should be adopted, concluding that the answer depends on too many currently unknown conditions. But its seventh part makes recommendations to decision-makers who might consider implementing such programs. [ABSTRACT FROM AUTHOR]

This document is a correction to an article titled "A catalogue of cataclysmic variables from 20 yr of the Sloan Digital Sky Survey with new classifications, periods, trends, and oddities" published in the Monthly Notices of the Royal Astronomical Society. The correction states that there were incorrect classifications of two cataclysmic variables (CVs) in Table 1 of the supplementary data. The CVs SDSSJ005217.22+315938.5 and SDSSJ162608.15+332827.7 were misclassified as a Polar and an AM CVn, respectively, when they should have been classified as an SU UMa and a Polar. The errors do not impact the analysis or conclusions of the article, and the supplementary material and machine-readable version are being updated to reflect the correction. [Extracted from the article]

Background Injuries represent one of the leading causes of preventable morbidity and mortality. For countries with ageing populations, admissions of injured older patients are increasing exponentially. Yet, we know little about hospital resource use for injured older patients. Our primary objective was to evaluate inter-hospital variation in the risk-adjusted resource use for injured older patients. Secondary objectives were to identify the determinants of resource use and evaluate its association with clinical outcomes. Methods We conducted a multicenter retrospective cohort study of injured older patients (≥65 years) admitted to any trauma centres in the province of Quebec (2013–2016, N  = 33,184). Resource use was estimated using activity-based costing and modelled with multilevel linear models. We conducted separate subgroup analyses for patients with trauma and fragility fractures. Results Risk-adjusted resource use varied significantly across trauma centres, more for older patients with fragility fractures (intra-class correlation coefficients [ICC] = 0.093, 95% CI [0.079, 0.102]) than with trauma (ICC = 0.047, 95% CI = 0.035–0.051). Risk-adjusted resource use increased with age, and the number of comorbidities, and varied with discharge destination (P  < 0.001). Higher hospital resource use was associated with higher incidence of complications for trauma (Pearson correlation coefficient r  = 0.5, 95% CI = 0.3–0.7) and fragility fractures (r  = 0.5, 95% CI = 0.3–0.7) and with higher mortality for fragility fractures (r  = 0.4, 95% CI = 0.2–0.6). Conclusions We observed significant inter-hospital variations in resource use for injured older patients. Hospitals with higher resource use did not have better clinical outcomes. Hospital resource use may not always positively impact patient care and outcomes. Future studies should evaluate mechanisms, by which hospital resource use impacts care. [ABSTRACT FROM AUTHOR]

The world was shocked in Nov. 25, 2018 by the revelation that He Jiankui had used clustered regularly interspaced short palindromic repeats ('CRISPR') to edit embryos—two of which had, sometime in October, become living babies. This article is an effort to provide some deep context for the He Jiankui affair and to begin analyzing it. It focuses on He's experiment, without delving into the broader ethical issues around 'human germline genome editing' in the abstract. It begins by carefully defining 'human germline genome editing'. It then describes the little we know about the experiment before providing background on CRISPR, the pre-He ethical and legal status of human germline genome editing, and on He himself. The fourth, and longest, section provides a detailed narrative of the revelation of the He experiment and its fallout. The fifth section critiques the experiment, which I believe merits unequivocal condemnation on several grounds. The last section suggests some important immediate reactions, by 'Science' and by China. [ABSTRACT FROM AUTHOR]

Nonexperimental studies of the effectiveness of seasonal influenza vaccine in older adults have found 40%–60% reductions in all-cause mortality associated with vaccination, potentially due to confounding by frailty. We restricted our cohort to initiators of medications in preventive drug classes (statins, antiglaucoma drugs, and β blockers) as an approach to reducing confounding by frailty by excluding frail older adults who would not initiate use of these drugs. Using a random 20% sample of US Medicare beneficiaries, we framed our study as a series of nonrandomized "trials" comparing vaccinated beneficiaries with unvaccinated beneficiaries who had an outpatient health-care visit during the 5 influenza seasons occurring in 2010–2015. We pooled data across trials and used standardized-mortality-ratio–weighted Cox proportional hazards models to estimate the association between influenza vaccination and all-cause mortality before influenza season, expecting a null association. Weighted hazard ratios among preventive drug initiators were generally closer to the null than those in the nonrestricted cohort. Restriction of the study population to statin initiators with an uncensored approach resulted in a weighted hazard ratio of 1.00 (95% confidence interval: 0.84, 1.19), and several other hazard ratios were above 0.95. Restricting the cohort to initiators of medications in preventive drug classes can reduce confounding by frailty in this setting, but further work is required to determine the most appropriate criteria to use. [ABSTRACT FROM AUTHOR]

Background: Immune checkpoint inhibitors such as pembrolizumab and nivolumab have emerged as active treatment options for patients with many cancers, including metastatic melanoma, but can also cause symptomatic or life‐threatening immune‐related adverse events, including encephalitis. Epididymitis and orchitis are rare complications of these therapies. Case Presentation: We describe herein a patient with metastatic melanoma who developed epididymo‐orchitis followed by encephalitis while receiving pembrolizumab. The patient developed testicular pain and fever after his third dose of pembrolizumab; ultrasound evaluation demonstrated bilateral epididymo‐orchitis. He then developed headaches, fever, and altered mental status over the next week and was admitted to the hospital. Lumbar puncture revealed inflammatory changes consistent with meningoencephalitis; he did not improve with broad‐spectrum antibiotics, and an extensive workup for infectious etiologies, including cerebrospinal fluid testing using a clinical metagenomic next‐generation sequencing assay, was negative. He received high‐dose steroids for suspected autoimmune encephalitis, and both his orchitis and meningoencephalitis improved rapidly after one dose. He fully recovered after a 5‐week taper of oral steroids. Discussion: Here, we report a case of epididymo‐orchitis complicating immune checkpoint inhibitor therapy. This patient subsequently developed severe encephalitis but rapidly improved with steroids. Clinicians should be aware of rare complications of these agents. Key Points: Epididymo‐orchitis is a rare and potentially life‐threatening complication of anti‐programmed death protein 1 (anti‐PD‐1) therapy.For patients on anti‐PD‐1 therapy who develop either epididymo‐orchitis or epididymitis without clear infectious cause, immune‐related adverse events should be considered in the differential diagnosis.If severe, epididymo‐orchitis related to anti‐PD‐1 therapy may be treated with high‐dose corticosteroids. Immune checkpoint inhibitors have emerged as treatment options for patients with many cancers, but the treatment is associated with immune‐related adverse events. Epididymitis and orchitis are rare complications of these therapies. This article presents the case of a patient with metastatic melanoma who developed epididymo‐orchitis as well as encephalitis while receiving pembrolizumab. [ABSTRACT FROM AUTHOR]

Introduction: Tactical Combat Casualty Care (TCCC) training imposes psychophysiological stress on medics. It is unclear whether these stress levels vary with the training modalities selected. It is also unclear how stress levels could have an impact on medical performance and skill uptake.Materials and Methods: We conducted a pilot study to compare the effects of live tissue (LT) with a high-fidelity patient simulator (SIM) on the level of stress elicited, performance, and skill uptake during battlefield trauma training course in an operating room (OR) and in a simulated battlefield scenario (field). In the report, we studied the effects of training modalities and their changes on stress levels by measuring different biomarkers (salivary amylase, plasma catecholamines, and neuropeptide Y) at various time points during the trauma training course.Results: We found that the training resulted in significant psychophysiological stress as indicated by elevated levels of various biomarkers relative to baseline immediately after both OR and field assessment (p < 0.05). Compared with pre-OR levels, the LT training in the OR resulted in significant increases in the plasma levels of epinephrine, norepinephrine, and neuropeptide (p = 0.013, 0.023, 0.004, respectively), whereas the SIM training in the OR resulted in significant increases in the plasma levels of norepinephrine and neuropeptide (p = 0.003 and 0.008). Compared with pre-field levels, we found significant increases in plasma epinephrine concentration in the SIM group (p = 0.016), plasma norepinephrine concentration in the LT group (p = 0.015), and plasma neuropeptide Y concentration in both LT (p = 0.006) and SIM groups (p = 0.029). No differences in the changes of biomarker levels were found between LT and SIM groups in the OR and field. Compared with pre-field levels, the testing on the same modality as that in the OR in the simulated battlefield resulted in significant increases in norepinephrine and neuropeptide levels (p = 0.013 and 0.015), whereas the testing on different modalities resulted in significant increases in amylase, epinephrine, and neuropeptide levels (p = 0.016, 0.05, 0.018, respectively). There was a significantly larger increase in plasma norepinephrine concentration (p = 0.031) and a trend toward a greater increase in the salivary amylase level (p = 0.052) when the field testing involved a different modality than the OR compared with when OR and field testing involved the same modality. Although most of the biomarkers returned to baseline levels after 24 h, plasma norepinephrine levels remained significantly higher regardless of whether field testing occurred on the same or different modality compared with OR (p = 0.040 and 0.002).Conclusion: TCCC training led to significant increase in psychophysiological stress, as indicated by elevated levels of various biomarkers. The training modalities did not result in any differences in stress levels, whereas the switch in training modalities appeared to elicit greater stress as evidenced by changes in specific biomarkers (amylase and norepinephrine). A comparative study with a larger sample size is warranted. [ABSTRACT FROM AUTHOR]

Grain legumes form an important component of the human diet, provide feed for livestock, and replenish soil fertility through biological nitrogen fixation. Globally, the demand for food legumes is increasing as they complement cereals in protein requirements and possess a high percentage of digestible protein. Climate change has enhanced the frequency and intensity of drought stress, posing serious production constraints, especially in rainfed regions where most legumes are produced. Genetic improvement of legumes, like other crops, is mostly based on pedigree and performance-based selection over the past half century. To achieve faster genetic gains in legumes in rainfed conditions, this review proposes the integration of modern genomics approaches, high throughput phenomics, and simulation modelling in support of crop improvement that leads to improved varieties that perform with appropriate agronomy. Selection intensity, generation interval, and improved operational efficiencies in breeding are expected to further enhance the genetic gain in experimental plots. Improved seed access to farmers, combined with appropriate agronomic packages in farmers' fields, will deliver higher genetic gains. Enhanced genetic gains, including not only productivity but also nutritional and market traits, will increase the profitability of farming and the availability of affordable nutritious food especially in developing countries. [ABSTRACT FROM AUTHOR]

Climate change has increased the occurrence of extreme weather patterns globally, causing significant reductions in crop production, and hence threatening food security. In order to meet the food demand of the growing world population, a faster rate of genetic gains leading to productivity enhancement for major crops is required. Grain legumes are an essential commodity in optimal human diets and animal feed because of their unique nutritional composition. Currently, limited water is a major constraint in grain legume production. Root system architecture (RSA) is an important developmental and agronomic trait, which plays vital roles in plant adaptation and productivity under water-limited environments. A deep and proliferative root system helps extract sufficient water and nutrients under these stress conditions. The integrated genetics and genomics approach to dissect molecular processes from genome to phenome is key to achieve increased water capture and use efficiency through developing better root systems. Success in crop improvement under drought depends on discovery and utilization of genetic variations existing in the germplasm. In this review, we summarize current progress in the genetic diversity in major legume crops, quantitative trait loci (QTLs) associated with RSA, and the importance and applications of recent discoveries associated with the beneficial root traits towards better RSA for enhanced drought tolerance and yield. [ABSTRACT FROM AUTHOR]

Background: Although evidence suggests that larger body size in early life confers lifelong protection from developing breast cancer, few studies have investigated the relationship between body size and breast cancer risk among BRCA mutation carriers. Therefore, we conducted a prospective evaluation of body size and the risk of breast cancer among BRCA mutation carriers.Methods: Current height and body mass index (BMI) at age 18 were determined from baseline questionnaires. Current BMI and weight change since age 18 were calculated from updated biennial follow-up questionnaires. Cox proportional hazards models were used to estimate the hazard ratio (HR) and 95% confidence interval (CI).Results: Among 3734 BRCA mutation carriers, there were 338 incident breast cancers over a mean follow-up of 5.5 years. There was no association between height, current BMI or weight change and breast cancer risk. Women with BMI at age 18 ≥22.1 kg/m2 had a decreased risk of developing post-menopausal breast cancer compared with women with a BMI at age 18 between 18.8 and 20.3 kg/m2 (HR 0.49; 95% CI 0.30-0.82; P = 0.006). BMI at age 18 was not associated with risk of pre-menopausal breast cancer.Conclusions: There was no observed association between height, current BMI and weight change and risk of breast cancer. The inverse relationship between greater BMI at age 18 and post-menopausal breast cancer further supports a role of early rather than current or adulthood exposures for BRCA-associated breast cancer development. Future studies with longer follow-up and additional measures of adiposity are necessary to confirm these findings. [ABSTRACT FROM AUTHOR]

Background: Beyond the acute illness phase, chikungunya constitutes a public health problem given its chronic disease phase, which may include long-term arthralgia, arthritis, fatigue, and depression. Currently, there is no consensus on how to define chikungunya chronicity.Methods: A comprehensive cross-sectional survey was performed in Curaçao in June and July 2015 to evaluate 304 adult laboratory-confirmed chikungunya patients 3-16 months after diagnosis. We developed a novel tool, the Curaçao Long-Term Chikungunya Sequelae (CLTCS) score, to classify chronic chikungunya disease and estimate its burden regarding disease duration, clinical presentation, and impact on quality of life.Results: Disease persistence was estimated to be 79% one month after symptom onset and 64% after 400 days. Chikungunya persistence was characterized by higher proportions of arthralgia, weakness, myalgia, and age 41-60 years. Individuals were classified as "highly affected," "mildly affected," and "recovered." "Highly affected" disease status was associated with clinical complaints (arthralgia, weakness, loss of vitality, and being diabetic) and major decreases in quality-of-life scores.Conclusions: In the Caribbean, a high proportion of chikungunya patients remains chronically affected. We propose the CLTCS as a suitable score to easily and rapidly classify the severity of chikungunya chronic disease and to assess the need for symptom-alleviating treatment. [ABSTRACT FROM AUTHOR]

We tested the hypothesis that increasing the number of metaxylem vessels would enhance the efficiency of water uptake in soybean (Glycine max) and decrease the yield gap in water-limited environments. A panel of 41 soybean accessions was evaluated in greenhouse, rainout shelter, and rain-fed field environments. The metaxylem number influenced the internal capture of CO2 and improved stomatal conductance, enhancing water uptake/use in soybeans exposed to stress during the reproductive stage. We determined that other root anatomical features, such as cortex cell area and the percentage of stele that comprised cortical cells, also affected seed yield under similar growth parameters. Seed yield was also impacted by pod retention rates under drought stress (24-80 pods/plant). We surmise that effective biomass allocation, that is, the transport of available photosynthates to floral structures at late reproductive growth stages (R6-R7), enables yield protection under drought stress. A mesocosm study of contrasting lines for yield under drought stress and root anatomical features revealed that increases in metaxylem number as an adaptation to drought in the high-yielding lines improved root hydraulic conductivity, which reduced the metabolic cost of exploring water in deeper soil strata and enhanced water transport. This allowed the maintenance of shoot physiological processes under water-limited conditions. [ABSTRACT FROM AUTHOR]

Drought and its interaction with high temperature are the major abiotic stress factors affecting soybean yield and production stability. Ongoing climate changes are anticipated to intensify drought events, which will further impact crop production and food security. However, excessive water also limits soybean production. The success of soybean breeding programmes for crop improvement is dependent on the extent of genetic variation present in the germplasm base. Screening for natural genetic variation in drought- and flooding tolerance-related traits, including root system architecture, water and nitrogen-fixation efficiency, and yield performance indices, has helped to identify the best resources for genetic studies in soybean. Genomic resources, including whole-genome sequences of diverse germplasms, millions of single-nucleotide polymorphisms, and high-throughput marker genotyping platforms, have expedited gene and marker discovery for translational genomics in soybean. This review highlights the current knowledge of the genetic diversity and quantitative trait loci associated with root system architecture, canopy wilting, nitrogen-fixation ability, and flooding tolerance that contributes to the understanding of drought- and flooding-tolerance mechanisms in soybean. Next-generation mapping approaches and high-throughput phenotyping will facilitate a better understanding of phenotype-genotype associations and help to formulate genomic-assisted breeding strategies, including genomic selection, in soybean for tolerance to drought and flooding stress. [ABSTRACT FROM AUTHOR]

Widespread use of medical records for research, without consent, attracts little scrutiny compared to biospecimen research, where concerns about genomic privacy prompted recent federal proposals to mandate consent. This paper explores an important consequence of the proliferation of electronic health records (EHRs) in this permissive atmosphere: with the advent of clinical gene sequencing, EHR-based secondary research poses genetic privacy risks akin to those of biospecimen research, yet regulators still permit researchers to call gene sequence data 'de-identified', removing such data from the protection of the federal Privacy Rule and federal human subjects regulations. Medical centers and other providers seeking to offer genomic 'personalized medicine' now confront the problem of governing the secondary use of clinical genomic data as privacy risks escalate. We argue that regulators should no longer permit HIPAA-covered entities to treat dense genomic data as de-identified health information. Even with this step, the Privacy Rule would still permit disclosure of clinical genomic data for research, without consent, under a data use agreement, so we also urge that providers give patients specific notice before disclosing clinical genomic data for research, permitting (where possible) some degree of choice andcontrol. To aid providers who offer clinical gene sequencing, we suggest both general approaches and specific actions to reconcile patients' rights and interests with genomic research. [ABSTRACT FROM AUTHOR]

Background: Whether oophorectomy reduces breast cancer risk among BRCA mutation carriers is a matter of debate. We undertook a prospective analysis of bilateral oophorectomy and breast cancer risk in BRCA mutation carriers.Methods: Subjects had no history of cancer, had both breasts intact, and had information on oophorectomy status (n = 3722). Women were followed until breast cancer diagnosis, prophylactic bilateral mastectomy, or death. A Cox regression model was used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of breast cancer associated with oophorectomy (coded as a time-dependent variable). All statistical tests were two-sided.Results: Over a mean follow-up of 5.6 years, 350 new breast cancers were diagnosed. Among women with a BRCA1 or BRCA2 mutation, oophorectomy was not associated with breast cancer risk compared with women who did not undergo an oophorectomy. The age-adjusted hazard ratio associated with oophorectomy was 0.96 (95% CI = 0.73 to 1.26, P = 76) for BRCA1 and was 0.65 (95% CI = 0.37 to 1.16, P = 14) for BRCA2 mutation carriers. In stratified analyses, the effect of oophorectomy was statistically significant for breast cancer in BRCA2 mutation carriers diagnosed prior to age 50 years (age-adjusted HR = 0.18, 95% CI = 0.05 to 0.63, P = 007). Oophorectomy was not associated with risk of breast cancer prior to age 50 years among BRCA1 mutation carriers (age-adjusted HR = 0.79, 95% CI = 0.55 to 1.13, P = 51).Conclusions: Findings from this large prospective study support a role of oophorectomy for the prevention of premenopausal breast cancer in BRCA2, but not BRCA1 mutation carriers. These findings warrant further evaluation. [ABSTRACT FROM AUTHOR]

Background: Human papillomavirus (HPV) has been associated with the development of head and neck cancers. In this study, we investigated whether the risk factors for head and neck cancer in relation to HPV infection are different from those in the absence of HPV infection and whether HPV detected in oral exfoliated cells is an independent predictor of head and neck cancer risk.Methods: We conducted a case-control study in 201 head and neck cancer case patients and 333 control subjects, frequency matched for age and sex. Oral exfoliated cells and tumor tissue were evaluated for HPV using polymerase chain reaction and DNA sequencing to type HPV. Logistic regression was used to calculate odds ratios (ORs) for head and neck cancer with HPV infection and 95% confidence intervals (CIs), adjusted for age, tobacco use, and alcohol consumption.Results: Oncogenic, or high-risk (HR), HPV types were detected in oral cells from 22.9% of case patients and 10.8% of control subjects. HPV16 was the most frequently detected type (19% versus 10% of case patients and control subjects, respectively). After adjusting for age, tobacco use, and alcohol consumption, the risk of head and neck cancer was statistically significantly greater in individuals with HPV-HR types (adjusted OR = 2.6, 95% CI = 1.5 to 4.2) but not in individuals with nononcogenic HPV types (adjusted OR = 0.8, 95% CI = 0.4 to 1.7) compared with HPV-negative individuals. Compared with individuals who were HPV-negative and did not use alcohol or tobacco, there was a statistically significant synergistic effect between detection of HPV-HR and heavy alcohol consumption (OR = 18.8, 95% CI = 5.1 to 69.5) but an additive effect between detection of HPV-HR and tobacco use (OR = 5.5, 95% CI = 2.1 to 14.1). HPV-HR types detected in oral exfoliated cells were predictive of HPV-HR types in tumor tissue.Conclusion: Infection of oral exfoliated cells with HPV-HR types is a risk factor for head and neck cancer, independent of alcohol and tobacco use, and acts synergistically with alcohol consumption. HPV testing of an oral rinse may be predictive of an HPV-related head and neck cancer. [ABSTRACT FROM AUTHOR]

Several forensic sciences, especially of the pattern-matching kind, are increasingly seen to lack the scientific foundation needed to justify continuing admission as trial evidence. Indeed, several have been abolished in the recent past. A likely next candidate for elimination is bitemark identification. A number of DNA exonerations have occurred in recent years for individuals convicted based on erroneous bitemark identifications. Intense scientific and legal scrutiny has resulted. An important National Academies review found little scientific support for the field. The Texas Forensic Science Commission recently recommended a moratorium on the admission of bitemark expert testimony. The California Supreme Court has a case before it that could start a national dismantling of forensic odontology. This article describes the (legal) basis for the rise of bitemark identification and the (scientific) basis for its impending fall. The article explains the general logic of forensic identification, the claims of bitemark identification, and reviews relevant empirical research on bitemark identification--highlighting both the lack of research and the lack of support provided by what research does exist. The rise and possible fall of bitemark identification evidence has broader implications--highlighting the weak scientific culture of forensic science and the law's difficulty in evaluating and responding to unreliable and unscientific evidence. [ABSTRACT FROM AUTHOR]

Circadian clocks are a great evolutionary innovation and provide competitive advantage during the day/night cycle and under changing environmental conditions. The circadian clock mediates expression of a large proportion of genes in plants, achieving a harmonious relationship between energy metabolism, photosynthesis, and biotic and abiotic stress responses. Here it is shown that multiple paralogues of clock genes are present in soybean (Glycine max) and mediate flooding and drought responses. Differential expression of many clock and SUB1 genes was found under flooding and drought conditions. Furthermore, natural variation in the amplitude and phase shifts in PRR7 and TOC1 genes was also discovered under drought and flooding conditions, respectively. PRR3 exhibited flooding- and drought-specific splicing patterns and may work in concert with PRR7 and TOC1 to achieve energy homeostasis under flooding and drought conditions. Higher expression of TOC1 also coincides with elevated levels of abscisic acid (ABA) and variation in glucose levels in the morning and afternoon, indicating that this response to abiotic stress is mediated by ABA, endogenous sugar levels, and the circadian clock to fine-tune photosynthesis and energy utilization under stress conditions. It is proposed that the presence of multiple clock gene paralogues with variation in DNA sequence, phase, and period could be used to screen exotic germplasm to find sources for drought and flooding tolerance. Furthermore, fine tuning of multiple clock gene paralogues (via a genetic engineering approach) should also facilitate the development of flooding- and drought-tolerant soybean varieties. [ABSTRACT FROM AUTHOR]

The article focuses on policy issues in the U.S. related to marketing and the use of genetic testing products in children and teenagers; and debate regarding medically significant direct-to-consumer (DTC) testing and genetic testing that is lifestyle-oriented.

Investigation of melioidosis cases in eastern Puerto Rico revealed high rates of Burkholderia pseudomallei seropositivity, and the bacterium was isolated from soil, suggesting regional endemicity. Increased awareness of melioidosis is needed to enable early case identification and antimicrobial therapy.Background. Melioidosis results from infection with Burkholderia pseudomallei and is associated with case-fatality rates up to 40%. Early diagnosis and treatment with appropriate antimicrobials can improve survival rates. Fatal and nonfatal melioidosis cases were identified in Puerto Rico in 2010 and 2012, respectively, which prompted contact investigations to identify risk factors for infection and evaluate endemicity.Methods. Questionnaires were administered and serum specimens were collected from coworkers, neighborhood contacts within 250 m of both patients' residences, and injection drug user (IDU) contacts of the 2012 patient. Serum specimens were tested for evidence of prior exposure to B. pseudomallei by indirect hemagglutination assay. Neighborhood seropositivity results guided soil sampling to isolate B. pseudomallei.Results. Serum specimens were collected from contacts of the 2010 (n = 51) and 2012 (n = 60) patients, respectively. No coworkers had detectable anti–B. pseudomallei antibody, whereas seropositive results among neighborhood contacts was 5% (n = 2) for the 2010 patient and 23% (n = 12) for the 2012 patient, as well as 2 of 3 IDU contacts for the 2012 case. Factors significantly associated with seropositivity were having skin wounds, sores, or ulcers (odds ratio [OR], 4.6; 95% confidence interval [CI], 1.2–17.8) and IDU (OR, 18.0; 95% CI, 1.6–194.0). Burkholderia pseudomallei was isolated from soil collected in the neighborhood of the 2012 patient.Conclusions. Taken together, isolation of B. pseudomallei from a soil sample and high seropositivity among patient contacts suggest at least regional endemicity of melioidosis in Puerto Rico. Increased awareness of melioidosis is needed to enable early case identification and early initiation of appropriate antimicrobial therapy. [ABSTRACT FROM PUBLISHER]

Small RNAs are ubiquitous, versatile repressors and include (1) microRNAs (miRNAs), processed from mRNA forming stem-loops; and (2) small interfering RNAs (siRNAs), the latter derived in plants by a process typically requiring an RNA-dependent RNA polymerase. We constructed and analyzed an expression atlas of soybean (Glycine max) small RNAs, identifying over 500 loci generating 21-nucleotide phased siRNAs (phasiRNAs ; from PHAS loci), of which 483 overlapped annotated protein-coding genes. Via the integration of miRNAs with parallel analysis of RNA end (PARE) data, 20 miRNA triggers of 127 PHAS loci were detected. The primary class of PHAS loci (208 or 41% of the total) corresponded to NB-LRR genes; some of these small RNAs preferentially accumulate in nodules. Among the PHAS loci, novel representatives of TAS3 and noncanonical phasing patterns were also observed. A noncoding PHAS locus, triggered by miR4392, accumulated preferentially in anthers; the phasiRNAs are predicted to target transposable elements, with their peak abundance during soybean reproductive development. Thus, phasiRNAs show tremendous diversity in dicots. We identified novel miRNAs and assessed the veracity of soybean miRNAs registered in miRBase, substantially improving the soybean miRNA annotation, facilitating an improvement of miRBase annotations and identifying at high stringency novel miRNAs and their targets. [ABSTRACT FROM AUTHOR]

About one-third of the world’s rice area is in rain-fed lowlands and most are prone to water shortage. The identification of genes imparting tolerance to drought in the model cereal plant, rice, is an attractive strategy to engineer improved drought tolerance not only rice but other cereals as well. It is demonstrated that RNAi-mediated disruption of a rice farnesyltransferase/squalene synthase (SQS) by maize squalene synthase improves drought tolerance at both the vegetative and reproductive stages. Twenty-day-old seedlings of wild type (Nipponbare) and seven independent events of transgenic RNAi lines showed no difference in morphology. When subjected to water stress for a period of 32 d under growth chamber conditions, transgenic positives showed delayed wilting, conserved more soil water, and improved recovery. When five independent events along with wild-type plants were subjected to drought at the reproductive stage under greenhouse conditions, the transgenic plants lost water more slowly compared with the wild type, through reduced stomatal conductance and the retention of high leaf relative water content (RWC). After 28 d of slow progressive soil drying, transgenic plants recovered better and flowered earlier than wild-type plants. The yield of water-stressed transgenic positive plants ranged from 14–39% higher than wild-type plants. When grown in plates with Yoshida’s nutrient solution with 1.2% agar, transgenic positives from three independent events showed increased root length and an enhanced number of lateral roots. The RNAi-mediated inactivation produced reduced stomatal conductance and subsequent drought tolerance. [ABSTRACT FROM PUBLISHER]

Many rodent experiments have assessed effects of diets, drugs, genes, and other factors on life span. A challenge with such experiments is their long duration, typically over 3.5 years given rodent life spans, thus requiring significant time costs until answers are obtained. We collected longevity data from 15 rodent studies and artificially truncated them at 2 years to assess the extent to which one will obtain the same answer regarding mortality effects. When truncated, the point estimates were not significantly different in any study, implying that in most cases, truncated studies yield similar estimates. The median ratio of variances of coefficients for truncated to full-length studies was 3.4, implying that truncated studies with roughly 3.4 times as many rodents will often have equivalent or greater power. Cost calculations suggest that shorter studies will be more expensive but perhaps not so much to not be worth the reduced time. [ABSTRACT FROM PUBLISHER]

Women who carry a deleterious mutation in BRCA1 or BRCA2 have high lifetime risks of breast and ovarian cancers. However, the influence of a family history of these cancers on these risks in women with BRCA mutations is unclear. We calculated cancer incidence rates for a multinational cohort comprising 3011 women with BRCA1 or BRCA2 mutations who were followed up for a mean of 3.9 years, during which time 243 incident breast or ovarian cancers were recorded. The 10-year cumulative risks of breast cancer were 18.1% (95% confidence interval [CI] = 13.3% to 22.8%) for women with a BRCA1 mutation and 15.2% (95% CI = 9.1% to 21.2%) for women with a BRCA2 mutation. Among women with a BRCA1 mutation, the risk of breast cancer increased by 1.2-fold for each first-degree relative with breast cancer before age 50 years (hazard ratio [HR] = 1.21; 95% confidence interval [CI] = 0.94 to 1.57) and the risk of ovarian cancer increased by 1.6 fold for each first- or second-degree relative with ovarian cancer (HR = 1.61; 95% CI = 1.21 to 2.14). Among women with a BRCA2 mutation, the risk of breast cancer increased by 1.7-fold for each first-degree relative younger than 50 years with breast cancer (HR = 1.67; 95% CI = 1.04 to 2.07) [ABSTRACT FROM PUBLISHER]

Numerous environmental factors influence isoflavone accumulation and have long hampered their genetic dissection. Temperature and water regimes are two of the most significant abiotic factors. However, while the effects of temperature have been widely studied, little is known about how water scarcity might affect isoflavone concentration in seeds. Studies have shown that accumulation of isoflavones is promoted by well-watered conditions, but the molecular basis remains elusive. The length and severity of the water stress required to induce changes are also still unknown. In the present work, several intensities of water stress were evaluated at various critical stages for soybean [Glycine max (L.) Merr.] seed development, in both field and controlled environments. The results suggested that only long-term progressive drought, spanning most of the seed developmental stages, significantly decreased isoflavone content in seeds. The reduction is proportional to the intensity of the stress and appears to occur in a genotype-dependent manner. However, regardless of water regime, isoflavone compounds were mainly accumulated in the later seed developmental stages. Transcripts of the most important genes for isoflavone biosynthesis were also quantified from samples collected at key seed developmental stages under well-watered and long-term water deficit conditions. Expression of CHS7, CHS8 and IFS2 correlated with isoflavone accumulation under well-watered conditions. Interestingly, we found that the two isoflavone synthase genes in soybean (IFS1 and IFS2) showed different patterns of expression. The abundance of IFS1 transcripts was maintained at a constant rate, whereas IFS2 was down-regulated and highly correlated with isoflavone accumulation under both water deficit and well-watered conditions, suggesting IFS2 as a main contributor to isoflavone diminution under drought. [ABSTRACT FROM PUBLISHER]

Tolerant soybean (Glycine max [L.] Merr.) cultivars aid in reducing salt damage in problem fields. New genes are important to reduce losses from salt injury. Objectives of this study were to determine inheritance of salt tolerance in wild soybean (Glycine soja Sieb. and Zucc.) PI483463 and to test allelism of tolerance genes from genotypes PI483463 and S-100, a common ancestor of southern in US cultivars. Tolerant (T) PI483463 was crossed to sensitive (S) cultivar Hutcheson to study inheritance. PI483463 (T) was crossed with S-100 (T) to test for allelism. Parents, F1 plants, F2 populations, and F2:3 lines were assayed in a 100 mM salt solution to determine tolerance. F2 from T × S cross segregated 3(T):1 (S) and the F2:3 lines responded 1 (T): 2 (segregating):1 (S). F2 plants from PI483463 (T) × S-100 (T) segregated 15 (T):1 (S) indicating different genes from the 2 sources. Results showed that G. soja line PI483463 had a single dominant gene for salt tolerance, which was different than the gene in G. max line S-100. The symbol, Ncl2, was designated for this new salt tolerance allele. [ABSTRACT FROM PUBLISHER]

Nodulation is the result of a symbiosis between legumes and rhizobial bacteria in soil. This symbiosis is mutually beneficial, with the bacteria providing a source of nitrogen to the host while the plant supplies carbon to the symbiont. Nodule development is a complex process that is tightly regulated in the host plant cell through networks of gene expression. In order to examine this regulation in detail, a library of quantitative reverse transcription-polymerase chain reaction primer sets was developed for a large number of soybean (Glycine max) putative regulatory genes available in the current expressed sequence tag collection. This library contained primers specific to soybean transcription factor genes as well as genes involved in chromatin modification and translational regulation. Using this library, we analyzed the expression of this gene set during nodule development. A large number of genes were found to be differentially expressed, especially at the later stages of nodule development when active nitrogen fixation was occurring. Expression of these putative regulatory genes was also analyzed in response to the addition of nitrate as a nitrogen source. This comparative analysis identified genes that may be specifically involved in nitrogen assimilation, metabolism, and the maintenance of active nodules. To address this possibility, the expression of one such candidate was studied in more detail by expressing in soybean roots promoter β-glucuronidase and green fluorescent protein fusions. This gene, named Control of Nodule Development (CND), encoded a Myb transcription factor gene. When the CND gene was silenced, nodulation was reduced. These results, associated with a strong expression of the CND gene in the vascular tissues, suggest a role for CND in controlling soybean nodulation. [ABSTRACT FROM AUTHOR]