An exploration into the sleep of workers on block-calving, pasture-based dairy farms.

The benefits of sufficient and high-quality sleep for people are well documented. Insufficient sleep increases the risk of accidents, injuries, and negative health implications for people. This is especially relevant for farmers, as they work with large animals and machinery. Dairy farming often requires early start times and long days, particularly over the high workload calving period in block calving, pasture-based systems. However, there is little published data quantifying the sleep quantity and quality of farmers over this period. In this study, the sleep patterns of workers (n = 33) on 10 New Zealand dairy farms was measured for 90 d over the spring calving period using a sleep measuring device (OuraTM ring, Oura Health Ltd., Oulu, Finland). Total sleep time (TST) averaged 6 h 15 min, lower than the required 7 to 9 h for optimal wellbeing and cognitive functioning. TST decreased over the calving period and was significantly correlated with both sleep start and wake times. Factors such as work start time, farm location, and role on farm influenced sleep quantity and quality; indicating adjusting these on-farm factors could positively impact TST. Further research is required to better understand sleep and its effect on dairy farmers, over both the calving period and the remaining months of the year.

Behavioural responses of a large, heat-sensitive mammal to climatic variation at multiple spatial scales.

Climate warming creates energetic challenges for endothermic species by increasing metabolic and hydric costs of thermoregulation. Although endotherms can invoke an array of behavioural and physiological strategies for maintaining homeostasis, the relative effectiveness of those strategies in a climate that is becoming both warmer and drier is not well understood. In accordance with the heat dissipation limit theory which suggests that allocation of energy to growth and reproduction by endotherms is constrained by the ability to dissipate heat, we expected that patterns of habitat use by large, heat-sensitive mammals across multiple scales are critical for behavioural thermoregulation during periods of potential heat stress and that they must invest a large portion of time to maintain heat balance. To test our predictions, we evaluated mechanisms underpinning the effectiveness of bed sites for ameliorating daytime heat loads and potential heat stress across the landscape while accounting for other factors known to affect behaviour. We integrated detailed data on microclimate and animal attributes of moose Alces alces, into a biophysical model to quantify costs of thermoregulation at fine and coarse spatial scales. During summer, moose spent an average of 67.8% of daylight hours bedded, and selected bed sites and home ranges that reduced risk of experiencing heat stress. For most of the day, shade could effectively mitigate the risk of experiencing heat stress up to 10°C, but at warmer temperatures (up to 20°C) wet soil was necessary to maintain homeostasis via conductive heat loss. Consistent selection across spatial scales for locations that reduced heat load underscores the importance of the thermal environment as a driver of behaviour in this heat-sensitive mammal. Moose in North America have long been characterized as riparian-obligate species because of their dependence on woody plant species for food. Nevertheless, the importance of dissipating endogenous heat loads conductively through wet soil suggests riparian habitats also are critical thermal refuges for moose. Such refuges may be especially important in the face of a warming climate in which both high environmental temperatures and drier conditions will likely exacerbate limits to heat dissipation, especially for large, heat-sensitive animals.

The association of environmental factors with neurocognitive outcomes in survivors of childhood acute lymphoblastic leukemia (ALL).

PURPOSE: To investigate the association of environmental factors, rehabilitation services during therapy and socioeconomic status (SES - insurance type), with neurocognitive outcomes at the end of therapy for survivors of childhood acute lymphoblastic leukemia (ALL). METHODS: Survivors (n = 236) treated on the St. Jude Total Therapy Study 16 completed end of therapy testing with performance measures (IQ, attention, processing speed, fine motor skills, academics) and caregiver ratings (attention, executive function, adaptive skills). Environmental factors were abstracted from the medical record. RESULTS: Distribution of sex (47.3% female, p = 0.399), treatment arm (45.5% low risk, 54.5% standard/high risk p = 0.929), insurance type (47.7% private, 52.3% public/none, p = 0.117), and mean age at diagnosis (7.7 vs. 6.8 years, p = 0.143) were similar for groups with (n = 110; 46.6%) and without (n = 126; 53.6%) rehabilitation services during therapy. Compared to those without rehabilitation, the rehabilitation group (n = 110; 46.4%) had more caregiver reported problems with attention (Z = -0.28 vs. 0.43, p = 0.022), executive function (Z = -0.50 vs. -0.08, p = 0.003), and adaptive skills (Z = -0.41 vs.-0.13, p = 0.031). Among the rehabilitation group, there was no difference in outcomes by insurance status. Among those without rehabilitation, those with public insurance had worse neurocognitive outcomes than those with private insurance in IQ (Z = -0.04 vs. -0.45, p = 0.0115), processing speed (Z = -0.10 vs. -0.75, p = 0.0030), reading (Z = 0.18 vs. -0.59, p < 0.0001), and math (Z = -0.04 vs. -0.50, p = 0.0021). CONCLUSION: Participation in rehabilitation services during early intensive therapy is associated with end of therapy caregiver-reported neurocognitive outcomes in daily life.

Training during the COVID-19 pandemic: the experience of public health registrars in the London and Kent, Surrey, Sussex training programme.

BACKGROUND: Public Health registrars (SpRs) were an important component of the workforce that contributed to the COVID-19 response. This study explores their contribution and the impact the early stages of the pandemic had on their learning and training. METHODS: Data were collected from SpRs in the London and Kent, Surrey, Sussex training programme between July and September 2020 through a mixture of questionnaires and semi-structured interviews. A thematic analysis of interview transcripts was undertaken to identify themes. RESULTS: 35/128 SpRs responded to the survey and 11 were interviewed. SpRs were placed across a range of organizations and made a significant contribution to the COVID-19 response. Overall, SpRs learned important skills but working on the response may for some have impacted negatively on training. A number of facilitators and barriers to learning were identified. CONCLUSION: The study findings highlight the opportunities for learning created by the pandemic. However, changing projects and the desire of SpRs to contribute to the response meant the impacts on training were mixed. Future deployment of SpRs should consider the balance of responsibility and pace when delegating work, as well as the need to supervise effectively and support remote working to maintain good mental wellbeing.

Effect of altering milking interval when milking 3 times in 2 days on milk and component yields in pasture-based dairy systems.

Dairy farmers face challenges attracting and retaining staff, partly due to the difficulty meeting the desires of the modern workforce. These include flexible work hours and regular time off. The task of milking fundamentally affects the ability of dairy farmers to meet these desires. Milking contributes to a large proportion of the hours spent working on dairy farms. The number of milkings (milking frequency) and their timing (milking interval) within a day influence the number of hours spent milking and what time in the day they occur. Milking 3 times in 2 d (3-in-2) reduces the amount of time spent milking compared with milking twice a day (TAD), without reducing milk yield as much as milking once a day (OAD). However, long intervals between 3-in-2 milkings can still lead to a long workday if farmers are expected to work between milkings. The objective of this study was to determine the effect of milking interval within a 3-in-2 milking frequency on milk yield and composition at 2 stages of lactation and compare these with OAD and TAD milking. Cows (n = 200) were milked in 5 groups of 40 at 3 intervals of 3-in-2: 8-20-20 h, 10-19-19 h, and 12-18-18 h, along with 24 h (OAD), and 10 and 14 h (TAD), for 6 wk at early lactation (mean 24 d in milk ± 7 d, SD) and again at mid lactation (mean 136 d in milk ± 18 d). Milk yields were recorded at each milking and milk samples collected weekly to determine composition. At both early and mid lactation there were no significant differences in milk, fat, protein, or lactose yields between the three 3-in-2 intervals. Cows milked 3-in-2 produced 8% less milk than cows milked TAD and 14% more than cows milked OAD, with smaller differences observed at mid lactation between TAD and 3-in-2. For a 3-in-2 milking frequency, a shorter milking interval can be implemented on the days when cows are milked twice. This may allow farmers to shorten the working day when using 3-in-2, without compromising milk or component yields.

Impact of Frailty on Short-Term Outcomes After Laparoscopic and Open Hepatectomy.

BACKGROUND: Although laparoscopic hepatectomy (LH) is associated with improved short-term outcomes compared to open hepatectomy (OH), it is unknown whether frail patients also benefit from LH. The aim of this study was to evaluate the impact of frailty on post-operative outcomes after LH and OH. PATIENTS AND METHODS: Consecutive patients who underwent LH and OH between January 2011 and December 2018 were identified from a prospective database. Frailty was assessed using the modified Frailty Index (mFI), with patients scoring mFI ≥ 1 deemed to be frail. RESULTS: Of 1826 patients, 34.7% (N = 634) were frail and 18.6% (N = 340) were elderly (≥ 75 years). Frail patients had significantly higher 90-day mortality (6.6% vs. 2.9%, p < 0.001) and post-operative complications (36.3% vs. 26.1%, p < 0.001) than those who were not frail, effects that were independent of patient age on multivariate analysis. For those undergoing minor resections, the benefits of LH vs. OH were similar for frail and non-frail patients. Length of hospital stay was 53% longer in OH (vs. LH) in frail patients, compared to 58% longer in the subgroup of non-frail patients. CONCLUSIONS: Frailty is independently associated with inferior post-operative outcomes in patients undergoing hepatectomy. However, the benefits of laparoscopic (compared to open) hepatectomy are similar for frail and non-frail patients. Frailty should not be a contraindication to laparoscopic minor hepatectomy in carefully selected patients.

Changes to objective structured clinical examinations (OSCE) at Australian medical schools in response to the COVID-19 pandemic.

INTRODUCTION: Objective Structured Clinical Examinations (OSCE) are used to assess clinical skills. We investigated how exit OSCEs changed in Australian medical schools in response to the COVID-19 pandemic. MATERIALS AND METHODS: The lead ACCLAiM assessment academic from 12 eligible Australian medical school members of the Australian Collaboration for Clinical Assessment in Medicine (ACCLAiM) received a 45-item semi-structured online questionnaire. RESULTS: All schools (12/12) responded. Exit OSCEs were not used by one school in 2019, and 3/11 schools in 2020. Of eight remaining schools, four reduced station numbers and testing time. The minimum OSCE testing time decreased from 64 min in 2019 to 54 min in 2020. Other modifications included: a completely online 'e-OSCE' (n = 1); hybrid delivery (n = 4); stations using: videos of patient encounters (n = 3), telephone calls (n = 2), skill completion without face-to-face patient encounters (n = 3). The proportion of stations involving physical examination reduced from 33% to 17%. Fewer examiners were required, and university faculty staff formed a higher proportion of examiners. CONCLUSIONS: All schools changed their OSCEs in 2020 in response to COVID-19. Modifications varied from reducing station numbers and changing delivery methods to removing OSCE and complete assessment re-structuring. Several innovative methods of OSCE delivery were implemented to preserve OSCE validity and reliability whilst balancing feasibility.

Health service COVID-19 wellbeing and support initiatives: a mixed-methods evaluation.

BACKGROUND: Health services implemented a range of initiatives during the COVID-19 pandemic to support employee wellbeing and assist employees to manage the professional and personal challenges they experienced. However, it is not known if such initiatives were acceptable to employees or met their needs. AIMS: To evaluate the wellbeing and support initiatives implemented at an Australian health service during the COVID-19 pandemic from the perspectives of employees (both users and non-users) and key stakeholders. METHODS: A mixed-methods design (survey, interviews and data audit) to investigate employees' and key stakeholders' perceptions, experiences and use of the wellbeing and support initiatives implemented at a large tertiary metropolitan health service in Melbourne, Australia. RESULTS: Ten employees participated in an interview and 907 completed a survey. The initiatives were well used and appreciated by staff. There was no significant difference in the proportion of clinical staff who had used the initiatives compared to non-clinical staff (44% versus 39%; P=0.223). Survey respondents reported the initiatives improved their mental health (n = 223, 8%), ability to cope with COVID-19 related stress and anxiety (n = 206, 79%), do their work (n = 200, 77%) and relationships with colleagues (n = 174, 67%). Staff would like many of the initiatives (with some modifications) to continue after the COVID-19 pandemic. CONCLUSIONS: The findings suggest a high level of staff satisfaction with the implemented wellbeing and support initiatives, and confirm the need for, and importance of, developing and implementing initiatives to support health service staff during outbreaks of infectious diseases such as the COVID-19 pandemic.

High-throughput analysis suggests differences in journal false discovery rate by subject area and impact factor but not open access status.

BACKGROUND: A low replication rate has been reported in some scientific areas motivating the creation of resource intensive collaborations to estimate the replication rate by repeating individual studies. The substantial resources required by these projects limits the number of studies that can be repeated and consequently the generalizability of the findings. We extend the use of a method from Jager and Leek to estimate the false discovery rate for 94 journals over a 5-year period using p values from over 30,000 abstracts enabling the study of how the false discovery rate varies by journal characteristics. RESULTS: We find that the empirical false discovery rate is higher for cancer versus general medicine journals (p = 9.801E-07, 95% CI: 0.045, 0.097; adjusted mean false discovery rate cancer = 0.264 vs. general medicine = 0.194). We also find that false discovery rate is negatively associated with log journal impact factor. A two-fold decrease in journal impact factor is associated with an average increase of 0.020 in FDR (p = 2.545E-04). Conversely, we find no statistically significant evidence of a higher false discovery rate, on average, for Open Access versus closed access journals (p = 0.320, 95% CI - 0.015, 0.046, adjusted mean false discovery rate Open Access = 0.241 vs. closed access = 0.225). CONCLUSIONS: Our results identify areas of research that may need additional scrutiny and support to facilitate replicable science. Given our publicly available R code and data, others can complete a broad assessment of the empirical false discovery rate across other subject areas and characteristics of published research.

Experiences of using the i-PARIHS framework: a co-designed case study of four multi-site implementation projects.

BACKGROUND: The integrated-Promoting Action on Research Implementation in Health Services (i-PARIHS) framework is an implementation framework that has been developed and refined over the last 20 years. Its underlying philosophy is that implementing research into healthcare practice is complex, unpredictable and non-linear which therefore requires a flexible and responsive approach to implementation. Facilitation is recognized as the central ingredient of this approach, and i-PARIHS now provides a Facilitation Guide with associated tools. This multiple case study of four implementation projects explored how the i-PARIHS framework has been practically operationalized by diverse implementation project teams. METHODS: A co-design approach was used to elicit the experiences of four implementation project teams who used the i-PARIHS framework to guide their implementation approach. We conducted the established co-design steps of (i) setting up for success, (ii) gathering the experience, and (iii) understanding the experience. In particular we explored teams' approaches to setting up their projects; why and how they used the i-PARIHS framework and what they learnt from the experience. RESULTS: We found both commonalities and differences in the use of i-PARIHS across the four implementation projects: (i) all the projects used the Facilitation Checklist that accompanies i-PARIHS as a starting point, (ii) the projects differed in how facilitation was carried out, (iii) existing tools were adapted for distinct phases: pre-implementation, during implementation, and post-implementation stages; and (iv) project-specific tools were often developed for monitoring implementation activities and fidelity. CONCLUSIONS: We have provided a detailed overview of how current users of i-PARIHS are operationalising the framework, which existing tools they are using or adapting to use, and where they have needed to develop new tools to best utilise the framework. Importantly, this study highlights the value of existing tools from the published i-PARIHS Facilitation Guide and provides a starting point to further refine and add to these tools within a future Mobilising Implementation of i-PARIHS (or "Mi-PARIHS") suite of resources. Specifically, Mi-PARIHS might include more explicit guidance and/or tools for developing a structured implementation plan and monitoring fidelity to the implementation plan, including recording how strategies are tailored to an evolving context.

Quantum Bath Control with Nuclear Spin State Selectivity via Pulse-Adjusted Dynamical Decoupling.

Dynamical decoupling (DD) is a powerful method for controlling arbitrary open quantum systems. In quantum spin control, DD generally involves a sequence of timed spin flips (π rotations) arranged to either average out or selectively enhance coupling to the environment. Experimentally, errors in the spin flips are inevitably introduced, motivating efforts to optimize error-robust DD. Here we invert this paradigm: by introducing particular control "errors" in standard DD, namely, a small constant deviation from perfect π rotations (pulse adjustments), we show we obtain protocols that retain the advantages of DD while introducing the capabilities of quantum state readout and polarization transfer. We exploit this nuclear quantum state selectivity on an ensemble of nitrogen-vacancy centers in diamond to efficiently polarize the ^{13}C quantum bath. The underlying physical mechanism is generic and paves the way to systematic engineering of pulse-adjusted protocols with nuclear state selectivity for quantum control applications.

Behavioural plasticity modulates temperature-related constraints on foraging time for a montane mammal.

Contemporary climate change is altering temperature profiles across the globe. Increasing temperatures can reduce the amount of time during which conditions are suitable for animals to engage in essential activities, such as securing food. Behavioural plasticity, the ability to alter behaviour in response to the environment, may provide animals with a tool to adjust to changes in the availability of suitable thermal conditions. The extent to which individuals can alter fitness-enhancing behaviours, such as food collection, to proximately buffer variation in temperature, however, remains unclear. Even less well understood are the potential performance advantages of flexible strategies among endotherms. We examined the degree to which individuals altered rates of food collection in response to temperature, and two potential benefits, using the American pika (Ochotona princeps), a temperature-sensitive, food-hoarding mammal, as a model. From July-September 2013-2015, we used motion-activated cameras and in situ temperature loggers to examine pika food-caching activity for 72 individuals across 10 sites in the central Rocky Mountains, USA. We quantified % nitrogen by cache volume as a metric of cache quality, and the number of events during which pikas were active in temperatures ≥25°C as a measure of potential thermoregulatory stress. We found a strong negative effect of temperature on the rate at which pikas cached food. Individual responses to temperature varied substantially in both the level of food-collecting activity and in the degree to which individuals shifted activity with warming temperature. After accounting for available foraging time, individuals that exhibited greater plasticity collected a comparable amount of nitrogen, while simultaneously experiencing fewer occasions in which temperatures eclipsed estimated thermal tolerances. By varying food-collection norms of reaction, individuals were able to plastically respond to temperature-driven reductions in foraging time. Through this increased flexibility, individuals amassed food caches of comparable quality, while minimizing exposure to potentially stressful thermal conditions. Our results suggest that, given sufficient resource quality and availability, plasticity in foraging activity may help temperature-limited endotherms adjust to climate-related constraints on foraging time.

The potential benefits of repeated measure experiments for fish disease-challenge host-pathogen investigations.

The utility of molecular response data arising from in-vivo single and repeated measure fish disease-challenge experiments is compared. An in-silico 'experiment' involving the generation of two imaginary immune-molecule quantity response profiles over time for individual animals was carried out. Daily 'observed' molecule quantities were drawn from the 'known' individual response profiles to mimic the results of single and repeated measurement. The results indicate that repeated measure experiments are required to infer individual level response profiles, and that these experiments also provide more accurate summary statistics and data more suited to inferring the dependent ordering of the molecular response. Additionally repeated measure experiments utilise fewer animals than single measure experiments. These results are described alongside a discussion of experimental methodological issues pertinent to the adoption of aquatic animal repeated measure experimental designs. We conclude that investigators need to take particular care when making inferences from single measure experiments and that serious consideration should be given to using repeated measure experiments for in-vivo fish disease-challenge investigations.

Implementation of government-directed policy in the hospital setting: a modified Delphi study.

BACKGROUND: In the last 20 years governments have sought to introduce policy that improves the quality of care provided in hospitals, yet little research has been done to understand how these policies are implemented, factors that affect the implementation process or what should be considered by decision-makers during policy development or implementation planning. Experts with real-life experience in the introduction and implementation of policy are best placed to provide valuable insight into practical issues that affect implementation and the associated outcomes of these policies. METHODS: A modified Delphi study of experts in hospital policy development and implementation was undertaken to investigate factors influencing the implementation of government-directed policy in the hospital setting. This study built on the findings of two previous studies - a qualitative study of clinician perspectives of policy implementation and a systematic review and meta-synthesis, in which common contextual factors and policy characteristics associated with policy implementation were ascertained. International experts with extensive experience in government-directed policy implementation at global, national, corporate, jurisdictional and organisational levels were asked to provide opinions on predetermined factors and the feasibility of considering these in policy development and implementation planning. Survey design and analysis was guided by the Consolidated Framework for Implementation Research. RESULTS: Eleven experts from four countries and with different health system perspectives participated in the study. Consensus was reached on the importance of all predetermined factors in the first survey round with additional factors for investigation highlighted by participants for examination in subsequent rounds. On study completion, expert consensus was reached on 24 factors of importance; only 20 of these factors reached consensus for feasibility. CONCLUSIONS: Study findings indicated that, whilst there are multiple factors of importance in policy implementation across all Consolidated Framework for Implementation Research domains, some factors, such as establishment of roles and responsibilities for implementation and organisational lines of accountability, are feasible for consideration at a hospital level only. In addition, four factors did not reach consensus in terms of feasibility, indicating that it may not be practical to consider all factors of importance when implementing policy; this has important implications for implementation planning and resource allocation.

Evaluation of an Artificial Neural Network Retention Index Model for Chemical Structure Identification in Nontargeted Metabolomics.

Liquid chromatography coupled with electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) is a major analytical technique used for nontargeted identification of metabolites in biological fluids. Typically, in LC-ESI-MS/MS based database assisted structure elucidation pipelines, the exact mass of an unknown compound is used to mine a chemical structure database to acquire an initial set of possible candidates. Subsequent matching of the collision induced dissociation (CID) spectrum of the unknown to the CID spectra of candidate structures facilitates identification. However, this approach often fails because of the large numbers of potential candidates (i.e., false positives) for which CID spectra are not available. To overcome this problem, CID fragmentation predication programs have been developed, but these also have limited success if large numbers of isomers with similar CID spectra are present in the candidate set. In this study, we investigated the use of a retention index (RI) predictive model as an orthogonal method to help improve identification rates. The model was used to eliminate candidate structures whose predicted RI values differed significantly from the experimentally determined RI value of the unknown compound. We tested this approach using a set of ninety-one endogenous metabolites and four in silico CID fragmentation algorithms: CFM-ID, CSI:FingerID, Mass Frontier, and MetFrag. Candidate sets obtained from PubChem and the Human Metabolite Database (HMDB) were ranked with and without RI filtering followed by in silico spectral matching. Upon RI filtering, 12 of the ninety-one metabolites were eliminated from their respective candidate sets, i.e., were scored incorrectly as negatives. For the remaining seventy-nine compounds, we show that RI filtering eliminated an average of 58% from PubChem candidate sets. This resulted in an approximately 2-fold improvement in average rankings when using CFM-ID, Mass Frontier, and MetFrag. In addition, RI filtering slightly increased the occurrence of number one rankings for all 4 fragmentation algorithms. However, RI filtering did not significantly improve average rankings when HMDB was used as the candidate database, nor did it significantly improve average rankings when using CSI:FingerID. Overall, we show that the current RI model incorrectly eliminated more true positives (12) than were expected (4-5) on the basis of the filtering method. However, it slightly improved the number of correct first place rankings and improved overall average rankings when using CFM-ID, Mass Frontier, and MetFrag.

Polygenic risk for schizophrenia, transition and cortical gyrification: a high-risk study.

BACKGROUND: Schizophrenia is a highly heritable disorder, linked to several structural abnormalities of the brain. More specifically, previous findings have suggested that increased gyrification in frontal and temporal regions are implicated in the pathogenesis of schizophrenia. METHODS: The current study included participants at high familial risk of schizophrenia who remained well (n = 31), who developed sub-diagnostic symptoms (n = 28) and who developed schizophrenia (n = 9) as well as healthy controls (HC) (n = 16). We first tested whether individuals at high familial risk of schizophrenia carried an increased burden of trait-associated alleles using polygenic risk score analysis. We then assessed the extent to which polygenic risk was associated with gyral folding in the frontal and temporal lobes. RESULTS: We found that individuals at high familial risk of schizophrenia who developed schizophrenia carried a significantly greater burden of risk-conferring variants for the disorder compared to those at high risk (HR) who developed sub-diagnostic symptoms or remained well and HC. Furthermore, within the HR cohort, there was a significant and positive association between schizophrenia polygenic risk score and bilateral frontal gyrification. CONCLUSIONS: These results suggest that polygenic risk for schizophrenia impacts upon early neurodevelopment to confer greater gyral folding in adulthood and an increased risk of developing the disorder.

Genome-wide association study of alcohol consumption and genetic overlap with other health-related traits in UK Biobank (N=112 117).

Alcohol consumption has been linked to over 200 diseases and is responsible for over 5% of the global disease burden. Well-known genetic variants in alcohol metabolizing genes, for example, ALDH2 and ADH1B, are strongly associated with alcohol consumption but have limited impact in European populations where they are found at low frequency. We performed a genome-wide association study (GWAS) of self-reported alcohol consumption in 112 117 individuals in the UK Biobank (UKB) sample of white British individuals. We report significant genome-wide associations at 14 loci. These include single-nucleotide polymorphisms (SNPs) in alcohol metabolizing genes (ADH1B/ADH1C/ADH5) and two loci in KLB, a gene recently associated with alcohol consumption. We also identify SNPs at novel loci including GCKR, CADM2 and FAM69C. Gene-based analyses found significant associations with genes implicated in the neurobiology of substance use (DRD2, PDE4B). GCTA analyses found a significant SNP-based heritability of self-reported alcohol consumption of 13% (se=0.01). Sex-specific analyses found largely overlapping GWAS loci and the genetic correlation (rG) between male and female alcohol consumption was 0.90 (s.e.=0.09, P-value=7.16 × 10-23). Using LD score regression, genetic overlap was found between alcohol consumption and years of schooling (rG=0.18, s.e.=0.03), high-density lipoprotein cholesterol (rG=0.28, s.e.=0.05), smoking (rG=0.40, s.e.=0.06) and various anthropometric traits (for example, overweight, rG=-0.19, s.e.=0.05). This study replicates the association between alcohol consumption and alcohol metabolizing genes and KLB, and identifies novel gene associations that should be the focus of future studies investigating the neurobiology of alcohol consumption.

Development of a Reverse Phase HPLC Retention Index Model for Nontargeted Metabolomics Using Synthetic Compounds.

The MolFind application has been developed as a nontargeted metabolomics chemometric tool to facilitate structure identification when HPLC biofluids analysis reveals a feature of interest. Here synthetic compounds are selected and measured to form the basis of a new, more accurate, HPLC retention index model for use with MolFind. We show that relatively inexpensive synthetic screening compounds with simple structures can be used to develop an artificial neural network model that is successful in making quality predictions for human metabolites. A total of 1955 compounds were obtained and measured for the model. A separate set of 202 human metabolites was used for independent validation. The new ANN model showed improved accuracy over previous models. The model, based on relatively simple compounds, was able to make quality predictions for complex compounds not similar to training data. Independent validation metabolites with feature combinations found in three or more training compounds were predicted with 97% sensitivity while metabolites with feature combinations found in less than three training compounds were predicted with >90% sensitivity. The study describes the method used to select synthetic compounds and new descriptors developed to encode the relationship between lipophilic molecular subgraphs and HPLC retention. Finally, we introduce the QRI (qualitative range of interest) modification of neural network backpropagation learning to generate models simultaneously based on quantitative and qualitative data.

What to eat in a warming world: do increased temperatures necessitate hazardous duty pay?

Contemporary climate change affects nearly all biomes, causing shifts in animal distributions and resource availability. Changes in resource selection may allow individuals to offset climatic stress, thereby providing a mechanism for persistence amidst warming conditions. Whereas the role of predation risk in food choice has been studied broadly, the extent to which individuals respond to thermoregulatory risk by changing resource preferences is unclear. We addressed whether individuals compensated for temperature-related reductions in foraging time by altering forage preferences, using the American pika (Ochotona princeps) as a model species. We tested two hypotheses: (1) food-quality hypothesis-individuals exposed to temperature extremes should select higher-quality vegetation in return for accepting a physiologically riskier feeding situation; and (2) food-availability hypothesis-individuals exposed to temperature extremes should prioritize foraging quickly, thereby decreasing selection for higher-quality food. We quantified the composition and quality (% moisture, % nitrogen, and fiber content) of available and harvested vegetation, and deployed a network of temperature sensors to measure in situ conditions for 30 individuals, during July-Sept., 2015. Individuals exposed to more extreme daytime temperatures showed increased selection for high-nitrogen and for low-fiber vegetation, demonstrating strong support for the food-quality hypothesis. By contrast, pikas that experienced warmer conditions did not reduce selection for any of the three vegetation-quality metrics, as predicted by the food-availability hypothesis. By shifting resource-selection patterns, temperature-limited animals may be able to proximately buffer some of the negative effects associated with rapidly warming environments, provided that sufficient resources remain on the landscape.

An evaluation of an immunomodulatory feed ingredient in heat-stressed lactating Holstein cows: Effects on hormonal, physiological, and production responses.

Holstein cows (n = 30) were balanced by days in milk, milk production, and parity (91 ± 5.9 d in milk, 36.2 ± 2.5 kg/d, and 3.1 ± 1.4, respectively) and fed OmniGen-AF (OG; Phibro Animal Health, Teaneck, NJ), an immune stimulant, at 0 g/cow per d for control (CON) or 56 g/cow per d for OG for 52 d on a commercial dairy. At 52 d of the study cows were randomly selected (n = 12) from both groups (6 OG and 6 CON) and housed in environmentally controlled rooms at the Agricultural Research Complex for 21 d at the University of Arizona. Cows were subjected to 7 d of thermoneutral (TN) conditions, 10 d of heat stress (HS), and 4 d of recovery (REC) under TN conditions. Feed intake, milk production, and milk composition were measured daily. Rectal temperatures (RT) and respiration rates (RR) were recorded 3 times per day (600, 1400, and 1800 h). Blood samples were taken on d 7 (TN), 8 (HS), 10 (HS), 17 (HS), and 18 (TN) during the Agricultural Research Complex segment. Cows in HS had higher RR and RT and water intake and lower dry matter intake and milk yield than these measures in TN. There was a treatment × environment interaction with cows fed OG having lower RR and RT and higher dry matter intake during peak thermal loads than CON. However, milk yield did not differ between groups. Cows fed OG had lower milk fat percent than CON (3.7 vs 4.3%) during HS. The SCC content of milk did not differ between treatment groups but rose in both groups during the REC phase following HS. Plasma insulin and plasma glucose levels were not different between groups. However, plasma insulin in both groups was lower during acute HS, then rose across the HS period, and was highest during the REC phase. Plasma cortisol levels were highest in all cows on the first day of HS (d 8) but were lower in cows fed OG compared with CON. However, plasma ACTH concentrations were elevated in OG-fed animals at all times samples were collected. Plasma ACTH was also elevated in cows fed both OG and CON during HS. Feeding OG reduced plasma cortisol during acute but not chronic HS and increased basal plasma ACTH, suggesting that OG treatment may alter the hypothalamic pituitary adrenal axis.