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The genotype of an individual is an important predictor of their immune function, and subsequently, their ability to control or avoid infection and ultimately contribute offspring to the next generation. However, the same genotype, subjected to different intrinsic and/or extrinsic environments, can also result in different phenotypic outcomes, which can be missed in controlled laboratory studies. Natural wildlife populations, which capture both genotypic and environmental variability, provide an opportunity to more fully understand the phenotypic expression of genetic variation. We identified a synonymous polymorphism in the high-affinity Immunoglobulin E (IgE) receptor (GC and non-GC haplotypes) that has sex-dependent effects on immune gene expression, susceptibility to infection, and reproductive success of individuals in a natural population of field voles ( Microtus agrestis ). We found that the effect of the GC haplotype on the expression of immune genes differed between sexes. Regardless of sex, both pro-inflammatory and anti-inflammatory genes were more highly relatively expressed in individuals with the GC haplotype than individuals without the haplotype. However, males with the GC haplotype showed a stronger signal for pro-inflammatory genes, while females showed a stronger signal for anti-inflammatory genes. Furthermore, we found an effect of the GC haplotype on the probability of infection with a common microparasite , Babesia microti, in females - with females carrying the GC haplotype being more likely to be infected. Finally, we found an effect of the GC haplotype on reproductive success in males - with males carrying the GC haplotype having a lower reproductive success. This is a rare example of a polymorphism whose consequences we are able to follow across immunity, infection, and reproduction for both males and females in a natural population., Competing Interests: KW, MB, JB, IF, JJ, CT, SP No competing interests declared, (© 2023, Wanelik et al.)

Drosophila oogenesis is a powerful and tractable model for studies of cell and developmental biology due to the multitude of well-characterized events in both germline and somatic cells, the ease of genetic manipulation in fruit flies, and the large number of egg chambers produced by each fly. Recent improvements in live imaging and ex vivo culturing protocols have enabled researchers to conduct more detailed, longer-term studies of egg chamber development, enabling insights into fundamental biological processes. Here, we present a protocol for dissection, culturing, and imaging of late-stage egg chambers to study intercellular and directional cytoplasmic flow during "nurse cell dumping." This critical developmental process towards the latter stages of oogenesis (stages 10b/11) results in rapid growth of the oocyte and shrinkage of the nurse cells and is accompanied by dynamic changes in cell shape. We also describe a procedure to record high-time-resolution movies of the flow of unlabeled cytoplasmic contents within nurse cells and through cytoplasmic bridges in the nurse cell cluster using reflection microscopy, and we describe two ways to analyze data from nurse cell dumping., (© 2023. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Background Context: Degenerative changes due to cervical spondylosis (CS) can detrimentally affect work ability and quality of life yet understanding of how physical exposure affects disease progression is limited., Purpose: To assess the associations between occupational physical exposures and occurrence of surgically treated cervical spondylosis (ST-CS) and early exit from the labor market via disability pension., Study Design/setting: Prospective register study with 20 years follow-up period., Patient Sample: Swedish construction workers participating in a national health surveillance project conducted between 1971 and 1993., Outcome Measures: Surgically treated cervical spondylosis (ST-CS) and early labor market exit at a minimum rate of 25% time on disability pension., Methods: Associations between occupational physical exposures (job exposure matrix) and subsequent ST-CS (National Hospital in-patient register) and early labor market exit via disability pension (Swedish Social Insurance Agency register) were assessed in a cohort of male construction workers (n=237,699)., Results: A total of 1381 ST-CS cases were present and a 20 years incidence rate of 35.1 cases per 100,000 person years (95% confidence interval (CI) 33.2-36.9). Increased relative risk (RR) for ST-CS was found for workers exposed to non-neutral (RR 1.40, 95% CI 1.15-1.69), and awkward neck postures (1.52, 1.19-1.95), working with the hands above shoulder height (1.30, 1.06-1.60), and high upper extremity loading (1.35, 1.15-1.59). Increased risk was also present for workers who reported frequent neck (3.06, 2.18-4.30) and upper back (3.84, 2.57-5.73) pain in the 12 months prior to survey. Among workers with elevated arm exposure, higher risk was seen in those who also had more frequent neck pain. ST-CS cases took early retirement more often (41.3%) and at a younger age (53 years) than the total study cohort (14.8% and 56 years of age, respectively)., Conclusions: Occupational exposure to non-neutral neck postures, work with hands above shoulders and high loads born through the upper extremities increased the risk for ST-CS and early retirement due to disability. Decreasing postural and load exposure is salient for primary, secondary, and tertiary prevention of CS. Neck pain was shown to be a prognostic factor for ST-CS, which stresses the importance of acting early and taking preventative action to reduce workplace exposure, and the need for systematic medical check-ups within primary or occupational care to mitigate disease progression and early labour market exit due to disability., Competing Interests: Conflict of Interests One or more of the authors declare financial or professional relationships on ICMJE-NASSJ disclosure forms., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: High flow nasal cannula (HFNC) use reduces work of breathing and improves oxygenation for patients with hypoxemic respiratory failure. Limited prior work has explored protocolized use of HFNC for trauma patients outside the Intensive Care Unit (ICU). The purpose of this study is to describe and evaluate use of HFNC for patients with rib fractures when therapy was standard of care on all floors of the hospital., Methods: In 2018, the study hospital expanded use of HFNC (AIRVO; Fisher Paykel, Auckland, NZ) to all floors of the hospital, making it available in the ICU, Emergency Department (ED), and on general inpatient floors. The study group included adult patients with three or more rib fractures who received HFNC at any location in the hospital (Phase 2: January 2018-December 2019). The study group was compared to a historical control group when HFNC was available only in the ICU (Phase 1: March 2013-July 2015). Patients were excluded from the study if they received invasive mechanical ventilation prior to HFNC. Primary outcomes were mechanical ventilation rates, ICU days, length of hospitalization, and mortality., Results: During the study period, 63 patients received HFNC, with 35% of patients (n = 22) receiving the duration of therapy outside the ICU. When compared to the control group (N = 63), there were no significant differences in total hospital days (9 vs. 9, p=.64), mechanical ventilation (19% vs. 13%, p=.47), or mortality (3% vs. 5%, p = 1.00). Twenty-seven percent of patients (n = 17) in the study group avoided the ICU during hospitalization., Conclusions: Findings suggest that HFNC therapy can be safely initiated and managed on all hospital floors for patients with multiple rib fractures. Making the therapy available outside the ICU may reduce healthcare resource use without adversely affecting patient outcomes., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Competing Interests: Dr Vines discloses relationships with Teleflex Medical, the Rice Foundation, and Theravance Biopharma. Dr Scott discloses relationships Teleflex and Aerogen. Dr Kaur discloses a relationship with the American Association of Respiratory Care. Dr Trump discloses a relationship with Fisher and Paykel. Ms Jackson discloses a relationship with Fisher & Paykel. Dr Li discloses relationships with Fisher & Paykel Healthcare, Heyer, Aerogen, the Rice Foundation, the American Association for Respiratory Care, and also serves as Section Editor for Respiratory Care. The other authors have no conflict of interest to disclose.

Introduction: Human regular U-500 insulin (U-500R) is approved for subcutaneous (SC) injection in patients with diabetes requiring >200 units/day of insulin. Here, pharmacokinetic and pharmacodynamic (PK/PD) profiles following U-500R administered by continuous subcutaneous insulin infusion (CSII) and SC injection in adults with type 2 diabetes (T2D) on high-dose insulin were studied., Methods: In this randomized, crossover, euglycemic clamp study, patients received a 100-unit bolus of U-500R via SC injection or CSII with basal infusion using a U-500R specific pump. PK parameters were estimated using non-compartmental methods. PD estimates were derived from the glucose infusion rate during the euglycemic clamp procedure., Results: When corrected for the basal infusion, the PK profiles for the 100-unit bolus of U-500R were similar for CSII and SC injection. Without correction for basal infusion, PK and PD profiles showed a greater insulin concentration and effect when U-500R was administered via CSII compared to SC injection, primarily due to basal insulin infusion for CSII. The ratio of geometric least squares AUC 0-tlast means SC:CSII (90% CI) is 0.857 (0.729, 1.01) with correction (mean AUC 0-tlast : 5230 pmol*L/h [SC injection] and 6070 pmol*L/h [CSII, with correction]) and 0.424 (0.361, 0.499) without correction (mean AUC 0-tlast : 12300 pmol*L/h [CSII, without correction]). Median time-to-peak insulin concentration was six hours (range 0.5-8 hours) via SC injection and five hours (0.5-12 hours) via CSII., Conclusions: In adults with T2D on high-dose insulin, U-500R PK/PD parameters were similar for a 100-unit bolus when given by SC injection or CSII via a U-500R pump.

Nasal high flow therapy has been previously studied for the management of acute hypoxic respiratory failure in patients with chronic obstructive pulmonary disease but the data regarding its use outside of the intensive care unit are sparse. We aimed to evaluate safety and efficacy of nasal high flow therapy outside of the intensive care unit in patients with acute hypoxic respiratory failure and known chronic obstructive pulmonary disease. We conducted a retrospective matched historic cohort study of adult patients with diagnosed chronic obstructive pulmonary disease presenting with acute hypoxic respiratory failure between December 2017 to June 2019, after the initiation of a new protocol, which allowed patients to be managed with nasal high flow therapy on the medical/surgical wards instead of transferring them to the ICU per prior standard of care. Nasal high flow therapy was initiated either in the emergency department or on the medical/surgical wards. Patients were matched with historical cohorts who were managed with prior standard of care based on age, body mass index, comorbidities, and home oxygen use. Primary outcome of interest was difference in rates of mechanical ventilation. Secondary outcomes included hospital length of stay, total number of days spent in the intensive care unit, and in-hospital mortality. A total of 90 patients met study inclusion criteria and were matched to 90 historical control patients. Among the study group, 8% required mechanical ventilation versus 9% in the control group (p = 0.79). Hospital length of stay was 7 days in study group versus 6 days in control group (p = 0.02), and in-hospital mortality was the same in both study and control groups at 12% (p = 0.99). Nineteen percent of study group patients required ICU level of care at any time during the admission compared with 49% of control group (p < 0.001). Nasal high flow therapy use in patients with acute hypoxic respiratory failure and underlying chronic obstructive pulmonary disease outside of the intensive care unit may spare ICU resources and cost without delay in definitive care such as mechanical ventilation., (© 2021 The Authors. The Clinical Respiratory Journal published by John Wiley & Sons Ltd.)

Integrated working can be a means of providing efficient and cost-effective care, which benefits both service users and health professionals. However, it does require readiness of practitioners to work in new and innovative ways to achieve integration. This paper describes the findings of a qualitative study exploring the nature of practice-based education and training underpinning successful integrated care teams using an ecological systems theory lens. Nine teams in the West Midlands region of the United Kingdom (UK) participated in this study. A total of 27 participants were involved in semi-structured interviews during which they shared their views and experiences of learning in practice. Thematic analysis of interview transcripts highlighted the shifting context of working in integrated teams impacting on learning, the influence of leadership on education and training, the nature of in-service training, and the knowledge-sharing culture. The findings highlight that the learning climate is highly dependent on the leadership ethos in the practice context, which influences the allocation of time and resources for training and clinical supervision. Whilst formal education and training has an important role to play in fostering integrated working, informal learning is pivotal to successful integration and potentially has greater impact making it worthy of further study.

Background: Awake prone positioning (APP) has been advocated to improve oxygenation and prevent intubation of patients with acute hypoxemic respiratory failure due to coronavirus disease 2019 (COVID-19). This paper aims to synthesize the available evidence on the efficacy of APP., Methods: We performed a systematic review of proportional outcomes from observational studies to compare intubation rate in patients treated with APP or with standard care., Results: A total of 46 published and 4 unpublished observational studies that included 2,994 subjects were included, of which 921 were managed with APP and 870 were managed with usual care. APP was associated with significant improvement of oxygenation parameters in 381 cases of 19 studies that reported this outcome. Among the 41 studies assessing intubation rates (870 subjects treated with APP and 852 subjects treated with usual care), the intubation rate was 27% (95% CI 19-37%) as compared to 30% (95% CI 20-42%) ( P = .71), even when duration of application, use of adjunctive respiratory assist device (high-flow nasal cannula or noninvasive ventilation), and severity of oxygenation deficit were taken into account. There appeared to be a trend toward improved mortality when APP was compared with usual care (11% vs 22%), which was not statistically significant., Conclusions: APP was associated with improvement of oxygenation but did not reduce the intubation rate in subjects with acute respiratory failure due to COVID-19. This finding is limited by the high heterogeneity and the observational nature of included studies. Randomized controlled clinical studies are needed to definitively assess whether APP could improve key outcome such as intubation rate and mortality in these patients., (Copyright © 2022 by Daedalus Enterprises.)

Humpback whales (Megaptera novaeangliae) are a cosmopolitan species and perform long annual migrations between low-latitude breeding areas and high-latitude feeding areas. Their breeding populations appear to be spatially and genetically segregated due to long-term, maternally inherited fidelity to natal breeding areas. In the Southern Hemisphere, some humpback whale breeding populations mix in Southern Ocean waters in summer, but very little movement between Pacific and Atlantic waters has been identified to date, suggesting these waters constituted an oceanic boundary between genetically distinct populations. Here, we present new evidence of summer co-occurrence in the West Antarctic Peninsula feeding area of two recovering humpback whale breeding populations from the Atlantic (Brazil) and Pacific (Central and South America). As humpback whale populations recover, observations like this point to the need to revise our perceptions of boundaries between stocks, particularly on high latitude feeding grounds. We suggest that this "Southern Ocean Exchange" may become more frequent as populations recover from commercial whaling and climate change modifies environmental dynamics and humpback whale prey availability., (© 2021. The Author(s).)

Objective: HIV seroconversion during pregnancy disproportionately affects urban, minority pregnant individuals. In order to prevent perinatal HIV transmission, it is essential that individuals are aware of HIV risk factors and effective transmission prevention strategies are employed. Thus, we aimed to examine knowledge about HIV transmission and attitudes about HIV among low-income, minority pregnant individuals and their partners living in a high HIV prevalence area., Methods: In this qualitative study, pregnant participants were HIV-seronegative individuals receiving publicly-funded prenatal care in an urban academic center in the United States. Pregnant individuals and their partners were recruited to participate in a quality improvement program offering HIV testing to partners of pregnant people. Semi-structured guides were used to conduct individual interviews about participant sources of information about HIV, knowledge about transmission, and attitudes regarding those living with HIV. Transcripts were analyzed using the constant comparative method to determine themes and subthemes., Results: Of 51 participants, 29 were pregnant individuals and 22 were non-pregnant partners. We found that inaccurate knowledge about perinatal HIV transmission was prevalent. Sources of information about HIV included reputable literary information or educational experiences, broadcast media, and word-of-mouth sources. Participants held dichotomous perceptions of people living with HIV., Conclusions: Among low-income, minority pregnant people and their partners in a high HIV prevalence area, inaccuracies and lack of knowledge about HIV transmission were common. Efforts to educate pregnant individuals and their partners about HIV and perinatal HIV transmission should address common misconceptions and use popular sources of information., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Awake prone positioning (APP) is widely used in the management of patients with coronavirus disease (COVID-19). The primary objective of this study was to compare the outcome of COVID-19 patients who received early versus late APP., Methods: Post hoc analysis of data collected for a randomized controlled trial (ClinicalTrials.gov NCT04325906). Adult patients with acute hypoxemic respiratory failure secondary to COVID-19 who received APP for at least one hour were included. Early prone positioning was defined as APP initiated within 24 h of high-flow nasal cannula (HFNC) start. Primary outcomes were 28-day mortality and intubation rate., Results: We included 125 patients (79 male) with a mean age of 62 years. Of them, 92 (73.6%) received early APP and 33 (26.4%) received late APP. Median time from HFNC initiation to APP was 2.25 (0.8-12.82) vs 36.35 (30.2-75.23) hours in the early and late APP group (p < 0.0001), respectively. Average APP duration was 5.07 (2.0-9.05) and 3.0 (1.09-5.64) hours per day in early and late APP group (p < 0.0001), respectively. The early APP group had lower mortality compared to the late APP group (26% vs 45%, p = 0.039), but no difference was found in intubation rate. Advanced age (OR 1.12 [95% CI 1.0-1.95], p = 0.001), intubation (OR 10.65 [95% CI 2.77-40.91], p = 0.001), longer time to initiate APP (OR 1.02 [95% CI 1.0-1.04], p = 0.047) and hydrocortisone use (OR 6.2 [95% CI 1.23-31.1], p = 0.027) were associated with increased mortality., Conclusions: Early initiation (< 24 h of HFNC use) of APP in acute hypoxemic respiratory failure secondary to COVID-19 improves 28-day survival. Trial registration ClinicalTrials.gov NCT04325906., (© 2021. The Author(s).)

Environmental impacts of the 1986 Chernobyl Nuclear Power Plant accident are much debated, but the effects of radiation on host microbiomes have received little attention to date. We present the first analysis of small mammal gut microbiomes from the Chernobyl Exclusion Zone in relation to total absorbed dose rate, including both caecum and faeces samples. We provide novel evidence that host species determines fungal community composition, and that associations between microbiome (both bacterial and fungal) communities and radiation exposure vary between host species. Using ambient versus total weighted absorbed dose rates in analyses produced different results, with the latter more robust for interpreting microbiome changes at the individual level. We found considerable variation between results for faecal and gut samples of bank voles, suggesting faecal samples are not an accurate indicator of gut composition. Associations between radiation exposure and microbiome composition of gut samples were not robust against geographical variation, although we identified families of bacteria (Lachnospiraceae and Muribaculaceae) and fungi (Steccherinaceae and Strophariaceae) in the guts of bank voles that may serve as biomarkers of radiation exposure. Further studies considering a range of small mammal species are needed to establish the robustness of these potential biomarkers., (© 2021 The Authors. Journal of Animal Ecology published by John Wiley & Sons Ltd on behalf of British Ecological Society.)

Introduction: The biological consequences of absorbed radiation doses are ill-defined for radiopharmaceuticals, unlike for external beam radiotherapy (EBRT). A reliable assay that assesses the biological consequences of any radionuclide is much needed. Here, we evaluated the cell-free plasmid DNA assay to determine the relative biological effects of radionuclides such as Auger electron-emitting [ 67 Ga]GaCl 3 or [ 111 In]InCl 3 compared to EBRT., Methods: Supercoiled pBR322 plasmid DNA (1.25 or 5 ng/μL) was incubated with 0.5 or 1 MBq [ 67 Ga]GaCl 3 or [ 111 In]InCl 3 for up to 73 h or was exposed to EBRT ( 137 Cs; 5 Gy/min; 0-40 Gy). The induction of relaxed and linear plasmid DNA, representing single and double strand breaks, respectively, was assessed by gel electrophoresis. Chelated forms of 67 Ga were also investigated using DOTA and THP. Topological conversion rates for supercoiled-to-relaxed (k sr x ) or relaxed-to-linear (k rl x ) DNA were obtained by fitting a kinetic model., Results: DNA damage increased both with EBRT dose and incubation time for [ 67 Ga]GaCl 3 and [ 111 In]InCl 3 . Damage caused by [ 67 Ga]GaCl 3 decreased when chelated. [ 67 Ga]GaCl 3 proved more damaging than [ 111 In]InCl 3 ; 1.25 ng/μL DNA incubated with 0.5 MBq [ 67 Ga]GaCl 3 for 2 h led to a 70% decrease of intact plasmid DNA as opposed to only a 19% decrease for [ 111 In]InCl 3 . For both EBRT and radionuclides, conversion rates were slower for 5 ng/μL than 1.25 ng/μL plasmid DNA. DNA damage caused by 1 Gy EBRT was the equivalent to damage caused by 0.5 MBq unchelated [ 67 Ga]GaCl 3 and [ 111 In]InCl 3 after 2.05 ± 0.36 and 9.3 ± 0.77 h of incubation, respectively., Conclusions: This work has highlighted the power of the plasmid DNA assay for a rapid determination of the relative biological effects of radionuclides compared to external beam radiotherapy. It is envisaged this approach will enable the systematic assessment of imaging and therapeutic radionuclides, including Auger electron-emitters, to further inform radiopharmaceutical design and application., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Southern right whale vocalizations were recorded concurrently with visual observations off the sub-Antarctic Island of South Georgia, and the characteristics of these calls were described. Calls were also compared to those of humpback whales at South Georgia, to determine how the two species might reliably be distinguished acoustically. The southern right whale calls measured (which were all upcalls) had lower frequency with peak energy and were mostly shorter in duration than the calls measured from humpback whales. The frequency upsweep and the lack of harmonics of southern right whale calls were also diagnostic characteristics.

Helminth infections in wood mice (n = 483), trapped over a period of 26 years in the woods surrounding Malham Tarn in North Yorkshire, were analysed. Although 10 species of helminths were identified, the overall mean species richness was 1.01 species/mouse indicating that the helminth community was relatively depauperate in this wood mouse population. The dominant species was Heligmosomoides polygyrus, the prevalence (64.6%) and abundance (10.4 worms/mouse) of which declined significantly over the study period. Because of the dominance of this species, analyses of higher taxa (combined helminths and combined nematodes) also revealed significantly declining values for prevalence, although not abundance. Helminth species richness (HSR) and Brillouin's index of diversity (BID) did not show covariance with year, neither did those remaining species whose overall prevalence exceeded 5% (Syphacia stroma, Aonchotheca murissylvatici and Plagiorchis muris). Significant age effects were detected for the prevalence and abundance of all higher taxa, H. polygyrus and P. muris, and for HSR and BID, reflecting the accumulation of helminths with increasing host age. Only two cases of sex bias were found; male bias in abundance of P. muris and combined Digenea. We discuss the significance of these results and hypothesize about the underlying causes.

From insects to mice, oocytes develop within cysts alongside nurse-like sister germ cells. Prior to fertilization, the nurse cells' cytoplasmic contents are transported into the oocyte, which grows as its sister cells regress and die. Although critical for fertility, the biological and physical mechanisms underlying this transport process are poorly understood. Here, we combined live imaging of germline cysts, genetic perturbations, and mathematical modeling to investigate the dynamics and mechanisms that enable directional and complete cytoplasmic transport in Drosophila melanogaster egg chambers. We discovered that during "nurse cell (NC) dumping" most cytoplasm is transported into the oocyte independently of changes in myosin-II contractility, with dynamics instead explained by an effective Young-Laplace law, suggesting hydraulic transport induced by baseline cell-surface tension. A minimal flow-network model inspired by the famous two-balloon experiment and motivated by genetic analysis of a myosin mutant correctly predicts the directionality, intercellular pattern, and time scale of transport. Long thought to trigger transport through "squeezing," changes in actomyosin contractility are required only once NC volume has become comparable to nuclear volume, in the form of surface contractile waves that drive NC dumping to completion. Our work thus demonstrates how biological and physical mechanisms cooperate to enable a critical developmental process that, until now, was thought to be mainly biochemically regulated., Competing Interests: The authors declare no competing interest.

The diet of Antarctic fur seals (Arctocephalus gazella) at South Georgia is dominated by Antarctic krill (Euphausia superba). During the breeding season, foraging trips by lactating female fur seals are constrained by their need to return to land to provision their pups. Post-breeding, seals disperse in order to feed and recover condition; estimates indicate c.70% of females remain near to South Georgia, whilst others head west towards the Patagonian Shelf or south to the ice-edge. The krill fishery at South Georgia operates only during the winter, providing the potential for fur seal: fishery interaction during these months. Here we use available winter (May to September) tracking data from Platform Terminal Transmitter (PTT) tags deployed on female fur seals at Bird Island, South Georgia. We develop habitat models describing their distribution during the winters of 1999 and 2003 with the aim of visualising and quantifying the degree of spatial overlap between female fur seals and krill harvesting in South Georgia waters. We show that spatial distribution of fur seals around South Georgia is extensive, and that the krill fishery overlaps with small, highly localised areas of available fur seal habitat. From these findings we discuss the implications for management, and future work., Competing Interests: The authors have declared that no competing interests exist.

Background: High-flow nasal cannula (HFNC) is an option for respiratory support in patients with acute hypoxic respiratory failure. To improve patient outcomes, reduce ICU-associated costs, and ease ICU bed availability, a multi-phased, comprehensive strategy was implemented to make HFNC available outside the ICU under the supervision of pulmonology or trauma providers in cooperation with a dedicated respiratory therapy team. The purpose of this study was to describe the education and implementation process for initiating HFNC therapy outside the ICU and to convey key patient demographics and outcomes from the implementation period., Methods: HFNC therapy was implemented at a tertiary hospital in the Midwest, with systematic roll-out to all in-patient floors over a 9-month period. Utilization of the therapy and patient outcomes were tracked to ensure safety and efficacy of the effort., Results: During the implementation period, 346 unique subjects met study inclusion criteria. Median (interquartile range) hospital length of stay was 8 d (4-12), and median duration of HFNC therapy was 44 h (18-90). Two thirds of subjects ( n = 238) received the entire course of HFNC therapy outside the ICU, and more than half of subjects ( n = 184) avoided the ICU for their entire hospitalization. Moreover, 6% of subjects in the study group escalated from HFNC to noninvasive ventilation, and 5% of subjects escalated from HFNC to mechanical ventilation., Conclusions: A comprehensive implementation process and a robust therapy protocol were integral to initiating and managing HFNC in all hospital locations. Study findings indicate that patients with acute hypoxic respiratory failure can safely receive HFNC therapy outside the ICU with appropriate patient selection and staff education., Competing Interests: Fisher & Paykel Healthcare provided grant support and donated disposables to UnityPoint Health to support nurse and physician education during the implementation phase of the study. Ms Jackson and Dr Trump have disclosed relationships with Fisher & Paykel HealthCare. The other authors have disclosed no conflicts of interest., (Copyright © 2021 by Daedalus Enterprises.)

By determining susceptibility to disease, environment-driven variation in immune responses can affect the health, productivity and fitness of vertebrates. Yet how the different components of the total environment control this immune variation is remarkably poorly understood. Here, through combining field observation, experimentation and modelling, we are able to quantitatively partition the key environmental drivers of constitutive immune allocation in a model wild vertebrate (three-spined stickleback, Gasterosteus aculeatus). We demonstrate that, in natural populations, thermal conditions and diet alone are sufficient (and necessary) to explain a dominant (seasonal) axis of variation in immune allocation. This dominant axis contributes to both infection resistance and tolerance and, in turn, to the vital rates of infectious agents and the progression of the disease they cause. Our results illuminate the environmental regulation of vertebrate immunity (given the evolutionary conservation of the molecular pathways involved) and they identify mechanisms through which immunocompetence and host-parasite dynamics might be impacted by changing environments. In particular, we predict a dominant sensitivity of immunocompetence and immunocompetence-driven host-pathogen dynamics to host diet shifts., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

This paper reports the results of a multi-stage effort to develop a measure of Academic Entitlement. An empirical/rational approach was taken to develop items and reduce the item set for a final version of the Academic Entitlement Scale (AES). The measure includes seven dimensions: Accommodation, Reward for Effort, Responsibility Avoidance, Grade Haggling, Customer Orientation, Customer Service Expectations, and General Academic Entitlement. Fit, using Confirmatory Factor Analysis, for the seven-factor correlated model and a bifactor model including General AE and the six specific factors, was good. The full measure is reported along with descriptive statistics for the scale and preliminary validation evidence., Competing Interests: The authors have declared that no competing interests exist.

Background: There is a paucity of data relating to refugee eye health in Australia. This study aimed at investigating the spectrum of vision impairment and other ocular conditions in refugees utilising the Victorian Eyecare Service operated by the Australian College of Optometry., Methods: A cross-sectional study of electronic clinical records of 518 individuals (adults and children) recognised as refugees by the Australian College of Optometry and treated between January 2013 and May 2014 were identified. Extracted data included presenting visual acuities, best-corrected visual acuities, and final refraction values (using spherical equivalents), for both eyes. Diagnoses of presenting ocular conditions were also extracted., Results: Of all refugees examined, 129 (27.2 per cent) had some degree of vision impairment (≤ 6/9.5) based on presenting visual acuities in their better eye; five (1.0 per cent) being of a severe (≤ 6/60) or profound (≤ 6/120) nature. In contrast, 27 (6.3 per cent) refugees had some degree of vision impairment based on best-corrected visual acuities in their better eye; two (0.4 per cent) being of a severe or profound nature. The prevalence of myopia (≥ -0.50 D) in the better eye was 23.0 per cent (n = 114); 25 (5.0 per cent) being moderate (≥ -3.00 D) to high (≥ -6.00 D). The prevalence of hypermetropia (≥ +2.00 D) in the better eye was 3.2 per cent (n = 16); 12 (2.4 per cent) being moderate (≥ +2.25 D) to high (≥ +5.25 D). The most common ocular conditions diagnosed at initial presentation were refractive error (n = 104, 20.1 per cent) and dry eyes (n = 57, 11.0 per cent)., Conclusion: Mild vision impairment and refractive error are significant issues for refugees attending the Australian College of Optometry, emphasising the need for optometry, particularly refractive, services in this population., (© 2019 Optometry Australia.)

Biogeographic patterns of globally widespread species are expected to reflect regional structure, as well as connectivity caused by occasional long-distance dispersal. We assessed the level and drivers of population structure, connectivity, and timescales of population isolation in one of the most widespread and ruderal plants in the world - the common moss Ceratodon purpureus . We applied phylogenetic, population genetic, and molecular dating analyses to a global (n = 147) sampling data set, using three chloroplast loci and one nuclear locus. The plastid data revealed several distinct and geographically structured lineages, with connectivity patterns associated with worldwide, latitudinal "bands." These imply that connectivity is strongly influenced by global atmospheric circulation patterns, with dispersal and establishment beyond these latitudinal bands less common. Biogeographic patterns were less clear within the nuclear marker, with gene duplication likely hindering the detection of these. Divergence time analyses indicated that the current matrilineal population structure in C. purpureus has developed over the past six million years, with lineages diverging during the late Miocene, Pliocene, and Quaternary. Several colonization events in the Antarctic were apparent, as well as one old and distinct Antarctic clade, possibly isolated on the continent since the Pliocene. As C. purpureus is considered a model organism, the matrilineal biogeographic structure identified here provides a useful framework for future genetic and developmental studies on bryophytes. Our general findings may also be relevant to understanding global environmental influences on the biogeography of other organisms with microscopic propagules (e.g., spores) dispersed by wind., (Copyright © 2020 Biersma, Convey, Wyber, Robinson, Dowton, van de Vijver, Linse, Griffiths and Jackson.)

We introduce a graphene-based nanofluidic cell that facilitates in situ imaging of liquid samples via transmission electron microscopy. The cell combines the benefits of graphene liquid cells-namely, high resolution, reduced charging effects, and excellent sample stability-with the ability to introduce reactants and control fluid concentrations as provided by conventional silicon-nitride-windowed flow cells. The graphene flow cell offers significantly less window bowing compared to existing commercial holders. We demonstrate the performance of the flow cell by imaging gold nanoparticle dynamics and uranyl acetate crystallization. Our results confirm the utility of graphene flow cells in obtaining the high spatial and temporal resolution required for probing the complex dynamics of nanoparticles and nucleation pathways in aqueous solutions.

OBJECTIVE | Human regular U-500 insulin (U-500R) is concentrated insulin with basal and prandial activity that can be used as insulin monotherapy. The goal of this study was to better understand treatment patterns (total daily dose [TDD] and concomitant medications), adherence, and persistence in real-world patients treated with U-500R. DESIGN AND METHODS | We selected patients from the Truven Health MarketScan database who initiated U-500R between 2010 and 2013. We collected data for three periods: pre-index (12 months before initiation), post-index (12 months after initiation or until a gap of ≥60 days in U-500R claims), and follow-up (12 months after post-index). Data were analyzed using descriptive statistics and a regression model as appropriate. RESULTS | We identified 1,582 patients who met the selection criteria. The median TDD of U-500R during the post-index period was 333 units/day, with 70.0% of patients using 300-400 units/day. During the post-index period, 74.1% of patients had U-500R claims that did not overlap with prescriptions for other insulins, interpreted as U-500R monotherapy. Among patients with ≥1 U-500R fill in the post-index period ( n = 1,208), 54.4% had a medication possession ratio (MPR, a measure of adherence) ≥80%. Although 849 patients had a gap of ≥60 days in U-500R claims in the post-index period, 602 of those resumed U-500R in the follow-up period. Of the 733 patients who had no gap in U-500R claims in the post-index period, 286 had a gap of ≥60 days in claims in year 2, and 447 continued with U-500R treatment beyond 2 years. CONCLUSION | These results demonstrate that U-500R was commonly used as insulin monotherapy, with a median TDD >300 units/day. Compared with published, relevant studies of other insulins, U-500R showed similar or greater adherence and persistence rates. These new data may help guide clinical decision-making when choosing insulin therapy for patients requiring high doses of insulin., (© 2020 by the American Diabetes Association.)

As whales recover from commercial exploitation, they are increasing in abundance in habitats that they have been absent from for decades. However, studying the recovery and habitat use patterns of whales, particularly in remote and inaccessible regions, frequently poses logistical and economic challenges. Here we trial a new approach for measuring whale density in a remote area, using Very-High-Resolution WorldView-3 satellite imagery. This approach has capacity to provide sightings data to complement and assist traditional sightings surveys. We compare at-sea whale density estimates to estimates derived from satellite imagery collected at a similar time, and use suction-cup archival logger data to make an adjustment for surface availability. We demonstrate that satellite imagery can provide useful data on whale occurrence and density. Densities, when unadjusted for surface availability are shown to be considerably lower than those estimated by the ship survey. However, adjusted for surface availability and weather conditions (0.13 whales per km 2 , CV = 0.38), they fall within an order of magnitude of those derived by traditional line-transect estimates (0.33 whales per km 2 , CV = 0.09). Satellite surveys represent an exciting development for high-resolution image-based cetacean observation at sea, particularly in inaccessible regions, presenting opportunities for ongoing and future research.

Single cell manipulation is important in biosensing, biorobotics, and quantitative cell analysis. Although microbeads, droplets, and microrobots have been developed previously, it is still challenging to simultaneously excise, capture, and manipulate single cells in a biocompatible manner. Here, we describe untethered single cell grippers, that can be remotely guided and actuated on-demand to actively capture or excise individual or few cells. We describe a novel molding method to micropattern a thermally responsive wax layer for biocompatible motion actuation. The multifingered grippers derive their energy from the triggered release of residual differential stress in bilayer hinges composed of silicon oxides. A magnetic layer enables remote guidance through narrow conduits and fixed tissue sections ex vivo . Our results provide an important advance in high-throughput single cell scale biopsy tools important to lab-on-a-chip devices, microrobotics, and minimally invasive surgery.

As species recover from exploitation, continued assessments of connectivity and population structure are warranted to provide information for conservation and management. This is particularly true in species with high dispersal capacity, such as migratory whales, where patterns of connectivity could change rapidly. Here we build on a previous long-term, large-scale collaboration on southern right whales (Eubalaena australis) to combine new (nnew) and published (npub) mitochondrial (mtDNA) and microsatellite genetic data from all major wintering grounds and, uniquely, the South Georgia (Islas Georgias del Sur: SG) feeding grounds. Specifically, we include data from Argentina (npub mtDNA/microsatellite = 208/46), Brazil (nnew mtDNA/microsatellite = 50/50), South Africa (nnew mtDNA/microsatellite = 66/77, npub mtDNA/microsatellite = 350/47), Chile-Peru (nnew mtDNA/microsatellite = 1/1), the Indo-Pacific (npub mtDNA/microsatellite = 769/126), and SG (npub mtDNA/microsatellite = 8/0, nnew mtDNA/microsatellite = 3/11) to investigate the position of previously unstudied habitats in the migratory network: Brazil, SG, and Chile-Peru. These new genetic data show connectivity between Brazil and Argentina, exemplified by weak genetic differentiation and the movement of 1 genetically identified individual between the South American grounds. The single sample from Chile-Peru had an mtDNA haplotype previously only observed in the Indo-Pacific and had a nuclear genotype that appeared admixed between the Indo-Pacific and South Atlantic, based on genetic clustering and assignment algorithms. The SG samples were clearly South Atlantic and were more similar to the South American than the South African wintering grounds. This study highlights how international collaborations are critical to provide context for emerging or recovering regions, like the SG feeding ground, as well as those that remain critically endangered, such as Chile-Peru., (© The American Genetic Association 2020.)

Individuals vary in their immune response and, as a result, some are more susceptible to infectious disease than others. Little is known about the nature of this individual variation in natural populations, or which components of immune pathways are most responsible, but defining this underlying landscape of variation is an essential first step to understanding the drivers of this variation and, ultimately, predicting the outcome of infection. We describe transcriptome-wide variation in response to a standardised immune challenge in wild field voles. We find that genes (hereafter 'markers') can be categorised into a limited number of types. For the majority of markers, the response of an individual is dependent on its baseline expression level, with significant enrichment in this category for conventional immune pathways. Another, moderately sized, category contains markers for which the responses of different individuals are also variable but independent of their baseline expression levels. This category lacks any enrichment for conventional immune pathways. We further identify markers which display particularly high individual variability in response, and could be used as markers of immune response in larger studies. Our work shows how a standardised challenge performed on a natural population can reveal the patterns of natural variation in immune response.

Research suggests an association between motor variability (MV) during repetitive work and work-related musculoskeletal disorders (MSDs). However, whether MV is a consistent individual trait, even across working conditions or tasks, remains unknown. This study assessed whether individual MV traits were consistent during complex work performed under different temporal conditions. Fifteen women performed cyclic assembly under four conditions differing in pace and organisation (line-type, batch-type). MV of trapezius muscle activity and upper arm elevation was quantified and partitioned into variance components. For all MV metrics, a non-zero between-subjects variance was found, indicating consistent individual MV traits across conditions. Variance between subjects was higher for electromyography (EMG) MV metrics compared with kinematic metrics. Our results showed individuals exhibited consistent MV traits across working conditions differing in pace and production process. Further research is needed to understand whether MV is an individual predictive factor for MSD onset or progression., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Molecular radiopharmaceuticals based on bioconjugates of chelators with peptides and proteins have had significant clinical impact in the diagnosis and treatment of several types of cancers. In the 1990s, indium-111 and yttrium-90 labeled chelator-peptide/protein conjugates established the clinical utility of these radiopharmaceuticals for receptor-targeted γ-scintigraphy imaging and systemic radiotherapy. Second-generation bioconjugates based on peptides targeting the somatostatin II receptor and the prostate-specific membrane antigen are now widely used for management of neuroendocrine and prostate cancer, respectively. These bioconjugates are typically radiolabeled with gallium-68 for imaging of target receptor expression with positron emission tomography, and the β - -emitter, lutetium-177, for targeted radiotherapy. Innovations in radioisotope technology and biomolecular therapies are likely to drive the future clinical development of radiopharmaceuticals based on radiometals. New chelator-peptide and chelator-protein bioconjugates will underpin nuclear medicine advances in molecular imaging and radiotherapy.

We test the ability of Very High Resolution satellite (VHR) imagery to detect stranded whales using both manual and automated methods. We use the 2015 mass mortality event in the Gulf of Penas locality, central Patagonia, Chile, as an initial case study. This event was the largest known mass mortality of baleen whales, with at least 343 whales, mainly sei whales (Balaenoptera borealis), documented as stranding. However, even with such a large number of whales, due to the remote location of the gulf the strandings went unrecorded for several weeks. Aerial and boat surveys of the area were conducted two to four months after the mortality event. In this study we use 50cm resolution WorldView2 imagery to identify and count strandings from two archival images acquired just after the stranding event and two months before the aerial and ground surveys, and to test manual and automated methods of detecting stranded whales. Our findings show that whales are easily detected manually in the images but due to the heterogeneous colouration of decomposing whales, spectral indices are unsuitable for automatic detection. Our satellite counts suggest that, at the time the satellite images were taken, more whales were stranded than recorded in the aerial survey, possibly due to the non-comprehensive coverage of the aerial survey or movement of the carcases between survey acquisition. With even higher resolution imagery now available, satellite imagery may be a cost effective alternative to aerial surveys for future assessment of the extent of mass whale stranding events, especially in remote and inaccessible areas., Competing Interests: Consultora Paleosuchus Ltda loaned equipment for the aerial survey of the Gulf of Penas and employs Carolina S.Gutstein. We are extremely grateful for satellite images provided by DigitalGlobe (Maxar). Carolina S.Gutstein is employed by VH thanks the Blue Marine Foundation and the Huinay Foundation for their support. This does not alter our adherence to PLOS ONE policies on sharing data and materials.” (as detailed online in our guide for authors http://journals.plos.org/plosone/s/competing-interests). If this adherence statement is not accurate and there are restrictions on sharing of data and/or materials, please state these. Please note that we cannot proceed with consideration of your article until this information has been declared.

The recovery of whale populations from centuries of exploitation will have important management and ecological implications due to greater exposure to anthropogenic activities and increasing prey consumption. Here, a Bayesian population model integrates catch data, estimates of abundance, and information on genetics and biology to assess the recovery of western South Atlantic (WSA) humpback whales ( Megaptera novaeangliae ). Modelling scenarios evaluated the sensitivity of model outputs resulting from the use of different data, different model assumptions and uncertainty in catch allocation and in accounting for whales killed but not landed. A long period of exploitation drove WSA humpback whales to the brink of extinction. They declined from nearly 27 000 (95% PI = 22 800-33 000) individuals in 1830 to only 450 (95% PI = 200-1400) whales in the mid-1950s. Protection led to a strong recovery and the current population is estimated to be at 93% (95% PI = 73-100%) of its pre-exploitation size. The recovery of WSA humpback whales may result in large removals of their primary prey, the Antarctic krill ( Euphausia superba ), and has the potential to modify the community structure in their feeding grounds. Continued monitoring is needed to understand how these whales will respond to modern threats and to climate-driven changes to their habitats., Competing Interests: We declare we have no competing interests., (© 2019 The Authors.)

Immunity is a central component of fitness in wild animals, but its determinants are poorly understood. In particular, the importance of locomotory activity as a constraint on immunity is unresolved. Using a piscine model ( Gasterosteus aculeatus ), we combined a 25-month observational time series for a wild lotic habitat with an open flume experiment to determine the influence of locomotor activity (countercurrent swimming) on natural variation in immune function. To maximize the detectability of effects in our flume experiment, we set flow velocity and duration (10 cm/s for 48 hr) just below the point at which exhaustion would ensue. Following this treatment, we measured expression in a set of immune-associated genes and infectious disease resistance through a standard challenge with an ecologically relevant monogenean infection ( Gyrodactylus gasterostei ). In the wild, there was a strong association of water flow with the expression of immune-associated genes, but this association became modest and more complex when adjusted for thermal effects. Our flume experiment, although statistically well-powered and based on a scenario near the limits of swimming performance in stickleback, detected no countercurrent swimming effect on immune-associated gene expression or infection resistance. The field association between flow rate and immune expression could thus be due to an indirect effect, and we tentatively advance hypotheses to explain this. This study clarifies the drivers of immune investment in wild vertebrates; although locomotor activity, within the normal natural range, may not directly influence immunocompetence, it may still correlate with other variables that do., Competing Interests: None declared., (© 2019 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

Materials with a stochastic microstructure, like foams, typically exhibit low mechanical stiffness, whereas lattices with a designed microarchitecture often show notably improved stiffness. These periodic architected materials have previously been designed by rule, using the Maxwell criterion to ensure that their deformation is dominated by the stretching of their struts. Classical designs following this rule tend to be anisotropic, with stiffness depending on the load orientation, but recently, isotropic designs have been reported by superimposing complementary anisotropic lattices. We have designed stiff isotropic lattices de novo with topology optimization, an approach based on continuum finite element analysis. Here, we present results of experiments on these lattices, fabricated by additive manufacturing, that validate predictions of their performance and demonstrate that they are as efficient as those designed by rule, despite appearing to violate the Maxwell criterion. These findings highlight the enhanced potential of topology optimization to design materials with unprecedented properties., (Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)

We developed and evaluated calibration models predicting objectively measured sitting, standing and walking time from self-reported data using a compositional data analysis (CoDA) approach. A total of 98 office workers (48 women) at the Swedish Transport Administration participated. At baseline and three-months follow-up, time spent sitting, standing and walking at work was assessed for five working days using a thigh-worn accelerometer (Actigraph), as well as by self-report (IPAQ). Individual compositions of time spent in the three behaviors were expressed by isometric log-ratios (ILR). Calibration models predicting objectively measured ILRs from self-reported ILRs were constructed using baseline data, and then validated using follow-up data. Un-calibrated self-reports were inaccurate; root-mean-square (RMS) errors of ILRs for sitting, standing and walking were 1.21, 1.24 and 1.03, respectively. Calibration reduced these errors to 36% (sitting), 40% (standing), and 24% (walking) of those prior to calibration. Calibration models remained effective for follow-up data, reducing RMS errors to 33% (sitting), 51% (standing), and 31% (walking). Thus, compositional calibration models were effective in reducing errors in self-reported physical behaviors during office work. Calibration of self-reports may present a cost-effective method for obtaining physical behavior data with satisfying accuracy in large-scale cohort and intervention studies.

Objectives: The aim was to assess the association between occupational biomechanical exposure and the occurrence of radial nerve entrapment (RNE) in construction workers over a 13-year follow-up period., Methods: A cohort of 229 707 male construction workers who participated in a national occupational health surveillance programme (1971-1993) was examined prospectively (2001-2013) for RNE. Height, weight, age, smoking status and job title (construction trade) were obtained on health examination. RNE case status was defined by surgical release of RNE, with data from the Swedish national registry for out-patient surgery records. A job exposure matrix was developed, and biomechanical exposure estimates were assigned according to job title. Highly correlated exposures were summed into biomechanical exposure scores. Negative binomial models were used to estimate the relative risks (RR) (incidence rate ratios) of RNE surgical release for the biomechanical factors and exposure sum scores. Predicted incidence was assessed for each exposure score modelled as a continuous variable to assess exposure-response relationships., Results: The total incidence rate of surgically treated RNE over the 13-year observation period was 3.53 cases per 100 000 person-years. There were 92 cases with occupational information. Increased risk for RNE was seen in workers with elevated hand-grip forces (RR=1.79, 95% CI 0.97 to 3.28) and exposure to hand-arm vibration (RR=1.47, 95% CI 1.08 to 2.00)., Conclusions: Occupational exposure to forceful handgrip work and vibration increased the risk for surgical treatment of RNE., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Early examples of computers were almost exclusively based on mechanical devices. Although electronic computers became dominant in the past 60 years, recent advancements in three-dimensional micro-additive manufacturing technology provide new fabrication techniques for complex microstructures which have rekindled research interest in mechanical computations. Here we propose a new digital mechanical computation approach based on additively-manufacturable micro-mechanical logic gates. The proposed mechanical logic gates (i.e., NOT, AND, OR, NAND, and NOR gates) utilize multi-stable micro-flexures that buckle to perform Boolean computations based purely on mechanical forces and displacements with no electronic components. A key benefit of the proposed approach is that such systems can be additively fabricated as embedded parts of microarchitected metamaterials that are capable of interacting mechanically with their surrounding environment while processing and storing digital data internally without requiring electric power.

Natural interactions between the diet, microbiome, and immunity are largely unstudied. Here we employ wild three-spined sticklebacks as a model, combining field observations with complementary experimental manipulations of diet designed to mimic seasonal variation in the wild. We clearly demonstrate that season-specific diets are a powerful causal driver of major systemic immunophenotypic variation. This effect occurred largely independently of the bulk composition of the bacterial microbiome (which was also driven by season and diet) and of host condition, demonstrating neither of these, per se , constrain immune allocation in healthy individuals. Nonetheless, through observations in multiple anatomical compartments, differentially exposed to the direct effects of food and immunity, we found evidence of immune-driven control of bacterial community composition in mucus layers. This points to the interactive nature of the host-microbiome relationship, and is the first time, to our knowledge, that this causal chain (diet → immunity → microbiome) has been demonstrated in wild vertebrates. Microbiome effects on immunity were not excluded and, importantly, we identified outgrowth of potentially pathogenic bacteria (especially mycolic-acid producing corynebacteria) as a consequence of the more animal-protein-rich summertime diet. This may provide part of the ultimate explanation (and possibly a proximal cue) for the dramatic immune re-adjustments that we saw in response to diet change.

Food insecurity among U.S. older adults has more than doubled since 2001 and is higher in those who are frail. Given the growing aging population and the importance of physical functioning and adequate food intake, the increase in food insecurity is a public health concern. This study examined the association between domains of physical limitations and food security in U.S. older adults. Data were from the National Health and Nutrition Examination Survey (2007-2012) participants 60 years of age and older ( n  = 5969). Physical limitations were defined as some or much difficulty on 19 activities, categorized into 5 domains and an index score. Food security status was categorized as full, marginal, low, or very low, and also dichotomized into food secure and food insecure (marginal, low, or very low food security). Multinomial and logistic regression models were used to estimate odds ratios (OR) and adjusted ORs (aOR) with food security as the dependent variable and physical limitations as independent variables. Older adults with 4 or more physical limitations were more likely to report very low food security than older adults without limitations (aOR:2.62, 95% CI:1.43, 4.81). The strongest correlates of food insecurity were Instrumental Activities of Daily Living (aOR:1.49; 95% CI:1.10, 2.01), Leisure and Social Activities (aOR:1.56; 95% CI:1.37, 2.14), and General Physical Activities (aOR:1.50; 95% CI:1.08, 2.07). Physical functioning is important for food security among older adults. Interventions should incorporate assessment of physical functioning, and provide resources for food acquisition, preparation, and intake for older adults with physical limitations.

Objectives The aim of this study was to determine the association between occupational biomechanical exposures and occurrence of surgically treated ulnar nerve entrapment (UNE). Methods A cohort of 229 689 male construction workers who participated in a national occupational health surveillance program (1971-1993) were examined prospectively over a 13-year case ascertainment period (2001-2013) for surgically treated UNE. Job title (construction trade), smoking status, height, weight and age were recorded on examination. Job titles were merged into occupational groups of workers performing similar work tasks and having similar training. Occupational biomechanical exposure estimates were assigned to each occupational group with a job exposure matrix (JEM) developed for the study. Negative binomial models were used to assess the relative risks for each biomechanical exposure and the sums of highly correlated biomechanical exposures. Surgical treatment of UNE was determined via a linkage with the Swedish Hospital Outpatient Surgery Register. Results There were 555 cases of surgically treated UNE within the cohort. Workers exposed to forceful hand-grip factors had a 1.4-fold higher relative risk (95% CI 1.18-1.63) of undergoing surgical treatment for UNE compared to unexposed workers. Occupational groups comprising workers exposed to forceful hand-grip work showed the highest risks for UNE and included concrete workers, floor layers, ground preparatory workers, rock blasters, and sheet-metal workers. Conclusion Forceful hand-grip work increases the risk for surgically treated ulnar nerve entrapment.

Typically, mechanical metamaterial properties are programmed and set when the architecture is designed and constructed, and do not change in response to shifting environmental conditions or application requirements. We present a new class of architected materials called field responsive mechanical metamaterials (FRMMs) that exhibit dynamic control and on-the-fly tunability enabled by careful design and selection of both material composition and architecture. To demonstrate the FRMM concept, we print complex structures composed of polymeric tubes infilled with magnetorheological fluid suspensions. Modulating remotely applied magnetic fields results in rapid, reversible, and sizable changes of the effective stiffness of our metamaterial motifs.

For fish, there can be multiple consequences of parasitic infections, including the physical impacts on swimming and the pathological costs of infection. This study used the three-spined stickleback ( Gasterosteus aculeatus ) and the ectoparasitic fish louse, Argulus foliaceus , to assess both physical (including form drag and mass) and pathological effects of infection. Both sustained (prolonged swimming within an open channel flume) and burst (C-start) swimming performance were measured on individual fish before (trials 1-2) and after infection (trials 3-5). Experimental infection occurred shortly before the third trial, when the physical impacts of infection could be separated from any subsequent pathology as transmission of adult parasites causes instantaneous drag effects prior to observable pathology. Despite the relatively large size of the parasite and corresponding increase in hydrodynamic drag for the host, there were no observable physical effects of infection on either sustained or burst host swimming. By contrast, parasite-induced pathology is the most probable explanation for reduced swimming performance across both tests. All sticklebacks displayed a preference for flow refugia, swimming in low-velocity regions of the flume, and this preference increased with both flow rate and infection time. This study suggests that even with large, physically demanding parasites their induced pathology is of greater concern than direct physical impact., (© 2018 The Author(s).)

Compared to tedious, multi-step treatments for electroless gold plating of traditional thermoplastics, this communication describes a simpler three-step procedure for 3D printed crosslinked polyacrylate substrates. This allows for the synthesis of ultralight gold foam microlattice materials with great potential for architecture-sensitive applications in future energy, catalysis, and sensing.

'Nitro-gen mustard' bis-(2-chloro-eth-yl)amine derivatives (2 R ,4 S ,5 R )- and (2 S ,4 S ,5 R )-2-[bis-(2-chloro-eth-yl)amino]-3,4-dimethyl-5-phenyl-1,3,2-oxaza-phos-pho-lidin-2-one ( 2a and 2b , respectively), C 14 H 21 Cl 2 N 2 O 2 P, and (2 R ,4 R )- and (2 S ,4 R )-2-[bis-(2-chloro-eth-yl)amino]-4-isobutyl-1,3,2-oxaza-phospho-lidin-2-one ( 3a and 3b , respectively), C 10 H 21 Cl 2 N 2 O 2 P, were synthesized as a mixture of diastereomers through a 1:1 reaction of enanti-omerically pure chiral amino alcohols with bis-(2-chloro-eth-yl)phospho-ramidic dichloride. Flash column chromatography yielded diastereomerically pure products, as supported by 31 P NMR. The crystal structures of 2b and 3b were obtained to determine their absolute configuration at phospho-rus, and 31 P NMR chemical shift trends are proposed based on the spatial relationship of the bis-(2-chloro-eth-yl)amine moiety and the chiral substituent of the amino alcohol. Oxaza-phospho-lidinones were observed to have a more downfield 31 P NMR chemical shift when the aforementioned substituents are in a syn configuration and vice versa for when they are anti .

Brain aging is marked by cognitive decline and susceptibility to neurodegeneration. Calorie restriction (CR) increases neurogenesis, improves memory function, and protects from age-associated neurological disorders. Epigenetic mechanisms, including DNA methylation, are vital to normal central nervous system cellular and memory functions and are dysregulated with aging. The beneficial effects of CR have been proposed to work through epigenetic processes, but this is largely unexplored. We therefore tested whether life long CR prevents age-related hippocampal DNA methylation changes. Hippocampal DNA from young (3 months) and old (24 months) male mice fed ad libitum and 24-month-old mice fed a 40% calorie-restricted diet from 3 months of age were examined by genome-wide bisulfite sequencing to measure methylation with base specificity. Over 27 million CG and CH (non-CG) sites were examined. Of the ∼40,000 differentially methylated CG and ∼80,000 CH sites with aging, >1/3 were prevented by CR and were found across genomic regulatory regions and gene pathways. CR also caused alterations to CG and CH methylation at sites not differentially methylated with aging, and these CR-specific changes demonstrated a different pattern of regulatory element and gene pathway enrichment than those affected by aging. CR-specific DNA methyltransferase 1 and Tet methylcytosine dioxygenase 3 promoter hypermethylation corresponded to reduced gene expression. These findings demonstrate that CR attenuates age-related CG and CH hippocampal methylation changes, in combination with CR-specific methylation that may also contribute to the neuroprotective effects of CR. The prevention of age-related methylation alterations is also consistent with the prolongevity effects of CR working through an epigenetic mechanism., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: To compile, analyze, and summarize the literature on concentrated insulins (i.e. concentrations >100 units/mL) from randomized controlled trials and derive guidance on appropriate use of these agents., Methods: Searches were conducted in Medline, Embase, the Cochrane Central Register of Controlled Trials, Trialtrove (through April 2016) and ClinicalTrials.gov (through April 2017) for phase 1-4 clinical studies using concentrated insulins. Selected studies included multiple-arm, randomized controlled trials evaluating subcutaneously administered concentrated insulins. Trial registration numbers (selected studies) were searched in Medline, Embase and Google Scholar (through April 2017). Late-phase studies were graded using guidance from the Agency for Healthcare Research and Quality., Results: Thirty-eight completed trials (7900 participants) and 34 qualifying publications were identified. Four marketed concentrated insulins were evaluated: two long-acting basal (insulin glargine 300 units/mL and insulin degludec 200 units/mL [IDeg200]), one rapid-acting prandial (insulin lispro 200 units/mL [ILis200]), and one prandial/basal (human regular insulin 500 units/mL). Early-phase trials established bioequivalence for IDeg200 and ILis200 with the corresponding 100 units/mL formulations. Efficacy studies showed noninferior glycemic control between comparators for long-acting basal and prandial/basal products with generally low severe hypoglycemia. Six additional concentrated insulins with completed early-phase development were also identified., Conclusion: Concentrated-insulin products demonstrated efficacious and safe outcomes in appropriate patients. Clinical findings (HbA1c and hypoglycemia) and methodology (initiation and titration), patient factors (insulin experience and dosing requirements) and treatment characteristics (bioequivalence, potency and device features) are important considerations. This overview of these and other factors provides essential information and guidance for using concentrated insulins in clinical practice.

In contrast to the conditions in most laboratory studies, wild animals are routinely challenged by multiple infections simultaneously, and these infections can interact in complex ways. This means that the impact of a parasite on its host's physiology and fitness cannot be fully assessed in isolation, and requires consideration of the interactions with other co-infections. Here we examine the impact of two common blood parasites in the field vole (Microtus agrestis): Babesia microti and Bartonella spp., both of which have zoonotic potential. We collected longitudinal and cross-sectional data from four populations of individually tagged wild field voles. This included data on biometrics, life history, ectoparasite counts, presence/absence of microparasites, immune markers and, for a subset of voles, more detailed physiological and immunological measurements. This allowed us to monitor infections over time and to estimate components of survival and fecundity. We confirm, as reported previously, that B. microti has a preventative effect on infection with Bartonella spp., but that the reverse is not true. We observed gross splenomegaly following B. microti infection, and an increase in IL-10 production together with some weight loss following Bartonella spp. infection. However, these animals appeared otherwise healthy and we detected no impact of infection on survival or fecundity due to the two haemoparasite taxa. This is particularly remarkable in the case of B. microti which induces apparently drastic long-term changes to spleen sizes, but without major adverse effects. Our work sheds light on the ecologies of these important zoonotic agents, and more generally on the influence that interactions among multiple parasites have on their hosts in the wild., (Copyright © 2018 Australian Society for Parasitology. Published by Elsevier Ltd. All rights reserved.)