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Background Circulating levels of the endogenous inhibitor of nitric oxide synthase, asymmetric dimethylarginine (ADMA), are positively associated with the prevalence of metabolic syndrome (MetS) in cross-sectional investigations. It is unclear if circulating ADMA and other methylarginines are associated with incident MetS prospectively. Methods We related circulating ADMA, symmetric dimethylarginine (SDMA), L-arginine (ARG) concentrations (measured with a validated tandem mass spectrometry assay) and the ARG/ADMA ratio to MetS and its components in 2914 (cross-sectional analysis, logistic regression; mean age 58 years, 55% women) and 1656 (prospective analysis, Cox regression; mean age 56 years, 59% women) individuals from the Framingham Offspring Study who attended a routine examination. Results Adjusting for age, sex, smoking, and eGFR, we observed significant associations of ADMA (direct) and ARG/ADMA (inverse) with odds of MetS (N = 1461 prevalent cases; Odds Ratio [OR] per SD increment 1.13, 95%CI 1.04–1.22; and 0.89, 95%CI 0.82–0.97 for ADMA and ARG/ADMA, respectively). Upon further adjustment for waist circumference, systolic and diastolic blood pressure, glucose, high-density lipoprotein cholesterol, and triglycerides, we observed a positive relation between SDMA and MetS (OR per SD increment 1.15, 95% CI 1.01–1.30) but the other associations were rendered statistically non-significant. We did not observe statistically significant associations between any of the methylarginines and the risk of new-onset MetS (752 incident events) over a median follow-up of 11 years. Conclusion It is unclear whether dimethylarginines play an important role in the incidence of cardiometabolic risk in the community, notwithstanding cross-sectional associations. Further studies of larger samples are needed to replicate our findings.

Understanding diet is critical for conservation of endangered predators. Southern Resident killer whales (SRKW) (Orcinus orca) are an endangered population occurring primarily along the outer coast and inland waters of Washington and British Columbia. Insufficient prey has been identified as a factor limiting their recovery, so a clear understanding of their seasonal diet is a high conservation priority. Previous studies have shown that their summer diet in inland waters consists primarily of Chinook salmon (Oncorhynchus tshawytscha), despite that species’ rarity compared to some other salmonids. During other times of the year, when occurrence patterns include other portions of their range, their diet remains largely unknown. To address this data gap, we collected feces and prey remains from October to May 2004–2017 in both the Salish Sea and outer coast waters. Using visual and genetic species identification for prey remains and genetic approaches for fecal samples, we characterized the diet of the SRKWs in fall, winter, and spring. Chinook salmon were identified as an important prey item year-round, averaging ~50% of their diet in the fall, increasing to 70–80% in the mid-winter/early spring, and increasing to nearly 100% in the spring. Other salmon species and non-salmonid fishes, also made substantial dietary contributions. The relatively high species diversity in winter suggested a possible lack of Chinook salmon, probably due to seasonally lower densities, based on SRKW’s proclivity to selectively consume this species in other seasons. A wide diversity of Chinook salmon stocks were consumed, many of which are also at risk. Although outer coast Chinook samples included 14 stocks, four rivers systems accounted for over 90% of samples, predominantly the Columbia River. Increasing the abundance of Chinook salmon stocks that inhabit the whales’ winter range may be an effective conservation strategy for this population.

Streptococcus pyogenes or group A Streptococcus (GAS) is a leading cause of bacterial pharyngitis, skin and soft tissue infections, life-threatening invasive infections, and the post-infectious autoimmune syndromes of acute rheumatic fever and post-streptococcal glomerulonephritis. Genetic manipulation of this important pathogen is complicated by resistance of the organism to genetic transformation. Very low transformation efficiency is attributed to recognition and degradation of introduced foreign DNA by a type I restriction-modification system encoded by the hsdRSM locus. DNA sequence analysis of this locus in ten GAS strains that had been previously transformed with an unrelated plasmid revealed that six of the ten harbored a spontaneous mutation in hsdR, S, or M. The mutations were all different, and at least five of the six were predicted to result in loss of function of the respective hsd gene product. The unexpected occurrence of such mutations in previously transformed isolates suggested that the process of transformation selects for spontaneous inactivating mutations in the Hsd system. We investigated the possibility of exploiting the increased transformability of hsd mutants by constructing a deletion mutation in hsdM in GAS strain 854, a clinical isolate representative of the globally dominant M1T1 clonal group. Mutant strain 854ΔhsdM exhibited a 5-fold increase in electrotransformation efficiency compared to the wild type parent strain and no obvious change in growth or off-target gene expression. We conclude that genetic transformation of GAS selects for spontaneous mutants in the hsdRSM restriction modification system. We propose that use of a defined hsdM mutant as a parent strain for genetic manipulation of GAS will enhance transformation efficiency and reduce the likelihood of selecting spontaneous hsd mutants with uncharacterized genotypes.

Purpose This study aimed to examine the association between confidence in accessing HIV services, primary sources of HIV information, and primary care provider status for African American and Latinx individuals in Indiana. Methods An online survey was disseminated to African American and Latinx individuals using snowball and social media recruitment methods, resulting in a final sample size of n = 308. A multivariable linear regression analysis was performed to examine the relationships between confidence accessing HIV services, primary care provider status, sexual identification, and sources of HIV information. Results Of the total respondents, 62.5% (n = 193) identified as male and 36.9% (n = 114) identified as female. Most identified as African American (72.5%, n = 224), followed by 27.2% (n = 84) who identified as Latinx. Participants who used their primary care providers as a primary source of obtaining HIV information had a significantly higher level of comfort with accessing HIV services. Those who identified family members as a primary source of HIV information and those who identified as bisexual demonstrated a lower level of confidence in accessing HIV services. Discussion This study's results enhance our understanding of marginalization within minority groups regarding sexual identification and accessing HIV services. These results also offer insight into the importance of healthcare access because having a primary care provider was a strong predictor of increased confidence in accessing HIV services.

Lung cancer is the leading cause of cancer-related deaths. While the recent use of immune checkpoint inhibitors significantly improves patient outcomes, responsiveness remains restricted to a small proportion of patients. Conventional dendritic cells (DCs) play a major role in anticancer immunity. In mice, two subpopulations of DCs are found in the lung: DC2s (CD11b+Sirpα+) and DC1s (CD103+XCR1+), the latest specializing in the promotion of anticancer immune responses. However, the impact of lung cancer on DC populations and the consequent influence on the anticancer immune response remain poorly understood. To address this, DC populations were studied in murine models of Lewis Lung Carcinoma (LLC) and melanoma-induced lung metastasis (B16F10). We report that direct exposure to live or dead cancer cells impacts the capacity of DCs to differentiate into CD103+ DC1s, leading to profound alterations in CD103+ DC1 proportions in the lung. In addition, we observed the accumulation of CD103loCD11b+ DCs, which express DC2 markers IRF4 and Sirpα, high levels of T-cell inhibitory molecules PD-L1/2 and the regulatory molecule CD200. Finally, DC1s were injected in combination with an immune checkpoint inhibitor (anti-PD-1) in the B16F10 model of resistance to the anti-PD-1 immune checkpoint therapy; the co-injection restored sensitivity to immunotherapy. Thus, we demonstrate that lung tumor development leads to the accumulation of CD103loCD11b+ DCs with a regulatory potential combined with a reduced proportion of highly-specialized antitumor CD103+ DC1s, which could promote cancer growth. Additionally, promoting an anticancer DC signature could be an interesting therapeutic avenue to increase the efficacy of existing immune checkpoint inhibitors.

Health assessments have potential to improve health of older people. This study compares long-term health care utilisation, physical functioning, and mortality for women aged 75 years or over who have had a health assessment and those who have not. Prospective data on health service use, physical functioning, and deaths among a large cohort of women born 1921–26 were analysed. Propensity score matching was used to produce comparable groups of women according to whether they had a health assessment or not. The study population included 6128 (67.3%) women who had an assessment, and 2971 (32.7%) women who had no assessment. Propensity matching produced 2101 pairs. Women who had an assessment had more use of other health services, longer survival, and were more likely to survive with high physical functioning compared to women with no assessment. Among women who had good baseline physcial functioning scores, women who had an assessment had significantly lower odds of poor outcomes at 1000 days follow-up compared to women who had no assessment (OR: 0.67, 95%CI: 0.52, 0.85). This large observational study shows the real-world potential for assessments to improve health outcomes for older women. However, they also increased health service use. This increased healthcare is likely to be an important mechanism in improving the women’s health outcomes.

Breast ductal carcinoma in situ (DCIS) is a non-obligate precursor of invasive ductal carcinoma (IDC). It is still unclear which DCIS will become invasive and which will remain indolent. Patients often receive surgery and radiotherapy, but this early intervention has not produced substantial decreases in late-stage disease. Sprouty proteins are important regulators of ERK/MAPK signaling and have been studied in various cancers. We hypothesized that Sprouty4 is an endogenous inhibitor of ERK/MAPK signaling and that its loss/reduced expression is a mechanism by which DCIS lesions progress toward IDC, including triple-negative disease. Using immunohistochemistry, we found reduced Sprouty4 expression in IDC patient samples compared to DCIS, and that ERK/MAPK phosphorylation had an inverse relationship to Sprouty4 expression. These observations were reproduced using a 3D culture model of disease progression. Knockdown of Sprouty4 in MCF10.DCIS cells increased ERK/MAPK phosphorylation as well as their invasive capability, while overexpression of Sprouty4 in MCF10.CA1d IDC cells reduced ERK/MAPK phosphorylation, invasion, and the aggressive phenotype exhibited by these cells. Immunofluorescence experiments revealed reorganization of the actin cytoskeleton and relocation of E-cadherin back to the cell surface, consistent with the restoration of adherens junctions. To determine whether these effects were due to changes in ERK/MAPK signaling, MEK1/2 was pharmacologically inhibited in IDC cells. Nanomolar concentrations of MEK162/binimetinib restored an epithelial-like phenotype and reduced pericellular proteolysis, similar to Sprouty4 overexpression. From these data we conclude that Sprouty4 acts to control ERK/MAPK signaling in DCIS, thus limiting the progression of these premalignant breast lesions.

We aimed to apply the Systems Engineering Initiative for Patient Safety (SEIPS) model to increase effectiveness and sustainability of the World Health Organization’s (WHOs) hand hygiene (HH) guidelines within healthcare systems. Our cross-sectional, mixed-methods study took place at Jimma University Medical Center (JUMC), a tertiary care hospital in Jimma, Ethiopia, between November 2018 and August 2020 and consisted of three phases: baseline assessment, intervention, and follow-up assessment. We conducted questionnaires addressing HH knowledge and attitudes, interviews to identify HH barriers and facilitators within the SEIPS framework, and observations at the WHO’s 5 moments of HH amongst healthcare workers (HCWs) at JUMC. We then implemented HH interventions based on WHO guidelines and results from our baseline assessment. Follow-up HH observations were conducted months later during the Covid-19 pandemic. 250 HCWs completed questionnaires with an average knowledge score of 61.4% and attitude scores indicating agreement that HH promotes patient safety. Interview participants cited multiple barriers to HH including shortages and location of HH materials, inadequate training, minimal Infection Prevention Control team presence, and high workload. We found an overall baseline HH compliance rate of 9.4% and a follow-up compliance rate of 72.1%. Drastically higher follow-up compared to baseline compliance rates were likely impacted by our HH interventions and Covid-19. HCWs showed motivation for patient safety despite low HH knowledge. Utilizing the SEIPS model helped identify institution-specific barriers that informed targeted interventions beyond WHO guidelines aimed at increasing effectiveness and sustainability of HH efforts.

Large mammalian herbivores use a diverse array of strategies to survive predator encounters including flight, grouping, vigilance, warning signals, and fitness indicators. While anti-predator strategies appear to be driven by specific predator traits, no prior studies have rigorously evaluated whether predator hunting characteristics predict reactive anti-predator responses. We experimentally investigated behavioral decisions made by free-ranging impala, wildebeest, and zebra during encounters with model predators with different functional traits. We hypothesized that the choice of response would be driven by a predator’s hunting style (i.e., ambush vs. coursing) while the intensity at which the behavior was performed would correlate with predator traits that contribute to the prey’s relative risk (i.e., each predator’s prey preference, prey-specific capture success, and local predator density). We found that the choice and intensity of anti-predator behaviors were both shaped by hunting style and relative risk factors. All prey species directed longer periods of vigilance towards predators with higher capture success. The decision to flee was the only behavior choice driven by predator characteristics (capture success and hunting style) while intensity of vigilance, frequency of alarm-calling, and flight latency were modulated based on predator hunting strategy and relative risk level. Impala regulated only the intensity of their behaviors, while zebra and wildebeest changed both type and intensity of response based on predator traits. Zebra and impala reacted to multiple components of predation threat, while wildebeest responded solely to capture success. Overall, our findings suggest that certain behaviors potentially facilitate survival under specific contexts and that prey responses may reflect the perceived level of predation risk, suggesting that adaptive functions to reactive anti-predator behaviors may reflect potential trade-offs to their use. The strong influence of prey species identity and social and environmental context suggest that these factors may interact with predator traits to determine the optimal response to immediate predation threat.

Qualitative health data are rarely shared in the United States (U.S.). This is unfortunate because gathering qualitative data is labor and time-intensive, and data sharing enables secondary research, training, and transparency. A new U.S. federal policy mandates data sharing by 2023, and is agnostic to data type. We surveyed U.S. qualitative researchers (N = 425) on the barriers and facilitators of sharing qualitative health or sensitive research data. Most researchers (96%) have never shared qualitative data in a repository. Primary concerns were lack of participant permission to share data, data sensitivity, and breaching trust. Researcher willingness to share would increase if participants agreed and if sharing increased the societal impact of their research. Key resources to increase willingness to share were funding, guidance, and de-identification assistance. Public health and biomedical researchers were most willing to share. Qualitative researchers need to prepare for this new reality as sharing qualitative data requires unique considerations.

Non-communicable disease (NCD) prevention efforts have traditionally targeted high-risk and high-burden populations. We propose an alteration in prevention efforts to also include emphasis and focus on low-risk populations, predominantly younger individuals and low-prevalence populations. We refer to this approach as “proactive prevention.” This emphasis is based on the priority to put in place policies, programs, and infrastructure that can disrupt the epidemiological transition to develop NCDs among these groups, thereby averting future NCD crises. Proactive prevention strategies can be classified, and their implementation prioritized, based on a 2-dimensional assessment: impact and feasibility. Thus, potential interventions can be categorized into a 2-by-2 matrix: high impact/high feasibility, high impact/ low feasibility, low impact/high feasibility, and low impact/low feasibility. We propose that high impact/high feasibility interventions are ready to be implemented (act), while high impact/low feasibility interventions require efforts to foster buy-in first. Low impact/high feasibility interventions need to be changed to improve their impact while low impact/low feasibility might be best re-designed in the context of limited resources. Using this framework, policy makers, public health experts, and other stakeholders can more effectively prioritize and leverage limited resources in an effort to slow or prevent the evolving global NCD crisis. Fil: Njuguna, Benson. Moi Teaching & Referral Hospital; Kenia Fil: Fletcher, Sara L.. State University of Oregon; Estados Unidos Fil: Akwanalo, Constantine. Moi Teaching & Referral Hospital; Kenia Fil: Asante, Kwaku Poku. Kintampo Health Research Centre; Ghana Fil: Baumann, Ana. Washington University in St. Louis; Estados Unidos Fil: Brown, Angela. Washington University in St. Louis; Estados Unidos Fil: Davila Roman, Victor G.. Washington University in St. Louis; Estados Unidos Fil: Dickhaus, Julia. New York University Grossman School of Medicine; Estados Unidos Fil: Fort, Meredith. Colorado School Of Public Health; Estados Unidos Fil: Iwelunmor, Juliet. Saint Louis University; Estados Unidos Fil: Irazola, Vilma. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Epidemiología y Salud Pública. Instituto de Efectividad Clínica y Sanitaria. Centro de Investigaciones en Epidemiología y Salud Pública; Argentina Fil: Mohan, Sailesh. Centre For Chronic Disease Control; India. Public Health Foundation Of India; India Fil: Mutabazi, Vincent. Regional Alliance For Sustainable Development; Ruanda Fil: Newsome, Brad. Center for Translation Research and Implementation Science; Estados Unidos Fil: Ogedegbe, Olugbenga. New York University Grossman School of Medicine; Estados Unidos Fil: Pastakia, Sonak D.. Purdue University College Of Pharmacy; Estados Unidos Fil: Peprah, Emmanuel K.. University of New York; Estados Unidos Fil: Plange Rhule, Jacob. Ghana College Of Physicians And Surgeons; Ghana Fil: Roth, Gregory. University of Washington; Estados Unidos Fil: Shrestha, Archana. Kathmandu University School Of Medical Sciences; Nepal Fil: Watkins, David A.. University of Washington; Estados Unidos Fil: Vedanthan, Rajesh. New York University Grossman School of Medicine; Estados Unidos

Most species of modern iguanas (Iguania, Iguanidae) dig burrows for dwelling and nesting, yet neither type of burrow has been interpreted as trace fossils in the geologic record. Here we describe and diagnose the first known fossil example of an iguana nesting burrow, preserved in the Grotto Beach Formation (Early Late Pleistocene, ~115kya) on San Salvador Island, The Bahamas. The trace fossil, located directly below a protosol, is exposed in a vertical section of a cross-bedded oolitic eolianite. Abundant root traces, a probable land-crab burrow, and lack of ghost-crab burrows further indicate a vegetated inland dune as the paleoenvironmental setting. The trace fossil matches dimensions and overall forms of burrows made by modern iguanas, and internal structures indicate active backfilling consistent with modern iguana nesting burrows. The trace fossil is also located on an island with a modern native species of rock iguana (Cyclura riyeli riyeli), suggesting a presence of iguanas on San Salvador since the Late Pleistocene. This nesting burrow may provide a search image for more fossil iguana burrows in The Bahamas and other places with long-established iguana species and favorable geological conditions for preserving their burrows.

Background The gut microbiome may play a role in inflammation associated with type 2 diabetes (T2D) development. This cross-sectional study examined its relation with glycemic status within a subset of the Multiethnic Cohort (MEC) and estimated the association of circulating bacterial endotoxin (measured as plasma lipopolysaccharide-binding protein (LBP)) with T2D, which may be mediated by C-reactive protein (CRP). Methods In 2013–16, cohort members from five ethnic groups completed clinic visits, questionnaires, and stool and blood collections. Participants with self-reported T2D and/or taking medication were considered T2D cases. Those with fasting glucose >125 and 100–125 mg/dL were classified as undiagnosed (UT2D) and pre-diabetes (PT2D) cases, respectively. We characterized the gut microbiome through 16S rRNA gene sequencing and measured plasma LBP and CRP by standard assays. Linear regression was applied to estimate associations of the gut microbiome community structure and LBP with T2D status adjusting for relevant confounders. Results Among 1,702 participants (59.9–77.4 years), 735 (43%) were normoglycemic (NG), 506 (30%) PT2D, 154 (9%) UT2D, and 307 (18%) T2D. The Shannon diversity index decreased (ptrend = 0.05), while endotoxin, measured as LBP, increased (ptrend = 0.0003) from NG to T2D. Of 10 phyla, Actinobacteria (ptrend = 0.007), Firmicutes (ptrend = 0.003), and Synergistetes (ptrend = 0.02) were inversely associated and Lentisphaerae (ptrend = 0.01) was positively associated with T2D status. Clostridium sensu stricto 1, Lachnospira, and Peptostreptococcaceae were less, while Escherichia-Shigella and Lachnospiraceae were more abundant among T2D patients, but the associations with Actinobacteria, Clostridium sensu stricto 1, and Escherichia-Shigella may be due metformin use. PT2D/UT2D values were closer to NG than T2D. No indication was detected that CRP mediated the association of LBP with T2D. Conclusions T2D but not PT2D/UT2D status was associated with lower abundance of SCFA-producing genera and a higher abundance of gram-negative endotoxin-producing bacteria suggesting that the gut microbiome may contribute to chronic systemic inflammation and T2D through bacterial translocation.

The reasons for Thoroughbred (TB) horses not entering training or exiting the racing industry, are of interest to regulators, welfare groups and the broader community. Speculation about the outcomes of these horses threatens the community acceptance, or social license, of the TB breeding and racing industries. A representative survey of the 2010 Victorian born TB foal crop was used to determine the outcomes and reasons for exit for horses that had not entered training, or had exited training and racing by eight years of age. Horses exported for racing or breeding (4%), or that were still actively racing (7%) at the start of the follow up period were excluded from the study. An online questionnaire was sent to breeders or trainers of 3,176 TB horses eligible for enrolment in the study. Of the 2,005 (63%) responses received, the two most frequent outcomes were that the horse had either been retired or rehomed (65%), or deceased (16%). For the 1,637 TB horses that had entered training, the majority of retirements were voluntary (59%), followed by involuntary retirements due to health disorders (28%). For TBs that did not have an industry record of entering training (n = 368), death (34%), or retirement or being rehomed (27%), were the most frequent barriers to entering training. The median age of retirement for TBs that raced was five (Q1 4; Q3 6) years regardless of sex, or whether their first race start was at two, three or four years of age. Relatively large numbers of horses voluntarily retiring at five-years of age suggests that industry-level, rather than individual horse-level factors are the predominant influences on racing career duration.

Objective To develop and validate a prediction model for excess pregnancy weight gain using early pregnancy factors. Design Prospective cohort study Setting We recruited from 12 obstetrical, family medicine, and midwifery centers in Ontario, Canada Participants We recruited English-speaking women with singleton pregnancies between 8+0–20+6 weeks. Of 1296 women approached, 1050 were recruited (81%). Of those, 970 women had complete data (970/1050, 92%) and were recruited at a mean of 14.8 weeks. Primary outcome measure We collected data on psychological, physical, and social factors and used stepwise logistic regression analysis to develop a multivariable model predicting our primary outcome of excess pregnancy weight gain, with random selection of 2/3 of women for training data and 1/3 for testing data. Results Nine variables were included in the final model to predict excess pregnancy weight gain. These included nulliparity, being overweight, planning excessive gain, eating in front of a screen, low self-efficacy regarding pregnancy weight gain, thinking family or friends believe pregnant women should eat twice as much as before pregnancy, being agreeable, and having emotion control difficulties. Training and testing data yielded areas under the receiver operating characteristic curve of 0.76 (95% confidence interval, 0.72 to 0.80) and 0.62 (95% confidence interval 0.56 to 0.68), respectively. Conclusions In this first validated prediction model in early pregnancy, we found that nine psychological, physical, and social factors moderately predicted excess pregnancy weight gain in the final model. This research highlights the importance of several predictors, including relatively easily modifiable ones such as appropriate weight gain plans and mindfulness during eating, and lays an important methodological foundation for other future prediction models.

PurposeThis study investigated nicotine dependence as an independent risk factor for upper aerodigestive tract (UADT) cancers, including lung and head and neck cancers (HNC). The study aimed to isolate the direct effect of nicotine dependence, independent of tobacco smoking.MethodsA case-control study with a total of 4957 participants was conducted in Ontario, Canada, of which 2964 categorized as either current or former smokers were used in the analysis. Nicotine dependence of ever-smokers (2360 UADT cases and 604 controls) was measured using the Fagerström Test for Nicotine Dependence. Using mediation analyses and adjusted logistic regression models, we decomposed the direct effect of nicotine dependence and the mediated effect of smoking duration to quantify the risks of lung and HNC. The role of human papillomavirus (HPV) and cancer subtypes were assessed.ResultsMost individual nicotine dependence behaviours showed positive associations with lung cancer with approximately 1.8 to 3.5-fold risk increase, and to lesser extent with 1.4 to 2.3-fold risk for HNC. Nicotine dependence is partially accountable for increased risks of lung cancer (OR = 1.20, 95%CI = 1.13-1.28) and HNC (1.12, 95%CI = 1.04-1.19). Nicotine dependence had a greater effect on the risk of HPV-negative oropharyngeal cancer (OR = 3.06, 95%CI = 1.65-5.66) in comparison to HPV-positive oropharyngeal cancer (OR = 1.05, 95%CI = 0.67-1.65). The direct effects of nicotine dependence remained significant after accounting for cumulative tobacco exposures.ConclusionNicotine dependence increases the risks of lung and HNC cancers after accounting for tobacco smoking, suggesting potential toxic effects of nicotine. These results are informative for the safety consideration of nicotine exposures.

Background Choice of initial antiretroviral therapy regimen may help children with HIV maintain optimal, continuous therapy. We assessed treatment-naïve children for differences in time to treatment disruption across randomly-assigned protease inhibitor versus non-nucleoside reverse transcriptase inhibitor-based initial antiretroviral therapy. Methods We performed a secondary analysis of a multicenter phase 2/3, randomized, open-label trial in Europe, North and South America from 2002 to 2009. Children aged 31 days to Results The modified intention-to-treat analysis included 263 participants. Seventy-two percent (n = 190) of participants experienced at least one treatment disruption during study. At 4 years, treatment disruption probabilities were 70% (protease inhibitor) vs. 63% (non-nucleoside reverse transcriptase inhibitor). The unadjusted hazard ratio (HR) for treatment disruptions comparing protease inhibitor vs. non-nucleoside reverse transcriptase inhibitor-based regimens was 1.19, 95% confidence interval [CI] 0.88–1.61 (adjusted HR 1.24, 95% CI 0.91–1.68). By study end, treatment disruption probabilities converged (protease inhibitor 81%, non-nucleoside reverse transcriptase inhibitor 84%) with unadjusted HR 1.11, 95% CI 0.84–1.48 (adjusted HR 1.13, 95% CI 0.84–1.50). Reported reasons for treatment disruptions suggested that participants on protease inhibitors experienced greater tolerability problems. Conclusions Children had similar time to treatment disruption for initial protease inhibitor and non-nucleoside reverse transcriptase inhibitor-based antiretroviral therapy, despite greater reported tolerability problems with protease inhibitor regimens. Initial pediatric antiretroviral therapy with either a protease inhibitor or non-nucleoside reverse transcriptase inhibitor may be acceptable for maintaining optimal, continuous therapy.

Currently, there is a paucity of data on the barriers for Australian Thoroughbred horses transitioning from stud farm to racetrack. This paper reports the reasons why horses failed to enter race training and documents their exit destinations. Biographical records of Australian Thoroughbred horses born in 2014 were investigated to determine the number of horses that had not officially entered race training by the start of the 4-year old racing season (1 August 2018). Of the 13,677 foals born in 2014, 66% had commenced training and 51% had raced before the beginning of their 4-year-old season in Australia. A sampling frame based on the post code of the premises where foals were born and records from Racing Australia were used to select a geographically representative sample of the 2014 Australian Thoroughbred foal crop (n = 4,124). From the population eligible for sampling 1,275 horses that had not entered training were enrolled in the survey and their breeders were sent an online questionnaire with follow-up phone calls for those who had not responded. Of the 633 responses (50% of 1275) the most frequent outcomes for horses were: death (38%, n = 239), participation in the racing industry in their 4-year old racing season (24%, n = 154) and retirement (16%, n = 100) either as Australian Stud Book (ASB) bloodstock (n = 17), or as horses rehomed outside the Thoroughbred industry (n = 83). Illness or injury was the most frequent reason for horses not entering race training that were ASB bloodstock, rehomed or deceased. There was a loss of traceability at the point of sale with most horses sold at 1 year of age. This study provides important information on the reasons, alternative outcomes and gaps in traceability for horses not entering training prior to the 4-year-old racing season.

Environmental DNA (eDNA) can be used for early detection, population estimations, and assessment of potential spread of invasive species, but questions remain about factors that influence eDNA detection results. Efforts are being made to understand how physical, chemical, and biological factors—settling, resuspension, dispersion, eDNA stability/decay—influence eDNA estimations and potentially population abundance. In a series of field and controlled mesocosm experiments, we examined the detection and accumulation of eDNA in sediment and water and the transport of eDNA in a small stream in the Lake Michigan watershed, using the invasive round goby fish (Neogobius melanostomus) as a DNA source. Experiment 1: caged fish (average n = 44) were placed in a stream devoid of round goby; water was collected over 24 hours along 120-m of stream, including a simultaneous sampling event at 7 distances from DNA source; stream monitoring continued for 24 hours after fish were removed. Experiment 2: round goby were placed in laboratory tanks; water and sediment were collected over 14 days and for another 150 days post-fish removal to calculate eDNA shedding and decay rates for water and sediment. For samples from both experiments, DNA was extracted, and qPCR targeted a cytochrome oxidase I gene (COI) fragment specific to round goby. Results indicated that eDNA accumulated and decayed more slowly in sediment than water. In the stream, DNA shedding was markedly lower than calculated in the laboratory, but models indicate eDNA could potentially travel long distances (up to 50 km) under certain circumstances. Collectively, these findings show that the interactive effects of ambient conditions (e.g., eDNA stability and decay, hydrology, settling-resuspension) are important to consider when developing comprehensive models. Results of this study can help resource managers target representative sites downstream of potential invasion sites, thereby maximizing resource use.

IntroductionA growing body of evidence has demonstrated the importance of mentalization for adolescents' psychosocial functioning; however, further research is needed to understand links between mentalization and other socio-cognitive factors. The aim of this quantitative, cross-sectional study was to investigate the relationship between a teen's capacity to mentalize and three attachment-related factors: parent-teen trust, parent-teen communication, and parent-teen alienation.MethodsIn an online survey, 82 (mainly) Australian adolescents (57 female; 23 male; 2 non-binary; mean age 17.09 years) completed: i) The Children's Eyes Test, which measured mentalization; and ii) The Inventory of Parent and Peer Attachment-45, which measured trust, communication quality, and alienation.ResultsIn teens' relationships with both mothers and fathers, trust and communication quality were significantly positively correlated (p = .001) when controlling for age and gender. Both were significantly negatively correlated with alienation (p = .001) with control variables included. Capacity to mentalize did not correlate with trust, communication quality, or alienation in relationships with either mothers or fathers (p ≤ .05).ConclusionsPossible reasons are proposed for why no relationship was found between mentalization and trust, communication quality, or alienation. Implications for future research are discussed.

IntroductionNasopharyngeal (NP) colonization with antimicrobial-resistant bacteria is a global public health concern. Antimicrobial-resistance (AMR) genes carried by the resident NP microbiota may serve as a reservoir for transfer of resistance elements to opportunistic pathogens. Little is known about the NP antibiotic resistome. This study longitudinally investigated the composition of the NP antibiotic resistome in Streptococcus-enriched samples in a South African birth cohort.MethodsAs a proof of concept study, 196 longitudinal NP samples were retrieved from a subset of 23 infants enrolled as part of broader birth cohort study. These were selected on the basis of changes in serotype and antibiogram over time. NP samples underwent short-term enrichment for streptococci prior to total nucleic acid extraction and whole metagenome shotgun sequencing (WMGS). Reads were assembled and aligned to pneumococcal reference genomes for the extraction of streptococcal and non-streptococcal bacterial reads. Contigs were aligned to the Antibiotic Resistance Gene-ANNOTation database of acquired AMR genes.ResultsAMR genes were detected in 64% (125/196) of the samples. A total of 329 AMR genes were detected, including 36 non-redundant genes, ranging from 1 to 14 genes per sample. The predominant AMR genes detected encoded resistance mechanisms to beta-lactam (52%, 172/329), macrolide-lincosamide-streptogramin (17%, 56/329), and tetracycline antibiotics (12%, 38/329). MsrD, ermB, and mefA genes were only detected from streptococcal reads. The predominant genes detected from non- streptococcal reads included blaOXA-60, blaOXA-22, and blaBRO-1. Different patterns of carriage of AMR genes were observed, with only one infant having a stable carriage of mefA, msrD and tetM over a long period.ConclusionThis study demonstrates that WMGS can provide a broad snapshot of the NP resistome and has the potential to provide a comprehensive assessment of resistance elements present in this niche.

Zika virus infection during pregnancy is associated with miscarriage and with a broad spectrum of fetal and neonatal developmental abnormalities collectively known as congenital Zika syndrome (CZS). Symptomology of CZS includes malformations of the brain and skull, neurodevelopmental delay, seizures, joint contractures, hearing loss and visual impairment. Previous studies of Zika virus in pregnant rhesus macaques (Macaca mulatta) have described injury to the developing fetus and pregnancy loss, but neonatal outcomes following fetal Zika virus exposure have yet to be characterized in nonhuman primates. Herein we describe the presentation of rhesus macaque neonates with a spectrum of clinical outcomes, including one infant with CZS-like symptoms including cardiomyopathy, motor delay and seizure activity following maternal infection with Zika virus during the first trimester of pregnancy. Further characterization of this neonatal nonhuman primate model of gestational Zika virus infection will provide opportunities to evaluate the efficacy of pre- and postnatal therapeutics for gestational Zika virus infection and CZS.

Contains fulltext : 229156.pdf (Publisher’s version ) (Open Access) Previous evidence suggests that modifiable lifestyle factors, such as engagement in leisure activities, might slow the age-related decline of cognitive functions. Less is known, however, about which aspects of lifestyle might be particularly beneficial to healthy cognitive ageing, and whether they are associated with distinct cognitive domains (e.g. fluid and crystallized abilities) differentially. We investigated these questions in the cross-sectional Cambridge Centre for Ageing and Neuroscience (Cam-CAN) data (N = 708, age 18-88), using data-driven exploratory structural equation modelling, confirmatory factor analyses, and age-residualized measures of cognitive differences across the lifespan. Specifically, we assessed the relative associations of the following five lifestyle factors on age-related differences of fluid and crystallized age-adjusted abilities: education/SES, physical health, mental health, social engagement, and intellectual engagement. We found that higher education, better physical and mental health, more social engagement and a greater degree of intellectual engagement were each individually correlated with better fluid and crystallized cognitive age-adjusted abilities. A joint path model of all lifestyle factors on crystallized and fluid abilities, which allowed a simultaneous assessment of the lifestyle domains, showed that physical health, social and intellectual engagement and education/SES explained unique, complementary variance, but mental health did not make significant contributions above and beyond the other four lifestyle factors and age. The total variance explained for fluid abilities was 14% and 16% for crystallized abilities. Our results are compatible with the hypothesis that intellectually and physically challenging as well as socially engaging activities are associated with better crystallized and fluid performance across the lifespan.

ObjectiveObservational tuberculosis cohort studies are often limited by a lack of long-term data characterizing survival beyond the initial treatment outcome. Though Cox proportional hazards models are often applied to these data, differential risk of long-term survival, dependent on the initial treatment outcome, can lead to violations of model assumptions. We evaluate the performance of two alternate censoring approaches on reducing bias in treatment effect estimates.DesignWe simulate a typical multidrug-resistant tuberculosis cohort study and use Cox proportional hazards models to assess the relationship of an aggressive treatment regimen with hazard of death. We compare three assumptions regarding censored observations to determine which produces least biased treatment effect estimates: conventional non-informative censoring, an extension of short-term survival informed by literature, and incorporation of predicted long-term vital status.ResultsThe treatment regimen's protective effect on death is consistently underestimated by the conventional censoring method, up to 7.6%. Models using the two alternative censoring techniques produce treatment effect estimates consistently stronger and less biased than the conventional method, underestimating the treatment effect by less than 2.4% across all scenarios.ConclusionsWhen model assumptions are violated, alternative censoring techniques can more accurately estimate associations between treatment and long-term survival. In multidrug-resistant tuberculosis cohort analyses, this bias reduction may yield more accurate and, larger effect estimates. This bias reduction can be achieved through use of standard statistical procedures with a simple re-coding of the censoring indicator.

As global ocean-bound commerce increases, managing human activities has become important in reducing conflict with threatened wildlife. This study investigates environmental factors determining abundance and distribution of blue whales (Balaenoptera musculus), humpback whales (Megaptera novaeangliae) and their prey (Euphausia pacifica and Thysanoessa spinifera) in central California. We provide insights into environmental drivers of the ecology and distribution of these species, model whale distributions and determine coincident hotspots of whales and their prey that will help decrease human threats to whales and protect critical feeding habitat. We developed separate predictive models of whale abundances (using negative binomial regression on count data) and krill abundance (using a two-part hurdlemodel combining logistic and negative binomial regressions) over a 14 year period (2004-2017). Variables included in situ surface and midwater oceanographic measures (temperature, salinity, and fluorescence), basin-scale climate indices, and bathymetric- and distance-related data. Predictions were applied to 1 km2 cells spanning the study area for May, June, July, and September during each of the 14 years of surveys to identify persistent distribution patterns. Both whales and krill were found to consistently use the northeast region of Cordell Bank, the Farallon Escarpment, and the shelf-break waters. The main identified blue whale hotspots were also krill hotspots, while co-occurrence was more limited and varied seasonally for humpback whales and krill. These results are valuable in identifying patterns in important areas of ecological interaction to assist management of whales. Areas north of Cordell Bank are of particular management concern since they overlap with the end of the San Francisco Bay northern shipping lane. Our findings can help decrease threats to whales, particularly in important foraging areas, by supporting implementation of vessel management and informing potential conflicts with other human uses.

The Sinacanthida ordo nov. and Mongolepidida are spine- and scale-based taxa whose remains encompass some of the earliest reported fossils of chondrichthyan fish. Investigation of fragmentary material from the Early Silurian Tataertag and Ymogantau Formations of the Tarim Basin (Xinjiang Uygur Autonomous Region, China) has revealed a diverse mongolepidid and sinacanthid fauna dominated by mongolepids and sinacanthids in association with abundant dermoskeletal elements of the endemic ‘armoured’ agnathans known as galeaspids.Micro-computed tomography, scanning electron microscopy and histological sections were used to identify seven mongolepid genera (including Tielikewatielepis sinensis gen. et sp. nov., Xiaohaizilepis liui gen. et sp. nov. and Taklamakanolepis asiaticus gen. et sp. nov.) together with a new chondrichthyan (Yuanolepis bachunensis gen. et sp. nov.) with scale crowns consisting of a mongolepid-type atubular dentine (lamellin). Unlike the more elaborate crown architecture of mongolepids, Yuanolepis gen. nov. exhibits a single row of crown elements consistent with the condition reported in stem chondrichthyans from the Lower Devonian (e.g. in Seretolepis, Parexus). The results corroborate previous work by recognising lamellin as the main component of sinacanthid spines and point to corresponding developmental patterns shared across the dermal skeleton of taxa with lamellin and more derived chondrichthyans (e.g. Doliodus, Kathemacanthus, Seretolepis and Parexus).The Tarim mongolepid fauna is inclusive of coeval taxa from the South China Block and accounts for over two-thirds of the species currently attributed to Mongolepidida. This demonstrates considerable overlap between the Tarim and South China components of the Lower Silurian Zhangjiajie Vertebrate Fauna.

Purpose To evaluate the diagnostic value of symptoms used by daycares and schools to screen children and adolescents for SARS-CoV-2 infection, we analyzed data from a primary care setting. Methods This cohort study included all patients ≤17 years old who were evaluated at Providence Community Health Centers (PCHC; Providence, U.S.), for COVID-19 symptoms and/or exposure, and received SARS-CoV-2 polymerase chain reaction (PCR) testing between March-June 2020. Participants were identified from PCHC electronic medical records. For three age groups– 0–4, 5–11, and 12–17 years–we estimated the sensitivity, specificity, and area under the receiver operating curve (AUC) of individual symptoms and three symptom combinations: a case definition published by the Rhode Island Department of Health (RIDOH), and two novel combinations generated by different statistical approaches to maximize sensitivity, specificity, and AUC. We evaluated symptom combinations both with and without consideration of COVID-19 exposure. Myalgia, headache, sore throat, abdominal pain, nausea, anosmia, and ageusia were not assessed in 0–4 year-olds due to the lower reliability of these symptoms in this group. Results Of 555 participants, 217 (39.1%) were SARS-CoV-2-infected. Fever was more common among 0–4 years-olds (p = 0.002); older children more frequently reported fatigue (p = 0.02). In children ≥5 years old, anosmia or ageusia had 94–98% specificity. In all ages, exposure history most accurately predicted infection. With respect to individual symptoms, cough most accurately predicted infection in 95% but specificity Conclusions Anosmia or ageusia in children ≥5 years old should raise providers’ index of suspicion for COVID-19. However, our overall findings underscore the limited diagnostic value of symptoms.

The destinations of Thoroughbred (TB) racehorses exiting the racing industry is a high-profile issue with ethical and welfare implications of interest to both animal welfare groups and racing regulators. This cross-sectional study investigated the reasons that TBs temporarily or permanently exited racing and training in Australia in the 2017–2018 racing season and the outcomes for these horses post-racing. An online questionnaire was sent to the last registered trainers of a representative sample of 2,509 ‘inactive’ TBs. Inactive horses were defined as those horses that were recorded as ‘active’ but had not trialled or raced in the last 6 months of the racing season or had an inactive status recorded in the Racing Australia database. Of the 1,750 responses received, the largest group of inactive TBs had permanently exited the racing industry (45% retired, 5.3% deceased). A relatively large group exited racing temporarily (43%) but participated in the racing industry in the following season. The reasons for retirement were predominantly voluntary, such as poor performance or owner’s request. Almost one third of retirements were due to injuries with tendon or ligament problems the most frequently conditions listed. The median age at retirement was five (Q1 4; Q3 7) years. Extrapolation of the survey results to the population of horses racing or training in Australia in 2017–2018 (n = 37,750) show that that 17% of the population retire each year and 2.1% die. These estimates provide benchmarks for industry and animal welfare organisations to resource and measure the effectiveness of interventions.

Nature exposure has been linked to a plethora of health benefits, but the mechanism for this effect is not well understood. We conducted two studies to test a new model linking the health benefits of nature exposure to reduced impulsivity in decision-making (as measured by delay discounting) via psychologically expanding space perception. In study 1 we collected a nationwide U.S. sample (n = 609) to determine whether nature exposure was predictive of health outcomes and whether impulsive decision-making mediated the effect. Results indicated that Nature Accessibility and Nature Exposure From Home significantly predicted reduced scores on the Depression, Anxiety, Stress Scales (DASS) (p < .001, p = .03, respectively) and improved general health and wellbeing (p < .001, p < .01, respectively). Nature Accessibility also predicted reduced impulsive decision-making (p < .01), and Nature Accessibility showed significant indirect effects through impulsive decision-making on both the DASS (p = .02) and general health and wellbeing (p = .04). In Study 2, a lab-based paradigm found that nature exposure expanded space perception (p < .001), and while the indirect effect of nature exposure through space perception on impulsive decision-making did not meet conventional standards of significance (p < .10), the pattern was consistent with hypotheses. This combination of ecologically-valid and experimental methods offers promising support for an impulsivity-focused model explaining the nature-health relationship.

Outbreaks of avian influenza virus (AIV) infection included the spread of highly pathogenic AIV in commercial poultry and backyard flocks in the spring of 2015. This resulted in estimated losses of more than $8.5 million from federal government expenditures, $1.6 billion from direct losses to produces arising from destroyed turkey and chicken egg production, and economy-wide indirect costs of $3.3 billion from impacts on retailers and the food service industries. Additionally, these outbreaks resulted in the death or depopulation of nearly 50 million domestic birds. Domesticated male ferrets (Mustela putorius furo) were trained to display a specific conditioned behavior (i.e. active scratch alert) in response to feces from AIV-infected mallards in comparison to feces from healthy ducks. In order to establish that ferrets were identifying samples based on odors associated with infection, additional experiments controlled for potentially confounding effects, such as: individual duck identity, housing and feed, inoculation concentration, and day of sample collection (post-infection). A final experiment revealed that trained ferrets could detect AIV infection status even in the presence of samples from mallards inoculated with Newcastle disease virus or infectious laryngotracheitis virus. These results indicate that mammalian biodetectors are capable of discriminating the specific odors emitted from the feces of non-infected versus AIV infected mallards, suggesting that the health status of waterfowl can be evaluated non-invasively for AIV infection via monitoring of volatile fecal metabolites. Furthermore, in situ monitoring using trained biodetectors may be an effective tool for assessing population health.

During the past decade, over 3000 shell middens or shell matrix deposits have been discovered on the Farasan Islands in the southern Red Sea, dating to the period c. 7,360 to 4,700 years ago. Many of the sites are distributed along a palaeoshoreline which is now 2–3 m above present sea level. Others form clusters with some sites on the shoreline and others located inland over distances of c. 30 m to 1 km. We refer to these inland sites as ‘post-shore’ sites. Following Meehan, who observed a similar spatial separation in shell deposition in her ethnographic study of Anbarra shellgathering in the Northern Territory of Australia, we hypothesise that the shoreline sites are specialised sites for the processing or immediate consumption of shell food, and the post-shore sites are habitation sites used for a variety of activities. We test this proposition through a systematic analysis of 55 radiocarbon dates and measurement of shell quantities from the excavation of 15 shell matrix sites in a variety of locations including shoreline and post-shore sites. Our results demonstrate large differences in rates of shell accumulation between these two types of sites and selective removal of shoreline sites by changes in sea level. We also discuss the wider implications for understanding the differential preservation and visibility of shell-matrix deposits in coastal settings in other parts of the world extending back into the later Pleistocene in association with periods of lowersea level. Our results highlight the importance of taphonomic factors of post-depositional degradation and destruction, rates of shell accumulation, the influence on site location of factors other than shell food supply, and the relative distance of deposits from their nearest palaeoshorelines as key variables in the interpretation of shell quantities. Failure to take these variables into account when investigating shells and shell-matrix deposits in late Pleistocene and early Holocene contexts is likely to compromise interpretations of the role and significance of shell food in human evolutionary and socio-cultural development. © 2019 Hausmann et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Suburbanization is happening rapidly on a global scale, resulting in changes to the species assemblages present in previously undeveloped areas of land. Community-level changes after anthropogenic land-use change have been studied in a variety of organisms, but the effects on arthropods of medical and veterinary importance remain poorly characterized. Shifts in diversity, abundance, and community composition of such arthropods, like mosquitoes, can significantly impact vector-borne disease dynamics due to varying vectorial capacity between different species. In light of these potential implications for vector-borne diseases, we investigated changes in mosquito species assemblage after suburbanization by sampling mosquitoes in neighborhoods of different ages in Wake County, North Carolina, US. We found that independent of housing density and socioeconomic status, mosquito diversity measures decreased as suburban neighborhoods aged. In the oldest neighborhoods, the mosquito assemblage reached a distinct suburban climax community dominated by the invasive, peridomestic container-breeding Aedes albopictus, the Asian tiger mosquito. Aedes albopictus is a competent vector of many pathogens of human concern, and its dominance in suburban areas places it in close proximity with humans, allowing for heightened potential of host-vector interactions. While further research is necessary to explicitly characterize the effects of mosquito community simplification on vector-borne disease transmission in highly suburbanized areas, the current study demonstrates that suburbanization is disrupting mosquito communities so severely that they do not recover their diversity even 100 years after the initial disturbance. Our understanding of the community-level effects of anthropogenic land-use change on arthropod vectors will become increasingly important as we look to mitigate disease spread in a global landscape that is continually developed and altered by humans.

ObjectiveTo compare the diagnostic performance of the GenoType MRBDRplus assay with the gold standard phenotypic drug susceptibility testing in the detection of drug resistance among culture isolates obtained from patients in Karachi, Pakistan.DesignMycobacterium tuberculosis isolates were obtained from 96 consecutive tuberculosis patients found to have resistance to isoniazid from two health centers in Karachi (January-November 2017). Isolates were tested for drug resistance against rifampin and isoniazid using the MTBDRplus assay. Results were compared with conventional drug-susceptibility testing and the frequency of specific mutations were reported.ResultsThe MTBDRplus assay had a sensitivity for rifampin resistance of 98.8% (95% CI: 93.4-100) and for isoniazid resistance of 90.6% (95% CI: 83.0-95.6). The MTBDRplus assay showed mutations in rpoB in 81 of the 96 (84.4%) isolates. Of the 87 isolates showing resistance to isoniazid via the MTBDRplus assay, 71 (74.0%) isolates had mutations in the katG gene only, 15 (15.6%) isolates had mutations in the inhA promoter region, and 1 (1.0%) showed mutations in both genes.ConclusionThe GenoType MTBDRplus assay in Pakistan can identify subgroups at high-risk of having isolates with mutations in the katG and/or inhA genes. Understanding the local burden of these mutations have implications for local diagnostic and treatment guidelines.

Effective speech communication is critical to everyday quality of life and social well-being. In addition to the well-studied deficits in cognitive and motor function, depression also impacts communication. Here, we examined speech perception in individuals who were clinically diagnosed with major depressive disorder (MDD) relative to neurotypical controls. Forty-two normal-hearing (NH) individuals with MDD and 41 NH neurotypical controls performed sentence recognition tasks across three conditions with maskers varying in the extent of linguistic content (high, low, and none): 1-talker masker (1T), reversed 1-talker masker (1T_tr), and speech-shaped noise (SSN). Individuals with MDD, relative to neurotypical controls, demonstrated lower recognition accuracy in the 1T condition but not in the 1T_tr or SSN condition. To examine the nature of the listening condition-specific speech perception deficit, we analyzed speech recognition errors. Errors as a result of interference from masker sentences were higher for individuals with MDD (vs. neurotypical controls) in the 1T condition. This depression-related listening condition-specific pattern in recognition errors was not observed for other error types. We posit that this depression-related listening condition-specific deficit in speech perception may be related to heightened distractibility due to linguistic interference from background talkers.

BackgroundAcute kidney injury (AKI) is a risk factor for neurocognitive impairment in severe malaria (SM), but the impact of AKI on long-term behavioral outcomes following SM is unknown.MethodsWe conducted a prospective study on behavioral outcomes of Ugandan children 1.5 to 12 years of age with two forms of severe malaria, cerebral malaria (CM, n = 226) or severe malarial anemia (SMA, n = 214), and healthy community children (CC, n = 173). AKI was defined as a 50% increase in creatinine from estimated baseline. Behavior and executive function were assessed at baseline and 6, 12, and 24 months later using the Child Behavior Checklist and Behavior Rating Inventory of Executive Function, respectively. Age-adjusted z-scores were computed for each domain based on CC scores. The association between AKI and behavioral outcomes was evaluated across all time points using linear mixed effect models, adjusting for sociodemographic variables and disease severity.ResultsAKI was present in 33.2% of children with CM or SMA at baseline. Children ≥6 years of age with CM or SMA who had AKI on admission had worse scores in socio-emotional function in externalizing behaviors (Beta (95% CI), 0.52 (0.20, 0.85), p = 0.001), global executive function (0.48 (0.15, 0.82), p = 0.005) and behavioral regulation (0.66 (0.32, 1.01), p = 0.0002) than children without AKI. There were no behavioral differences associated with AKI in children ConclusionsAKI is associated with long-term behavioral problems in children ≥6 years of age with CM or SMA, irrespective of age at study enrollment.

From the perspective of Central and South America, the peopling of the New World was a complex process lasting thousands of years and involving multiple waves of Pleistocene and early Holocene period immigrants entering into the neotropics. These Paleoindian colonists initially brought with them technologies developed for adaptation to environments and resources found in North America. As the ice age ended across the New World people adapted more generalized stone tools to exploit changing environments and resources. In the neotropics these changes would have been pronounced as patchy forests and grasslands gave way to broadleaf tropical forests. We document a late Pleistocene/early Holocene stone tool tradition from Belize, located in southern Mesoamerica. This represents the first endogenous Paleoindian stone tool technocomplex recovered from well dated stratigraphic contexts for Mesoamerica. Previously designated Lowe, these artifacts share multiple features with contemporary North and South American Paleoindian tool types. Once hafted, these bifaces appear to have served multiple functions for cutting, hooking, thrusting, or throwing. The tools were developed at a time of technological regionalization reflecting the diverse demands of a period of pronounced environmental change and population movement. Combined stratigraphic, technological, and population paleogenetic data suggests that there were strong ties between lowland neotropic regions at the onset of the Holocene.

AimTo determine if there is an association between sarcopenia, physical function and self-reported fatigue in osteoarthritis (OA) and rheumatoid arthritis (RA).MethodsA cross-sectional analysis of measurements from a cohort of 157 participants with OA or RA was performed. The relationship between muscle mass (appendicular muscle index (AMI)), physical function (timed up and go, 30-seconds sit-to-stand test, 40-meter fast-paced walk test and grip-strength) and two fatigue measures (Multidimensional Assessment of Fatigue (MAF) and a fatigue Visual Analogue Scale (VAS)) was explored using hierarchical linear regression or logistic regression with established AMI cut-offs for sarcopenia.ResultsThere were no significant differences for perceived fatigue-related variables between OA or RA sarcopenic or non-sarcopenic participants. Participants with OA had worse physical function (TUG; P = 0.029, STS; P = 0.004, WS; P = 0.003), but participants with RA had lower grip strength (PConclusionSarcopenia, when assessed by AMI, does not appear to be strongly associated with self-reported fatigue or physical function in participants with either OA or RA. Higher body fat had a moderately strong association with sarcopenia in this cross-sectional study, suggesting that body composition may be an important factor in the health of patients with longstanding OA or RA.

Background Cardiovascular disease is common in patients with systemic lupus erythematosis (SLE) and lupus nephritis (LN). Up to 80% of children with SLE develop kidney disease, which is also associated with increased risk for cardiovascular disease and death compared to those without renal involvement. Hepcidin is an iron-regulatory protein which may contribute to atherosclerosis and is elevated in autoimmune disease. Pulse wave velocity (PWV) is a validated indicator of arterial stiffness, an early marker of cardiovascular risk, and is increased in children with SLE versus healthy controls. Our objective was to quantify hepcidin and PWV in children with SLE and investigate if those with biopsy-proven LN have higher hepcidin levels and higher PWV compared to those without kidney disease. Methods Cross-sectional analysis with hepcidin was measured via ELISA assay in 16 children aged 10–21 years with SLE recruited from a single center. Subjects were classified as having LN if histologic evidence of the disease was documented on a clinical renal biopsy. Serum hepcidin was quantified using a validated competitive enzyme-linked immunoassay. Carotid-femoral PWV was measured using applanation tonometry. Wilcoxon rank sum testing was used to compare median levels of hepcidin, PWV, and other continuous variables by nephritis status. Results The cohort (n = 16) was 93.8% female and 68.8% African-American with mean (SD) 16 (3.6) years. 37.5% (n = 6) had LN. Overall median (IQR) hepcidin was 34.4 (18.9, 91.9) ng/ml, and PWV 4.4 (4, 4.6) meters/second. Although significance was limited by small sample size, both hepcidin and PWV were higher in the subjects with LN. Median (IQR) hepcidin in subjects with LN was 71.5 (26.4, 116.4) ng/ml compared to 27.9 (18.7, 59.7) ng/ml in those with SLE(p = 0.19). Similarly, median (IQR) PWV in those with LN was 4.4 (4.4, 4.9) meters/second compared to 3 (3.75, 4.55) meters/second in those with without kidney involvement (p = 0.10). Conclusion PWV and serum hepcidin were higher in subjects with LN compared to those with SLE alone, suggesting that elevated hepcidin levels may be associated with morbid CV changes in children with LN. This association, along with identification of additional predictors of arterial stiffness in patients with LN, warrants further investigation.

The ability to selectively respond to one's own name is important for social and language development, and is disrupted in atypically developing populations (e.g., autism spectrum disorder). Research with typically developing samples using event-related potentials (ERPs) has demonstrated that the subject's own name (SON) is differentiated from other stimuli at both early sensory and later cognitive stages of auditory processing. While neural indices of response to name have been researched extensively in adults, no such studies have been conducted with typically developing preschool children or children with autism spectrum disorder (ASD). The present study investigated ERP response to name in a sample of typically developing (TD) preschoolers (n = 19; mean age = 4.3 years) as well as a small, exploratory comparison group of preschoolers with ASD (n = 13; mean age = 4.4 years). TD preschoolers exhibited significantly greater negativity to SON over frontal regions than to an unfamiliar nonsense name, consistent with the adult SON negativity component. This component was present whether the name was spoken by a parent or an unfamiliar adult, suggesting that it reflects SON-specific processing rather than broad self-relevant information processing. Comparing preschoolers with ASD to the TD children revealed a significant SON negativity component across both groups. The amplitude of the SON negativity response was significantly correlated with social variables in the ASD group, though these correlations did not survive correction for multiple comparisons. This study is the first to demonstrate the presence of the SON component in preschool children with and without ASD.

Miscarriage occurs in up to one in four pregnancies and can be a devastating event affecting both men and women. Unfortunately, the male partner's experience of miscarriage is seldom researched, particularly within Australia. This qualitative study involved semi-structured telephone interviews with 10 Australian men, whose partners miscarried between three months and ten years ago. Participants were recruited through professional networks and support organisations. Interviews explored men's general miscarriage experience and the support received or lacking from both healthcare providers and social networks. Online health seeking behaviour and opinions on online support were also discussed. Data was transcribed verbatim and analysed thematically. Most men described feeling significant grief following miscarriage and felt that there was little acknowledgment of their loss, both from healthcare providers and within their social networks. Feelings of sadness, devastation, powerlessness, fear, shock and a loss of identity were common. All men felt their primary role at the time of miscarriage was to support their partner. Most men did not want to burden their partner with their emotions or grief, and struggled to find people within their social networks to talk to about their loss, leading to feelings of isolation. Overall participants felt there was inadequate support offered to men affected by miscarriage. Men wanted information, informed professionals to talk to and male-orientated support networks. A website was one mechanism suggested by men which could adequately contribute to information and support needs during this time. Men are often greatly affected by miscarriage and yet there is all too often little acknowledgement or support available to them at this time. Men affected by miscarriage want and need further support, including reputable, Australian based information and resources tailored their needs.

Context Standard pregnancy intentions measures do not always align with how people approach pregnancy. Studies that have investigated beyond a binary framework found that those with “ambivalent” feelings towards pregnancy are less likely to use contraception consistently, but the reasons for this are unclear. We sought to gain a nuanced understanding of pregnancy desires, and how perceptions about pregnancy are associated with contraceptive use. Methods We used non-probability quota sampling based on sex, age, and geographic region for a web-based survey of heterosexual men and women, aged 21–44 years, who could become pregnant/impregnate and were not currently pregnant (n = 1,477; 51% female). The survey was created using unique items informed by recent literature. Bivariate and multivariable analyses explored relationships between various perceptions about pregnancy with pregnancy desires categorized as: wanting a pregnancy, not wanting a pregnancy, and not trying but would be okay with a pregnancy. We conducted a sub-group analysis of those who were not trying but would be okay with a pregnancy (n = 460), using descriptive statistics to examine how consistent contraceptive use was associated with emotions and beliefs about avoiding pregnancy. Results After adjustment, those who felt that pregnancy may not always be avoidable, but instead determined by fate/higher power, or a natural process that happens when it is meant to, were significantly more likely (aOR: 1.83, 95% CI: 1.05–3.36; aOR: 2.21, 95% CI: 1.29–3.76, respectively) to report not trying but being okay with pregnancy, whereas those with negative feelings about a pregnancy were less likely to feel okay about a pregnancy (aOR: 0.11, 95% CI: 0.08–0.15), versus not wanting a pregnancy. In the sub-group analysis, those who felt pregnancy was determined by fate/higher power or a natural process were more likely to report not using contraception consistently (70%, 68%, respectively). Conclusions Those who state they are not trying but would be okay with pregnancy may not use contraception consistently because of beliefs that pregnancy is predetermined. Our findings support less categorical and more multidimensional approaches to measuring fertility intentions, with important implications for reproductive health service provision.

This article examines men’s involvement in an institutional gender equity award scheme and how their self-concept as allies develops over time. It draws specifically on a subset of qualitative data from the four men participating in a study involving in-depth interviews with university staff involved in the self-assessment team of one Australian institution’s Science in Australia Gender Equality (SAGE) Athena SWAN pilot. Data related to the men’s experiences is the article’s focus. Key themes from the data include: 1) men’s motivations for engagement; 2) men’s self-understandings as ‘champions for change’ 3) the barriers/risks associated with male championship; and 4) men’s evolving perceptions and critiques of the male champions model. Findings show that men demonstrated personal growth and increased awareness through their participation in the pilot. Yet, their frustration with how equity and diversity was managed in their organisational context highlights pitfalls in the concept of a male ‘champion’. This article provides timely guidance for institutions seeking to engage allies in gender equity initiatives.

Understanding how perceptions around motivation, capacity, and climate change’s impacts relate to the adoption of adaptation practices in light of experiences with extreme weather events is important in assessing farmers’ adaptive capacity. However, very little of this work has occurred in islands, which may have different vulnerabilities and capacities for adaptation. Data of surveyed farmers throughout Puerto Rico after Hurricane Maria (n = 405, 87% response rate) were used in a structural equation model to explore the extent to which their adoption of agricultural practices and management strategies was driven by perceptions of motivation, vulnerability, and capacity as a function of their psychological distance of climate change. Our results show that half of farmers did not adopt any practice or strategy, even though the majority perceived themselves capable and motivated to adapt to climate change, and understood their farms to be vulnerable to future extreme events. Furthermore, adoption was neither linked to these adaptation perceptions, nor to their psychological distance of climate change, which we found to be both near and far. Puerto Rican farmers’ showed a broad awareness of climate change’s impacts both locally and globally in different dimensions (temporal, spatial, and social), and climate distance was not linked to reported damages from Hurricane Maria or to previous extreme weather events. These results suggest that we may be reaching a tipping point for extreme events as a driver for climate belief and action, especially in places where there is a high level of climate change awareness and continued experience of compounded impacts. Further, high perceived capacity and motivation are not linked to actual adaptation behaviors, suggesting that broadening adaptation analyses beyond individual perceptions and capacities as drivers of climate adaptation may give us a better understanding of the determinants to strengthen farmers’ adaptive capacity.

Comprehensive assessment of food insecurity across all college community members is lacking. This research surveyed a random sample of an entire campus population at a Northeast University in two surveys (spring 2017, n = 1,037 and fall 2017, n = 1,123). Analysis of variance, t-tests, and multivariable logit models were used to understand food insecurity outcomes and comparisons among groups. The overall rate of food insecurity on campus was 19.6% (spring) and 15.0% (fall). Food insecurity rates were highest among undergraduates, graduate and medical students, and staff as compared to faculty. First generation students and off-campus students were also more likely to be food insecure in both surveys, while people of color were more likely to be food insecure in the spring survey. Findings suggest university members beyond undergraduates also face high rates of food insecurity, which has important implications for efforts to reduce food insecurity on college campuses.

Acute viral wheeze in children is a major cause of hospitalisation and a major risk factor for the development of asthma. However, the role of the respiratory tract microbiome in the development of acute wheeze is unclear. To investigate whether severe wheezing episodes in children are associated with bacterial dysbiosis in the respiratory tract, oropharyngeal swabs were collected from 109 children with acute wheezing attending the only tertiary paediatric hospital in Perth, Australia. The bacterial community from these samples was explored using next generation sequencing and compared to samples from 75 non-wheezing controls. No significant difference in bacterial diversity was observed between samples from those with wheeze and healthy controls. Within the wheezing group, attendance at kindergarten or preschool was however, associated with increased bacterial diversity. Rhinovirus (RV) infection did not have a significant effect on bacterial community composition. A significant difference in bacterial richness was observed between children with RV-A and RV-C infection, however this is likely due to the differences in age group between the patient cohorts. The bacterial community within the oropharynx was found to be diverse and heterogeneous. Age and attendance at day care or kindergarten were important factors in driving bacterial diversity. However, wheeze and viral infection were not found to significantly relate to the bacterial community. Bacterial airway microbiome is highly variable in early life and its role in wheeze remains less clear than viral influences.

Smut caused by biotrophic fungus Sporisorium scitamineum is a major disease of cultivated sugarcane that can cause considerable yield losses. It has been suggested in literature that there are at least two types of resistance mechanisms in sugarcane plants: an external resistance, due to chemical or physical barriers in the sugarcane bud, and an internal resistance governed by the interaction of plant and fungus within the plant tissue. Detailed molecular studies interrogating these two different resistance mechanisms in sugarcane are scarce. Here, we use light microscopy and global expression profiling with RNA-seq to investigate these mechanisms in sugarcane cultivar CP74-2005, a cultivar that possibly possesses both internal and external defence mechanisms. A total of 861 differentially expressed genes (DEGs) were identified in a comparison between infected and non-infected buds at 48 hours post-inoculation (hpi), with 457 (53%) genes successfully annotated using BLAST2GO software. This includes genes involved in the phenylpropanoid pathway, cell wall biosynthesis, plant hormone signal transduction and disease resistance genes. Finally, the expression of 13 DEGs with putative roles in S. scitamineum resistance were confirmed by quantitative real-time reverse transcription PCR (qRT-PCR) analysis, and the results were consistent with the RNA-seq data. These results highlight that the early sugarcane response to S. scitamineum infection is complex and many of the disease response genes are attenuated in sugarcane cultivar CP74-2005, while others, like genes involved in the phenylpropanoid pathway, are induced. This may point to the role of the different disease resistance mechanisms that operate in cultivars such as CP74-2005, whereby the early response is dominated by external mechanisms and then as the infection progresses, the internal mechanisms are switched on. Identification of genes underlying resistance in sugarcane will increase our knowledge of the sugarcane-S. scitamineum interaction and facilitate the introgression of new resistance genes into commercial sugarcane cultivars.

A mixed-methods approach was used to evaluate and improve the “late-night dining” options in a university dining hall. Surveys assessed student desires for late-night offerings, and evaluated students’ habits and motivations during late-night dining. Two interventions were implemented to see if students could be “nudged” into different choice patterns. In the first, a “veggie-heavy” entree was added at the beginning of the entree line, so that students would substitute an entree containing vegetables for the alternatives. In the second, a snack-food bar was set up to cater to students who didn’t want to stand in the long entree line, and preferred a snack. Data on food choice was collected during the interventions. Survey responses showed significant differences in the reasons females and males utilized late-night dining (p

Future climate changes will affect smallholder farmers in the developing world, posing threats to household food security. Nevertheless, there remains limited comparable evidence across multiple countries and regions regarding the global extent of climate shocks affecting smallholder food security. We examine data from 5,299 household surveys across 15 countries in Latin America, Africa and South Asia to assess the extent of climate shocks and their association with food insecurity, as well as what strategies may help buffer against climate shocks. We find that 71% of households reported experiencing a climate shock in the previous five years. Fifty-four percent reported experiencing food insecurity during one or more months annually. A multilevel statistical model estimated factors correlated with food insecurity as well as factors correlated with food insecurity among households that had experienced a climate shock. Households that reported experiencing a climate shock were 1.73 times more likely to be food insecure. As well, larger and poorer households were associated with higher odds of food insecurity while using pesticides, keeping large livestock, and being more educated are associated with lower odds of food insecurity. Among households that had experienced a climate shock, additional factors are correlated with lower odds of food insecurity when compared to otherwise similar households: use of fertilizers, pesticides, veterinary medicines, large livestock, and household assets. Together, these results demonstrate the extent of existing climate shocks affecting smallholder farmers and how interventions may potentially support adaptation and reduce food insecurity.

The production of envelope glycoproteins (Envs) for use as HIV vaccines is challenging. The yield of Envs expressed in stable Chinese Hamster Ovary (CHO) cell lines is typically 10–100 fold lower than other glycoproteins of pharmaceutical interest. Moreover, Envs produced in CHO cells are typically enriched for sialic acid containing glycans compared to virus associated Envs that possess mainly high-mannose carbohydrates. This difference alters the net charge and biophysical properties of Envs and impacts their antigenic structure. Here we employ a novel robotic cell line selection strategy to address the problems of low expression. Additionally, we employed a novel gene-edited CHO cell line (MGAT1- CHO) to address the problems of high sialic acid content, and poor antigenic structure. We demonstrate that stable cell lines expressing high levels of gp120, potentially suitable for biopharmaceutical production can be created using the MGAT1- CHO cell line. Finally, we describe a MGAT1- CHO cell line expressing A244-rgp120 that exhibits improved binding of three major families of bN-mAbs compared to Envs produced in normal CHO cells. The new strategy described has the potential to eliminate the bottleneck in HIV vaccine development that has limited the field for more than 25 years.

Improving diet quality while simultaneously reducing environmental impact is a critical focus globally. Metrics linking diet quality and sustainability have typically focused on a limited suite of indicators, and have not included food waste. To address this important research gap, we examine the relationship between food waste, diet quality, nutrient waste, and multiple measures of sustainability: use of cropland, irrigation water, pesticides, and fertilizers. Data on food intake, food waste, and application rates of agricultural amendments were collected from diverse US government sources. Diet quality was assessed using the Healthy Eating Index-2015. A biophysical simulation model was used to estimate the amount of cropland associated with wasted food. This analysis finds that US consumers wasted 422g of food per person daily, with 30 million acres of cropland used to produce this food every year. This accounts for 30% of daily calories available for consumption, one-quarter of daily food (by weight) available for consumption, and 7% of annual cropland acreage. Higher quality diets were associated with greater amounts of food waste and greater amounts of wasted irrigation water and pesticides, but less cropland waste. This is largely due to fruits and vegetables, which are health-promoting and require small amounts of cropland, but require substantial amounts of agricultural inputs. These results suggest that simultaneous efforts to improve diet quality and reduce food waste are necessary. Increasing consumers' knowledge about how to prepare and store fruits and vegetables will be one of the practical solutions to reducing food waste.