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Monosodium glutamate (MSG) is a widely used food additive with conflicting evidence regarding its potential effects on human health, with proposed relevance for obesity and metabolic syndrome (MetS) or chronic kidney disease. As being able to accurately quantify the MSG dietary intake would help clarify the open issues, we constructed a predictive formula to estimate the daily intake of MSG in a rat model based on the urinary metabolic profile. Adult male Wistar rats were divided into groups receiving different daily amounts of MSG in drinking water (0.5, 1.5, and 3.0 g%), no MSG, and MSG withdrawal after 3.0% MSG treatment for 4 weeks. We then analyzed 24-hour urine samples for chemistries and metabolites using 1H NMR spectrometry and observed a strong correlation between urine pH, sodium, bicarbonate, alpha-ketoglutarate, citrate, fumarate, glutamate, methylamine, N-methyl-4-pyridone-3-carboxamide, succinate, and taurine and the daily MSG intake. Following the multiple linear regression analysis a simple formula model based on urinary Na+, citrate, and glutamate was most accurate and could be validated for estimating daily MSG intake. In conclusion, we propose that the daily MSG intake correlates with urinary metabolites in a rat model and that this new tool for monitoring the impact of MSG on health measures.

[This corrects the article DOI: 10.1371/journal.pone.0266608.].

[This corrects the article DOI: 10.1371/journal.pone.0240437.].

We assessed the humoral immune responses to a COVID-19 vaccine in a well-controlled rhesus macaque model compared to humans immunized with two mRNA vaccines over several months post-second dose. The plasma IgG levels against seven coronaviruses (including SARS-CoV-2) and antibody subtypes (IgG 1-4 and IgM) against SARS-CoV-2 were evaluated using multiplex assays. The neutralization capacity of plasma antibodies against the original SAR-CoV-2 isolate and nine variants was evaluated in vaccinated humans and non-human primates. Immunization of macaques and humans with SARS-CoV-2 vaccines induced a robust neutralizing antibody response. In non-SIV-infected adult macaques immunized with an adenoviral vector expressing S-RBD (n = 7) or N protein (n = 3), elevated levels of IgG and neutralizing antibodies were detected 2 weeks post-second dose. Immune responses to the S-RBD vaccine in SIV-infected adult macaques (n = 2) were similar to the non-SIV-infected animals. Adult humans immunized with Pfizer (n = 35) or Moderna (n = 18) vaccines developed IgG and neutralizing antibodies at 4 weeks post-second dose. In both vaccine groups, IgG 1 was the predominant subtype, followed by IgG 3. The IgG levels, including total and IgG 1,2,3 elicited by the Moderna vaccine, were significantly higher than the corresponding levels elicited by the Pfizer vaccine at 4 weeks post-second dose. A significant correlation was observed between the plasma total IgG antibody levels and neutralization titers in both macaques and humans. Furthermore, broad-spectrum neutralization antibodies against several variants of SARS-CoV-2 were detected in the plasma of both macaques and humans after two vaccinations.

The All of Us (AoU) Research Program is making available one of the largest and most diverse collections of health data in the US to researchers. Using the All of Us database, we evaluated family and personal histories of five common types of cancer in 89,453 individuals, comparing these data to 24,305 participants from the 2015 National Health Interview Survey (NHIS). Comparing datasets, we found similar family cancer history (33%) rates, but higher personal cancer history in the AoU dataset (9.2% in AoU vs. 5.11% in NHIS), Methodological (e.g. survey-versus telephone-based data collection) and demographic variability may explain these between-data differences, but more research is needed.

El Gigante rockshelter in western Honduras provides a deeply stratified archaeological record of human-environment interaction spanning the entirety of the Holocene. Botanical materials are remarkably well preserved and include important tree (e.g., ciruela (Spondias), avocado (Persea americana)) and field (maize (Zea mays), beans (Phaseolus), and squash (Cucurbita)) crops. Here we provide a major update to the chronology of tree and field crop use evident in the sequence. We report 375 radiocarbon dates, a majority of which are for short-lived botanical macrofossils (e.g., maize cobs, avocado seeds, or rinds). Radiocarbon dates were used in combination with stratigraphic details to establish a Bayesian chronology for ~9,800 identified botanical samples spanning the last 11,000 years. We estimate that at least 16 discrete intervals of use occurred during this time, separated by gaps of ~100-2,000 years. The longest hiatus in rockshelter occupation was between ~6,400 and 4,400 years ago and the deposition of botanical remains peaked at ~2,000 calendar years before present (cal BP). Tree fruits and squash appeared early in the occupational sequence (~11,000 cal BP) with most other field crops appearing later in time (e.g., maize at ~4,400 cal BP; beans at ~2,200 cal BP). The early focus on tree fruits and squash is consistent with early coevolutionary partnering with humans as seed dispersers in the wake of megafaunal extinction in Mesoamerica. Tree crops predominated through much of the Holocene, and there was an overall shift to field crops after 4,000 cal BP that was largely driven by increased reliance on maize farming.

ImportanceSARS-CoV-2 infection can result in ongoing, relapsing, or new symptoms or other health effects after the acute phase of infection; termed post-acute sequelae of SARS-CoV-2 infection (PASC), or long COVID. The characteristics, prevalence, trajectory and mechanisms of PASC are ill-defined. The objectives of the Researching COVID to Enhance Recovery (RECOVER) Multi-site Observational Study of PASC in Adults (RECOVER-Adult) are to: (1) characterize PASC prevalence; (2) characterize the symptoms, organ dysfunction, natural history, and distinct phenotypes of PASC; (3) identify demographic, social and clinical risk factors for PASC onset and recovery; and (4) define the biological mechanisms underlying PASC pathogenesis.MethodsRECOVER-Adult is a combined prospective/retrospective cohort currently planned to enroll 14,880 adults aged ≥18 years. Eligible participants either must meet WHO criteria for suspected, probable, or confirmed infection; or must have evidence of no prior infection. Recruitment occurs at 86 sites in 33 U.S. states, Washington, DC and Puerto Rico, via facility- and community-based outreach. Participants complete quarterly questionnaires about symptoms, social determinants, vaccination status, and interim SARS-CoV-2 infections. In addition, participants contribute biospecimens and undergo physical and laboratory examinations at approximately 0, 90 and 180 days from infection or negative test date, and yearly thereafter. Some participants undergo additional testing based on specific criteria or random sampling. Patient representatives provide input on all study processes. The primary study outcome is onset of PASC, measured by signs and symptoms. A paradigm for identifying PASC cases will be defined and updated using supervised and unsupervised learning approaches with cross-validation. Logistic regression and proportional hazards regression will be conducted to investigate associations between risk factors, onset, and resolution of PASC symptoms.DiscussionRECOVER-Adult is the first national, prospective, longitudinal cohort of PASC among US adults. Results of this study are intended to inform public health, spur clinical trials, and expand treatment options.RegistrationNCT05172024.

OBJECTIVE: Whether short-term, low-potency opioid prescriptions for acute pain lead to future at-risk opioid use remains controversial and inadequately characterized. Our objective was to measure the association between emergency department (ED) opioid analgesic exposure after a physical, trauma-related event and subsequent opioid use. We hypothesized ED opioid analgesic exposure is associated with subsequent at-risk opioid use. METHODS: Participants were enrolled in AURORA, a prospective cohort study of adult patients in 29 U.S., urban EDs receiving care for a traumatic event. Exclusion criteria were hospital admission, persons reporting any non-medical opioid use (e.g., opioids without prescription or taking more than prescribed for euphoria) in the 30 days before enrollment, and missing or incomplete data regarding opioid exposure or pain. We used multivariable logistic regression to assess the relationship between ED opioid exposure and at-risk opioid use, defined as any self-reported non-medical opioid use after initial ED encounter or prescription opioid use at 3-months. RESULTS: Of 1441 subjects completing 3-month follow-up, 872 participants were included for analysis. At-risk opioid use occurred within 3 months in 33/620 (5.3%, CI: 3.7,7.4) participants without ED opioid analgesic exposure; 4/16 (25.0%, CI: 8.3, 52.6) with ED opioid prescription only; 17/146 (11.6%, CI: 7.1, 18.3) with ED opioid administration only; 12/90 (13.3%, CI: 7.4, 22.5) with both. Controlling for clinical factors, adjusted odds ratios (aORs) for at-risk opioid use after ED opioid exposure were: ED prescription only: 4.9 (95% CI 1.4, 17.4); ED administration for analgesia only: 2.0 (CI 1.0, 3.8); both: 2.8 (CI 1.2, 6.5). CONCLUSIONS: ED opioids were associated with subsequent at-risk opioid use within three months in a geographically diverse cohort of adult trauma patients. This supports need for prospective studies focused on the long-term consequences of ED opioid analgesic exposure to estimate individual risk and guide therapeutic decision-making.

INTRODUCTION: There is paucity of culturally adapted tools for assessing depression and anxiety in children and adolescents in low-and middle-income countries. This hinders early detection, provision of appropriate and culturally acceptable interventions. In a partnership with the University of Nairobi, Nairobi County, Kenyatta National Hospital, and UNICEF, a rapid cultural adaptation of three adolescent mental health scales was done, i.e., Revised Childrens Anxiety and Depression Scale, Patient Health Questionnaire-9 and additional scales in the UNICEF mental health module for adolescents. MATERIALS AND METHODS: Using a qualitative approach, we explored adolescent participants views on cultural acceptability, comprehensibility, relevance, and completeness of specific items in these tools through an adolescent-centered approach to understand their psychosocial needs, focusing on gender and age-differentiated nuances around expression of distress. Forty-two adolescents and 20 caregivers participated in the study carried out in two primary care centers where we conducted cognitive interviews and focused group discussions assessing mental health knowledge, literacy, access to services, community, and family-level stigma. RESULTS: We reflect on process and findings of adaptations of the tools, including systematic identification of words adolescents did not understand in English and Kiswahili translations of these scales. Some translated words could not be understood and were not used in routine conversations. Response options were changed to increase comprehensibility; some statements were qualified by adding extra words to avoid ambiguity. Participants suggested alternative words that replaced difficult ones and arrived at culturally adapted tools. DISCUSSION: Study noted difficult words, phrases, dynamics in understanding words translated from one language to another, and differences in comprehension in adolescents ages 10-19 years. There is a critical need to consider cultural adaptation of depression and anxiety tools for adolescents. CONCLUSION: Results informed a set of culturally adapted scales. The process was community-driven and adhered to the principles of cultural adaptation for assessment tools.

BackgroundHypertension (HTN) is highly prevalent among people with HIV (PWH) in Namibia, but screening and treatment for HTN are not routinely offered as part of HIV care delivery. We report the implementation of a quality improvement collaborative (QIC) to accelerate integration of HTN and HIV care within public-sector health facilities in Namibia.MethodsTwenty-four facilities participated in the QIC with the aim of increasing HTN screening and treatment among adult PWH (>15 years). HTN was defined according to national treatment guidelines (i.e., systolic blood pressure >140 and/or diastolic blood pressure >90 across three measurements and at least two occasions), and decisions regarding initiation of treatment were made by physicians only. Teams from participating hospitals used quality improvement methods, monthly measurement of performance indicators, and small-scale tests of change to implement contextually tailored interventions. Coaching of sites was performed on a monthly basis by clinical officers with expertise in QI and HIV, and sites were convened as part of learning sessions to facilitate diffusion of effective interventions.ResultsBetween March 2017 and March 2018, hypertension screening occurred as part of 183,043 (86%) clinical encounters at participating facilities. Among 1,759 PWH newly diagnosed with HTN, 992 (56%) were initiated on first-line treatment. Rates of treatment initiation were higher in facilities with an on-site physician (61%) compared to those without one (51%). During the QIC, facility teams identified fourteen interventions to improve HTN screening and treatment. Among barriers to implementation, teams pointed to malfunctions of blood pressure machines and stock outs of antihypertensive medications as common challenges.ConclusionsImplementation of a QIC provided a structured approach for integrating HTN and HIV services across 24 high-volume facilities in Namibia. As rates of HTN treatment remained low despite ongoing facility-level changes, policy-level interventions-such as task sharing and supply chain strengthening-should be pursued to further improve delivery of HTN care among PWH beyond initial screening.

Asthma currently affects more than 339 million people worldwide. In the present preliminary study, we examined the efficacy of a new, inhalable soluble epoxide hydrolase inhibitor (sEHI), 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU), to attenuate airway inflammation, mucin secretion, and hyper-responsiveness (AHR) in an ovalbumin (OVA)-sensitized murine model. Male BALB/c mice were divided into phosphate-buffered saline (PBS), OVA, and OVA+TPPU (2- or 6-h) exposure groups. On days 0 and 14, the mice were administered PBS or sensitized to OVA in PBS. From days 26-38, seven challenge exposures were performed with 30 min inhalation of filtered air or OVA alone. In the OVA+TPPU groups, a 2- or 6-h TPPU inhalation preceded each 30-min OVA exposure. On day 39, pulmonary function tests (PFTs) were performed, and biological samples were collected. Lung tissues were used to semi-quantitatively evaluate the severity of inflammation and airway constriction and the volume of stored intracellular mucosubstances. Bronchoalveolar lavage (BAL) and blood samples were used to analyze regulatory lipid mediator profiles. Significantly (p < 0.05) attenuated alveolar, bronchiolar, and pleural inflammation; airway resistance and constriction; mucosubstance volume; and inflammatory lipid mediator levels were observed with OVA+TPPU relative to OVA alone. Cumulative findings indicated TPPU inhalation effectively inhibited inflammation, suppressed AHR, and prevented mucosubstance accumulation in the murine asthmatic model. Future studies should determine the pharmacokinetics (i.e., absorption, distribution, metabolism, and excretion) and pharmacodynamics (i.e., concentration/dose responses) of inhaled TPPU to explore its potential as an asthma-preventative or -rescue treatment.

Understanding reproductive biology and performance of fish is essential to formulate effective conservation and management programs. Here, we studied reproductive strategies of female Delta Smelt Hypomesus transpacificus, an endangered fish species in the State of California, the United States, focusing on (1) better understanding their distribution pattern during the winter and spring spawning season at very fine scale to predict their possible spawning grounds and (2) assessing impacts of a recent, severe drought on their reproductive performance. We formulated our hypotheses as follows; (1) female Delta Smelt migrate to particular locations for spawning so that mature females can be frequently found in those locations throughout the spawning season and (2) reproductive performance of individual female fish declined during the drought. To test the first hypotheses, we analyzed relationships between water quality parameters and maturity/distribution pattern of Delta Smelt. Salinity better explained the distribution pattern of Delta Smelt at subadult and adult stages compared with water temperature or turbidity. Although there are some freshwater locations where mature Delta Smelt can frequently be found during the spawning season, Delta Smelt at the final maturation stage (Stage 5: hydration) and post spawners appeared to be widespread in the area where salinity was below 1.0 during the spawning season. Therefore, Delta Smelt could theoretically spawn in any freshwater locations, with more specific spawning requirements in the wild (e.g., substrate type and depth) still unknown. Delta Smelt, which experienced dry and critically dry conditions (the 2013 and 2014 year-classes), showed smaller oocytes, and lower clutch size and gonadosomatic index compared with the fish caught in a wet year (2011 year-class) at the late vitellogenic stage (Stage 4 Late), suggesting reproductive performance was negatively affected by environmental conditions during the drought.

Tuberculosis (TB) preventive therapy (TPT) reduces the incidence of TB among people living with the human immunodeficiency virus (PLHIV). However, despite an increase in TPT uptake, TB/HIV coinfection remains stagnant in Uganda especially in areas of increasing HIV incidence such as the Bunyoro sub-region. This study was a retrospective review records (antiretroviral therapy [ART] files) of PLHIV who were active on ART and completed TPT in 2019/2020 at three major hospitals in the Bunyoro sub-region, Uganda: Masindi General Hospital, Hoima Regional Referral Hospital, and Kiryandongo General Hospital. The sample size (987) for each facility was determined using a proportionate sampling method to ensure the study's power and precision. Factors independently associated with acquiring TB disease post TPT were determined using modified Poisson regression analysis. An adjusted prevalence risk ratio (aPRR) with corresponding 95% confidence intervals were reported. The participants' mean age was 38.23 (±11.70) and the majority were female (64.94%). Overall, 9.63% developed active TB disease post TPT completion. In the adjusted analysis, factors associated with active TB disease were a history of an unsuppressed viral load after TPT (aPRR 4.64 (2.85-7.56), p

Assisted coral recovery (ACR) initiatives are establishing rapidly in coral reefs worldwide, using a variety of devices and techniques. In the Great Barrier Reef (GBR, the Reef), site-scale ACR field trials are occurring at multiple sites in the Cairns-Port Douglas region through Reef stewardship activities involving GBR tourism operators, Traditional Owners, and not-for-profit organisations. It is hypothesised that these field trials and the presence of ACR devices at reef tourism sites do not negatively affect visitor experiences, and when accompanied by appropriate educational information, can potentially help to raise awareness of Reef stewardship and conservation efforts. We tested these hypotheses using a survey of 708 Reef visitors on five tourism vessels, 346 of whom reported observing ACR devices in situ during their coral reef experience. Ordinal regression tests of survey responses found no statistical relationship between respondents' observation of ACR devices and (i) their overall Reef trip satisfaction, (ii) the perceived aesthetic beauty of the site(s) they visited, and (iii) their concern about the future health of the GBR. However, Reef visitors who observed ACR devices showed significantly lower levels of concern about the use of these devices on the Reef. The perceived quality of educational information presented to respondents was among the significant factors associated with their reef trip satisfaction and perceived beauty of reef sites. Our findings have implications for ACR practitioners and proponents who are concerned about public visibility, perceptions, and support for ACR initiatives, as the scale of such initiatives is expected to increase.

Monosodium glutamate (MSG) is a widely used food additive with conflicting evidence regarding its potential effects on human health, with proposed relevance for obesity and metabolic syndrome (MetS) or chronic kidney disease. As being able to accurately quantify the MSG dietary intake would help clarify the open issues, we constructed a predictive formula to estimate the daily intake of MSG in a rat model based on the urinary metabolic profile. Adult male Wistar rats were divided into groups receiving different daily amounts of MSG in drinking water (0.5, 1.5, and 3.0 g%), no MSG, and MSG withdrawal after 3.0% MSG treatment for 4 weeks. We then analyzed 24-hour urine samples for chemistries and metabolites using 1H NMR spectrometry and observed a strong correlation between urine pH, sodium, bicarbonate, alpha-ketoglutarate, citrate, fumarate, glutamate, methylamine, N-methyl-4-pyridone-3-carboxamide, succinate, and taurine and the daily MSG intake. Following the multiple linear regression analysis a simple formula model based on urinary Na+, citrate, and glutamate was most accurate and could be validated for estimating daily MSG intake. In conclusion, we propose that the daily MSG intake correlates with urinary metabolites in a rat model and that this new tool for monitoring the impact of MSG on health measures.

BackgroundWe previously developed a prediction score for MRI-quantified abdominal visceral adipose tissue (VAT) based on concurrent measurements of height, body mass index (BMI), and nine blood biomarkers, for optimal performance in five racial/ethnic groups. Here we evaluated the VAT score for prediction of future VAT and examined if enhancement with additional biomarkers, lifestyle behavior information, and medical history improves the prediction.MethodsWe examined 500 participants from the Multiethnic Cohort (MEC) with detailed data (age 50-66) collected 10 years prior to their MRI assessment of VAT. We generated three forecasted VAT prediction models: first by applying the original VAT equation to the past data on the predictors ("original"), second by refitting the past data on anthropometry and biomarkers ("refit"), and third by building a new prediction model based on the past data enhanced with lifestyle and medical history ("enhanced"). We compared the forecasted prediction scores to future VAT using the coefficient of determination (R2). In independent nested case-control data in MEC, we applied the concurrent and forecasted VAT models to assess association of the scores with subsequent incident breast cancer (950 pairs) and colorectal cancer (831 pairs).ResultsCompared to the VAT prediction by the concurrent VAT score (R2 = 0.70 in men, 0.68 in women), the forecasted original VAT score (R2 = 0.54, 0.48) performed better than past anthropometry alone (R2 = 0.47, 0.40) or two published scores (VAI, METS-VF). The forecasted refit (R2 = 0.61, 0.51) and enhanced (R2 = 0.62, 0.55) VAT scores each showed slight improvements. Similar to the concurrent VAT score, the forecasted VAT scores were associated with breast cancer, but not colorectal cancer. Both the refit score (adjusted OR for tertile 3 vs. 1 = 1.27; 95% CI: 1.00-1.62) and enhanced score (1.27; 0.99-1.62) were associated with breast cancer independently of BMI.ConclusionsPredicted VAT from midlife data can be used as a surrogate to assess the effect of VAT on incident diseases associated with obesity, as illustrated for postmenopausal breast cancer.

[This corrects the article DOI: 10.1371/journal.pone.0266608.].

BackgroundAmyotrophic lateral sclerosis (ALS), also known as Lou Gehrig´s disease, is a rare neurological condition and is the most common motor neurone disease. It is a fatal disease with specific loss of motor neurons in the spinal cord, brain stem, and motor cortex leading to progressive paralysis and usually death within five years of diagnosis. There remains no cure for ALS, and management is focused on a combination of neuroprotective medication, respiratory support, and management by multidisciplinary clinics.Patients and methodsThis prospective, single-arm, open-label phase II clinical trial of sustained weekly administration of 2 mg/kg ILB® (a low-molecular weight dextran sulphate) was conducted in a single UK hospital. Eligible patients were at least 18 years and had a definite diagnosis of ALS according to El Escorial Criteria. The co-primary outcomes were safety, tolerability, and quantity of ILB® administered. EudraCT number. 2018-000668-28.FindingsBetween 18-Apr-2019 and 27-Mar-2020, 11 patients were recruited and treated for up to 38 weeks. There were no treatment terminations or withdrawals. One serious adverse event was reported, which was not related to ILB® and resolved without sequalae. 270 mild/moderate adverse events were reported with no intolerable events occurring during the trial. The total number of ILB® treatments administered per patient ranged from 4 to 38, with a cumulative dose ranging from 745 to 6668 mg. As a result of the COVID-19 pandemic and the high-risk status of study participants, recruitment and treatment was suspended early in Mar-2020. At the long-term follow-up, three patients had died after the trial was halted, between 53 and 62 weeks after their final ILB® injection.InterpretationLong-term weekly ILB® injections of 2 mg/kg was well tolerated and had an acceptable safety profile in patients with ALS.Trial registrationEudraCT: 2018-000668-28. clinicaltrials.gov: NCT03705390. This trial adheres to the principles of GCP in the design, conduct, recording and reporting of clinical trials as listed in part 2, "Conditions and Principles which apply to all Clinical Trials" under the header "Principles based on Articles 2 to 5 of the EU GCP Directive" in the Medicines for Human Use Clinical Trials Regulations (as amended in SI 2006/1928). For clarity, the study did not conform to all aspects of the International Conference on Harmonisation (ICH) E6 R2 Guidelines for GCP (also known as 'ICH GCP'). Of note, we did not use an external database, perform 100% source data verification, and only primary outcome data were analysed in parallel by a second, independent statistician.

Many habitat-specialist organisms occur in distinct, patchy habitat, yet do not occupy all patches, and an important question is why apparently suitable habitat remains unoccupied. We examined factors influencing patch occupancy in near-threatened, little-known Diademed Plovers (Phegornis mitchellii), arguably the bird most specialized to life in High Andean peatlands. Andean peatlands are well-suited to occupancy modelling because they are discrete patches of humid habitat within a matrix of high-altitude steppe. We hypothesized that Diademed Plovers occupy preferably larger and more humid peatlands, and avoid peatlands used for grazing by llamas and vicuñas, which may trample vegetation and nests. From December 2021 to February 2022 (breeding season), we conducted plover occupancy surveys (2-4) on 40 peatlands at Lagunas de Vilama, a landscape of arid steppe and wetlands above 4,500 m in NW Argentina. We measured peatland size, grazing pressure, topographic and remotely-sensed variables that correlate with humidity, and incorporated these as covariates in occupancy models. Occupancy models showed that more than 50% of the studied peatlands were used by Diademed Plovers and most showed signs of reproduction, highlighting the importance of the Vilama Wetlands for Diademed Plover conservation. Within peatlands, Diademed Plovers were most often associated with headwaters. The top ranked occupancy model included constant detection, random spatial effects, and a single occupancy covariate: mean NDWI (Normalized Difference Water Index, an index correlated with water content and humidity) over the previous three years. Contrary to our prediction, Diademed Plovers preferred less water-saturated peatlands (lower NDWI), possibly to avoid nest flooding. This may be especially important in wet years, like the year when we conducted our surveys. Neither peatland size nor grazing by llamas and vicuñas affected peatland use by Diademed Plovers, suggesting that llama grazing at current levels may be compatible with plover conservation. For organisms that specialize on humid habitats, such as peatlands, factors affecting occupancy may vary temporally with variation in climate, and we recommend follow-up surveys across multi-year timescales to untangle the impact of climate on animals' use of humid habitats.

ObjectivesChildren with medical complexity experienced health disparities during the coronavirus disease 2019 (COVID-19) pandemic. Language may compound these disparities since people speaking languages other than English (LOE) also experienced worse COVID-19 outcomes. Our objective was to investigate associations between household language for children with medical complexity and caregiver COVID-19 vaccine intentions, testing knowledge, and trusted sources of information.MethodsThis cross-sectional survey of caregivers of children with medical complexity ages 5 to 17 years was conducted from April-June 2022. Children with medical complexity had at least 1 Complex Chronic Condition. Households were considered LOE if they reported speaking any language other than English. Multivariable logistic regression examined associations between LOE and COVID-19 vaccine intentions, interpretation of COVID-19 test results, and trusted sources of information.ResultsWe included 1,338 caregivers of children with medical complexity (49% response rate), of which 133 (10%) had household LOE (31 total languages, 58% being Spanish). There was no association between household LOE and caregiver COVID-19 vaccine intentions. Caregivers in households with LOE had similar interpretations of positive COVID-19 test results, but significantly different interpretations of negative results. Odds of interpreting a negative test as expected (meaning the child does not have COVID-19 now or can still get the virus from others) were lower in LOE households (aOR [95% CI]: 0.56 [0.34-0.95]). Households with LOE were more likely to report trusting the US government to provide COVID-19 information (aOR [95% CI]: 1.86 [1.24-2.81]).ConclusionDifferences in COVID-19 test interpretations based on household language for children with medical complexity were observed and could contribute to disparities in outcomes. Opportunities for more inclusive public health messaging likely exist.

We propose a fold change transform that demonstrates a combination of visualization properties exhibited by log and linear plots of fold change. A fold change visualization should ideally exhibit: (1) readability, where fold change values are recoverable from datapoint position; (2) proportionality, where fold change values of the same direction are proportionally distant from the point of no change; (3) symmetry, where positive and negative fold changes of the same magnitude are equidistant to the point of no change; and (4) high dynamic range, where datapoint values are distinguishable across orders of magnitude within a fixed plot area and pixel resolution. A linear visualization has readability and partial proportionality but lacks high dynamic range and symmetry (because negative direction fold changes are bound between [0, 1] while positive are between (1, ∞)). Log plots of fold change have partial readability, high dynamic range, and symmetry, but lack proportionality because of the log transform. We outline a new transform, named mirrored axis distortion of fold change (MAD-FC), that extends a linear visualization of fold change data to exhibit readability, proportionality, and symmetry (but still has the limited dynamic range of linear plots). We illustrate the use of MAD-FC with biomedical data using various fold change plots. We argue that MAD plots may be a more useful visualization than log or linear plots for applications that do not require a high dynamic range (less than 8 units in log2 space).

BackgroundAlthough breastfeeding is recommended as the optimal form of nutrition in the first six months, it is not sustained as the predominant mode of feeding infants in Scotland. This study estimated the impact of infant feeding choices on primary and secondary healthcare service costs in a 13-year birth cohort.MethodUsing linked administrative datasets, in a retrospective cohort design of 502,948 singletons born in Scotland between 1997 and 2009, we estimated the cost of GP consultations and hospital admissions by area deprivation and mode of infant feeding up to 6-8 weeks for ten common childhood conditions from birth to 27 months. Additionally, we calculated the potential healthcare savings if all infants in the cohort had been exclusively breastfed at 6-8 weeks. Discounting of 1.5% was applied following current health economic conventions and 2009/10 used as the base year.ResultsOver the study period, the estimated cost of hospital admissions in the cohort was £111 million and £2 million for the 2% subset of the cohort with primary care records. Within each quintile of deprivation, exclusively breastfed infants used fewer healthcare services and incurred lower costs compared to infants fed (any) formula milk. At least £10 million of healthcare costs may have been avoided if formula-fed infants had been exclusively breastfed within the first 6-8 weeks of birth.ConclusionsThis study using a representative birth cohort demonstrates how breastmilk can promote equitable child health by reducing childhood illness and healthcare utilisation in the early years.

The Stroop task is a well-established tool to investigate the influence of competing visual categories on decision making. Neuroimaging as well as rTMS studies have demonstrated the involvement of parietal structures, particularly the intraparietal sulcus (IPS), in this task. Given its reliability, the numerical Stroop task was used to compare the effects of different TMS targeting approaches by Sack and colleagues (Sack AT 2009), who elegantly demonstrated the superiority of individualized fMRI targeting. We performed the present study to test whether fMRI-guided rTMS effects on numerical Stroop task performance could still be observed while using more advanced techniques that have emerged in the last decade (e.g., electrical sham, robotic coil holder system, etc.). To do so we used a traditional reaction time analysis and we performed, post-hoc, a more advanced comprehensive drift diffusion modeling approach. Fifteen participants performed the numerical Stroop task while active or sham 10 Hz rTMS was applied over the region of the right intraparietal sulcus (IPS) showing the strongest functional activation in the Incongruent > Congruent contrast. This target was determined based on individualized fMRI data collected during a separate session. Contrary to our assumption, the classical reaction time analysis did not show any superiority of active rTMS over sham, probably due to confounds such as potential cumulative rTMS effects, and the effect of practice. However, the modeling approach revealed a robust effect of rTMS on the drift rate variable, suggesting differential processing of congruent and incongruent properties in perceptual decision-making, and more generally, illustrating that more advanced computational analysis of performance can elucidate the effects of rTMS on the brain where simpler methods may not.

This research aimed to investigate the mediating function of Green Employee Empowerment (GEE) in the relationship between Green Human Resource Management practices (GHRM) and the environmental performance of small and medium-sized enterprises (SMEs) in Ghana, drawing on the Ability-Motivation-Opportunity (AMO) theory. This study assessed the hypotheses in the established research model using structural equation modeling based on data collected from 320 participants from small and medium-sized firms in Ghana. The study's results revealed that GHRM practices were significantly correlated with the firm's environmental performance. The study found significant GHRM's indirect consequences on environmental performance through GEE in all models examined. These findings suggest that GEE plays a crucial role in translating the impact of GHRM practices into improved environmental performance. The study overlooked other potential mediators or moderators in the relationship between GHRM practices and environmental performance, focusing on GEE. To better understand the complex dynamics behind GHRM techniques' environmental performance, future research might examine business culture, leadership style, and employee sustainability attitudes.

Cybercrime is a major challenge facing the world, with estimated costs ranging from the hundreds of millions to the trillions. Despite the threat it poses, cybercrime is somewhat an invisible phenomenon. In carrying out their virtual attacks, offenders often mask their physical locations by hiding behind online nicknames and technical protections. This means technical data are not well suited to establishing the true location of offenders and scholarly knowledge of cybercrime geography is limited. This paper proposes a solution: an expert survey. From March to October 2021 we invited leading experts in cybercrime intelligence/investigations from across the world to participate in an anonymized online survey on the geographical location of cybercrime offenders. The survey asked participants to consider five major categories of cybercrime, nominate the countries that they consider to be the most significant sources of each of these types of cybercrimes, and then rank each nominated country according to the impact, professionalism, and technical skill of its offenders. The outcome of the survey is the World Cybercrime Index, a global metric of cybercriminality organised around five types of cybercrime. The results indicate that a relatively small number of countries house the greatest cybercriminal threats. These findings partially remove the veil of anonymity around cybercriminal offenders, may aid law enforcement and policymakers in fighting this threat, and contribute to the study of cybercrime as a local phenomenon.

In 2021, an estimated 10.6 million people fell ill with tuberculosis (TB) globally and 11.3% were children. About 40% of children aged five to fourteen years with TB are missed annually. In Uganda, 44% of adolescents with chronic cough of more than two weeks do not seek care from health facilities. Therefore, strategies to promote health care-seeking behaviour among adolescents were urgently needed to resolve the gap. In regard to this, the research project utilized a before and after design, in which the number of adolescents (10-19years) enrolled in the project health facilities were compared before and after the intervention. The intervention package that comprised of tuberculosis awareness and screening information was developed together with adolescents, thus; a human-centred approach was used. The package consisted of TB screening cards, poster messages and a local song. The song was broadcasted in the community radios. Poster messages were deployed in the community by the village health teams (VHTS). The TB screening cards were given to TB positive and presumptive adults to screen adolescents at home. Adolescents that were found with TB symptoms were referred to the project health facilities. Socio-demographic and clinical characteristics of eligible adolescents were collected in a period of six months from Kawolo, Iganga, Gombe and Kiwoko health facilities. To determine the effectiveness of the package, before and after intervention data were equally collected. A total of 394 adolescents were enrolled, majority (76%) were school going. The intervention improved adolescent TB care seeking in the four project health facilities. The average number of adolescents screened increased from 159 to 309 (incidence rate ratio (IRR) = 1.9, P

Sharing of resources is a common feature of human societies. Yet, there is substantial societal variation in children's generosity, and this variation emerges during middle childhood. Societal differences in self-construal orientation may be one factor influencing the ontogeny of generosity. Here, we examine anonymous Dictator Game sharing in 7-and-8-year-olds from two distinct societies: India and the UK (N = 180). We used self-construal manipulations to investigate whether priming self- or other-focused conversations would differentially influence children's generosity. There were no differences in generosity between populations. While a significant reduction in generosity was found following self-priming in both societies, other-priming was ineffectual. The findings are discussed in relation to experimental features and the role of anonymity and reputational concerns.

BackgroundFrailty is characterised by a reduced resilience to adversity. In this analysis we examined changes in frailty in people aged 50+ before and during a period of austere public spending in England.MethodsData from the English Longitudinal Study of Ageing 2002-2018 were analysed. Associations between austerity and frailty were examined using (1) Multilevel interrupted times series analysis (ITSA); and (2) Accelerated longitudinal modelling comparing frailty trajectories in people of the same age in 2002 and 2012.ResultsThe analysis included 16,410 people (mean age 67 years, 55% women), with mean frailty index score of 0.16. Mean scores in women (0.16) where higher than in men (mean 0.14), and higher in the poorest tertile (mean 0.20) than the richest (mean 0.12). In the ITSA, frailty index scores increased more quickly during austerity than before, with the additional increase in frailty 2012-2018 being similar in magnitude to the difference in mean frailty score between people aged 65-69 and 70-74 years. Steeper increases in frailty after 2012 were experienced across the wealth-spectrum and in both sexes but were greater in the very oldest (80+). In the accelerated longitudinal analysis, frailty was lower in 2012 than 2002, but increased more rapidly in the 2012 cohort compared to the 2002 cohort; markedly so in people aged 80+.ConclusionThe period of austerity politics was associated with steeper increases in frailty with age compared to the pre-austerity period, consistent with previously observed increases in mortality.

Criminal legal system involvement (CLI) is a critical social determinant of health that lies at the intersection of multiple sources of health disparities. The COVID-19 pandemic exacerbates many of these disparities, and specific vulnerabilities faced by the CLI population. This study investigated the prevalence of COVID-19-related misinformation, as well as its relationship with COVID-19 information sources used among Americans experiencing CLI. A nationally representative sample of American adults aged 18+ (N = 1,161), including a subsample of CLI individuals (n = 168), were surveyed in February-March 2021. On a 10-item test, CLI participants endorsed a greater number of misinformation statements (M = 1.88 vs. 1.27) than non-CLI participants, p < .001. CLI participants reported less use of government and scientific sources (p = .017) and less use of personal sources (p = .003) for COVID-19 information than non-CLI participants. Poisson models showed that use of government and scientific sources was negatively associated with misinformation endorsement for non-CLI participants (IRR = .841, p < .001), but not for CLI participants (IRR = .957, p = .619). These findings suggest that building and leveraging trust in important information sources are critical to the containment and mitigation of COVID-19-related misinformation in the CLI population.

COVID-19 serological test must have high sensitivity as well as specificity to rule out cross-reactivity with common coronaviruses (HCoVs). We have developed a quantitative multiplex test, measuring antibodies against spike (S) proteins of SARS-CoV-2, SARS-CoV, MERS-CoV, and common human coronavirus strains (229E, NL63, OC43, HKU1), and nucleocapsid (N) protein of SARS-CoV viruses. Receptor binding domain of S protein of SARS-CoV-2 (S-RBD), and N protein, demonstrated sensitivity (94% and 92.5%, respectively) in COVID-19 patients (n = 53), with 98% specificity in non-COVID-19 respiratory-disease (n = 98), and healthy-controls (n = 129). Anti S-RBD and N antibodies appeared five to ten days post-onset of symptoms, peaking at approximately four weeks. The appearance of IgG and IgM coincided while IgG subtypes, IgG1 and IgG3 appeared soon after the total IgG; IgG2 and IgG4 remained undetectable. Several inflammatory cytokines/chemokines were found to be elevated in many COVID-19 patients (e.g., Eotaxin, Gro-α, CXCL-10 (IP-10), RANTES (CCL5), IL-2Rα, MCP-1, and SCGF-b); CXCL-10 was elevated in all. In contrast to antibody titers, levels of CXCL-10 decreased with the improvement in patient health suggesting it as a candidate for disease resolution. Importantly, anti-N antibodies appear before S-RBD and differentiate between vaccinated and infected people-current vaccines (and several in the pipeline) are S protein-based.

Maternal nutrition during gestation has been investigated for its role in child neurodevelopment. However, little is known about the potential impact of gestational caffeine exposure on child autistic behaviors. Here, we assess the relation between maternal caffeine intake during pregnancy and children's behavioral traits related to Autism Spectrum Disorder (ASD). We harmonized data from two pregnancy cohorts, Early Autism Risk Longitudinal Investigation (EARLI) (n = 120), an enriched-risk cohort of mothers who previously had a child with ASD, from Pennsylvania, Maryland, and Northern California (2009-2012), and the Health Outcomes and Measures of the Environment (HOME) Study (n = 269), a general population cohort from Cincinnati, Ohio (2003-2006). Mothers self-reported caffeine intake twice during pregnancy. Caregivers reported child behavioral traits related to ASD using the Social Responsiveness Scale (SRS) when children were aged 3-8 years. Higher scores indicate more ASD-related behaviors. We estimated covariate-adjusted differences in continuous SRS T-scores per interquartile range increase in caffeine intake. Self-reported caffeine intake during pregnancy was positively associated with SRS T-scores among children in EARLI (β: 2.0; 95% CI -0.1, 4.0), but to a lesser extent in HOME (β: 0.6; 95% CI -0.5, 1.6). In HOME, pre-pregnancy body mass index (BMI) modified the association between caffeine intake and SRS T-scores, where more positive associations were observed among women with higher BMIs. Our findings suggest gestational caffeine intake may represent a marker of vulnerability to childhood ASD-related behaviors. Additional studies are warranted to extend these findings.

PurposeThe phosphodiesterase inhibitor sildenafil is a promising treatment for neurodegenerative disease, but it can cause oxidative stress in photoreceptors ex vivo and degrade visual performance in humans. Here, we test the hypotheses that in wildtype mice sildenafil causes i) wide-spread photoreceptor oxidative stress in vivo that is linked with ii) impaired vision.MethodsIn dark or light-adapted C57BL/6 mice ± sildenafil treatment, the presence of oxidative stress was evaluated in retina laminae in vivo by QUEnch-assiSTed (QUEST) magnetic resonance imaging, in the subretinal space in vivo by QUEST optical coherence tomography, and in freshly excised retina by a dichlorofluorescein assay. Visual performance indices were also evaluated by QUEST optokinetic tracking.ResultsIn light-adapted mice, 1 hr post-sildenafil administration, oxidative stress was most evident in the superior peripheral outer retina on both in vivo and ex vivo examinations; little evidence was noted for central retina oxidative stress in vivo and ex vivo. In dark-adapted mice 1 hr after sildenafil, no evidence for outer retina oxidative stress was found in vivo. Evidence for sildenafil-induced central retina rod cGMP accumulation was suggested as a panretinally thinner, dark-like subretinal space thickness in light-adapted mice at 1 hr but not 5 hr post-sildenafil. Cone-based visual performance was impaired by 5 hr post-sildenafil and not corrected with anti-oxidants; vision was normal at 1 hr and 24 hr post-sildenafil.ConclusionsThe sildenafil-induced spatiotemporal pattern of oxidative stress in photoreceptors dominated by rods was unrelated to impairment of cone-based visual performance in wildtype mice.

This study combined a social network analysis and whole-genome sequencing (WGS) to test for general patterns of contagious spread of a mycobacterial infection for which pathways of disease acquisition are not well understood. Our population included 275 cases diagnosed with avian mycobacteriosis that were nested in a source population of 16,430 birds at San Diego Zoo Wildlife Alliance facilities from 1992 through mid-2014. Mycobacteria species were determined using conventional methods and whole genome sequencing (WGS). Mycobacterium avium avium (MAA) and Mycobacterium genavense were the most common species of mycobacteria identified and were present in different proportions across bird taxa. A social network for the birds was constructed from the source population to identify directly and indirectly connected cases during time periods relevant to disease transmission. Associations between network connectivity and genetic similarity of mycobacteria (as determined by clusters of genotypes separated by few single nucleotide polymorphisms, or SNPs) were then evaluated in observed and randomly generated network permutations. Findings showed that some genotypes clustered along pathways of bird connectivity, while others were dispersed throughout the network. The proportion of directly connected birds having a similar mycobacterial genotype was 0.36 and significant (p

BackgroundLead, a toxic metal, affects cognitive development at the lowest measurable concentrations found in children, but little is known about its direct impact on brain development. Recently, we reported widespread decreases in cortical surface area and volume with increased risks of lead exposure, primarily in children of low-income families.Methods and findingsWe examined associations of neighborhood-level risk of lead exposure with cognitive test performance and subcortical brain volumes. We also examined whether subcortical structure mediated associations between lead risk and cognitive performance. Our analyses employed a cross-sectional analysis of baseline data from the observational Adolescent Brain Cognitive Development (ABCD) Study. The multi-center ABCD Study used school-based enrollment to recruit a demographically diverse cohort of almost 11,900 9- and 10-year-old children from an initial 22 study sites. The analyzed sample included data from 8,524 typically developing child participants and their parents or caregivers. The primary outcomes and measures were subcortical brain structure, cognitive performance using the National Institutes of Health Toolbox, and geocoded risk of lead exposure. Children who lived in neighborhoods with greater risks of environmental lead exposure exhibited smaller volumes of the mid-anterior (partial correlation coefficient [rp] = -0.040), central (rp = -0.038), and mid-posterior corpus callosum (rp = -0.035). Smaller volumes of these three callosal regions were associated with poorer performance on cognitive tests measuring language and processing speed. The association of lead exposure risk with cognitive performance was partially mediated through callosal volume, particularly the mid-posterior corpus callosum. In contrast, neighborhood-level indicators of disadvantage were not associated with smaller volumes of these brain structures.ConclusionsEnvironmental factors related to the risk of lead exposure may be associated with certain aspects of cognitive functioning via diminished subcortical brain structure, including the anterior splenium (i.e., mid-posterior corpus callosum).

BackgroundGenome-wide association studies have identified multiple genomic loci associated with coronary artery disease, but most are common variants in non-coding regions that provide limited information on causal genes and etiology of the disease. To overcome the limited scope that common variants provide, we focused our investigation on low-frequency and rare sequence variations primarily residing in coding regions of the genome.Methods and resultsUsing samples of individuals of European ancestry from ten cohorts within the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, both cross-sectional and prospective analyses were conducted to examine associations between genetic variants and myocardial infarction (MI), coronary heart disease (CHD), and all-cause mortality following these events. For prevalent events, a total of 27,349 participants of European ancestry, including 1831 prevalent MI cases and 2518 prevalent CHD cases were used. For incident cases, a total of 55,736 participants of European ancestry were included (3,031 incident MI cases and 5,425 incident CHD cases). There were 1,860 all-cause deaths among the 3,751 MI and CHD cases from six cohorts that contributed to the analysis of all-cause mortality. Single variant and gene-based analyses were performed separately in each cohort and then meta-analyzed for each outcome. A low-frequency intronic variant (rs988583) in PLCL1 was significantly associated with prevalent MI (OR = 1.80, 95% confidence interval: 1.43, 2.27; P = 7.12 × 10-7). We conducted gene-based burden tests for genes with a cumulative minor allele count (cMAC) ≥ 5 and variants with minor allele frequency (MAF) < 5%. TMPRSS5 and LDLRAD1 were significantly associated with prevalent MI and CHD, respectively, and RC3H2 and ANGPTL4 were significantly associated with incident MI and CHD, respectively. No loci were significantly associated with all-cause mortality following a MI or CHD event.ConclusionThis study identified one known locus (ANGPTL4) and four new loci (PLCL1, RC3H2, TMPRSS5, and LDLRAD1) associated with cardiovascular disease risk that warrant further investigation.

The incidence of type 2 diabetes is increasing more rapidly in adolescents than in any other age group. We identified and compared metabolite signatures in obese children with type 2 diabetes (T2D), obese children without diabetes (OB), and healthy, age- and gender-matched normal weight controls (NW) by measuring 273 analytes in fasting plasma and 24-hour urine samples from 90 subjects by targeted LC-MS/MS. Diabetic subjects were within 2 years of diagnosis in an attempt to capture early-stage disease prior to declining renal function. We found 22 urine metabolites that were uniquely associated with T2D when compared to OB and NW groups. The metabolites most significantly elevated in T2D youth included members of the betaine pathway, nucleic acid metabolism, and branched-chain amino acids (BCAAs) and their catabolites. Notably, the metabolite pattern in OB and T2D groups differed between urine and plasma, suggesting that urinary BCAAs and their intermediates behaved as a more specific biomarker for T2D, while plasma BCAAs associated with the obese, insulin resistant state independent of diabetes status. Correlative analysis of metabolites in the T2D signature indicated that betaine metabolites, BCAAs, and aromatic amino acids were associated with hyperglycemia, but BCAA acylglycine derivatives and nucleic acid metabolites were linked to insulin resistance. Of major interest, we found that urine levels of succinylaminoimidazole carboxamide riboside (SAICA-riboside) were increased in diabetic youth, identifying urine SAICA-riboside as a potential biomarker for T2D.

Islet autoantibodies are predominantly measured by radioassay to facilitate risk assessment and diagnosis of type 1 diabetes. However, the reliance on radioactive components, large sample volumes and limited throughput renders radioassay testing costly and challenging. We developed a multiplex analysis platform based on antibody detection by agglutination-PCR (ADAP) for the sample-sparing measurement of GAD, IA-2 and insulin autoantibodies/antibodies in 1 μL serum. The assay was developed and validated in 7 distinct cohorts (n = 858) with the majority of the cohorts blinded prior to analysis. Measurements from the ADAP assay were compared to radioassay to determine correlation, concordance, agreement, clinical sensitivity and specificity. The average overall agreement between ADAP and radioassay was above 91%. The average clinical sensitivity and specificity were 96% and 97%. In the IASP 2018 workshop, ADAP achieved the highest sensitivity of all assays tested at 95% specificity (AS95) rating for GAD and IA-2 autoantibodies and top-tier performance for insulin autoantibodies. Furthermore, ADAP correctly identified 95% high-risk individuals with two or more autoantibodies by radioassay amongst 39 relatives of T1D patients tested. In conclusion, the new ADAP assay can reliably detect the three cardinal islet autoantibodies/antibodies in 1μL serum with high sensitivity. This novel assay may improve pediatric testing compliance and facilitate easier community-wide screening for islet autoantibodies.

Disease transmission can be identified in a social network from the structural patterns of contact. However, it is difficult to separate contagious processes from those driven by homophily, and multiple pathways of transmission or inexact information on the timing of infection can obscure the detection of true transmission events. Here, we analyze the dynamic social network of a large, and near-complete population of 16,430 zoo birds tracked daily over 22 years to test a novel "friends-of-friends" strategy for detecting contagion in a social network. The results show that cases of avian mycobacteriosis were significantly clustered among pairs of birds that had been in direct contact. However, since these clusters might result due to correlated traits or a shared environment, we also analyzed pairs of birds that had never been in direct contact but were indirectly connected in the network via other birds. The disease was also significantly clustered among these friends of friends and a reverse-time placebo test shows that homophily could not be causing the clustering. These results provide empirical evidence that at least some avian mycobacteriosis infections are transmitted between birds, and provide new methods for detecting contagious processes in large-scale global network structures with indirect contacts, even when transmission pathways, timing of cases, or etiologic agents are unknown.

Recently emerging evidence indicates accelerated age-related changes in the structure and function of the brain in schizophrenia, raising a question about its potential consequences on cognitive function. Using a large sample of schizophrenia patients and controls and a battery of tasks across multiple cognitive domains, we examined whether patients show accelerated age-related decline in cognition and whether an age-related effect differ between females and males. We utilized data of 1,415 schizophrenia patients and 1,062 healthy community collected by the second phase of the Consortium on the Genetics of Schizophrenia (COGS-2). A battery of cognitive tasks included the Letter-Number Span Task, two forms of the Continuous Performance Test, the California Verbal Learning Test, Second Edition, the Penn Emotion Identification Test and the Penn Facial Memory Test. The effect of age and gender on cognitive performance was examined with a general linear model. We observed age-related changes on most cognitive measures, which was similar between males and females. Compared to controls, patients showed greater deterioration in performance on attention/vigilance and greater slowness of processing social information with increasing age. However, controls showed greater age-related changes in working memory and verbal memory compared to patients. Age-related changes (η2p of 0.001 to .008) were much smaller than between-group differences (η2p of 0.005 to .037). This study found that patients showed continued decline of cognition on some domains but stable impairment or even less decline on other domains with increasing age. These findings indicate that age-related changes in cognition in schizophrenia are subtle and not uniform across multiple cognitive domains.

Ocean acidification (OA) represents a serious challenge to marine ecosystems. Laboratory studies addressing OA indicate broadly negative effects for marine organisms, particularly those relying on calcification processes. Growing evidence also suggests OA combined with other environmental stressors may be even more deleterious. Scaling these laboratory studies to ecological performance in the field, where environmental heterogeneity may mediate responses, is a critical next step toward understanding OA impacts on natural communities. We leveraged an upwelling-driven pH mosaic along the California Current System to deconstruct the relative influences of pH, ocean temperature, and food availability on seasonal growth, condition and shell thickness of the ecologically dominant intertidal mussel Mytilus californianus. In 2011 and 2012, ecological performance of adult mussels from local and commonly sourced populations was measured at 8 rocky intertidal sites between central Oregon and southern California. Sites coincided with a large-scale network of intertidal pH sensors, allowing comparisons among pH and other environmental stressors. Adult California mussel growth and size varied latitudinally among sites and inter-annually, and mean shell thickness index and shell weight growth were reduced with low pH. Surprisingly, shell length growth and the ratio of tissue to shell weight were enhanced, not diminished as expected, by low pH. In contrast, and as expected, shell weight growth and shell thickness were both diminished by low pH, consistent with the idea that OA exposure can compromise shell-dependent defenses against predators or wave forces. We also found that adult mussel shell weight growth and relative tissue mass were negatively associated with increased pH variability. Including local pH conditions with previously documented influences of ocean temperature, food availability, aerial exposure, and origin site enhanced the explanatory power of models describing observed performance differences. Responses of local mussel populations differed from those of a common source population suggesting mussel performance partially depended on genetic or persistent phenotypic differences. In light of prior research showing deleterious effects of low pH on larval mussels, our results suggest a life history transition leading to greater resilience in at least some performance metrics to ocean acidification by adult California mussels. Our data also demonstrate "hot" (more extreme) and "cold" (less extreme) spots in both mussel responses and environmental conditions, a pattern that may enable mitigation approaches in response to future changes in climate.

No single neuroimaging technique or sequence is capable of reflecting the functional deficits manifest in MS. Given the interest in imaging biomarkers for short- to medium-term studies, we aimed to assess which imaging metrics might best represent functional impairment for monitoring in clinical trials. Given the complexity of functional impairment in MS, however, it is useful to isolate a particular functionally relevant pathway to understand the relationship between imaging and neurological function. We therefore analyzed existing data, combining multiparametric MRI and OCT to describe MS associated visual impairment. We assessed baseline data from fifty MS patients enrolled in ReBUILD, a prospective trial assessing the effect of a remyelinating drug (clemastine). Subjects underwent 3T MRI imaging, including Neurite Orientation Dispersion and Density Imaging (NODDI), myelin content quantification, and retinal imaging, using OCT. Visual function was assessed, using low-contrast letter acuity. MRI and OCT data were studied to model visual function in MS, using a partial, least-squares, regression analysis. Measures of neurodegeneration along the entire visual pathway, described most of the observed variance in visual disability, measured by low contrast letter acuity. In those patients with an identified history of ON, however, putative myelin measures also showed correlation with visual performance. In the absence of clinically identifiable inflammatory episodes, residual disability correlates with neurodegeneration, whereas after an identifiable exacerbation, putative measures of myelin content are additionally informative.

There is an extensive literature establishing, validating, and quantifying a wide range of responses of fishes to fasting. Our study complements this work by comparing fed and unfed treatments of hatchery-raised Delta Smelt (Hypomesus transpacificus)-an imperiled fish that is endemic to the San Francisco Estuary and its tributaries in California, USA-across a diverse suite of endpoints over a two-month time series. The experiment was conducted at 15.9°C, and individuals were sampled at 12 time points as starvation became increasingly severe. We found that hepatosomatic index and condition factor were relatively sensitive to starvation, becoming significantly depressed at Day 4 and 7, respectively. Histological analysis of liver showed elevated cytoplasmic inclusion bodies at Day 7, followed by increased glycogen depletion, single cell necrosis, and hydropic vacuolar degeneration at Day 14, 21, and 28, respectively. Of four antioxidants measured, glutathione decreased at Day 4, superoxide dismutase increased at Day 14, catalase increased at Day 56, and glutathione peroxidase was not affected by starvation. The net result was a ~2-fold increase in lipid peroxidation (malondialdehyde) in fasted fish that was highly inconsistent through time. RNA to DNA ratio and triglycerides in muscle were relatively insensitive to starvation, only consistently decreasing with fasting after mortality began increasing in the 'No Feeding' treatment, at Day 21. Together, these results suggest that Delta Smelt mobilize hepatic energy stores far more rapidly than lipids in muscle when subjected to fasting, leading to rapid atrophy of liver and the development of cytoplasmic inclusion bodies-possibly autophagosomes-in hepatocytes.

Islet autoantibodies are predominantly measured by radioassay to facilitate risk assessment and diagnosis of type 1 diabetes. However, the reliance on radioactive components, large sample volumes and limited throughput renders radioassay testing costly and challenging. We developed a multiplex analysis platform based on antibody detection by agglutination-PCR (ADAP) for the sample-sparing measurement of GAD, IA-2 and insulin autoantibodies/antibodies in 1 μL serum. The assay was developed and validated in 7 distinct cohorts (n = 858) with the majority of the cohorts blinded prior to analysis. Measurements from the ADAP assay were compared to radioassay to determine correlation, concordance, agreement, clinical sensitivity and specificity. The average overall agreement between ADAP and radioassay was above 91%. The average clinical sensitivity and specificity were 96% and 97%. In the IASP 2018 workshop, ADAP achieved the highest sensitivity of all assays tested at 95% specificity (AS95) rating for GAD and IA-2 autoantibodies and top-tier performance for insulin autoantibodies. Furthermore, ADAP correctly identified 95% high-risk individuals with two or more autoantibodies by radioassay amongst 39 relatives of T1D patients tested. In conclusion, the new ADAP assay can reliably detect the three cardinal islet autoantibodies/antibodies in 1μL serum with high sensitivity. This novel assay may improve pediatric testing compliance and facilitate easier community-wide screening for islet autoantibodies.

BackgroundPoor diets contribute to metabolic complications of obesity, insulin resistance and dyslipidemia. Metabolomic biomarkers may serve as early nutrition-sensitive health indicators. This family-based lifestyle change program compared metabolic outcomes in an intervention group (INT) that consumed 2 nutrient bars daily for 2-months and a control group (CONT).MethodsOverweight, predominantly minority and female adolescent (Teen)/parent adult caretaker (PAC) family units were recruited from a pediatric obesity clinic. CONT (8 Teen, 8 PAC) and INT (10 Teen, 10 PAC) groups randomized to nutrient bar supplementation attended weekly classes that included group nutrition counseling and supervised exercise. Pre-post physical and behavioral parameters, fasting traditional biomarkers, plasma sphingolipids and amino acid metabolites were measured.ResultsIn the full cohort, a baseline sphingolipid ceramide principal component composite score correlated with adiponectin, triglycerides, triglyceride-rich very low density lipoproteins, and atherogenic small low density lipoprotein (LDL) sublasses. Inverse associations were seen between a sphingomyelin composite score and C-reactive protein, a dihydroceramide composite score and diastolic blood pressure, and the final principal component that included glutathionone with fasting insulin and the homeostatic model of insulin resistance. In CONT, plasma ceramides, sphinganine, sphingosine and amino acid metabolites increased, presumably due to increased physical activity. Nutrient bar supplementation (INT) blunted this rise and significantly decreased ureagenic, aromatic and gluconeogenic amino acid metabolites. Metabolomic changes were positively correlated with improvements in clinical biomarkers of dyslipidemia.ConclusionNutrient bar supplementation with increased physical activity in obese Teens and PAC elicits favorable metabolomic changes that correlate with improved dyslipidemia. The trial from which the analyses reported upon herein was part of a series of nutrient bar clinical trials registered at clinicaltrials.gov as NCT02239198.