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The etiologies of meningitis range in severity from benign and self-limited to life-threatening with potentially severe morbidity. Bacterial meningitis is a medical emergency that requires prompt recognition and treatment. Mortality remains high despite the introduction of vaccinations for common pathogens that have reduced the incidence of meningitis worldwide. Aseptic meningitis is the most common form of meningitis with an annual incidence of 7.6 per 100,000 adults. Most cases of aseptic meningitis are viral and require supportive care. Viral meningitis is generally self-limited with a good prognosis. Examination maneuvers such as Kernig sign or Brudzinski sign may not be useful to differentiate bacterial from aseptic meningitis because of variable sensitivity and specificity. Because clinical findings are also unreliable, the diagnosis relies on the examination of cerebrospinal fluid obtained from lumbar puncture. Delayed initiation of antibiotics can worsen mortality. Treatment should be started promptly in cases where transfer, imaging, or lumbar puncture may slow a definitive diagnosis. Empiric antibiotics should be directed toward the most likely pathogens and should be adjusted by patient age and risk factors. Dexamethasone should be administered to children and adults with suspected bacterial meningitis before or at the time of initiation of antibiotics. Vaccination against the most common pathogens that cause bacterial meningitis is recommended. Chemoprophylaxis of close contacts is helpful in preventing additional infections.

Camera traps (CTs) have become cemented as an important tool of wildlife research, yet their utility is now extending beyond academics, as CTs can contribute to inclusive place‐based wildlife management. From advances in analytics and technology, CT‐based density estimates of wildlife are an emerging field of research. Most CT‐based density methods require an estimate of the size of the viewshed monitored by each CT, a parameter that may be highly variable and difficult to quantify. We developed and tested a standardized field and analytical method allowing us to predict the probability of photographic capture as it varies within CT viewshed. We investigated how capture probability changes due to environmental influences (vegetation structure, ambient temperature, speed of subject and time of day), in addition to internal factors from CTs themselves (sensitivity settings, number of photographs taken and CT brand). We then summarize these spatial capture probability kernels into a Realised Viewshed Size (RVS)—the capture probability corrected size of a CTs viewshed for use in the denominator of photograph‐based Random Encounter Staying Time (REST) or Time in Front of Camera (TIFC) estimators. We found that RVS values are heavily influenced by location‐specific environmental factors (vegetation structure), technological delays associated with CTs themselves, (refractory period) and internal CT settings. RVS values computed using our methodology are substantially smaller than viewshed sizes reported values in the literature. Imprecision surrounding CT viewshed areas propagate bias when implementing CT‐based density estimators. Our method can change how practitioners consider photographs for use in CT density estimators thus increasing the reliability of CT‐based density estimation, and contributing to more accessible wildlife management practices.

Purpose: The endoplasmic reticulum–associated degradation pathway is responsible for the translocation of misfolded proteins across the endoplasmic reticulum membrane into the cytosol for subsequent degradation by the proteasome. To define the phenotype associated with a novel inherited disorder of cytosolic endoplasmic reticulum–associated degradation pathway dysfunction, we studied a series of eight patients with deficiency of N-glycanase 1. Methods: Whole-genome, whole-exome, or standard Sanger sequencing techniques were employed. Retrospective chart reviews were performed in order to obtain clinical data. Results: All patients had global developmental delay, a movement disorder, and hypotonia. Other common findings included hypolacrima or alacrima (7/8), elevated liver transaminases (6/7), microcephaly (6/8), diminished reflexes (6/8), hepatocyte cytoplasmic storage material or vacuolization (5/6), and seizures (4/8). The nonsense mutation c.1201A>T (p.R401X) was the most common deleterious allele. Conclusion: NGLY1 deficiency is a novel autosomal recessive disorder of the endoplasmic reticulum–associated degradation pathway associated with neurological dysfunction, abnormal tear production, and liver disease. The majority of patients detected to date carry a specific nonsense mutation that appears to be associated with severe disease. The phenotypic spectrum is likely to enlarge as cases with a broader range of mutations are detected. Genet Med 16 10, 751–758.

Adult mortality is often the most sensitive vital rate affecting at-risk wildlife populations. Therefore, road ecology studies often focus on adult mortality despite the possibility for roads to be hazardous to juvenile individuals during natal dispersal. Failure to quantify concurrent variation in mortality risk and population sensitivity across demographic states can mislead the efforts to understand and mitigate the effects of population threats. To compare relative population impacts from road mortality among demographic classes, we weighted mortality observations by applying reproductive value analysis to quantify expected stage-specific contributions to population growth. We demonstrate this approach for snapping turtles (Chelydra serpentina) observed on roads at two focal sites in Ontario, Canada, where we collected data for both live and dead individuals observed on roads. We estimated reproductive values using stage-classified matrix models to compare relative population-level impacts of adult and juvenile mortality. Reproductive value analysis is a tractable approach to assessing demographically variable effects for applications covering large spatial scales, nondiscrete populations, or where abundance data are lacking. For one site with longterm life-history data, we compared demographic frequency on roads to expected general population frequencies predicted by the matrix model. Our application of reproductive value is sex specific but, as juvenile snapping turtles lack external secondary sex characters, we estimated the sex ratio of road-crossing juveniles after dissecting and sexing carcasses collected on roads at five sites across central Ontario, Canada. Juveniles were more abundant on roads than expected, suggesting a substantial dispersal contribution, and the road-killed juvenile sex ratio approached 1:1. A higher proportion of juveniles were also found dead compared with adults, and cumulative juvenile mortality had similar population-level importance as adult mortality. This suggests that the impact of roads needs to be considered across all life stages, even in wildlife species with slow life histories, such as snapping turtles, that are particularly sensitive to adult mortality.

To explore whether ultra-sensitive circulating tumor DNA (ctDNA) profiling enables earlier prediction of treatment response and detection of disease progression, we applied NeXT Personal, an ultra-sensitive bespoke tumor-informed liquid biopsy platform, to profile tumor samples from the KeyLargo study, a phase II trial in which metastatic esophagogastric cancer (mEGC) patients received capecitabine, oxaliplatin, and pembrolizumab. A total of 24 patients were evaluated, and all were ctDNA-positive at baseline. ctDNA levels varied from 406,067 down to 1.5 parts per million (PPM) with a median limit of detection of 2.03 PPM. ctDNA dynamics were highly correlated with changes in tumor size (ρ = 0.59, p = 7.3 × 10 ). Lack of early molecular response (50% or greater decrease in ctDNA levels at first available time point after 30 days, C2D1 or C4D1) was associated with worse overall survival (OS) (HR 4.5, 95% CI 1.2-16.7, p = 0.02) and progression-free survival (PFS) (HR 10.4, 95% CI 2.2-49.8, p = 0.003). Lack of molecular clearance of ctDNA was associated with worse OS (HR 7.1, 95% CI 1.6-31.7, p = 0.01) and PFS (HR 19.9, 95% CI 2.5-158.2, p = 0.005). Molecular progression (ctDNA increase) preceded imaging-derived progression by a median lead time of 65 days. These results suggest that ultra-sensitive liquid biopsy approaches could improve treatment decision-making for mEGC patients receiving chemotherapy and immunotherapy.

Coding of information in the peripheral olfactory system depends on two fundamental factors: interaction of individual odors with subsets of the odorant receptor repertoire and mode of signaling that an individual receptor-odor interaction elicits, activation or inhibition. We develop a cheminformatics pipeline that predicts receptor–odorant interactions from a large collection of chemical structures (>240,000) for receptors that have been tested to a smaller panel of odorants (∼100). Using a computational approach, we first identify shared structural features from known ligands of individual receptors. We then use these features to screen in silico new candidate ligands from >240,000 potential volatiles for several Odorant receptors (Ors) in the Drosophila antenna. Functional experiments from 9 Ors support a high success rate (∼71%) for the screen, resulting in identification of numerous new activators and inhibitors. Such computational prediction of receptor–odor interactions has the potential to enable systems level analysis of olfactory receptor repertoires in organisms. Although our sense of smell is regarded as inferior to that of many other species, we can nevertheless distinguish between roughly 10,000 different odors. These are made up of molecules called odorants, each of which activates a specific subset of odorant receptors in the nose. However, much of what we know about this process has come from studying the fruit fly, Drosophila, which detects odors using receptors located mainly on its antennae. The number of potential odorants in nature is vast, and only a tiny fraction of the interactions between odorants and receptors can be physically tested. To address this challenge, Boyle et al. have used a computational approach to study in depth the interactions between a subset of 24 odorant receptors in Drosophila antennae and 109 odorants. After developing a method to identify structural features shared by the odorants that activate each receptor, Boyle et al. used this information to perform a computational (in silico) screen of more than 240,000 different odorant-like volatile compounds. For each receptor, they compiled a list of the 500 odorants predicted to interact most strongly with it. They then tested their predictions for a subset of the receptors by performing experiments in living flies, and found that roughly 71% of predicted compounds did indeed activate or inhibit their receptors, compared to only 10% of a control sample. In addition to providing new insights into the nature of the interactions between odorants and their receptors, the computational screen devised by Boyle et al. could aid the development of novel insect repellents, or compounds that mask the odors used by disease-causing insects to identify their hosts. It could also be used in the future to develop novel flavors and fragrances.

Roads are one of the most severe threats to wildlife globally because of their pervasive and linear nature. Despite considerable attention afforded to road-effects on animals generally, little information is available concerning the specific impacts of road widening, also known as twinning or highway expansion. To address this gap, we monitored the abundance and distribution of large mammals adjacent to an 18-km section of highway in Ontario, Canada, that underwent expansion from a two-lane to a four-lane, divided highway, over 4 years. We expected to observe an initial decrease in large mammal track abundance and an increased distance from the highway, followed by a period of habituation during which track abundance and proximity to the highway would return to baseline levels. To quantify the effects of highway expansion, we monitored snow-tracks of three ungulates, two felids, and three canids on transects extending perpendicular and parallel to the highway. Our analyses revealed that proximity was species-specific and varied seasonally, but we found little evidence that the new four-lane highway alignment affected the movement ecology of large mammals in our study area. Limited increases in traffic volume could partially explain why we detected no change; however, traffic volume will rise. Although road widening is common for accommodating increased traffic volume, no studies have explicitly investigated its effects on animal movement ecology. Our findings suggest that increasing the footprint of existing roads, rather than building new roads, may be a suitable solution for accommodating increasing traffic with minimal impacts on adjacent large mammal communities.

Spotted cucumber beetle ( Diabrotica undecimpunctata howardi ; also known as southern corn rootworm) is a pest feeding on many crops, including cucurbits, corn (maize), peanuts, beans, and other crops and wild plants in North America. On cucurbit crops, where it co-occurs with striped cucumber beetle ( Acalymma vittatum ), both are key pests that vector Erwinia tracheiphila, a destructive pathogen that causes bacterial wilt. Here we deployed synthetic vittatalactone, the male-produced aggregation pheromone of A. vittatum , as lures in the field, to measure attraction of the target and non-target insects. Both sexes of D. u. howardi were strongly attracted to the vittatalactone lures (5–7.5-fold compared to blank trap) throughout the growing season in Maryland and Virginia, USA. Moreover, D. u. howardi was more attracted to live A. vittatum males feeding on squash plants than to plants with females or without any beetles, confirming the genuine organismal cross-attraction between these two key pests. The kairomonal attraction to vittatalactone suggests that it functions as a “keystone semiochemical,” mediating the colonization of cucurbits by multiple herbivore species. Such cross attraction could allow for use of vittatalactone in management of multiple pest species, with potential reduction of pesticide use in cucurbit crops.

The squash bug, Anasa tristis (De Geer), is a serious pest of cucurbit crops across the United States, especially within summer squash (Cucurbita pepo L.) systems. Using their piercing sucking mouthparts, squash bugs feed on both leaf tissue and fruits, often leading to leaf necrosis, marketable fruit loss, and even plant death. To date, the relationship between squash bug presence and plasticulture has not been adequately investigated. This 2-yr study evaluated the effects of white, black, and reflective plastic mulch colors on the occurrence of all squash bug life stages and marketable zucchini yield in Virginia. In both years, A. tristis adults and egg masses were more numerous on zucchini plants grown in white and reflective plastic mulch compared to bare ground plants. Greater nymphal densities and marketable fruit yield were observed in certain plastic mulch treatments versus the bare ground treatment, yet these differences were not consistent in both years. Contrary to the repellency effects reflective mulches have on other cucurbit insect pests, our research suggests that reflective and other plastic mulch colors can negatively impact squash bug management, especially in regions with high A. tristis pressure. Our study offers new insights for cucurbit growers to use when considering whether they should implement plasticulture in their growing systems.

Circulating tumor DNA (ctDNA)-based response assessment is appealing but limited by conventional analytical thresholds. We utilized a whole genome sequencing based, tumor-informed ultrasensitive ctDNA assay which tracked ~1800 somatic mutations to analyze 227 longitudinal plasma samples from 39 patients with advanced/metastatic cancers receiving immune checkpoint inhibitors (ICIs). ctDNA was detected from 2.0-239,315 PPM (median limit of detection: 1.77 PPM), with 33% of positive detections below 100 PPM. Early molecular response, defined as >50% ctDNA reduction or sustained ctDNA negativity from baseline to first follow-up, strongly predicted improved progression-free survival (PFS) (hazard ratio (HR) = 0.09, 95% CI: 0.02-0.39, p = 0.001) and was independently prognostic of PFS. Molecular complete response (mCR), defined as any ctDNA clearance, predicted overall survival and PFS, with 1-year PFS of 87% in mCR patients versus 16% in non-mCR patients (HR = 0.14, 95% CI: 0.04-0.50, p = 0.003). The high-sensitivity ctDNA monitoring may enable precise, real-time evaluation of ICI response to guide clinical decision-making.