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Background: Given the aging of the overall U.S. population, the resulting changes in healthcare needs especially among veterans, and the high prevalence of traumatic brain injury (TBI) among older adults, additional research is needed on community participation after TBI in older veterans. The current study examined predictors of community participation trajectories over the 5 years after TBI in veterans who were 55 years of age or older upon injury. Method: This study included data from 185 participants in the U.S. Department of Veterans Affairs TBI Model System national study who had sustained a TBI at age 55 or older and had completed at least one of each Participation Assessment with Recombined Tools-Objective (PART-O) subscale scores at one or more follow-up time points (1, 2, and 5 years post-TBI). Results: PART-O Productivity, Social, and Out and About scores remained constant over time. Lower PART-O Productivity trajectories were seen among participants who were unemployed at the time of injury (p = 0.023). Lower PART-O Social trajectories were seen among participants who had a lower education level (p = 0.021), were unmarried at injury (p < 0.001), and had private insurance coverage (p < 0.033). Conclusion: These findings add to the growing body of literature on TBI and community participation by focusing on an older adult veteran population. There is an urgency to understand the needs of this group, many of whom are aging with service-connected disabilities including TBI. Veterans with characteristics identified herein as being associated with lower community participation trajectories would be prime candidates for interventions that aim to increase community and social engagement after later-life TBI.

Electrical synapses are neuronal gap junction (GJ) channels associated with a macromolecular complex called the electrical synapse density (ESD), which regulates development and dynamically modifies electrical transmission. However, the proteomic makeup and molecular mechanisms utilized by the ESD that direct electrical synapse formation are not well understood. Using the Mauthner cell of zebrafish as a model, we previously found that the intracellular scaffolding protein ZO1b is a member of the ESD, localizing postsynaptically, where it is required for GJ channel localization, electrical communication, neural network function, and behavior. Here, we show that the complexity of the ESD is further diversified by the genomic structure of the ZO1b gene locus. The ZO1b gene is alternatively initiated at three transcriptional start sites resulting in isoforms with unique N-termini that we call ZO1b-Alpha, -Beta, and -Gamma. We demonstrate that ZO1b-Beta and ZO1b-Gamma are broadly expressed throughout the nervous system and localize to electrical synapses. By contrast, ZO1b-Alpha is expressed mainly non-neuronally and is not found at synapses. We generate mutants in all individual isoforms, as well as double mutant combinations in cis on individual chromosomes, and find that ZO1b-Beta is necessary and sufficient for robust GJ channel localization. ZO1b-Gamma, despite its localization to the synapse, plays an auxiliary role in channel localization. This study expands the notion of molecular complexity at the ESD, revealing that an individual genomic locus can contribute distinct isoforms to the macromolecular complex at electrical synapses. Further, independent scaffold isoforms have differential contributions to developmental assembly of the interneuronal GJ channels. We propose that ESD molecular complexity arises both from the diversity of unique genes and from distinct isoforms encoded by single genes. Overall, ESD proteomic diversity is expected to have critical impacts on the development, structure, function, and plasticity of electrical transmission.

Humans are known to have significant and consistent differences in thickness throughout the cortex, with thick outer gyral folds and thin inner sulcal folds. Our previous work has suggested a mechanical basis for this thickness pattern, with the forces generated during cortical folding leading to thick gyri and thin sulci, and shown that cortical thickness varies along a gyral–sulcal spectrum in humans. While other primate species are expected to exhibit similar patterns of cortical thickness, it is currently unknown how these patterns scale across different sizes, forms, and foldedness. Among primates, brains vary enormously from roughly the size of a grape to the size of a grapefruit, and from nearly smooth to dramatically folded; of these, human brains are the largest and most folded. These variations in size and form make comparative neuroanatomy a rich resource for investigating common trends that transcend differences between species. In this study, we examine 12 primate species in order to cover a wide range of sizes and forms, and investigate the scaling of their cortical thickness relative to the surface geometry. The 12 species were selected due to the public availability of either reconstructed surfaces and/or population templates. After obtaining or reconstructing 3D surfaces from publicly available neuroimaging data, we used our surface-based computational pipeline (https://github.com/mholla/curveball) to analyze patterns of cortical thickness and folding with respect to size (total surface area), geometry (i.e. curvature, shape, and sulcal depth), and foldedness (gyrification). In all 12 species, we found consistent cortical thickness variations along a gyral–sulcal spectrum, with convex shapes thicker than concave shapes and saddle shapes in between. Furthermore, we saw an increasing thickness difference between gyri and sulci as brain size increases. Our results suggest a systematic folding mechanism relating local cortical thickness to geometry. Finally, all of our reconstructed surfaces and morphometry data are available for future research in comparative neuroanatomy.

(1) Background: Incomplete excision of vestibular schwannomas (VSs) is sometimes preferable for facial nerve preservation. On the other hand, subtotal resection may be associated with higher tumor recurrence. We evaluated the correlation between intra-operative assessment of residual tumor and early and follow-up imaging. (2) Methods: The charts of all patients undergoing primary surgery for sporadic vestibular schwannoma during the study period were retrospectively reviewed. Data regarding surgeons’ assessments of the extent of resection, and the residual size of the tumor on post-operative day (POD) one and follow-up MRI were extracted. (3) Results: Of 109 vestibular schwannomas meeting inclusion criteria, gross-total resection (GTR) was achieved in eighty-four, near-total (NTR) and sub-total resection (STR) in twenty-two and three patients, respectively. On follow up imaging, volumetric analysis revealed that of twenty-two NTRs, eight were radiographic GTR and nine were radiographic STR (mean volume ratio 11.9%), while five remained NTR (mean volume ratio 1.8%). Of the three STRs, two were radiographic GTR while one remained STR. Therefore, of eighteen patients with available later follow up MRIs, radiographic classification of the degree of resection changed in six. (4) Conclusions: An early MRI (POD#1) establishes a baseline for the residual tumor that may be more accurate than the surgeon’s intraoperative assessment and may provide a beneficial point of comparison for long-term surveillance.

As microservices become more popular, more drawbacks become apparent to developers. One issue that many teams face today is the failure to visualize the entire system architecture holistically. Without a full view of the system, the architecture can become convoluted as teams add and subtract from their system without reconciling their changes. One established practice to determine a view on the entire system involves dynamic analysis of microservice interaction and dependencies. In this mapping study, we investigate dynamic analysis as a way to visualize system architecture. Capturing the architectural view with dynamic analysis has the ability to build the system and then show its behavior at run-time. We identify dynamic analysis techniques, the corresponding tools, and the models that these practices can generate. The findings of this study are relevant to developers of decentralized systems looking for a way to visualize their system architecture in a dynamic perspective.

Many antibiotic-resistant bacteria carry resistance genes on conjugative plasmids that are transferable to commensals and pathogens. We determined the ability of multiple enteric bacteria to acquire and retransfer a broad-host-range plasmid RP4. We used human-derived commensal Escherichia coli LM715-1 carrying a chromosomal red fluorescent protein gene and green fluorescent protein (GFP)-labeled broad-host-range RP4 plasmid with ampR, tetR, and kanR in in vitro matings to rifampicin-resistant recipients, including Escherichia coli MG1655, Dec5α, Vibrio cholerae, Pseudomonas putida, Pseudomonas aeruginosa, Klebsiella pneumoniae, Citrobacter rodentium, and Salmonella Typhimurium. Transconjugants were quantified on selective media and confirmed using fluorescence microscopy and PCR for the GFP gene. The plasmid was transferred from E. coli LM715-1 to all tested recipients except P. aeruginosa. Transfer frequencies differed between specific donor–recipient pairings (10−2 to 10−8). Secondary retransfer of plasmid from transconjugants to E. coli LM715-1 occurred at frequencies from 10−2 to 10−7. A serial passage plasmid persistence assay showed plasmid loss over time in the absence of antibiotics, indicating that the plasmid imposed a fitness cost to its host, although some plasmid-bearing cells persisted for at least ten transfers. Thus, the RP4 plasmid can transfer to multiple clinically relevant bacterial species without antibiotic selection pressure.

Lateral-flow immunoassays (LFIAs) are a widely used point-of-care technology because they are simple to perform and easy to read. LFIAs typically use colloidal gold or colored latex beads, however the sensitivity of LFIAs is ultimately limited by the label's extinction coefficients as enough material must be localized to be observed. Greater sensitivity requires visualization of fewer labels and herein we substitute palladium nanoparticles as a catalyst to produce a stable, blue indamine dye that precipitates at the capture line. We term our system cLFIA™ for catalytic LFIAs. The catalytic chemistry requires that three chemicals react with the palladium, and we have incorporate all three elements onto the cLFIA™ in the chemistry release fiber (CRF). With the CRF, cLFIA™ strips operate exactly as traditional LFIA strips, requiring no additional steps from the user, however the resulting lines are blue not red and provide much greater sensitivity. The all-in-one nature of cLFIA™ assays and the nature of the Pd conjugates we utilize sets this technology apart from other approaches that enhance LFIA sensitivity. We demonstrate that 2 nm Pd nanoparticles have a 40× catalytic advantage over 50 nm Pd-coated nanoparticles for our dye system. Our dye system is more robust than common peroxidase dyes (TMB), providing 8× signal and at a fast rate. Lastly, we demonstrate that the cLFIA™ approach is 1000× more sensitivity for detection of human chorionic gonadotropin than commercial pregnancy assays. The preparation of the palladium catalyst, the dye chemistry, and their facile use in cLFIA™ assays are described.

ABSTRACT Despite 50% of biology Ph.D. graduates being women, the number of women that advance in academia decreases at each level (e.g., from graduate to postdoctorate to tenure track). Recently, scientific societies and publishers have begun examining internal submissions data to evaluate representation and evaluation of women in their peer review processes; however, representation and attitudes differ by scientific field, and to date, no studies have investigated academic publishing in the field of microbiology. Using manuscripts submitted between January 2012 and August 2018 to the 15 journals published by the American Society for Microbiology (ASM), we describe the representation of women at ASM journals and the outcomes of their manuscripts. Senior women authors at ASM journals were underrepresented compared to global and society estimates of microbiology researchers. Additionally, manuscripts submitted by corresponding authors that were women received more negative outcomes than those submitted by men. These negative outcomes were somewhat mediated by whether or not the corresponding author was based in the United States and by the type of institution for United States-based authors. Nonetheless, the pattern for women corresponding authors to receive more negative outcomes on their submitted manuscripts held. We conclude with suggestions to improve the representation of women and decrease structural penalties against women. IMPORTANCE Barriers in science and academia have prevented women from becoming researchers and experts that are viewed as equivalent to their colleagues who are men. We evaluated the participation and success of women researchers at ASM journals to better understand their success in the field of microbiology. We found that women are underrepresented as expert scientists at ASM journals. This is, in part, due to a combination of both low submissions from senior women authors and more negative outcomes on submitted manuscripts for women compared to men.

Introduction: Symptomatic leukostasis is an exceptionally atypical presentation of blast crisis; and when coupled with an enlarged neoplastic mediastinal mass in a four-year-old female, an extremely rare and challenging pediatric emergency arises. Case Report: We present a unique case of a four-year-old female who arrived via emergency medical services in cardiopulmonary arrest with clinical and radiographic evidence suggestive of bilateral pneumothoraces, prompting bilateral chest tube placement. Further evaluation revealed a large mediastinal mass and a concurrent white blood cell count of 428,400 per milliliter (/mL) (4,400–12,900/mL), with a 96% blast differential, consistent with complications of T-cell acute lymphoblastic leukemia. Conclusion: This case highlights how pulmonary capillary hypoperfusion secondary to leukostasis, coupled with a ventilation/perfusion mismatch due to compression atelectasis by an enlarged thymus, resulted in this patient’s respiratory arrest. Furthermore, the case highlights how mediastinal masses in pediatric patients present potential diagnostic challenges for which ultrasound may prove beneficial.

Background: Recurrent Clostridium difficile infection (rCDI) is becoming increasingly common. Faecal microbiota transplantation (FMT) is effective for rCDI, but the costs of an FMT and hospital cost savings related to FMT are unknown. The aim of this study was to calculate the cost of an FMT and the total hospital costs before and after FMT. Methods: This was an observational single-centre study, carried out in a public teaching hospital. We included all patients referred for rCDI from January 2014 through December 2015 and documented costs related to donor screening, laboratory processing, and clinical FMT application. We calculated patient-related hospital costs 1 year before FMT (pre-FMT) and 1 year after FMT (post-FMT). Sensitivity analyses were applied to assess the robustness of the results. Results: We included 50 consecutive adult patients who had a verified diagnosis of rCDI and were referred for FMT. The average cost of an outpatient FMT procedure if donor faeces were applied by colonoscopy was €3,326 per patient and €2,864 if donor faeces were applied using a nasojejunal tube. The total annual pre-FMT hospital costs per patient were €56,415 (95% confidence interval (CI) 41,133–71,697), and these costs dropped by 42% to €32,816 (22,618–42,014) post-FMT ( p = 0.004). The main cost driver was hospital admissions. Sensitivity analyses demonstrated cost reductions in all scenarios. Conclusions: In a public hospital with an implemented FMT service, the average cost of FMT applied by either colonoscopy or nasojejunal tube was €3,095. Total hospital costs dropped by 42% the first year after FMT. The reduction was mainly caused by reductions in the number of hospital admissions and in length of stay.

Background Dogs have human-directed social skills that allow them to communicate and cooperate with humans. We have previously identified two loci on chromosome 26 associated with human contact-seeking behaviors during an unsolvable problem task in laboratory beagles (Persson et al., 2016). The aim of the present study was to verify the single nucleotide polymorphisms (SNPs) in additional dog breeds. We also studied how the allele frequencies have changed during domestication and recent selection. Methods Dogs of two breeds, 61 golden retrievers and 100 Labrador retrievers, were phenotyped and genotyped, and 19 wolves were genotyped. The Labrador retrievers were divided into common and field type by pedigree data to make it possible to study the effects of recent selection. All dogs were tested in an unsolvable problem task where human-directed social behaviors were scored. DNA from dogs (buccal swabs) and wolves (blood or brain tissue) was analyzed for genotype on two of the previously identified SNP markers, BICF2G630798942 (SNP1) and BICF2S23712114 (SNP2), by pyrosequencing. Results There was genetic variation for SNP1 in both dog breeds whereas the wolves were fixed for this polymorphism, and for SNP2 there was variation in both dogs and wolves. For both SNPs, Labrador retriever types differed significantly in allele frequencies. We found associations between SNPs and human-directed social behavior in both dog breeds. In golden retrievers, SNP1 was associated with physical contact variables, for example, with the duration of physical contact with the owner (F2,56 = 4.389, p = 0.017). SNP2 was associated with several behavioral variables in both breeds, among others owner gazing frequency in both golden retrievers (F2,55 = 6.330, p = 0.003) and Labradors (F1,93 = 5.209, p = 0.025). Discussion Our results verify the association between the previously identified SNPs and human-directed social behavior scored in an unsolvable problem task. Differences in allele frequencies suggest that these loci have been affected by selection. The results indicate that these genomic regions are involved in human-directed social behavior in not only beagles but in other dog breeds as well. We hypothesize that they may have been important during dog domestication.

In humans, more difficult decisions result in behavioural and physiological changes suggestive of increased arousal, but little is known about the effect of decision difficulty in other species. A difficult decision can have a number of characteristics; we aimed to monitor how finely balanced decisions, compared to unbalanced ones, affected the behaviour and physiology of chickens. An unbalanced decision was one in which the two options were of unequal net value (1 (Q1) vs. 6 (Q6) pieces of sweetcorn with no cost associated with either option); a finely balanced decision was one in which the options were of equal net value (i.e. hens were "indifferent" to both options). To identify hens' indifference, a titration procedure was used in which a cost (electromagnetic weight on an access door) was applied to the Q6 option, to find the individual point at which hens chose this option approximately equally to Q1 via a non-weighted door. We then compared behavioural and physiological indicators of arousal (head movements, latency to choose, heart-rate variability and surface body temperature) when chickens made decisions that were unbalanced or finely balanced. Significant physiological (heart-rate variability) and behavioural (latency to pen) differences were found between the finely balanced and balanced conditions, but these were likely to be artefacts of the greater time and effort required to push through the weighted doors. No other behavioural and physiological measures were significantly different between the decision categories. We suggest that more information is needed on when best to monitor likely changes in arousal during decision-making and that future studies should consider decisions defined as difficult in other ways.