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Treating perimeters of vegetation with residual insecticides for protection from mosquito vectors has potential for U.S. military force health protection. However, for current U.S. military operations in hot-arid environments with little or no vegetation, residual applications on portable artificial materials may be a viable alternative. We evaluated bifenthrin residual treatments of U.S. military camouflage netting under hot-arid field conditions in a desert area in southern California exposed to abundant wild Culex tarsalis mosquitoes. We assessed the ability of the treatment to reduce the numbers of mosquitoes penetrating perimeters of netting and reaching CO2-baited mosquito traps. Treated camouflage netting barriers reduced mosquitoes by > or = 50% for 7-14 days and by 20-35% for 21-28 days compared to untreated barriers. Although reductions may be translated into reductions in risk of exposure to mosquito-borne diseases, we emphasize that barrier treatments should be a component in a suite of insect control measures to be effective. [ABSTRACT FROM AUTHOR]

Purpose: Glioblastoma (GBM) that presents as leptomeningeal disease (LMD) is extremely rare and fatal. Limited data are available regarding incidence, clinical presentation, and management. Prognosis is poor and no treatment is known to improve survival., Methods and Results: We present a case report of a 72-year-old female who presented with depressed sensorium, ataxia, and myelopathy. Magnetic resonance imaging (MRI) showed diffuse supratentorial and spinal LMD. There was an absence of any detectable and distinct intraparenchymal lesion on neuroaxis imaging. Biopsy of the Sylvian fissure nodule revealed GBM. Steroid therapy was ineffective for symptom relief. She opted for palliative care and expired shortly after diagnosis., Conclusion: To our knowledge, this is the first reported case of GBM presenting exclusively as LMD without a primary lesion. If systemic imaging techniques do not provide a biopsy target and cerebrospinal fluid (CSF) studies are non-diagnostic, tissue diagnosis from leptomeningeal biopsy is recommended. Palliative chemoradiation or best supportive care are reasonable treatment options., Competing Interests: Declarations. Ethics approval: N/A. Consent to publish: N/A. Competing interests: The authors declare no competing interests. Consent to participate: N/A., (© 2024. The Author(s).)

Context.—: Next-generation sequencing (NGS)-based assays are used for diagnosis of diverse inherited disorders. Limited data are available pertaining to interlaboratory analytical performance of these assays., Objective.—: To report on the College of American Pathologists (CAP) NGS Germline Program, which is methods based, and explore the evolution in laboratory testing practices., Design.—: Results from the NGS Germline Program from 2016-2020 were analyzed for interlaboratory analytical performance. Self-reported laboratory testing practices were also evaluated., Results.—: From 2016-2020, a total of 297 laboratories participated in at least 1 program mailing. Of the 289 laboratories that provided information on tests offered, 138 (47.8%) offered only panel testing throughout their enrollment, while 35 (12.1%) offered panels and exome testing, 30 (10.4%) offered only exomes, 9 (3.1%) offered only genomes, and 15 (5.2%) offered panels, exomes, and genomes. The remainder (62 laboratories, 21.4%) changed their test offerings during the 2016-2020 timeframe. Considering each genomic position/interval, the median detection percentage at variant positions across the 2016-2020 mailings ranged from 94.3% to 100%, while at reference positions (no variant detected), the median correct response percentage was 100% across all mailings. When considering performance of individual laboratories, 89.5% (136 of 152) to 98.0% (149 of 152) of laboratories successfully met the detection threshold (≥90% of the variants present), while 94.6% (87 of 92) to 100% (163 of 163) of laboratories met the 95% specificity threshold across mailings., Conclusions.—: Since the inception of this program, laboratories have consistently performed well. The median sensitivity and specificity of detection of sequence variants included in this program (eg, single nucleotide variants, insertions, and deletions) were 100.0%., (© 2024 College of American Pathologists.)

Glioblastoma (GBM) remains an untreatable malignant tumor with poor patient outcomes, characterized by palisading necrosis and microvascular proliferation. While single-cell technology made it possible to characterize different lineage of glioma cells into neural progenitor-like (NPC-like), oligodendrocyte-progenitor-like (OPC-like), astrocyte-like (AC-like) and mesenchymal like (MES-like) states, it does not capture the spatial localization of these tumor cell states. Spatial transcriptomics empowers the study of the spatial organization of different cell types and tumor cell states and allows for the selection of regions of interest to investigate region-specific and cell-type-specific pathways. Here, we obtained paired 10x Chromium single-nuclei RNA-sequencing (snRNA-seq) and 10x Visium spatial transcriptomics data from three GBM patients to interrogate the GBM microenvironment. Integration of the snRNA-seq and spatial transcriptomics data reveals patterns of segregation of tumor cell states. For instance, OPC-like tumor and NPC-like tumor significantly segregate in two of the three samples. Our differentially expressed gene and pathway analyses uncovered significant pathways in functionally relevant niches. Specifically, perinecrotic regions were more immunosuppressive than the endogenous GBM microenvironment, and perivascular regions were more pro-inflammatory. Our gradient analysis suggests that OPC-like tumor cells tend to reside in areas closer to the tumor vasculature compared to tumor necrosis, which may reflect increased oxygen requirements for OPC-like cells. In summary, we characterized the localization of cell types and tumor cell states, the gene expression patterns, and pathways in different niches within the GBM microenvironment. Our results provide further evidence of the segregation of tumor cell states and highlight the immunosuppressive nature of the necrotic and perinecrotic niches in GBM., (© 2024. The Author(s).)

Background: Strengthening health systems through planned safety and quality improvement initiatives is an imperative to achieve more equitable, resilient, and effective care. And yet, years of organizational behavior research demonstrate that change initiatives often fall short because managers fail to account for organizational readiness for change. This finding remains true especially among surgical safety and quality improvement initiatives in low-income countries and middle-income countries. In this study, our aim was to psychometrically assess the construct validity and internal consistency of the Safe Surgery Organizational Readiness Tool (SSORT), a short survey tool designed to provide change leaders with insight into facility infrastructure that supports learning and readiness to undertake change., Materials and Methods: To demonstrate generalizability and achieve a large sample size ( n =1706) to conduct exploratory factor analysis (EFA) and confirmatory factor analysis (CFA), a collaboration between seven surgical and anesthesia safety and quality improvement initiatives was formed. Collected survey data from health care workers were divided into pilot, exploration, and confirmation samples. The pilot sample was used to assess feasibility. The exploration sample was used to conduct EFA, while the confirmation sample was used to conduct CFA. Factor internal consistency was assessed using Cronbach's alpha coefficient., Results: Results of the EFA retained 9 of the 16 proposed factors associated with readiness to change. CFA results of the identified 9 factor model, measured by 28 survey items, demonstrated excellent fit to data. These factors (appropriateness, resistance to change, team efficacy, team learning orientation, team valence, communication about change, learning environment, vision for sustainability, and facility capacity) were also found to be internally consistent., Conclusion: Our findings suggest that communication, team learning, and supportive environment are components of change readiness that can be reliably measured prior to implementation of projects that promote surgical safety and quality improvement in low-income countries and middle-income countries. Future research can link performance on identified factors to outcomes that matter most to patients., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Atypical teratoid rhabdoid tumors (AT/RT) are rare and highly malignant CNS neoplasms primarily affecting children. Adult cases are extremely uncommon, with only approximately 92 reported. Spinal AT/RT in adults is particularly rare. Here, we present the case of a 50-year-old patient diagnosed with AT/RT of the spine. Initially, they were diagnosed and treated for a spinal ependymoma. However, after 10 years, a recurrence was detected through magnetic resonance imaging (MRI) and the tumor was reclassified as AT/RT. We discuss the significance of SMARCB1 gene mutations in diagnosing AT/RT and describe our unique treatment approach involving surgery, radiation and anti-PD1 therapy in this patient.

Antibodies reactive with the SARS-CoV-2 receptor-binding domain (RBD) of the spike protein are associated with viral neutralization, however low antibody titers, specifically against SARS-CoV-2 variants, may result in reduced viral immunity post naturally acquired infection. A cohort study comprised of 121 convalescent individuals from northern Nevada was conducted looking at anti-RBD antibody levels by enzyme-linked immunosorbent assay. Serum was collected from volunteers by staff at the University of Nevada, Reno School of Medicine Clinical Research Center and assessed for antibodies reactive to various SARS-CoV-2 RBD domains relevant to the time of the study (2020-2021). A nonpaired group of vaccinated individuals were assessed in parallel. The goal of the study was to identify antibody levels against the RBD subunit in convalescent and vaccinated individuals from northern Nevada., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Peer review is a well-established cornerstone of the scientific process, yet it is not immune to biases like status bias, which we explore in this paper. Merton described this bias as prominent researchers getting disproportionately great credit for their contribution, while relatively unknown researchers get disproportionately little credit [R. K. Merton, Science 159, 56-63 (1968)]. We measured the extent of this bias in the peer-review process through a preregistered field experiment. We invited more than 3,300 researchers to review a finance research paper jointly written by a prominent author (a Nobel laureate) and by a relatively unknown author (an early career research associate), varying whether reviewers saw the prominent author's name, an anonymized version of the paper, or the less-well-known author's name. We found strong evidence for the status bias: More of the invited researchers accepted to review the paper when the prominent name was shown, and while only 23% recommended "reject" when the prominent researcher was the only author shown, 48% did so when the paper was anonymized, and 65% did when the little-known author was the only author shown. Our findings complement and extend earlier results on double-anonymized vs. single-anonymized review [R. Blank, Am. Econ. Rev. 81, 1041-1067 (1991); M. A. Ucci, F. D'Antonio, V. Berghella, Am. J. Obstet. Gynecol. MFM 4, 100645 (2022)].

Age and intraocular pressure (IOP) are the two most important risk factors for the development and progression of open-angle glaucoma. While IOP is commonly considered in models of experimental glaucoma (EG), most studies use juvenile or adult animals and seldom older animals which are representative of the human disease. This paper provides a concise review of how retinal ganglion cell (RGC) loss, the hallmark of glaucoma, can be evaluated in EG with a special emphasis on serial in vivo imaging, a parallel approach used in clinical practice. It appraises the suitability of EG models for the purpose of in vivo imaging and argues for the use of models that provide a sustained elevation of IOP, without compromise of the ocular media. In a study with parallel cohorts of adult (3-month-old, equivalent to 20 human years) and old (2-year-old, equivalent to 70 human years) mice, we compare the effects of elevated IOP on serial ganglion cell complex thickness and individual RGC dendritic morphology changes obtained in vivo. We also evaluate how age modulates the impact of elevated IOP on RGC somal and axonal density in histological analysis as well the density of melanopsin RGCs. We discuss the challenges of using old animals and emphasize the potential of single RGC imaging for understanding the pathobiology of RGC loss and evaluating new therapeutic avenues., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Sex-specific differences in fetal lung maturation have been well described; however, little is known about the sex-specific differences in microRNA (miRNA) expression during human fetal lung development. Interestingly, many adult chronic lung diseases also demonstrate sex-specific differences in prevalence. The developmental origins of health and disease hypothesis suggests that these sex-specific differences in fetal lung development may influence disease susceptibility later in life. In this study, we performed miRNA sequencing on human fetal lung tissue samples to investigate differential expression of miRNAs between males and females in the pseudoglandular stage of lung development. We hypothesized that differences in miRNA expression are present between sexes in early human lung development and may contribute to the sex-specific differences seen in pulmonary diseases later in life. Methods: RNA was isolated from human fetal lung tissue samples for miRNA sequencing. The count of each miRNA was modeled by sex using negative binomial regression models in DESeq2, adjusting for post-conception age, age 2 , smoke exposure, batch, and RUV factors. We tested for differential expression of miRNAs by sex, and for the presence of sex-by-age interactions to determine if miRNA expression levels by age were distinct between males and females. Results: miRNA expression profiles were generated on 298 samples (166 males and 132 females). Of the 809 miRNAs expressed in human fetal lung tissue during the pseudoglandular stage of lung development, we identified 93 autosomal miRNAs that were significantly differentially expressed by sex and 129 miRNAs with a sex-specific pattern of miRNA expression across the course of the pseudoglandular period. Conclusion: Our study demonstrates differential expression of numerous autosomal miRNAs between the male and female developing human lung. Additionally, the expression of some miRNAs are modified by age across the pseudoglandular stage in a sex-specific way. Some of these differences in miRNA expression may impact susceptibility to pulmonary disease later in life. Our results suggest that sex-specific miRNA expression during human lung development may be a potential mechanism to explain sex-specific differences in lung development and may impact subsequent disease susceptibility., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lin, Liu, Yang, Maier, DeMeo, Wood, Ye, Cruse, Smith, Vyhlidal, Kechris and Sharma.)

Depilation (that is, hair removal) is a necessary prerequisite for many small animal surgeries and optical imaging experiments. Over-the-counter depilatory creams are widely used, owing to their efficacy, safety, and low rates of skin irritation and infection. However, the use of these creams is generally messy and time-consuming and generates considerable waste. Furthermore, the process itself varies markedly among laboratories. Here we present a 3D-printed device that simplifies the depilation procedure by integrating 3 key elements: 1) a multiple-port, self-scavenging anesthesia manifold, 2) curved animal holders with flow-through slats, and 3) a removable waste collection tray. Reflecting insights gained from an international survey about depilatory lab procedures that highlighted the lack of standardized protocols, this apparatus is designed to improve the neatness, throughput, and safety of mouse depilation, resulting in efficient and repeatable processes that bolster the welfare of both researchers and subjects.

Here we report the results of an experiment that tests the reciprocal risk reduction 1 and 'tolerated theft' or taking hypotheses 2 for why the human species is unique in having extensive exchange of resources among non-kin. We designed an experiment to determine whether, in response to variance of resource acquisition, people exchange food resources via taking or, alternatively, form reciprocal relationships based on giving. In the experiment, subjects forage individually, experience variation in resource acquisition, and then consume either by actions in which resources are taken from, or moved to, others in a group environment. The key feature of the experimental design is that individuals can transfer resources to others, attempt to take resources from others and defend against take-away attempts. Many subjects begin by attempting to take resources from others, who can resist those attempts at a cost to each. Over time, subjects shift to a cooperative strategy of voluntary reciprocal giving, a response not suggested by the instructions. These results provide evidence that people are independently able to overcome initial use of taking strategies, evaluate gains from exchange, and create endogenous reciprocal trading relationships as a response to unsynchronized variance in resource availability.

Frontline nurses encounter operational failures (OFs), or breakdowns in system processes, that hinder care, erode quality, and threaten patient safety. Previous research has relied on external observers to identify OFs; nurses have been passive participants in the identification of system failures that impede their ability to deliver safe and effective care. To better understand frontline nurses' direct experiences with OFs in hospitals, we conducted a multi-site study within a national research network to describe the rate and categories of OFs detected by nurses as they provided direct patient care. Data were collected by 774 nurses working in 67 adult and pediatric medical-surgical units in 23 hospitals. Nurses systematically recorded data about OFs encountered during 10 work shifts over a 20-day period. In total, nurses reported 27,298 OFs over 4,497 shifts, a rate of 6.07 OFs per shift. The highest rate of failures occurred in the category of Equipment/Supplies, and the lowest rate occurred in the category of Physical Unit/Layout. No differences in OF rate were detected based on hospital size, teaching status, or unit type. Given the scale of this study, we conclude that OFs are frequent and varied across system processes, and that organizations may readily obtain crucial information about OFs from frontline nurses. Nurses' detection of OFs could provide organizations with rich, real-time information about system operations to improve organizational reliability. © 2017 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)

Mycobacterium tuberculosis-infected macrophages and dendritic cells are limited in their ability to present antigen to CD4+ T cells suggesting that other mechanism of antigen presentation are driving the robust T cell response observed during an M. tuberculosis infection. These mechanisms could include antigens present in apoptotic bodies, necrotic debris, exosomes or even release of non-vesicular antigen from infected cells. However, there is limited data to support any of these mechanisms as important in driving T cell activation in vivo. In the present study we use Rab27a-deficient mice which show diminished trafficking of mycobacterial components to exosomes as well as M. tuberculosis strains that express recombinant proteins which traffic or fail to traffic to exosomes. We observed that exosomes released during a mouse M. tuberculosis infection contribute significantly to its T cell response. These finding imply that exosomes function to promote T cell immunity during a bacterial infection and are an important source of extracellular antigen.

We present the solution-state NMR structures and preliminary functional characterizations of three venom peptides identified from the spitting spider Scytodes thoracica. Despite little sequence identity to other venom peptides, structural characterization reveals that these peptides contain an inhibitor cystine knot motif common to many venom peptides. These are the first structures for any peptide or protein from spiders of the Scytodidae family. Many venom peptides target neuronal ion channels or receptors. However, we have not been able to determine the target of these Scytodes peptides so we can only state with certainty the channels and receptors that they do not target.

Prior studies have shown that traders quickly converge to the price-quantity equilibrium in markets for goods that are immediately consumed, but they produce speculative price bubbles in resalable asset markets. We present a stock-flow model of durable assets in which the existing stock of assets is subject to depreciation and producers may produce additional units of the asset. In our laboratory experiments inexperienced consumers who can resell their units disregard the consumption value of the assets and compete vigorously with producers, depressing prices and production. Consumers who have first participated in experiments without resale learn to heed their consumption values and, when they are given the option to resell, trade at equilibrium prices. Reproducibility is therefore the most natural and most effective treatment for suppression of bubbles in asset market experiments.

Exosomes are extracellular vesicles of endocytic origin that function in intercellular communication. Our previous studies indicate that exosomes released from Mycobacterium tuberculosis-infected macrophages contain soluble mycobacterial proteins. However, it was unclear how these secreted proteins were targeted to exosomes. In this study, we determined that exosome production by the murine macrophage cell line RAW264.7 requires the endosomal sorting complexes required for transport and that trafficking of mycobacterial proteins from phagocytosed bacilli to exosomes was dependent on protein ubiquitination. Moreover, soluble mycobacterial proteins, when added exogenously to RAW264.7 or human HEK293 cells, were endocytosed, ubiquitinated, and released via exosomes. This suggested that endocytosed proteins could be recycled from cells through exosomes. This hypothesis was supported using the tumor-associated protein He4, which, when endocytosed by RAW264.7 or HEK293 cells, was transported to exosomes in a ubiquitin-dependent manner. Our data suggest that ubiquitination is a modification sufficient for trafficking soluble proteins within the phagocytic/endocytic network to exosomes., (Copyright © 2015 by The American Association of Immunologists, Inc.)

Transcutaneous and epidural electrical spinal cord stimulation techniques are becoming more valuable as electrophysiological and clinical tools. Recently, we observed selective activation of proximal and distal motor pools during epidural spinal stimulation. In the present study, we hypothesized that the characteristics of recruitment curves obtained from leg muscles will reflect a relative preferential activation of proximal and distal motor pools based on their arrangement along the lumbosacral enlargement. The purpose was to describe the electrophysiological responses to transcutaneous stimulation in leg muscles innervated by motoneurons from different segmental levels. Stimulation delivered along the rostrocaudal axis of the lumbosacral enlargement in the supine position resulted in a selective topographical recruitment of proximal and distal leg muscles, as described by threshold intensity, slope of the recruitment curves, and plateau point intensity and magnitude. Relatively selective recruitment of proximal and distal motor pools can be titrated by optimizing the site and intensity level of stimulation to excite a given combination of motor pools. The slope of the recruitment of particular muscles allows characterization of the properties of afferents projecting to specific motoneuron pools, as well as to the type and size of the motoneurons. The location and intensity of transcutaneous spinal electrical stimulation are critical to target particular neural structures across different motor pools in investigation of specific neuromodulatory effects. Finally, the asymmetry in bilateral evoked potentials is inevitable and can be attributed to both anatomical and functional peculiarities of individual muscles or muscle groups., (Copyright © 2015 the American Physiological Society.)

An effective immune response requires the engagement of host receptors by pathogen-derived molecules and the stimulation of an appropriate cellular response. Therefore, a crucial factor in our ability to control an infection is the accessibility of our immune cells to the foreign material. Exosomes-which are extracellular vesicles that function in intercellular communication-may play a key role in the dissemination of pathogen- as well as host-derived molecules during infection. In this review, we highlight the composition and function of exosomes and other extracellular vesicles produced during viral, parasitic, fungal and bacterial infections and describe how these vesicles could function to either promote or inhibit host immunity., (© 2014 The Authors.)

Sprayer comparisons and larval morality assays were conducted following SR450 backpack mist blower and Superhawk XP thermal fogger applications of Vectobac® WDG Bacillus thuringiensis israelensis (Bti) against Culex quinquefasciatus. Bacillus thuringiensis israelensis was applied at maximum label rate in a 232.26-m(2) field plot located in north-central Florida with containers placed at 2 heights (ground level and 1.52 m above ground) on stakes positioned 3.04, 6.09, 9.14, 12.19, and 15.24 m from the spray line. Results indicated that there was no significant (P > 0.05) difference in 24- and 48-h larval mortality between the 2 sprayers or between the 2 heights. There was significant difference (P < 0.05) among the 5 rows, with mortality continuously decreasing with increasing distance from sprayer. Both sprayers provided on average >70% larval mortality 3.04-9.14 m from the spray line, and <60% mortality at 12.19 and 15.24 m. The data suggest that the SR450 and Superhawk XP may be comparable sprayers for use with Bti to control mosquito larvae.

Unlabelled: Navajo Nation children have the greatest prevalence of early childhood caries in the United States. This protocol describes an innovative combination of community-based participatory research and clinical trial methods to rigorously test a lay native Community Oral Health Specialists-delivered oral health intervention, with the goal of reducing the progression of disease and improving family knowledge and behaviors., Methods/design: This cluster-randomized trial designed by researchers at the Center for Native Oral Health Research at the University of Colorado in conjunction with members of the Navajo Nation community compares outcomes between the manualized 2-year oral health fluoride varnish-oral health promotion intervention and usual care in the community (child-caregiver dyads from 26 Head Start classrooms in each study arm; total of 1016 dyads). Outcome assessment includes annual dental screening and an annual caregiver survey of knowledge, attitudes and behaviors; collection of cost data will support cost-benefit analyses., Discussion: The study protocol meets all standards required of randomized clinical trials. Aligned with principles of community-based participatory research, extended interaction between members of the Navajo community and researchers preceded study initiation, and collaboration between project staff and a wide variety of community members informed the study design and implementation. We believe that the benefits of adding CBPR methods to those of randomized clinical studies outweigh the barriers and constraints, especially in studies of health disparities and in challenging settings. When done well, this innovative mix of methods will increase the likelihood of valid results that communities can use., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Compared with other species, exchange among non-kin is a hallmark of human sociality in both the breadth of individuals and total resources involved. One hypothesis is that extensive exchange evolved to buffer the risks associated with hominid dietary specialization on calorie dense, large packages, especially from hunting. 'Lucky' individuals share food with 'unlucky' individuals with the expectation of reciprocity when roles are reversed. Cross-cultural data provide prima facie evidence of pair-wise reciprocity and an almost universal association of high-variance (HV) resources with greater exchange. However, such evidence is not definitive; an alternative hypothesis is that food sharing is really 'tolerated theft', in which individuals possessing more food allow others to steal from them, owing to the threat of violence from hungry individuals. Pair-wise correlations may reflect proximity providing greater opportunities for mutual theft of food. We report a laboratory experiment of foraging and food consumption in a virtual world, designed to test the risk-reduction hypothesis by determining whether people form reciprocal relationships in response to variance of resource acquisition, even when there is no external enforcement of any transfer agreements that might emerge. Individuals can forage in a high-mean, HV patch or a low-mean, low-variance (LV) patch. The key feature of the experimental design is that individuals can transfer resources to others. We find that sharing hardly occurs after LV foraging, but among HV foragers sharing increases dramatically over time. The results provide strong support for the hypothesis that people are pre-disposed to evaluate gains from exchange and respond to unsynchronized variance in resource availability through endogenous reciprocal trading relationships.

More than 2 billion people are infected with Mycobacterium. tuberculosis; however, only 5-10% of those infected will develop active disease. Recent data suggest that containment is controlled locally at the level of the granuloma and that granuloma architecture may differ even within a single infected individual. Formation of a granuloma likely requires exposure to mycobacterial components released from infected macrophages, but the mechanism of their release is still unclear. We hypothesize that exosomes, which are small membrane vesicles containing mycobacterial components released from infected macrophages, could promote cellular recruitment during granuloma formation. In support of this hypothesis, we found that C57BL/6 mouse-derived bone marrow macrophages treated with exosomes released from M. tuberculosis-infected RAW264.7 cells secrete significant levels of chemokines and can induce migration of CFSE-labeled macrophages and splenocytes. Exosomes isolated from the serum of M. bovis bacillus Calmette-Guérin-infected mice could also stimulate macrophage production of chemokines and cytokines ex vivo, but the level and type differed during the course of a 60-d infection. Of interest, the exosome concentration in serum correlated strongly with mouse bacterial load, suggesting some role in immune regulation. Finally, hollow fiber-based experiments indicated that macrophages treated with exosomes released from M. tuberculosis-infected cells could promote macrophage recruitment in vivo. Exosomes injected intranasally could also recruit CD11b(+) cells into the lung. Overall, our study suggests that exosomes may play an important role in recruiting and regulating host cells during an M. tuberculosis infection.

This work reports droplet-size data measured as part of a collaborative testing program between the US Department of Agriculture, Agricultural Research Service, and the US Navy, Navy Entomological Center for Excellence. This is an ongoing relationship that seeks to test new and revised spray technologies that may potentially be used by deployed personnel. As new equipment comes to market or when existing equipment is modified they are all integrated into this annual testing. During the 2011 equipment evaluations, 24 sprayers were operated across their range of available settings (pressure and flow rate), using both water and oil solutions. Droplet-size data as measured with laser diffraction ranged from 4 to 223 microm (volume median diameter). Generally, as the spray rate increased, droplet size increased, and as the pressure increased at a given same spray rate, droplet size decreased. This information allows users to set up and operate these sprayers in a manner such that a particular droplet size is applied optimizing efficiency and efficacy of applications.

Objectives: To review immediate results, patency rates, hemodynamic success, and incidence of concomitant procedures with external iliac artery stenting (EIAS)., Methods: Demographic features, category and clinical grade, Trans-Atlantic Inter-Society Consensus II classification lesion type, pre- and postprocedure ankle-brachial indices, and primary patency were compared between group 1 (EIAS without distal revascularization) and group 2 (EIAS with concomitant distal revascularization)., Results: No mortality and a 100% immediate technical success rate was recorded in group 1 (n = 12) and group 2 (n = 24). Eleven patients (30.6%) also had stenting of the adjacent common iliac artery. Two thirds of group 2 patients required concomitant femoral or distal revascularization., Conclusions: No difference in stent patency rates was found between patients in group 1 versus group 2. Patients requiring EIAS tend to have more diffuse arterial disease necessitating complicated open reconstruction and/or distal revascularization, as well as more proximal iliac stenting.

The current Department of Defense pest management system does not provide adequate protection from arthropod disease vectors to personnel deployed in support of US military operations. We hypothesized that military camouflage netting, ubiquitous around living and working areas in current US military operations in Africa and the Middle East, treated with a residual pesticide such as bifenthrin may reduce the presence of biting insects and improve the military pest management system. In this study, we examined the longevity and efficacy of bifenthrin applied to camouflage netting material at the maximum label rate of 0.03 liter formulation (7.9% AI) per 92.9 m2 against field populations of mosquitoes in southern California in a hot-arid environment similar to regions of Iraq, Afghanistan, and the Horn of Africa. We showed that bifenthrin treatment of camouflage netting was effective at reducing mosquito populations, predominantly Psorophora columbiae and Aedes vexans, by an average of up to 46% for 56 days, and could cause as much as 40% mortality in Culex quinquefasciatus in laboratory bioassays for nearly 2 months postapplication. These population reductions could translate to commensurate reductions in risk of exposure to mosquito-borne pathogens, and could potentially be effective against sand flies and filth flies.

Glycemic control in the critically ill patient has remained a controversial issue over the last decade. Several large trials, with widely varying results, have generated significant interest in defining the optimal target for blood-glucose control necessary for improving care while minimizing morbidity. Nutritional support has evolved into an additional area of critical care where appropriate practices have been associated with improved patient outcomes. Carbohydrate provision can impact blood-glucose levels, and the relationship between nutrition and glucose levels has become more complex in the era of improved glycemic control. This review discusses the controversy surrounding intensive-insulin therapy in the intensive care unit and explores the relationship with nutritional support, both in the enteral and parenteral form. Achieving realistic goals in both carbohydrate provision and glycemic control may improve patient outcome, and are not mutually exclusive practices.

Protein utilization and requirements in critical illness are much researched and debated topics. The enhanced turnover and catabolism of protein in the setting of critical illness is well described and multifactorial in nature. The need to preserve lean body mass and enhance nitrogen retention in this state to improve immunologic function and reduce morbidity is well described. Debates as to the optimum amount of protein to provide in such states still exist, and a significant amount of research has contributed to our understanding of not only how much protein to supply to these patients, but how best to do so. Small peptide formulations, intact protein formulations, branched chain amino acids, and specialty formulas all exist, and their benefits, drawbacks, and potential uses have been investigated. Specific amino acid therapy has become part of the concept of immunonutrition, or the modification and enhancement of the immune response with specific nutrients. In this article, we describe the changes in outcomes demonstrated through the provision of protein, both as a macronutrient and as specific amino acids.

Purpose: To investigate the safety, tolerability, and pharmacokinetics (PKs) of topical SAR 1118 Ophthalmic Solution in healthy adults. SAR 1118 is an investigational small molecule lymphocyte function-associated antigen-1 (LFA-1; CD11a/CD18; αLβ2) antagonist that inhibits LFA-1 binding to intercellular adhesion molecule-1 (ICAM-1; CD54) targeting T-cell-mediated inflammation., Methods: A randomized, double-masked, placebo-controlled, dose-escalation study of SAR 1118 was performed in 4 cohorts with 7 randomized subjects per cohort (2 placebo: 5 active drug subjects; 0.1%, 0.3%, 1.0%, 5.0%) in 28 healthy adults. Dosing was divided into 3 periods each separated by a 72-h treatment-free observation: once-daily (QD) × 1, twice-daily (BID) × 10, and thrice-daily (TID) × 10 days. Data obtained at the beginning and end of each period included: slit-lamp, best-corrected visual acuity (BCVA), Schirmer tear test (STT) without anesthesia, tear film break-up time (TBUT), intraocular pressure (IOP), and tear/plasma samples for PK analysis., Results: All subjects completed the study; there were no tolerability issues or missed treatments (total, 1,428 administered doses). No serious ocular or nonocular adverse events (AEs) occurred over 1,148 subject study days (41 days/subject) and no significant abnormalities were identified on ocular exam. There were 38 ocular AEs (N = 11 subjects) and 21 nonocular AEs (N = 11 subjects). Most AEs were mild in severity and occurred in the 0.3% and placebo groups. No changes were observed in CD3, CD4, and CD8 blood lymphocyte counts. Tear PK profiles support a QD/BID dosing schedule. Plasma levels of SAR 1118 in the 0.1% and 0.3% groups were below level of quantitation (BLQ; <0.50  ng/mL) at all time points and transiently detected within the first 5 min to ∼1  h following administration in the 1.0% and 5.0% groups., Conclusion: SAR 1118 Ophthalmic Solution appears safe and well-tolerated up to 5.0% TID in healthy adult subjects. PK analysis shows adequate ocular exposure with minimal systemic exposure.

A study was conducted to analyze the performance of 3 electrostatic (Electrolon BP-2.5, Spectrum Electrostatic 4010, and Spectrum Electrostatic head on a Stihl 420) and 2 conventional (Buffalo Turbine CSM2 and Stihl 420) sprayers for barrier sprays to suppress an adult mosquito population in an enclosed area. Sprayer characteristics such as charge-mass ratio, air velocity, flow rate, and droplet spectra were measured while spraying water. Dispersion of the spray cloud from these sprayers was determined using coverage on water-sensitive cards at various heights (0.5 m, 1.0 m, 1.5 m, 2.0 m, 2.5 m, and 3.0 m) and depths (1 m, 3 m, and 5 m) into the under-forest vegetation while spraying bifenthrin (Talstar 7.9% AI; FMC Corporation, Philadelphia, PA) at the rate of 21.8 ml/300 m of treated row. The charge-mass ratio data show that Electrostatic head on a Stihl 420 did not impart enough charge to the droplets to be considered as an electrostatic sprayer. In general, the charged spray cloud moved down toward the ground. The Electrolon BP 2.5 had significantly lower spray coverage on cards, indicating lack of spray dispersion. This sprayer had the lowest air velocity and did not have the air capacity needed to deliver droplets close to the target for electrostatic force to affect deposition. The analysis shows that these 2 sprayers are not a suitable choice for barrier sprays on vegetation. The results indicate that the Buffalo Turbine is suitable for barriers wider than 3 m, and the Spectrum 4010 and Stihl 420 are suitable for 1-3-m-wide barriers.

Ultra-low-volume (ULV) and thermal fog aerosol dispersals of pesticides have been used against mosquitoes and other insects for half a century. Although each spray technology has advantages and disadvantages, only 7 studies have been identified that directly compare their performance in the field. US military personnel currently operating in hot-arid environments are impacted by perpetual nuisance and disease vector insect problems, despite adulticide operations using modern pesticide-delivery equipment such as ULV. None of the identified comparative studies has looked at the relative feasibility and efficacy of ULV and thermal fog equipment against mosquitoes in hot-arid environments. In this study we examine the impact of ULV and thermal fog applications of malathion against caged sentinel mosquitoes in the field in a warm temperate area of Florida, followed by a similar test in a hot-dry desert area of southern California. Patterns of mortality throughout 150 m x 150 m grids of sentinel mosquitoes indicate greater efficacy from the thermal fog application in both environments under suboptimal ambient weather conditions. We discuss the implications of these findings for future military preventive medicine activities and encourage further investigations into the relative merits of the 2 technologies for force health protection.

A field study was conducted to explore the suitability of 5 pesticide deposition samplers for airborne spray and ground deposits from ultra-low-volume (ULV) space sprays. Samplers included horizontally stretched stationary cotton ribbons at 2 heights, rotating ribbon, rotating Teflon slides, and filter paper. Slides were also used for droplet-size analysis. A set of 7 samplers of each type was placed at 1, 7, 15, 25, 40, 65, and 90 m from the spray line along the spray swath. Water and BVA13 oil with fluorescent dyes as tracers were sprayed with the use of a truck-mounted ULV sprayer at dusk and dawn. Results suggest that the horizontal and rotating cotton ribbons are best for quantification of airborne spray and filter paper is best for ground deposition collection. The rotating slide samplers only detected the BVA13 oil-based sprays.

An experimental study was conducted to investigate the usefulness of electrostatic and conventional sprayers for barrier applications. Two conventional and three electrostatic sprayers were used in the study. Usefulness of the sprayers was rated based on penetration of spray into and deposition onto 2 sides of leaves on natural vegetation. Bifenthrin (Talstar adulticide) was applied at labeled rate, fluorescent dye was added to the tank mix as tracer, and all sprayers applied the dye and insecticide at the same rate. The results indicated that sprayers producing larger droplets produced significantly higher deposition on vegetation in barrier applications than the sprayers producing smaller droplets. Sprayers with higher air velocity at the nozzle discharge proved significantly better for barrier sprays than the sprayers with lower air velocity. Electrostatic sprayers did not show any improvement in deposition on vegetation or in penetration into vegetation over the conventional sprayers. There was no difference in deposition between truck-mounted and backpack sprayers.

Numerous spray machines are used to apply pesticides for the control of human disease vectors, such as mosquitoes and flies, and the selection and setup of these machines significantly affects the level of control achieved during an application. The droplet spectra produced by 9 different ultra-low-volume sprayers with oil- and water-based spray solutions were evaluated along with 2 thermal foggers with the use of diesel-based spray solutions. The droplet spectra from the sprayers were measured with the use of laser diffraction droplet sizing equipment. The volume median diameter from the sprayers ranged from 14.8 to 61.9 microm for the oil-based spray solutions and 15.5 to 87.5 microm for the water-based spray solutions. The 2 thermal foggers generated sprays with a volume median diameter of 3.5 microm. The data presented will allow spray applicators to select the spray solution and sprayer that generate the droplet-size spectra that meet the desired specific spray application scenarios.

Treating perimeters with residual insecticides for protection from mosquito vectors has shown promise. These barrier treatments are typically evaluated in temperate or tropical areas using abundant vegetation as a substrate. However, there is an emerging interest to develop this technology to protect deployed US troops in extreme desert environments with sparse vegetation. We used a remote desert area in the Coachella Valley, California, to 1) evaluate bifenthrin barrier treatments on native xeric vegetation and 2) compare treatments applied with electrostatic and conventional spray technologies. Through a combination of laboratory bioassays on treated and control vegetation sampled at specific intervals over 63 days, synchronized with field surveillance of mosquitoes, we measured the temporal pattern of bioactivity of bifenthrin barriers under natural hot, dry, and dusty desert conditions. Regardless of spray technology, mosquito catch in treated plots was about 80% lower than the catch in control plots 1 day after treatment. This reduction in mosquito numbers in treated plots declined each week after treatment but remained at about 40% lower than control plots after 28 days. Field data were corroborated by results from bioassays that showed significantly higher mosquito mortality on treated vegetation over controls out to 28 days postspray. We concluded that barrier treatments in desert environments, when implemented as part of a suite of integrated control measures, may offer a significant level of protection from mosquitoes for deployed troops. Given the comparable performance of the tested spray technologies, we discuss considerations for choosing a barrier treatment sprayer for military scenarios.

The main objective of this paper is to design and test a decentralized exchange mechanism that generates the location-specific pricing necessary to achieve efficient allocations in the presence of instream flow values. Although a market-oriented approach has the potential to improve upon traditional command and control regulations, questions remain about how these rights-based institutions can be implemented such that the potential gains from liberalized trade can be realized. This article uses laboratory experiments to test three different water market institutions designed to incorporate instream flow values into the allocation mechanism through active participation of an environmental trader. The smart, computer-coordinated market described herein offers the potential to significantly reduce coordination problems and transaction costs associated with finding mutually beneficial trades that satisfy environmental constraints. We find that direct environmental participation in the market can achieve highly efficient and stable outcomes, although the potential does exist for the environmental agent to influence outcomes.

Droplet size spectra from different sprayers used to generate insecticide-laden fogs for controlling flying insects were measured by a laser diffraction instrument and Teflon-coated slides. The objectives of this work were to present not only information on spray-system droplet size generated by different sprayers, but to compare methodologies by which other similar systems can be evaluated and give applicators sprayer-system performance data. Data from 45 replicated spray tests, comprising 11 sprayers and 5 pesticides, showed a wide range in the droplet size spectra produced. The volume median diameter measurements ranged from 2.6 to 75.5 microm for diesel-diluted sprays and from 27.9 to 59.9 microm for water-diluted sprays. Similarly, the percent volume <20 microm ranged between 12.0-100% and 8.5-30.7%, for diesel- and water-diluted sprays, respectively. The droplet sizes measured by the swinging slide and laser diffraction methods were not consistent. The information presented aids users in sprayer selection and operation to produce the specific droplet size spectra required for a particular application.

The control of medically important arthropod vectors of human and animal disease is a high priority for both public health and military officials. Because droplet size of pesticide spray material is a critical factor affecting vector control applications, the droplet-size spectra produced by 11 sprayers and 3 spray formulations were evaluated. Droplet-size spectra were measured by a laser diffraction instrument, a hot-wire system, and rotating slides. There were considerable differences in the droplet-size spectra produced by the different sprayers tested. The volume median diameter (Dv0.5) for the water-based sprays ranged from 4.7 to 211 microm, depending on the sprayer, and the percent of spray volume contained in droplets less than 20 microm (%vol <20 microm) ranged between 0.5% and 98.9%. The Dv0.5 measurements for the oil-based sprays ranged from 9.4 to 125.3 microm and the %vol <20 microm ranged between 2.4% and 97.9%. The correlations between the Dv0.5 measured by the laser system (Dv0.5-laser) and the mass median diameter, Sauter diameter, and Dv0.5 measured by the AIMS probe were all significant. Generally, the slide Dv0.5s were numerically similar to the Dv0.5 from the laser system and the Sauter diameter from the Army Insecticide Measuring System probe. There was less consistent agreement between the % <32 microm values obtained from the slides and those from the other 2 samplers. The information presented can be used by applicators to select the sprayer that produces the droplet-size spectra needed for their particular application situation.

The atomization characteristics of 4 handheld sprayers (Leco P-1, Colt ULV Aerosol Generator, ULVAFAN MK2, Turbair ElectraFan 12) and a Stih1 SR400 backpack sprayer were evaluated with the use of water- and oil-based solutions. The effects on droplet-size spectrum (i.e., droplet size) for 3 insecticides (Tempo SC Ultra, Anvil 10+10, and Aqua-Reslin) were also evaluated. Generic solutions were used to simulate the physical properties of the active-ingredient solutions in some tests. Significant differences were observed in the droplet spectrum generated by the different sprayers. The volume median diameter of the equipment tested ranged from 14.9 to 90.5 microm for the water-based solutions and from 11.7 to 92.4 microm for the oil-based solutions. The Colt ULV sprayer was the only one tested that complied with label requirements for aerosols, yielding acceptable Dv0.5 values of 14.9 16.0 microm with water-based Aqua-Reslin and 14.1 microm with Anvil 10+10. The information presented will allow equipment operators to make an informed decision when selecting equipment and operational parameters.

We report experimental results examining the properties of a bidding mechanism, the "Compensation Election," which is designed to implement a simple binary choice between two options. We may think of the group decision problem as a choice between a new rule and the status quo. The rule and the status quo are each common outcomes that apply across all individuals, but the value or cost that they induce on each individual differs according to each individual's circumstances: some gain, some lose, and others are unaffected by a change to the new from the old. Rather than casting votes, each subject submits a bid reflecting his willingness to pay to induce the group to select one option and the amount he wishes to be paid if the alternative option is selected. The Compensation Election chooses the option that receives the highest sum of bids. We find that, although the Compensation Election allows subjects to strategically bid above their value (or even for the option they do not prefer), such behavior is not the norm. We also find that subjects' bids more truthfully reveal their values when there are more bidders in the election.

Previous case reports have suggested a strong concordance of intestinal malrotation among identical twins. This has led to the recommendation that the asymptomatic twin undergo screening when malrotation is discovered in the identical sibling. We present a case of monozygotic twins in which one twin presented with intestinal malrotation with midgut volvulus while the other twin was found to have normal gastrointestinal anatomy.

Chronic nurse turnover and attendant personnel shortages threaten patient care. Inadequate pay and benefits are primary factors leading to nurses' job dissatisfaction and, subsequently, to turnover. However, recent meta-analyses suggest that a favorable practice setting can improve nurses' satisfaction and minimize turnover. The practice environment's potential to positively influence nurses' job satisfaction is analyzed in a large academic medical center. Nurse supervisors, job characteristics, management style, and service quality emphasis--not just money and benefits--surface as key factors associated with a positive practice milieu. Implications for raising nurses' job satisfaction, reducing turnover, and improving care delivery are discussed.

In this article we report an experiment that examines how demand-side bidding can discipline generators in a market for electric power. First we develop a treatment without demand-side bidding; two large firms are allocated baseload and intermediate cost generators such that either firm might unilaterally withhold the capacity of its intermediate cost generators from the market to benefit from the supracompetitive prices that would result from only selling its baseload units. In a converse treatment, ownership of some of the intermediate cost generators is transferred from each of these firms to two other firms such that no one firm could unilaterally restrict output to spawn supracompetitive prices. Having established a well controlled data set with price spikes paralleling those observed in the naturally occurring economy, we also extend the design to include demand-side bidding. We find that demand-side bidding completely neutralizes the exercise of market power and eliminates price spikes even in the presence of structural market power.