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\"The Global Response Force (GRF) is built for rapid response to unforeseen or, more specifically, unplanned operations. Selected Army airborne forces provide a large portion of the GRF and are dependent on joint concepts for deployment and access. This study illustrates a method for determining the best access strategies given constraints in aircraft, intermediate staging bases, operational capabilities, and other factors. The study applies this method to each geographic combatant command and develops specific, tailored strategies for each. The access strategies are built from multiple analytic techniques: historical aircraft data and platform specifications to determine capabilities and limitations of the air fleet; several airfield databases, site reports, and expert judgments to determine probable intermediate staging base locations and their likely capabilities; multiple deployment concepts for access to minimize operational risks; and detailed geographic and operational analysis to determine global coverage and reach. In the end, we were able to deduce a preferred strategy for each of the combatant commands. Global access for the GRF is provided partially through the use of well-established staging bases but will necessarily rely on austere basing and complex deployment concepts for particular locations in multiple combatant commands. The study concludes with several recommendations to close those risks, which span the services, combatant commands, and joint staff\"--Back cover.

The mammalian brain controls heat generation and heat loss mechanisms that regulate body temperature and energy metabolism. Thermoeffectors include brown adipose tissue, cutaneous blood flow and skeletal muscle, and metabolic energy sources include white adipose tissue. Neural and metabolic pathways modulating the activity and functional plasticity of these mechanisms contribute not only to the optimization of function during acute challenges, such as ambient temperature changes, infection and stress, but also to longitudinal adaptations to environmental and internal changes. Exposure of humans to repeated and seasonal cold ambient conditions leads to adaptations in thermoeffectors such as habituation of cutaneous vasoconstriction and shivering. In animals that undergo hibernation and torpor, neurally regulated metabolic and thermoregulatory adaptations enable survival during periods of significant reduction in metabolic rate. In addition, changes in diet can activate accessory neural pathways that alter thermoeffector activity. This knowledge may be harnessed for therapeutic purposes, including treatments for obesity and improved means of therapeutic hypothermia.Exposure to acute and long-term exposure to cold temperatures results in the activation of thermoregulatory mechanisms that are under CNS control. In this Review, Mota and Madden discuss long-term physiological adaptations to cold exposure, with an emphasis on the specific states of hibernation, torpor and obesity.

Humans have infected a wide range of animals with SARS-CoV-2 1 – 5 , but the establishment of a new natural animal reservoir has not been observed. Here we document that free-ranging white-tailed deer ( Odocoileus virginianus ) are highly susceptible to infection with SARS-CoV-2, are exposed to multiple SARS-CoV-2 variants from humans and are capable of sustaining transmission in nature. Using real-time PCR with reverse transcription, we detected SARS-CoV-2 in more than one-third (129 out of 360, 35.8%) of nasal swabs obtained from O. virginianus in northeast Ohio in the USA during January to March 2021. Deer in six locations were infected with three SARS-CoV-2 lineages (B.1.2, B.1.582 and B.1.596). The B.1.2 viruses, dominant in humans in Ohio at the time, infected deer in four locations. We detected probable deer-to-deer transmission of B.1.2, B.1.582 and B.1.596 viruses, enabling the virus to acquire amino acid substitutions in the spike protein (including the receptor-binding domain) and ORF1 that are observed infrequently in humans. No spillback to humans was observed, but these findings demonstrate that SARS-CoV-2 viruses have been transmitted in wildlife in the USA, potentially opening new pathways for evolution. There is an urgent need to establish comprehensive ‘One Health’ programmes to monitor the environment, deer and other wildlife hosts globally. More than one-third of wild deer tested in northeast Ohio showed evidence of SARS-CoV-2 infection of human origin.

Obesity increases sympathetic nerve activity (SNA) via activation of proopiomelanocortin neurons in the arcuate nucleus (ArcN), and this action requires simultaneous withdrawal of tonic neuropeptide Y (NPY) sympathoinhibition. However, the sites and neurocircuitry by which NPY decreases SNA are unclear. Here, using designer receptors exclusively activated by designer drugs (DREADDs) to selectively activate or inhibit ArcN NPY neurons expressing agouti-related peptide (AgRP) in mice, we have demonstrated that this neuronal population tonically suppresses splanchnic SNA (SSNA), arterial pressure, and heart rate via projections to the paraventricular nucleus (PVN) and dorsomedial hypothalamus (DMH). First, we found that ArcN NPY/AgRP fibers closely appose PVN and DMH presympathetic neurons. Second, nanoinjections of NPY or an NPY receptor Y1 (NPY1R) antagonist into PVN or DMH decreased or increased SSNA, respectively. Third, blockade of DMH NPY1R reversed the sympathoinhibition elicited by selective, DREADD-mediated activation of ArcN NPY/AgRP neurons. Finally, stimulation of ArcN NPY/AgRP terminal fields in the PVN and DMH decreased SSNA. Considering that chronic obesity decreases ArcN NPY content, we propose that the ArcN NPY neuropathway to the PVN and DMH is pivotal in obesity-induced elevations in SNA.

The prognostic value of glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase L1 (UCH-L1) as day-of-injury predictors of functional outcome after traumatic brain injury is not well understood. GFAP is a protein found in glial cells and UCH-L1 is found in neurons, and these biomarkers have been cleared to aid in decision making regarding whether brain CT should be performed after traumatic brain injury. We aimed to quantify their prognostic accuracy and investigate whether these biomarkers contribute novel prognostic information to existing clinical models. We enrolled patients from the Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) observational cohort study. TRACK-TBI includes patients 17 years and older who are evaluated for TBI at 18 US level 1 trauma centres. All patients receive head CT at evaluation, have adequate visual acuity and hearing preinjury, and are fluent in either English or Spanish. In our analysis, we included participants aged 17–90 years who had day-of-injury plasma samples for measurement of GFAP and UCH-L1 and completed 6-month assessments for outcome due to traumatic brain injury with the Glasgow Outcome Scale–Extended (GOSE-TBI). Biomarkers were analysed as continuous variables and in quintiles. This study is registered with ClinicalTrials.gov, NCT02119182. We enrolled 2552 patients from Feb 26, 2014, to Aug 8, 2018. Of the 1696 participants with brain injury and data available at baseline and at 6 months who were included in the analysis, 120 (7·1%) died (GOSE-TBI=1), 235 (13·9%) had an unfavourable outcome (ie, GOSE-TBI ≤4), 1135 (66·9%) had incomplete recovery (ie, GOSE-TBI <8), and 561 (33·1%) recovered fully (ie, GOSE-TBI=8). The area under the curve (AUC) of GFAP for predicting death at 6 months in all patients was 0·87 (95% CI 0·83–0·91), for unfavourable outcome was 0·86 (0·83–0·89), and for incomplete recovery was 0·62 (0·59–0·64). The corresponding AUCs for UCH-L1 were 0·89 (95% CI 0·86–0·92) for predicting death, 0·86 (0·84–0·89) for unfavourable outcome, and 0·61 (0·59–0·64) for incomplete recovery at 6 months. AUCs were higher for participants with traumatic brain injury and Glasgow Coma Scale (GCS) score of 3–12 than for those with GCS score of 13–15. Among participants with GCS score of 3–12 (n=353), adding GFAP and UCH-L1 (alone or combined) to each of the three International Mission for Prognosis and Analysis of Clinical Trials in traumatic brain injury models significantly increased their AUCs for predicting death (AUC range 0·90–0·94) and unfavourable outcome (AUC range 0·83–0·89). However, among participants with GCS score of 13–15 (n=1297), adding GFAP and UCH-L1 to the UPFRONT study model modestly increased the AUC for predicting incomplete recovery (AUC range 0·69–0·69, p=0·025). In addition to their known diagnostic value, day-of-injury GFAP and UCH-L1 plasma concentrations have good to excellent prognostic value for predicting death and unfavourable outcome, but not for predicting incomplete recovery at 6 months. These biomarkers contribute the most prognostic information for participants presenting with a GCS score of 3–12. US National Institutes of Health, National Institute of Neurologic Disorders and Stroke, US Department of Defense, One Mind, US Army Medical Research and Development Command.

The availability of dissolved inorganic and organic nutrients and their transformations along the fresh to marine continuum are being modified by various natural and anthropogenic activities and climate-related changes. Subtropical central and eastern Florida Bay, located at the southern end of the Florida peninsula, is classically considered to have inorganic nutrient conditions that are in higher-than-Redfield ratio proportions, and high levels of organic and chemically-reduced forms of nitrogen. However, salinity, pH and nutrients, both organic and inorganic, change with changes in freshwater flows to the bay. Here, using a time series of water quality and physico-chemical conditions from 2009 to 2019, the impacts of distinct changes in managed flow, drought, El Niño-related increases in precipitation, and intensive storms and hurricanes are explored with respect to changes in water quality and resulting ecosystem effects, with a focus on understanding why picocyanobacterial blooms formed when they did. Drought produced hyper-salinity conditions that were associated with a seagrass die-off. Years later, increases in precipitation resulting from intensive storms and a hurricane were associated with high loads of organic nutrients, and declines in pH, likely due to high organic acid input and decaying organic matter, collectively leading to physiologically favorable conditions for growth of the picocyanobacterium, Synechococcus spp. These conditions, including very high concentrations of NH4+, were likely inhibiting for seagrass recovery and for growth of competing phytoplankton or their grazers. Given projected future climate conditions, and anticipated cycles of drought and intensive storms, the likelihood of future seagrass die-offs and picocyanobacterial blooms is high.

Mutations in isocitrate dehydrogenases 1 and 2 ( IDH1 and IDH2 ) in the majority of people with grade 2 and 3 gliomas is associated with elevated levels of 2-hydroxyglutarate (2HG) within the tumor. As harboring IDH1 or IDH2 mutations confers a considerable survival benefit in these individuals, there has been considerable interest in studying this metabolite as a potential biomarker. Here, Changho Choi et al . report the successful noninvasive detection of 2HG in 30 subjects with gliomas using a proton magnetic resonance spectroscopy approach. Mutations in isocitrate dehydrogenases 1 and 2 ( IDH1 and IDH2 ) have been shown to be present in most World Health Organization grade 2 and grade 3 gliomas in adults. These mutations are associated with the accumulation of 2-hydroxyglutarate (2HG) in the tumor. Here we report the noninvasive detection of 2HG by proton magnetic resonance spectroscopy (MRS). We developed and optimized the pulse sequence with numerical and phantom analyses for 2HG detection, and we estimated the concentrations of 2HG using spectral fitting in the tumors of 30 subjects. Detection of 2HG correlated with mutations in IDH1 or IDH2 and with increased levels of D -2HG by mass spectrometry of the resected tumors. Noninvasive detection of 2HG may prove to be a valuable diagnostic and prognostic biomarker.

Whether leptin acts in the paraventricular nucleus (PVN) to increase sympathetic nerve activity (SNA) is unclear, since PVN leptin receptors (LepR) are sparse. We show in rats that PVN leptin slowly increases SNA to muscle and brown adipose tissue, because it induces the expression of its own receptor and synergizes with local glutamatergic neurons. PVN LepR are not expressed in astroglia and rarely in microglia; instead, glutamatergic neurons express LepR, some of which project to a key presympathetic hub, the rostral ventrolateral medulla (RVLM). In PVN slices from mice expressing GCaMP6, leptin excites glutamatergic neurons. LepR are expressed mainly in thyrotropin-releasing hormone (TRH) neurons, some of which project to the RVLM. Injections of TRH into the RVLM and dorsomedial hypothalamus increase SNA, highlighting these nuclei as likely targets. We suggest that this neuropathway becomes important in obesity, in which elevated leptin maintains the hypothalamic pituitary thyroid axis, despite leptin resistance.