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Introduction Major depressive disorder is a serious, recurrent, and disabling psychiatric illness. Despite many proven treatments with multiple medications or therapies, approximately 30% of patients fail to achieve remission and are considered to have treatment-refractory depression (TRD). Recently, there has been a growing interest in the use of intravenous (IV) ketamine for the treatment of TRD. There is limited yet increasing evidence to support the use of ketamine, a glutamate receptor antagonist, in the management of depression; however, the lack of data regarding the safety and tolerability of therapy has limited its clinical use. By analyzing a cohort of veterans with TRD and comorbid psychiatric conditions treated with IV ketamine infusions for a 24-month study period, we aim to provide critical information about ketamine’s clinical effectiveness and safety. Materials and Methods Based on a retrospective chart review, we identified eight veterans with TRD receiving treatment with repeated-dose IV ketamine from 2018 to 2020. The magnitude of clinical response was based on the Beck Depression Inventory self-report scale and the Patient Health Questionnaire-9, both measured at the initial patient consultation and before the beginning of each ketamine infusion treatment. Safety analysis included changes to pre- and post-ketamine infusion on vital signs, effects on alertness and sedation, and potential psychosis-like effects. For all outcomes, we estimated a linear mixed-effects model that allowed heterogeneous residual variances for each veteran. The effect of continuous predictor variables was estimated using restricted cubic splines with knot points specified at the 5th, 35th, 65th, and 95th percentiles. All the analyses were conducted using SAS v.9.4, with P Results During the study period, the median number of ketamine infusions was 15 across a median of 164 days of treatment follow-up with a median time between ketamine infusions of 4 days. For both Beck Depression Inventory and Patient Health Questionnaire-9 scores, there was a statistically significant reduction across infusions (both P Conclusions In this study, repeated-dose IV ketamine infusions over a 24-month study period resulted in a significant reduction in depression scores in a group of veterans with TRD. The rapid onset of significant response, absence of psychosis-like effects or dissociative symptoms despite psychiatric comorbidities, and minimal effects on vital signs support the clinical efficacy and safety of this exciting new treatment option for patients with TRD. Limitations include a 2-year study period, lack of information on long-term effects, and the retrospective nature of the study. Prospective studies of longer duration are needed to assess the long-term efficacy and safety of IV ketamine for TRD.

Objective Heart Failure (HF) is one of the leading causes of hospitalization in the United States accounting for ≈800,000 hospital discharges and $11 billion in annual costs. Delirium occurs in approximately 30% of elderly hospitalized patients and its incidence is significantly higher among those admitted to the critical care units. Despite this, there has been limited exploration of the clinical and economic impact of delirium in patients hospitalized with acute HF. We hypothesized that delirium in HF is associated with excess mortality and hospital costs. Methods We queried the 2001-2014 Nationwide Inpatient Sample to identify hospitalizations that included a primary discharge diagnosis of HF (ICD-9-CM: 428.xx) and stratified them by presence or absence of delirium (ICD-9-CM: 239.0, 290.41, 293.0, 293.1, 348.31). Differences in in-hospital mortality, length of stay (LOS), and hospital costs were assessed using propensity-score matched cohorts. Results Major predictors of delirium included advanced age, Caucasian race, underlying dementia or psychiatric diagnoses, higher Elixhauser Comorbidity Index, renal failure, cardiogenic shock, and coronary artery bypass surgery. In the propensity-score matched analysis of 76,411 hospitalization with delirium compared to 76,612 without delirium, in-hospital mortality (odds ratio: 1.67, 95% CI: 1.51–1.77), LOS (rate ratio [RR]: 1.47, 95% CI: 1.45–1.51), and hospital costs (RR: 1.44, 95% CI: 1.41–1.48) were all statistically higher in the presence of delirium (all p Conclusion In patients hospitalized with HF, delirium is an independent predictor of increased in-hospital mortality, longer LOS, and excess hospital costs despite adjustment for baseline characteristics.

We show from experiments and simulations on vibration-activated granular matter that self-propelled polar rods in an elastic medium on a substrate turn and move towards each other. We account for this effective attraction through a coarse-grained theory of a motile particle as a moving point-force density that creates elastic strains in the medium that reorient other particles. Our measurements confirm qualitatively the predicted features of the distortions created by the rods, including the $|x|^{-1/2}$ tail of the trailing displacement field and non-reciprocal sensing and pursuit. A discrepancy between the magnitudes of displacements along and transverse to the direction of motion remains. Our theory should be of relevance to the interaction of motile cells in the extracellular matrix or in a supported layer of gel or tissue., Comment: Revised the draft structure with supplementary included in the main draft, added some new analysis, some figures and bibliography modified, See Supplementary movies here https://www.dropbox.com/sh/od5lg00cxijk7b9/AAB3j6el7jFdaZ0q1xOo0Eqza?dl=0

In equilibrium hard-rod fluids, and in effective hard-rod descriptions of anisotropic soft-particle systems, the transition from the isotropic (I) phase to the nematic phase (N) is observed above the rod aspect ratio L/D = 3.70 as predicted by Onsager. We examine the fate of this criterion in a molecular dynamics study of a system of soft repulsive spherocylinders rendered active by coupling half the particles to a heat bath at a higher temperature than that imposed on the other half. We show that the system phase separates and self-organizes into various liquid-crystalline phases that are not observed in equilibrium for the respective aspect ratios. In particular, we find a nematic phase for L/D = 3 and a smectic phase for L/D = 2 above a critical activity., 13 pages, 15 figures

Planar cell polarity (PCP) - asymmetric localization of proteins at cell-cell interface - is essential for embryonic development and physiological functions. Abnormalities in PCP can lead to neural tube closure defects, misalignment in hair follicles etc. Thus, decoding the mechanism responsible for PCP establishment and maintenance remains an open fundamental question. While various molecules - broadly classified into "global" and "local" modules - have been well investigated, their necessity and sufficiency in explaining PCP and connecting their perturbations and defects in experimentally observed patterns has not been examined. Here, we develop a minimal model that captures the proposed features of these two modules- a global tissue level gradient and local asymmetric distribution of protein complexes. Our model results suggest that while polarity can emerge in absence of a gradient, the gradient can provide the direction of polarity as well as offer robustness for maintenance of PCP in presence of stochastic perturbations. We also recapitulated swirling patterns (seen experimentally) and the features of non-domineering autonomy, using only three free parameters in the model - protein binding rate, concentration of proteins forming heterodimer across cell boundaries and steepness of gradient. Our results explain how self-stabilizing asymmetric localisations in presence of tissue-level gradient can lead to robust PCP patterns in diverse biological systems and reveals the minimal design principles for a polarized system.

Introduction Cognitive processing therapy (CPT) is a recommended first-line psychotherapy treatment for veterans with PTSD. Veterans with PTSD are at higher risk for sleep disorders including obstructive sleep apnea (OSA), and there is evidence that OSA can exacerbate PTSD and vice versa. Several studies have shown that CPAP use is associated with improvement in PTSD symptoms. CPT is an effective, yet time and resource intensive treatment option, making it critical to identify potential health factors impacting its efficacy. This retrospective chart analysis of veterans diagnosed with OSA and PTSD evaluated the effect of CPAP adherence on response to CPT. Methods Medical records of patients seen in a VA Health Care System were reviewed to identify veterans diagnosed with OSA and PTSD that received between 1-12 sessions of CPT with documented weekly PTSD Checklist for DSM-5 (PCL-5) scores, Patient Health Questionnaire-9 (PHQ-9) scores, and were issued a CPAP machine for OSA. Data collected included demographics, CPAP adherence (mean CPAP use, % days with greater than 4 hrs./night of CPAP use, mean residual apnea hypopnea index, mask leak), and PTSD symptoms (PCL-5 and PHQ-9 scores). For each outcome, we estimated a linear mixed-effects model; models for PCL-5 allowed heterogeneous residual variances for each veteran. Results This study identified 25 veterans receiving CPT for PTSD with access to a CPAP machine for OSA. The median age of patients was 43 years, median BMI was 35.6, and median residual AHI was 2.4. Patients received CPT for a median duration of 11.0 weeks. There was significant improvement in weekly PCL-5 and PHQ-9 scores over the course of CPT (both p < .001). CPAP adherence of at least 4 hrs./night for ≥70% of days did not significantly impact PCL-5 and PHQ-9 scores during CPT. Residual AHI and mask leak were not associated with PTSD symptoms during CPT. Conclusion While CPAP nonadherence appears to be a potential contributing factor to the reduced effectiveness of evidence-based treatments for veterans with PTSD, our study revealed significant improvement in PTSD symptoms during CPT regardless of CPAP adherence. Given the retrospective nature and small sample size of this study, further research is needed to expand on these findings. Support (If Any)

This study examined physical health problems and health service use among homeless veterans with a reported mental health diagnosis. The current sample included a total of 156 homeless male veteran...

International audience; In equilibrium liquid crystals, chirality leads to a variety of spectacular three-dimensional structures, but chiral and achiral phases with the same broken continuous symmetries have identical long-time, large-scale dynamics. In this Letter, starting from active model H∗, the general hydrodynamics of a pseudoscalar in a momentum-conserving fluid, we demonstrate that chirality qualitatively modifies the dynamics of layered liquid crystals in active systems in both two and three dimensions due to an active “odder” elasticity. In three dimensions, we demonstrate that the hydrodynamics of active cholesterics differs fundamentally from smectic-A liquid crystals, unlike their equilibrium counterpart. This distinction can be used to engineer a columnar array of vortices, with an antiferromagnetic vorticity alignment, that can be switched on and off by external strain. A two-dimensional chiral layered state—an array of lines on an incompressible, freestanding film of chiral active fluid with a preferred normal direction—is generically unstable. However, this instability can be tuned in easily realizable experimental settings when the film is either on a substrate or in an ambient fluid.

We report phase separation and liquid-crystal ordering induced by scalar activity in a system of Soft Repulsive Spherocylinders (SRS) of aspect ratio $L/D = 5 $. Activity was introduced by increasing the temperature of half of the SRS (labeled \textit{`hot'}) while maintaining the temperature of the other half constant at a lower value (labeled \textit{`cold'}). The difference between the two temperatures scaled by the lower temperature provides a measure of the activity. Starting from different equilibrium initial phases, we find that activity leads to segregation of the hot and cold particles. Activity also drives the cold particles through a phase transition to a more ordered state and the hot particles to a state of less order compared to the initial equilibrium state. The cold components of a homogeneous isotropic (I) structure acquire nematic (N) and, at higher activity, crystalline (K) order. Similarly, the cold zone of a nematic initial state undergoes smectic (Sm) and crystal ordering above a critical value of activity while the hot component turns isotropic. We find that the hot particles occupy a larger volume and exert an extra kinetic pressure, confining, compressing and provoking an ordering transition of the cold-particle domains., Comment: 19 pages, 21 figures

This article summarizes some of the open questions in the field of active matter that have emerged during Active20, a nine-week program held at the Kavli Institute for Theoretical Physics (KITP) in Spring 2020. The article does not provide a review of the field, but rather a personal view of the authors, informed by contributions of all participants, on new directions in active matter research. The topics highlighted include: the ubiquitous occurrence of spontaneous flows and active turbulence and the theoretical and experimental challenges associated with controlling and harnessing such flows; the role of motile topological defects in ordered states of active matter and their possible biological relevance; the emergence of non-reciprocal effective interactions and the role of chirality in active systems and their intriguing connections to non-Hermitian quantum mechanics; the progress towards a formulation of the thermodynamics of active systems thanks to the feedback between theory and experiments; the impact of the active matter framework on our understanding of the emergent mechanics of biological tissue. These seemingly diverse phenomena all stem from the defining property of active matter - assemblies of self-driven entities that individually break time-reversal symmetry and collectively organize in a rich variety of nonequilibrium states., Comment: 23 pages, 10 figures

Introduction: Heart Failure (HF) is one of the leading causes of hospitalization in USA accounting for ≈ 800,000 hospital discharges and $11 billion annually. Delirium is a common problem in the elderly hospitalized patients and can occur in 30-80%. Hypothesis: Given the increasing age of the HF population, we hypothesized that rate of delirium in HF hospitalizations is increasing and that delirium is associated adverse outcomes in HF hospitalizations. Methods: We queried the 2001-2014 Nationwide Inpatient Sample to identify hospitalizations that included a primary discharge diagnosis of HF (ICD-9-CM: 428.xx) stratified by presence or absence of delirium (ICD-9-CM: 239.0, 290.41, 293.0, 293.1, 348.31). The delirium trend was evaluated using orthogonal polynomial contrasts, whereas differences between delirium and non-delirium for in-hospital mortality, length of stay (LOS), and hospital costs were evaluated using propensity-score matched cohorts; match robustness was evaluated via propensity distributions and standardized mean differences. Results: Of the 12.8 million hospitalizations with HF, 89,489 (0.7%) had a diagnosis of delirium. The rate of delirium increased slightly from 0.3% in 2001 to 0.4% in 2007 and increased significantly to 1.6% by 2014 (quadratic p trend < .001). Major predictors of delirium included advanced age, Caucasian race, underlying dementia or psychiatric diagnoses, higher Elixhauser Comorbidity Index, renal failure, cardiogenic shock, and coronary artery bypass surgery. In the propensity-score matched analysis of 76,411 hospitalization with delirium compared to 76,612 without delirium, in-hospital mortality (odds ratio: 1.67, 95% CI: 1.51-1.77), LOS (rate ratio [RR]: 1.47, 95% CI: 1.45-1.51), and hospital costs (RR: 1.44, 95% CI: 1.41-1.48) were all statistically higher in the presence of delirium (all p < 0.001). Conclusions: In patients hospitalized with HF, delirium is an independent predictor of increased in-hospital mortality, longer LOS, and excess hospital costs despite adjustment for baseline characteristics. Whether interventions targeting prevention, early recognition, and treatment of delirium will mitigate this excess risk requires evaluation in future studies.

We create controllable active particles in the form of metal-dielectric Janus colloids which acquire motility through a nematic liquid crystal film by transducing the energy of an imposed perpendicular AC electric field. We achieve complete command over trajectories by varying field amplitude and frequency, piloting the colloids at will in the plane spanned by the axes of the particle and the nematic. The underlying mechanism exploits the sensitivity of electro-osmotic flow to the asymmetries of the particle surface and the liquid-crystal defect structure. We present a calculation of the dipolar force density produced by the interplay of the electric field with director anchoring and the contrasting electrostatic boundary conditions on the two hemispheres, that accounts for the dielectric-forward (metal-forward) motion of the colloids due to induced puller (pusher) force dipoles. These findings open unexplored directions for the use of colloids and liquid crystals in controlled transport, assembly and collective dynamics., Comment: 11 pages, 9 figures

We present a large-scale numerical study, supplemented by experimental observations, on a quasi-two-dimensional active system of polar rods and spherical beads confined between two horizontal plates and energised by vertical vibration. For a low rod concentration Φr, our observations are consistent with a direct phase transition, as bead concentration Φb is increased, from the isotropic phase to a homogeneous flock. For Φr above a threshold value, an ordered band dense in both rods and beads occurs between the disordered phase and the homogeneous flock, in both experiments and simulations. Within the size ranges accessible, we observe only a single band, whose width increases with Φr. Deep in the ordered state, we observe broken-symmetry “sound” modes and giant number fluctuations. The direction-dependent sound speeds and the scaling of fluctuations are consistent with the predictions of field theories of flocking; sound damping rates show departures from such theories, but the range of wavenumbers explored is modest. At very high densities, we see phase separation into rod-rich and bead-rich regions, both of which move coherently.

As the constituent particles of a flock are polar and in a driven state, their interactions must, in general, be fore-aft asymmetric and non-reciprocal. Within a model that explicitly retains the classical spin angular momentum field of the particles we show that the resulting asymmetric contribution to interparticle torques, if large enough, leads to a buckling instability of the flock. Precisely this asymmetry also yields a natural mechanism for a difference between the speed of advection of information along the flock and the speed of the flock itself, concretely establishing that the absence of detailed balance, and not merely the breaking of Galilean invariance, is crucial for this distinction. To highlight this we construct a model of asymmetrically interacting spins fixed to lattice points and demonstrate that the speed of advection of polarisation remains non-zero. We delineate the conditions on parameters and wavenumber for the existence of the buckling instability. Our theory should be consequential for interpreting the behaviour of real animal groups as well as experimental studies of artificial flocks composed of polar motile rods on substrates., This paper supersedes our earlier version arXiv:1605.00981 and contains a substantially revised theoretical treatment

Rural homelessness is an undeniable public health issue that is understudied in the research literature. The purpose of this study was to determine the sociodemographics, physical and mental health...

There is evidence that immune system dysregulation and inflammation may play a role in the development of post-traumatic stress disorder (PTSD). Previous studies have reported elevated levels of inflammatory markers such as C-reactive protein (CRP) in individuals with PTSD. However, it is unclear whether exacerbation of PTSD symptoms late in life is also associated with elevated inflammation. The purpose of this pilot study was to examine the relationship between inflammation and late-life PTSD.We recruited veterans either diagnosed with PTSD after the age of 55 or with no diagnosis of PTSD. Six veterans did not meet all eligibility criteria, including five who did not meet criteria for PTSD and one with celiac disease. The final sample included a total of 32 male veterans (16 veterans diagnosed with PTSD after 55 and 16 veterans without PTSD). The groups were matched as closely as possible on age, body mass index, and combat exposure. PTSD symptoms were assessed using the Clinician-Administered PTSD Scale for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, and depressive symptoms were assessed using the Hamilton Rating Scale for Depression. Inflammation was measured using serum CRP level.The two groups did not differ on sample characteristics including age, body mass index, tobacco use, medication use, and military history. CRP level was found to be significantly higher in the PTSD group than in the comparison group (Z = -3.047, p = 0.002), which was also observed after adjusting for depression scores (F(1, 27) = 8.30, p = 0.0077).The results from this pilot study suggest that late-life PTSD may be associated with increased inflammation. Further research in larger samples is needed to corroborate these findings and to clarify the relationship between inflammation and PTSD, which may lead to improved methods of diagnosis and treatment.

We present a complete analysis of the linearized dynamics of active solids with uniaxial orientational order, taking into account a hitherto overlooked consequence of rotation invariance. Our predictions include a purely active response of two-dimensional orientationally ordered solids to shear, the possibility of stable active solids with quasi-long-range order in two dimensions and long-range order in three dimensions, generic instability of the solid for one sign of active forcing, and the instability of the uniaxially ordered phase in momentum-conserved systems for large active forcing irrespective of its sign.

We study theoretically an active colloid whose polar axis of self-propulsion rotates to point parallel (antiparallel) to an imposed chemical gradient. We show that the coupling of this ‘chemotactic’ (‘antichemotactic’) response to phoretic translational motion yields remarkable two-particle dynamics reflecting the non-central and non-reciprocal character of the interaction. A pair of mutually chemotactic colloids trap each other in a final state of fixed separation resulting in a self-propelled active dimer. A second type of bound state is observed when the polar axes undergo periodic cycles leading to phase-locked circular motion around a common centre. A pair of swimmers with mismatched phoretic mobilities execute a dance in which they twirl around one another while moving jointly in a wide circle. For sufficiently small initial separation, the speed of self-propulsion controls the transition from bound to scattering states. Mutually anti-chemotactic swimmers always scatter apart. For the special case in which one of the two colloids has uniform surface activity we succeed in exactly classifying the fixed points underlying the bound states, and identify the bifurcations leading to transitions from one type of bound state to another. The varied dynamical behaviours are accessible by tuning the swimmer design and are summarised in state diagrams.

We show experimentally that a pair of disks settling at negligible Reynolds number (∼10^{-4}) displays two classes of bound periodic orbits, each with transitions to scattering states. We account for these dynamics, at leading far-field order, through an effective Hamiltonian in which gravitational driving endows orientation with the properties of momentum. This treatment is successfully compared against the measured properties of orbits and critical parameters of transitions between types of orbits. We demonstrate a precise correspondence with the Kepler problem of planetary motion for a wide range of initial conditions, find and account for a family of orbits with no Keplerian analog, and highlight the role of orientation as momentum in the many-disk problem.

Ecosystems can undergo abrupt transitions between alternative stable states when the driver crosses a critical threshold. Dynamical systems theory shows that when ecosystems approach the point of loss of stability associated with these transitions, they take a long time to recover from perturbations, a phenomenon known as critical slowing down. This generic feature of dynamical systems can offer early warning signals of abrupt transitions. However, these signals are qualitative and cannot quantify the thresholds of drivers at which transition may occur. Here, we propose a method to estimate critical thresholds from spatial data. We show that two spatial metrics, spatial variance and autocorrelation of ecosystem state variable, computed along driver gradients can be used to estimate critical thresholds. First, we investigate cellular-automaton models of ecosystem dynamics that show a transition from a high-density state to a bare state. Our models show that critical thresholds can be estimated as the ecosystem state and the driver values at which spatial variance and spatial autocorrelation of the ecosystem state are maximum. Next, to demonstrate the application of the method, we choose remotely sensed vegetation data (Enhanced Vegetation Index, EVI) from regions in central Africa and northeast Australia that exhibit alternative states in woody cover. We draw transects (8 × 90 km) that span alternative stable states along rainfall gradients. Our analyses of spatial variance and autocorrelation of EVI along transects yield estimates of critical thresholds. These estimates match reasonably well with those obtained by an independent method that uses large-scale (250 × 200 km) spatial data sets. Given the generality of the principles that underlie our method, our method can be applied to a variety of ecosystems that exhibit alternative stable states.

The current study examined differences between urban homeless veterans and non-veterans on sociodemographics, housing, clinical characteristics, and psychosocial factors. We recruited a sample of 196 homeless men (101 veterans, 95 non-veterans) from the Omaha, Nebraska metropolitan area. Structured interviews were conducted by research staff. The results showed that the two groups were similar in most respects, though there were several notable differences. Homeless veterans were found to be older and more educated than non-veterans, more likely to have married, and reported having fewer non-adult children. Multivariable models controlling for age further showed that veterans reported a higher number of medical problems and were more likely to report being diagnosed with major depression or PTSD than non-veterans. Comparison with previous studies suggests changes in certain characteristics of homeless veterans over the past few decades that may reflect the growing proportion of veterans from the a...

Inspired by experiments on dynamic extensile gels of biofilaments and motors, we propose a model of a network of linear springs with a kinetics consisting of growth at a prescribed rate, death after a lifetime drawn from a distribution, and birth at a randomly chosen node. The model captures features such as the build-up of self-stress, that are not easily incorporated into hydrodynamic theories. We study the model numerically and show that our observations can largely be understood through a stochastic effective-medium model. The resulting dynamically extending force-dipole network displays many features of yielded plastic solids, and offers a way to incorporate strongly non-affine effects into theories of active solids. A rather distinctive form for the stress distribution, and a Herschel-Bulkley dependence of stress on activity, are our major predictions.

How fast must an oriented collection of extensile swimmers swim to escape the instability of viscous active suspensions? We show that the answer lies in the dimensionless combination $R=\rho v_0^2/2\sigma_a$, where $\rho$ is the suspension mass density, $v_0$ the swim speed and $\sigma_a$ the active stress. Linear stability analysis shows that for small $R$ disturbances grow at a rate linear in their wavenumber $q$, and that the dominant instability mode involves twist. The resulting steady state in our numerical studies is isotropic hedgehog-defect turbulence. Past a first threshold $R$ of order unity we find a slower growth rate, of $O(q^2)$; the numerically observed steady state is {\it phase-turbulent}: noisy but {\it aligned} on average. We present numerical evidence in three and two dimensions that this inertia driven flocking transition is continuous, with a correlation length that grows on approaching the transition. For much larger $R$ we find an aligned state linearly stable to perturbations at all $q$. Our predictions should be testable in suspensions of mesoscale swimmers [D Klotsa, Soft Matter \textbf{15}, 8946 (2019)]., Comment: Version of the manuscript accepted in PRX

We present an experimental realization of the collective trapping phase transition [Kaiser et al., PRL 108, 268307 (2012)], using motile polar granular rods in the presence of a V-shaped obstacle. We offer a theory of this transition based on the interplay of motility-induced condensation and liquid-crystalline ordering and show that trapping occurs when persistent influx overcomes the collective expulsion of smectic defect structures. In agreement with the theory, our experiments find that a trap fills to the brim when the trap angle $\theta$ is below a threshold $\theta_c$, while all particles escape for $\theta > \theta_c$. Our simulations support a further prediction, that $\theta_c$ goes down with increasing rotational noise. We exploit the sensitivity of trapping to the persistence of directed motion to sort particles based on the statistical properties of their activity, Comment: 6 pages, 5 figures, for supplementary mpg files, see "https://www.dropbox.com/sh/3cmswfoysdn0sb6/AACpEp-G3768B6Y62nDFj_Hea?dl=0". This paper supersedes our earlier version arXiv:1603.08535 and contains substantial new results including revised theoretical treatment

This study explored differences between homeless male veterans in metropolitan and micropolitan cities in Nebraska on sociodemographic, housing, clinical, and psychosocial characteristics as well as health service use. A convenience sample of 151 homeless male veterans (112 metropolitan, 39 micropolitan) were recruited from Veterans Affairs facilities and area shelters in Omaha, Lincoln, Grand Island, and Hastings in Nebraska. Research staff conducted structured interviews with homeless veterans. Results showed that compared to homeless veterans in metropolitans, those in micropolitans were more likely to be White, unmarried, living in transitional settings, and were far more transient but reported greater social support and housing satisfaction. Veterans in micropolitans also reported more medical problems, diagnoses of anxiety and personality disorders, and unexpectedly, were more likely to report using various health services and less travel time for services. Together, these findings suggest access to homeless and health services for veterans in micropolitan areas may be facilitated through Veterans Affairs facilities and community providers that work in close proximity to one another. Many homeless veterans in these areas are transient, making them a difficult population to study and serve. Innovative ways to provide outreach to homeless veterans in micropolitan and more rural areas are needed.

International audience; Suspensions of actively driven anisotropic objects exhibit distinctively nonequilibrium behaviors, and current theories predict that they are incapable of sustaining orientational order at high activity. By contrast, here we show that nematic suspensions on a substrate can display order at arbitrarily high activity due to a previously unreported, potentially stabilizing active force. This force moreover emerges inevitably in theories of active orientable fluids under geometric confinement. The resulting nonequilibrium ordered phase displays robust giant number fluctuations that cannot be suppressed even by an incompressible solvent. Our results apply to virtually all experimental assays used to investigate the active nematic ordering of self-propelled colloids, bacterial sus-pensions, and the cytoskeleton and have testable implications in interpreting their nonequilibrium behaviors.

We consider a collection of self-driven apolar particles on a substrate that organize into an active nematic phase at sufficiently high density or low noise. Using the dynamical renormalization group, we systematically study the two-dimensional fluctuating ordered phase in a coarse-grained hydrodynamic description involving both the nematic director and the conserved density field. In the presence of noise, we show that the system always displays only quasi-long-ranged orientational order beyond a crossover scale. A careful analysis of the nonlinearities permitted by symmetry reveals that activity is dangerously irrelevant over the linearized description, allowing giant number fluctuations to persist although now with strong finite-size effects and a nonuniversal scaling exponent. Nonlinear effects from the active currents lead to power-law correlations in the density field, thereby preventing macroscopic phase separation in the thermodynamic limit.

Ecosystems can undergo abrupt transitions from one state to an alternative stable state when the driver crosses a threshold or a critical point. Dynamical systems theory suggests that systems take long to recover from perturbations near such transitions. This leads to characteristic changes in the dynamics of the system, which can be used as early warning signals of imminent transitions. However, these signals are qualitative and cannot quantify the critical points. Here, we propose a method to estimate critical points quantitatively from spatial data. We employ a spatial model of vegetation that shows a transition from vegetated to bare state. We show that the critical point can be estimated as the ecosystem state and the driver values at which spatial variance and autocorrelation are maximum. We demonstrate the validity of this method by analysing spatial data from regions of Africa and Australia that exhibit alternative vegetation biomes.

Importance Less than one-third of patients with major depressive disorder (MDD) achieve remission with their first antidepressant. Objective To determine the relative effectiveness and safety of 3 common alternate treatments for MDD. Design, Setting, and Participants From December 2012 to May 2015, 1522 patients at 35 US Veterans Health Administration medical centers who were diagnosed with nonpsychotic MDD, unresponsive to at least 1 antidepressant course meeting minimal standards for treatment dose and duration, participated in the study. Patients were randomly assigned (1:1:1) to 1 of 3 treatments and evaluated for up to 36 weeks. Interventions Switch to a different antidepressant, bupropion (switch group, n = 511); augment current treatment with bupropion (augment-bupropion group, n = 506); or augment with an atypical antipsychotic, aripiprazole (augment-aripiprazole group, n = 505) for 12 weeks (acute treatment phase) and up to 36 weeks for longer-term follow-up (continuation phase). Main Outcomes and Measures The primary outcome was remission during the acute treatment phase (16-item Quick Inventory of Depressive Symptomatology-Clinician Rated [QIDS-C 16 ] score ≤5 at 2 consecutive visits). Secondary outcomes included response (≥50% reduction in QIDS-C 16 score or improvement on the Clinical Global Impression Improvement scale), relapse, and adverse effects. Results Among 1522 randomized patients (mean age, 54.4 years; men, 1296 [85.2%]), 1137 (74.7%) completed the acute treatment phase. Remission rates at 12 weeks were 22.3% (n = 114) for the switch group, 26.9% (n = 136)for the augment-bupropion group, and 28.9% (n = 146) for the augment-aripiprazole group. The augment-aripiprazole group exceeded the switch group in remission (relative risk [RR], 1.30 [95% CI, 1.05-1.60]; P = .02), but other remission comparisons were not significant. Response was greater for the augment-aripiprazole group (74.3%) than for either the switch group (62.4%; RR, 1.19 [95% CI, 1.09-1.29]) or the augment-bupropion group (65.6%; RR, 1.13 [95% CI, 1.04-1.23]). No significant treatment differences were observed for relapse. Anxiety was more frequent in the 2 bupropion groups (24.3% in the switch group [n = 124] vs 16.6% in the augment-aripiprazole group [n = 84]; and 22.5% in augment-bupropion group [n = 114]). Adverse effects more frequent in the augment-aripiprazole group included somnolence, akathisia, and weight gain. Conclusions and Relevance Among a predominantly male population with major depressive disorder unresponsive to antidepressant treatment, augmentation with aripiprazole resulted in a statistically significant but only modestly increased likelihood of remission during 12 weeks of treatment compared with switching to bupropion monotherapy. Given the small effect size and adverse effects associated with aripiprazole, further analysis including cost-effectiveness is needed to understand the net utility of this approach. Trial Registration clinicaltrials.gov Identifier:NCT01421342

The enzyme N-acetylmannosamine kinase (NanK) catalyzes the second step of the bacterial sialic acid catabolic pathway. Here, the structure of F. nucleatum NanK is presented at 2.23 Å resolution., Sialic acids comprise a varied group of nine-carbon amino sugars that are widely distributed among mammals and higher metazoans. Some human commensals and bacterial pathogens can scavenge sialic acids from their environment and degrade them for use as a carbon and nitrogen source. The enzyme N-acetylmannosamine kinase (NanK; EC 2.7.1.60) belongs to the transcriptional repressors, uncharacterized open reading frames and sugar kinases (ROK) superfamily. NanK catalyzes the second step of the sialic acid catabolic pathway, transferring a phosphate group from adenosine 5′-triphos­phate to the C6 position of N-acetylmannosamine to generate N-acetylmannosamine 6-phosphate. The structure of NanK from Fusobacterium nucleatum was determined to 2.23 Å resolution by X-ray crystallography. Unlike other NanK enzymes and ROK family members, F. nucleatum NanK does not have a conserved zinc-binding site. In spite of the absence of the zinc-binding site, all of the major structural features of enzymatic activity are conserved.

Objective To determine the efficacy, safety, and tolerability of vilazodone in the treatment of posttraumatic stress disorder (PTSD) with comorbid mild-to-moderate depression. Methods A 12-week randomized, double-blind, placebo-controlled trial was conducted in adult outpatients who met DSM-IV criteria for PTSD with comorbid depression between February 2013 and September 2015. Participants were randomly assigned to receive vilazodone 40 mg/d or placebo, and outcome measures were obtained at scheduled visits. Primary outcome measures included change in PTSD symptoms from baseline to end of study as indexed by the Clinician-Administered PTSD Scale (CAPS) and PTSD Symptom Scale-Self-Report (PSS-SR). Secondary outcome measures of anxiety, depression, and impairment were obtained, as well as biomarker assessment at baseline and end of study. Results A total of 59 patients were randomly assigned to receive vilazodone (n = 29) or placebo (n = 30). Of those who were randomized, there were 25 completers in the vilazodone group and 22 completers in the placebo group. No significant differences were observed between the groups on any of the primary or secondary outcome measures. Vilazodone was generally well tolerated with few differences in the rate of adverse events between groups. Conclusions Treatment with vilazodone 40 mg/d did not improve symptoms of PTSD and comorbid depression. Further investigation of the biological mechanisms underlying PTSD may lead to identification of improved therapeutic targets. Trial registration ClinicalTrials.gov identifier: NCT01715519.

Diabetes mellitus is a worldwide prevalent chronic disease with a significant disease burden. The associated dyslipidemia adds to the lethality of type 2 diabetes mellitus and requires newer and better treatment strategies. Peroxisome proliferator activated receptor (PPAR) α and γ agonists are approved hypolipidemic and anti-diabetic agents respectively and combining them together provides a dual benefit in type 2 diabetes mellitus associated with dyslipidemia. This novel class of dual PPAR agonists are termed as “Glitazars” and in 2013, Saroglitazar, a member of this class of drugs; was approved by the Indian regulatory authority Drug Controller General of India (DCGI) for the treatment of diabetic dyslipidemia. It is the first glitazar to gain regulatory approval anywhere in the world and is also the first New Chemical Entity (NCE) to be discovered in India. This review provides an overview of this novel drug including its mechanism of action and prospective uses. Key words: Diabetic dyslipidemia, Glitazars, PPAR agonists, Type 2 diabetes.

This review summarizes theoretical progress in the field of active matter, placing it in the context of recent experiments. This approach offers a unified framework for the mechanical and statistical properties of living matter: biofilaments and molecular motors in vitro or in vivo, collections of motile microorganisms, animal flocks, and chemical or mechanical imitations. A major goal of this review is to integrate several approaches proposed in the literature, from semimicroscopic to phenomenological. In particular, first considered are ``dry'' systems, defined as those where momentum is not conserved due to friction with a substrate or an embedding porous medium. The differences and similarities between two types of orientationally ordered states, the nematic and the polar, are clarified. Next, the active hydrodynamics of suspensions or ``wet'' systems is discussed and the relation with and difference from the dry case, as well as various large-scale instabilities of these nonequilibrium states of matter, are highlighted. Further highlighted are various large-scale instabilities of these nonequilibrium states of matter. Various semimicroscopic derivations of the continuum theory are discussed and connected, highlighting the unifying and generic nature of the continuum model. Throughout the review, the experimental relevance of these theories for describing bacterial swarms and suspensions, the cytoskeleton of living cells, and vibrated granular material is discussed. Promising extensions toward greater realism in specific contexts from cell biology to animal behavior are suggested, and remarks are given on some exotic active-matter analogs. Last, the outlook for a quantitative understanding of active matter, through the interplay of detailed theory with controlled experiments on simplified systems, with living or artificial constituents, is summarized.