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Upper extremity abscesses frequently present to the acute care setting with inconclusive physical examination and imaging findings. We sought to investigate the diagnostic accuracy of inflammatory markers including white blood cell (WBC) count, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). A retrospective cohort study was performed to identify subjects ≥18 years treated with surgical debridement of upper extremity abscesses at our institution between January 2012 and December 2015. In this study, 188 patients were screened, and 72 met the inclusion criteria. A confirmed abscess as defined by culture positivity was present in 67 (93.1 %) cases. The sensitivity of WBC, ESR, or CRP individually was 0.45, 0.71, and 0.81. The specificity of WBC, ESR, or CRP individually was 0.80, 0.80, and 0.40. In combination all three markers when positive had a sensitivity of 0.26 and specificity of 1.0. These values were similar among patients with diabetes and those with obesity. With the highest sensitivity and lowest specificity, CRP exhibited the most utility as a screening test (level IV).

Schizophrenia is a neuropsychiatric condition that is associated with impaired attentional processing and performance. Failure to support increasing attentional load may result, in part, from abnormally overactive basal forebrain projections to the prefrontal cortex, and available antipsychotics often fail to address this issue. Orexin/hypocretin receptors are expressed on corticopetal cholinergic neurons, and their blockade has been shown to decrease the activity of cortical basal forebrain outputs and prefrontal cortical cholinergic neurotransmission. In the present experiment, rats (N = 14) trained in a visual sustained attention task that required discrimination of trials which presented a visual signal from trials during which no signal was presented. Once trained, rats were then co-administered the psychotomimetic N-methyl-D-aspartate (NMDA) receptor antagonist dizocilpine (MK-801: 0 or 0.1 mg/kg, intraperitoneal injections) and the dual orexin receptor antagonist filorexant (MK-6096: 0, 0.1, or 1 mM, intracerebroventricular infusions) prior to task performance across six sessions. Dizocilpine impaired overall accuracy during signal trials, slowed reaction times for correctly-responded trials, and increased the number of omitted trials throughout the task. Dizocilpine-induced increases in signal trial deficits, correct response latencies, and errors of omission were reduced following infusions of the 0.1 mM, but not 1 mM, dose of filorexant. Orexin receptor blockade, perhaps through anticholinergic mechanisms, may improve attentional deficits in a state of NMDA receptor hypofunction.HighlightsSchizophrenia is associated with attentional deficits that may stem from abnormally reactive BF projections to the prefrontal cortexOrexin receptor antagonists decrease acetylcholine release and reduce prefrontal cortical activityThe dual orexin receptor antagonist filorexant alleviated impairments of attention following NMDA receptor blockade

The management of pathologic fractures differs from nonpathologic fractures with respect to preoperative evaluation, surgical strategies, adjuvant therapies, and complication rates. These issues must be understood to provide appropriate musculoskeletal care for patients with metastatic disease.

Behavioral flexibility-that is, the ability to deviate from established behavioral sequences-is critical for navigating dynamic environments and requires the durable encoding and retrieval of new memories to guide future choice. The orbitofrontal cortex (OFC) supports outcome-guided behaviors. However, the coordinated neural circuitry and cellular mechanisms by which OFC connections sustain flexible learning and memory remain elusive. Here we demonstrate in mice that basolateral amygdala (BLA)→OFC projections bidirectionally control memory formation when familiar behaviors are unexpectedly not rewarded, whereas OFC→dorsomedial striatum (DMS) projections facilitate memory retrieval. OFC neuronal ensembles store a memory trace for newly learned information, which appears to be facilitated by circuit-specific dendritic spine plasticity and neurotrophin signaling within defined BLA-OFC-DMS connections and obstructed by cocaine. Thus, we describe the directional transmission of information within an integrated amygdalo-fronto-striatal circuit across time, whereby novel memories are encoded by BLA→OFC inputs, represented within OFC ensembles and retrieved via OFC→DMS outputs during future choice.

The effective treatment of bipolar disorder (BD) represents a significant unmet medical need. Although lithium remains a mainstay of treatment for BD, limited knowledge regarding how it modulates affective behavior has proven an obstacle to discovering more effective mood stabilizers with fewer adverse side effects. One potential mechanism of action of lithium is through inhibition of the serine/threonine protein kinase GSK3β, however, relevant substrates whose change in phosphorylation may mediate downstream changes in neuroplasticity remain poorly understood. Here, we used human induced pluripotent stem cell (hiPSC)-derived neuronal cells and stable isotope labeling by amino acids in cell culture (SILAC) along with quantitative mass spectrometry to identify global changes in the phosphoproteome upon inhibition of GSK3α/β with the highly selective, ATP-competitive inhibitor CHIR-99021. Comparison of phosphorylation changes to those induced by therapeutically relevant doses of lithium treatment led to the identification of collapsin response mediator protein 2 (CRMP2) as being highly sensitive to both treatments as well as an extended panel of structurally distinct GSK3α/β inhibitors. On this basis, a high-content image-based assay in hiPSC-derived neurons was developed to screen diverse compounds, including FDA-approved drugs, for their ability to mimic lithium’s suppression of CRMP2 phosphorylation without directly inhibiting GSK3β kinase activity. Systemic administration of a subset of these CRMP2-phosphorylation suppressors were found to mimic lithium’s attenuation of amphetamine-induced hyperlocomotion in mice. Taken together, these studies not only provide insights into the neural substrates regulated by lithium, but also provide novel human neuronal assays for supporting the development of mechanism-based therapeutics for BD and related neuropsychiatric disorders.

We present the open-source Bayesian Atmospheric Radiative Transfer (BART) retrieval package, which produces estimates and uncertainties for an atmosphere’s thermal profile and chemical abundances from observations. Several BART components are also stand-alone packages, including the parallel Multi-Core Markov-chain Monte Carlo (MC3), which implements several Bayesian samplers; a line-by-line radiative-transfer model, transit; a code that calculates Thermochemical Equilibrium Abundances (TEA), and a test suite for verifying radiative-transfer and retrieval codes, BARTTest. The codes are in Python and C. BART and TEA are under a Reproducible Research (RR) license, which requires reviewed-paper authors to publish a compendium of all inputs, codes, and outputs supporting the paper’s scientific claims. BART and TEA produce the compendium’s content. Otherwise, these codes are under permissive open-source terms, as are MC3 and BARTTest, for any purpose. This paper presents an overview of the code, BARTTest, and an application to eclipse data for exoplanet HD 189733b. Appendices address RR methodology for accelerating science, a reporting checklist for retrieval papers, the spectral resolution required for synthetic tests, and a derivation of the effective sample size required to estimate any Bayesian posterior distribution to a given precision, which determines how many iterations to run. Paper II, by Cubillos et al., presents the underlying radiative-transfer scheme and an application to transit data for exoplanet HAT-P-11b. Paper III, by Blecic et al., discusses the initialization and post-processing routines, with an application to eclipse data for exoplanet WASP-43b. We invite the community to use and improve BART and its components at http://GitHub.com/ExOSPORTS/BART/.

This and companion papers by Harrington et al. and Blecic et al. present the Bayesian Atmospheric Radiative Transfer (bart) code, an open-source, open-development package to characterize extrasolar planet atmospheres. bart combines a thermochemical equilibrium abundance (tea), a radiative transfer (Transit), and a Bayesian statistical (mc3) module to constrain atmospheric temperatures and molecular abundances for given spectroscopic observations. Here we describe the Transit radiative transfer package, an efficient line-by-line radiative transfer C code for one-dimensional atmospheres, developed by P. Rojo and further modified by the UCF exoplanet group. This code produces transmission and hemisphere-integrated emission spectra. Transit handles line-by-line opacities from HITRAN, Partridge & Schwenke (H2O), Schwenke (TiO), and Plez (VO) and collision-induced absorption from Borysow, HITRAN, and ExoMol. Transit emission spectra models agree with models from C. Morley (private communication) within a few percent. We applied bart to the Spitzer and Hubble transit observations of the Neptune-sized planet HAT-P-11b. Our analysis of the combined HST and Spitzer data generally agrees with those from previous studies, finding atmospheric models with enhanced metallicity (≳100× solar) and high-altitude clouds (≲1 mbar level). When analyzing only the HST data, our models favor high-metallicity atmospheres, in contrast with the previous analysis by Chachan et al. We suspect that this discrepancy arises from the different choice of chemistry modeling (free constant-with-altitude versus thermochemical equilibrium) and the enhanced parameter correlations found when neglecting the Spitzer observations. The bart source code and documentation are available at https://github.com/exosports/BART.

This and companion papers by Harrington et al. and Cubillos et al. describe an open-source retrieval framework, Bayesian Atmospheric Radiative Transfer (BART), available to the community under the reproducible-research license via https://github.com/exosports/BART. BART is a radiative transfer code (transit; https://github.com/exosports/transit; Rojo et al.), initialized by the Thermochemical Equilibrium Abundances (TEA; https://github.com/dzesmin/TEA) code (Blecic et al.), and driven through the parameter phase space by a differential-evolution Markov Chain Monte Carlo (MC3; https://github.com/pcubillos/mc3) sampler (Cubillos et al.). In this paper we give a brief description of the framework and its modules that can be used separately for other scientific purposes; outline the retrieval analysis flow; present the initialization routines, describing in detail the atmospheric profile generator and the temperature and species parameterizations; and specify the post-processing routines and outputs, concentrating on the spectrum band integrator, the best-fit model selection, and the contribution functions. We also present an atmospheric analysis of WASP-43b secondary eclipse data obtained from space- and ground-based observations. We compare our results with the results from the literature and investigate how the inclusion of additional opacity sources influences the best-fit model.

Multiple laboratories have shown that the stimulation of μ-opioid receptors in the nucleus accumbens (NAcc) powerfully increases intake of palatable and high-fat diets. Separate studies have demonstrated that serotonin agonists advance satiety processes, and several serotonin-targeting agents have been prescribed to promote weight loss. However, it is unknown if serotonin signaling can modulate the increased feeding elicited by activation of NAcc μ-opioid receptors. These experiments assessed the effects of systemic treatments with the serotonin agonists d -fenfluramine and lorcaserin on the binge-like feeding induced by μ-opioid receptor stimulation of the NAcc in Sprague-Dawley rats. Consistent with previous reports, stimulation of NAcc μ-opioid receptors (with 0.025 μg/0.5 μl/side DAMGO) significantly increased consumption of high-fat vegetable shortening, and systemic treatment with d -fenfluramine and lorcaserin dose-dependently decreased intake. Interestingly, d -fenfluramine and lorcaserin reversed the binge-like feeding observed following stimulation of NAcc μ-opioid receptors. Both serotonergic drugs also attenuated the increases of ambulation observed following administration of DAMGO in the NAcc. These data demonstrate that serotonergic anorectics, in addition to their known role in advancing satiety processes during normal feeding, can also inhibit the binge-like feeding that is elicited by activation of μ-opioid receptors within the ventral striatum.

Early philosophers and psychologists defined and began to describe attention. Beginning in the 1950’s, numerous models of attention were developed. This corresponded with an increased understanding of pharmacological approaches to manipulate neurotransmitter systems. The present review focuses on the knowledge that has been gained about these neurotransmitter systems with respect to attentional processing, with emphasis on the functions mediated within the medial prefrontal cortex. Additionally, the use of pharmacotherapies to treat psychiatric conditions characterized by attentional dysfunction are discussed. Future directions include developing a more comprehensive understanding of the neural mechanisms underlying attentional processing and novel pharmacotherapeutic targets for conditions characterized by aberrant attentional processing.

Modular implants are currently widely used in total hip arthroplasty because they give surgeons versatility during the operation, allow for easier revision surgery, and can be adjusted to better fit the anatomy of the specific patient. However, modular implants, specifically those that have metal-on-metal junctions, are susceptible to crevice and fretting corrosion. This can ultimately cause implant failure, inflammation, and adverse local tissue reaction, among other possible side effects. Surgeons should be aware of the possibility of implant corrosion and should follow a set of recommended guidelines to systematically diagnose and treat patients with corroded implants. Ultimately, surgeons will continue to use modular implants because of their widespread benefits. However, more research is needed to determine how to minimize corrosion and the negative side effects that have been associated with modular junctions in total hip arthroplasty. [ Orthopedics. 2017; 40(6):355–366.]

Helium is the second-most abundant element in the Universe after hydrogen and is one of the main constituents of gas-giant planets in our Solar System. Early theoretical models predicted helium to be among the most readily detectable species in the atmospheres of exoplanets, especially in extended and escaping atmospheres. Searches for helium, however, have hitherto been unsuccessful. Here we report observations of helium on an exoplanet, at a confidence level of 4.5 standard deviations. We measured the near- infrared transmission spectrum of the warm gas giant WASP-107b and identified the narrow absorption feature of excited metastable helium at 10,833 angstroms. The amplitude of the feature, in transit depth, is 0.049 +/- 0.011 per cent in a bandpass of 98 angstroms, which is more than five times greater than what could be caused by nominal stellar chromospheric activity. This large absorption signal suggests that WASP-107b has an extended atmosphere that is eroding at a total rate of 10^10 to 3 x 10^11 grams per second (0.1-4 per cent of its total mass per billion years), and may have a comet-like tail of gas shaped by radiation pressure., Comment: Accepted in Nature

The hypothalamus is the major CNS locus that links physiological homeostasis with behavior, including cognitive components of adaptive responses to homeostatic challenges. The hypothalamic orexin/hypocretin neuropeptide system has widespread projections to cerebral and brainstem regions that are important for cognitive function. These anatomical connections allow for orexins to interact with, and regulate, neurotransmitter systems classically implicated in cognitive domains that prominently include attention. Indeed, attentional deficits are associated with conditions, including narcolepsy and age-related cognitive decline, which are either caused by or associated with varying degrees of orexin deficiency. Animal models further support a significant role for the orexin system in cognitive function. Here, we review the experimental and clinical evidence suggesting a role for the orexin system in cognitive function and conclude with a brief discussion of the prospect of orexin-targeted therapies as cognitive enhancers.

We present an atmospheric transmission spectrum for the ultra-hot Jupiter WASP-121b, measured using the Space Telescope Imaging Spectrograph (STIS) onboard the Hubble Space Telescope (HST). Across the 0.47-1 micron wavelength range, the data imply an atmospheric opacity comparable to - and in some spectroscopic channels exceeding - that previously measured at near-infrared wavelengths (1.15-1.65 micron). Wavelength-dependent variations in the opacity rule out a gray cloud deck at a confidence level of 3.8-sigma and may instead be explained by VO spectral bands. We find a cloud-free model assuming chemical equilibrium for a temperature of 1500K and metal enrichment of 10-30x solar matches these data well. Using a free-chemistry retrieval analysis, we estimate a VO abundance of -6.6(-0.3,+0.2) dex. We find no evidence for TiO and place a 3-sigma upper limit of -7.9 dex on its abundance, suggesting TiO may have condensed from the gas phase at the day-night limb. The opacity rises steeply at the shortest wavelengths, increasing by approximately five pressure scale heights from 0.47 to 0.3 micron in wavelength. If this feature is caused by Rayleigh scattering due to uniformly-distributed aerosols, it would imply an unphysically high temperature of 6810+/-1530K. One alternative explanation for the short-wavelength rise is absorption due to SH (mercapto radical), which has been predicted as an important product of non-equilibrium chemistry in hot Jupiter atmospheres. Irrespective of the identity of the NUV absorber, it likely captures a significant amount of incident stellar radiation at low pressures, thus playing a significant role in the overall energy budget, thermal structure, and circulation of the atmosphere., Comment: Accepted for publication in The Astronomical Journal

Background While antidepressant treatment response appears to be partially heritable, no consistent genetic associations have been identified. Large, rare copy number variants (CNVs) play a role in other neuropsychiatric diseases, so we assessed their association with treatment-resistant depression (TRD). Methods We analyzed data from two genome-wide association studies comprising 1263 Caucasian patients with major depressive disorder. One was drawn from a large health system by applying natural language processing to electronic health records (i2b2 cohort). The second consisted of a multicenter study of sequential antidepressant treatments, Sequenced Treatment Alternatives to Relieve Depression. The Birdsuite package was used to identify rare deletions and duplications. Individuals without symptomatic remission, despite two antidepressant treatment trials, were contrasted with those who remitted with a first treatment trial. Results CNV data were derived for 778 subjects in the i2b2 cohort, including 300 subjects (37%) with TRD, and 485 subjects in Sequenced Treatment Alternatives to Relieve Depression cohort, including 152 (31%) with TRD. CNV burden analyses identified modest enrichment of duplications in cases (empirical p = .04 for duplications of 100–200 kilobase) and a particular deletion region spanning gene PABPC4L (empirical p = .02, 6 cases: 0 controls). Pathway analysis suggested enrichment of CNVs intersecting genes regulating actin cytoskeleton. However, none of these associations survived genome-wide correction. Conclusions Contribution of rare CNVs to TRD appears to be modest, individually or in aggregate. The electronic health record-based methodology demonstrated here should facilitate collection of larger TRD cohorts necessary to further characterize these effects.

IMPORTANCE: Short-term studies suggest antidepressants are associated with modest weight gain but little is known about longer-term effects and differences between individual medications in general clinical populations. OBJECTIVE: To estimate weight gain associated with specific antidepressants over the 12 months following initial prescription in a large and diverse clinical population. DESIGN, SETTING, AND PARTICIPANTS: We identified 22 610 adult patients who began receiving a medication of interest with available weight data in a large New England health care system, including 2 academic medical centers and affiliated outpatient primary and specialty care clinics. We used electronic health records to extract prescribing data and recorded weights for any patient with an index antidepressant prescription including amitriptyline hydrochloride, bupropion hydrochloride, citalopram hydrobromide, duloxetine hydrochloride, escitalopram oxalate, fluoxetine hydrochloride, mirtazapine, nortriptyline hydrochloride, paroxetine hydrochloride, venlafaxine hydrochloride, and sertraline hydrochloride. As measures of assay sensitivity, additional index prescriptions examined included the antiasthma medication albuterol sulfate and the antiobesity medications orlistat, phentermine hydrochloride, and sibutramine hydrochloride. Mixed-effects models were used to estimate rate of weight change over 12 months in comparison with the reference antidepressant, citalopram. MAIN OUTCOME AND MEASURE: Clinician-recorded weight at 3-month intervals up to 12 months. RESULTS: Compared with citalopram, in models adjusted for sociodemographic and clinical features, significantly decreased rate of weight gain was observed among individuals treated with bupropion (β [SE]: −0.063 [0.027]; P = .02), amitriptyline (β [SE]: −0.081 [0.025]; P = .001), and nortriptyline (β [SE]: −0.147 [0.034]; P < .001). As anticipated, differences were less pronounced among individuals discontinuing treatment prior to 12 months. CONCLUSIONS AND RELEVANCE: Antidepressants differ modestly in their propensity to contribute to weight gain. Short-term investigations may be insufficient to characterize and differentiate this risk.

Objectives Motivated by genetic association data implicating L-type calcium channels in bipolar disorder liability, we sought to estimate the tolerability, safety, and efficacy of isradipine in the adjunctive treatment of bipolar depression. Methods A total of 12 patients with bipolar I or II depression entered this pilot, proof-of-concept eight-week investigation and 10 returned for at least one post-baseline visit. They were initiated on isradipine at 2.5 mg and titrated up to 10 mg daily, with blinded assessments of depression using the Montgomery–Asberg Depression Rating Scale (MADRS) as well as adverse effects. Results Among the 10 patients, three had bipolar II disorder; all but two reported current episode duration longer than six months. In all, four of 10 completed the study; no significant adverse events were observed, although one subject discontinued treatment per protocol because of possible hypomanic symptoms which had resolved prior to study visit. In a mixed-effects model, mean improvement in depression severity, assessed by MADRS, was 2.1 (standard error = 0.36) points/week (p