The representation of authors of color in schizophrenia research articles published in high-impact psychiatric journals.

OBJECTIVE: We evaluate how often scholars of color publish papers on schizophrenia in high-impact psychiatric journals, and whether they are more likely than white authors to prioritize race/ethnicity as a primary variable of interest in analyses. METHODS: Prior work categorized the types of ethnoracial analyses reported in 474 papers about schizophrenia published in high-impact psychiatric journals between 2014 and 2016. In this study, the photographs of the first and last author for each paper were coded as "person of color" (POC) or "white". Additionally, each author was asked to self-report their race and ethnicity. The percentage of papers published by white versus POC authors was calculated. Chi-square analyses tested the hypotheses that (a) white scholars are more likely than POC scholars to conduct any sort of racial analysis; (b) POC scholars are more likely to conduct primary analyses by race/ethnicity; and (c) white scholars are more likely to analyze race/ethnicity as extraneous variables. RESULTS: Eighteen percent of papers were published by POC first authors, and 17% were published by POC last authors. There were minimal differences in the types of analyses conducted by POC and white authors. Self-reported race/ethnicity showed that Asian scholars were the most highly represented within POC authors (9% of respondents), but only 3% of authors identified as Hispanic/Latinx and none identified as Black or Indigenous American. CONCLUSIONS: People of color are underrepresented as authors in US-based schizophrenia research published in high-impact journals. Culturally-informed mentorship as well as prioritization of race/ethnicity in funding structures are important to increase representation of POC authors.

Women and Men National Collegiate Athletic Association Ice Hockey Players Were Similarly Likely to Suffer Lumbar Spine Injuries.

PURPOSE: To describe and compare the epidemiology of lumbar spine injuries (LSIs) in women's and men's ice hockey during the 2009-2010 to 2013-2014 academic years and to investigate sex-specific differences, using data from the National Collegiate Athletic Association (NCAA) Injury Surveillance Program (ISP) database. METHODS: The incidence and characteristics of LSIs were identified utilizing the NCAA ISP. Rates of injury were calculated as number of injuries divided by total number of athlete exposures (AEs). AEs were defined as any student participation in one NCAA-sanctioned practice or competition. Incidence rate ratios (IRRs) were calculated to compare rates of injury between season, event type, mechanism, injury recurrence, and time lost from sport, and injury proportion ratios (IPRs) were calculated to examine the differences in injury rates between men and women. RESULTS: There were a total of 165 LSIs from an average of 10 and 19 women's and men's teams, respectively, calculated to 1,254 LSIs nationally. Women were 2.48 times more likely to suffer a noncontact injury than men (95% CI: 1.33-4.61), whereas men were more likely than women to suffer contact LSIs (IPR: .51 [95% CI: .28-.92]). In Divisions II and III, women were 6.64 (95% CI: 4.14-10.64) and 1.28 (95% CI: 1.12-1.46) times more likely to suffer LSIs than men, respectively. CONCLUSIONS: Women and men were similarly likely to suffer an LSI, but sex-specific differences existed in a mechanism of injury and likelihood of injury within NCAA Divisions.

Positioning for success: building capacity in academic competencies for early-career researchers in sub-Saharan Africa.

BACKGROUND: Capacity building is essential in low- and middle-income countries (LMICs) to address the gap in skills to conduct and implement research. Capacity building must not only include scientific and technical knowledge, but also broader competencies, such as writing, disseminating research and achieving work-life balance. These skills are thought to promote long-term career success for researchers in high-income countries (HICs) but the availability of such training is limited in LMICs. METHODS: This paper presents the contextualisation and implementation of the Academic Competencies Series (ACES). ACES is an early-career researcher development programme adapted from a UK university. Through consultation between HIC and LMIC partners, an innovative series of 10 workshops was designed covering themes of self-development, engagement and writing skills. ACES formed part of the African Mental Health Research Initiative (AMARI), a multi-national LMIC-led consortium to recruit, train, support and network early-career mental health researchers from four sub-Saharan African countries. RESULTS: Of the 10 ACES modules, three were HIC-LMIC co-led, four led by HIC facilitators with LMIC training experience and three led by external consultants from HICs. Six workshops were delivered face to face and four by webinar. Course attendance was over 90% and the delivery cost was approximately US$4500 per researcher trained. Challenges of adaptation, attendance and technical issues are described for the first round of workshops. CONCLUSIONS: This paper indicates that a skills development series for early-career researchers can be contextualised and implemented in LMIC settings, and is feasible for co-delivery with local partners at relatively low cost.

The Mass Casualty Incident in Turin, 2017: A Case Study of Disaster Responders' Mental Health in an Italian Level I Hospital.

OBJECTIVE: To assess the psychological impact of a mass casualty incident (MCI) in a subset of personnel in a level I hospital. METHODS: Emergency department staff responded to an MCI in June 2017 in Turin, Italy by an unexpected sudden surge of casualties following a stampede (mass escape). Participants completed the Psychological Simple Triage and Rapid Treatment Responder Self-Triage System (PsySTART-R), which classified the potential risk of psychological distress in "no risk" versus "at risk" categorization and identified a range of impacts aggregated for the population of medical responders. Participants were administered a questionnaire on the perceived effectiveness of management of the MCI. Two months later, the participants were evaluated using the Hospital Anxiety and Depression Scale (HADS), the Kessler Psychological Distress Scale (K6), and the Posttraumatic Stress Disorder Checklist (PCL-5). RESULTS: The majority of the responders were classified as "no risk" by the PsySTART-R; no significant differences on HADS, K6, and PCL-5 were found in the participants grouped by the PsySTART-R categories. The personnel acquainted to work in emergency contexts (emergency department and intensive care unit) scored significantly lower in the HADS than the personnel usually working in other wards. The number of positive PsySTART-R criteria correlated with the HADS depression score. CONCLUSIONS: Most of the adverse psychological implications of the MCI were well handled and averted by the responders. A possible explanation could be related to factors such as the clinical condition of the victims (most were not severely injured, no fatalities), the small number of casualties (87) brought to the hospital, the event not being considered life-threatening, and its brief duration, among others. Responders had mainly to cope with a sudden surge in casualties and with organizational issues.

Multi-species sensing using multi-mode absorption spectroscopy with mid-infrared interband cascade lasers.

The application of an interband cascade laser, ICL, to multi-mode absorption spectroscopy, MUMAS, in the mid-infrared region is reported. Measurements of individual mode linewidths of the ICL, derived from the pressure dependence of lineshapes in MUMAS signatures of single, isolated, lines in the spectrum of HCl, were found to be in the range 10-80 MHz. Multi-line spectra of methane were recorded using spectrally limited bandwidths, of approximate width 27 cm-1, defined by an interference filter, and consist of approximately 80 modes at spectral locations spanning the 100 cm-1 bandwidth of the ICL output. Calibration of the methane pressures derived from MUMAS data using a capacitance manometer provided measurements with an uncertainty of 1.1 %. Multi-species sensing is demonstrated by the simultaneous detection of methane, acetylene and formaldehyde in a gas mixture. Individual partial pressures of the three gases are derived from best fits of model MUMAS signatures to the data with an experimental error of 10 %. Using an ICL, with an inter-mode interval of ~10 GHz, MUMAS spectra were recorded at pressures in the range 1-10 mbar, and, based on the data, a potential minimum detection limit of the order of 100 ppmv is estimated for MUMAS at atmospheric pressure using an inter-mode interval of 80 GHz.

Gain and loss as a function of current density and temperature in interband cascade lasers.

We characterize the internal efficiency, internal loss, and optical gain versus current density in 7-stage interband cascade lasers operating at λ=3.1 and 3.45 µm using a cavity-length study of the external differential quantum efficiency (EDQE) and threshold current density at temperatures between 300 and 345 K. We find that the pronounced efficiency droop of the EDQE at high current densities is primarily due to an increase in the internal loss rather than a reduction in the internal efficiency. On the other hand, if the current density J is fixed, the temperature variation of the EDQE at that J is due primarily to a decrease of the internal efficiency. The gain versus current density is fit well by a logarithmic relationship, although the magnitude of the experimental gain is >20% below the theoretical estimate.

Interband cascade lasers with long lifetimes.

Narrow-ridge interband cascade lasers were subjected to accelerated aging. The aging curves were statistically evaluated by a log-normal distribution of the failure time, and by the mixed effects of the degradation parameters. Based on 10,000 h of output power trend data for lasers operating at 90°C and the maximum cw power, an unexpectedly long lifetime is predicted. The projected lifetimes range from about 500,000 h (57 years) for the linear degradation model to 183,000 h (21 years) for the exponential one.

Mid-infrared multi-mode absorption spectroscopy using interband cascade lasers for multi-species sensing.

An interband cascade laser (ICL) operating at 3.7 µm has been used to perform multimode absorption spectroscopy, MUMAS, at scan rates up to 10 kHz. Line widths of individual modes in the range 10-80 MHz were derived from isolated lines in the MUMAS signatures of HCl. MUMAS data for methane covering a spectral range of 30 nm yielded a detection level of 30 µbar·m for 1 s measurement time at 100 Hz. Simultaneous detection of methane, acetylene, and formaldehyde in a gas mixture containing all three species is reported.

Three species of Schrödinger cat states in an infinite-range spin model.

We explore a transverse-field Ising model that exhibits both spontaneous symmetry breaking and eigenstate thermalization. Within its ferromagnetic phase, the exact eigenstates of the Hamiltonian of any large but finite-sized system are all Schrödinger cat states: superpositions of states with "up" and "down" spontaneous magnetization. This model exhibits two dynamical phase transitions within its ferromagnetic phase: In the lowest-temperature phase the magnetization can macroscopically oscillate between up and down. The relaxation of the magnetization is always overdamped in the remainder of the ferromagnetic phase, which is divided into phases where the system thermally activates itself over the barrier between the up and down states, and where it quantum tunnels.

Water access points and hydration pathways in CLC H+/Cl- transporters.

CLC transporters catalyze transmembrane exchange of chloride for protons. Although a putative pathway for Cl(-) has been established, the pathway of H(+) translocation remains obscure. Through a highly concerted computational and experimental approach, we characterize microscopic details essential to understanding H(+)-translocation. An extended (0.4 µs) equilibrium molecular dynamics simulation of membrane-embedded, dimeric ClC-ec1, a CLC from Escherichia coli, reveals transient but frequent hydration of the central hydrophobic region by water molecules from the intracellular bulk phase via the interface between the two subunits. We characterize a portal region lined by E202, E203, and A404 as the main gateway for hydration. Supporting this mechanism, site-specific mutagenesis experiments show that ClC-ec1 ion transport rates decrease as the size of the portal residue at position 404 is increased. Beyond the portal, water wires form spontaneously and repeatedly to span the 15-Å hydrophobic region between the two known H(+) transport sites [E148 (Glu(ex)) and E203 (Glu(in))]. Our finding that the formation of these water wires requires the presence of Cl(-) explains the previously mystifying fact that Cl(-) occupancy correlates with the ability to transport protons. To further validate the idea that these water wires are central to the H(+) transport mechanism, we identified I109 as the residue that exhibits the greatest conformational coupling to water wire formation and experimentally tested the effects of mutating this residue. The results, by providing a detailed microscopic view of the dynamics of water wire formation and confirming the involvement of specific protein residues, offer a mechanism for the coupled transport of H(+) and Cl(-) ions in CLC transporters.

Dynamic response of model lipid membranes to ultrasonic radiation force.

Low-intensity ultrasound can modulate action potential firing in neurons in vitro and in vivo. It has been suggested that this effect is mediated by mechanical interactions of ultrasound with neural cell membranes. We investigated whether these proposed interactions could be reproduced for further study in a synthetic lipid bilayer system. We measured the response of protein-free model membranes to low-intensity ultrasound using electrophysiology and laser Doppler vibrometry. We find that ultrasonic radiation force causes oscillation and displacement of lipid membranes, resulting in small (<1%) changes in membrane area and capacitance. Under voltage-clamp, the changes in capacitance manifest as capacitive currents with an exponentially decaying sinusoidal time course. The membrane oscillation can be modeled as a fluid dynamic response to a step change in pressure caused by ultrasonic radiation force, which disrupts the balance of forces between bilayer tension and hydrostatic pressure. We also investigated the origin of the radiation force acting on the bilayer. Part of the radiation force results from the reflection of the ultrasound from the solution/air interface above the bilayer (an effect that is specific to our experimental configuration) but part appears to reflect a direct interaction of ultrasound with the bilayer, related to either acoustic streaming or scattering of sound by the bilayer. Based on these results, we conclude that synthetic lipid bilayers can be used to study the effects of ultrasound on cell membranes and membrane proteins.

Lithium in patients with amyotrophic lateral sclerosis (LiCALS): a phase 3 multicentre, randomised, double-blind, placebo-controlled trial.

BACKGROUND: Lithium has neuroprotective effects in cell and animal models of amyotrophic lateral sclerosis (ALS), and a small pilot study in patients with ALS showed a significant effect of lithium on survival. We aimed to assess whether lithium improves survival in patients with ALS. METHODS: The lithium carbonate in amyotrophic lateral sclerosis (LiCALS) trial is a randomised, double-blind, placebo-controlled trial of oral lithium taken daily for 18 months in patients with ALS. Patients aged at least 18 years who had ALS according to the revised El Escorial criteria, had disease duration between 6 and 36 months, and were taking riluzole were recruited from ten centres in the UK. Patients were randomly assigned (1:1) to receive either lithium or matched placebo tablets. Randomisation was via an online system done at the level of the individual by block randomisation with randomly varying block sizes, stratified by study centre and site of disease onset (limb or bulbar). All patients and assessing study personnel were masked to treatment assignment. The primary endpoint was the rate of survival at 18 months and was analysed by intention to treat. This study is registered with Eudract, number 2008-006891-31. FINDINGS: Between May 26, 2009, and Nov 10, 2011, 243 patients were screened, 214 of whom were randomly assigned to receive lithium (107 patients) or placebo (107 patients). Two patients discontinued treatment and one died before the target therapeutic lithium concentration could be achieved. 63 (59%) of 107 patients in the placebo group and 54 (50%) of 107 patients in the lithium group were alive at 18 months. The survival functions did not differ significantly between groups (Mantel-Cox log-rank χ(2) on 1 df=1·64; p=0·20). After adjusting for study centre and site of onset using logistic regression, the relative odds of survival at 18 months (lithium vs placebo) was 0·71 (95% CI 0·40-1·24). 56 patients in the placebo group and 61 in the lithium group had at least one serious adverse event. INTERPRETATION: We found no evidence of benefit of lithium on survival in patients with ALS, but nor were there safety concerns, which had been identified in previous studies with less conventional designs. This finding emphasises the importance of pursuing adequately powered trials with clear endpoints when testing new treatments. FUNDING: The Motor Neurone Disease Association of Great Britain and Northern Ireland.

A designed inhibitor of a CLC antiporter blocks function through a unique binding mode.

The lack of small-molecule inhibitors for anion-selective transporters and channels has impeded our understanding of the complex mechanisms that underlie ion passage. The ubiquitous CLC "Chloride Channel" family represents a unique target for biophysical and biochemical studies because its distinctive protein fold supports both passive chloride channels and secondary-active chloride-proton transporters. Here, we describe the synthesis and characterization of a specific small-molecule inhibitor directed against a CLC antiporter (ClC-ec1). This compound, 4,4'-octanamidostilbene-2,2'-disulfonate (OADS), inhibits ClC-ec1 with low micromolar affinity and has no specific effect on a CLC channel (ClC-1). Inhibition of ClC-ec1 occurs by binding to two distinct intracellular sites. The location of these sites and the lipid dependence of inhibition suggest potential mechanisms of action. This compound will empower research to elucidate differences between antiporter and channel mechanisms and to develop treatments for CLC-mediated disorders.

Biochemistry to the rescue: a ClC-2 auxiliary subunit provides a tangible link to leukodystrophy.

ClC-2 is a broadly distributed chloride channel with an enigmatic neurophysiological function. In this issue of Neuron, Jeworutzki et al. (2012) use a biochemical approach to identify GlialCAM, a protein with a defined link to leukodystrophy, as a ClC-2 auxiliary subunit.

Rebalancing of internally generated carriers for mid-infrared interband cascade lasers with very low power consumption.

The interband cascade laser differs from any other class of semiconductor laser, conventional or cascaded, in that most of the carriers producing population inversion are generated internally, at semimetallic interfaces within each stage of the active region. Here we present simulations demonstrating that all previous interband cascade laser performance has suffered from a significant imbalance of electron and hole densities in the active wells. We further confirm experimentally that correcting this imbalance with relatively heavy n-type doping in the electron injectors substantially reduces the threshold current and power densities relative to all earlier devices. At room temperature, the redesigned devices require nearly two orders of magnitude less input power to operate in continuous-wave mode than the quantum cascade laser. The interband cascade laser is consequently the most attractive option for gas sensing and other spectroscopic applications requiring low output power and minimum heat dissipation at wavelengths extending from 3 µm to beyond 6 µm.

Substrate-driven conformational changes in ClC-ec1 observed by fluorine NMR.

The CLC 'Cl(-) channel' family consists of both Cl(-)/H(+) antiporters and Cl(-) channels. Although CLC channels can undergo large, conformational changes involving cooperativity between the two protein subunits, it has been hypothesized that conformational changes in the antiporters may be limited to small movements localized near the Cl(-) permeation pathway. However, to date few studies have directly addressed this issue, and therefore little is known about the molecular movements that underlie CLC-mediated antiport. The crystal structure of the Escherichia coli antiporter ClC-ec1 provides an invaluable molecular framework, but this static picture alone cannot depict the protein movements that must occur during ion transport. In this study we use fluorine nuclear magnetic resonance (NMR) to monitor substrate-induced conformational changes in ClC-ec1. Using mutational analysis, we show that substrate-dependent (19)F spectral changes reflect functionally relevant protein movement occurring at the ClC-ec1 dimer interface. Our results show that conformational change in CLC antiporters is not restricted to the Cl(-) permeation pathway and show the usefulness of (19)F NMR for studying conformational changes in membrane proteins of known structure.

Hypertensive emergencies in children: identification and management of dangerously high blood pressure.

The prevalence of hypertension in the pediatric population is rising, coincident with the rise in childhood obesity worldwide. While most hypertensive children do not require emergent care, hypertensive urgencies and emergencies may be encountered in the outpatient clinic, the emergency department or the inpatient ward. To avoid the life-threatening complications associated with both hypertension and its treatment, the treating physician should be familiar with the presentation and management of pediatric hypertension. This review will serve to examine some of the important aspects of pediatric hypertensive urgencies and emergencies, including common causes, important features of diagnosis and options for medical management.