To send content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send content items to your Kindle, first ensure email@example.com
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
Sexual dysfunction occurs in 40%-60% of patients with major depressive disorder (MDD), due to either the illness itself and/or the effects of antidepressant treatment. The phase-2 CLARITY trial recently demonstrated the efficacy of adjunctive pimavanserin (PIM) for MDD when added to ongoing selective serotonin or serotonin–norepinephrine reuptake inhibitor (SSRI/SNRI) treatment. No new safety observations were reported in this study. This post-hoc analysis examines the potential impact of PIM treatment on sexual function.
Study methodology has been presented previously (APA 2019). Adult male and female patients with moderate-to-severe MDD were randomized to PIM 34 mg/day (n=51) or placebo (PBO, n=152) added to ongoing SSRI/SNRI treatment. Massachusetts General Hospital–Sexual Functioning Inventory (MGH-SFI) and Hamilton Depression Rating Scale, 17-item version (HAMD-17) item 14 (sexual interest) scores were examined by analysis of covariance.
Adjunctive PIM resulted in significantly greater 5-week reduction (improvement) relative to SSRI/SNRI treatment plus placebo on mean MGH-SFI scores (difference –0.634, SE 0.167; P<0.001; effect size [ES], Cohen’s d 0.614). Similarly, PIM resulted in greater improvement compared with placebo on individual MGH-SFI items that applied to both males and females: Interest in Sex (P=0.006; ES=0.483), Ability to Get Sexually Aroused/Excited (P=0.001; ES=0.560), Ability to Achieve Orgasm (P<0.001; ES=0.609), Overall Sexual Satisfaction (P=0.003; ES=0.524). HAMD-17 item 14 scores were also significantly more reduced (improved) with PIM (P<0.001; ES=0.574).
These results underscore the potential of adjunctive PIM for improving sexual function in patients with MDD and inadequate response to SSRIs/SNRIs. Potential benefits should be confirmed in further studies.
Depression is the leading cause of disability worldwide, with fewer than 50% of treated patients achieving full remission. This study (“CLARITY,” ACP-103-042: NCT03018340) examined the 5-HT2A inverse agonist pimavanserin (PIM) as a potential adjunctive treatment for major depressive disorder (MDD).
Adult female and male subjects with a DSM-5 primary diagnosis of a major depressive episode as part of MDD, inadequate response to ongoing SSRIs or SNRIs of adequate dose and duration as confirmed by the Massachusetts General Hospital Antidepressant Treatment History Questionnaire, and a MADRS total score >20 were randomized to PIM 34 mg/day or placebo (PBO) added to their SSRI/SNRI treatment. A sequential parallel comparison design was used, consisting of two 5-week stages. PBO nonresponders in Stage-1 who met prespecified criteria were re-randomized to PIM or PBO for the second period (Stage-2). The primary efficacy measure was the weighted average of Stage-1 and Stage-2 total scores of the HAMD-17.
Of the 207 patients enrolled, 52 received PIM, and 155 received PBO in Stage 1. Mean age was 46.2 years, and 72.9% of patients were female. Baseline MADRS total (mean [SD]: 31.5 [0.4]) and HAMD-17 total scores (22.2 [0.3]) indicated a moderate overall severity of illness. PIM met the primary endpoint, reducing the weighted Stage-1/Stage-2 HAMD-17 total score relative to PBO (least-square means [LSM] difference, –1.7; standard error [SE], 0.9; P=0.04). Stage-1 PIM patients demonstrated highly significant 5-week improvement on the HAMD-17 (LSM difference=–4.0, SE=1.1; P<0.001; effect size, Cohen’s d: 0.626), separating from placebo by the end of Week 1 (LSM difference=–1.7, SE=0.8; P=0.04). Stage-2 results showed no significant separation among Stage-1 placebo nonresponders (P=0.69). In Stage 2, a substantively smaller number of subjects (n=58) were rerandomized than planned, likely due to restrictive criteria for re-randomization. Greater overall improvement was seen with PIM relative to PBO on the key secondary endpoint, the Sheehan Disability Scale (LSM difference=–0.8, SE=0.3; P=0.004), and positive results were also seen on 7 of the 11 other secondary endpoints, including responder rate (≥50% reduction in HAMD-17 total; P=0.007), Massachusetts General Hospital Sexual Functioning Index (P<0.001), and Karolinska Sleepiness Scale for daytime sleepiness (P=0.02). Discontinuations due to adverse events were low (PIM 1.2%, PBO 3.2%). One serious adverse event was reported in each treatment group, deemed unrelated to treatment. No deaths were reported. Laboratory assessments, electrocardiography, and changes in vital signs were unremarkable, and no new safety signals were reported.
Study data provide evidence of the efficacy, safety, and tolerability of adjunctive PIM in treating MDD inadequately responsive to SSRI or SNRI therapy. Efforts to confirm these results are ongoing in a Phase 3 program.
Contact guidance is vital to many physiological processes, yet is still poorly understood. This is partly due to the variability of experimental platforms, making comparisons difficult. To combat this, a multiplexed approach was used to fabricate topographical cues on single quartz coverslips for high-throughput screening. Furthermore, this method offers control of surface roughness and protein adsorption characterization, two critical aspects to the in vitro environment often overlooked in contact guidance platforms. The quartz surface can be regenerated, is compatible with versatile microscopy modes, and can scale up for manufacturing offering a novel platform that could serve as a potential standard assay.
A primary barrier to translation of clinical research discoveries into care delivery and population health is the lack of sustainable infrastructure bringing researchers, policymakers, practitioners, and communities together to reduce silos in knowledge and action. As National Institutes of Healthʼs (NIH) mechanism to advance translational research, Clinical and Translational Science Award (CTSA) awardees are uniquely positioned to bridge this gap. Delivering on this promise requires sustained collaboration and alignment between research institutions and public health and healthcare programs and services. We describe the collaboration of seven CTSA hubs with city, county, and state healthcare and public health organizations striving to realize this vision together. Partnership representatives convened monthly to identify key components, common and unique themes, and barriers in academic–public collaborations. All partnerships aligned the activities of the CTSA programs with the needs of the city/county/state partners, by sharing resources, responding to real-time policy questions and training needs, promoting best practices, and advancing community-engaged research, and dissemination and implementation science to narrow the knowledge-to-practice gap. Barriers included competing priorities, differing timelines, bureaucratic hurdles, and unstable funding. Academic–public health/health system partnerships represent a unique and underutilized model with potential to enhance community and population health.
This article presents a brief review of our case studies of data-driven Integrated Computational Materials Engineering (ICME) for intelligently discovering advanced structural metal materials, including light-weight materials (Ti, Mg, and Al alloys), refractory high-entropy alloys, and superalloys. The basic bonding in terms of topology and electronic structures is recommended to be considered as the building blocks/units constructing the microstructures of advanced materials. It is highlighted that the bonding charge density could not only provide an atomic and electronic insight into the physical nature of chemical bond of materials but also reveal the fundamental strengthening/embrittlement mechanisms and the local phase transformations of planar defects, paving a path in accelerating the development of advanced metal materials via interfacial engineering. Perspectives on the knowledge-based modeling/simulations, machine-learning knowledge base, platform, and next-generation workforce for sustainable ecosystem of ICME are highlighted, thus to call for more duty on the developments of advanced structural metal materials and enhancement of research productivity and collaboration.
Diagnosis, treatment, and prevention of vector-borne disease (VBD) in pets is one cornerstone of companion animal practices. Veterinarians are facing new challenges associated with the emergence, reemergence, and rising incidence of VBD, including heartworm disease, Lyme disease, anaplasmosis, and ehrlichiosis. Increases in the observed prevalence of these diseases have been attributed to a multitude of factors, including diagnostic tests with improved sensitivity, expanded annual testing practices, climatologic and ecological changes enhancing vector survival and expansion, emergence or recognition of novel pathogens, and increased movement of pets as travel companions. Veterinarians have the additional responsibility of providing information about zoonotic pathogen transmission from pets, especially to vulnerable human populations: the immunocompromised, children, and the elderly. Hindering efforts to protect pets and people is the dynamic and ever-changing nature of VBD prevalence and distribution. To address this deficit in understanding, the Companion Animal Parasite Council (CAPC) began efforts to annually forecast VBD prevalence in 2011. These forecasts provide veterinarians and pet owners with expected disease prevalence in advance of potential changes. This review summarizes the fidelity of VBD forecasts and illustrates the practical use of CAPC pathogen prevalence maps and forecast data in the practice of veterinary medicine and client education.
When Hurricane Harvey landed along the Texas coast on August 25, 2017, it caused massive flooding and damage and displaced tens of thousands of residents of Harris County, Texas. Between August 29 and September 23, Harris County, along with community partners, operated a megashelter at NRG Center, which housed 3365 residents at its peak. Harris County Public Health conducted comprehensive public health surveillance and response at NRG, which comprised disease identification through daily medical record reviews, nightly “cot-to-cot” resident health surveys, and epidemiological consultations; messaging and communications; and implementation of control measures including stringent isolation and hygiene practices, vaccinations, and treatment. Despite the lengthy operation at the densely populated shelter, an early seasonal influenza A (H3) outbreak of 20 cases was quickly identified and confined. Influenza outbreaks in large evacuation shelters after a disaster pose a significant threat to populations already experiencing severe stressors. A holistic surveillance and response model, which consists of coordinated partnerships with onsite agencies, in-time epidemiological consultations, predesigned survey tools, trained staff, enhanced isolation and hygiene practices, and sufficient vaccines, is essential for effective disease identification and control. The lessons learned and successes achieved from this outbreak may serve for future disaster response settings. (Disaster Med Public Health Preparedness. 2019;13:97-101)
While more and more long-period giant planets are discovered by direct imaging, the distribution of planets at these separations (≳5 AU) has remained largely uncertain, especially compared to planets in the inner regions of solar systems probed by RV and transit techniques. The low frequency, the detection challenges, and heterogeneous samples make determining the mass and orbit distributions of directly imaged planets at the end of a survey difficult. By utilizing Monte Carlo methods that incorporate the age, distance, and spectral type of each target, we can use all stars in the survey, not just those with detected planets, to learn about the underlying population. We have produced upper limits and direct measurements of the frequency of these planets with the most recent generation of direct imaging surveys. The Gemini NICI Planet-Finding Campaign observed 220 young, nearby stars at a median H-band contrast of 14.5 magnitudes at 1”, representing the largest, deepest search for exoplanets by the completion of the survey. The Gemini Planet Imager Exoplanet Survey is in the process of surveying 600 stars, pushing these contrasts to a few tenths of an arcsecond from the star. With the advent of large surveys (many hundreds of stars) using advanced planet-imagers we gain the ability to move beyond measuring the frequency of wide-separation giant planets and to simultaneously determine the distribution as a function of planet mass, semi-major axis, and stellar mass, and so directly test models of planet formation and evolution.
We have discovered that 2MASS 08355977-3042306 is an accreting K7, double-lined, spectroscopic binary younger than ~20 Myr. The age of a dispersed young star can best be determined if it is a member of a known young moving group. However, the three dimensional space velocities (UVW) we calculate using radial velocity measurements, proper motions, and plausible photometric distances make membership in any known young moving group unlikely.
In recent years, all-sky surveys have uncovered a new and interesting population of young (≈10–200 Myr), nearby substellar objects. Many of these objects have inferred masses and temperatures that overlap those of directly imaged exoplanets. These young brown dwarfs provide valuable analogs to young, dusty exoplanets in a context where detailed spectroscopic observations across a broad range of wavelengths and at high S/N are possible. How do the temperatures inferred by atmospheric models and evolutionary models compare? Can we determine the formation mechanism of a young planetary-mass object? How well do we understand the role that disequilibrium chemistry and dust clouds play in the atmospheres of these objects? We review the successes and challenges in determining the fundamental properties (mass, log(g), effective temperature) of young substellar objects, both brown dwarfs and gas-giant exoplanets.
I present a highly biased and skewed summary of IAU Symposium 314, “Young Stars and Planets Near the Sun,” held in May 2015. This summary includes some takeaway thoughts about the rapidly evolving state of the field, as well as some crowd-sourced predictions for progress over the next ~10 years. We predict the elimination of 1–2 of the currently recognized young moving groups, the addition of 3 or more new moving groups within 100 pc, the continued lack of a predictive theory of stellar mass, robust measurements of the gas and dust content of circumstellar disks, and an ongoing struggle to achieve a consensus definition for a planet.
Young moving groups (YMGs) are coeval, comoving groups of stars which have migrated from their birthsites after formation. In the substellar regime, YMG members are key benchmarks to empirically define brown dwarf evolution with age and to study the lowest mass end of the initial mass function. We have combined Pan-STARRS1 (PS1) proper motions with optical+IR photometry from PS1, 2MASS and WISE to perform a large-scale (≈30,000 deg2) systematic search for substellar members down to ≈10 MJup. We have obtained near-IR spectroscopy of a large sample of ultracool candidate YMG members to assess their youth via gravity-sensitive absorption features. We have identified several new intermediate-gravity candidate members of the AB Dor Moving Group, potentially greatly expanding the substellar membership. These new candidate members bridge the gap between the known low-mass stellar and planetary-mass members and yield valuable insight into the spectral characteristics of young brown dwarfs.
The purpose of this study was to describe the longitudinal trajectories and bidirectional relationships of the physical-social and emotional functioning (EF) dimensions of positive aging and to identify their baseline characteristics.
Women age 65 and older who enrolled in one or more Women's Health Initiative clinical trials (WHI CTs) and who had positive aging indicators measured at baseline and years 1, 3, 6, and 9 were included in these analyses (N = 2281). Analytic strategies included latent class growth modeling to identify longitudinal trajectories and multinomial logistic regression to examine the effects of baseline predictors on these trajectories.
A five-trajectory model was chosen to best represent the data. For Physical-Social Functioning (PSF), trajectory groups included Low Maintainer (8.3%), Mid-Low Improver (10.4%), Medium Decliner (10.7%), Mid-High Maintainer (31.2%), and High Maintainer (39.4%); for EF, trajectories included Low Maintainer (3%), Mid-Low Improver (9%), Medium Decliner (7.7%), Mid-High Maintainer (22.8%), and High Maintainer (57.5%). Cross-classification of the groups of trajectories demonstrated that the impact of a high and stable EF on PSF might be greater than the reverse. Low depression symptoms, low pain, and high social support were the most consistent predictors of high EF trajectories.
Aging women are heterogeneous in terms of positive aging indicators for up to 9 years of follow-up. Interventions aimed at promoting sustainable EF might have diffused effects on other domains of healthy aging.
Conversion of biomass to electricity is often not economically feasible as a result of large transportation costs and low output prices. We build a model of an adaptable biorefinery situated at an agri-processing facility that already has biomass on-site and consider the optimal scale of the plant to achieve a price premium by selling peaking power given uncertain biomass deliveries year over year as a result of climatic variability. We find that, for conservative electricity prices, a plant situated near cotton gins in Texas could operate with positive expected net revenue while converting on average only 38% of available biomass for peak electricity prices.
Scanning acoustic microscopy (SAM), when applied to biological samples has the potential to resolve the longitudinal acoustic wave speed and hence stiffness of discrete tissue components. The heterogeneity of biological materials combined with the action of cryosectioning and rehydrating can, however, create variations in section topography. Here, we set out to determine how variations in specimen thickness influence apparent acoustic wave speed measurements
Cryosections (5μm nominal thickness) of human skin biopsies were adhered to glass slides before washing and rehydrating in water. Multiple regions (200x200 μm; n = 3) were imaged by SAM to generate acoustic wave speed maps. Subsequently co-localised 30x30 μm sub-regions were imaged by atomic force microscopy (AFM) in fluid. The images were then registered using Image J. Each pixel was allocated both a height and wave speed value before their relationship was then plotted on a scattergram. The mean section thickness measured by AFM was 3.48 ± 1.12 (SD) μm. Regional height variations influenced apparent wave speed measurements. A 3.5 μm height difference was associated with a 400 ms-1 increase in wave speed. In the present study we show that local variations in specimen thickness influence apparent wave speed. We also show that a true measure of wave speed can be calculated if the thickness of the specimen is known at each sampling point.
We have carried out high contrast imaging of 70 young, nearby B and A stars to search for brown dwarf and planetary companions as part of the Gemini NICI Planet-Finding Campaign. Our survey represents the largest, deepest survey for planets around high-mass stars (≈1.5–2.5 M⊙) conducted to date and includes the planet hosts β Pic and Fomalhaut. Despite detecting two new brown dwarfs, our observations did not detect new planets around our target stars, and we present upper limits on the fraction of high-mass stars that can host giant planets that are consistent with our null result.