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The National Cryo-Electron Microscopy Facility (NCEF) at the National Cancer Institute was launched in May of 2017 to provide free and rapid access to high-resolution cryo-EM data collection to United States researchers working on problems of broad general relevance to cancer biology. The decision about suitability of projects for data collection is made on a first-come, first-served basis by NCEF staff and is based solely on the quality of the screening images provided, without need for a scientific proposal. Here we provide an overview of the operation of the facility, typical data collection procedures, and some insights that have emerged from the structures reported from data collected at the facility.
We report on the successful demonstration of a 150 J nanosecond pulsed cryogenic gas cooled, diode-pumped multi-slab Yb:YAG laser operating at 1 Hz. To the best of our knowledge, this is the highest energy ever recorded for a diode-pumped laser system.
A national need is to prepare for and respond to accidental or intentional disasters categorized as chemical, biological, radiological, nuclear, or explosive (CBRNE). These incidents require specific subject-matter expertise, yet have commonalities. We identify 7 core elements comprising CBRNE science that require integration for effective preparedness planning and public health and medical response and recovery. These core elements are (1) basic and clinical sciences, (2) modeling and systems management, (3) planning, (4) response and incident management, (5) recovery and resilience, (6) lessons learned, and (7) continuous improvement. A key feature is the ability of relevant subject matter experts to integrate information into response operations. We propose the CBRNE medical operations science support expert as a professional who (1) understands that CBRNE incidents require an integrated systems approach, (2) understands the key functions and contributions of CBRNE science practitioners, (3) helps direct strategic and tactical CBRNE planning and responses through first-hand experience, and (4) provides advice to senior decision-makers managing response activities. Recognition of both CBRNE science as a distinct competency and the establishment of the CBRNE medical operations science support expert informs the public of the enormous progress made, broadcasts opportunities for new talent, and enhances the sophistication and analytic expertise of senior managers planning for and responding to CBRNE incidents.
Dust vortices with a void at the centre are reported in this paper. The role of the spatial variation of the plasma potential in the rotation of dust particles is studied in a parallel plate glow discharge plasma. Probe measurements reveal the existence of a local potential minimum in the region of formation of the dust vortex. The minimum in the potential well attracts positively charged ions, while it repels the negatively charged dust particles. Dust rotation is caused by the interplay of the two oppositely directed ion drag and Coulomb forces. The balance between these two forces is found to play a major role in the radial confinement of the dust particles above the cathode surface. Evolution of the dust vortex is studied by increasing the discharge current from 15 to 20 mA. The local minimum of the potential profile is found to coincide with the location of the dust vortex for both values of discharge currents. Additionally, it is found that the size of the dust vortex as well as the void at the centre increases with the discharge current.
Movement disorders associated with exposure to antipsychotic drugs are common and stigmatising but underdiagnosed.
To develop and evaluate a new clinical procedure, the ScanMove instrument, for the screening of antipsychotic-associated movement disorders for use by mental health nurses.
Item selection and content validity assessment for the ScanMove instrument were conducted by a panel of neurologists, psychiatrists and a mental health nurse, who operationalised a 31-item screening procedure. Interrater reliability was measured on ratings for 30 patients with psychosis from ten mental health nurses evaluating video recordings of the procedure. Criterion and concurrent validity were tested comparing the ScanMove instrument-based rating of 13 mental health nurses for 635 community patients from mental health services with diagnostic judgement of a movement disorder neurologist based on the ScanMove instrument and a reference procedure comprising a selection of commonly used rating scales.
Interreliability analysis showed no systematic difference between raters in their prediction of any antipsychotic-associated movement disorders category. On criterion validity testing, the ScanMove instrument showed good sensitivity for parkinsonism (90%) and hyperkinesia (89%), but not for akathisia (38%), whereas specificity was low for parkinsonism and hyperkinesia, and moderate for akathisia.
The ScanMove instrument demonstrated good feasibility and interrater reliability, and acceptable sensitivity as a mental health nurse-administered screening tool for parkinsonism and hyperkinesia.
During the Third Reich, alcohol served as both a literal and metaphorical lubricant for acts of violence and atrocity by the men of the Sturmabteilung (SA), the Schutzstaffel (SS), and the police. Scholars have extensively documented its use and abuse on the part of the perpetrators. For the SA, the SS, and the police, the consumption of alcohol was part of a ritual that not only bound the perpetrators together, but also became a facilitator of acts of “performative masculinity”—a type of masculinity expressly linked to physical or sexual violence. In many respects, the relationship among alcohol, masculinity, sex, and violence permeated all aspects of the Nazi killing process in the camps, the ghettos, and the killing fields. After the outbreak of war in September 1939, such practices were increasingly radicalized, with drinking and celebratory rituals becoming key elements for these closed male communities of perpetrators, who used them to prepare for acts of mass killing and, ultimately, genocide.
Glyphosate-resistant (GR) Italian ryegrass is one of the most troublesome weeds in Mississippi row crop production. Fall-applied residual herbicide applications are recommended for control of GR Italian ryegrass. However, carryover of residual herbicides applied in fields for rice production can have a negative impact on rice performance. Field studies were conducted in Stoneville, MS, to determine the effects of fall-applied residual herbicides on rice growth and yield. Herbicide treatments included suggested use rates (1×) of clomazone at 840 g ai ha–1, pyroxasulfone 170 g ai ha–1, S-metolachlor 1,420 g ai ha–1, and trifluralin 1,680 g ai ha–1, and two times (2×) the suggested use rates in the fall before rice seeding. Pooled across application rate, pyroxasulfone, S-metolachlor, and trifluralin injured rice to an extent 28% to 36% greater than clomazone 14 d after emergence (DAE). Rice seedling density and height 14 DAE and rice maturity were negatively affected by all fall-applied herbicides except clomazone. Applications at 2× rates reduced rough rice yields in plots treated with pyroxasulfone, S-metolachlor, and trifluralin compared with clomazone. Pyroxasulfone applied at the 2× rate reduced rough rice yield 22% compared with the 1× rate. Rough rice yield was 90% or greater of the nontreated control in plots treated with either rate of S-metolachlor, and these were comparable with rough rice yields from plots treated with both rates of trifluralin and the 1× rate of pyroxasulfone. Early-season injury and reductions in seedling density and height 14 DAE, would preclude even 1× applications of pyroxasulfone, S-metolachlor, and trifluralin from being viable options for residual herbicide treatments targeting GR Italian ryegrass in the fall before rice seeding. Of the herbicides evaluated, only clomazone should be utilized as a fall-applied residual herbicide treatment targeting GR Italian ryegrass before seeding rice.
In 785 mother–child (50% male) pairs from a longitudinal epidemiological birth cohort, we investigated associations between inflammation-related epigenetic polygenic risk scores (i-ePGS), environmental exposures, cognitive function, and child and adolescent internalizing and externalizing problems. We examined prenatal and postnatal effects. For externalizing problems, one prenatal effect was found: i-ePGS at birth associated with higher externalizing problems (ages 7–15) indirectly through lower cognitive function (age 7). For internalizing problems, we identified two effects. For a prenatal effect, i-ePGS at birth associated with higher internalizing symptoms via continuity in i-ePGS at age 7. For a postnatal effect, higher postnatal adversity exposure (birth through age 7) associated with higher internalizing problems (ages 7–15) via higher i-ePGS (age 7). Hence, externalizing problems were related mainly to prenatal effects involving lower cognitive function, whereas internalizing problems appeared related to both prenatal and postnatal effects. The present study supports a link between i-ePGS and child and adolescent mental health.
We examine the influence of outside directors’ industry experience on segment investment, segment operating performance, and firm valuation for conglomerates. Given board composition is endogenous, we instrument for the presence of industry expert directors using the supply of experienced executives near conglomerate firms’ headquarters. We find that industry expert representation on the board causes increased segment investment. Consistent with experienced directors playing favorites rather than acting as dispassionate advisors, segment profitability (firm value) is lower for segments (firms) with industry expert outside directors. We do not find analogous negative profitability or valuation effects of director experience for single-segment firms.
Insomnia and depression are highly comorbid and mutually exacerbate clinical trajectories and outcomes. Cognitive behavioral therapy for insomnia (CBT-I) effectively reduces both insomnia and depression severity, and can be delivered digitally. This could substantially increase the accessibility to CBT-I, which could reduce the health disparities related to insomnia; however, the efficacy of digital CBT-I (dCBT-I) across a range of demographic groups has not yet been adequately examined. This randomized placebo-controlled trial examined the efficacy of dCBT-I in reducing both insomnia and depression across a wide range of demographic groups.
Of 1358 individuals with insomnia randomized, a final sample of 358 were retained in the dCBT-I condition and 300 in the online sleep education condition. Severity of insomnia and depression was examined as a dependent variable. Race, socioeconomic status (SES; household income and education), gender, and age were also tested as independent moderators of treatment effects.
The dCBT-I condition yielded greater reductions in both insomnia and depression severity than sleep education, with significantly higher rates of remission following treatment. Demographic variables (i.e. income, race, sex, age, education) were not significant moderators of the treatment effects, suggesting that dCBT-I is comparably efficacious across a wide range of demographic groups. Furthermore, while differences in attrition were found based on SES, attrition did not differ between white and black participants.
Results provide evidence that the wide dissemination of dCBT-I may effectively target both insomnia and comorbid depression across a wide spectrum of the population.
Little is known about terrestrial climate dynamics in the Levant during the penultimate interglacial-glacial period. To decipher the palaeoclimatic history of the Marine Oxygen Isotope Stage (MIS) 6 glacial period, a well-dated stalagmite (~194 to ~154 ka) from Kanaan Cave on the Mediterranean coast in Lebanon was analyzed for its petrography, growth history, and stable isotope geochemistry. A resolved climate record has been recovered from this precisely U–Th dated speleothem, spanning the late MIS 7 and early MIS 6 at low resolution and the mid–MIS 6 at higher resolution. The stalagmite grew discontinuously from ~194 to ~163 ka. More consistent growth and higher growth rates between ~163 and ~154 ka are most probably linked to increased water recharge and thus more humid conditions. More distinct layering in the upper part of the speleothem suggests strong seasonality from ~163 ka to ~154 ka. Short-term oxygen and carbon isotope excursions were found between ~155 and ~163 ka. The inferred Kanaan Cave humid intervals during the mid–MIS 6 follow variations of pollen records in the Mediterranean basins and correlate well with the synthetic Greenland record and East Asian summer monsoon interstadial periods, indicating short warm/wet periods similar to the Dansgaard-Oeschger events during MIS 4–3 in the eastern Mediterranean region.
Attention-deficit hyperactivity disorder (ADHD) shows clear, albeit heterogeneous, cognitive dysfunctions. However, personality traits are not well understood in adults with ADHD, and it is unclear whether they are predisposing factors or phenotypical facets of the condition.
To assess whether personality traits of impulsivity, sensation seeking and sensitivity to punishment and reward are predisposing factors for ADHD or aspects of the clinical phenotype.
Twenty adults with ADHD, 20 unaffected first-degree relatives and 20 controls completed rating scales assessing traits of impulsivity, sensation seeking and sensitivity to punishment/reward.
Compared with relatives and controls, individuals with ADHD showed increased impulsive personality traits, were more susceptible to boredom and presented hypersensitivity to reward but normal sensitivity to punishment.
High impulsivity traits, heightened sensitivity to reward and boredom are associated with the phenotype of ADHD, rather than being predisposing factors, as these traits were not shared between ADHD probands and their relatives.
Depression is a prevalent long-term condition that is associated with substantial resource use. Telehealth may offer a cost-effective means of supporting the management of people with depression.
To investigate the cost-effectiveness of a telehealth intervention (‘Healthlines’) for patients with depression.
A prospective patient-level economic evaluation conducted alongside a randomised controlled trial. Patients were recruited through primary care, and the intervention was delivered via a telehealth service. Participants with a confirmed diagnosis of depression and PHQ-9 score ≥10 were recruited from 43 English general practices. A series of up to 10 scripted, theory-led, telephone encounters with health information advisers supported participants to effect a behaviour change, use online resources, optimise medication and improve adherence. The intervention was delivered alongside usual care and was designed to support rather than duplicate primary care. Cost-effectiveness from a combined health and social care perspective was measured by net monetary benefit at the end of 12 months of follow-up, calculated from incremental cost and incremental quality-adjusted life years (QALYs). Cost–consequence analysis included cost of lost productivity, participant out-of-pocket expenditure and the clinical outcome.
A total of 609 participants were randomised – 307 to receive the Healthlines intervention plus usual care and 302 to receive usual care alone. Forty-five per cent of participants had missing quality of life data, 41% had missing cost data and 51% of participants had missing data on either cost or utility, or both. Multiple imputation was used for the base-case analysis. The intervention was associated with incremental mean per-patient National Health Service/personal social services cost of £168 (95% CI £43 to £294) and an incremental QALY gain of 0.001 (95% CI −0.023 to 0.026). The incremental cost-effectiveness ratio was £132 630. Net monetary benefit at a cost-effectiveness threshold of £20 000 was –£143 (95% CI –£164 to –£122) and the probability of the intervention being cost-effective at this threshold value was 0.30. Productivity costs were higher in the intervention arm, but out-of-pocket expenses were lower.
The Healthlines service was acceptable to patients as a means of condition management, and response to treatment after 4 months was higher for participants randomised to the intervention. However, the positive average intervention effect size was modest, and incremental costs were high relative to a small incremental QALY gain at 12 months. The intervention is not likely to be cost-effective in its current form.