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Conventional alloy design based on a single primary element has reached its limits in terms of performance optimization. An alloy design strategy with multi-principal elements has recently been uncovered to overcome this bottleneck. Multicomponent alloys, generally referred to as high-entropy alloys (HEAs), exhibit many promising properties, especially outstanding mechanical performance at cryogenic, ambient, and elevated temperatures. In this article, we focus on precipitation-hardened HEAs, which are potential candidates for next-generation structural materials, especially at high temperatures. The key issues involved include precipitation behaviors, phase stability, and phase control, all of which provide useful guidelines for further development of high-temperature materials with superior performance. In particular, we address the formation of cellular γ′ precipitates at grain boundaries, which is closely related to the embrittlement of HEAs at intermediate temperatures. Critical issues and design strategies in developing HEAs for high-temperature applications are also discussed.
Item 9 of the Patient Health Questionnaire-9 (PHQ-9) queries about thoughts of death and self-harm, but not suicidality. Although it is sometimes used to assess suicide risk, most positive responses are not associated with suicidality. The PHQ-8, which omits Item 9, is thus increasingly used in research. We assessed equivalency of total score correlations and the diagnostic accuracy to detect major depression of the PHQ-8 and PHQ-9.
We conducted an individual patient data meta-analysis. We fit bivariate random-effects models to assess diagnostic accuracy.
16 742 participants (2097 major depression cases) from 54 studies were included. The correlation between PHQ-8 and PHQ-9 scores was 0.996 (95% confidence interval 0.996 to 0.996). The standard cutoff score of 10 for the PHQ-9 maximized sensitivity + specificity for the PHQ-8 among studies that used a semi-structured diagnostic interview reference standard (N = 27). At cutoff 10, the PHQ-8 was less sensitive by 0.02 (−0.06 to 0.00) and more specific by 0.01 (0.00 to 0.01) among those studies (N = 27), with similar results for studies that used other types of interviews (N = 27). For all 54 primary studies combined, across all cutoffs, the PHQ-8 was less sensitive than the PHQ-9 by 0.00 to 0.05 (0.03 at cutoff 10), and specificity was within 0.01 for all cutoffs (0.00 to 0.01).
PHQ-8 and PHQ-9 total scores were similar. Sensitivity may be minimally reduced with the PHQ-8, but specificity is similar.
Micronutrient supplementation is recommended in Ebola Virus Disease (EVD). However, there is limited data on its therapeutic impacts. This study evaluated the association between vitamin A supplementation and mortality outcomes in EVD patients.
This retrospective cohort study accrued patients with EVD admitted to five International Medical Corps run Ebola Treatment Units (ETU) in two countries from 2014-2015. Protocolized treatments with antimicrobials and micronutrients were used at all ETUs. However, due to resource limitations and care variations, only a subset of patients received vitamin A. Standardized data on demographics, clinical characteristics, malaria status, and Ebola virus RT-PCR cycle threshold (CT) values were collected. The outcome of interest was mortality compared between cases treated with 200,000 International Units of vitamin A on care days one and two and those not. Propensity scores (PS) based on the first 48-hours of care were derived using the covariates of age, duration of ETU function, malaria status, CT values, symptoms of confusion, hemorrhage, diarrhea, dysphagia, and dyspnea. Treated and non-treated cases were matched 1:1 based on nearest neighbors with replacement. Covariate balance met predefined thresholds. Mortality proportions between cases treated and untreated with vitamin A were compared using generalized estimating equations to calculate relative risks (RR) with associated 95% confidence intervals (CI).
There were 424 cases analyzed, with 330 (77.8%) being vitamin A-treated cases. The mean age was 30.5 years and 57.0% were female. The most common symptoms were diarrhea (86%), anorexia (81%), and vomiting (77%). Mortality proportions among cases untreated and treated with vitamin A were 71.9% and 55.0%, respectively. In a propensity-matched analysis, mortality was significantly lower among cases receiving vitamin A (RR = 0.77 95%; CI:0.59-0.99; p = 0.041).
Early vitamin A supplementation was associated with reduced mortality in EVD patients and should be provided routinely during future epidemics.
Information about the ice volume stored in glaciers is of high importance for sustainable water management in many arid regions of Central Asia. Several methods to estimate the ice volume exist. However, none of them take the specific characteristics of flat terminus debris-covered glaciers into account. We present a method for deriving spatially-distributed ice thickness for debris-covered dendritic glaciers, which are common not only in Central Tien Shan but also in several other mountain ranges in High Asia. The method relies on automatically generated branch lines, observed surface velocities and surface topographic parameters as basic input. Branch lines were generated using Thiessen polygons and Dijkstra's path algorithm. Ice thicknesses for four debris-covered glaciers – South Inylchek, Kaindy, Tomur and Koxkar glaciers – have been estimated along the branch line network solving the equation of laminar flow. For Koxkar and South Inylchek glaciers, respectively, maximum thicknesses of ~250 and 380 m were estimated. These results differ by ~50 m compared with GPR measurements with an uncertainty for the debris-covered parts of ~40%. Based on geodetic mass balances, we estimate that the investigated glaciers lost between 6 and 28% of their volume from 1975 to the early 2000s.
Switching antipsychotic medications is common in patients with schizophrenia who are experiencing persistent symptoms or tolerability issues associated with their current drug regimen. This analysis assessed the safety of switching from an oral antipsychotic to the long-acting injectable antipsychotic aripiprazole lauroxil (AL).
This was a post hoc analysis of outpatients with schizophrenia who were prescribed an oral antipsychotic and who enrolled in an international, open-label, long-term (52-week) safety study of AL. The analysis focused on the first 3 injections of AL 882 mg over 12 weeks, divided into the immediate 4-week crossover period between the first and second AL injections (initiation phase) and the subsequent 8 weeks (stabilization phase). Patients were grouped by preswitch oral antipsychotic medication, and safety and clinical symptoms were assessed.
In total, 190 patients had switched from one of the following oral antipsychotic medications: aripiprazole, conventional antipsychotics, risperidone/paliperidone, olanzapine, or quetiapine. The 12-week completion rate was high (92.1%) and similar across the different preswitch oral antipsychotic groups. Overall, adverse event (AE) rates experienced over 12 weeks were modest; no AEs were considered serious. The most common AEs in the initiation phase were injection site pain (5.8%), insomnia (5.8%), and akathisia (3.2%). No apparent relationship was observed between preswitch medication and early-onset AEs. Mean Positive and Negative Syndrome Scale total scores remained stable during this period across preswitch antipsychotic groups.
Switching from an oral antipsychotic to AL was feasible in an outpatient setting for patients with schizophrenia, and the 12-week retention rate was favorable.
Typical electron transport (2,2′,2″-(1,3,5-benzinetriyl)-tris(1-phenyl-1-H-benzimidazole) (TPBi)) and injection (Cs2CO3) materials are successfully replaced by zirconium tetrakis(8-hydroxyquinolinolate) (Zrq4) and lithium 2-((o-tolylimino)methyl)-phenolate (EI-111) in simplified OLED (organic light-emitting diodes) processed by organic vapor phase deposition (OVPD). The performance of combining Zrq4 and EI-111 is analyzed in unipolar devices and compared to devices with configurations of Zrq4/Cs2CO3, TPBi/EI-111 and TPBi/Cs2CO3. Current density-voltage (J-V) measurements are performed and correlated to different carrier injection and transport properties. The investigated material combinations are implemented in the simplified OLED structures and compared to each other. To account for the high HOMO level of Zrq4, 5 nm of TPBi are added to confine holes and excitons in the emissive layer (EML) and to improve device performance. After tailoring the organic stack for OLED with Zrq4, a remarkable boost in device efficiency is observed. The luminous efficacy increased from 3.0 to 21.9 lm/W and the EQE from 2.1 to 11.0 % for a device with Zrq4/EI-111. Furthermore, OLED having Zrq4/Cs2CO3 show an even greater enhancement to 26.3 lm/W and 11.7 %.
Functionally graded materials (FGMs) in which the elemental composition intentionally varies with position can be fabricated using directed energy deposition additive manufacturing (AM). This work examines an FGM that is linearly graded from V to Invar 36 (64 wt% Fe, 36 wt% Ni). This FGM cracked during fabrication, indicating the formation of detrimental phases. The microstructure, composition, phases, and microhardness of the gradient zone were analyzed experimentally. The phase composition as a function of chemistry was predicted through thermodynamic calculations. It was determined that a significant amount of the intermetallic σ-FeV phase formed within the gradient zone. When the σ phase constituted the majority phase, catastrophic cracking occurred. The approach presented illustrates the suitability of using equilibrium thermodynamic calculations for the prediction of phase formation in FGMs made by AM despite the nonequilibrium conditions in AM, providing a route for the computationally informed design of FGMs.
A hypoeutectic CoCrFeNiNbχ system was synthesized to investigate the effect of Nb content on the thermal stability, mechanical properties, and corrosion behaviors. The hypoeutectic CoCrFeNiNbχ alloy, which contained the Laves phase, possessed two-phase eutectic structures. The elevated temperature may have an impact on the stability of the Laves phase. Nanoindentation measurements showed that the Laves phase is much harder than the FCC phase, which could be confirmed by the shallower maximum penetration depth in the typical P–h curve. Furthermore, the plasticity of the Laves phase was characterized by nanoindentation measurements. Compared with the FCC phase, the activation energy of dislocation nucleation in the Laves phase is much higher due to the large atomic size difference and the phase difference. Corrosion and passivation behaviors of CoCrFeNiNbχ were investigated in 3.5% NaCl solution. All the alloys exhibited spontaneous passivity and low current densities in 3.5% NaCl solution. Furthermore, the corrosion potential increased with the increasing Nb content, which indicated that the corrosion resistance enhanced with a higher Nb content.
Different diagnostic interviews are used as reference standards for major depression classification in research. Semi-structured interviews involve clinical judgement, whereas fully structured interviews are completely scripted. The Mini International Neuropsychiatric Interview (MINI), a brief fully structured interview, is also sometimes used. It is not known whether interview method is associated with probability of major depression classification.
To evaluate the association between interview method and odds of major depression classification, controlling for depressive symptom scores and participant characteristics.
Data collected for an individual participant data meta-analysis of Patient Health Questionnaire-9 (PHQ-9) diagnostic accuracy were analysed and binomial generalised linear mixed models were fit.
A total of 17 158 participants (2287 with major depression) from 57 primary studies were analysed. Among fully structured interviews, odds of major depression were higher for the MINI compared with the Composite International Diagnostic Interview (CIDI) (odds ratio (OR) = 2.10; 95% CI = 1.15–3.87). Compared with semi-structured interviews, fully structured interviews (MINI excluded) were non-significantly more likely to classify participants with low-level depressive symptoms (PHQ-9 scores ≤6) as having major depression (OR = 3.13; 95% CI = 0.98–10.00), similarly likely for moderate-level symptoms (PHQ-9 scores 7–15) (OR = 0.96; 95% CI = 0.56–1.66) and significantly less likely for high-level symptoms (PHQ-9 scores ≥16) (OR = 0.50; 95% CI = 0.26–0.97).
The MINI may identify more people as depressed than the CIDI, and semi-structured and fully structured interviews may not be interchangeable methods, but these results should be replicated.
Declaration of interest
Drs Jetté and Patten declare that they received a grant, outside the submitted work, from the Hotchkiss Brain Institute, which was jointly funded by the Institute and Pfizer. Pfizer was the original sponsor of the development of the PHQ-9, which is now in the public domain. Dr Chan is a steering committee member or consultant of Astra Zeneca, Bayer, Lilly, MSD and Pfizer. She has received sponsorships and honorarium for giving lectures and providing consultancy and her affiliated institution has received research grants from these companies. Dr Hegerl declares that within the past 3 years, he was an advisory board member for Lundbeck, Servier and Otsuka Pharma; a consultant for Bayer Pharma; and a speaker for Medice Arzneimittel, Novartis, and Roche Pharma, all outside the submitted work. Dr Inagaki declares that he has received grants from Novartis Pharma, lecture fees from Pfizer, Mochida, Shionogi, Sumitomo Dainippon Pharma, Daiichi-Sankyo, Meiji Seika and Takeda, and royalties from Nippon Hyoron Sha, Nanzando, Seiwa Shoten, Igaku-shoin and Technomics, all outside of the submitted work. Dr Yamada reports personal fees from Meiji Seika Pharma Co., Ltd., MSD K.K., Asahi Kasei Pharma Corporation, Seishin Shobo, Seiwa Shoten Co., Ltd., Igaku-shoin Ltd., Chugai Igakusha and Sentan Igakusha, all outside the submitted work. All other authors declare no competing interests. No funder had any role in the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review or approval of the manuscript; and decision to submit the manuscript for publication.
A foundation diet, an intermediate blend and a summit diet were formulated with different levels of soyabean meal, casein and crystalline amino acids to compare ‘slow’ and ‘rapid’ protein diets. The diets were offered to male Ross 308 chicks from 7 to 28 d post-hatch and assessed parameters included growth performance, nutrient utilisation, apparent digestibility coefficients and disappearance rates of starch and protein (N) in four small intestinal segments. Digestibility coefficients and disappearance rates of sixteen amino acids in three small intestinal segments and amino acid concentrations in plasma from portal and systemic circulations from the foundation and summit diets were determined. The dietary transition significantly accelerated protein (N) disappearance rates in the distal jejunum and ileum. The transition from foundation to summit diets significantly increased starch digestibility coefficients in the ileum and disappearance rates in all four small intestinal segments. These starch responses were associated with significant enhancements in nutrient utilisation. The dietary transition linearly increased digestibility coefficients and disappearance rates of amino acids in the majority of cases. The summit diet increased plasma concentrations of five amino acids but decreased those of four amino acids relative to the foundation diet to significant extents. Plasma concentrations of free amino acids were higher in the portal than systemic circulations. Rapid protein disappearance rates advantaged poultry performance and influenced post-enteral availability of amino acids. If the underlying mechanisms are to be identified, further research into the impact of protein digestive dynamics on broiler performance is required but appears justified.
A total of ten experimental diets with protein concentrations ranging from 154 to 400 g/kg and two lipid levels (46 and 85 g/kg) with identical energy densities were offered to 240 male Ross 308 broilers from 7 to 28 d post-hatch. Growth performance was monitored and nutrient utilisation (apparent metabolisable energy (AME), N-corrected AME (AMEn), AME daily intake, AME:gross energy ratios, N retention) was determined. The weight gain response of broiler chickens to dietary protein concentrations in diets containing high and low lipid levels was diverse, with the relevant quadratic regressions being significantly different (P<0·05). With low lipid levels, the predicted maximum weight gain of 1809 g/bird equated to 342 g/kg dietary protein, whereas, for high lipid levels the predicted maximum weight gain of 1694 g/bird equated to 281 g/kg dietary protein. AME was linearly correlated with dietary protein concentration but regressions in diets with different lipid content were not significantly different (P>0·05). AMEn was also linearly (P<0·0001) increased with dietary protein concentrations but regressions in diets with low and high lipid content were significantly different (P<0·03). Carcass protein content increased linearly with dietary protein content in diets containing high lipid concentrations (r 0·933, P<0·0001); by contrast, this relationship was quadratic (R2=0·93, P<0·0001) in diets with low lipid levels. In conclusion, predictably, the effects of dietary protein concentrations on broiler performance were profound; however, the impact of dietary protein on performance in broiler chickens was modified by dietary lipid concentrations.