Role of interactions in ferrofluid thermal ratchets

Orientational fluctuations of colloidal particles with magnetic moments may be rectified with the help of external magnetic fields with suitably chosen time dependence. As a result a noise-driven rotation of particles occurs giving rise to a macroscopic torque per volume of the carrier liquid. We investigate the influence of mutual interactions between the particles on this ratchet effect by studying a model system with mean-field interactions. The stochastic dynamics may be described by a nonlinear Fokker-Planck equation for the collective orientation of the particles which we solve approximately by using the effective field method. We determine an interval for the ratio between coupling strength and noise intensity for which a self-sustained rectification of fluctuations becomes possible. The ratchet effect then operates under conditions for which it were impossible in the absence of interactions.Comment: 18 pages, 10 figure

Emotion and performance

The study of emotions in organizational settings has attained considerable prominence in recent years, but I critical issue remains unresolved. This is the relationship between emotion and performance. in this special issue, 5 articles address this topic from a variety of viewpoints. Two are theoretical essays that deal, respectively, with emotion and creativity and the relationships between individual and team performance. Three are empirical studies that canvass the emotion-performance nexus across levels of analysis: within person, between persons, and in groups. Between them, the 5 articles present a strong case for the nexus of emotions and performance, but, more important, they provide a platform for potentially fruitful future research in this burgeoning area

Intraperitoneal bevacizumab for control of malignant ascites due to advanced-stage gastrointestinal cancers: A multicentre double-blind, placebo-controlled phase II study - AIO SUP-0108

PURPOSE: Malignant ascites is debilitating for patients with advanced cancer. As shown previously, tumour cell production of vascular endothelial growth factor might be a major cause of the formation of malignant ascites. Intraperitoneal bevacizumab could therefore be an option for symptom control in refractory ascites. PATIENTS AND METHODS: Patients with advanced gastrointestinal cancer and malignant ascites who had undergone paracentesis at least twice within the past 4 weeks were randomly assigned in a 2:1 ratio to intraperitoneal bevacizumab (400 mg absolute) or placebo after paracentesis. During the 8-week treatment period, a minimum interval of 14 d was kept between the applications of the study drug. Primary end-point was paracentesis-free survival (ParFS). RESULTS: Fifty-three patients (median age 63 years) were randomised. Forty-nine patients received at least one study drug application and qualified for the main analysis. The proportion of patients with at least one common toxicity criteria grade III-V event was similar with 20/33 (61%) on bevacizumab and 11/16 (69%) on placebo. Median ParFS was 14 d (95% confidence interval [CI]: 11-17) in the bevacizumab arm and 10.5 d (95% CI: 7-21) on placebo (hazard ratio 0.74, 95% CI: 0.40-1.37; P = 0.16). The longest paracentesis-free period was 19 d on bevacizumab (range 6-66 d) and 17.5 d in the placebo arm (range 4-42) (P = 0.85). Median overall survival was 64 d (95% CI: 45-103) on bevacizumab compared to 31.5 d (95% CI: 20-117) on placebo (P = 0.31). CONCLUSION: Intraperitoneal bevacizumab was well tolerated. Overall, treatment did not result in a significantly better symptom control of malignant ascites. However, patients defined by specific immune characteristics may benefit

Clinical decision making and outcome in the routine care of people with severe mental illness across Europe (CEDAR)

Aims. There is a lack of knowledge on clinical decision making and its relation to outcome in the routine treatment of people with severe mental illness. This study examined preferred and experienced clinical decision making from the perspectives of patients and staff, and how these affect treatment outcome. Methods. CEDAR (ISRCTN75841675) is a naturalistic prospective observational study with bimonthly assessments during a 12-month observation period. 588 adults with severe mental illness were consecutively recruited from caseloads of community mental health services at the six study sites (Germany, UK, Italy, Hungary, Denmark, and Switzerland). Clinical decision making was measured using two instruments (Clinical Decision Making Style Scale. CDMS;Clinical Decision Making Involvement and Satisfaction Scale, CDIS) from patient and staff perspectives. Outcomes assessed were unmet needs (Camberwell Assessment of Need Short Appraisal Schedule, CANSAS). Mixed-effects multinomial regression was used to examine differences in involvement in and satisfaction with actual decision making. The effect of clinical decision making on outcome was examined using hierarchical linear modelling controlling for covariates. Results. Shared decision making was preferred by patients (2=135.08; p<0.001) and staff (2=368.17; p<0.001). Decision making style of staff significantly affected unmet needs over time, with unmet needs decreasing more in patients whose clinicians preferred active to passive (-0.406 unmet needs per two months, p=0.007) or shared (-0.303 unmet needs per two months, p=0.015) decision making. Conclusions. A shift from shared to active involvement of patients is indicated, including the development and rigorous test of targeted interventions

Perturbing HIV-1 Ribosomal Frameshifting Frequency Reveals a cis Preference for Gag-Pol Incorporation into Assembling Virions

HIV-1 virion production is driven by Gag and Gag-Pol (GP) proteins, with Gag forming the bulk of the capsid and driving budding, while GP binds Gag to deliver the essential virion enzymes protease, reverse transcriptase, and integrase. Virion GP levels are traditionally thought to reflect the relative abundances of GP and Gag in cells (;1:20), dictated by the frequency of a 21 programmed ribosomal frameshifting (PRF) event occurring in gag-pol mRNAs. Here, we exploited a panel of PRF mutant viruses to show that mechanisms in addition to PRF regulate GP incorporation into virions. First, we show that GP is enriched ;3-fold in virions relative to cells, with viral infectivity being better maintained at subphysiological levels of GP than when GP levels are too high. Second, we report that GP is more efficiently incorporated into virions when Gag and GP are synthesized in cis (i.e., from the same gag-pol mRNA) than in trans, suggesting that Gag/GP translation and assembly are spatially coupled processes. Third, we show that, surprisingly, virions exhibit a strong upper limit to trans-delivered GP incorporation; an adaptation that appears to allow the virus to temper defects to GP/Gag cleavage that may negatively impact reverse transcription. Taking these results together, we propose a "weighted Goldilocks"scenario for HIV-1 GP incorporation, wherein combined mechanisms of GP enrichment and exclusion buffer virion infectivity over a broad range of local GP concentrations. These results provide new insights into the HIV-1 virion assembly pathway relevant to the anticipated efficacy of PRF-targeted antiviral strategies.National Institutes of Health R01AI110221, P01CA022332, R35GM118131, T32GM00834

Reducing the Impact of the Next Influenza Pandemic Using Household-Based Public Health Interventions

BACKGROUND: The outbreak of highly pathogenic H5N1 influenza in domestic poultry and wild birds has caused global concern over the possible evolution of a novel human strain [1]. If such a strain emerges, and is not controlled at source [2,3], a pandemic is likely to result. Health policy in most countries will then be focused on reducing morbidity and mortality. METHODS AND FINDINGS: We estimate the expected reduction in primary attack rates for different household-based interventions using a mathematical model of influenza transmission within and between households. We show that, for lower transmissibility strains [2,4], the combination of household-based quarantine, isolation of cases outside the household, and targeted prophylactic use of anti-virals will be highly effective and likely feasible across a range of plausible transmission scenarios. For example, for a basic reproductive number (the average number of people infected by a typically infectious individual in an otherwise susceptible population) of 1.8, assuming only 50% compliance, this combination could reduce the infection (symptomatic) attack rate from 74% (49%) to 40% (27%), requiring peak quarantine and isolation levels of 6.2% and 0.8% of the population, respectively, and an overall anti-viral stockpile of 3.9 doses per member of the population. Although contact tracing may be additionally effective, the resources required make it impractical in most scenarios. CONCLUSIONS: National influenza pandemic preparedness plans currently focus on reducing the impact associated with a constant attack rate, rather than on reducing transmission. Our findings suggest that the additional benefits and resource requirements of household-based interventions in reducing average levels of transmission should also be considered, even when expected levels of compliance are only moderate

Evaluation of the 3-Minute Diagnostic Confusion Assessment Method for identification of postoperative delirium in older patients

Importance: Delirium is a common postoperative complication in older patients that often goes undetected and might lead to worse outcomes. The 3-Minute Diagnostic Confusion Assessment Method (3D-CAM) might be a practical tool for routine clinical diagnosis of delirium. Objective: To assess the 3D-CAM for detecting postoperative delirium compared with the long-form CAM used for research purposes. Design, Setting, and Participants: This cohort study of older patients enrolled in ongoing clinical trials between 2015 and 2018 was conducted at a single tertiary US hospital. Included participants were aged 60 years or older undergoing major elective surgical procedures that required at least a 2-day hospital stay. Data were analyzed between February and April 2019. Exposures: Surgical procedures of at least 2 hours in length requiring general anesthesia with planned extubation. Main Outcomes and Measures: Patients were concurrently assessed for delirium using the 3D-CAM assessment and the long-form CAM, scored based on a standardized cognitive assessment. Agreement between these 2 methods was tested using Cohen κ with repeated measures, a generalized linear mixed-effects model, and Bland-Altman analysis. Results: Sixteen raters conducted 471 concurrent CAM and 3D-CAM interviews including 299 patients (mean [SD] age, 69 [6.5] years), the majority of whom were men (152 [50.8%]), were White (263 [88.0%]), and had noncardiac operations (211 [70.6%]). Both instruments had good intraclass correlation (0.84 for the CAM and 0.98 for the 3D-CAM). Cohen κ demonstrated good overall agreement between the CAM and 3D-CAM (κ = 0.71; 95% CI, 0.58 to 0.83). According to the mixed-effects model, there was statistically significant disagreement between the 3D-CAM and CAM (estimated difference in fixed effect, -0.68; 95% CI, -1.32 to -0.05; P = .04). Bland-Altman analysis showed the probability of a delirium diagnosis with the 3D-CAM was more than twice the probability of a delirium diagnosis with the CAM (probability ratio, 2.78; 95% CI, 2.44 to 3.23). Conclusions and Relevance: The 3D-CAM instrument demonstrated agreement with the long-form CAM and might provide a pragmatic and sensitive clinical tool for detecting postoperative delirium, with the caveat that the 3D-CAM might overdiagnose delirium