Patients' and relatives' assessment of clozapine treatment

Published version: http://journals.cambridge.org/action/displayJournal?jid=PS

Multi-Granular Trend Detection for Time-Series Analysis

Time series (such as stock prices) and ensembles (such as model runs for weather forecasts) are two important types of one-dimensional time-varying data. Such data is readily available in large quantities but visual analysis of the raw data quickly becomes infeasible, even for moderately sized data sets. Trend detection is an effective way to simplify time-varying data and to summarize salient information for visual display and interactive analysis. We propose a geometric model for trend-detection in one-dimensional time-varying data, inspired by topological grouping structures for moving objects in two- or higher-dimensional space. Our model gives provable guarantees on the trends detected and uses three natural parameters: granularity, support-size, and duration. These parameters can be changed on-demand. Our system also supports a variety of selection brushes and a time-sweep to facilitate refined searches and interactive visualization of (sub-)trends. We explore different visual styles and interactions through which trends, their persistence, and evolution can be explored

Advancement of Nucleic Acid-Based Tools for Monitoring in Situ Reductive Dechlorination

Regulatory protocols generally recognize that destructive processes are the most effective mechanisms that support natural attenuation of chlorinated solvents. In many cases, these destructive processes will be biological processes and, for chlorinated compounds, will often be reductive processes that occur under anaerobic conditions. The existing EPA guidance (EPA, 1998) provides a list of parameters that provide indirect evidence of reductive dechlorination processes. In an effort to gather direct evidence of these processes, scientists have identified key microorganisms and are currently developing tools to measure the abundance and activity of these organisms in subsurface systems. Drs. Edwards and Luffler are two recognized leaders in this field. The research described herein continues their development efforts to provide a suite of tools to enable direct measures of biological processes related to the reductive dechlorination of TCE and PCE. This study investigated the strengths and weaknesses of the 16S rRNA gene-based approach to characterizing the natural attenuation capabilities in samples. The results suggested that an approach based solely on 16S rRNA may not provide sufficient information to document the natural attenuation capabilities in a system because it does not distinguish between strains of organisms that have different biodegradation capabilities. The results of the investigations provided evidence that tools focusing on relevant enzymes for functionally desired characteristics may be useful adjuncts to the 16SrRNA methods

Sex differences in pain expressed by patients across diverse disease states: individual patient data meta-analysis of 33,957 participants in 10 randomized controlled trials

The experience of pain is determined by many factors and has a significant impact on quality of life. This study aimed to determine sex differences in pain prevalence and intensity reported by participants with diverse disease states in several large international clinical trials. Individual participant data meta-analysis was conducted using EuroQol-5 Dimension (EQ-5D) questionnaire pain data from randomised controlled trials published between January 2000 and January 2020 and undertaken by investigators at the George Institute for Global Health. Proportional odds logistic regression models, comparing pain scores between females and males and fitted with adjustments for age and randomized treatment, were pooled in a random-effects meta-analysis. In 10 trials involving 33,957 participants (38% females) with EQ-5D pain score data, the mean age ranged between 50 and 74. Pain was reported more frequently by females than males (47% vs 37%; P < 0.001). Females also reported greater levels of pain than males (adjusted odds ratio 1.41, 95% CI 1.24-1.61; P < 0.001). In stratified analyses, there were differences in pain by disease group (P for heterogeneity <0.001), but not by age group or region of recruitment. Females were more likely to report pain, and at a higher level, compared with males across diverse diseases, all ages, and geographical regions. This study reinforces the importance of reporting sex-disaggregated analysis to identify similarities and differences between females and males that reflect variable biology and may affect disease profiles and have implications for management

Formation of Giant Quasibound Cold Diatoms by Strong Atom-Cavity Coupling

We show that giant quasi-bound diatomic complexes, whose size is typically hundreds of nm, can be formed by intra-cavity cold diatom photoassociation or photodissociation in the strong atom-cavity coupling regime.Comment: 4 pages, 3 figure

Genomic catastrophes frequently arise in esophageal adenocarcinoma and drive tumorigenesis

Oesophageal adenocarcinoma (EAC) incidence is rapidly increasing in Western countries. A better understanding of EAC underpins efforts to improve early detection and treatment outcomes. While large EAC exome sequencing efforts to date have found recurrent loss-offunction mutations, oncogenic driving events have been underrepresented. Here we use a combination of whole-genome sequencing (WGS) and single-nucleotide polymorphism-array profiling to show that genomic catastrophes are frequent in EAC, with almost a third (32%, n¼40/123) undergoing chromothriptic events. WGS of 22 EAC cases show that catastrophes may lead to oncogene amplification through chromothripsis-derived double-minute chromosome formation (MYC and MDM2) or breakage-fusion-bridge (KRAS, MDM2 and RFC3). Telomere shortening is more prominent in EACs bearing localized complex rearrangements. Mutational signature analysis also confirms that extreme genomic instability in EAC can be driven by somatic BRCA2 mutations. These findings suggest that genomic catastrophes have a significant role in the malignant transformation of EAC

Pitfalls in the characterization of circulating and tissue-resident human γδ T cells

Dissection of the role and function of human γδ T cells and their heterogeneous subsets in cancer, inflammation, and auto-immune diseases is a growing and dynamic research field of increasing interest to the scientific community. Therefore, harmonization and standardization of techniques for the characterization of peripheral and tissue-resident γδ T cells is crucial to facilitate comparability between published and emerging research. The application of commercially available reagents to classify γδ T cells, in particular the combination of multiple Abs, is not always trouble-free, posing major demands on researchers entering this field. Occasionally, even entire γδ T cell subsets may remain undetected when certain Abs are combined in flow cytometric analysis with multicolor Ab panels, or might be lost during cell isolation procedures. Here, based on the recent literature and our own experience, we provide an overview of methods commonly employed for the phenotypic and functional characterization of human γδ T cells including advanced polychromatic flow cytometry, mass cytometry, immunohistochemistry, and magnetic cell isolation. We highlight potential pitfalls and discuss how to circumvent these obstacles

Characterization and Comparison of 2 Distinct Epidemic Community-Associated Methicillin-Resistant Staphylococcus aureus Clones of ST59 Lineage.

Sequence type (ST) 59 is an epidemic lineage of community-associated (CA) methicillin-resistant Staphylococcus aureus (MRSA) isolates. Taiwanese CA-MRSA isolates belong to ST59 and can be grouped into 2 distinct clones, a virulent Taiwan clone and a commensal Asian-Pacific clone. The Taiwan clone carries the Panton-Valentine leukocidin (PVL) genes and the staphylococcal chromosomal cassette mec (SCCmec) VT, and is frequently isolated from patients with severe disease. The Asian-Pacific clone is PVL-negative, carries SCCmec IV, and a frequent colonizer of healthy children. Isolates of both clones were characterized by their ability to adhere to respiratory A549 cells, cytotoxicity to human neutrophils, and nasal colonization of a murine and murine sepsis models. Genome variation was determined by polymerase chain reaction of selected virulence factors and by multi-strain whole genome microarray. Additionally, the expression of selected factors was compared between the 2 clones. The Taiwan clone showed a much higher cytotoxicity to the human neutrophils and caused more severe septic infections with a high mortality rate in the murine model. The clones were indistinguishable in their adhesion to A549 cells and persistence of murine nasal colonization. The microarray data revealed that the Taiwan clone had lost the ø3-prophage that integrates into the β-hemolysin gene and includes staphylokinase- and enterotoxin P-encoding genes, but had retained the genes for human immune evasion, scn and chps. Production of the virulence factors did not differ significantly in the 2 clonal groups, although more α-toxin was expressed in Taiwan clone isolates from pneumonia patients. In conclusion, the Taiwan CA-MRSA clone was distinguished by enhanced virulence in both humans and an animal infection model. The evolutionary acquisition of PVL, the higher expression of α-toxin, and possibly the loss of a large portion of the β-hemolysin-converting prophage likely contribute to its higher pathogenic potential than the Asian-Pacific clone

Attitudes to antipsychotic drugs and their side effects: a comparison between general practitioners and the general population

BACKGROUND: Attitudes towards antipsychotic medication play an important part in the treatment for schizophrenia and related disorders. We aimed measuring general practitioners' attitudes to antipsychotic drugs and their adverse side effects and comparing these with the attitudes of the general population. METHODS: Analysis and comparison of two representative samples, one comprising 100 General Practitioners (GPs), the other 791 individuals randomly selected from the general population. The setting was the German speaking cantons of Switzerland. RESULTS: General practitioners have significantly more positive attitudes towards anti-psychotic drugs than the general public. They reject widespread prejudices about the use of anti-psychotic medication significantly more than the general population. In particular the risk of dependency was assessed as 'low' by GP's (80%), in contrast to only 18% of the general population sample. In no instance did a majority of the GPs advise not tolerating any of the 10 possible adverse effects presented in this study. This is in marked contrast to the general population sample, where a majority recommended discontinuation for movement disorder (63%), strong tremor (59%), risk of dependency (55%) and feelings of unrest (54%). CONCLUSION: As well as effective management of side-effects being a vital aspect of patient and carer education, prescribing doctors need to be aware that their mentally ill patients are likely to be confronted with extremely negative public attitudes towards antipsychotic medication and with strong pressures to stop taking their medication in the event of side-effects

Unfolding the Neutron Flux Spectrum on the Surface of Mars Using the MSL‐RAD and Odyssey‐HEND Data

Understanding the long-term radiation environment at the surface of Mars allows us to estimate the exposure for future robotic and crewed missions. Typically, the radiation environment includes charged particles (i.e., protons and heavier ions) and neutral particles (i.e., gamma rays and secondary neutrons). Previous studies used in-situ measurements, models, or both to determine the characteristics of the radiation at Mars. For example, the Mars Science Laboratory instrument, the Radiation Assessment Detector (RAD), has provided invaluable in-situ data since landing in 2012. However, the RAD instrument is only sensitive to neutrons with energies > ∼6 MeV and therefore misses what is expected to be a substantial flux of lower-energy neutrons. To address this gap, we have developed an approach to derive the surface neutron spectrum using the MSL RAD data augmented by orbital data from the High Energy Neutron Detector (HEND) onboard Mars Odyssey (neutron energy < ∼10 MeV). Using a power law fit, we determine neutron flux spectra that reproduce the measurements recorded by both RAD and HEND. Our approach involves a series of Monte Carlo simulations to develop a set of atmospheric transmission functions that enables us to convert the on-orbit HEND data to their corresponding surface neutron flux spectra. The combined RAD—HEND data present a unique opportunity to obtain a complete picture of the surface neutron environment