Definitions of relapse in trials comparing antipsychotic maintenance with discontinuation or reduction for schizophrenia spectrum disorders: A systematic review

INTRODUCTION: Avoidance of relapse is the main aim of long-term antipsychotic treatment in schizophrenia, yet how 'relapse' is defined in trials is not well-known. METHODS: We conducted a systematic review of definitions of relapse in trials of continuous antipsychotic treatment compared with discontinuation, intermittent treatment or dose reduction for people with schizophrenia spectrum disorders. Trials were identified from previous Cochrane reviews and a new search. The quality of relapse definitions was rated in terms of reliability and clinical relevance and associations between quality of definitions and trial characteristics and outcome were explored. RESULTS: We identified 82 reports of 81 trials which employed 54 different definitions of relapse. There were 33 definitions in the 35 trials published since 1990, with recent trials employing complex definitions often involving alternative criteria. Only ten primary definitions of relapse required the presence of psychotic symptoms in all cases, and only three specified this in combination with a measure of overall severity or functional decline. Only two definitions specified a duration longer than two days. Relapse definitions were rated as showing good reliability in 37 trials, but only seven showed good clinical relevance. Six trials with definitions that were both reliable and clinically relevant were slightly longer, but did not differ from remaining trials in other characteristics or overall or relative risk of relapse. CONCLUSIONS: Antipsychotic trials define relapse in numerous different ways, and few definitions consistently reflect suggested indications of a clinically significant relapse

Aspects of structural health and condition monitoring of offshore wind turbines

Wind power has expanded significantly over the past years, although reliability of wind turbine systems, especially of offshore wind turbines, has been many times unsatisfactory in the past. Wind turbine failures are equivalent to crucial financial losses. Therefore, creating and applying strategies that improve the reliability of their components is important for a successful implementation of such systems. Structural health monitoring (SHM) addresses these problems through the monitoring of parameters indicative of the state of the structure examined. Condition monitoring (CM), on the other hand, can be seen as a specialized area of the SHM community that aims at damage detection of, particularly, rotating machinery. The paper is divided into two parts: in the first part, advanced signal processing and machine learning methods are discussed for SHM and CM on wind turbine gearbox and blade damage detection examples. In the second part, an initial exploration of supervisor control and data acquisition systems data of an offshore wind farm is presented, and data-driven approaches are proposed for detecting abnormal behaviour of wind turbines. It is shown that the advanced signal processing methods discussed are effective and that it is important to adopt these SHM strategies in the wind energy sector

Sea ice working group (SIP)

The sea ice is a crucial component of the polar climate system, and has an impact on albedo, heat and gas ex- change, primary productivity and car- bon export, atmospheric and ocean circulation, freshwater budget, ocean stratification, and deep water mass for- mation. It is therefore critical that it is correctly specified as a forcing or pre- dicted as a feedback in modeling stud- ies

Small-scale EUV features as the drivers of coronal upflows in the quiet Sun

Context. Coronal upflows in the quiet Sun are seen in a wide range of features, including jets and filament eruptions. The in situ measurements from Parker Solar Probe within ≈0.2 au have demonstrated that the solar wind is highly structured, showing abrupt and near-ubiquitous magnetic field reversals (i.e., switchbacks) on different timescales. The source of these structures has been associated with supergranular structures on the solar disc. This raises the question of whether there are additional small coronal features that contribute energy to the corona and produce plasma that potentially feeds into the solar wind. / Aims. During the Solar Orbiter first science perihelion, high-resolution images of the solar corona were recorded using the Extreme Ultraviolet High Resolution Imager (HRIEUV) from the Extreme Ultraviolet Imager (EUI). The Hinode spacecraft was also observing at the same location providing coronal spectroscopic measurements. Combining the two datasets allows us to determine the cause of the weak upflows observed in the quiet Sun and the associated activity. / Methods. We used a multi-spacecraft approach to characterise regions of upflows. The upflows were identified in the Fe XII emission line by the Hinode EUV Imaging Spectrometer (EIS). We then used imaging data from the Atmospheric Imaging Assembly on board the Solar Dynamics Observatory (SDO/AIA) and the High Resolution Imagers (HRI) from EUI on board the Solar Orbiter to identify coronal features and magnetic field data from the SDO Helioseismic and Magnetic Imager (HMI). Interface Region Imaging Spectrograph (IRIS) observations were also used to understand the photospheric and chromospheric driving mechanisms. / Results. We have identified two regions of coronal upflows in the quiet Sun, with respective sizes and lifetimes of (20 Mm2, 20 min) and (180 Mm2, several hours), which are contrasting dynamic events. Both examples show weak flux cancellation, indicating that the source of the upflows and enhancements is related to the magnetic field changes. The first event, a larger upflow region, shows velocities of up to −8.6 km s−1 at the footpoint of a complex loop structure. We observe several distinct extreme ultraviolet (EUV) features including frequent loop brightenings and plasma blobs travelling along closed coronal loops. The second upflow region has velocities of up to −7.2 km s−1. Within it, a complex EUV feature that lasts for about 20 min can be seen. This main feature has several substructures. During its appearance, a clear mini-filament eruption takes place at its location, before the EUV feature disappears. / Conclusions. Two features, with contrasting properties, show upflows with comparable magnitudes. The first event, a complex loop structure, shares several similarities with active region upflows. The second one, a complex small-scale feature that could not have been well resolved with previous instruments, triggered a cascade of events, including a mini-filament that lead to a measurable upflow. This is remarkable for an EUV feature that many instruments can barely resolve. The complexity of the two events, including small loop brightenings and travelling plasma blobs for the first and EUV small-scale loops and mini-filament for the second one would not have been identifiable as the sources of upflow without an instrument with the spatial resolution of HRIEUV at this distance to the Sun. These results reinforce the importance of the smallest-scale features in the Sun and their potential relevance for and impact on the solar corona and the solar wind

Targeting BRAF for patients with melanoma

The prognosis of patients with metastatic melanoma is poor and not influenced by systemic therapy with cytotoxic drugs. New targeted agents directed against the RAS-RAF-MEK-ERK pathway show promising activity in early clinical development and particular interest is focused on selective inhibitors of mutant BRAF, which is present in one half of the cases of metastatic melanoma. The majority of patients on early trials of these drugs develop secondary resistance and subsequent disease progression and it is, therefore, critical to understand the underlying escape mechanisms leading to resistance

First shark from the late Devonian (Frasnian) gogo formation, Western Australia sheds new light on the development of tessellated calcified cartilage

Background: Living gnathostomes (jawed vertebrates) comprise two divisions, Chondrichthyes (cartilaginous fishes, including euchondrichthyans with prismatic calcified cartilage, and extinct stem chondrichthyans) and Osteichthyes (bony fishes including tetrapods). Most of the early chondrichthyan (‘shark’) record is based upon isolated teeth, spines, and scales, with the oldest articulated sharks that exhibit major diagnostic characters of the group—prismatic calcified cartilage and pelvic claspers in males—being from the latest Devonian, c. 360 Mya. This paucity of information about early chondrichthyan anatomy is mainly due to their lack of endoskeletal bone and consequent low preservation potential. Methodology/Principal Findings: Here we present new data from the first well-preserved chondrichthyan fossil from the early Late Devonian (ca. 380–384 Mya) Gogo Formation Lägerstatte of Western Australia. The specimen is the first Devonian shark body fossil to be acid-prepared, revealing the endoskeletal elements as three-dimensional undistorted units: Meckel’s cartilages, nasal, ceratohyal, basibranchial and possible epibranchial cartilages, plus left and right scapulocoracoids, as well as teeth and scales. This unique specimen is assigned to Gogoselachus lynnbeazleyae n. gen. n. sp.Conclusions/Significance: The Meckel’s cartilages show a jaw articulation surface dominated by an expansive cotylus, and a small mandibular knob, an unusual condition for chondrichthyans. The scapulocoracoid of the new specimen shows evidence of two pectoral fin basal articulation facets, differing from the standard condition for early gnathostomes which have either one or three articulations. The tooth structure is intermediate between the ‘primitive’ ctenacanthiform and symmoriiform condition, and more derived forms with a euselachian-type base. Of special interest is the highly distinctive type of calcified cartilage forming the endoskeleton, comprising multiple layers of nonprismatic subpolygonal tesserae separated by a cellular matrix, interpreted as a transitional step toward the tessellated prismatic calcified cartilage that is recognized as the main diagnostic character of the chondrichthyans

Comparison of Population-Based Association Study Methods Correcting for Population Stratification

Population stratification can cause spurious associations in population–based association studies. Several statistical methods have been proposed to reduce the impact of population stratification on population–based association studies. We simulated a set of stratified populations based on the real haplotype data from the HapMap ENCODE project, and compared the relative power, type I error rates, accuracy and positive prediction value of four prevailing population–based association study methods: traditional case-control tests, structured association (SA), genomic control (GC) and principal components analysis (PCA) under various population stratification levels. Additionally, we evaluated the effects of sample sizes and frequencies of disease susceptible allele on the performance of the four analytical methods in the presence of population stratification. We found that the performance of PCA was very stable under various scenarios. Our comparison results suggest that SA and PCA have comparable performance, if sufficient ancestral informative markers are used in SA analysis. GC appeared to be strongly conservative in significantly stratified populations. It may be better to apply GC in the stratified populations with low stratification level. Our study intends to provide a practical guideline for researchers to select proper study methods and make appropriate inference of the results in population-based association studies

Lipid-dependent gating of a voltage-gated potassium channel

Recent studies hypothesized that phospholipids stabilize two voltage-sensing arginine residues of certain voltage-gated potassium channels in activated conformations. It remains unclear how lipids directly affect these channels. Here, by examining the conformations of the KvAP in different lipids, we showed that without voltage change, the voltage-sensor domains switched from the activated to the resting state when their surrounding lipids were changed from phospholipids to nonphospholipids. Such lipid-determined conformational change was coupled to the ion-conducting pore, suggesting that parallel to voltage gating, the channel is gated by its annular lipids. Our measurements recognized that the energetic cost of lipid-dependent gating approaches that of voltage gating, but kinetically it appears much slower. Our data support that a channel and its surrounding lipids together constitute a functional unit, and natural nonphospholipids such as cholesterol should exert strong effects on voltage-gated channels. Our first observation of lipid-dependent gating may have general implications to other membrane proteins