Second-generation antipsychotic use during pregnancy and risk of congenital malformations

Purpose To study if second-generation antipsychotic (S-GA) use during the first trimester of pregnancy is associated with an increased risk of major congenital malformations (MCM). Methods A population-based birth cohort study using national register data extracted from the Drugs and Pregnancy database in Finland, years 1996-2017. The sampling frame included 1,273,987 pregnant women. We included singleton pregnancies ending in live or stillbirth or termination of pregnancy due to severe malformation. Pregnancies with exposure to known teratogens were excluded. Women were categorized into three groups: exposed to S-GAs (n = 3478), exposed to first-generation antipsychotics (F-GAs) (n = 1030), and unexposed (no purchases of S-GAs or F-GAs during pregnancy, n = 22,540). We excluded genetic conditions and compared the prevalence of MCMs in S-GA users to the two comparison groups using multiple logistic regression models. Results Use of S-GAs during early pregnancy was not associated with an increased risk of overall MCMs compared to unexposed (adjusted odds ratio, OR 0.92; 95% CI 0.72-1.19) or to F-GA users (OR 0.82; 95% CI 0.56-1.20). Of individual S-GAs, olanzapine use was associated with an increased risk of overall MCMs (OR 2.12; 95% CI 1.19-3.76), and specifically, an increased risk of musculoskeletal malformations (OR 3.71; 95% CI 1.35-10.1) when compared to unexposed, while comparisons to F-GA users did not show significant results. Conclusions Olanzapine use is associated with an increased risk of major congenital malformations and specifically, musculoskeletal malformations. Use during pregnancy should be restricted to situations where no safer alternatives exist.Peer reviewe

Potential role of monkey inferior parietal neurons coding action semantic equivalences as precursors of parts of speech

The anterior portion of the inferior parietal cortex possesses comprehensive representations of actions embedded in behavioural contexts. Mirror neurons, which respond to both self-executed and observed actions, exist in this brain region in addition to those originally found in the premotor cortex. We found that parietal mirror neurons responded differentially to identical actions embedded in different contexts. Another type of parietal mirror neuron represents an inverse and complementary property of responding equally to dissimilar actions made by itself and others for an identical purpose. Here, we propose a hypothesis that these sets of inferior parietal neurons constitute a neural basis for encoding the semantic equivalence of various actions across different agents and contexts. The neurons have mirror neuron properties, and they encoded generalization of agents, differentiation of outcomes, and categorization of actions that led to common functions. By integrating the activities of these mirror neurons with various codings, we further suggest that in the ancestral primates' brains, these various representations of meaningful action led to the gradual establishment of equivalence relations among the different types of actions, by sharing common action semantics. Such differential codings of the components of actions might represent precursors to the parts of protolanguage, such as gestural communication, which are shared among various members of a society. Finally, we suggest that the inferior parietal cortex serves as an interface between this action semantics system and other higher semantic systems, through common structures of action representation that mimic language syntax

Sea lice management measures for farmed Atlantic salmon (Salmo salar) in Scotland: Costs and effectiveness

Cultured and wild Atlantic salmon around the world are affected by sea lice. Salmon culturing countries have policies in place to minimize sea lice abundance on cultured salmon in open net pens in the marine environment. To adhere to these policies, salmon producers deploy a range of management measures against sea lice throughout the production cycle. The cost effectiveness of these sea lice management measures is not well quantified. This study provides estimates for cost effectiveness in Scotland of (1) individual sea lice management measures and (2) integrated management strategies that span an entire production cycle. Estimates were based on the cost-effectiveness ratio, in which costs consist of those associated with equipment, implementation, environment and side effects (mortality). Effectiveness was based on interviews and expert opinions. For single measures, skirts and the use of in-feed medicines had the best cost-effectiveness. Cleaner fish, fresh or brackish water baths, the physical removal measures (thermolicer and hydrolicer) and medicinal baths were among the next most cost-effective measures, followed by hydrogen peroxide baths. Tarpaulins were more cost-effective than well boats due to lower costs under the assumption of equal effectiveness. Direct comparison of cost effectiveness among measures may not always be constructive as they are deployed at different times in the production cycle and their functionality is different. A holistic approach to sea lice management, a common practice in industry as shown by the integrated management strategies, may reduce risk of developing resistance. For the single measures, carbon costs were insignificant compared to other costs. If measures would have a lasting effect on production through to harvest, such as ongoing increased mortality as a result of a management measure, carbon costs may become significant. Better quantification of effectiveness is important because the scarcity of data led to uncertainty that had a large impact on cost-effectiveness estimates. Generally, this study demonstrated a lack of reliable publicly available data and lack of standardization of data, which constrains research. Highlighted gaps in knowledge can serve as a guide to improve further understanding.<br/

Using big data to explore worldwide trends in objective sleep in the transition to adulthood

Background: Development induces changes in sleep, and its duration has been reported to change as a function of aging. Additionally, sleep timing is a marker of pubertal maturation, where during adolescence, the circadian rhythm shifts later. Typically, this is manifested in a later sleep onset in the evening and later awakening in the morning. These changes across development seem to be universal around the world but are unlikely to persist into adulthood. Methods: This study utilized accelerometer data from 17,355 participants aged 16-30 years (56% female) measured by validated Polar wearables over a 14-day period. We compared sleep duration, chronotype (sleep midpoint) and weekend catch-up (ie, social jetlag) sleep across ages and regions over 242,948 nights. Results: The data indicate a decline in sleep duration as well as a dramatic shift in sleep onset times throughout adolescence. This continues well into early adulthood and stabilizes nearer age 30. Differences in sleep duration across ages were significant, and ranged from 7:53 h at age 16 to 7:29 h at age 30 in the sample. Additionally, there was a clear difference between females and males throughout adolescence and young adulthood: girls had longer sleep duration and earlier timed sleep in the current study. Differences in sleep were found between regions across the world, and across European areas. Conclusions: Both sleep duration and sleep timing go through a clear developmental pattern, particularly in early adulthood. Females had an earlier sleep midpoint and obtained more sleep. Regional differences in sleep occurred across the world. Crown Copyright (C) 2019 Published by Elsevier B.V. All rights reserved.Peer reviewe

Microseminoprotein-Beta Expression in Different Stages of Prostate Cancer

Microseminoprotein-beta (MSMB, MSMB) is an abundant secretory protein contributed by the prostate, and is implicated as a prostate cancer (PC) biomarker based on observations of its lower expression in cancerous cells compared with benign prostate epithelium. However, as the current literature on MSMB is inconsistent, we assessed the expression of MSMB at the protein and mRNA levels in a comprehensive set of different clinical stages of PC. Immunohistochemistry using monoclonal and polyclonal antibodies against MSMB was used to study protein expression in tissue specimens representing prostatectomies (n = 261) and in diagnostic needle biopsies from patients treated with androgen deprivation therapy (ADT) (n = 100), and in locally recurrent castration-resistant PC (CRPC) (n = 105) and CRPC metastases (n = 113). The transcript levels of MSMB, nuclear receptor co-activator 4 (NCOA4) and MSMB-NCOA4 fusion were examined by qRT-PCR in prostatectomy samples and by RNA-sequencing in benign prostatic hyperplasia, PC, and CRPC samples. We also measured serum MSMB levels and genotyped the single nucleotide polymorphism rs10993994 using DNA from the blood of 369 PC patients and 903 controls. MSMB expression in PC (29% of prostatectomies and 21% of needle biopsies) was more frequent than in CRPC (9% of locally recurrent CRPCs and 9% of CRPC metastases) (p<0.0001). Detection of MSMB protein was inversely correlated with the Gleason score in prostatectomy specimens (p = 0.024). The read-through MSMB-NCOA4 transcript was detected at very low levels in PC. MSMB levels in serum were similar in cases of PC and controls but were significantly associated with PC risk when adjusted for age at diagnosis and levels of free or total PSA (p<0.001). Serum levels of MSMB in both PC patients and controls were significantly associated with the rs10993994 genotype (p<0.0001). In conclusion, decreased expression of MSMB parallels the clinical progression of PC and adjusted serum MSMB levels are associated with PC risk

Holistic corpus-based dialectology

This paper is concerned with sketching future directions for corpus-based dialectology. We advocate a holistic approach to the study of geographically conditioned linguistic variability, and we present a suitable methodology, 'corpusbased dialectometry', in exactly this spirit. Specifically, we argue that in order to live up to the potential of the corpus-based method, practitioners need to (i) abandon their exclusive focus on individual linguistic features in favor of the study of feature aggregates, (ii) draw on computationally advanced multivariate analysis techniques (such as multidimensional scaling, cluster analysis, and principal component analysis), and (iii) aid interpretation of empirical results by marshalling state-of-the-art data visualization techniques. To exemplify this line of analysis, we present a case study which explores joint frequency variability of 57 morphosyntax features in 34 dialects all over Great Britain