Alcohol drinking in one's thirties and forties is associated with body mass index in men, but not in women: A longitudinal analysis of the 1970 British Cohort Study

Our objective was to investigate longitudinal associations between alcohol drinking and body mass index (BMI). Alcohol drinking (exposure), BMI (outcome), smoking habit, occupation, longstanding illness, and leisure time physical activity (potential confounders) were assessed at ages 30, 34, 42, and 46 in the 1970 British Birth Cohort Study. Multilevel models were used to cope with the problem of correlated observations. There were 15,708 observations in 5931 men and 14,077 observations in 5656 women. Drinking was associated with BMI in men. According to the regression coefficients, BMI was expected to increase by 0.36 (95% confidence interval: 0.11, 0.60) kg/m2 per year in men who drank once a week and by 0.40 (0.14, 0.15) kg/m2 per year in men who drank most days. In ten years, BMI was expected to increase by 5.4 kg/m2 in men who drank and by 2.9 kg/m2 in men who drank and were physically active. Drinking was not associated with BMI in women. Rather, BMI was expected to increase by 0.25 (0.07, 0.43) kg/m2 per year in women who were former smokers. In ten years, BMI was expected to increase by 4.3 kg/m2 in women who were former smokers and by 0.8 kg/m2 in women who were former smokers and who were physically active. Associations between drinking and BMI were similar after further adjustment for problematic drinking and diet. These longitudinal data suggest that drinking is associated with BMI in men and that drinking is not associated with BMI in women independent of other lifestyle risk factors

Revealing dynamics, communities and criticality from data

Complex systems such as ecological communities and neuron networks are essential parts of our everyday lives. These systems are composed of units which interact through intricate networks. The ability to predict sudden changes in the dynamics of these networks, known as critical transitions, from data is important to avert disastrous consequences of major disruptions. Predicting such changes is a major challenge as it requires forecasting the behaviour for parameter ranges for which no data on the system is available. We address this issue for networks with weak individual interactions and chaotic local dynamics. We do this by building a model network, termed an {}, consisting of the underlying local dynamics and a statistical description of their interactions. We show that behaviour of such networks can be decomposed in terms of an emergent deterministic component and a {} term. Traditionally, such fluctuations are filtered out. However, as we show, they are key to accessing the interaction structure. { We illustrate this approach on synthetic time-series of realistic neuronal interaction networks of the cat cerebral cortex and on experimental multivariate data of optoelectronic oscillators. } We reconstruct the community structure by analysing the stochastic fluctuations generated by the network and predict critical transitions for coupling parameters outside the observed range

Alcohol intake and mortality risk of COVID-19, pneumonia, and other infectious diseases: An analysis of 437191 UK biobank participants

This study aims to investigate the association between alcohol consumption and COVID-19, infectious diseases, and pneumonia mortality. This is a prospective analysis of 437,191 UK Biobank participants (age 56.3 years, 54% female). The main exposure was self-reported alcohol consumption. In addition to never and previous drinkers, we applied quartiles-based and UK guidelines-based criteria to divide current drinkers by weekly consumption into four groups. Outcomes included COVID-19, infectious diseases, and pneumonia mortality, obtained from the national death registries until May 2020. After an 11-year follow-up, compared to never drinkers, previous drinkers had higher mortality risks of infectious diseases and pneumonia (adjusted HR: 1.29 [95% CI 1.06–1.57] and 1.35 [1.07–1.70], respectively), but not COVID-19. There was a curvilinear association of alcohol consumption with infectious diseases and pneumonia mortality. Drinking within-guidelines (<14 UK units/wk) and amounts up to double the recommendation (14 to < 28 UK units/wk) was associated with the lowest mortality risks of infectious diseases (0.70 [0.59–0.83] and 0.70 [0.59–0.83], respectively) and pneumonia (0.71 [0.58–0.87] and 0.72 [0.58–0.88], respectively). Alcohol consumption was associated with lower risks of COVID-19 mortality (e.g., drinking within-guidelines: 0.53 [0.33–0.86]). Drinkers reporting multiples of the recommended alcohol drinking amounts did not have higher mortality risks of COVID-19 and other infectious diseases than never drinkers. Despite the well-established unfavorable effects on general health, we found no deleterious associations between alcohol consumption and the risk of infectious diseases, including COVID-19. Future research with other study designs is needed to confirm the causality

Phase II clinical trial evaluating docetaxel, vinorelbine and GM-CSF in stage IV melanoma

PurposeMetastatic melanoma patients have a poor prognosis. No chemotherapy regimen has improved overall survival. More effective treatments are needed. Docetaxel has clinical activity in melanoma and may be more active when combined with vinorelbine. Granulocyte-macrophage colony-stimulating factor (GM-CSF) has shown activity as an adjuvant melanoma therapy. We carried out a phase II study of these agents in patients with stage IV melanoma.MethodsPatients had documented stage IV melanoma and may have had prior immuno or chemotherapy. Previously treated brain metastases were allowed. Docetaxel (40&nbsp;mg/m(2) IV) and vinorelbine (30&nbsp;mg/m(2) IV) were administered every 14&nbsp;days, followed by GM-CSF (250&nbsp;mg/m2 SC on days 2 to 12). The primary endpoint of the study was 1-year overall survival (OS). Secondary objectives were median overall survival, response rate (per RECIST criteria), and the toxicity profiles.ResultsFifty-two patients were enrolled; 80% had stage M1c disease. Brain metastases were present in 21%. Fifty-two percent of patients had received prior chemotherapy, including 35% who received prior biochemotherapy. Toxicity was manageable. Grade III/IV toxicities included neutropenia (31%), anemia (14%), febrile neutropenia (11.5%), and thrombocytopenia (9%). DVS chemotherapy demonstrated clinical activity, with a partial response in 15%, and disease stabilization in 37%. Six-month PFS was 37%. Median OS was 11.4&nbsp;months and 1-year OS rate was 48.1%.ConclusionsThe DVS regimen was active in patients with advanced, previously treated melanoma, with manageable toxicity. The favorable 1-year overall survival and median survival rates suggest that further evaluation of the DVS regimen is warranted

Using Nonlinear Static Procedures for the Seismic Assessment of Irregular RC Buildings

The application of Nonlinear Static Procedures (NSPs) to assess the seismic vulnerability of existing structures has become widely accepted and extensively used in the literature as well as in engineering practice. Nevertheless, their success in predicting the response of irregular buildings is not yet fully verified. The main goal of the present study is to evaluate the capability and accuracy of some of the existing nonlinear static procedures (N2 and ACSM, in this case) to estimate the seismic performance of irregular structures. In order to accomplish this objective, four existing buildings, irregular in plan and elevation, were subjected to an extensive number of nonlinear static and dynamic analyses. The comparisons, focused on both global and local response parameters provide first indications on the reliability of static procedures to estimate the actual response of irregular RC buildings.N/

Effect of Different Modelling Assumptions on the Seismic Response of RC Structures

The introduction of new regulations for seismic assessment of structures established stricter performance requirements for existing buildings. In order to account for the poor seismic behaviour of such buildings, recent seismic codes, namely Eurocode 8 (EC8), introduce a number of prescriptions regarding issues such as analysis type, load distribution, accidental eccentricity, etc. At the same time, these codes give room for engineering judgment to be used with reference to the definition of structural and non-structural elements such as slabs or infill walls, and obviously leave the modelling assumptions, such as Finite Elements typology, meshing, mass modelling, etc. to the analyst decision. As such, four existing RC buildings, representative of traditional Mediterranean construction, considering different modelling assumptions, were subjected to an extensive number of nonlinear static analyses. The interpretation of possible deviations in the results will hopefully provide indications on the relative importance of each modelling parameter or decision.N/

Local differences of the position of the mental foramen

The mental foramen has been reported to vary in position in different ethnic groups. Repeated failures during injections and operative procedures involving the mental foramen suggest the presence of local differences in a given population. The aim of the present study was to investigate possible local differences of the mental foramen in Eastern Anatolian individuals in the Turkish population. The present investigation is based on the examination of 70 adult mandibles. The study consisted of three measurements, to include the relations of the mental foramen to the following: 1) the lower teeth; 2) the body of mandible; 3) the mandibular symphysis and posterior border of the ramus of the mandible. The most common position of the foramen was in line with the longitudinal axis of the second premolar tooth (relation IV), at the midpoint of the mandibular body height and at 1/3.5 of the distance from the mandibular symphysis to the posterior border of the ramus. Local differences of the mental foramen may occur in a population. Prior to surgery knowledge of the most common location of the foramen peculiar to a local population may enable effective mental block anaesthesia to be provided. (Folia Morphol 2008; 67: 32-35)

Circuit-Selective Striatal Synaptic Dysfunction in the Sapap3 Knockout Mouse Model of Obsessive-Compulsive Disorder

Background: Synapse-associated protein 90/postsynaptic density protein 95-associated protein 3 (SAPAP3) is an excitatory postsynaptic protein implicated in the pathogenesis of obsessive-compulsive behaviors. In mice, genetic deletion of Sapap3 causes obsessive-compulsive disorder (OCD)-like behaviors that are rescued by striatal expression of Sapap3, demonstrating the importance of striatal neurotransmission for the OCD-like behaviors. In the striatum, there are two main excitatory synaptic circuits, corticostriatal and thalamostriatal. Neurotransmission defects in either or both of these circuits could potentially contribute to the OCD-like behaviors of Sapap3 knockout (KO) mice. Previously, we reported that Sapap3 deletion reduces corticostriatal alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid-type glutamate receptor-mediated synaptic transmission. Methods: Whole-cell electrophysiological recording techniques in acute brain slices were used to measure synaptic transmission in the corticostriatal and thalamostriatal circuits of Sapap3 KO mice and littermate control animals. Transgenic fluorescent reporters identified striatopallidal and striatonigral projection neurons. SAPAP isoforms at corticostriatal and thalamostriatal synapses were detected using immunostaining techniques. Results: I n contrast to corticostriatal synapses, thalamostriatal synaptic activity is unaffected by Sapap3 deletion. At the molecular level, we find that another SAPAP family member, SAPAP4, is present at thalamostriatal, but not corticostriatal, synapses. This finding provides a molecular rationale for the functional divergence we observe between thalamic and cortical striatal circuits in Sapap3 KO mice. Conclusions: These findings define the circuit-level neurotransmission defects in a genetic mouse model for OCD-related behaviors, focusing attention on the corticostriatal circuit for mediating the behavioral abnormalities. Our results also provide the first evidence that SAPAP isoforms may be localized to synapses according to circuit-selective principles.National Institute of Mental Health (U.S.) (Grant MH081201

A highly sensitive and specific enzyme-linked immunosorbent assay of antibodies to hepatitis C virus

In this study, a 178 amino acids long portion of the hepatitis C virus (HCV) core gene was cloned, sequenced, expressed in Escherichia coli, and purified. The resulting antigen (C178) was tested with human sera enzyme-linked immunosorbent assay (ELISA) in order to assess its ability to diagnose HCV. It was shown by ELISA that 92% of the patients sera, diagnosed previously by a 3(rd) generation enzyme immunoassay (EIA) as HCV-positive, had antibodies against the C178 antigen. This antigen gave no false positive results when tested with anti-HCV-negative sera

See-saw relationship of the Holocene East Asian-Australian summer monsoon

D.E. and N.M. acknowledge support by the Leibniz Association (WGL) under Grant No. SAW-2013-IZW-2. F.H.M.’s research is funded through an Australian Postgraduate Award. I.O. is financially supported from TUBITAK under 2214/A program and by Ege University under the Research Project number 2015FEN028. This study received funding from the European Union’s Horizon 2020 Research and Innovation programme under the Marie Skłodowska-Curie grant agreement No 691037. The publication of this article was funded by the Open Access Fund of the Leibniz Association. K.H.W. thank Rhawn F. Denniston for his wider involvement in the northwest Australian monsoon project and the Kimberley Foundation Australia for financial support for this project and Paul Wyrwoll for helpful comments. We are also grateful to Yanjun Cai for providing the Lake Qinghai record.Peer reviewedPublisher PD