Raman spectroscopy study on terephthalamide crystal at high pressures.

In this study, we have investigated the structural stability of terephthalamide (TPA) crystal at pressure from ambient to 15 GPa in the diamond anvil cell at room temperature by Raman spectroscopy. Assignment for the Raman vibration modes of TPA crystal at ambient conditions has been performed based on the density functional theory (DFT) calculations. Pressure-induced structural transition was monitored using in-situ Raman spectroscopy. Remarkable changes (including the appearance of new Raman peaks, disappearance of original Raman bands, discontinuous changes in the pressure dependence of some Raman wavenumbers at different pressures) in Raman spectra were observed at approximately 1.3 and 5.2 GPa, provided clear evidences for two pressure-induced phase transitions: phase I to phase II at ∼1.3 GPa, phase II to phase III at ∼5.2 GPa.

Loneliness in young people: a multilevel exploration of social ecological influences and geographic variation.

BACKGROUND: Loneliness is a growing public health concern, yet little is known about loneliness in young people. The current study aimed to identify social ecological factors related to loneliness and examine the extent to which geographic region may account for differences in loneliness. METHODS: The data come from a cross-sectional sample of 6503 young people living in the UK. Loneliness was measured using the UCLA 3-item scale. Bivariate analyses were used to test associations between each predictor and loneliness. Multilevel models were used to identify key social ecological factors related to loneliness, and the extent to which loneliness may vary across geographic regions (local authority districts). RESULTS: Sociodemographic, social, health and well-being, and community factors were found to be associated with loneliness. Geographic region was associated with 5-8% of the variation in loneliness. The effect of gender, sexual orientation and minority ethnic background on loneliness differed across regions. CONCLUSIONS: This is the first study to highlight modifiable social and community factors related to youth loneliness, and individual vulnerabilities, such as poor mental well-being. Results related to geographic differences suggest that local-level initiatives may be most appropriate in tackling loneliness, rather than wider, less contextualized national efforts.

Systematic review of the effects of environmental factors on virus inactivation: implications for coronavirus disease 2019.

Environmental factors such as temperature and relative humidity can affect the inactivation and transmission of coronaviruses. By reviewing medical experiments on virus survival and virus transmission between infected and susceptible species in different temperature and humidity conditions, this study explores the influence of temperature and relative humidity on the survival and transmission of viruses, and provides suggestions, with experimental evidence, for the environmental control measures of Coronavirus Disease 2019. The results indicated that (1) virus viability and infectivity is increased at a low temperature of 5 â„ƒ and reduced at higher temperatures. (2) Virus survival and transmission is highly efficient in a dry environment with low relative humidity, and also in a wet environment with high relative humidity, and it is minimal at intermediate relative humidity. Therefore, in indoor environments, the lack of heating in winter or overventilation, leading to low indoor temperature, can help virus survival and help susceptible people being infected. On the contrary, modulating the indoor relative humidity at an intermediate level is conducive to curb epidemic outbreaks.

A new measure to understand the role of science in US Congress: lessons learned from the Legislative Use of Research Survey (LURS).

Background: There is growing interest in and recognition of the need to use scientific evidence to inform policymaking. However, many of the existing studies on the use of research evidence (URE) have been largely qualitative, and the majority of existing quantitative measures are underdeveloped or were tested in regional or context-dependent settings. We are unaware of any quantitative measures of URE with national policymakers in the US. Aims and objectives: Explore how to measure URE quantitatively by validating a measure of congressional staff's attitudes and behaviors regarding URE, the Legislative Use of Research Survey (LURS), and by discussing the lessons learned through administering the survey. Methods: A 68-item survey was administered to 80 congressional staff to measure their reported research use, value of research, interactions with researchers, general information sources, and research information sources. Confirmatory factor analyses were conducted on each of these five scales. We then trimmed the number of items, based on a combination of poor factor loadings and theoretical rationale, and ran the analyses on the trimmed subscales. Findings: We substantially improved our model fits for each scale over the original models and all items had acceptable factor loadings with our trimmed 35-item survey. We also describe the unique set of challenges and lessons learned from surveying congressional staff. Discussion and conclusions: This work contributes to the transdisciplinary field of URE by offering a tool for studying the mechanisms that can bridge research and policy and shedding light into best practices for measuring URE with national policymakers in the US.

Risk factors for prostate cancer in male patients with MRI-negative and PSA-abnormal findings / 中华男科学杂志

Objective@#To investigate the risk factors for clinically significant PCa diagnosed by transrectal ultrasound-guided systematic prostate biopsy in patients with MRI-negative and PSA-abnormal findings.@*METHODS@#From January 2014 to December 2017, 335 male patients with MRI-negative (PI-RADS 2.0 score ≤ 2) and PSA-abnormal (4－30 ng/ml ) findings underwent systematic prostate biopsy guided by transrectal ultrasound under local anesthesia in our department. We collected and analyzed the demographic data, clinical symptoms, complications, past history and PSA density (PSAD) of the patients.@*RESULTS@#Clinically significant PCa was diagnosed in 21 (6.3%) of the 335 patients. Multivariate logistic regression analysis showed that the independent risk factors were higher age (AUC: 0.704, P 71 years old or with PSAD >0.18 ng/ml/ml so as to avoid missed diagnosis and unnecessary invasive biopsy as well. /.

Transmission risk of infectious droplets in physical spreading process at different times: A review.

Droplets provide a well-known transmission media in the COVID-19 epidemic, and the particle size is closely related to the classification of the transmission route. However, the term "aerosol" covers most particle sizes of suspended particulates because of information asymmetry in different disciplines, which may lead to misunderstandings in the selection of epidemic prevention and control strategies for the public. In this review, the time when these droplets are exhaled by a patient was taken as the initial time. Then, all available viral loads and numerical distribution of the exhaled droplets was analyzed, and the evaporation model of droplets in the air was combined with the deposition model of droplet nuclei in the respiratory tract. Lastly, the perspective that physical spread affects the transmission risk of different size droplets at different times was summarized for the first time. The results showed that although the distribution of exhaled droplets was dominated by small droplets, droplet volume was proportional to the third power of particle diameter, meaning that the viral load of a 100 µm droplet was approximately 106 times that of a 1 µm droplet at the initial time. Furthermore, the exhaled droplets are affected by heat and mass transfer of evaporation, water fraction, salt concentration, and acid-base balance (the water fraction > 98%), which lead them to change rapidly, and the viral survival condition also deteriorates dramatically. The time required for the initial diameter (do) of a droplet to shrink to the equilibrium diameter (de, about 30% of do) is approximately proportional to the second power of the particle diameter, taking only a few milliseconds for a 1 µm droplet but hundreds of milliseconds for a 10 µm droplet; in other words, the viruses carried by the large droplets can be preserved as much as possible. Finally, the infectious droplet nuclei maybe inhaled by the susceptible population through different and random contact routes, and the droplet nuclei with larger de decompose more easily into tiny particles on account of the accelerated collision in a complex airway, which can be deposited in the higher risk alveolar region. During disease transmission, the infectious droplet particle size varies widely, and the transmission risk varies significantly at different time nodes; therefore, the fuzzy term "aerosol" is not conducive to analyzing disease exposure risk. Recommendations for epidemic prevention and control strategies are: 1) Large droplets are the main conflict in disease transmission; thus, even if they are blocked by a homemade mask initially, it significantly contains the epidemic. 2) The early phase of contact, such as close-contact and short-range transmission, has the highest infection risk; therefore, social distancing can effectively keep the susceptible population from inhaling active viruses. 3) The risk of the fomite route depends on the time in contact with infectious viruses; thus, it is important to promote good health habits (including frequent hand washing, no-eye rubbing, coughing etiquette, normalization of surface cleaning), although blind and excessive disinfection measures are not advisable. 4) Compared with the large droplets, the small droplets have larger numbers but carry fewer viruses and are more prone to die through evaporation.

Different Characteristics and Heritabilities of Alcohol Use Disorder Classes: A Population-Based Swedish Study.

AIMS: The aims of the present study are to identify alcohol use disorder (AUD) classes among a population-based Swedish sample, determine if these classes differ by variables known to be associated with AUD and determine whether some AUD classes have stronger genetic influences than others. METHODS: A latent class analysis (LCA), based on types of registrations, was conducted on Swedish individuals with an AUD registration born between 1960 and 1990 (N = 184,770). These classes were then validated using demographics; patterns of comorbidity with drug abuse, psychiatric disorders and criminal behavior; and neighborhood-level factors, i.e. peer AUD and neighborhood deprivation. The degree of genetic and environmental influence was also investigated. RESULTS: The best-fit LCA had four classes: (a) outpatient/prescription, characterized by a mix of outpatient medical and prescription registrations, (b) low-frequency inpatient, characterized entirely by inpatient medical registrations, with the majority of individuals having one AUD registration, (c) high-frequency mixed, characterized by a mix of all four registration types, with the majority having four or more registrations and (d) crime, characterized almost entirely by criminal registrations. The highest heritability for both males and females was found for Class 3 (61% and 65%, respectively) and the lowest for Class 1 (20% for both), with shared environmental influences accounting for 10% or less of the variance in all Classes. CONCLUSIONS: Using comprehensive, nationwide registry data, we showed evidence for four distinct, meaningful classes of AUD with varying degrees of heritability.

HNF1α Controls Liver Lipid Metabolism and Insulin Resistance via Negatively Regulating the SOCS-3-STAT3 Signaling Pathway.

This study is aimed at evaluating the effects, functions, and mechanism of HNF1α on hepatic glycolipid metabolism. In this study, free fatty acid- (FFA-) induced steatosis of hepatocyte liver cell LO2 was used as an in vitro model. The methods of Oil Red O staining, RT-qPCR, western blot, and immunofluorescence staining were used to detect LO2-regulated HNF1α expression and its effects on FFA-induced LO2 cell steatosis, the insulin signaling and SOCS-3-STAT3 signaling pathways, the expression of lipid metabolism-related regulators, and phosphorylation. With increased FFA induction time, the expression of HNF1α in the LO2 fatty degeneration hepatic cells gradually decreased. Downregulation of HNF1α expression aggravated FFA-induced steatosis of LO2 hepatocytes. HNF1α promotes activation of the insulin pathway and oxidative breakdown of fat and inhibits lipid anabolism. Inhibitors of STAT3 can reverse the regulation of decreased HNF1α expression on the insulin signaling pathway and fat metabolism. We also confirmed this pathway using HNF1α-/- mice combining treatment with STAT3 inhibitor NSC 74859 in vivo. HNF1α regulates hepatic lipid metabolism by promoting the expression of SOCS-3 and negatively regulating the STAT3 signaling pathway.

Optical diagnostics studies of air flow and powder fluidisation in Nexthaler®. Part II: Use of fluorescent imaging to characterise transient release of fines from a dry powder inhaler.

The fine particle fraction is a key indicator of therapeutic effectiveness of inhaled pharmaceutical aerosols. This paper presents a fluorescence imaging technique to visualise and characterise the emission of active pharmaceutical ingredient (API) fines in model formulations containing coarse lactose carrier and 1.5-2 µm diameter fluorescent microspheres (model API fines). A two-camera arrangement was used to acquire simultaneous images of spatial and temporal distribution of model API fines and fluidised powder formulation near the mouthpiece exit of a DPI. Digital image analysis showed that the model API fines were released along with the bulk of the powder dose. More rapidly accelerating airflows were found to cause earlier release of API fines. The fluorescence imaging technique analyses a substantial fraction of the aerosol plume and was found to provide effective time-resolved characterisation of the de-aggregation and release of API fines with consistent results across a wide range of model API concentrations. Future studies should demonstrate the usefulness of the fluorescence imaging technique across different formulations and DPI devices.

The role of parent and offspring sex on risk for externalizing psychopathology in offspring with parental alcohol use disorder: a national Swedish study.

PURPOSE: The substantial literature showing that offspring of parents with alcohol use disorder (AUD) is at increased risk for externalizing psychopathology rarely examines the differential effects of parental and offspring sex. This literature also has other important limitations, such as modest sample sizes and use of unrepresentative samples. Using a large, nationwide Swedish sample, we aim to investigate the roles of parental and offspring sex in externalizing psychopathology among offspring with parental AUD. METHODS: AUD diagnosis and externalizing measures were obtained from national registries. Associations between outcomes and parental AUD were examined using logistic regressions. Parental and offspring sex effects were examined with interaction terms. RESULTS: Risks for externalizing disorders were increased in sons and daughters with parental AUD, with significant differences between sons and daughters for criminal behavior; maternal AUD had a greater impact than paternal AUD (regardless of offspring sex), but having two parents with AUD increased risk for all outcomes substantially more than having one parent; and maternal AUD increased risk of drug abuse for daughters more than sons, while paternal AUD increased risk of AUD and criminal behavior for sons more than daughters. CONCLUSIONS: Offspring of parents with AUD are at increased risk for externalizing psychopathology. Maternal and paternal AUD differentially affected sons' vs. daughters' risks for AUD, drug abuse, and criminal behavior. The transmission of psychopathology within the externalizing spectrum appears to have sex-specific elements.

A glimpse of gluons through deeply virtual compton scattering on the proton.

The internal structure of nucleons (protons and neutrons) remains one of the greatest outstanding problems in modern nuclear physics. By scattering high-energy electrons off a proton we are able to resolve its fundamental constituents and probe their momenta and positions. Here we investigate the dynamics of quarks and gluons inside nucleons using deeply virtual Compton scattering (DVCS)-a highly virtual photon scatters off the proton, which subsequently radiates a photon. DVCS interferes with the Bethe-Heitler (BH) process, where the photon is emitted by the electron rather than the proton. We report herein the full determination of the BH-DVCS interference by exploiting the distinct energy dependences of the DVCS and BH amplitudes. In the regime where the scattering is expected to occur off a single quark, measurements show an intriguing sensitivity to gluons, the carriers of the strong interaction.

Eimeria tenella protein trafficking: differential regulation of secretion versus surface tethering during the life cycle.

Eimeria spp. are intracellular parasites that have a major impact on poultry. Effective live vaccines are available and the development of reverse genetic technologies has raised the prospect of using Eimeria spp. as recombinant vectors to express additional immunoprotective antigens. To study the ability of Eimeria to secrete foreign antigens or display them on the surface of the sporozoite, transiently transfected populations of E. tenella expressing the fluorescent protein mCherry, linked to endogenous signal peptide (SP) and glycophosphatidylinositol-anchor (GPI) sequences, were examined. The SP from microneme protein EtMIC2 (SP2) allowed efficient trafficking of mCherry to cytoplasmic vesicles and following the C-terminal addition of a GPI-anchor (from surface antigen EtSAG1) mCherry was expressed on the sporozoite surface. In stable transgenic populations, mCherry fused to SP2 was secreted into the sporocyst cavity of the oocysts and after excystation, secretion was detected in culture supernatants but not into the parasitophorous vacuole after invasion. When the GPI was incorporated, mCherry was observed on the sporozites surface and in the supernatant of invading sporozoites. The proven secretion and surface exposure of mCherry suggests that antigen fusions with SP2 and GPI of EtSAG1 may be promising candidates to examine induction of protective immunity against heterologous pathogens.

Contributions of Genes and Environment to Developmental Change in Alcohol Use.

The precise nature of how genetic and environmental risk factors influence changes in alcohol use (AU) over time has not yet been investigated. Therefore, the aim of the present study is to examine the nature of longitudinal changes in these risk factors to AU from mid-adolescence through young adulthood. Using a large sample of male twins, we compared five developmental models that each makes different predictions regarding the longitudinal changes in genetic and environmental risks for AU. The best-fitting model indicated that genetic influences were consistent with a gradual growth in the liability to AU, whereas unique environmental risk factors were consistent with an accumulation of risks across time. These results imply that two distinct processes influence adolescent AU between the ages of 15-25. Genetic effects influence baseline levels of AU and rates of change across time, while unique environmental effects are more cumulative.

EUV spectral analysis of ns-laser produced bismuth plasmas at 8-17 nm.

Extreme ultraviolet (EUV) spectra from laser produced bismuth plasmas were recorded in the 8-17 nm spectral region using a Nd:YAG laser with a pulse length of 8 ns operating at a range of laser power densities. Due to the broad-band emission at 8-17 nm, bismuth plasmas show promise as sources of quasicontinuous radiation in the extreme ultraviolet. When varying the incident laser power density, ionic populations of Bi ions at different power densities were estimated by the collisional-radiative (CR) model for explanation of changes in the spectral profile. Comparison of experimental spectra with atomic structure calculations using the Hartree-Fock with configuration interaction (HFCI) code of Cowan was performed in order to identify most of the features in the spectra.

The association between personality disorders with alcohol use and misuse: A population-based twin study.

BACKGROUND: A clearer understanding of the etiological overlap between DSM-IV personality disorders (PDs) and alcohol use (AU) and alcohol use disorder (AUD) is needed. To our knowledge, no study has modeled the association between all 10 DSM-IV PDs and lifetime AU and AUD. The aim of the present study is to identify which PDs are most strongly associated with the phenotypic, genetic, and environmental risks of lifetime AU and AUD, and to determine if these associations are stable across time. METHODS: Participants were Norwegian twins assessed at two waves. At Wave 1, 2801 twins were assessed for all 10 DSM-IV PD criteria, lifetime AU, and DSM-IV AUD criteria. At Wave 2, six of the 10 PDs were again assessed along with AU and AUD among 2393 twins. Univariate and multiple logistic regressions were run. Significant predictors were further analyzed using bivariate twin Cholesky decompositions. RESULTS: Borderline and antisocial PD criteria were the strongest predictors of AU and AUD across the two waves. Despite moderate phenotypic and genetic correlations, genetic variation in these PD criteria explained only 4% and 3% of the risks in AU, and 5% to 10% of the risks in AUD criteria, respectively. At Wave 2, these estimates increased to 8% and 23% for AU, and 17% and 33% for AUD. CONCLUSIONS: Among a large Norwegian twin sample, borderline and antisocial PD criteria were the strongest predictors of the phenotypic and genotypic liability to AU and AUD. This effect remained consistent across time.

BAY 81-8973, a full-length recombinant factor VIII: manufacturing processes and product characteristics.

BAY 81-8973 (Kovaltry® , Bayer, Berkeley, CA, USA) is an unmodified, full-length recombinant human factor VIII (FVIII) approved for prophylaxis and on-demand treatment of bleeding episodes in patients with haemophilia A. The BAY 81-8973 manufacturing process is based on the process used for sucrose-formulated recombinant FVIII (rFVIII-FS), with changes and enhancements made to improve production efficiency, further augment pathogen safety, and eliminate animal- and human-derived raw materials from the production processes. The baby hamster kidney cell line used for BAY 81-8973 was developed by introducing the gene for human heat shock protein 70 into the rFVIII-FS cell line, a change that improved cell line robustness and productivity. Pathogen safety was enhanced by including a 20-nm filtration step, which can remove viruses, transmissible spongiform encephalopathy agents and potential protein aggregates. No human- or animal-derived proteins are added to the cell culture process, purification or final formulation. The BAY 81-8973 manufacturing process results in a product of enhanced purity with a consistently high degree of sialylation of N-linked glycans on the molecular surface. The innovative manufacturing techniques used for BAY 81-8973 yield an effective rFVIII product with a favourable safety profile for treatment of haemophilia A.

Acute sacral nerve stimulation reduces visceral mechanosensitivity in a cross-organ sensitization model.

BACKGROUND: Sacral nerve stimulation (SNS) is a surgical treatment of fecal and urinary incontinence that consists of inserting a stimulating electrode into one of the s3 or s4 sacral holes. In addition to the benefit of SNS in the treatment of incontinence, recent studies showed that SNS is effective in the treatment of irritable bowel syndrome as well as bladder pain syndrome. The aim of this study was to evaluate the effect of SNS on visceral mechanosensitivity in a cross-organ sensitization rat model. METHODS: Hypersensitive model was obtained by instillation of acetic acid into the bladder of rats during 5 minutes, 30 minutes before the start of the experiments. Visceral sensitivity was assessed by monitoring the change in mean arterial pressure in response to graded isobaric colorectal distension series. To decipher the mechanisms underlying SNS effect, rats were administered intravenously either a nonselective opioid receptor antagonist (naloxone) or a nitric oxide synthesis antagonist (L-NAME). Neuronal activation in the dorsal horn of the sacral spinal cord was measured by counting c-fos immunoreactive cells in response to colorectal distension and NMS. KEY RESULTS: Intravesical acetic acid instillation increased mean arterial pressure variation in response to colorectal distension when compared to saline group. SNS reduced the variation in arterial pressure. Colorectal distension induced a rise in c-fos immunoreactive cells in the dorsal horn of the spinal cord. This effect was reduced by SNS. CONCLUSIONS & INFERENCES: SNS reduces visceral mechanosensitivity in a cross-organ sensitization model.

The role of TGF-ß1 in osteoarthritis of the temporomandibular joint in two genetic mouse models.

OBJECTIVE: The objective of this study is to elucidate osteoarthritis (OA) progression in the temporomandibular joint (TMJ) in two genetic mouse models by assessing the expression of an identified inflammatory marker associated with OA, viz., Tgf-ß1. This study provides mechanistic insight into disease progression based on the temporal expression of Tgf-ß1 in the TMJ. DESIGN: The two models included the heterozygous chondrodysplasia mutation (cho/+), a Coll11a1 mutation, and the autosomal semidominant disproportionate micromelia mutation (Dmm/+), a Col2a1 mutation. To determine OA status histologically, TMJs from each mutant were fixed, sectioned and stained with Safranin O to identify proteoglycans in condylar cartilage and counterstained with Fast Green. The extent of staining and onset of OA-like changes were quantified using the Modified Mankin scoring system. Using immunofluorescence, selected tissue sections of each genotype were stained for the presence of Tgf-ß1, HtrA1, and p-Smad2. RESULTS: The results revealed Mankin scores of the condylar cartilage of both mutants that are consistent with established histopathological changes of OA. Immunofluorescence indicated increased expression of all three molecular markers and their co-localization within condylar chondrocytes of both mutants. CONCLUSIONS: Elevated Tgf-ß1 expression in mutant condylar cartilage supports the hypothesis that this inflammatory mediator is mechanistically involved in the pathogenesis of TMJ OA. Compared to basal expression in control TMJs, the positive co-localized staining for Tgf-ß1, HtrA1, and p-Smad2 in both mutants demonstrates involvement of these molecules in the degradative pathway of OA. Tgf-ß1 therefore is a potential target for further study for the diagnosis and treatment of TMJ OA.

Optical diagnostics study of air flow and powder fluidisation in Nexthaler®--Part I: Studies with lactose placebo formulation.

Effective drug delivery to the lungs by a DPI device requires the air-stream through the device to have sufficient power to aerosolise the powder. Furthermore, sufficient turbulence must be induced, along with particle-wall and particle-particle collisions, in order to de-aggregate small drug particles from large carrier particles. As a result, the emitted and the fine particle doses produced by many commercially available DPI devices tend to be strongly affected by the natural inter-patient variability of the inhaled air flow. The Nexthaler® is a multi-dose breath-actuated dry-powder inhaler with minimum drug delivery-flow rate dependency and incorporating a dose protector. The actuation mechanism of the dose-protector ensures that the dose is only exposed to the inhaled air flow if the flow has sufficient power to cause complete aerosolisation. For this study, a proprietary lactose placebo powder blend was filled into "transparent" Nexthaler® to allow application of high-speed imaging and particle image velocimetry (PIV) techniques to successfully interrogate and reveal details of the powder entrainment and emission processes coupled with characterisation of the flow environment in the vicinity of the mouthpiece exit. The study showed that fluidisation of the bulk of the powder occurs very quickly (∼20ms) after withdrawal of the dose protector followed by powder emission from the device within ∼50ms thereafter. The bulk of the metered placebo dose was emitted within 100-200ms. The visualisation study also revealed that a very small fraction of powder fines is emitted whilst the dose protector still covers the dosing cup as the flow rate through the device accelerates. The PIV results show that the flow exiting the device is highly turbulent with a rotating flow structure, which forces the particles to follow internal paths having a high probability of wall impacts, suggesting that the flow environment inside the Nexthaler® DPI will be very beneficial for carrier-drug de-aggregation.