The association between socioeconomic status and C-reactive protein in Bayesian perspective.

•This study analyzed the total health inequality on risks of chronic inflammation.•We used Bayesian multiple and distributional regression models.•Between-group posterior distributions show a robust educational gradient in health.•Within-group posterior distributions show polarized risks for individuals.

Associations between sedentary behavior and health and the moderating role of physical activity in young people within a cross-sectional investigation.

The purpose of this study was to determine the influence of sedentary behavior (SB) on the frequency of health complaints (fHC) as well as on self-rated health (SRH) and body mass index (BMI), and to determine whether physical activity (PA) moderated this influence. Data were obtained from the Youth Survey Luxembourg 2019 (N = 2,802), a nationally representative stratified random sample of all youths aged 16 to 29 years who were living in Luxembourg. fHC is a composite measure of eight common psychosomatic health complaints, SRH was measured on a five-point scale, and BMI was calculated by dividing participants' body weight by the square of their body height (kg/m2). PA and SB values were obtained from factor analyses of the relevant questionnaire items. SB was evaluated as both leisure-time SB and gaming-associated SB. Multiple regression analyses adjusted for age, sex, socioeconomic status, and migration status were used to determine the association between SB, fHC, BMI, and SRH. We found that leisure-time SB was positively associated with fHC, but not with SRH or BMI. Gaming-associated SB was positively associated with fHC and BMI but was negatively associated with SRH. PA was negatively associated with fHC, BMI and SRH. No statistically significant moderating effects were observed. We found that both leisure-time and gaming-associated SB showed statistically significant impacts on health. Although PA is known to be beneficial to health, we conclude that its potential to mitigate the negative effects of SB is limited in young people.

Distribution of Psychological Instability Among Surgeons.

BACKGROUND: High emotional instability (i.e., neuroticism) is associated with poor mental health. Conversely, traumatic experiences may increase neuroticism. Stressful experiences such as complications are common in the surgical profession, with neurosurgeons being particularly affected. We compared the personality trait neuroticism between physicians in a prospective cross-sectional study. METHODS: We used an online survey using the Ten-Item Personality Inventory, an internationally validated measure of the 5-factor model of personality dimensions. It was distributed to board-certified physicians, residents, and medical students in several European countries and Canada (n = 5148). Multivariate linear regression was used to model differences between surgeons, nonsurgeons, and specialties with occasional surgical interventions with respect to neuroticism, adjusting for sex, age, age squared, and their interactions, then testing equality of parameters of adjusted predictions separately and jointly using Wald tests. RESULTS: With an expected variability within disciplines, average levels of neuroticism are lower in surgeons than nonsurgeons, especially in the first part of their career. However, the course of neuroticism across age follows a quadratic pattern, that is, an increase after the initial decrease. The acceleration of neuroticism with age is specifically significant in surgeons. Levels of neuroticism are lowest towards mid-career, but exhibit a strong secondary increase towards the end of the surgeon's career. This pattern seems driven by neurosurgeons. CONCLUSIONS: Despite initially lower levels of neuroticism, surgeons suffer a stronger increase of neuroticism together with age. Because, beyond well-being, neuroticism influences professional performance and health care systems costs, explanatory studies are mandatory to enlighten causes of this burden.

Survey Report on Complaints Related to the Interconnectivity between Vial Containers and Transfer Devices.

To address the challenges related to the interconnectivity between vial container closure systems and vial transfer devices, pharmaceutical, elastomer, and transfer device manufacturers have formed a working group under the Product Quality Research Institute (PQRI) to establish best practices for the evaluation of the assembly of vial transfer devices and vial systems. As part of the project, the first activity was to quantify the nature and frequency of issues (complaints). To this end, the working group conducted a survey with questionnaires related to categories and numbers of complaints, regions/countries where complaints were received, and the nature of the manufacturers who received the complaints. The survey was distributed to the 16 companies participating in the working group, and 11 companies submitted a response. Besides quantifying and ranking the frequency of issues, the survey determined what issues are common across all companies and what issues may be product-specific or specific by manufacturer. In this article, the analysis and outcomes of the survey will be presented, and the next steps will be discussed.

Neurologists, neurosurgeons, and psychiatrists' personality traits: a comparison.

BACKGROUND: Clinicians in neuroscientific disciplines may present distinct personality profiles. Despite of potential relevance to clinical practice, this has not yet been studied. We therefore aimed to compare personality profiles of physicians working in the three main disciplines of clinical neuroscience, i.e., neurologists, neurosurgeons, and psychiatrists, between each other, across levels of training and to other specialties. METHODS: An online survey using the Ten-Item Personality Inventory (TIPI), an internationally validated measure of the five-factor model of personality dimensions, was distributed to board-certified physicians, residents, and medical students in several European countries and Canada. Differences in personality profiles were analyzed using multivariate analysis of variance and canonical linear discriminant analysis on age- and sex-standardized z-scores of personality traits. Single personality traits were analyzed using robust t tests. RESULTS: Of the 5148 respondents who completed the survey, 723 indicated the specialties neurology, neurosurgery, or psychiatry. Compared to all other specialties, personality profiles of training and trained physicians in these three main clinical neuroscience disciplines ("NN&P") significantly differed, with significantly higher scores in openness to experience. Within NN&P, there were significant differences in personality profiles, driven by lower neuroticism in neurosurgeons, higher conscientiousness in neurosurgeons and neurologists, and higher agreeableness in psychiatrists. Across levels of training, NN&P personality profiles did not differ significantly. CONCLUSION: The distinct clinical neuroscience personality profile is characterized by higher levels of openness to experience compared to non-neuroscience specialties. Despite high variability within each discipline, moderate, but solid differences in the personality profiles of neurologists, neurosurgeons and psychiatrists exist.

Conscious Experience and Psychological Consequences of Awake Craniotomy.

BACKGROUND: Experiencing cranial surgery under awake conditions may expose patients to considerable psychological strain. METHODS: This study aimed to investigate the occurrence and course of psychological sequelae following awake craniotomy (AC) for brain tumors in a series of 20 patients using a broad, validated psychological assessment preoperatively, intraoperatively, postoperatively and a standardized follow-up of 3 months. In addition, the association of the preoperative psychological condition (including, but not limited to, anxiety and fear) with perioperative pain perception and interference was assessed. RESULTS: AC did not induce any shift in the median levels of anxiety, depression, and stress symptoms already present prior to the procedure. Furthermore, anxiety and depression were all moderately to strongly associated over time (all P < 0.05). Stress symptoms also correlated positively over all times of measurement. Stress 3 days after surgery was strongly associated with stress 3 months after surgery (P < 0.001), whereas the correlation between preoperative and immediate postoperative stress showed a statistical trend (P = 0.07). Preoperative fear was not related to intraoperative pain, but to pain and its interference with daily activity on the third postoperative day (P < 0.001 and P < 0.01, respectively). CONCLUSIONS: Postoperative psychological symptoms clearly correlated with their corresponding preoperative symptoms. Thus, mental health was not negatively affected by the AC experience in our series. Intraoperative fear and pain were not related to the preoperative psychological condition. However, preoperative fear and anxiety were positively related with pain and its interference with daily activity in the immediate postoperative period.

Demographic and clinical predictors of response to internet-enabled cognitive-behavioural therapy for depression and anxiety.

BACKGROUND: Common mental health problems affect a quarter of the population. Online cognitive-behavioural therapy (CBT) is increasingly used, but the factors modulating response to this treatment modality remain unclear. AIMS: This study aims to explore the demographic and clinical predictors of response to one-to-one CBT delivered via the internet. METHOD: Real-world clinical outcomes data were collected from 2211 NHS England patients completing a course of CBT delivered by a trained clinician via the internet. Logistic regression analyses were performed using patient and service variables to identify significant predictors of response to treatment. RESULTS: Multiple patient variables were significantly associated with positive response to treatment including older age, absence of long-term physical comorbidities and lower symptom severity at start of treatment. Service variables associated with positive response to treatment included shorter waiting times for initial assessment and longer treatment durations in terms of the number of sessions. CONCLUSIONS: Knowledge of which patient and service variables are associated with good clinical outcomes can be used to develop personalised treatment programmes, as part of a quality improvement cycle aiming to drive up standards in mental healthcare. This study exemplifies translational research put into practice and deployed at scale in the National Health Service, demonstrating the value of technology-enabled treatment delivery not only in facilitating access to care, but in enabling accelerated data capture for clinical research purposes. DECLARATION OF INTEREST: A.C., S.B., V.T., K.I., S.F., A.R., A.H. and A.D.B. are employees or board members of the sponsor. S.R.C. consults for Cambridge Cognition and Shire. Keywords: Anxiety disorders; cognitive behavioural therapies; depressive disorders; individual psychotherapy.

Different but similar: personality traits of​ surgeons and internists-results of a cross-sectional observational study.

OBJECTIVES: Medical practice may attract and possibly enhance distinct personality profiles. We set out to describe the personality profiles of surgical and medical specialties focusing on board-certified physicians. DESIGN: Prospective, observational. SETTING: Online survey containing the Ten-Item Personality Inventory (TIPI), an internationally validated measure of the Five Factor Model of personality dimensions, distributed to board-certified physicians, residents and medical students in several European countries and Canada. Differences in personality profiles were analysed using multivariate analysis of variance and Canonical Linear Discriminant Analysis on age-standardised and sex-standardised z-scores of the personality traits. Single personality traits were analysed using robust t-tests. PARTICIPANTS: The TIPI was completed by 2345 board-certified physicians, 1453 residents and 1350 medical students, who also provided demographic information. RESULTS: Normal population and board-certified physicians' personality profiles differed (p<0.001). The latter scored higher on conscientiousness, extraversion and agreeableness, but lower on neuroticism (all p<0.001). There was no difference in openness to experience. Board-certified surgical and medical doctors' personality profiles were also different (p<0.001). Surgeons scored higher on extraversion (p=0.003) and openness to experience (p=0.002), but lower on neuroticism (p<0.001). There was no difference in agreeableness and conscientiousness. These differences in personality profiles were reproduced at other levels of training, that is, in students and training physicians engaging in surgical versus medical practice. CONCLUSION: These results indicate the existence of a distinct and consistent average 'physician personality'. Despite high variability within disciplines, there are moderate but solid and reproducible differences between surgical and medical specialties.

How unemployment scarring affects skilled young workers: evidence from a factorial survey of Swiss recruiters.

We ask how employers contribute to unemployment scarring in the recruitment process in the German-speaking part of Switzerland. By drawing on recruitment theories, we aim to better understand how recruiters assess different patterns of unemployment in a job candidate's CV and how this affects the chances of young applicants being considered for a vacancy. We argue that in contexts with tight school-work linkage and highly standardised Vocational Education and Training systems, the detrimental effect of early unemployment depends on how well the applicant's profile matches the requirements of the advertised position. To test this assumption, we surveyed Swiss recruiters who were seeking to fill positions during the time of data collection. We employed a factorial survey experiment that tested how the (un)employment trajectories in hypothetical young job applicants' CV affected their chances of being considered for a real vacancy. Our results show that unemployment decreases the perceived suitability of an applicant for a specific job, which implies there is a scarring effect of unemployment that increases with the duration of being unemployed. But we also found that these effects are moderated by how well the applicant's profile matches the job's requirements. Overall, the worse the match between applicant's profile and the job profile, the smaller are the scarring effects of unemployment. In sum, our findings contribute to the literature by revealing considerable heterogeneity in the scarring effects of unemployment. Our findings further suggest that the scarring effects of unemployment need to be studied with regard to country-specific institutional settings, the applicants' previous education and employment experiences, and the job characteristics.

Sexual Dysfunction After Good-Grade Aneurysmal Subarachnoid Hemorrhage.

OBJECTIVE: To assess the consequences of aneurysmal subarachnoid hemorrhage (aSAH) on sexual pleasure in patients with an otherwise favorable neurologic outcome. METHODS: Anonymous, standardized questionnaires concerning sexual function, including the International Index of Erectile Function (IIEF), Female Sexual Function Index (FSFI), and a statement on subjective change in sexual pleasure after aSAH, were completed by 33 patients treated at the Cantonal Hospital St Gallen between 2005 and 2013. All had favorable neurologic outcomes (Glasgow Outcome Scale score 4 or 5). RESULTS: Ten patients (31.3%) reported a subjective worsening of sexual pleasure after aSAH. Sexual dysfunction according to FSFI criteria affected 9 of the 19 female patients (47.4%). All 19 women had a hypoactive sexual desire disorder. Erectile dysfunction was present in 7 of the 14 male patients (50%). Patients with World Federation of Neurosurgical Societies (WFNS) grade 2 aSAH were significantly more likely to report a subjective worsening of sexual experience after hemorrhage than those with WFNS grade 1. CONCLUSIONS: This is the first known evaluation of sexual health following aSAH with otherwise favorable neurologic outcomes, and confirms that sexual dysfunction is common in this population. Sexual health should be explored during follow-up with these patients.

The Recombinant Sea Urchin Immune Effector Protein, rSpTransformer-E1, Binds to Phosphatidic Acid and Deforms Membranes.

The purple sea urchin, Strongylocentrotus purpuratus, possesses a sophisticated innate immune system that functions without adaptive capabilities and responds to pathogens effectively by expressing the highly diverse SpTransformer gene family (formerly the Sp185/333 gene family). The swift gene expression response and the sequence diversity of SpTransformer cDNAs suggest that the encoded proteins have immune functions. Individual sea urchins can express up to 260 distinct SpTransformer proteins, and their diversity suggests that different versions may have different functions. Although the deduced proteins are diverse, they share an overall structure of a hydrophobic leader, a glycine-rich N-terminal region, a histidine-rich region, and a C-terminal region. Circular dichroism analysis of a recombinant SpTransformer protein, rSpTransformer-E1 (rSpTrf-E1) demonstrates that it is intrinsically disordered and transforms to α helical in the presence of buffer additives and binding targets. Although native SpTrf proteins are associated with the membranes of perinuclear vesicles in the phagocyte class of coelomocytes and are present on the surface of small phagocytes, they have no predicted transmembrane region or conserved site for glycophosphatidylinositol linkage. To determine whether native SpTrf proteins associate with phagocyte membranes through interactions with lipids, when rSpTrf-E1 is incubated with lipid-embedded nylon strips, it binds to phosphatidic acid (PA) through both the glycine-rich region and the histidine-rich region. Synthetic liposomes composed of PA and phosphatidylcholine show binding between rSpTrf-E1 and PA by fluorescence resonance energy transfer, which is associated with leakage of luminal contents suggesting changes in lipid organization and perhaps liposome lysis. Interactions with liposomes also change membrane curvature leading to liposome budding, fusion, and invagination, which is associated with PA clustering induced by rSpTrf-E1 binding. Longer incubations result in the extraction of PA from the liposomes, which form disorganized clusters. CD shows that when rSpTrf-E1 binds to PA, it changes its secondary structure from disordered to α helical. These results provide evidence for how SpTransformer proteins may associate with molecules that have exposed phosphates including PA on cell membranes and how the characteristic of protein multimerization may drive changes in the organization of membrane lipids.

The Role of Perceived Stress and Self-Efficacy in Young People's Life Satisfaction: A Longitudinal Study.

Life satisfaction is an important indicator of successful development. However, adolescents' life satisfaction tends to be relatively unsteady, and environmental influences play a critical role in shaping life satisfaction among adolescents in the transition to young adulthood. Given the paramount importance that education plays in adolescents' lives, adolescents' life satisfaction may vary as a function of school-related stress experience. At the same time, coping resources may help reduce adverse effects of stress on life satisfaction. With this in mind, we examined whether, and to what extent, perceived stress in education and general self-efficacy (a resource that facilitates coping) affect the life satisfaction of adolescents in transition to young adulthood. We distinguished between baseline levels of stress and self-efficacy and within-person change in stress and self-efficacy to determine whether life satisfaction is sensitive to fluctuations in stress and self-efficacy when person-specific levels of stress and self-efficacy are taken into account. Estimating growth curve models on data from a panel study on the life trajectories of compulsory-school leavers (n = 5126, 55.3 % female), we found that baseline levels of stress and self-efficacy, as well as within-person change in stress and self-efficacy, affected adolescents' life satisfaction. Moreover, our results showed that baseline self-efficacy mitigated the negative effect of baseline stress on life satisfaction. These findings improve our understanding of two major psychological determinants of adolescents' life satisfaction and extend our knowledge of life satisfaction trajectories during the transition to young adulthood.

Membrane phase characteristics control NA-CATH activity.

Our studies presented in this report focus on the behavior of NA-CATH, an α-helical cathelicidin antimicrobial peptide, originally discovered in the Naja atra snake. It has demonstrated high potency against gram-positive and gram-negative bacteria with minimal hemolysis. Here we examine the kinetics, behaviors and potential mechanisms of the peptide in the presence of membrane liposome, modeling Escherichia coli, whose membrane exhibits distinct lipid phases. To understand NA-CATH interactions, the role of lipid phases is critical. We test three different lipid compositions to detangle the effect of phase on NA-CATH's activity using a series of leakage experiments. From these studies, we observe that NA-CATH changes from membrane disruption to pore-based lysing, depending on phases and lipid composition. This behavior also plays a major role in its kinetics.

The structure and behavior of the NA-CATH antimicrobial peptide with liposomes.

Naja atra cathelicidin (NA-CATH) is a 34-amino acid highly cationic peptide identified in Chinese cobras to possess potent toxicity against gram-negative and gram-positive bacteria and low toxicity against host cells. Here, we report the NMR solution structure of the full-length NA-CATH peptide and its interaction with liposomes. The structure shows a well-defined α-helix between residues Phe3 to Lys23, on which one surface is lined by the side-chains of one arginine and 11 lysine residues, while the other side is populated by hydrophobic residues. The last eleven amino acids, which are predominately aromatic and hydrophobic in nature, have no defined structure. NMR data reveal that these residues do not interact with the hydrophobic residues of the helix, indicating that the C-terminal residues have random conformations. Fluorescence requenching experiments, in which liposomes serve as a mimic of the bacterial membranes, result in fluorophore leakage that is consistent with a membrane thinning or transient pore formation mechanism. NMR titration studies of the peptide-liposome interaction reveal that the peptide is in fast exchange with the liposome, consistent with the fluorescent studies. These data indicate that full length NA-CATH possesses a helical segment and unstructured C-terminal tail that disrupts the bilayer to induce leakage and lysing.

Toward single-molecule optical mapping of the epigenome.

The past decade has seen an explosive growth in the utilization of single-molecule techniques for the study of complex systems. The ability to resolve phenomena otherwise masked by ensemble averaging has made these approaches especially attractive for the study of biological systems, where stochastic events lead to inherent inhomogeneity at the population level. The complex composition of the genome has made it an ideal system to study at the single-molecule level, and methods aimed at resolving genetic information from long, individual, genomic DNA molecules have been in use for the last 30 years. These methods, and particularly optical-based mapping of DNA, have been instrumental in highlighting genomic variation and contributed significantly to the assembly of many genomes including the human genome. Nanotechnology and nanoscopy have been a strong driving force for advancing genomic mapping approaches, allowing both better manipulation of DNA on the nanoscale and enhanced optical resolving power for analysis of genomic information. During the past few years, these developments have been adopted also for epigenetic studies. The common principle for these studies is the use of advanced optical microscopy for the detection of fluorescently labeled epigenetic marks on long, extended DNA molecules. Here we will discuss recent single-molecule studies for the mapping of chromatin composition and epigenetic DNA modifications, such as DNA methylation.