Quantum physics in inertial and gravitational fields

Covariant generalizations of well-known wave equations predict the existence of inertial-gravitational effects for a variety of quantum systems that range from Bose-Einstein condensates to particles in accelerators. Additional effects arise in models that incorporate Born reciprocity principle and the notion of a maximal acceleration. Some specific examples are discussed in detail.Comment: 25 pages,1 figure,to appear in "Relativity in Rotating Frame

Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty

Perspectives of Patients with Insulin-Treated Type 1 and Type 2 Diabetes on Hypoglycemia: Results of the HAT Observational Study in Central and Eastern European Countries

INTRODUCTION: The aim of this study was to determine the level of awareness of hypoglycemia, the level of fear for hypoglycemia, and the response to hypoglycemic events among insulin-treated diabetes patients from Central and Eastern Europe (CEE). The impact of hypoglycemia on the use of healthcare resources and patient productivity was also assessed. METHODS: This was a multicenter, non-interventional, two-part, patient self-reported questionnaire study that comprised both a retrospective cross-sectional evaluation and a prospective observational evaluation. Study participants were insulin-treated adult patients with type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM) from CEE. RESULTS: Most patients (85.4% T1DM and 83.6% T2DM) reported normal hypoglycemia awareness. The median hypoglycemia fear score was 5 out of 10 for T1DM and 4 out of 10 for T2DM patients. Patients increased glucose monitoring, consulted a doctor/nurse, and/or reduced the insulin dose in response to hypoglycemia. As a consequence of hypoglycemia, patients took leave from work/studies or arrived late and/or left early. Hospitalization was required for 31 (1.2%) patients with T1DM and 66 (2.1%) patients with T2DM. CONCLUSION: Hypoglycemia impacts patients' personal and social functioning, reduces productivity, and results in additional costs, both direct (related to increased use of healthcare resources) and indirect (related to absenteeism. FUNDING: Novo Nordisk

A mathematical model of aging-related and cortisol induced hippocampal dysfunction

<p>Abstract</p> <p>Background</p> <p>The hippocampus is essential for declarative memory synthesis and is a core pathological substrate for Alzheimer's disease (AD), the most common aging-related dementing disease. Acute increases in plasma cortisol are associated with transient hippocampal inhibition and retrograde amnesia, while chronic cortisol elevation is associated with hippocampal atrophy. Thus, cortisol levels could be monitored and managed in older people, to decrease their risk of AD type hippocampal dysfunction. We generated an in silico<it/>model of the chronic effects of elevated plasma cortisol on hippocampal activity and atrophy, using the systems biology mark-up language (SBML). We further challenged the model with biologically based interventions to ascertain if cortisol associated hippocampal dysfunction could be abrogated.</p> <p>Results</p> <p>The in silico<it/>SBML model reflected the in vivo<it/>aging of the hippocampus and increased plasma cortisol and negative feedback to the hypothalamic pituitary axis. Aging induced a 12% decrease in hippocampus activity (HA), increased to 30% by acute and 40% by chronic elevations in cortisol. The biological intervention attenuated the cortisol associated decrease in HA by 2% in the acute cortisol simulation and by 8% in the chronic simulation.</p> <p>Conclusion</p> <p>Both acute and chronic elevations in cortisol secretion increased aging-associated hippocampal atrophy and a loss of HA in the model. We suggest that this first SMBL model, in tandem with in vitro<it/>and in vivo<it/>studies, may provide a backbone to further frame computational cortisol and brain aging models, which may help predict aging-related brain changes in vulnerable older people.</p

Role of PCSK5 Expression in Mouse Ovarian Follicle Development: Identification of the Inhibin α- and β-Subunits as Candidate Substrates

Inhibin and activin are essential dimeric glycoproteins belonging to the transforming growth factor-beta (TGFβ) superfamily. Inhibin is a heterodimer of α- and β-subunits, whereas activin is a homodimer of β-subunits. Production of inhibin is regulated during the reproductive cycle and requires the processing of pro-ligands to produce mature hormone. Furin is a subtilisin-like proprotein convertase (proconvertase) that activates precursor proteins by cleavage at basic sites during their transit through the secretory pathway and/or at the cell surface. We hypothesized that furin-like proconvertases are central regulators of inhibin α- and β-subunit processing within the ovary. We analyzed the expression of the proconvertases furin, PCSK5, PCSK6, and PCSK7 in the developing mouse ovary by real-time quantitative RT-PCR. The data showed that proconvertase enzymes are temporally expressed in ovarian cells. With the transition from two-layer secondary to pre-antral follicle, only PCSK5 mRNA was significantly elevated. Activin A selectively enhanced expression of PCSK5 mRNA and decreased expression of furin and PCSK6 in cultured two-layer secondary follicles. Inhibition of proconvertase enzyme activity by dec-RVKR-chloromethylketone (CMK), a highly specific and potent competitive inhibitor of subtilisin-like proconvertases, significantly impeded both inhibin α- and β-subunit maturation in murine granulosa cells. Overexpression of PC5/6 in furin-deficient cells led to increased inhibin α- and βB-subunit maturation. Our data support the role of proconvertase PCSK5 in the processing of ovarian inhibin subunits during folliculogenesis and suggest that this enzyme may be an important regulator of inhibin and activin bioavailability

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Development of burnout over time and the causal order of the three dimensions of burnout among male and female GPs. A three-wave panel study

<p>Abstract</p> <p>Background</p> <p>A good understanding of the aetiology and development of burnout facilitates its early recognition, prevention and treatment. Since the prevalence and onset of this health problem is thought to differ between men and women, sex must be taken into account. This study aims to assess the prevalence and development of burnout among General Practitioners (GPs). In this population the prevalence of burnout is high.</p> <p>Methods</p> <p>We performed a three-wave longitudinal study (2002, 2004, 2006) in a random sample of Dutch GPs. Data were collected by means of self-report questionnaires including the Maslach Burnout Inventory. Our final sample consisted of 212 GPs of which 128 were male. Data were analyzed by means of SPSS and LISREL.</p> <p>Results</p> <p>Results indicate that about 20% of the GPs is clinically burned out (but still working). For both sexes, burnout decreased after the first wave, but increased again after the second wave. The prevalence of depersonalization is higher among men. With regard to the process of burnout we found that for men burnout is triggered by depersonalization and by emotional exhaustion for women.</p> <p>Conclusions</p> <p>As regards the developmental process of burnout, we found evidence for the fact that the aetiological process of burnout, that is the causal order of the three burnout dimensions, differs between men and women. These sex differences should be taken into account in vocational training and policy development, especially since general practice is feminizing rapidly.</p

Highly variable response to cytotoxic chemotherapy in carcinoma-associated fibroblasts (CAFs) from lung and breast

<p>Abstract</p> <p>Background</p> <p>Carcinoma-associated fibroblasts (CAFs) can promote carcinogenesis and tumor progression. Only limited data on the response of CAFs to chemotherapy and their potential impact on therapy outcome are available. This study was undertaken to analyze the influence of chemotherapy on carcinoma-associated fibroblasts (CAFs) <it>in vitro </it>and <it>in vivo</it>.</p> <p>Methods</p> <p>The <it>in vivo </it>response of stromal cells to chemotherapy was investigated in 22 neoadjuvant treated breast tumors on tissue sections before and after chemotherapy. Response to chemotherapy was analyzed <it>in vitro </it>in primary cultures of isolated CAFs from 28 human lung and 9 breast cancer tissues. The response was correlated to <it>Mdm2</it>, <it>ERCC1 </it>and <it>TP53 </it>polymorphisms and <it>TP53 </it>mutation status. Additionally, the cytotoxic effects were evaluated in an <it>ex vivo </it>experiment using cultured tissue slices from 16 lung and 17 breast cancer specimens.</p> <p>Results</p> <p>Nine of 22 tumors showed a therapy-dependent reduction of stromal activity. Pathological response of tumor or stroma cells did not correlate with clinical response. Isolated CAFs showed little sensitivity to paclitaxel. In contrast, sensitivity of CAFs to cisplatinum was highly variable with a GI50 ranging from 2.8 to 29.0 μM which is comparable to the range observed in tumor cell lines. No somatic <it>TP53 </it>mutation was detected in any of the 28 CAFs from lung cancer tissue. In addition, response to cisplatinum was not significantly associated with the genotype of <it>TP53 </it>nor <it>Mdm2 </it>and <it>ERCC1 </it>polymorphisms. However, we observed a non-significant trend towards decreased sensitivity in the presence of <it>TP53 </it>variant genotype. In contrast to the results obtained in isolated cell culture, in tissue slice culture breast cancer CAFs responded to paclitaxel within their microenvironment in the majority of cases (9/14). The opposite was observed in lung cancer tissues: only few CAFs were sensitive to cisplatinum within their microenvironment (2/15) whereas a higher proportion responded to cisplatinum in isolated culture.</p> <p>Conclusion</p> <p>Similar to cancer cells, CAF response to chemotherapy is highly variable. Beside significant individual/intrinsic differences the sensitivity of CAFs seems to depend also on the cancer type as well as the microenvironment.</p