The effect of 12C + 12C rate uncertainties on the evolution and nucleosynthesis of massive stars

[Shortened] The 12C + 12C fusion reaction has been the subject of considerable experimental efforts to constrain uncertainties at temperatures relevant for stellar nucleosynthesis. In order to investigate the effect of an enhanced carbon burning rate on massive star structure and nucleosynthesis, new stellar evolution models and their yields are presented exploring the impact of three different 12C + 12C reaction rates. Non-rotating stellar models were generated using the Geneva Stellar Evolution Code and were later post-processed with the NuGrid Multi-zone Post-Processing Network tool. The enhanced rate causes core carbon burning to be ignited more promptly and at lower temperature. This reduces the neutrino losses, which increases the core carbon burning lifetime. An increased carbon burning rate also increases the upper initial mass limit for which a star exhibits a convective carbon core. Carbon shell burning is also affected, with fewer convective-shell episodes and convection zones that tend to be larger in mass. Consequently, the chance of an overlap between the ashes of carbon core burning and the following carbon shell convection zones is increased, which can cause a portion of the ashes of carbon core burning to be included in the carbon shell. Therefore, during the supernova explosion, the ejecta will be enriched by s-process nuclides synthesized from the carbon core s process. The yields were used to estimate the weak s-process component in order to compare with the solar system abundance distribution. The enhanced rate models were found to produce a significant proportion of Kr, Sr, Y, Zr, Mo, Ru, Pd and Cd in the weak component, which is primarily the signature of the carbon-core s process. Consequently, it is shown that the production of isotopes in the Kr-Sr region can be used to constrain the 12C + 12C rate using the current branching ratio for a- and p-exit channels.Comment: The paper contains 17 figures and 7 tables. Table 7 will be published in full online onl

The Expression of ERCC1, RRM1, and BRCA1 in Breast Cancer According to the Immunohistochemical Phenotypes

We studied the expression of BRCA1, ERCC1, and RRM1 which play an important role in DNA repair systems in breast cancer. Immunohistochemical staining for EGFR, BRCA1, ERCC1, and RRM1 were performed by using a tissue microarray made from 230 breast cancer patients. Patients were classified into luminal A, luminal B, HER-2, and triple negative breast cancer (TNBC) types according to ER, PR, and HER-2 expression. The expression of ERCC1, RRM1, and BRCA1 were correlated (P < 0.05). The expression level of ERCC1 was the lowest in TNBC type (P = 0.031), ERCC1 negativity was more prominent in TNBC and luminal B groups than luminal A and HER-2 groups (P = 0.013). Cases with EGFR overexpression showed high expression of RRM1 and BRCA1 (P = 0.046, and 0.004, respectively). In conclusion, the expression of ERCC1 is particularly lower in TNBCs than other types of breast cancers

Winter cancellations of elective surgical procedures in the United Kingdom: A questionnaire survey of patients on the economic and psychological impact

Objectives: To quantify the economic and psychological impact of the cancellation of operations due to winter pressures on patients, their families and the economy.Design: This questionnaire study was designed with the help of patient groups. Data were collected on the economic and financial burden of cancellations. Emotions were also quantified on a 5-point Likert scale.Setting: Five NHS Hospital Trusts in the East Midlands region of England.Participants: We identified 796 participants who had their elective operations cancelled between 1 November 2017 and 31 March 2018 and received responses from 339 (43%) participants.Interventions: Participants were posted a modified version of a validated quality of life questionnaire with a prepaid return envelope.Main outcome measures: The primary outcome measures were the financial and psychological impact of the cancellation of elective surgery on patients and their families.Results: Of the 339 respondents, 163 (48%) were age

Influence of Prior Influenza Vaccination on Antibody and B-Cell Responses

Currently two vaccines, trivalent inactivated influenza vaccine (TIV) and live attenuated influenza vaccine (LAIV), are licensed in the USA. Despite previous studies on immune responses induced by these two vaccines, a comparative study of the influence of prior influenza vaccination on serum antibody and B-cell responses to new LAIV or TIV vaccination has not been reported. During the 2005/6 influenza season, we quantified the serum antibody and B-cell responses to LAIV or TIV in adults with differing influenza vaccination histories in the prior year: LAIV, TIV, or neither. Blood samples were collected on days 0, 7–9 and 21–35 after immunization and used for serum HAI assay and B-cell assays. Total and influenza-specific circulating IgG and IgA antibody secreting cells (ASC) in PBMC were detected by direct ELISPOT assay. Memory B cells were also tested by ELISPOT after polyclonal stimulation of PBMC in vitro. Serum antibody, effector, and memory B-cell responses were greater in TIV recipients than LAIV recipients. Prior year TIV recipients had significantly higher baseline HAI titers, but lower HAI response after vaccination with either TIV or LAIV, and lower IgA ASC response after vaccination with TIV than prior year LAIV or no vaccination recipients. Lower levels of baseline HAI titer were associated with a greater fold-increase of HAI titer and ASC number after vaccination, which also differed by type of vaccine. Our findings suggest that the type of vaccine received in the prior year affects the serum antibody and the B-cell responses to subsequent vaccination. In particular, prior year TIV vaccination is associated with sustained higher HAI titer one year later but lower antibody response to new LAIV or TIV vaccination, and a lower effector B-cell response to new TIV but not LAIV vaccination

Fasting and surgery timing (FaST) audit

Background & aimsInternational guidance advocates the avoidance of prolonged preoperative fasting due to its negative impact on perioperative hydration. This study aimed to assess the adherence to these guidelines for fasting in patients undergoing elective and emergency surgery in the East Midlands region of the UK.MethodsThis prospective audit was performed over a two-month period at five National Health Service (NHS) Trusts across the East Midlands region of the UK. Demographic data, admission and operative details, and length of preoperative fasting were collected on adult patients listed for emergency and elective surgery.ResultsOf the 343 surgical patients included within the study, 50% (n = 172) were male, 78% (n = 266) had elective surgery and 22% (n = 77) underwent emergency surgery. Overall median fasting times (Q1, Q3) were 16.1 (13.0, 19.4) hours for food and 5.8 (3.5, 10.7) hours for clear fluids. Prolonged fasting >12 h was documented in 73% (n = 250) for food, and 21% (n = 71) for clear fluids. Median fasting times from clear fluids and food were longer in the those undergoing emergency surgery when compared with those undergoing elective surgery: 13.0 (6.4, 22.6) vs. 4.9 (3.3, 7.8) hours, and 22.0 (14.0, 37.4) vs. 15.6 (12.9, 17.8) hours respectively, p < 0.0001.ConclusionsDespite international consensus on the duration of preoperative fasting, patients continue to fast from clear fluids and food for prolonged lengths of time. Patients admitted for emergency surgery were more likely to fast for longer than those having elective surgery

Blood pressure and associated factors in a North African adolescent population. a national cross-sectional study in Tunisia

<p>Abstract</p> <p>Background</p> <p>In southern and eastern Mediterranean countries, changes in lifestyle and the increasing prevalence of excess weight in childhood are risk factors for high blood pressure (BP) during adolescence and adulthood. The aim of this study was to evaluate the BP status of Tunisian adolescents and to identify associated factors.</p> <p>Methods</p> <p>A cross-sectional study in 2005, based on a national, stratified, random cluster sample of 1294 boys and 1576 girls aged 15-19 surveyed in home visits. The socio-economic and behavioral characteristics of the adolescents were recorded. Overweight/obesity were assessed by Body Mass Index (BMI) from measured height and weight (WHO, 2007), abdominal obesity by waist circumference (WC). BP was measured twice during the same visit. Elevated BP was systolic (SBP) or diastolic blood pressure (DBP) ≥ 90th of the international reference or ≥ 120/80 mm Hg for 15-17 y., and SBP/DBP ≥ 120/80 mm Hg for 18-19 y.; hypertension was SBP/DBP ≥ 95th for 15-17 y. and ≥ 140/90 mm Hg for 18-19 y. Adjusted associations were assessed by logistic regression.</p> <p>Results</p> <p>The prevalence of elevated BP was 35.1%[32.9-37.4]: higher among boys (46.1% vs. 33.3%; <it>P </it>< 0.0001); 4.7%[3.8-5.9] of adolescents had hypertension. Associations adjusted for all covariates showed independent relationships with BMI and WC: - obesity vs. no excess weight increased elevated BP (boys OR = 2.1[1.0-4.2], girls OR = 2.3[1.3-3.9]) and hypertension (boys OR = 3.5[1.4-8.9], girls OR = 5.4[2.2-13.4]), - abdominal obesity (WC) was also associated with elevated BP in both genders (for boys: 2nd vs. 1st tertile OR = 1.7[1.3-2.3], 3rd vs.1st tertile OR = 2.8[1.9-4.2]; for girls: 2nd vs. 1st tertile OR = 1.6[1.2-2.1], 3rd vs.1st tertile OR = 2.1[1.5-3.0]) but only among boys for hypertension. Associations with other covariates were weaker: for boys, hypertension increased somewhat with sedentary lifestyle, while elevated BP was slightly more prevalent among urban girls and those not attending school.</p> <p>Conclusion</p> <p>Within the limits of BP measurement on one visit only, these results suggest that Tunisian adolescents of both genders are likely not spared from early elevated BP. Though further assessment is likely needed, the strong association with overweight/obesity observed suggests that interventions aimed at changing lifestyles to reduce this main risk factor may also be appropriate for the prevention of elevated BP.</p

Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.

Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition

Superior antigen-specific CD4+ T-cell response with AS03-adjuvantation of a trivalent influenza vaccine in a randomised trial of adults aged 65 and older

BACKGROUND: The effectiveness of trivalent influenza vaccines may be reduced in older versus younger adults because of age-related immunosenescence. The use of an adjuvant in such a vaccine is one strategy that may combat immunosenescence, potentially by bolstering T-cell mediated responses. METHODS: This observer-blind study, conducted in the United States (US) and Spain during the 2008-2009 influenza season, evaluated the effect of Adjuvant System AS03 on specific T-cell responses to a seasonal trivalent influenza vaccine (TIV) in >/=65 year-old adults.Medically-stable adults aged >/=65 years were randomly allocated to receive a single dose of AS03-adjuvanted TIV (TIV/AS03) or TIV. Healthy adults aged 18-40 years received only TIV. Blood samples were collected on Day 0, Day 21, Day 42 and Day 180. Influenza-specific CD4+ T cells, defined by the induction of the immune markers CD40L, IL-2, IFN-gamma, or TNF-alpha, were measured in ex vivo cultures of antigen-stimulated peripheral blood mononuclear cells. RESULTS: A total of 192 adults were vaccinated: sixty nine and seventy three >/=65 year olds received TIV/AS03 and TIV, respectively; and fifty 18 - 40 year olds received TIV. In the >/=65 year-old group on Day 21, the frequency of CD4+ T cells specific to the three vaccine strains was superior in the TIV/AS03 recipients to the frequency in TIV (p /=65 year-old recipients of TIV/AS03 than in the 18 - 40 year old recipients of TIV on Days 21 (p = 0.006) and 42 (p = 0.011). CONCLUSION: This positive effect of AS03 Adjuvant System on the CD4+ T-cell response to influenza vaccine strains in older adults could confer benefit in protection against clinical influenza disease in this population. TRIAL REGISTRATION: (Clinicaltrials.gov.). NCT00765076

Intranasal Delivery of Influenza Subunit Vaccine Formulated with GEM Particles as an Adjuvant

Nasal administration of influenza vaccine has the potential to facilitate influenza control and prevention. However, when administered intranasally (i.n.), commercially available inactivated vaccines only generate systemic and mucosal immune responses if strong adjuvants are used, which are often associated with safety problems. We describe the successful use of a safe adjuvant Gram-positive enhancer matrix (GEM) particles derived from the food-grade bacterium Lactococcus lactis for i.n. vaccination with subunit influenza vaccine in mice. It is shown that simple admixing of the vaccine with the GEM particles results in a strongly enhanced immune response. Already after one booster, the i.n. delivered GEM subunit vaccine resulted in hemagglutination inhibition titers in serum at a level equal to the conventional intramuscular (i.m.) route. Moreover, i.n. immunization with GEM subunit vaccine elicited superior mucosal and Th1 skewed immune responses compared to those induced by i.m. and i.n. administered subunit vaccine alone. In conclusion, GEM particles act as a potent adjuvant for i.n. influenza immunization

Genetic overlap between endometriosis and endometrial cancer: evidence from cross-disease genetic correlation and GWAS meta-analyses.

Epidemiological, biological, and molecular data suggest links between endometriosis and endometrial cancer, with recent epidemiological studies providing evidence for an association between a previous diagnosis of endometriosis and risk of endometrial cancer. We used genetic data as an alternative approach to investigate shared biological etiology of these two diseases. Genetic correlation analysis of summary level statistics from genomewide association studies (GWAS) using LD Score regression revealed moderate but significant genetic correlation (rg  = 0.23, P = 9.3 × 10-3 ), and SNP effect concordance analysis provided evidence for significant SNP pleiotropy (P = 6.0 × 10-3 ) and concordance in effect direction (P = 2.0 × 10-3 ) between the two diseases. Cross-disease GWAS meta-analysis highlighted 13 distinct loci associated at P ≤ 10-5 with both endometriosis and endometrial cancer, with one locus (SNP rs2475335) located within PTPRD associated at a genomewide significant level (P = 4.9 × 10-8 , OR = 1.11, 95% CI = 1.07-1.15). PTPRD acts in the STAT3 pathway, which has been implicated in both endometriosis and endometrial cancer. This study demonstrates the value of cross-disease genetic analysis to support epidemiological observations and to identify biological pathways of relevance to multiple diseases