Evidence of Josephson-coupled superconducting regions at the interfaces of Highly Oriented Pyrolytic Graphite

Transport properties of a few hundreds of nanometers thick (in the graphene plane direction) lamellae of highly oriented pyrolytic graphite (HOPG) have been investigated. Current-Voltage characteristics as well as the temperature dependence of the voltage at different fixed input currents provide evidence for Josephson-coupled superconducting regions embedded in the internal two-dimensional interfaces, reaching zero resistance at low enough temperatures. The overall behavior indicates the existence of superconducting regions with critical temperatures above 100 K at the internal interfaces of oriented pyrolytic graphite.Comment: 6 Figures, 5 page

The Heritability of Prostate Cancer in the Nordic Twin Study of Cancer

BACKGROUND: Prostate cancer is thought to be the most heritable cancer, although little is known about how this genetic contribution varies across age. METHODS: To address this question, we undertook the world's largest prospective study in the Nordic Twin Study of Cancer cohort, including 18,680 monozygotic and 30,054 dizygotic same sex male twin pairs. We incorporated time-to-event analyses to estimate the risk concordance and heritability while accounting for censoring and competing risks of death, essential sources of biases that have not been accounted for in previous twin studies modeling cancer risk and liability. RESULTS: The cumulative risk of prostate cancer was similar to that of the background population. The cumulative risk for twins whose co-twin was diagnosed with prostate cancer was greater for MZ than for DZ twins across all ages. Among concordantly affected pairs, the time between diagnoses was significantly shorter for MZ than DZ pairs (median 3.8 versus 6.5 years, respectively). Genetic differences contributed substantially to variation in both the risk and the liability (heritability=58% (95% CI 52%–63%) of developing prostate cancer. The relative contribution of genetic factors was constant across age through late life with substantial genetic heterogeneity even when diagnosis and screening procedures vary. CONCLUSIONS: Results from the population based twin cohort, indicate a greater genetic contribution to the risk of developing prostate cancer when addressing sources of bias. The role of genetic factors is consistently high across age IMPACT: Findings impact the search for genetic and epigenetic markers and frame prevention efforts

Male reproductive health and environmental xenoestrogens

EHP is a publication of the U.S. government. Publication of EHP lies in the public domain and is therefore without copyright. Research articles from EHP may be used freely; however, articles from the News section of EHP may contain photographs or figures copyrighted by other commercial organizations and individuals that may not be used without obtaining prior approval from both the EHP editors and the holder of the copyright. Use of any materials published in EHP should be acknowledged (for example, "Reproduced with permission from Environmental Health Perspectives") and a reference provided for the article from which the material was reproduced.Male reproductive health has deteriorated in many countries during the last few decades. In the 1990s, declining semen quality has been reported from Belgium, Denmark, France, and Great Britain. The incidence of testicular cancer has increased during the same time incidences of hypospadias and cryptorchidism also appear to be increasing. Similar reproductive problems occur in many wildlife species. There are marked geographic differences in the prevalence of male reproductive disorders. While the reasons for these differences are currently unknown, both clinical and laboratory research suggest that the adverse changes may be inter-related and have a common origin in fetal life or childhood. Exposure of the male fetus to supranormal levels of estrogens, such as diethlylstilbestrol, can result in the above-mentioned reproductive defects. The growing number of reports demonstrating that common environmental contaminants and natural factors possess estrogenic activity presents the working hypothesis that the adverse trends in male reproductive health may be, at least in part, associated with exposure to estrogenic or other hormonally active (e.g., antiandrogenic) environmental chemicals during fetal and childhood development. An extensive research program is needed to understand the extent of the problem, its underlying etiology, and the development of a strategy for prevention and intervention.Supported by EU Contract BMH4-CT96-0314

Dynamic predicting by landmarking as an alternative for multi-state modeling: an application to acute lymphoid leukemia data

This paper considers the problem of obtaining a dynamic prediction for 5-year failure free survival after bone marrow transplantation in ALL patients using data from the EBMT, the European Group for Blood and Marrow Transplantation. The paper compares the new landmark methodology as developed by the first author and the established multi-state modeling as described in a recent Tutorial in Biostatistics in Statistics in Medicine by the second author and colleagues. As expected the two approaches give similar results. The landmark methodology does not need complex modeling and leads to easy prediction rules. On the other hand, it does not give the insight in the biological processes as obtained for the multi-state model

Joint effects of alcohol use, smoking and body mass index as an explanation for the alcohol harm paradox : causal mediation analysis of eight cohort studies

Background and aims Lower socio-economic status (SES) is associated with higher alcohol-related harm despite lower levels of alcohol use. Differential vulnerability due to joint effects of behavioural risk factors is one potential explanation for this 'alcohol harm paradox'. We analysed to what extent socio-economic inequalities in alcohol-mortality are mediated by alcohol, smoking and body mass index (BMI), and their joint effects with each other and with SES. DesignCohort study of eight health examination surveys (1978-2007) linked to mortality data. Setting Finland.ParticipantsA total of 53 632 Finnish residents aged 25+ years.MeasurementsThe primary outcome was alcohol-attributable mortality. We used income as an indicator of SES. We assessed the joint effects between income and mediators (alcohol use, smoking and BMI) and between the mediators, adjusting for socio-demographic indicators. We used causal mediation analysis to calculate the total, direct, indirect and mediated interactive effects using Aalen's additive hazards models. Findings During 1 085 839 person-years of follow-up, we identified 865 alcohol-attributable deaths. We found joint effects for income and alcohol use and income and smoking, resulting in 46.8 and 11.4 extra deaths due to the interaction per 10 000 person-years. No interactions were observed for income and BMI or between alcohol and other mediators. The lowest compared with the highest income quintile was associated with 5.5 additional alcohol deaths per 10 000 person-years (95% confidence interval = 3.7, 7.3) after adjusting for confounders. The proportion mediated by alcohol use was negative (-69.3%), consistent with the alcohol harm paradox. The proportion mediated by smoking and BMI and their additive interactions with income explained 18.1% of the total effect of income on alcohol-attributable mortality. Conclusions People of lower socio-economic status appear to be more vulnerable to the effects of alcohol use and smoking on alcohol-attributable mortality. Behavioural risk factors and their joint effects with income may explain part of the alcohol harm paradox.Peer reviewe

Lung cancer, genetic predisposition and smoking : the Nordic Twin Study of Cancer

Background We aimed to disentangle genetic and environmental causes in lung cancer while considering smoking status. Methods Four Nordic twin cohorts (43 512 monozygotic (MZ) and 71 895 same sex dizygotic (DZ) twin individuals) had smoking data before cancer diagnosis. We used time-to-event analyses accounting for censoring and competing risk of death to estimate incidence, concordance risk and heritability of liability to develop lung cancer by smoking status. Results During a median of 28.5 years of follow-up, we recorded 1508 incident lung cancers. Of the 30 MZ and 28 DZ pairs concordant for lung cancer, nearly all were current smokers at baseline and only one concordant pair was seen among never smokers. Among ever smokers, the case-wise concordance of lung cancer, that is the risk before a certain age conditional on lung cancer in the co-twin before that age, was significantly increased compared with the cumulative incidence for both MZ and DZ pairs. This ratio, the relative recurrence risk, significantly decreased by age for MZ but was constant for DZ pairs. Heritability of lung cancer was 0.41 (95% CI 0.26 to 0.56) for currently smoking and 0.37 (95% CI 0.25 to 0.49) for ever smoking pairs. Among smoking discordant pairs, the pairwise HR for lung cancer of the ever smoker twin compared to the never smoker co-twin was 5.4 (95% CI 2.1 to 14.0) in MZ pairs and 5.0 (95% CI 3.2 to 7.9) in DZ pairs. Conclusions The contribution of familial effects appears to decrease by age. The discordant pair analysis confirms that smoking causes lung cancer.Peer reviewe

Multiple imputation for estimating hazard ratios and predictive abilities in case-cohort surveys

<p>Abstract</p> <p>Background</p> <p>The weighted estimators generally used for analyzing case-cohort studies are not fully efficient and naive estimates of the predictive ability of a model from case-cohort data depend on the subcohort size. However, case-cohort studies represent a special type of incomplete data, and methods for analyzing incomplete data should be appropriate, in particular multiple imputation (MI).</p> <p>Methods</p> <p>We performed simulations to validate the MI approach for estimating hazard ratios and the predictive ability of a model or of an additional variable in case-cohort surveys. As an illustration, we analyzed a case-cohort survey from the Three-City study to estimate the predictive ability of D-dimer plasma concentration on coronary heart disease (CHD) and on vascular dementia (VaD) risks.</p> <p>Results</p> <p>When the imputation model of the phase-2 variable was correctly specified, MI estimates of hazard ratios and predictive abilities were similar to those obtained with full data. When the imputation model was misspecified, MI could provide biased estimates of hazard ratios and predictive abilities. In the Three-City case-cohort study, elevated D-dimer levels increased the risk of VaD (hazard ratio for two consecutive tertiles = 1.69, 95%CI: 1.63-1.74). However, D-dimer levels did not improve the predictive ability of the model.</p> <p>Conclusions</p> <p>MI is a simple approach for analyzing case-cohort data and provides an easy evaluation of the predictive ability of a model or of an additional variable.</p

Weight change during the first week of life and a new method for retrospective prediction of birthweight among exclusively breastfed newborns

Introduction: Identification of low birthweight and small for gestational age is pivotal in clinical management and many research studies, but in low‐income countries, birthweight is often unavailable within 24 h of birth. Newborn weights measured within days after birth and knowledge of the growth patterns in the first week of life can help estimate the weight at birth retrospectively. This study aimed to generate sex‐specific prediction maps and weight reference charts for the retrospective estimation of birthweight for exclusively breastfed newborns in a low‐resource setting. Material and methods: This was a prospective cohort study nested in a clinical trial of intermittent preventive treatment in pregnancy for malaria with either dihydroartemisinin–piperaquine with/without azithromycin or sulfadoxine–pyrimethamine in Korogwe District, north‐eastern Tanzania (Clinicaltrials.gov: NCT03208179). Newborns were weighed at birth or in the immediate hours after birth and then daily for 1 week. Reference charts, nadir, time to regain weight, and prediction maps were generated using nonlinear mixed‐effects models fitted to the longitudinal data, incorporating interindividual variation as random effects. Predictions and prediction standard deviations were computed using a linear approximation approach. Results: Between March and December 2019, 513 live newborns with birthweights measured within 24 h of delivery were weighed daily for 1 week. Complete datasets were available from 476 exclusively breastfed newborns. There was a rapid decline in weight shortly after delivery. The average weight loss, time of nadir, and time to regain weight were 4.3% (95% confidence interval [CI] 3.8–4.9) at 27 h (95% CI 24–30) and 105 h (95% CI 91–120) in boys and 4.9% (95% CI 4.2–5.6) at 28 h (95% CI 23–33) and 114 h (95% CI 93–136) in girls, respectively. The data were used to generate prediction maps with 1‐h time intervals and 0.05 kg weight increments showing the predicted birthweights and weight‐for‐age and weight‐change‐for‐age reference charts depicting variation in weight loss from 10%. Conclusions: The prediction maps and reference charts can be used by researchers in low‐resource settings to retrospectively estimate birthweights using weights collected up to 168 h after delivery, thereby maximizing data utilization. Clinical practitioners can also use the prediction maps to retrospectively classify newborns as low birthweight or small for gestational age

Male gonadal dose of ionizing radiation delivered during X-ray examinations and monthly probability of pregnancy: a population-based retrospective study

BACKGROUND: Male gonadal exposure to ionizing radiation may disrupt spermatogenesis, but its influence on the fecundity of couples has been rarely studied. We aimed to characterize the influence of male gonadal dose of ionizing radiation delivered during radiodiagnostic on the monthly probability of pregnancy. METHODS: We recruited a random sample of women who retrospectively described 1110 periods of unprotected intercourse beginning between 1985 and 1999 and leading either to a live birth or to no pregnancy; their duration was censored after 13 months. The male partner answered a telephone questionnaire on radiodiagnostic examinations. We assigned a mean gonadal dose to each type of radiodiagnostic examination. We defined male dose for each period of unprotected intercourse as the sum of the gonadal doses of the X-ray examinations experienced between 18 years of age and the date of discontinuation of contraception. Time to pregnancy was analysed using a discrete Cox model with random effect allowing to estimate hazard ratios of pregnancy. RESULTS: After adjustment for female factors likely to influence fecundity, there was no evidence of an association between male dose and the probability of pregnancy (test of homogeneity, p = 0.55). When compared to couples with a male gonadal dose between 0.01 and 0.20 milligrays (n = 321 periods of unprotected intercourse), couples with a gonadal dose above 10 milligrays had a hazard ratio of pregnancy of 1.44 (95% confidence interval, 0.73–2.86, n = 31). CONCLUSION: Our study provides no evidence of a long-term detrimental effect of male gonadal dose of ionizing radiation delivered during radiodiagnostic on the monthly probability of pregnancy during the year following discontinuation of contraceptive use. Classification errors due to the retrospective assessment of male gonadal exposure may have limited the statistical power of our study