Search

Objective: Despite the damaging effects of water pipe on physical health, there is little information about the potential harmful effects of this tobacco on stroke. This study aims to investigate the relationship between water pipe smoking and stroke. Method: A systematic review was conducted including Ovid SP, Embase, Pubmed, Web of Science, Scopus, and Google Scholar databases with focus on cohort, case–control, and cross‐sectional studies. We reviewed all studies reporting on water pipe smoking and stroke. The funnel plot and the Egger regression test were used to assess publication bias. Results: In the four eligible studies, there were a total of 2759 participants that 555 patients had at least once experienced stroke. Meta‐analysis revealed positive association between water pipe smoking and stroke with pooled adjusted OR 2.79 (95% CI: 1.74–3.84; I2=0,p=.741${I^2}\; = \;\;0,{\mathrm{\;}}p\;\; = {\mathrm{\;\;}}.741$) and the funnel plot shows asymmetry publication bias. Conclusions: We found a higher effect of water pipe smoking on stroke compared to cigarette smoking and concluded that water pipe increases the risk of stroke by 2.79. Hence, because most of the water pipe consumer society is young, especially women, policies and decisions need to be taken to control the supply of this tobacco to the market and more provide education on the health problem of water pipe smoking. Implications: This study provides a higher effect of water pipe smoking on stroke. Physicians and researchers who intend to study in the field of stroke should better examine the effects of water pipe (including time of use, dose–response, long‐term effects, and risk factors) on stroke. [ABSTRACT FROM AUTHOR]

Aim: In Australia, the risk of hepatitis B virus (HBV) transmission from single sexual contact is low. This, combined with assumed widespread immunity from vaccination, has resulted in a lack of clarity surrounding the necessity for hepatitis B post-exposure prophylaxis following recent sexual assault.Methods: This retrospective audit was conducted through the Victorian Forensic Paediatric Medical Service (VFPMS) at the Royal Children's Hospital, Melbourne, Australia. Subjects were patients aged 13-17 years who presented to VFPMS between 1 January 2007 and 31 December 2016 for forensic medical examination following an alleged penetrative sexual assault. Data collected included subject demographics, immunisation status, route of potential HBV exposure, time between alleged sexual assault and presentation, whether HBsAb levels were tested and the results and whether HBV prophylaxis was administered to the subject and its timing.Results: A total of 2121 records were reviewed, and 420 subjects were found to be eligible for inclusion; 26.2% (n = 110) had HBsAb levels measured at initial presentation. Of these 110 subjects, 45.5% (n = 50) had titre levels less than 10 (deemed to be non-protective) and were therefore vulnerable to HBV infection. Of the 420 subjects, 4.5% (n = 19) received HBV prophylaxis as a result of their assessment.Conclusions: Results suggest that a high proportion of Australian adolescents presenting following recent sexual assault may be at risk of hepatitis B infection. Very few received timely prophylaxis. Follow-up attendance rates were poor. Administration of the hepatitis B booster vaccine at the point of contact may reduce the risk of HBV infection in this group of adolescents. [ABSTRACT FROM AUTHOR]

Background: It is plausible that night shift work could affect breast cancer risk, possibly by melatonin suppression or circadian clock disruption, but epidemiological evidence is inconclusive.Methods: Using serial questionnaires from the Generations Study cohort, we estimated hazard ratios (HR) and 95% confidence intervals (95%CI) for breast cancer in relation to being a night shift worker within the last 10 years, adjusted for potential confounders.Results: Among 102,869 women recruited in 2003-2014, median follow-up 9.5 years, 2059 developed invasive breast cancer. The HR in relation to night shift work was 1.00 (95%CI: 0.86-1.15). There was a significant trend with average hours of night work per week (P = 0.035), but no significantly raised risks for hours worked per night, nights worked per week, average hours worked per week, cumulative years of employment, cumulative hours, time since cessation, type of occupation, age starting night shift work, or age starting in relation to first pregnancy.Conclusions: The lack of overall association, and no association with all but one measure of dose, duration, and intensity in our data, does not support an increased risk of breast cancer from night shift work in women. [ABSTRACT FROM AUTHOR]

A balanced robertsonian translocation (rob) results from fusion of 2 acrocentric chromosomes. Carriers are phenotypically normal and are often diagnosed because of recurrent miscarriages, infertility, or aneuploid offspring. Mortality and site-specific cancer risks in carriers have not been prospectively investigated. We followed 1,987 carriers diagnosed in Great Britain for deaths and cancer risk, over an average of 24.1 years. Standardized mortality and incidence ratios were calculated comparing the number of observed events against population rates. Overall mortality was higher for carriers diagnosed before age 15 years (standardized mortality ratio (SMR) = 2.00, 95% confidence interval (CI): 1.09, 3.35), similar for those diagnosed aged 15–44 years (SMR = 1.06, 95% CI: 0.86–1.28), and lower for those diagnosed aged 45–84 years (SMR = 0.81, 95% CI: 0.68, 0.95). Cancer incidence was higher for non-Hodgkin lymphoma (standardized incidence ratio (SIR) = 1.90, 95% CI: 1.01, 3.24) and childhood leukemia (SIR = 14.5, 95% CI: 1.75, 52.2), the latter particularly in rob(15;21) carriers (SIR = 447.8, 95% CI: 11.3, 2,495). Rob(13;14) carriers had a higher breast cancer risk (SIR = 1.58, 95% CI: 1.12, 2.15). Mortality risks relative to the population in diagnosed carriers depend on age at cytogenetic diagnosis, possibly reflecting age-specific cytogenetic referral reasons. Carriers might be at greater risk of childhood leukemia and non-Hodgkin lymphoma and those diagnosed with rob(13;14) of breast cancer. [ABSTRACT FROM AUTHOR]

Presents a study which examined steady-state plasma production and fluid flow in ion beams with step-function density profiles. Basic equations; Numerical solutions; Treatment of the beam edge as a neutral and a non-neutral sheath.

Presents information on a study which characterized the dynamics of the plasma-erosion-opening switch with the aid of two-dimensional three-fluid simulation using the ANTHEM implicit simulation code, for plasma fill densities. Calculations performed with the implicit ANTHEM code; Electric field component produced by the passage above the cathode toward the generator; Simulations performed for a two-times larger void region downstream of the fill plasma.

The C-Band All-Sky Survey (C-BASS) is an all-sky full-polarization survey at a frequency of 5 GHz, designed to provide complementary data to the all-sky surveys of WMAP and Planck, and future CMB B -mode polarization imaging surveys. The observing frequency has been chosen to provide a signal that is dominated by Galactic synchrotron emission, but suffers little from Faraday rotation, so that the measured polarization directions provide a good template for higher frequency observations, and carry direct information about the Galactic magnetic field. Telescopes in both northern and southern hemispheres with matched optical performance are used to provide all-sky coverage from a ground-based experiment. A continuous-comparison radiometer and a correlation polarimeter on each telescope provide stable imaging properties such that all angular scales from the instrument resolution of 45 arcmin up to full sky are accurately measured. The northern instrument has completed its survey and the southern instrument has started observing. We expect that C-BASS data will significantly improve the component separation analysis of Planck and other CMB data, and will provide important constraints on the properties of anomalous Galactic dust and the Galactic magnetic field. [ABSTRACT FROM AUTHOR]

Background:Circadian disruption caused by exposure to light at night (LAN) has been proposed as a risk factor for breast cancer and a reason for secular increases in incidence. Studies to date have largely been ecological or case-control in design and findings have been mixed.Methods:We investigated the relationship between LAN and breast cancer risk in the UK Generations Study. Bedroom light levels and sleeping patterns at age 20 and at study recruitment were obtained by questionnaire. Analyses were conducted on 105 866 participants with no prior history of breast cancer. During an average of 6.1 years of follow-up, 1775 cases of breast cancer were diagnosed. Cox proportional hazard models were used to calculate hazard ratios (HRs), adjusting for potential confounding factors.Results:There was no association between LAN level and breast cancer risk overall (highest compared with lowest LAN level at recruitment: HR=1.01, 95% confidence interval (CI): 0.88-1.15), or for invasive (HR=0.98, 95% CI: 0.85-1.13) or in situ (HR=0.96, 95% CI: 0.83-1.11) breast cancer, or oestrogen-receptor (ER) positive (HR=0.98, 95% CI: 0.84-1.14); or negative (HR=1.16, 95% CI: 0.82-1.65) tumours separately. The findings did not differ by menopausal status. Adjusting for sleep duration, sleeping at unusual times (non-peak sleep) and history of night work did not affect the results. Night waking with exposure to light, occurring around age 20, was associated with a reduced risk of premenopausal breast cancer (HR for breast cancer overall=0.74, 95% CI: 0.55-0.99; HR for ER-positive breast cancer=0.69, 95% CI: 0.49-0.97).Conclusions:In this prospective cohort analysis of LAN, there was no evidence that LAN exposure increased the risk of subsequent breast cancer, although the suggestion of a lower breast cancer risk in pre-menopausal women with a history of night waking in their twenties may warrant further investigation. [ABSTRACT FROM AUTHOR]

BACKGROUND/OBJECTIVE Management of keloids of the pinna, in particular, those located in the helix and antihelix and lobule that occur as complications of ear piercing. MATERIALS AND METHODS Retrospective analysis of 49 patients treated with extralesional surgical excision of keloids localized to the ear followed by the application of autologous platelet-rich plasma (PRP) to wound site and postoperative in-office superficial radiation therapy (SRT). Radiation protocol consisted of 1 to 3 fractions, with cumulative dosage ranging from 1,300 to 1,800 cGy. Average follow-up was 24 months to assess for evidence of recurrence and adverse side effects. RESULTS Fifty ear keloids were treated with this method, age from 15 to 66 (mean = 32, SD = 16) of which 14 were male and 35 female. Almost 30% (n = 14) of patients acknowledged the source of injury that led to the development of the keloid was ear piercing. Treatment protocol achieved a 94% success rate with 3 patients who reported recurrence. CONCLUSION Surgical excision combined with intraoperative PRP, adjuvant postoperative in-office SRT achieved a 94% nonrecurrence rate on follow-up over a 2-year period. Outcomes provide preliminary, albeit, strong evidence to support this multimodal method as a viable alternative in the management of keloids localized to the ear. [ABSTRACT FROM AUTHOR]

Background: Menopausal hormone therapy (MHT) increases breast cancer risk; however, most cohort studies omit MHT use after enrolment and many infer menopausal age.Methods: We used information from serial questionnaires from the UK Generations Study cohort to estimate hazard ratios (HRs) for breast cancer among post-menopausal women with known menopausal age, and examined biases induced when not updating data on MHT use and including women with inferred menopausal age.Results: Among women recruited in 2003-2009, at 6 years of follow-up, 58 148 had reached menopause and 96% had completed a follow-up questionnaire. Among 39 183 women with known menopausal age, 775 developed breast cancer, and the HR in relation to current oestrogen plus progestogen MHT use (based on 52 current oestrogen plus progestogen MHT users in breast cancer cases) relative to those with no previous MHT use was 2.74 (95% confidence interval (CI): 2.05-3.65) for a median duration of 5.4 years of current use, reaching 3.27 (95% CI: 1.53-6.99) at 15+ years of use. The excess HR was underestimated by 53% if oestrogen plus progestogen MHT use was not updated after recruitment, 13% if women with uncertain menopausal age were included, and 59% if both applied. The HR for oestrogen-only MHT was not increased (HR=1.00; 95% CI: 0.66-1.54).Conclusions: Lack of updating MHT status through follow-up and inclusion of women with inferred menopausal age is likely to result in substantial underestimation of the excess relative risks for oestrogen plus progestogen MHT use in studies with long follow-up, limited updating of exposures, and changing or short durations of use. [ABSTRACT FROM AUTHOR]

Proper modelling of astronomical receivers is vital: it describes the systematic errors in the raw data, guides the receiver design process, and assists data calibration. In this paper, we describe a method of analytically modelling the full signal and noise behaviour of arbitrarily complex radio receivers. We use electrical scattering matrices to describe the signal behaviour of individual components in the receiver, and noise correlation matrices to describe their noise behaviour. These are combined to produce the full receiver model. We apply this approach to a specified receiver architecture: a hybrid of a continuous comparison radiometer and correlation polarimeter designed for the C-Band All-Sky Survey. We produce analytic descriptions of the receiver Mueller matrix and noise temperature, and discuss how imperfections in crucial components affect the raw data. Many of the conclusions drawn are generally applicable to correlation polarimeters and continuous comparison radiometers. [ABSTRACT FROM AUTHOR]

Background The polymerase chain reaction amplifies and quantifies small amounts of DNA. It is a cyclic process, during each cycle of which each strand of template DNA is copied with probability approaching one: the amount of DNA approximately doubles and this amount can be estimated fluorimetrically each cycle, producing a set of fluorescence values hereafter referred to as the amplification curve. Commonly the biological question of relevance is one of the ratio of DNA concentrations in two samples: a ratio that is deduced by comparing the two amplification curves, usually by way of a plot of fluorescence against cycle number. Central to this analysis is measuring the extent to which one amplification curve is shifted relative to the other, a measurement often accomplished by defining a threshold or quantification cycle, Cq, for each curve: the fractional cycle number at which fluorescence reaches some threshold or at which some other criterion (maximum slope, maximum rate of change of slope) is satisfied. We propose an alternative where position is measured relative to a reference curve; position equates to the cycle shift which maximizes the correlation between the reference and the observed fluorescence sequence. A key parameter of the reference curve is obtained by fixed-point convergence. Results We consider the analysis of dilution series constructed for the estimation of qPCR amplification efficiency. The estimate of amplification efficiency is based on the slope of the regression line when the Cq is plotted against the logarithm of dilution. We compare the approach to three commonly used methods for determining Cq; each is applied to publicly accessible calibration data sets, and to ten from our own laboratory. As in the established literature we judge their relative merits both from the standard deviation of the slope of the calibration curve, and from the variance in Cq for replicate fluorescence curves. Conclusions The approach does not require modification of experimental protocols, and can be applied retrospectively to existing data. We recommend that it be added to the methodological toolkit with which laboratories interpret their real-time PCR data. [ABSTRACT FROM AUTHOR]

There has been a worldwide epidemic of obesity in recent decades. In animal studies, there is convincing evidence that light exposure causes weight gain, even when calorie intake and physical activity are held constant. Disruption of sleep and circadian rhythms by exposure to light at night (LAN) might be one mechanism contributing to the rise in obesity, but it has not been well-investigated in humans. Using multinomial logistic regression, we examined the association between exposure to LAN and obesity in questionnaire data from over 100,000 women in the Breakthrough Generations Study, a cohort study of women aged 16 years or older who were living in the United Kingdom and recruited during 2003–2012. The odds of obesity, measured using body mass index, waist:hip ratio, waist:height ratio, and waist circumference, increased with increasing levels of LAN exposure (P < 0.001), even after adjustment for potential confounders such as sleep duration, alcohol intake, physical activity, and current smoking. We found a significant association between LAN exposure and obesity which was not explained by potential confounders we could measure. While the possibility of residual confounding cannot be excluded, the pattern is intriguing, accords with the results of animal experiments, and warrants further investigation. [ABSTRACT FROM PUBLISHER]

Prospective cohort studies examining sex hormones in relation to cancer risk have generally collected blood samples at 1 time point, with an assumption that hormone levels measured in these samples will be reliable markers of true levels at other times. In postmenopausal women, body fat is a major source of estradiol; therefore, changes in adiposity may affect the correlation of single measurements to more relevant long-term averages. To estimate the intraclass correlation coefficient (ICC) for estradiol and testosterone, we collected repeat blood samples from 119 postmenopausal women (average age = 59.4 (standard deviation, 4.7) years) from the United Kingdom during 2004–2005 and again during 2010–2011. The ICCs (adjusted for assay variation) were 0.73 (95% confidence interval: 0.63, 0.82) for total estradiol and 0.59 (95% confidence interval: 0.47, 0.72) for total testosterone. The ICCs were 3%–5% larger after adjustment for change in body mass index (weight (kg)/height (m)2) or leptin, which are 2 markers of change in adiposity. There was no increase in ICCs after adjustment for change in age, alcohol consumption, smoking, exercise, time between waking and blood collection, or season. The results suggest that other factors account for within-woman variation in these sex hormones. [ABSTRACT FROM PUBLISHER]

The authors examined the effect of women’s lifestyles on the timing of natural menopause using data from a cross-sectional questionnaire used in the United Kingdom-based Breakthrough Generations Study in 2003–2011. The analyses included 50,678 women (21,511 who had experienced a natural menopause) who were 40–98 years of age at study entry and did not have a history of breast cancer. Cox competing risks proportional hazards models were fitted to examine the relation of age at natural menopause to lifestyle and anthropometric factors. Results were adjusted for age at reporting, smoking status at menopause, parity, and body mass index at age 40 years, as appropriate. All P values were 2-sided. High adult weight (Ptrend < 0.001), high body mass index (Ptrend < 0.001), weight gain between the ages of 20 and 40 years (Ptrend = 0.01), not smoking (P < 0.001), increased alcohol consumption (Ptrend < 0.001), regular strenuous exercise (P < 0.01), and not being a vegetarian (P < 0.001) were associated with older age at menopause. Neither height nor history of an eating disorder was associated with menopausal age. These findings show the importance of lifestyle factors in determining menopausal age. [ABSTRACT FROM PUBLISHER]

Objectives: To assess familial resemblance for height, arm span, and components of these, and differences between concordance for short and tall heights. Methods: We examined whether female relatives were similar for six anthropometric measurements (height, arm span, leg, trunk and arm length, and leg:trunk length ratio). Subjects were 31,622 related individuals aged 16-102 yr participating in the UK Breakthrough Generations Study. Height and arm span were self-reported, limb and trunk length were measured in a subset ( N = 508) by study investigators, and paternal height was reported by the daughter. Data were analyzed using correlations and Poisson regression. Results: Correlation coefficients within families were 0.4 for height, 0.3 for arm span, and 0.5 for leg length, trunk length, leg:trunk ratio, and arm length. Women had a relative risk (RR) of being short (i.e., in the lowest height quintile) of 2.3 (95% confidence interval [CI] = 2.1-2.5) if their mother was short, 2.1 (95% CI = 1.9-2.3) if their father was short, and 3.7 (95% CI = 3.4-4.0) if both parents were short. RRs of being tall (i.e., in the highest height quintile) were 2.3 (95% CI = 2.1-2.5), 2.4 (95% CI = 2.2-2.6), and 4.4 (95% CI = 4.1-4.8) if their mother, father or both were tall, respectively. Conclusions: We have shown, for the first time, that leg:trunk length ratio and arm length aggregate within families. Concordance seemed to be stronger for tall than short heights. Am. J. Hum. Biol., 2012. © 2011 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

ABSTRACT We describe an upgrade to the Cosmic Background Imager instrument to increase its surface brightness sensitivity at small angular scales. The upgrade consisted of replacing the 13 0.9-m antennas with 1.4-m antennas incorporating a novel combination of design features, which provided excellent sidelobe and spillover performance for low manufacturing cost. Off-the-shelf spun primaries were used, and the secondary mirrors were oversized and shaped relative to a standard Cassegrain in order to provide an optimum compromise between aperture efficiency and low spillover lobes. Low-order distortions in the primary mirrors were compensated for by custom machining of the secondary mirrors. The secondaries were supported on a transparent dielectric foam cone to minimize scattering. The antennas were tested in the complete instrument, and the beam shape and spillover noise contributions were as expected. We demonstrate the performance of the telescope and the intercalibration with the previous system using observations of the Sunyaev-Zel'dovich effect in the cluster Abell 1689. The enhanced instrument has been used to study the cosmic microwave background, the Sunyaev-Zel'dovich effect and diffuse Galactic emission. [ABSTRACT FROM AUTHOR]

Menarcheal age decreased over time in Western countries until cohorts born in the mid-20th century. It then stabilised, but limited data are available for recent cohorts. Menarche data were collected retrospectively by questionnaire in 2003-10 from 94,170 women who were participating in the Breakthrough Generations Study, aged 16-98 years, born 1908-93 and resident in the UK. Average menarcheal age declined from women born in 1908-19 (mean=13.5 years) to those born in 1945-49 (mean=12.6 years). It was then stable for several birth cohorts, but resumed its downward trend in recent cohorts (mean=12.3 years in 1990-93 cohort). Trends differed between socio-economic groups, but the recent decline was present in each group. In conclusion, menarcheal age appears to have decreased again in recent cohorts after a period of stabilisation. [ABSTRACT FROM AUTHOR]

Age at menarche is correlated within families, but estimates of the heritability of menarcheal age have a wide range (0.45-0.95). We examined the familial resemblance for age at menarche and the extent to which this is due to genetic and shared environmental factors. Between 2003 and 2010 data were retrospectively collected by questionnaire from participants within the UK-based Breakthrough Generations Study. These analyses included 25,970 female participants aged 16-98 with at least one female relative who was also a study participant. A woman's menarche was significantly delayed for each yearly increase in the menarcheal age of her monozygotic twin (average increase = 7.2 months, P < 0.001), dizygotic twin (average increase = 3.0 months, P = 0.03), older sister (average increase = 3.3 months, P < 0.001), mother (average increase = 3.4 months, P < 0.001), maternal grandmother (average increase = 1.5 months, P = 0.04), maternal aunt (average increase = 1.4 months, P < 0.001) and paternal aunt (average increase = 3.0 months, P < 0.001). There was not a significant association between the menarcheal ages of half-sister pairs or of paternal grandmother-granddaughter pairs, based on small numbers. Heritability was estimated as 0.57 [95% confidence interval 0.53, 0.61]. Shared environmental factors did not have an effect in the model. In conclusion, approximately half of the variation in age at menarche was attributable to additive genetic effects with the remainder attributable to non-shared environmental effects. [ABSTRACT FROM AUTHOR]

Background: Methylation of DNA is a common mechanism for silencing genes, and aberrant methylation is increasingly being implicated in many diseases such as cancer. There is a need for robust, inexpensive methods to quantitate methylation across a region containing a number of CpGs. We describe and validate a rapid, in-tube method to quantitate DNA methylation using the melt data obtained following amplification of bisulfite modified DNA in a real-time thermocycler. Methods: We first describe a mathematical method to normalise the raw fluorescence data generated by heating the amplified bisulfite modified DNA. From this normalised data the temperatures at which melting begins and finishes can be calculated, which reflect the less and more methylated template molecules present respectively. Also the T50, the temperature at which half the amplicons are melted, which represents the summative methylation of all the CpGs in the template mixture, can be calculated. These parameters describe the methylation characteristics of the region amplified in the original sample. Results: For validation we used synthesized oligonucleotides and DNA from fresh cells and formalin fixed paraffin embedded tissue, each with known methylation. Using our quantitation we could distinguish between unmethylated, partially methylated and fully methylated oligonucleotides mixed in varying ratios. There was a linear relationship between T50 and the dilution of methylated into unmethylated DNA. We could quantitate the change in methylation over time in cell lines treated with the demethylating drug 5-aza-2'-deoxycytidine, and the differences in methylation associated with complete, clonal or no loss of MGMT expression in formalin fixed paraffin embedded tissues. Conclusion: We have validated a rapid, simple in-tube method to quantify methylation which is robust and reproducible, utilizes easily designed primers and does not need proprietary algorithms or software. The technique does not depend on any operator manipulation or interpretation of the melt curves, and is suitable for use in any laboratory with a real-time thermocycler. The parameters derived provide an objective description and quantitation of the methylation in a specimen, and can be used to for statistical comparisons of methylation between specimens. [ABSTRACT FROM AUTHOR]

OBJECTIVE -- Mortality from acute diabetes-related events is greatly raised in young adults with type 1 diabetes. Psychosocial and socioeconomic risk factors are examined for deaths from acute events separately from deaths due to other causes. RESEARCH DESIGN AND METHODS -- This study had a nested case-control design. The cases were patients from the Diabetes UK cohort who died before age 40 years. Deaths were categorized as acute events or chronic conditions related to diabetes. Where possible, two matched control subjects were selected for each case. Data relating to psychosocial and socioeconomic factors and variables related to diabetes complications were extracted from the case notes. Risks of death were estimated by calculation of odds ratios (ORs). RESULTS -- Case notes were obtained for 98 case and 137 control subjects. Fifty-one deaths were attributed to acute causes, 34 to chronic conditions related to diabetes, and the remaining 13 were unrelated to diabetes. Living alone (OR 4.4), past drug abuse (5.7), and previous psychiatric referral (4.6) were all significantly associated with death from acute events but not death from chronic conditions. There was no association between deaths from acute events and nephropathy, hypertension, neuropathy, or retinopathy, although all of these were associated with deaths from chronic conditions. CONCLUSIONS -- The results indicate that psychosocial factors are powerful risk factors for mortality from acute events in patients with type 1 diabetes, although not for mortality from chronic conditions. The data enable the identification of a high-risk group suitable for targeting with preventive measures to reduce acute event mortality. [ABSTRACT FROM AUTHOR]

Background: Tamoxifen treatment of breast cancer is associated with an increased risk of endometrial cancer, but tamoxifen-related risks of endometrial cancer are unclear in premenopausal women, in long-term users of tamoxifen, and in women for whom several years have passed since ending treatment. We conducted a case-control study in Britain to investigate these risks. Methods: We compared treatment information on 813 case patients who had endometrial cancer after their diagnosis for breast cancer and 1067 control patients who had breast cancer but not subsequent endometrial cancer. We assessed risk by conditional logistic regression analysis. All statistical tests were two-sided. Results: Overall, tamoxifen treatment, compared with no treatment, was associated with an increased risk of endometrial cancer (odds ratio IORI = 2.4; 95% confidence interval [CI] = 1.8 to 3.0). Risk increased statistically significantly (Ptrend<.001) with duration of treatment (for ≥5 years of treatment compared with no treatment, OR = 3.6, 95% CI = 2.6 to 4.8). As an indication of background levels of treatment, 16% of control patients received 5 years or more of treatment. Risk of endometrial cancer adjusted for treatment duration did not diminish in follow-up to at least 5 years after the last treatment ended. Risk of endometrial cancer was not associated with the daily dose of tamoxifen and was comparable in pre- and postmenopausal women. Ever treatment with tamoxifen was associated with a much greater risk of Mullerian and mesodermal mixed endometrial tumors (OR = 13.5, 95% CI = 4.1 to 44.5) than of adenocarcinoma (OR = 2.1, 95% CI = 1.6 to 2.7) or clear cell and papillary serous tumors (OR = 3.1, 95% CI = 0.8 to 17.9). Conclusions: There is an increasing risk of endometrial cancer associated with longer tamoxifen treatment, extending well beyond 5 years. The increased risk of endometrial cancer associated with tamoxifen treatment should be considered clinically for both premenopausal and postmenopausal women during treatment and for at least 5 years after the last treatment. [ABSTRACT FROM AUTHOR]

We have observed the Sunyaev–Zel'dovich (SZ) effect in a sample of five moderate-redshift clusters with the Ryle Telescope, and used them in conjunction with X-ray imaging and spectral data fromROSATandASCAto measure the Hubble constant. This sample was chosen with a strict X-ray flux limit using both the Bright Cluster Sample and the NorthernROSATAll-Sky Survey (RASS) cluster catalogues to be well above the surface brightness limit of the RASS, and hence to be unbiased with respect to the orientation of the cluster. This controls a major potential systematic effect in the SZ/X-ray method of measuringH0. Taking the weighted geometric mean of the results and including the main sources of error, namely the noise in the SZ measurement, the uncertainty in the X-ray temperatures and the unknown ellipticity and substructure of the clusters, we findassuming a standard cold dark matter model withorif. [ABSTRACT FROM AUTHOR]

We evaluate experimentally the effect of carbonate saturation state at the sediment--water interface (SWI) on survivorship of various size classes of the juvenile bivalve Mercenaria mercenaria. Populations of 0.2-mm, 0.3-mm, 1-mm, and 2-mm M. mercenaria were introduced to sediments realistically undersaturated (experimental, saturation state with respect to aragonite = Ωaragonite = IMP/K'sp = ∼0.3) and saturated (control, Ωaragonite =&sim:1.5) with respect to aragonite in order to evaluate the impact of saturation state and dissolution on survivorship. Linear regression analysis was used to examine mortality within each treatment over time and show significant mortality for each size class in experimental-undersaturated treatments only (P < 0.05). Mortality rates in experimental-undersaturated sediments were - 11.8, -4.8, - 1.9, and - 1.1% d-1 for the 0.2-, 0.3-, 1.0-, and 2.0-mm bivalves, respectively. Analysis of covariance (ANCOVA) was used to examine differences in mortality between treatments over time and show significantly different mortality rates for the 0.2-, 0.3-, and 1-mm individuals (P < 0.05). Dissolution may represent a previously unrecognized yet significant source of mortality for "just-set" juvenile bivalves, particularly the very small individuals that have been largely ignored in recruitment studies to date. Dissolution-induced mortality may help explain the exponential losses of juvenile bivalves following their transition from the pelagic larval phase to the benthic juvenile phase. [ABSTRACT FROM AUTHOR]

ASEAN has formulated a planned integration among its ten member nations and has challenged its citizens to embrace a regional identity. This article raises and attempts to answer the following questions: How might ASEAN develop strategies to enable citizens in transitioning from nation-state mentalities to regional and possible cultural citizenry? How will the regional and national governing bodies facilitate the necessary empowerment of diverse populations to form an ASEAN identity? What sorts of affiliations will engender the necessary social capital to develop civic-minded people with a sense of belonging together? How might education play a role in this process? These questions are raised on the basis of the argument that the call for ASEAN identity delivers a challenge to construct dynamic institutions and foster sufficient amounts of social capital. The underlying assumption is that the creation of a regional identity is of primary special interest to ASEAN and the intent of the Vision policy document was to reassert the belief in a regional framework designed as an action plan related to human development and civic empowerment. Accordingly, these assumptions will be the basis for recommendations and strategies in developing a participatory regional identity. [ABSTRACT FROM AUTHOR]

Glycolysis from [6-3 H]glucose and gluconeogenesis from [U-14 C]glycerol were examined in isolated hepatocytes from fasted rats. A 5 mm bolus of glycerol inhibited phosphorylation of 40 mm glucose by 50% and glycolysis by more than 60%, and caused cellular ATP depletion and glycerol 3-phosphate accumulation. Gluconeogenesis from 5 mm glycerol was unaffected by the presence of 40 mm glucose. When nonsaturating concentrations of glycerol (< 200 µm) were maintained in the medium by infusion of glycerol, cellular ATP concentrations remained normal. The rate of uptake of infused glycerol was unaffected by 40 mm glucose, but carbohydrate synthesis from glycerol was inhibited 25%, a corresponding amount of glycerol being diverted to glycolytic products, whereas 10 mm glucose had no inhibitory effect on conversion of infused glycerol into carbohydrate. Glycerol infusion depressed glycolysis from 10 mm and 40 mm glucose by 15 and 25%, respectively; however, the overall rates of glycolysis were unchanged because of a concomitant increase in glycolysis from the infused glycerol. These studies show that exposure of hepatocytes to glucose and low quasi-steady-state concentrations of glycerol result in the simultaneous occurrence, at substantial rates, of glycolysis from glucose and gluconeogenesis from the added glycerol. We interpret our results as demonstrating that, in hepatocytes from normal rats, segments of the pathways of glycolysis from glucose and gluconeogenesis from glycerol are compartmentalized and that this segregation prevents substantial cross-over of phosphorylated intermediates from one pathway to the other. The competition between glucose and glycerol implies that glycolysis and phosphorylation of glycerol take place in the same cells, and that the occurrence of simultaneous glycolysis and gluconeogenesis may indicate channelling within the cytoplasm of individual hepatocytes. [ABSTRACT FROM AUTHOR]

We discuss prospects for cluster detection via the Sunyaev–Zel'dovich (SZ) effect in a blank field survey with the interferometer array, the Arcminute MicroKelvin Imager (AMI). Clusters of galaxies selected in the SZ effect probe cosmology and structure formation with little observational bias, because the effect measures integrated gas pressure directly, and does so independently of cluster redshift. We use hydrodynamical simulations in combination with the Press–Schechter expression to simulate SZ cluster sky maps. These are used with simulations of the observation process to gauge the expected SZ cluster counts. Even with a very conservative choice of parameters we find that AMI will discover at least several tens of clusters every year with the numbers depend on factors such as the mean matter density, the density fluctuation power spectrum and cluster gas evolution. The AMI survey itself can distinguish between these to some degree, and parameter degeneracies are largely eliminated given optical and X-ray follow-up of these clusters; this will also permit direct investigation of cluster physics and what drives the evolution. [ABSTRACT FROM AUTHOR]

A general analysis of the electromagnetic wakefields for an axisymmetric charge distribution moving through a cold uniform plasma is presented. Particular attention is given to the electromagnetic and relativistic effects influencing the waves. It is shown that the plasma provides shielding of the transverse wakefields on a scale length of a few electromagnetic skin depths (c/ω[sub p]). The implications for plasma wakefield accelerators are that driving beams with radii of a few skin depths will experience severe pinching, whereas larger beams will be subject to filamentation instabilities. These conclusions are supported by self-consistent particle-in-cell simulations. The deleterious effects of transverse wakefields will severely limit the accelerating gradients that can be obtained even if a magnetic field is used to guide the driving beam. [ABSTRACT FROM AUTHOR]

Studies ion interpenetration, stagnation and energization processes in colliding laser-produced plasma configurations relevant to Trident experiments. Numerical methods used; Comparison with plasmas generated with gold and deuterated polyethylene targets; Initial expansion of plasmas and their collisional interaction.

We describe an allergic reaction to both mouse brain-derived BIKEN and Vero cell-derived IXIARO Japanese encephalitis (JE) vaccines in a single traveler. In the absence of the stabilizers and murine proteins in the BIKEN vaccine, a common factor in both vaccines is likely to be responsible, possibly JE virus antigen itself. [ABSTRACT FROM AUTHOR]

Background: During the COVID-19 lockdown, referrals via the 2-week-wait urgent pathway for suspected cancer in England, UK, are reported to have decreased by up to 84%. We aimed to examine the impact of different scenarios of lockdown-accumulated backlog in cancer referrals on cancer survival, and the impact on survival per referred patient due to delayed referral versus risk of death from nosocomial infection with severe acute respiratory syndrome coronavirus 2.Methods: In this modelling study, we used age-stratified and stage-stratified 10-year cancer survival estimates for patients in England, UK, for 20 common tumour types diagnosed in 2008-17 at age 30 years and older from Public Health England. We also used data for cancer diagnoses made via the 2-week-wait referral pathway in 2013-16 from the Cancer Waiting Times system from NHS Digital. We applied per-day hazard ratios (HRs) for cancer progression that we generated from observational studies of delay to treatment. We quantified the annual numbers of cancers at stage I-III diagnosed via the 2-week-wait pathway using 2-week-wait age-specific and stage-specific breakdowns. From these numbers, we estimated the aggregate number of lives and life-years lost in England for per-patient delays of 1-6 months in presentation, diagnosis, or cancer treatment, or a combination of these. We assessed three scenarios of a 3-month period of lockdown during which 25%, 50%, and 75% of the normal monthly volumes of symptomatic patients delayed their presentation until after lockdown. Using referral-to-diagnosis conversion rates and COVID-19 case-fatality rates, we also estimated the survival increment per patient referred.Findings: Across England in 2013-16, an average of 6281 patients with stage I-III cancer were diagnosed via the 2-week-wait pathway per month, of whom 1691 (27%) would be predicted to die within 10 years from their disease. Delays in presentation via the 2-week-wait pathway over a 3-month lockdown period (with an average presentational delay of 2 months per patient) would result in 181 additional lives and 3316 life-years lost as a result of a backlog of referrals of 25%, 361 additional lives and 6632 life-years lost for a 50% backlog of referrals, and 542 additional lives and 9948 life-years lost for a 75% backlog in referrals. Compared with all diagnostics for the backlog being done in month 1 after lockdown, additional capacity across months 1-3 would result in 90 additional lives and 1662 live-years lost due to diagnostic delays for the 25% backlog scenario, 183 additional lives and 3362 life-years lost under the 50% backlog scenario, and 276 additional lives and 5075 life-years lost under the 75% backlog scenario. However, a delay in additional diagnostic capacity with provision spread across months 3-8 after lockdown would result in 401 additional lives and 7332 life-years lost due to diagnostic delays under the 25% backlog scenario, 811 additional lives and 14 873 life-years lost under the 50% backlog scenario, and 1231 additional lives and 22 635 life-years lost under the 75% backlog scenario. A 2-month delay in 2-week-wait investigatory referrals results in an estimated loss of between 0·0 and 0·7 life-years per referred patient, depending on age and tumour type.Interpretation: Prompt provision of additional capacity to address the backlog of diagnostics will minimise deaths as a result of diagnostic delays that could add to those predicted due to expected presentational delays. Prioritisation of patient groups for whom delay would result in most life-years lost warrants consideration as an option for mitigating the aggregate burden of mortality in patients with cancer.Funding: None. [ABSTRACT FROM AUTHOR]

The cosmic microwave background (CMB) B -mode signal is potentially weaker than the diffuse Galactic foregrounds over most of the sky at any frequency. A common method of separating the CMB from these foregrounds is via pixel-based parametric-model fitting. There are not currently enough all-sky maps to fit anything more than the most simple models of the sky. By simulating the emission in seven representative pixels, we demonstrate that the inclusion of a 5 GHz data point allows for more complex models of low-frequency foregrounds to be fitted than at present. It is shown that the inclusion of the C-BASS data will significantly reduce the uncertainties in a number of key parameters in the modelling of both the galactic foregrounds and the CMB. The extra data allow estimates of the synchrotron spectral index to be constrained much more strongly than is presently possible, with corresponding improvements in the accuracy of the recovery of the CMB amplitude. However, we show that to place good limits on models of the synchrotron spectral curvature will require additional low-frequency data. [ABSTRACT FROM AUTHOR]

The Andromeda galaxy (M 31) is our closest neighbouring spiral galaxy, making it an ideal target for studying the physics of the interstellar medium in a galaxy very similar to our own. Using new observations of M 31 at 4.76 GHz by the C-Band All-Sky Survey (C-BASS), and all available radio data at 1° resolution, we produce the integrated spectrum and put new constraints on the synchrotron spectral index and anomalous microwave emission (AME) from M 31. We use aperture photometry and spectral modelling to fit for the integrated spectrum of M 31, and subtract a comprehensive model of nearby background radio sources. The AME in M 31 is detected at 3σ significance with a peak near 30 GHz and flux density 0.27 ± 0.09 Jy. The synchrotron spectral index of M 31 is flatter than our own Galaxy at α =−0.66 ± 0.03 with no strong evidence of spectral curvature. The emissivity of AME averaged over the total emission from M 31 is lower than typical AME sources in our Galaxy, implying that AME is not uniformly distributed throughout M 31 and instead is likely confined to sub-regions – this will need to be confirmed using future higher resolution observations around 20–30 GHz. [ABSTRACT FROM AUTHOR]

It is proposed that, through restriction to individuals delineated as high risk, polygenic risk scores (PRSs) might enable more efficient targeting of existing cancer screening programmes and enable extension into new age ranges and disease types. To address this proposition, we present an overview of the performance of PRS tools (ie, models and sets of single nucleotide polymorphisms) alongside harms and benefits of PRS-stratified cancer screening for eight example cancers (breast, prostate, colorectal, pancreas, ovary, kidney, lung, and testicular cancer). For this modelling analysis, we used age-stratified cancer incidences for the UK population from the National Cancer Registration Dataset (2016–18) and published estimates of the area under the receiver operating characteristic curve for current, future, and optimised PRS for each of the eight cancer types. For each of five PRS-defined high-risk quantiles (ie, the top 50%, 20%, 10%, 5%, and 1%) and according to each of the three PRS tools (ie, current, future, and optimised) for the eight cancers, we calculated the relative proportion of cancers arising, the odds ratios of a cancer arising compared with the UK population average, and the lifetime cancer risk. We examined maximal attainable rates of cancer detection by age stratum from combining PRS-based stratification with cancer screening tools and modelled the maximal impact on cancer-specific survival of hypothetical new UK programmes of PRS-stratified screening. The PRS-defined high-risk quintile (20%) of the population was estimated to capture 37% of breast cancer cases, 46% of prostate cancer cases, 34% of colorectal cancer cases, 29% of pancreatic cancer cases, 26% of ovarian cancer cases, 22% of renal cancer cases, 26% of lung cancer cases, and 47% of testicular cancer cases. Extending UK screening programmes to a PRS-defined high-risk quintile including people aged 40–49 years for breast cancer, 50–59 years for colorectal cancer, and 60–69 years for prostate cancer has the potential to avert, respectively, a maximum of 102, 188, and 158 deaths annually. Unstratified screening of the full population aged 48–49 years for breast cancer, 58–59 years for colorectal cancer, and 68–69 years for prostate cancer would use equivalent resources and avert, respectively, an estimated maximum of 80, 155, and 95 deaths annually. These maximal modelled numbers will be substantially attenuated by incomplete population uptake of PRS profiling and cancer screening, interval cancers, non-European ancestry, and other factors. Under favourable assumptions, our modelling suggests modest potential efficiency gain in cancer case detection and deaths averted for hypothetical new PRS-stratified screening programmes for breast, prostate, and colorectal cancer. Restriction of screening to high-risk quantiles means many or most incident cancers will arise in those assigned as being low-risk. To quantify real-world clinical impact, costs, and harms, UK-specific cluster-randomised trials are required. The Wellcome Trust. [ABSTRACT FROM AUTHOR]

This article cites a study in Normal, Illinois that examined the hypothesis that differences between family members and professionals in attitudes toward causes and treatments of schizophrenia affect family members' satisfaction with the professionals. When family members perceived the professional's attitudes as similar to their own, they will be more attracted to the professional and more satisfied than if they perceived the professional's attitudes as different from their own attitudes. Twenty-eight family members of individuals diagnosed by Diagnostic and Statistical Manual of Mental Disorders-III criteria as having schizophrenia completed a questionnaire that assessed their attitudes with regard to causes and treatments of schizophrenia.

Stabilizing the gain of a radio astronomy receiver is of great importance for sensitive radio intensity mapping. In this paper we discuss a stabilization method using a continuous-wave reference signal injected into the signal chain and tracked in a single channel of the spectrometer to correct for the gain variations of the receiver. This method depends on the fact that gain fluctuations of the receiver are strongly correlated across the frequency band, which we can show is the case for our experimental set-up. This method is especially suited for receivers with a digital back-end with high spectral resolution and moderate dynamic range. The sensitivity of the receiver is unaltered except for one lost frequency channel. We present experimental results using a new 4–8.5 GHz receiver with a digital back-end that shows substantial reduction of the 1/ f noise and the 1/ f knee frequency. [ABSTRACT FROM AUTHOR]

The C-Band All-Sky Survey (C-BASS) is an all-sky full-polarization survey at a frequency of 5 GHz, designed to provide data complementary to the all-sky surveys of WMAP and Planck and future CMB B -mode polarization imaging surveys. We describe the design and performance of the digital backend used for the northern part of the survey. In particular, we describe the features that efficiently implement the demodulation and filtering required to suppress contaminating signals in the time-ordered data, and the capability for real-time correction of detector non-linearity and receiver balance. [ABSTRACT FROM AUTHOR]

Background: Circadian disruption caused by exposure to light at night (LAN) has been proposed as a risk factor for breast cancer and a reason for secular increases in incidence. Studies to date have largely been ecological or case-control in design and findings have been mixed.Methods: We investigated the relationship between LAN and breast cancer risk in the UK Generations Study. Bedroom light levels and sleeping patterns at age 20 and at study recruitment were obtained by questionnaire. Analyses were conducted on 105 866 participants with no prior history of breast cancer. During an average of 6.1 years of follow-up, 1775 cases of breast cancer were diagnosed. Cox proportional hazard models were used to calculate hazard ratios (HRs), adjusting for potential confounding factors.Results: There was no association between LAN level and breast cancer risk overall (highest compared with lowest LAN level at recruitment: HR=1.01, 95% confidence interval (CI): 0.88-1.15), or for invasive (HR=0.98, 95% CI: 0.85-1.13) or in situ (HR=0.96, 95% CI: 0.83-1.11) breast cancer, or oestrogen-receptor (ER) positive (HR=0.98, 95% CI: 0.84-1.14); or negative (HR=1.16, 95% CI: 0.82-1.65) tumours separately. The findings did not differ by menopausal status. Adjusting for sleep duration, sleeping at unusual times (non-peak sleep) and history of night work did not affect the results. Night waking with exposure to light, occurring around age 20, was associated with a reduced risk of premenopausal breast cancer (HR for breast cancer overall=0.74, 95% CI: 0.55-0.99; HR for ER-positive breast cancer=0.69, 95% CI: 0.49-0.97).Conclusions: In this prospective cohort analysis of LAN, there was no evidence that LAN exposure increased the risk of subsequent breast cancer, although the suggestion of a lower breast cancer risk in pre-menopausal women with a history of night waking in their twenties may warrant further investigation. [ABSTRACT FROM AUTHOR]

Background: Rigorous evaluation of the calibration and discrimination of breast-cancer risk-prediction models in prospective cohorts is critical for applications under clinical guidelines. We comprehensively evaluated an integrated model incorporating classical risk factors and a 313-variant polygenic risk score (PRS) to predict breast-cancer risk.Methods: Fifteen prospective cohorts from six countries with 239 340 women (7646 incident breast-cancer cases) of European ancestry aged 19-75 years were included. Calibration of 5-year risk was assessed by comparing expected and observed proportions of cases overall and within risk categories. Risk stratification for women of European ancestry aged 50-70 years in those countries was evaluated by the proportion of women and future cases crossing clinically relevant risk thresholds.Results: Among women <50 years old, the median (range) expected-to-observed ratio for the integrated model across 15 cohorts was 0.9 (0.7-1.0) overall and 0.9 (0.7-1.4) at the highest-risk decile; among women ≥50 years old, these were 1.0 (0.7-1.3) and 1.2 (0.7-1.6), respectively. The proportion of women identified above a 3% 5-year risk threshold (used for recommending risk-reducing medications in the USA) ranged from 7.0% in Germany (∼841 000 of 12 million) to 17.7% in the USA (∼5.3 of 30 million). At this threshold, 14.7% of US women were reclassified by adding the PRS to classical risk factors, with identification of 12.2% of additional future cases.Conclusion: Integrating a 313-variant PRS with classical risk factors can improve the identification of European-ancestry women at elevated risk who could benefit from targeted risk-reducing strategies under current clinical guidelines. [ABSTRACT FROM AUTHOR]

The article presents an obituary for British general practice physician Edward Somerset Short.

Background: The etiology of male breast cancer (MBC) is poorly understood. In particular, the extent to which the genetic basis of MBC differs from female breast cancer (FBC) is unknown. A previous genome-wide association study of MBC identified 2 predisposition loci for the disease, both of which were also associated with risk of FBC.Methods: We performed genome-wide single nucleotide polymorphism genotyping of European ancestry MBC case subjects and controls in 3 stages. Associations between directly genotyped and imputed single nucleotide polymorphisms with MBC were assessed using fixed-effects meta-analysis of 1380 cases and 3620 controls. Replication genotyping of 810 cases and 1026 controls was used to validate variants with P values less than 1 × 10-06. Genetic correlation with FBC was evaluated using linkage disequilibrium score regression, by comprehensively examining the associations of published FBC risk loci with risk of MBC and by assessing associations between a FBC polygenic risk score and MBC. All statistical tests were 2-sided.Results: The genome-wide association study identified 3 novel MBC susceptibility loci that attained genome-wide statistical significance (P < 5 × 10-08). Genetic correlation analysis revealed a strong shared genetic basis with estrogen receptor-positive FBC. Men in the top quintile of genetic risk had a fourfold increased risk of breast cancer relative to those in the bottom quintile (odds ratio = 3.86, 95% confidence interval = 3.07 to 4.87, P = 2.08 × 10-30).Conclusions: These findings advance our understanding of the genetic basis of MBC, providing support for an overlapping genetic etiology with FBC and identifying a fourfold high-risk group of susceptible men. [ABSTRACT FROM AUTHOR]