2D Time-Domain Spectroscopy for Determination of Energy and Momentum Relaxation Rates of Hydrogen-Like Donor States in Germanium.

We present measurements of the coherence times of excited states of hydrogen-like arsenic impurities in germanium (Ge:As) using a table-top two-dimensional time-domain spectroscopy (2D-TDS) system. We show that this laboratory system is capable of resolving the coherence lifetimes of atomic-like excited levels of impurity centers in semiconductors, such as those used in solid-state quantum information technologies, on a subpicosecond time scale. By fitting the coherent nonlinear response of the system with the known intracenter transition frequencies, we are able to monitor coherent population transfer and decay of the transitions from the 2p0 and 2p± states for different low excitation pulse fields. Furthermore, by examining the off-diagonal resonances in the 2D frequency-domain map, we are able to identify coherences between excited electronic states that are not visible via conventional single-frequency pump-probe or Hahn-echo measurements.

Sleep and Risk of Pancreatic Cancer in the UK Biobank.

BACKGROUND: Light at night, which may cause circadian disruption, is a potential pancreatic cancer risk factor. However, evidence from related exposures such as poor sleep health and shift work remains inconclusive and sparsely investigated. METHODS: We evaluated associations between self-reported typical sleep duration, chronotype, shift work, insomnia symptoms, snoring, and daytime sleeping and pancreatic ductal adenocarcinomas (PDAC) incidence among 475,286 UK Biobank participants. We used Cox proportional hazards models to estimate HRs and 95% confidence intervals (CI) adjusting for age, sex, body mass index, smoking status, duration, and frequency, alcohol intake, diabetes status, race, and employment/shift work. RESULTS: Over 14 years of follow-up, 1,079 adults were diagnosed with PDAC. There were no associations observed between sleep characteristics, including sleep duration [<7 vs. 7-<9 hours; HR, 1.03; 95% CI, 0.90-1.19; ≥9 hours; HR, 1.00 (0.81-1.24), evening chronotype ("definitely" an evening person vs. "definitely" a morning person; HR, 0.99 (0.77-1.29)], shift work, insomnia symptoms, snoring, or daytime sleep and PDAC risk. CONCLUSIONS: Self-reported typical sleep characteristics and shift work were not associated with PDAC risk. IMPACT: Considering the role of light at night and shift work in circadian disruption and cancer risk, it is plausible that poor sleep health among a general population may be related to cancer risk through similar sleep and circadian disrupting processes. This work may suggest that typical sleep characteristics and shift work are not associated with PDAC, although additional work is needed to confirm these findings.

Associations between actigraphy-measured sleep duration, continuity, and timing with mortality in the UK Biobank.

STUDY OBJECTIVES: To examine the associations between sleep duration, continuity, timing, and mortality using actigraphy among adults. METHODS: Data were from a cohort of 88 282 adults (40-69 years) in UK Biobank that wore a wrist-worn triaxial accelerometer for 7 days. Actigraphy data were processed to generate estimates of sleep duration and other sleep characteristics including wake after sleep onset (WASO), number of 5-minute awakenings, and midpoint for sleep onset/wake-up and the least active 5 hours (L5). Data were linked to mortality outcomes with follow-up to October 31, 2021. We implemented Cox models (hazard ratio, confidence intervals [HR, 95% CI]) to quantify sleep associations with mortality. Models were adjusted for demographics, lifestyle factors, and medical conditions. RESULTS: Over an average of 6.8 years 2973 deaths occurred (1700 cancer, 586 CVD deaths). Overall sleep duration was significantly associated with risk for all-cause (p < 0.01), cancer (p < 0.01), and CVD (p = 0.03) mortality. For example, when compared to sleep durations of 7.0 hrs/d, durations of 5 hrs/d were associated with a 29% higher risk for all-cause mortality (HR: 1.29 [1.09, 1.52]). WASO and number of awakenings were not associated with mortality. Individuals with L5 early or late midpoints (<2:30 or ≥ 3:30) had a ~20% higher risk for all-cause mortality, compared to those with intermediate L5 midpoints (3:00-3:29; p ≤ 0.01; e.g. HR ≥ 3:30: 1.19 [1.07, 1.32]). CONCLUSIONS: Shorter sleep duration and both early and late sleep timing were associated with a higher mortality risk. These findings reinforce the importance of public health efforts to promote healthy sleep patterns in adults.

Actigraphy-derived measures of sleep and risk of prostate cancer in the UK Biobank.

BACKGROUND: Studies of sleep and prostate cancer are almost entirely based on self-report, with limited research using actigraphy. Our goal was to evaluate actigraphy-measured sleep and prostate cancer and to expand on findings from prior studies of self-reported sleep. METHODS: We prospectively examined 34 260 men without a history of prostate cancer in the UK Biobank. Sleep characteristics were measured over 7 days using actigraphy. We calculated sleep duration, onset, midpoint, wake-up time, social jetlag (difference in weekend-weekday sleep midpoints), sleep efficiency (percentage of time spent asleep between onset and wake-up time), and wakefulness after sleep onset. Cox proportional hazards models were used to estimate covariate-adjusted hazards ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Over 7.6 years, 1152 men were diagnosed with prostate cancer. Sleep duration was not associated with prostate cancer risk. Sleep midpoint earlier than 4:00 am was not associated with prostate cancer risk, though sleep midpoint of 5:00 am or later was suggestively associated with lower prostate cancer risk but had limited precision (earlier than 4:00 am vs 4:00-4:59 am HR = 1.00, 95% CI = 0.87 to 1.16; 5:00 am or later vs 4:00-4:59 am HR = 0.79, 95% CI = 0.57 to 1.10). Social jetlag was not associated with greater prostate cancer risk (1 to <2 hours vs <1 hour HR = 1.06, 95% CI = 0.89 to 1.25; ≥2 hours vs <1 hour HR = 0.90, 95% CI = 0.65 to 1.26). Compared with men who averaged less than 30 minutes of wakefulness after sleep onset per day, men with 60 minutes or more had a higher risk of prostate cancer (HR = 1.20, 95% CI = 1.00 to 1.43). CONCLUSIONS: Of the sleep characteristics studied, higher wakefulness after sleep onset-a measure of poor sleep quality-was associated with greater prostate cancer risk. Replication of our findings between wakefulness after sleep onset and prostate cancer are warranted.

Variability in Sleep Duration and Biomarkers of Cardiovascular Disease Across the Menstrual Cycle.

Variability in sleep duration and cardiovascular health have been infrequently investigated, particularly among reproductive-age women. We examined these associations across the menstrual cycle among a cohort of 250 healthy premenopausal women, aged 18-44 years. The BioCycle study (New York, 2005-2007) collected cardiovascular biomarkers (serum high- and low-density lipoprotein (HDL, LDL), total cholesterol, triglycerides, and C-reactive protein (CRP)) at key time points along the menstrual cycle (follicular, ovulatory, and luteal phases). Women also recorded sleep duration in daily diaries. From these data, we computed L-moments, robust versions of location, dispersion, skewness, and kurtosis. We fitted linear mixed models with random intercepts and inverse probability weighting to estimate associations between sleep variability and cardiovascular biomarkers, accounting for demographic, lifestyle, health, and reproductive factors. Sleep dispersion (any deviation from mean duration) was associated with lower mean LDL for nonshift workers and non-White women. Skewed sleep duration was associated with higher mean CRP and lower mean total cholesterol. Sleep durations with extreme short and long bouts (kurtosis) were associated with a lower mean HDL, but not mean CRP, LDL, or triglycerides. Sleep duration modified associations between sleep dispersion and LDL, HDL, and total cholesterol. Even in young and healthy women, sleep duration variability could influence cardiovascular health.

Association of Accelerometer-Measured Physical Activity Level With Risks of Hospitalization for 25 Common Health Conditions in UK Adults.

Importance: Higher physical activity levels are associated with lower risks of cancer, cardiovascular disease, and diabetes, but associations with many common and less severe health conditions are not known. These conditions impose large health care burdens and reduce quality of life. Objectives: To investigate the association between accelerometer-measured physical activity and the subsequent risk of hospitalization for 25 common reasons for hospitalization and to estimate the proportion of these hospitalizations that might have been prevented if participants had higher levels of physical activity. Design, Setting, and Participants: This prospective cohort study used data from a subset of 81 717 UK Biobank participants aged 42 to 78 years. Participants wore an accelerometer for 1 week (between June 1, 2013, and December 23, 2015) and were followed up over a median (IQR) of 6.8 (6.2-7.3) years; follow-up for the current study ended in 2021 (exact date varied by location). Exposures: Mean total and intensity-specific accelerometer-measured physical activity. Main Outcomes and Measures: Hospitalization for the most common health conditions. Cox proportional hazards regression analysis was used to estimate hazard ratios (HRs) and 95% CIs for mean accelerometer-measured physical activity (per 1-SD increment) and risks of hospitalization for 25 conditions. Population-attributable risks were used to estimate the proportion of hospitalizations for each condition that might be prevented if participants increased their moderate to vigorous physical activity (MVPA) by 20 minutes per day. Results: Among 81 717 participants, the mean (SD) age at accelerometer assessment was 61.5 (7.9) years; 56.4% were female, and 97.0% self-identified as White. Higher levels of accelerometer-measured physical activity were associated with lower risks of hospitalization for 9 conditions: gallbladder disease (HR per 1 SD, 0.74; 95% CI, 0.69-0.79), urinary tract infections (HR per 1 SD, 0.76; 95% CI, 0.69-0.84), diabetes (HR per 1 SD, 0.79; 95% CI, 0.74-0.84), venous thromboembolism (HR per 1 SD, 0.82; 95% CI, 0.75-0.90), pneumonia (HR per 1 SD, 0.83; 95% CI, 0.77-0.89), ischemic stroke (HR per 1 SD, 0.85; 95% CI, 0.76-0.95), iron deficiency anemia (HR per 1 SD, 0.91; 95% CI, 0.84-0.98), diverticular disease (HR per 1 SD, 0.94; 95% CI, 0.90-0.99), and colon polyps (HR per 1 SD, 0.96; 95% CI, 0.94-0.99). Positive associations were observed between overall physical activity and carpal tunnel syndrome (HR per 1 SD, 1.28; 95% CI, 1.18-1.40), osteoarthritis (HR per 1 SD, 1.15; 95% CI, 1.10-1.19), and inguinal hernia (HR per 1 SD, 1.13; 95% CI, 1.07-1.19), which were primarily induced by light physical activity. Increasing MVPA by 20 minutes per day was associated with reductions in hospitalization ranging from 3.8% (95% CI, 1.8%-5.7%) for colon polyps to 23.0% (95% CI, 17.1%-28.9%) for diabetes. Conclusions and Relevance: In this cohort study of UK Biobank participants, those with higher physical activity levels had lower risks of hospitalization across a broad range of health conditions. These findings suggest that aiming to increase MVPA by 20 minutes per day may be a useful nonpharmaceutical intervention to reduce health care burdens and improve quality of life.

Preconception sleep duration, sleep timing, and shift work in association with fecundability and live birth among women with a history of pregnancy loss.

OBJECTIVE: To evaluate the associations between preconception sleep characteristics and shift work with fecundability and live birth. DESIGN: Secondary analysis of the Effects of Aspirin in Gestation and Reproduction study, a preconception cohort. SETTING: Four US academic medical centers. PATIENT(S): Women aged 18-40 with a history of 1-2 pregnancy losses who were attempting to conceive again. INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURES(S): We evaluated baseline, self-reported sleep duration, sleep midpoint, social jetlag, and shift work among 1,228 women who were observed for ≤6 cycles of pregnancy attempts to ascertain fecundability. We ascertained live birth at the end of follow up via chart abstraction. We estimated fecundability odds ratios (FORs) using discrete, Cox proportional hazards models and risk ratios (RRs) for live birth using log-Poisson models. RESULT(S): Sleep duration ≥9 vs. 7 to <8 hours (FOR: 0.81, 95% confidence interval [CI], 0.61; 1.08), later sleep midpoints (3rd tertile vs. 2nd tertile: FOR: 0.85; 95% CI, 0.69, 1.04) and social jetlag (continuous per hour; FOR: 0.93, 95% CI: 0.86, 1.00) were not associated with reduced fecundability. In sensitivity analyses, excluding shift workers, sleep duration ≥9 vs. 7 to <8 hours (FOR: 0.62; 95% CI, 0.42; 0.93) was associated with low fecundability. Night shift work was not associated with fecundability (vs. non-night shift work FOR: 1.17, 95% CI, 0.96; 1.42). Preconception sleep was not associated with live birth. CONCLUSION(S): Overall, there does not appear to be a strong association between sleep characteristics, fecundability, and live birth. Although these findings may suggest weak and imprecise associations with some sleep characteristics, our findings should be evaluated in larger cohorts of women with extremes of sleep characteristics. CLINICAL TRIAL REGISTRATION NUMBER: Clinicaltrials.gov NCT00467363.

The Role of Maternal Preconception Adiposity in Human Offspring Sex and Sex Ratio.

We evaluated relationships between preconception adiposity and human offspring sex and sex ratio. Using data from a prospective preconception cohort nested within a randomized controlled trial based at 4 US clinical sites (2006-2012), we used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for male:female sex ratio, and log-identity regression to estimate risk differences (RDs) and 95% CIs for male and female livebirth according to preconception adiposity measures. Inverse-probability weights accounted for potential selection bias. Among 603 women attempting pregnancy, there were meaningful reductions in sex ratio for the highest category of each adiposity measure. The lowest sex ratios were observed for obesity (body mass index of ≥30, calculated as weight (kg)/height (m)2, OR = 0.48, 95% CI: 0.26, 0.88) relative to normal body mass index, and the top tertiles (tertile 3) of serum leptin (OR = 0.50, 95% CI: 0.32, 0.80) and skinfold measurements (OR = 0.50, 95% CI: 0.32, 0.79) relative to the lowest tertiles. Reductions were driven by 11-15 fewer male livebirths per 100 women (for obesity, RD = -15, 95% CI: -23, -6.7; for leptin tertile 3, RD = -11, 95% CI: -20, -3.2; and for skinfolds tertile 3, RD = -11, 95% CI: -19, -3.3). We found that relationships between preconception adiposity measures and reduced sex ratio were driven by a reduction in male births.

Association of Leisure Time Physical Activity Types and Risks of All-Cause, Cardiovascular, and Cancer Mortality Among Older Adults.

Importance: Higher amounts of physical activity are associated with increased longevity. However, whether different leisure time physical activity types are differentially associated with mortality risk is not established. Objectives: To examine whether participation in equivalent amounts of physical activity (7.5 to <15 metabolic equivalent of task [MET] hours per week) through different activity types is associated with mortality risk and to investigate the shape of the dose-response association. Design, Setting, and Participants: Participants in this cohort were respondents from the National Institutes of Health-AARP Diet and Health Study who completed the follow-up questionnaire between 2004 and 2005. This questionnaire collected data on weekly durations of different types of physical activities. Mortality was ascertained through December 31, 2019. Exposures: MET hours per week spent participating in the following activities: running, cycling, swimming, other aerobic exercise, racquet sports, golf, and walking for exercise. Main Outcomes and Measures: All-cause, cardiovascular, and cancer mortality. Separate multivariable-adjusted Cox proportional hazards regression models were fitted to estimate hazard ratios (HRs) and 95% CIs of mortality for each of the 7 types of leisure time physical activities, as well as the sum of these activities. Results: A total of 272 550 participants (157 415 men [58%]; mean [SD] age at baseline, 70.5 [5.4] years [range, 59-82 years]) provided information on types of leisure time activity, and 118 153 (43%) died during a mean (SD) follow-up of 12.4 (3.9) years. In comparison with those who did not participate in each activity, 7.5 to less than 15 MET hours per week of racquet sports (HR, 0.84; 95% CI, 0.75-0.93) and running (HR, 0.85; 95% CI, 0.78-0.92) were associated with the greatest relative risk reductions for all-cause mortality, followed by walking for exercise (HR, 0.91; 95% CI, 0.89-0.93), other aerobic activity (HR, 0.93; 95% CI, 0.90-0.95), golf (HR, 0.93; 95% CI, 0.90-0.97), swimming (HR, 0.95; 95% CI, 0.92-0.98), and cycling (HR, 0.97; 95% CI, 0.95-0.99). Each activity showed a curvilinear dose-response association with mortality risk; low MET hours per week of physical activity for any given activity type were associated with a large reduction in mortality risk, with diminishing returns for each increment in activity thereafter. Associations were similar for cardiovascular and cancer mortality. Conclusions and Relevance: This cohort study of older individuals found differences between different types of leisure time activities and mortality risk, but there were significant associations between participating in 7.5 to less than 15 MET hours per week of any activity and mortality risk.

Is Alcohol Consumption Associated With Risk of Early Menopause?

Earlier age at menopause is associated with increased long-term health risks. Moderate alcohol intake has been suggested to delay menopause onset, but it is unknown whether alcohol subtypes are associated with early menopause onset at age 45 years. Therefore, we aimed to evaluate risk of early natural menopause among 107,817 members of the Nurses' Health Study II who were followed from 1989 to 2011. Alcohol consumption overall and by subtypes, including beer, red wine, white wine, and liquor, was assessed throughout follow-up. We estimated hazard ratios in multivariable models that were adjusted for age, body mass index, parity, smoking, and other potential confounders. Women who reported moderate current alcohol consumption had lower risks of early menopause than did nondrinkers. Those who reported consuming 10.0-14.9 g/day had a lower risk of early menopause than did nondrinkers (hazard ratio = 0.81, 95% confidence interval: 0.68, 0.97). Among specific beverages, evidence of lower early menopause risk was confined to consumption of white wine and potentially red wine and liquor, but not to beer. Data from this large prospective study suggest a weak association of moderate alcohol intake with lower risk of early menopause, which was most pronounced for consumption of white and red wine and liquor. High consumption was not related to lower risk of early menopause.

The role of maternal preconception vitamin D status in human offspring sex ratio.

Evolutionary theory suggests that some animal species may experience shifts in their offspring sex ratio in response to maternal health and environmental conditions, and in some unfavorable conditions, females may be less likely to bear sons. Experimental data in both animals and humans indicate that maternal inflammation may disproportionately impact the viability of male conceptuses; however, it is unknown whether other factors associated with both pregnancy and inflammation, such as vitamin D status, are associated with the offspring sex ratio. Here, we show that among 1,228 women attempting pregnancy, preconception 25-hydroxyvitamin D concentrations are positively associated with the live birth of a male infant, with notably stronger associations among women with elevated high sensitivity C-reactive protein, a marker of systemic low-grade inflammation. Our findings suggest that vitamin D may mitigate maternal inflammation that would otherwise be detrimental to the implantation or survival of male conceptuses in utero.

Photoconductive arrays on insulating substrates for high-field terahertz generation.

We report on the design, fabrication and characterisation of large-area photoconductive THz array structures, consisting of a thin LT-GaAs active region transferred to an insulating substrate using a wafer-scale bonding process. The electrically insulating, transparent substrate reduces the parasitic currents in the devices, allowing peak THz-fields as high as 120 kV cm-1 to be generated over a bandwidth >5 THz. These results are achieved using lower pulse energies than demanded by conventional photoconductive arrays and other popular methods of generating high-field THz radiation. Two device sizes are fully characterised and the emission properties are compared to generation by optical rectification in ZnTe. The device can be operated in an optically saturated regime in order to suppress laser noise.

Physical activity and incidence of subclinical and clinical pregnancy loss: a secondary analysis in the effects of aspirin in gestation and reproduction randomized trial.

OBJECTIVE: To estimate the association between physical activity and risk of subclinical and clinical pregnancy loss among women with a history of pregnancy loss. DESIGN: Prospective cohort study as a secondary analysis of the Effects of Aspirin in Gestation and Reproduction randomized controlled trial of preconception-initiated low-dose aspirin among women with one or two prior pregnancy losses. SETTING: Four U.S. clinical centers, 2007-2011. PATIENT(S): Women with confirmed pregnancy (n = 785) as determined from hCG testing in longitudinally collected biospecimens. MAIN OUTCOME MEASURE(S): Subclinical loss of pregnancy detected only by hCG testing and clinically recognized loss. RESULT(S): Among 785 women (mean [SD] age, 28.7 [4.6] years) with an hCG-confirmed pregnancy, 188 (23.9%) experienced pregnancy loss. In multivariable models adjusted for confounders, compared with the first tertile of physical activity (median = 7.7 metabolic equivalent of task hours/week), there was a roughly twofold higher risk of subclinical loss in the second (risk ratio = 2.06; 95% confidence interval, 1.03-4.14) and third tertiles (risk ratio = 1.92; 95% confidence interval, 0.94-3.90), with median metabolic equivalent of task hours/week of 27.8 and 95.7, respectively. No relations were observed between physical activity and clinically recognized loss. CONCLUSION(S): Risk related to physical activity is different for pregnancy failure close to the time of implantation compared with that for later, clinical pregnancy loss. Higher physical activity levels were associated with an elevated risk of subclinical loss (i.e., pregnancies detected only by hCG, n = 55); however, no relationship was observed with clinically recognized loss. Further work is required to confirm these findings, assess generalizability to women without prior losses, and evaluate mechanisms. ETHICAL APPROVAL: Each participating center's Institutional Review Board approved the study, and participants provided written informed consent. The trial was registered on ClinicalTrials.gov (NCT00467363), and a Data Safety and Monitoring Board provided oversight.

Correlates of At-Risk and Problem Gambling Among Veterans in Massachusetts.

Few studies have examined problem gambling among veterans and, of those studies, there are conflicting conclusions surrounding correlates of problem gambling in veterans. Our study aims to assess problem gambling prevalence among veterans using non-Veterans Affairs data and to evaluate correlates of problem gambling among veterans in a general population sample. We obtained a probability sample of adult Massachusetts residents using address based sampling in 2013-2014. Participants completed a questionnaire on demographics, veteran status, and gambling behaviors and motivations. We identified n = 129 problem gamblers from a sample of n = 9578 participants. Of the problem gamblers who had veteran status information, 20.6% were veterans. Due to sample size limitations, we analyzed veteran problem and at-risk gamblers compared to veteran recreational gamblers. Having friends and family members engaged in gambling and engaging in more gambling formats were significantly, positively associated with veteran problem and at-risk gambler status. Participating in raffles in the past year was associated with lower odds of being a veteran problem and at-risk gambler compared to veteran recreational gamblers (OR 0.31, 95% CI 0.18-0.52). These discriminators of at-risk and problem gambling may be useful in developing clinical treatment approaches for veteran problem gamblers. Future studies should focus on changes in the prevalence of veteran problem gambling and additional correlates that may better capture social support domains and gambling activity among veterans.

The influences of sleep duration, chronotype, and nightwork on the ovarian cycle.

Despite research indicating that sleep disorders influence reproductive health, the effects of sleep on reproductive hormone concentrations are poorly characterized. We prospectively followed 259 regularly menstruating women across one to two menstrual cycles (the BioCycle Study, 2005-2007), measuring fasting serum hormone concentrations up to eight times per cycle. Women provided information about daily sleep in diaries and chronotype and night/shift work on a baseline questionnaire. We evaluated percent differences in mean hormone concentrations, the magnitude of shifts in the timing and amplitude of hormone peaks, and the risk for sporadic anovulation associated with self-reported sleep patterns and night/shift work. We estimated chronotype scores - categorizing women below and above the interquartile range (IQR) as "morning" and "evening" chronotypes, respectively. For every hour increase in daily sleep duration, mean estradiol concentrations increased by 3.9% (95% confidence interval [CI] 2.0, 5.9%) and luteal phase progesterone by 9.4% (CI 4.0, 15.2%). Receiving less than 7 hours of sleep per day was associated with slightly earlier rises in peak levels for several hormones. Women reporting night/shift work (n = 77) had lower testosterone relative to women employed without night/shift work (percent difference: -9.9%, CI -18.4, -0.4%). Women with morning chronotypes (n = 47) had earlier rises in estradiol during their cycles and potentially an earlier rise in luteinizing hormone. Compared to those who had intermediate chronotypes, women with evening chronotypes (n = 42) had a later luteinizing hormone peak of borderline statistical significance. A reduced risk for sporadic anovulation was suggested, but imprecise, for increasing hours of daily sleep leading up to ovulation (risk ratio 0.79, CI 0.59, 1.06), while an imprecise increased risk was observed for women with morning chronotypes (risk ratio 2.50, CI 0.93, 6.77). Sleep-related hormonal changes may not greatly alter ovarian function in healthy women, but have the potential to influence gynecologic health.

Appraising the causal relevance of DNA methylation for risk of lung cancer.

BACKGROUND: DNA methylation changes in peripheral blood have recently been identified in relation to lung cancer risk. Some of these changes have been suggested to mediate part of the effect of smoking on lung cancer. However, limitations with conventional mediation analyses mean that the causal nature of these methylation changes has yet to be fully elucidated. METHODS: We first performed a meta-analysis of four epigenome-wide association studies (EWAS) of lung cancer (918 cases, 918 controls). Next, we conducted a two-sample Mendelian randomization analysis, using genetic instruments for methylation at CpG sites identified in the EWAS meta-analysis, and 29 863 cases and 55 586 controls from the TRICL-ILCCO lung cancer consortium, to appraise the possible causal role of methylation at these sites on lung cancer. RESULTS: Sixteen CpG sites were identified from the EWAS meta-analysis [false discovery rate (FDR) < 0.05], for 14 of which we could identify genetic instruments. Mendelian randomization provided little evidence that DNA methylation in peripheral blood at the 14 CpG sites plays a causal role in lung cancer development (FDR > 0.05), including for cg05575921-AHRR where methylation is strongly associated with both smoke exposure and lung cancer risk. CONCLUSIONS: The results contrast with previous observational and mediation analysis, which have made strong claims regarding the causal role of DNA methylation. Thus, previous suggestions of a mediating role of methylation at sites identified in peripheral blood, such as cg05575921-AHRR, could be unfounded. However, this study does not preclude the possibility that differential DNA methylation at other sites is causally involved in lung cancer development, especially within lung tissue.

Author Correction: Ultrafast switch-on dynamics of frequency-tuneable semiconductor lasers.

The original version of this Article contained an error in the Acknowledgements, which incorrectly omitted the following: 'We also acknowledge support from the Australian Research Council's Discovery Projects Funding Scheme (Grant DP 160 103910).' This has been corrected in both the PDF and HTML versions of the Article.

Ultrafast switch-on dynamics of frequency-tuneable semiconductor lasers.

Single-mode frequency-tuneable semiconductor lasers based on monolithic integration of multiple cavity sections are important components, widely used in optical communications, photonic integrated circuits and other optical technologies. To date, investigations of the ultrafast switching processes in such lasers, essential to reduce frequency cross-talk, have been restricted to the observation of intensity switching over nanosecond-timescales. Here, we report coherent measurements of the ultrafast switch-on dynamics, mode competition and frequency selection in a monolithic frequency-tuneable laser using coherent time-domain sampling of the laser emission. This approach allows us to observe hopping between lasing modes on picosecond-timescales and the temporal evolution of transient multi-mode emission into steady-state single mode emission. The underlying physics is explained through a full multi-mode, temperature-dependent carrier and photon transport model. Our results show that the fundamental limit on the timescales of frequency-switching between competing modes varies with the underlying Vernier alignment of the laser cavity.

A pilot longitudinal study of anti-Müllerian hormone levels throughout gestation in low risk pregnancy.

BACKGROUND: Anti-Mϋllerian hormone (AMH) plays an important role regulating ovarian sensitivity to follicle-stimulating hormone and luteinizing hormone in folliculogenesis. Anti-Mϋllerian hormone is well established as a biomarker of ovarian reserve but may also have utility in predicting pregnancy outcomes. Few studies have described AMH levels in pregnancy and, among those that have, most have used cross-sectional study designs and are limited to participants seeking fertility treatment. Our aim was to analyze AMH longitudinally in low-risk pregnancies. METHODS: We conducted a prospective cohort study at Baystate Medical Center, a large tertiary care hospital in Springfield, MA, USA. We recruited women (n = 30) with low risk, singleton pregnancies, aged 18 to 35 years, with BMI between 18 and 40 kg/m2, and without preexisting disease. Anti-Mϋllerian hormone (pmol/L) was measured in plasma samples collected at 5 prenatal care visits throughout gestation. RESULTS: Anti-Mϋllerian hormone levels varied significantly over gestation (Friedman's analysis of variance, P value < .0001). At gestational weeks 7 to 10, average AMH was 36.7 pmol/L (standard error = 8.1) and at weeks 34 to 37 was 9.5 pmol/L (standard error = 1.9). Initial AMH varied between women, and an overall significant log-linear decline was observed. CONCLUSIONS: Anti-Mϋllerian hormone varies between women and declines exponentially during pregnancy. The biological mechanism of the heterogeneity of AMH decline over gestation is unclear. Future studies evaluating AMH throughout pregnancy that also assess gravid health and pregnancy outcomes are warranted.

Terahertz generation mechanism in nano-grating electrode photomixers on Fe-doped InGaAsP.

We report the generation mechanism associated with nano-grating electrode photomixers fabricated on Fe-doped InGaAsP substrates. Two different emitter designs incorporating nano-gratings coupled to the same broadband antenna were characterized in a continuous-wave terahertz (THz) frequency system employing telecommunications wavelength lasers for generation and coherent detection. The current-voltage characteristics and THz emission bandwidth of the emitters is compared for different bias polarities and optical polarisations. The THz output from the emitters is also mapped as a function of the position of the laser excitation spot for both continuous-wave and pulsed excitation. This mapping, together with full-wave simulations of the structures, confirms the generation mechanism to be due to an enhanced optical electric field at the grating tips resulting in increased optical absorption, coinciding with a concentration of the electrostatic field.