High-speed optical links are often used in trigger and data acquisition systems of High Energy Physics (HEP) experiments for data transfer, trigger and fast control distribution. Many experiments ...prefer the use of commercial off-the-shelf components (COTS) if possible, in order to avoid the non-recurrent engineering (NRE) costs and risks associated with the design of application specific integrated circuits. For the mentioned reason, static random access memory-based field programmable gate arrays (SRAM-based FPGAs) are usually deployed. However they are mostly used off-detector, where little or no radiation is present, since single event upsets in the configuration memory may alter the design functionality. In order to benefit from SRAM-based FPGAs also in radiation environments expected on-detector, suitable soft-error mitigation strategies must be adopted. In this work we evaluate the design trade-offs between performance and radiation-tolerance in a high-speed fixed-latency link based on a Virtex-5 SRAM-based FPGA. We evaluate different radiation mitigation strategies. Moreover, we experimentally verify some custom-developed placement and routing rules aimed at improving the FPGA firmware robustness against configuration upsets.
A novel electrochemical approach to access alkyl alkenesulfonates via a multicomponent reaction was developed. The metal-free method features easy-to-use SO
stock solution forming monoalkylsulfites ...from alcohols with an auxiliary base in-situ. These intermediates serve a dual role as starting materials and as supporting electrolyte enabling conductivity. Anodic oxidation of the substrate styrene, radical addition of these monoalkylsulfites and consecutive second oxidation and deprotonation preserve the double bond and form alkyl β-styrenesulfonates in a highly regio- and stereoselective fashion. The feasibility of this electrosynthetic method is demonstrated in 44 examples with yields up to 81 %, employing various styrenes and related substrates as well as a diverse set of alcohols. A gram-scale experiment underlines the applicability of this process, which uses inexpensive and readily available electrode materials.
The Sister Study was designed to address gaps in the study of environment and breast cancer by taking advantage of more frequent breast cancer diagnoses among women with a sister history of breast ...cancer and the presumed enrichment of shared environmental and genetic exposures.
The Sister Study sought a large cohort of women never diagnosed with breast cancer but who had a sister (full or half) diagnosed with breast cancer.
A multifaceted national effort employed novel strategies to recruit a diverse cohort, and collected biological and environmental samples and extensive data on potential breast cancer risk factors.
The Sister Study enrolled 50,884 U.S. and Puerto Rican women 35-74y of age (median 56 y). Although the majority were non-Hispanic white, well educated, and economically well off, substantial numbers of harder-to-recruit women also enrolled (race/ethnicity other than non-Hispanic white: 16%; no college degree: 35%; household income <$50,000: 26%). Although all had a biologic sister with breast cancer, 16.5% had average or lower risk of breast cancer according to the Breast Cancer Risk Assessment Tool (Gail score). Most were postmenopausal (66%), parous with a first full-term pregnancy <30y of age (79%), never-smokers (56%) with body mass indexes (BMIs) of <29.9
kg/m
(70%). Few (5%) reported any cancer prior to enrollment.
The Sister Study is a unique cohort designed to efficiently study environmental and genetic risk factors for breast cancer. Extensive exposure data over the life-course and baseline specimens provide important opportunities for studying breast cancer and other health outcomes in women. Collaborations are welcome. https://doi.org/10.1289/EHP1923.
Delay Locked Loops (DLLs) and Phase Locked Loops (PLLs) are available as embedded hard-macros in the latest Field Programmable Gate Arrays (FPGAs). Their main features are clock phase de-skewing, ...frequency multiplication and division. Moreover, the availability of PLLs allows the user to perform jitter filtering too. The clock signal at the output of a DLL or a PLL has a phase noise, which has to be taken into account in timing sensitive applications, such as analog-to-digital conversion, time measurements or high-speed serial links.
Fixed-latency serial links find application in trigger and data acquisition systems of high energy physics (HEP) experiments requiring a predictable data transfer timing. In some architectures, there ...is the need to clock the data in and out from the link synchronously with a system clock (i.e., synchronous transfers) instead of using the clock recovered from the serial stream. In this work, we present a synchronous link architecture based on high-speed transceivers embedded in latest generation field programmable gate arrays (FPGAs). These transceivers are typically designed for applications that tolerate latency variations. However, we have developed two configurations and a clocking scheme to implement fixed-latency operation. The latency is constant during the transfer, after a loss of lock or a power cycle. Once locked, the link can be considered as a synchronous pipeline. The configurations do not depend on a particular serial encoding, the encoder/decoder being external to the transceiver. We discuss the latency performance for each configuration and show an implementation of the architecture we propose. We also present experimental results showing the stability of the latency of the link.
Earlier age at menarche is an established risk factor for breast cancer. While age at menarche has been fairly stable over the past half-century, age at breast development (thelarche) has continued ...to decrease. Recently, earlier age at thelarche and a longer time between thelarche and menarche (pubertal tempo) were shown to be associated with increased breast cancer risk. Our objective was to examine how breast cancer risk was associated with pubertal timing and tempo in a prospective US cohort.
Women ages 35-74 years without a history of breast cancer, but who had a sister previously diagnosed with breast cancer, were enrolled in the Sister Study from 2003 to 2009 (N = 50,884). At enrollment, participants reported their ages at thelarche and menarche. Pubertal tempo was age at menarche minus age at thelarche. We estimated adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for each pubertal milestone and risk of breast cancer (invasive or ductal carcinoma in situ) using Cox proportional hazards regression. We examined whether associations between age at thelarche and breast cancer risk were modified by birth cohort, race/ethnicity, weight at age 10, and extent of breast cancer family history, as characterized by a Bayesian score based on first-degree family structure.
During follow-up (mean = 9.3 years), 3295 eligible women were diagnosed with breast cancer. Early ages at thelarche (HR = 1.23, 95% CI 1.03-1.46 for < 10 vs. 12-13 years) and menarche (HR = 1.10, 95% CI 1.01-1.20 for < 12 vs. 12-13 years) were positively associated with breast cancer risk. Pubertal tempo was not associated with breast cancer risk (HR = 0.99, 95% CI 0.97-1.02 per 1-year longer tempo). When considering early thelarche (< 10 years) and early menarche (< 12 years) jointly, women with both had a 30% greater risk of breast cancer compared with women with neither risk factor (95% CI 1.07-1.57). The association between age at thelarche and breast cancer risk did not significantly vary by birth cohort, race/ethnicity, childhood weight, or Bayesian family history score.
Earlier ages at thelarche and menarche may enhance susceptibility to breast carcinogenesis. Age at thelarche is an important risk factor to consider given secular trends towards earlier development.
Exposure to traumatic childhood experiences (TCEs) may contribute to poor sleep in adulthood. Previous studies have been limited to mainly investigating physical and sexual abuse and did not consider ...betrayal trauma, or whether the victim regarded the perpetrator as someone socially close to them, the age group at occurrence, and trauma-related distress/anxiety.
We used a large cohort of US women, 35-74 years old, enrolled in the Sister Study from 2003 to 2009. Self-reports of specific TCEs occurring before the age of 18 years included sexual, physical, and psychological/emotional trauma; natural disasters; major accidents; and household dysfunction. Participants self-reported average sleep duration (short: <7 hours vs recommended: 7-9 hours), sleep onset latency (SOL) at least 30 vs less than 30 minutes, at least 3 night awakenings once asleep at least 3 times/week (Night awakenings NA, yes vs no), and napping at least 3 vs less than 3 times/week.
Among 40 082 women, 55% reported a TCE, with 82% reporting betrayal trauma. Compared to women reporting no TCE, women with any TCE were more likely to report short sleep (prevalence ratio PR = 1.08, 95% confidence interval (CI) = 1.04 to 1.11), longer SOL (1.11, 1.06 to 1.16), frequent NAs (1.06, 1.00 to 1.11), and frequent napping (1.05, 0.99 to 1.12). The relationship between experiencing any TCE and short sleep was stronger for TCEs by a perpetrator considered socially close vs not close (1.12, 1.09 to 1.16), SOL (1.27, 1.22 to 1.33), NA (1.20, 1.14 to 1.27), and napping (1.24, 1.17 to 1.32).
TCEs were associated with poor sleep in women with greater impact when the perpetrator was regarded as close. More research is warranted to better understand pathways between childhood trauma and sleep health in adulthood to develop effective interventions.
We investigated the electrochemical sulfenylation reaction in both batch and continuous flow regimes, involving thiophenols/thiols and enol-acetates to yield α-sulfenylated ketones, without using ...additional oxidants or catalysts. Studies with different electrolytes were also performed, revealing that quaternary ammonium salts are the best mediators for this reaction. Notably, during the study of the reaction scope, a Boc-cysteine proved to be extremely tolerant to our protocol, thus increasing its relevance. The methodology also proved to be scalable in both batch and continuous flow conditions, opening up possibilities for further studies since these relevant functional groups are important moieties in organic synthesis.
To evaluate the efficacy of levetiracetam as prophylactic treatment for migraine with aura with high frequency of attacks.
Migraine with aura with high frequency of attacks could represent a very ...demanding therapeutic problem. Efficacy of the antiepileptic drug, lamotrigine, has been reported in this form of migraine. Levetiracetam is a new antiepileptic drug with an excellent tolerability profile. Mechanisms of action of this drug remain largely unknown, but recently, it has been shown to exert inhibitory effects on neuronal-type calcium channels.
We performed a small open-label trial treating 16 patients affected by migraine with aura with high frequency of attacks. After a 1-month run-in period, patients were treated with levetiracetam at a dosage of 1000 mg/d for 6 months.
The number of attacks per month was significantly reduced during the first month (compared with run-in; P < 0.001), and it was reduced further during the second (second month vs first month; P < 0.001) and the third months (third month vs second month; P < 0.001) of the treatment. This improvement persisted unchanged for the remaining 3 months of treatment. In 7 (44%) of the 16 patients, the attacks were completely abolished after 3 months of treatment. Severity of headache and duration of headache and aura were also significantly reduced at the third and sixth months of treatment (P < 0.001). Levetiracetam was well tolerated (6 patients complained of slight dizziness, nervousness, and somnolence).
Levetiracetam seems to be a safe and effective treatment for migraine with aura. Controlled trials are needed to confirm the observed results.
Abstract
STUDY QUESTION
Does maternal age at a daughter's birth predict her subsequent probability of lifelong childlessness?
SUMMARY ANSWER
In this study population, women born to older mothers were ...more likely to be childless.
WHAT IS KNOWN ALREADY
Although maternal age at childbearing is increasing in many countries, there is limited evidence on whether being born to older parents may influence offspring fertility.
STUDY DESIGN SIZE AND DURATION
This analysis included 43 135 women from the US-based Sister Study, a cohort study of 50 884 sisters of women with breast cancer recruited between 2003 and 2009.
PARTICIPANTS/MATERIALS, SETTING, METHODS
Participants had no breast cancer at baseline. Women were included in the analytic sample if they were born between 1930 and 1964 and were at least 44 years old at enrolment. Median age when reproductive history was last ascertained was 63.8 years. We estimated relative risks (RR) and 95% CI of lifelong childlessness as a function of maternal age at birth, using multivariable log-binomial models, including total number of siblings, birth order, socioeconomic indicators of the family of origin, race and birth cohort. We examined the association in different subgroups and in a sibling-matched analysis including 802 sister pairs discordant for childlessness.
MAIN RESULTS AND ROLE OF CHANCE
Compared with women born to 20-24-year-old mothers, those born to mothers aged 25-29, 30-34 and ≥35 years were more likely to be childless RR (95% CI): 1.21 (1.14-1.29), 1.30 (1.22-1.39) and 1.40 (1.31-1.50), respectively. The association was consistent in strata defined by birth cohort, number of siblings, birth order, and participant's educational level, as well as within sister pairs. Overall, we found weak evidence for an independent contribution of paternal age at birth to the daughter's probability of childlessness.
LIMITATIONS REASONS FOR CAUTION
All participants had at least one sister, and all information was self-reported. We had no knowledge of whether childlessness was intentional and found only a modest association between maternal age at birth and self-reported indicators of infertility. Still, the association with childlessness was highly consistent.
WIDER IMPLICATIONS OF THE FINDING
Given the widespread tendency to delay childbearing, evaluating the influence of maternal age at birth on offspring fertility is a public health priority.
STUDY FUNDING/COMPETING INTERESTS
This research was supported in part by the Intramural Research Programme of the NIH, National Institute of Environmental Health Sciences (Z01-ES044005). The authors report no conflict of interest.
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