Oral Contraceptives and Reproductive Cancers: Weighing the Risks and Benefits

The hypothetical incidence of reproductive cancers resulting from oral contraceptive use was estimated in several models comparing the cumulative lifetime incidence of cancer of the breast, cervix, ovary and endometrium expected in pill users with the incidence expected in nonusers. The potential number of cancer-free days that would be gained or lost by pill users was com- pared with similar estimates among nonusers. If five years or more of pill use were associated with a 20% increase in the risk of breast cancerbeing diagnosed before age 50, a 20% increase in cervical cancer risk and a 50% reduction in the risks of ovarian and endometrial cancers, then every 100,000 pill users would experience 44 fewer reproductive cancers during their lifetime than would nonusers, and would gain one more day free of cancer. If higher estimates of the five-yearpill-associated risks of breast and cervical cancer are used-a 50% increased risk of each, for example-then pill users would experience more reproductive cancers than nonusers and would have 11 fewer cancer-free days of life

On the homology of the Harmonic Archipelago

We calculate the singular homology and \v{C}ech cohomology groups of the Harmonic archipelago. As a corollary, we prove that this space is not homotopy equivalent to the Griffiths space. This is interesting in view of Eda's proof that the first singular homology groups of these spaces are isomorphic

The GOAL study: a prospective examination of the impact of factor V Leiden and ABO(H) blood groups on haemorrhagic and thrombotic pregnancy outcomes

Factor V Leiden (FVL) and ABO(H) blood groups are the common influences on haemostasis and retrospective studies have linked FVL with pregnancy complications. However, only one sizeable prospective examination has taken place. As a result, neither the impact of FVL in unselected subjects, any interaction with ABO(H) in pregnancy, nor the utility of screening for FVL is defined. A prospective study of 4250 unselected pregnancies was carried out. A venous thromboembolism (VTE) rate of 1·23/1000 was observed, but no significant association between FVL and pre-eclampsia, intra-uterine growth restriction or pregnancy loss was seen. No influence of FVL and/or ABO(H) on ante-natal bleeding or intra-partum or postpartum haemorrhage was observed. However, FVL was associated with birth-weights >90th centile [odds ratio (OR) 1·81; 95% confidence interval (CI<sub>95</sub>) 1·04–3·31] and neonatal death (OR 14·79; CI<sub>95</sub> 2·71–80·74). No association with ABO(H) alone, or any interaction between ABO(H) and FVL was observed. We neither confirmed the protective effect of FVL on pregnancy-related blood loss reported in previous smaller studies, nor did we find the increased risk of some vascular complications reported in retrospective studies

NASCaps: A Framework for Neural Architecture Search to Optimize the Accuracy and Hardware Efficiency of Convolutional Capsule Networks

Deep Neural Networks (DNNs) have made significant improvements to reach the desired accuracy to be employed in a wide variety of Machine Learning (ML) applications. Recently the Google Brain's team demonstrated the ability of Capsule Networks (CapsNets) to encode and learn spatial correlations between different input features, thereby obtaining superior learning capabilities compared to traditional (i.e., non-capsule based) DNNs. However, designing CapsNets using conventional methods is a tedious job and incurs significant training effort. Recent studies have shown that powerful methods to automatically select the best/optimal DNN model configuration for a given set of applications and a training dataset are based on the Neural Architecture Search (NAS) algorithms. Moreover, due to their extreme computational and memory requirements, DNNs are employed using the specialized hardware accelerators in IoT-Edge/CPS devices. In this paper, we propose NASCaps, an automated framework for the hardware-aware NAS of different types of DNNs, covering both traditional convolutional DNNs and CapsNets. We study the efficacy of deploying a multi-objective Genetic Algorithm (e.g., based on the NSGA-II algorithm). The proposed framework can jointly optimize the network accuracy and the corresponding hardware efficiency, expressed in terms of energy, memory, and latency of a given hardware accelerator executing the DNN inference. Besides supporting the traditional DNN layers, our framework is the first to model and supports the specialized capsule layers and dynamic routing in the NAS-flow. We evaluate our framework on different datasets, generating different network configurations, and demonstrate the tradeoffs between the different output metrics. We will open-source the complete framework and configurations of the Pareto-optimal architectures at https://github.com/ehw-fit/nascaps.Comment: To appear at the IEEE/ACM International Conference on Computer-Aided Design (ICCAD '20), November 2-5, 2020, Virtual Event, US

Informatics Enhanced SNP Microarray Analysis of 30 Miscarriage Samples Compared to Routine Cytogenetics

Purpose: The metaphase karyotype is often used as a diagnostic tool in the setting of early miscarriage; however this technique has several limitations. We evaluate a new technique for karyotyping that uses single nucleotide polymorphism microarrays (SNP). This technique was compared in a blinded, prospective fashion, to the traditional metaphase karyotype. Methods: Patients undergoing dilation and curettage for first trimester miscarriage between February and August 2010 were enrolled. Samples of chorionic villi were equally divided and sent for microarray testing in parallel with routine cytogenetic testing. Results: Thirty samples were analyzed, with only four discordant results. Discordant results occurred when the entire genome was duplicated or when a balanced rearrangement was present. Cytogenetic karyotyping took an average of 29 days while microarray-based karytoyping took an average of 12 days. Conclusions: Molecular karyotyping of POC after missed abortion using SNP microarray analysis allows for the ability to detect maternal cell contamination and provides rapid results with good concordance to standard cytogenetic analysis

Testicular Dysgenesis Syndrome and the Estrogen Hypothesis: A Quantitative Meta-Analysis

BACKGROUND: Male reproductive tract abnormalities such as hypospadias and cryptorchidism, and testicular cancer have been proposed to comprise a common syndrome together with impaired spermatogenesis with a common etiology resulting from the disruption of gonadal development during fetal life, the testicular dysgenesis syndrome (TDS). The hypothesis that in utero exposure to estrogenic agents could induce these disorders was first proposed in 1993. The only quantitative summary estimate of the association between prenatal exposure to estrogenic agents and testicular cancer was published over 10 years ago, and other systematic reviews of the association between estrogenic compounds, other than the potent pharmaceutical estrogen diethylstilbestrol (DES), and TDS end points have remained inconclusive. OBJECTIVES: We conducted a quantitative meta-analysis of the association between the end points related to TDS and prenatal exposure to estrogenic agents. Inclusion in this analysis was based on mechanistic criteria, and the plausibility of an estrogen receptor (ER)-–mediated mode of action was specifically explored. RESULTS: We included in this meta-analysis eight studies investigating the etiology of hypospadias and/or cryptorchidism that had not been identified in previous systematic reviews. Four additional studies of pharmaceutical estrogens yielded a statistically significant updated summary estimate for testicular cancer. CONCLUSIONS: The doubling of the risk ratios for all three end points investigated after DES exposure is consistent with a shared etiology and the TDS hypothesis but does not constitute evidence of an estrogenic mode of action. Results of the subset analyses point to the existence of unidentified sources of heterogeneity between studies or within the study population

Knowledge, Perceptions and Information about Hormone Therapy (HT) among Menopausal Women: A Systematic Review and Meta-Synthesis

BACKGROUND: The use of hormone therapy (HT) by menopausal women has declined since the Women's Health Initiative randomized trial (WHI) in 2002 demonstrated important harms associated with long-term use. However, how this information has influenced women's knowledge and attitudes is uncertain. We aimed to evaluate the attitudes and perceptions towards HT use, as well as specific concerns and information sources on HT since the WHI trial. METHOD/RESULTS: We did a systematic review to assess the attitudes and knowledge towards HT in women, and estimate the magnitude of the issue by pooling across the studies. Using meta-synthesis methods, we reviewed qualitative studies and surveys and performed content analysis on the study reports. We pooled quantitative studies using a random-effects meta-analysis. We analyzed 11 qualitative studies (n = 566) and 27 quantitative studies (n = 39251). Positive views on HT included climacteric symptom control, prevention of osteoporosis and a perceived improvement in quality of life. Negative factors reported included concerns about potential harmful effects, particularly cancer risks. Sources of information included health providers, media, and social contact. By applying a meta-synthesis approach we demonstrate that these findings are broadly applicable across large groups of patients. CONCLUSIONS: Although there are clear hazards associated with long-term HT use, many women view HT favorably for climacteric symptom relief. Media, as a source of information, is often valued as equivalent to health providers

Гемодинамические нарушения в магистральных сосудах глаза и орбиты при эндокринной офтальмопатии как фактор риска развития оптической нейропатии

PURPOSE: The search and identification of factor revealing the hemodynamic disturbances in magistral ocular and orbital blood vessels in endocrine ophthalmopathy (EOP) increasing the risk of the optic neuropathy development. METHODS: 86 patients with EOP were examined. EOP was associated with Graves' disease (GD, n=72, 144 orbits) and autoimmune thyroiditis (AIT, n=14, 28 orbits). All patients were examined by an ophthalmologist and an endo-crinologist. The diagnostic of GD and AIT was based on the medical history, examination, the level of thyroid hormones (free T4, free T3), thyroid-stimulating hormone (TSH), rTSH antibodies and thyroid sonography. Normal range for TSH levels was 0.25-3.5 mlU/l; free Т4 - 9.0-20.0 pmol/L; free ТЗ - 4.26-8.1 pmol/L. Patients with EOP were evaluated using the EUGOGO protocol. Every orbit was assessed separately. Ophthalmic examination included patients history and clinical assessment of EOP. All patients underwent similar eye examination (visometry, perimetry, biomicroscopy, tono-metry, ophthalmoscopy, Hertel exophthalmometry). Orbit pathology was verified by multispiral computed tomography. Orbit echography was carried out for all patients. Eyeball, retrobulbar space and magistral vessels were the anatomic objects of investigation. Blood flow was examined by ultrasound diagnostic system Voluson 730 PRO («Kretz», Austria) in regimen of triplexic screening (B-regimen, CDK in combination with impulse value dopplrography). Hemodynamic indices were analysed in a. ophthalmica, a. et v. retinae centralis, a. ciliaris posterior brevis et longae. Thyroid dysfunction type, endocrine disease duration, patient's age, orbital inflammation and the compressive factor were considered as factors of hemodynamic orbit disturbances. RESULTS: Different hemodynamic disturbances were present in all patients with EOP (100%). Statistic correlative analysis showed, that thyroid dysfunction is one of the most important factors, determining hemodynamic disturbances of orbit blood flow. The severity of these disturbances depended on the type of thyroid dysfunction. The obtained data showed that the age of the patient and the duration of the endocrine disease is the important factor of the hemodynamic disturbances of orbit blood flow in EOP. The age (over 50) and the duration of the disease result in hemodynamic disturbances, reaching the value of «chronic eye ischemic syndrome». The intensity of autoimmune inflammation was revealed to determine the depth of hemodynamic disturbances in orbit. At the same time the severity of EOP reflected intraorbital pressure that may cause hemodynamic disturbances changing the blood flow in the orbit. CONCLUSION: Factors determining the character of hemo-dynamic disturbances in main vessels of the eye and orbit in EOP are found and identified such as thyroid dysfunction type, orbital inflammation intensity, compressive factor, endocrine disease duration and the age of the patient.ЦЕЛЬ. Поиск и идентификация факторов, определяющих гемодинамические нарушения в магистральных сосудах глаза и орбиты при эндокринной офтальмопатии (ЭОП), повышающие риск развития оптической нейропатии. МЕТОДЫ. Обследованы 86 пациентов с ЭОП, ассоциированной с диффузным токсическим зобом (ДТЗ, 72 человека, 144 орбиты) и аутоиммунным тиреоидитом (АИТ, 14 человек, 28 орбит). Все пациенты были осмотрены офтальмологом и эндокринологом. Диагноз ДТЗ и АИТ устанавливали на основании анамнеза, осмотра, уровня тиреоидных гормонов (св.Т4, св.ТЗ), тирео- тропного гормона (ПТ), показателей АТ к рТТГ, АТ-ТПО, АТ-ТГ, эхографии щитовидной железы. Границы нормы для базального уровня ТТГ - 0,25-3,5 мЕд/л; св.Т4 - 9,0-20,0 пмоль/л; св.ТЗ - 4,26-8,1 пмоль/л. ЭОП верифицировали по протоколу EUG0G0. Каждую орбиту оценивали отдельно. Офтальмологический осмотр включал: сбор жалоб, анамнез, клиническую оценку ЭОП. Всем пациентам проводили: визометрию, периметрию, биомикроскопию, тонометрию, офтальмоскопию, экзофтальмометрию по Гертелю. Структуры орбиты исследовали мультиспиральной компьютерной томографией. Всем пациентам проводили эхографию орбиты. Анатомическими объектами исследования служили: глазное яблоко, ретробульбарное пространство и его магистральные сосуды. Кровоток исследовали на ультразвуковой диагностической системе Voluson 730 PRO («Kretz», Австрия) в режиме триплексного сканирования (В-режим, ЦДК в комбинации с импульсно-волновой допплерографией). Анализировали гемодинамические показатели в a. ophthalmica, a. etv. retinae centralis, a. ciliaris posterior brevis et longae. В качестве факторов, определяющих гемодинамические нарушения в орбите, рассматривали: уровень тиреоидных гормонов и ТТГ, длительность заболевания щитовидной железы, возраст пациента, орбитальное воспаление, компрессионный фактор. РЕЗУЛЬТАТЫ. У всех пациентов с ЭОП (100%) присутствовали различные гемодинамические нарушения. Статистический корреляционный анализ показал, что отклонение уровня тиреоидных гормонов и ТТГ от нормы - один из наиболее значимых факторов, определяющих гемодинамические нарушения орбитального кровотока. Выраженность этих нарушений зависит от вида дисфункции щитовидной железы. Полученные результаты свидетельствовали о том, что возраст и длительность заболевания щитовидной железы являются важными факторами, определяющими гемодинамические нарушения орбитального кровотока при ЭОП. С увеличением возраста (после 50 лет) и длительности заболевания гемодинамические нарушения усиливаются, достигая значений, укладывающихся в понятие «хронического глазного ишемического синдрома». Выявили, что интенсивность аутоиммунного воспаления определяет глубину гемодинамических нарушений в орбите. Наряду с этим тяжесть ЭОП отражает интраорбитальное давление, что также может вызывать гемодинамические нарушения, изменяя кровоток в орбите. ЗАКЛЮЧЕНИЕ. Найдены и идентифицированы факторы, определяющие характер гемодинамических нарушений в магистральных сосудах глаза и орбиты при ЭОП. К ним относятся: вид дисфункции щитовидной железы, интенсивность орбитального воспаления, компрессионный фактор, длительность заболевания щитовидной железы и возраст пациента

Parental and household smoking and the increased risk of bronchitis, bronchiolitis and other lower respiratory infections in infancy: systematic review and meta-analysis

<p>Abstract</p> <p>Background</p> <p>Passive smoke exposure increases the risk of lower respiratory infection (LRI) in infants, but the extensive literature on this association has not been systematically reviewed for nearly ten years. The aim of this paper is to provide an updated systematic review and meta-analysis of studies of the association between passive smoking and LRI, and with diagnostic subcategories including bronchiolitis, in infants aged two years and under.</p> <p>Methods</p> <p>We searched MEDLINE and EMBASE (to November 2010), reference lists from publications and abstracts from major conference proceedings to identify all relevant publications. Random effect pooled odds ratios (OR) with 95% confidence intervals (CI) were estimated.</p> <p>Results</p> <p>We identified 60 studies suitable for inclusion in the meta-analysis. Smoking by either parent or other household members significantly increased the risk of LRI; odds ratios (OR) were 1.22 (95% CI 1.10 to 1.35) for paternal smoking, 1.62 (95% CI 1.38 to 1.89) if both parents smoked, and 1.54 (95% CI 1.40 to 1.69) for any household member smoking. Pre-natal maternal smoking (OR 1.24, 95% CI 1.11 to 1.38) had a weaker effect than post-natal smoking (OR 1.58, 95% CI 1.45 to 1.73). The strongest effect was on bronchiolitis, where the risk of any household smoking was increased by an OR of 2.51 (95% CI 1.96 to 3.21).</p> <p>Conclusions</p> <p>Passive smoking in the family home is a major influence on the risk of LRI in infants, and especially on bronchiolitis. Risk is particularly strong in relation to post-natal maternal smoking. Strategies to prevent passive smoke exposure in young children are an urgent public and child health priority.</p

Alternative Strategies to Reduce Maternal Mortality in India: A Cost-Effectiveness Analysis

A cost-effectiveness study by Sue Goldie and colleagues finds that better family planning, provision of safe abortion, and improved intrapartum and emergency obstetrical care could reduce maternal mortality in India by 75% in 5 years