Maternal smoking and the risk of still birth: systematic review and meta-analysis

BACKGROUND: Smoking in pregnancy is known to be associated with a range of adverse pregnancy outcomes, yet there is a high prevalence of smoking among pregnant women in many countries, and it remains a major public health concern. We have conducted a systematic review and meta-analysis to provide contemporary estimates of the association between maternal smoking in pregnancy and the risk of stillbirth. METHODS: We searched four databases namely MEDLINE, EMBASE, Psych Info and Web of Science for all relevant original studies published until 31(st) December 2012. We included observational studies that measured the association between maternal smoking during pregnancy and the risk of stillbirth. RESULTS: 1766 studies were screened for title analysis, of which 34 papers (21 cohorts, 8 case controls and 5 cross sectional studies) met the inclusion criteria. In meta-analysis smoking during pregnancy was significantly associated with a 47% increase in the odds of stillbirth (OR 1.47, 95% CI 1.37, 1.57, p  <  0.0001). In subgroup analysis, smoking 1-9 cig/day and ≥10 cig/day was associated with an 9% and 52% increase in the odds of stillbirth respectively. Subsequently, studies defining stillbirth at ≥ 20 weeks demonstrated a 43% increase in odds for smoking mothers compared to mothers who do not smoke, (OR 1.43, 95% CI 1.32, 1.54, p  <  0.0001), whereas studies with stillbirth defined at ≥ 24 weeks and ≥ 28 weeks showed 58% and 33% increase in the odds of stillbirth respectively. CONCLUSION: Our review confirms a dose-response effect of maternal smoking in pregnancy on risk of stillbirth. To minimise the risk of stillbirth, reducing current smoking prevalence in pregnancy should continue to be a key public health high priority

Finding the Patient’s Voice Using Big Data: Analysis of Users’ Health-Related Concerns in the ChaCha Question-and-Answer Service (2009–2012)

Background: The development of effective health care and public health interventions requires a comprehensive understanding of the perceptions, concerns, and stated needs of health care consumers and the public at large. Big datasets from social media and question-and-answer services provide insight into the public&#8217;s health concerns and priorities without the financial, temporal, and spatial encumbrances of more traditional community-engagement methods and may prove a useful starting point for public-engagement health research (infodemiology). Objective: The objective of our study was to describe user characteristics and health-related queries of the ChaCha question-and-answer platform, and discuss how these data may be used to better understand the perceptions, concerns, and stated needs of health care consumers and the public at large. Methods: We conducted a retrospective automated textual analysis of anonymous user-generated queries submitted to ChaCha between January 2009 and November 2012. A total of 2.004 billion queries were read, of which 3.50% (70,083,796/2,004,243,249) were missing 1 or more data fields, leaving 1.934 billion complete lines of data for these analyses. Results: Males and females submitted roughly equal numbers of health queries, but content differed by sex. Questions from females predominantly focused on pregnancy, menstruation, and vaginal health. Questions from males predominantly focused on body image, drug use, and sexuality. Adolescents aged 12&#8211;19 years submitted more queries than any other age group. Their queries were largely centered on sexual and reproductive health, and pregnancy in particular. Conclusions: The private nature of the ChaCha service provided a perfect environment for maximum frankness among users, especially among adolescents posing sensitive health questions. Adolescents&#8217; sexual health queries reveal knowledge gaps with serious, lifelong consequences. The nature of questions to the service provides opportunities for rapid understanding of health concerns and may lead to development of more effective tailored interventions. [J Med Internet Res 2016;18(3):e44

Mutations in pericentrin cause Seckel syndrome with defective ATR-dependent DNA damage signaling

Large brain size is one of the defining characteristics of modern humans. Seckel syndrome (MIM 210600), a disorder of markedly reduced brain and body size, is associated with defective ATR-dependent DNA damage signaling. Only a single hypomorphic mutation of ATR has been identified in this genetically heterogeneous condition. We now report that mutations in the gene encoding pericentrin (PCNT)--resulting in the loss of pericentrin from the centrosome, where it has key functions anchoring both structural and regulatory proteins--also cause Seckel syndrome. Furthermore, we find that cells of individuals with Seckel syndrome due to mutations in PCNT (PCNT-Seckel) have defects in ATR-dependent checkpoint signaling, providing the first evidence linking a structural centrosomal protein with DNA damage signaling. These findings also suggest that other known microcephaly genes implicated in either DNA repair responses or centrosomal function may act in common developmental pathways determining human brain and body size

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Original research: Trauma exposure and posttraumatic stress disorder among employees of New York City companies affected by the september 11, 2001 attacks on the World Trade Center

OBJECTIVE: Several studies have provided prevalence estimates of posttraumatic stress disorder (PTSD) related to the September 11, 2001 (9/11) attacks in broadly affected populations, although without sufficiently addressing qualifying exposures required for assessing PTSD and estimating its prevalence. A premise that people throughout the New York City area were exposed to the attacks on the World Trade Center (WTC) towers and are thus at risk for developing PTSD has important implications for both prevalence estimates and service provision. This premise has not, however, been tested with respect to DSM-IV-TR criteria for PTSD. This study examined associations between geographic distance from the 9/11 attacks on the WTC and reported 9/11 trauma exposures, and the role of specific trauma exposures in the development of PTSD. METHODS: Approximately 3 years after the attacks, 379 surviving employees (102 with direct exposures, including 65 in the towers, and 277 with varied exposures) recruited from 8 affected organizations were interviewed using the Diagnostic Interview Schedule/Disaster Supplement and reassessed at 6 years. The estimated closest geographic distance from the WTC towers during the attacks and specific disaster exposures were compared with the development of 9/11–related PTSD as defined by the Diagnostic and Statistical Manual, Fourth Edition, Text Revision. RESULTS: The direct exposure zone was largely concentrated within a radius of 0.1 mi and completely contained within 0.75 mi of the towers. PTSD symptom criteria at any time after the disaster were met by 35% of people directly exposed to danger, 20% of those exposed only through witnessed experiences, and 35% of those exposed only through a close associate’s direct exposure. Outside these exposure groups, few possible sources of exposure were evident among the few who were symptomatic, most of whom had preexisting psychiatric illness. CONCLUSIONS: Exposures deserve careful consideration among widely affected populations after large terrorist attacks when conducting clinical assessments, estimating the magnitude of population PTSD burdens, and projecting needs for specific mental health interventions

Synthesis and Characterisation of Strontium Bismuth TitanateCeramics via High-energy Mechanical Milling

The processing conditions, microstructure, and dielectric properties of strontium bismuthtitanate (SBT) were systematically studied. The specimen was synthesised by a mechano-chemicalprocessing route using a planetary ball mill.  It is important that the action is vigorous enoughto break up loose aggregates and a fine particle size is obtained.  The specimen was calcinedat 800 oC for 4 h.  The calcined samples were subjected to cold isostatic pressing (CIP) processand finally sintered at 1200 oC for 2 h. A relative density  90 per cent of the theoretical densitywas obtained. Pellets having a diameter of 1cm and thickness of 1 mm were prepared from thesintered compacts for electrical measurements. X-ray diffraction showed that a single phase withthe layered perovskite structure of SBT was formed. Morphological studies were carried out bySEM analysis. Frequency dependence of impedance can provide additional insight intomechanisms controlling the electrical response. Resonance studies were made on poled samplein the frequency range 100 kHz – 20 MHz using an impedance analyser (HP-4294A) interfacedto a computer at room temperature. Dielectric measurements in the frequency range 100 Hz–1 MHz were made using an impedance analyser (HP-4192A) interfaced to a computer and themeasurements were carried out from room temperature to 550 oC. The ferroelectric hysteresis loopwas measured using a standard ferroelectric analyser based on Sawyer-tower circuit. Elasticcompliance (s33, s11) coupling factor (k33, k31)were also obtained.  These materials can be utilisedin practical applications as substitutes for lead titanate and lead zirconate titanate (PZT)-basedceramics, where high temperature applications are foreseen

Mutations of AKT3 are associated with a wide spectrum of developmental disorders including extreme megalencephaly

Mutations of genes within the phosphatidylinositol-3-kinase (PI3K)-AKT-MTOR pathway are well known causes of brain overgrowth (megalencephaly) as well as segmental cortical dysplasia (such as hemimegalencephaly, focal cortical dysplasia and polymicrogyria). Mutations of the AKT3 gene have been reported in a few individuals with brain malformations, to date. Therefore, our understanding regarding the clinical and molecular spectrum associated with mutations of this critical gene is limited, with no clear genotype–phenotype correlations. We sought to further delineate this spectrum, study levels of mosaicism and identify genotype–phenotype correlations of AKT3-related disorders. We performed targeted sequencing of AKT3 on individuals with these phenotypes by molecular inversion probes and/or Sanger sequencing to determine the type and level of mosaicism of mutations. We analysed all clinical and brain imaging data of mutation-positive individuals including neuropathological analysis in one instance. We performed ex vivo kinase assays on AKT3 engineered with the patient mutations and examined the phospholipid binding profile of pleckstrin homology domain localizing mutations. We identified 14 new individuals with AKT3 mutations with several phenotypes dependent on the type of mutation and level of mosaicism. Our comprehensive clinical characterization, and review of all previously published patients, broadly segregates individuals with AKT3 mutations into two groups: patients with highly asymmetric cortical dysplasia caused by the common p.E17K mutation, and patients with constitutional AKT3 mutations exhibiting more variable phenotypes including bilateral cortical malformations, polymicrogyria, periventricular nodular heterotopia and diffuse megalencephaly without cortical dysplasia. All mutations increased kinase activity, and pleckstrin homology domain mutants exhibited enhanced phospholipid binding. Overall, our study shows that activating mutations of the critical AKT3 gene are associated with a wide spectrum of brain involvement ranging from focal or segmental brain malformations (such as hemimegalencephaly and polymicrogyria) predominantly due to mosaic AKT3 mutations, to diffuse bilateral cortical malformations, megalencephaly and heterotopia due to constitutional AKT3 mutations. We also provide the first detailed neuropathological examination of a child with extreme megalencephaly due to a constitutional AKT3 mutation. This child has one of the largest documented paediatric brain sizes, to our knowledge. Finally, our data show that constitutional AKT3 mutations are associated with megalencephaly, with or without autism, similar to PTEN-related disorders. Recognition of this broad clinical and molecular spectrum of AKT3 mutations is important for providing early diagnosis and appropriate management of affected individuals, and will facilitate targeted design of future human clinical trials using PI3K-AKT pathway inhibitors

A note on comonotonicity and positivity of the control components of decoupled quadratic FBSDE

In this small note we are concerned with the solution of Forward-Backward Stochastic Differential Equations (FBSDE) with drivers that grow quadratically in the control component (quadratic growth FBSDE or qgFBSDE). The main theorem is a comparison result that allows comparing componentwise the signs of the control processes of two different qgFBSDE. As a byproduct one obtains conditions that allow establishing the positivity of the control process.Comment: accepted for publicatio