Time-to-pregnancy and pregnancy outcomes in a South African population

<p>Abstract</p> <p>Background</p> <p>Time-to-pregnancy (TTP) has never been studied in an African setting and there are no data on the rates of adverse pregnancy outcomes in South Africa. The study objectives were to measure TTP and the rates of adverse pregnancy outcomes in South Africa, and to determine the reliability of the questionnaire tool.</p> <p>Methods</p> <p>The study was cross-sectional and applied systematic stratified sampling to obtain a representative sample of reproductive age women for a South African population. Data on socio-demographic, work, health and reproductive variables were collected on 1121 women using a standardized questionnaire. A small number (n = 73) of randomly selected questionnaires was repeated to determine reliability of the questionnaire. Data was described using simple summary statistics while Kappa and intra-class correlation statistics were calculated for reliability.</p> <p>Results</p> <p>Of the 1121 women, 47 (4.2%) had never been pregnant. Mean gravidity was 2.3 while mean parity was 2.0 There were a total of 2467 pregnancies; most (87%) resulted in live births, 9.5% in spontaneous abortion and 2.2% in still births. The proportion of planned pregnancies was 39% and the median TTP was 6 months. The reliability of the questionnaire for TTP data was good; 63% for all participants and 97% when censored at 14 months. Overall reliability of reporting adverse pregnancy outcomes was very high, ranging from 90 - 98% for most outcomes.</p> <p>Conclusion</p> <p>This is the first comprehensive population-based reproductive health study in South Africa, to describe the biologic fertility of the population, and provides rates for planned pregnancies and adverse pregnancy outcomes. The reliability of the study questionnaire was substantial, with most outcomes within 70 - 100% reliability index. The study provides important public information for health practitioners and researchers in reproductive health. It also highlights the need for public health intervention programmes and epidemiological research on biologic fertility and adverse pregnancy outcomes in the population.</p

Anatomical Network Comparison of Human Upper and Lower, Newborn and Adult, and Normal and Abnormal Limbs, with Notes on Development, Pathology and Limb Serial Homology vs. Homoplasy

How do the various anatomical parts (modules) of the animal body evolve into very different integrated forms (integration) yet still function properly without decreasing the individual's survival? This long-standing question remains unanswered for multiple reasons, including lack of consensus about conceptual definitions and approaches, as well as a reasonable bias toward the study of hard tissues over soft tissues. A major difficulty concerns the non-trivial technical hurdles of addressing this problem, specifically the lack of quantitative tools to quantify and compare variation across multiple disparate anatomical parts and tissue types. In this paper we apply for the first time a powerful new quantitative tool, Anatomical Network Analysis (AnNA), to examine and compare in detail the musculoskeletal modularity and integration of normal and abnormal human upper and lower limbs. In contrast to other morphological methods, the strength of AnNA is that it allows efficient and direct empirical comparisons among body parts with even vastly different architectures (e.g. upper and lower limbs) and diverse or complex tissue composition (e.g. bones, cartilages and muscles), by quantifying the spatial organization of these parts-their topological patterns relative to each other-using tools borrowed from network theory. Our results reveal similarities between the skeletal networks of the normal newborn/adult upper limb vs. lower limb, with exception to the shoulder vs. pelvis. However, when muscles are included, the overall musculoskeletal network organization of the upper limb is strikingly different from that of the lower limb, particularly that of the more proximal structures of each limb. Importantly, the obtained data provide further evidence to be added to the vast amount of paleontological, gross anatomical, developmental, molecular and embryological data recently obtained that contradicts the long-standing dogma that the upper and lower limbs are serial homologues. In addition, the AnNA of the limbs of a trisomy 18 human fetus strongly supports Pere Alberch's ill-named "logic of monsters" hypothesis, and contradicts the commonly accepted idea that birth defects often lead to lower integration (i.e. more parcellation) of anatomical structures

Neutrophil cannibalism – a back up when the macrophage clearance system is insufficient

BACKGROUND: During a lipopolysaccharide-induced lung inflammation, a massive accumulation of neutrophils occurs, which is normally cleared by macrophage phagocytosis following neutrophil apoptosis. However, in cases of extensive apoptosis the normal clearance system may fail, resulting in extensive neutrophil secondary necrosis. The aim of this study was to explore the hypothesis that neutrophils, in areas of the lung with extensive cellular infiltration, contribute to clearance by phagocytosing apoptotic cells and/or cell debris derived from secondary necrosis. METHODS: Intranasal lipopolysaccharide administration was used to induce lung inflammation in mice. The animals were sacrificed at seven time points following administration, bronchoalveolar lavage was performed and tissue samples obtained. Electron microscopy and histochemistry was used to assess neutrophil phagocytosis. RESULTS: Electron microscopic studies revealed that phagocytosing neutrophils was common, at 24 h after LPS administration almost 50% of the total number of neutrophils contained phagosomes, and the engulfed material was mainly derived from other neutrophils. Histochemistry on bronchoalvolar lavage cells further showed phagocytosing neutrophils to be frequently occurring. CONCLUSION: Neutrophils are previously known to phagocytose invading pathogens and harmful particles. However, this study demonstrates that neutrophils are also able to engulf apoptotic neutrophils or cell debris resulting from secondary necrosis of neutrophils. Neutrophils may thereby contribute to clearance and resolution of inflammation, thus acting as a back up system in situations when the macrophage clearance system is insufficient and/or overwhelmed

Circulating protein biomarkers of pharmacodynamic activity of sunitinib in patients with metastatic renal cell carcinoma: modulation of VEGF and VEGF-related proteins

<p>Abstract</p> <p>Background</p> <p>Sunitinib malate (SUTENT^®) is an oral, multitargeted tyrosine kinase inhibitor, approved multinationally for the treatment of advanced RCC and of imatinib-resistant or – intolerant GIST. The purpose of this study was to explore potential biomarkers of sunitinib pharmacological activity via serial assessment of plasma levels of four soluble proteins from patients in a phase II study of advanced RCC: VEGF, soluble VEGFR-2 (sVEGFR-2), placenta growth factor (PlGF), and a novel soluble variant of VEGFR-3 (sVEGFR-3).</p> <p>Methods</p> <p>Sunitinib was administered at 50 mg/day on a 4/2 schedule (4 weeks on treatment, 2 weeks off treatment) to 63 patients with metastatic RCC after failure of first-line cytokine therapy. Predose plasma samples were collected on days 1 and 28 of each cycle and analyzed via ELISA.</p> <p>Results</p> <p>At the end of cycle 1, VEGF and PlGF levels increased >3-fold (relative to baseline) in 24/54 (44%) and 22/55 (40%) cases, respectively (P < 0.001). sVEGFR-2 levels decreased ≥ 30% in 50/55 (91%) cases and ≥ 20% in all cases (P < 0.001) during cycle 1, while sVEGFR-3 levels were decreased ≥ 30% in 48 of 55 cases (87%), and ≥ 20% in all but 2 cases. These levels tended to return to near-baseline after 2 weeks off treatment, indicating that these effects were dependent on drug exposure. Overall, significantly larger changes in VEGF, sVEGFR-2, and sVEGFR-3 levels were observed in patients exhibiting objective tumor response compared with those exhibiting stable disease or disease progression (P < 0.05 for each analyte; analysis not done for PlGF).</p> <p>Conclusion</p> <p>Sunitinib treatment in advanced RCC patients leads to modulation of plasma levels of circulating proteins involved in VEGF signaling, including soluble forms of two VEGF receptors. This panel of proteins may be of value as biomarkers of the pharmacological and clinical activity of sunitinib in RCC, and of angiogenic processes in cancer and other diseases.</p

Effect of age, impaction types and operative time on inflammatory tissue reactions following lower third molar surgery

<p>Abstract</p> <p>Background</p> <p>Postoperative mobidity following third molar surgery is affected by a number of factors. The study of these factors is essential for effective planning and limitation of morbidity. The aim of this study was to determine the effect of age, type of impaction and operative time on immediate postoperative tissue reactions following mandibular third molar surgery.</p> <p>Methods</p> <p>Consecutive patients with impacted mandibular third molar teeth were studied. All the third molars were classified according to Winter's classification. Surgical extraction was performed on all the patients by a single surgeon under local anaesthesia. The operation time was determined by the time lapse between incision and completion of suturing. Postoperative pain, swelling and trismus were evaluated.</p> <p>Results</p> <p>There were 120 patients with an age range of 19-42 years. Patients in the age range of 35-42 years recorded a lower pain score (p = 0.5) on day 1. The mouth opening was much better in the lower age group on day 2 and 5 (p = 0.007 and p = 0.01 respectively). Pain, swelling and trismus increased with increasing operative time. Distoangular impaction was significantly associated with higher VAS score on day 1 and 2 (p = 0.01, 0.0, 04). Distoangular and horizontal impaction are associated with a higher degree of swelling and reduced mouth opening on postoperative review days. Vertical impaction was associated with the least degree of facial swelling and best mouth opening.</p> <p>Conclusions</p> <p>Increasing operating time and advancing age are associated with more postoperative morbidity, likewise distoangular and horizontal impaction types.</p

Monitoring of total positive end-expiratory pressure during mechanical ventilation by artificial neural networks

Ventilation treatment of acute lung injury (ALI) requires the application of positive airway pressure at the end of expiration (PEEPapp) to avoid lung collapse. However, the total pressure exerted on the alveolar walls (PEEPtot) is the sum of PEEPapp and intrinsic PEEP (PEEPi), a hidden component. To measure PEEPtot, ventilation must be discontinued with an end-expiratory hold maneuver (EEHM). We hypothesized that artificial neural networks (ANN) could estimate the PEEPtot from flow and pressure tracings during ongoing mechanical ventilation. Ten pigs were mechanically ventilated, and the time constant of their respiratory system (τRS) was measured. We shortened their expiratory time (TE) according to multiples of τRS, obtaining different respiratory patterns (Rpat). Pressure (PAW) and flow (V′AW) at the airway opening during ongoing mechanical ventilation were simultaneously recorded, with and without the addition of external resistance. The last breath of each Rpat included an EEHM, which was used to compute the reference PEEPtot. The entire protocol was repeated after the induction of ALI with i.v. injection of oleic acid, and 382 tracings were obtained. The ANN had to extract the PEEPtot, from the tracings without an EEHM. ANN agreement with reference PEEPtot was assessed with the Bland–Altman method. Bland Altman analysis of estimation error by ANN showed −0.40 ± 2.84 (expressed as bias ± precision) and ±5.58 as limits of agreement (data expressed as cmH2O). The ANNs estimated the PEEPtot well at different levels of PEEPapp under dynamic conditions, opening up new possibilities in monitoring PEEPi in critically ill patients who require ventilator treatment

A Metagenomic Approach to Characterization of the Vaginal Microbiome Signature in Pregnancy

While current major national research efforts (i.e., the NIH Human Microbiome Project) will enable comprehensive metagenomic characterization of the adult human microbiota, how and when these diverse microbial communities take up residence in the host and during reproductive life are unexplored at a population level. Because microbial abundance and diversity might differ in pregnancy, we sought to generate comparative metagenomic signatures across gestational age strata. DNA was isolated from the vagina (introitus, posterior fornix, midvagina) and the V5V3 region of bacterial 16S rRNA genes were sequenced (454FLX Titanium platform). Sixty-eight samples from 24 healthy gravidae (18 to 40 confirmed weeks) were compared with 301 non-pregnant controls (60 subjects). Generated sequence data were quality filtered, taxonomically binned, normalized, and organized by phylogeny and into operational taxonomic units (OTU); principal coordinates analysis (PCoA) of the resultant beta diversity measures were used for visualization and analysis in association with sample clinical metadata. Altogether, 1.4 gigabytes of data containing >2.5 million reads (averaging 6,837 sequences/sample of 493 nt in length) were generated for computational analyses. Although gravidae were not excluded by virtue of a posterior fornix pH >4.5 at the time of screening, unique vaginal microbiome signature encompassing several specific OTUs and higher-level clades was nevertheless observed and confirmed using a combination of phylogenetic, non-phylogenetic, supervised, and unsupervised approaches. Both overall diversity and richness were reduced in pregnancy, with dominance of Lactobacillus species (L. iners crispatus, jensenii and johnsonii, and the orders Lactobacillales (and Lactobacillaceae family), Clostridiales, Bacteroidales, and Actinomycetales. This intergroup comparison using rigorous standardized sampling protocols and analytical methodologies provides robust initial evidence that the vaginal microbial 16S rRNA gene catalogue uniquely differs in pregnancy, with variance of taxa across vaginal subsite and gestational age

Taxonomic and functional turnover are decoupled in European peat bogs

In peatland ecosystems, plant communities mediate a globally significant carbon store. The effects of global environmental change on plant assemblages are expected to be a factor in determining how ecosystem functions such as carbon uptake will respond. Using vegetation data from 56 Sphagnum-dominated peat bogs across Europe, we show that in these ecosystems plant species aggregate into two major clusters that are each defined by shared response to environmental conditions. Across environmental gradients, we find significant taxonomic turnover in both clusters. However, functional identity and functional redundancy of the community as a whole remain unchanged. This strongly suggests that in peat bogs, species turnover across environmental gradients is restricted to functionally similar species. Our results demonstrate that plant taxonomic and functional turnover are decoupled, which may allow these peat bogs to maintain ecosystem functioning when subject to future environmental change

Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015

SummaryBackground The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. Methods We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors—the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). Findings Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57·8% (95% CI 56·6–58·8) of global deaths and 41·2% (39·8–42·8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. Interpretation Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. Funding Bill & Melinda Gates Foundation

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente