Obstetric Interventions: Assessment of Differential Practices by Race/Ethnicity

Cesarean sections constitute approximately 30% of the over 4 million live births a year in the United States, and a rising number of primary cesarean sections contribute significantly to the overall rate. Studies suggest that the rate of primary cesarean section is disproportionately higher among non-white women, even when controlling for demographic, behavioral and medical risk factors. Our study investigates the interrelationships between racial/ethnic characteristics and obstetric interventions among low risk pregnancies. We included nulliparous women with full term, singleton pregnancies and fetus in vertex presentation who delivered at UMass between April 2006 and March 2011. We excluded non-live births, women with antepartum complications or pre-labor indications for cesarean, and cases with unspecified race or missing data. Our sample consisted of 4,483 subjects, of which 7% were black, 70% white, 4% Asian, and 17% Hispanic. 74% had spontaneous vaginal deliveries, 9% had operative vaginal deliveries, and 17% had cesarean sections. 40% of the indications for cesarean were related to fetal distress, 25% to first stage labor, and 34% to second stage labor. Average maternal age was 26.2, average BMI was 24.9, average birth weight was 3381g, and average gestational age at delivery was 39.7 weeks; there were no significant differences in these variables across racial groups. We examined racial/ethnic differences in mode of delivery (spontaneous vaginal, operative vaginal and cesarean) using logistic regression models while adjusting for maternal age, BMI, and birth weight. We found that Asian women were more likely than white women to undergo cesarean section compared with spontaneous vaginal delivery (OR 1.49, 95% CI (1.02, 2.17)). We also found that Black women were more likely than white women to undergo cesarean section compared with spontaneous vaginal delivery (OR 1.43, 95% CI 1.07, 1.91)). This may warrant further investigation of racial differences in risk adjusted primary cesarean rates

Racial and ethnic differences in primary, unscheduled cesarean deliveries among low-risk primiparous women at an academic medical center: a retrospective cohort study

BACKGROUND: Cesarean sections are the most common surgical procedure for women in the United States. Of the over 4 million births a year, one in three are now delivered in this manner and the risk adjusted prevalence rates appear to vary by race and ethnicity. However, data from individual studies provides limited or contradictory information on race and ethnicity as an independent predictor of delivery mode, precluding accurate generalizations. This study sought to assess the extent to which primary, unscheduled cesarean deliveries and their indications vary by race/ethnicity in one academic medical center. METHODS: A retrospective, cross-sectional cohort study was conducted of 4,483 nulliparous women with term, singleton, and vertex presentation deliveries at a major academic medical center between 2006-2011. Cases with medical conditions, risk factors, or pregnancy complications that can contribute to increased cesarean risk or contraindicate vaginal birth were excluded. Multinomial logistic regression analysis was used to evaluate differences in delivery mode and caesarean indications among racial and ethnic groups. RESULTS: The overall rate of cesarean delivery in our cohort was 16.7%. Compared to White women, Black and Asian women had higher rates of cesarean delivery than spontaneous vaginal delivery, (adjusted odds ratio {AOR}: 1.43; 95% CI: 1.07, 1.91, and AOR: 1.49; 95% CI: 1.02, 2.17, respectively). Black women were also more likely, compared to White women, to undergo cesarean for fetal distress and indications diagnosed in the first stage as compared to the second stage of labor. CONCLUSIONS: Racial and ethnic differences in delivery mode and indications for cesareans exist among low-risk nulliparas at our institution. These differences may be best explained by examining the variation in clinical decisions that indicate fetal distress and failure to progress at the hospital-level

Incorporating physiology into species distribution models moderates the projected impact of warming on Mediterranean marine species

Species distribution models (SDMs) correlate species occurrences with environmental predictors, and can be used to forecast distributions under future climates. SDMs have been criticized for not explicitly including the physiological processes underlying the species response to the environment. Recently, new methods have been suggested to combine SDMs with physiological estimates of performance (physiology-SDMs). In this study, we compare SDM and physiology-SDM predictions for select marine species in the Mediterranean Sea, a region subjected to exceptionally rapid climate change. We focused on six species and created physiology-SDMs that incorporate physiological thermal performance curves from experimental data with species occurrence records. We then contrasted projections of SDMs and physiology-SDMs under future climate (year 2100) for the entire Mediterranean Sea, and particularly the ‘warm’ trailing edge in the Levant region. Across the Mediterranean, we found cross-validation model performance to be similar for regular SDMs and physiology-SDMs. However, we also show that for around half the species the physiology-SDMs substantially outperform regular SDM in the warm Levant. Moreover, for all species the uncertainty associated with the coefficients estimated from the physiology-SDMs were much lower than in the regular SDMs. Under future climate, we find that both SDMs and physiology-SDMs showed similar patterns, with species predicted to shift their distribution north-west in accordance with warming sea temperatures. However, for the physiology-SDMs predicted distributional changes are more moderate than those predicted by regular SDMs. We conclude, that while physiology-SDM predictions generally agree with the regular SDMs, incorporation of the physiological data led to less extreme range shift forecasts. The results suggest that climate-induced range shifts may be less drastic than previously predicted, and thus most species are unlikely to completely disappear with warming climate. Taken together, the findings emphasize that physiological experimental data can provide valuable supplemental information to predict range shifts of marine species

A synthetic biology approach for evaluating the functional contribution of designer cellulosome components to deconstruction of cellulosic substrates

BACKGROUND: Select cellulolytic bacteria produce multi-enzymatic cellulosome complexes that bind to the plant cell wall and catalyze its efficient degradation. The multi-modular interconnecting cellulosomal subunits comprise dockerin-containing enzymes that bind cohesively to cohesin-containing scaffoldins. The organization of the modules into functional polypeptides is achieved by intermodular linkers of different lengths and composition, which provide flexibility to the complex and determine its overall architecture. RESULTS: Using a synthetic biology approach, we systematically investigated the spatial organization of the scaffoldin subunit and its effect on cellulose hydrolysis by designing a combinatorial library of recombinant trivalent designer scaffoldins, which contain a carbohydrate-binding module (CBM) and 3 divergent cohesin modules. The positions of the individual modules were shuffled into 24 different arrangements of chimaeric scaffoldins. This basic set was further extended into three sub-sets for each arrangement with intermodular linkers ranging from zero (no linkers), 5 (short linkers) and native linkers of 27–35 amino acids (long linkers). Of the 72 possible scaffoldins, 56 were successfully cloned and 45 of them expressed, representing 14 full sets of chimaeric scaffoldins. The resultant 42-component scaffoldin library was used to assemble designer cellulosomes, comprising three model C. thermocellum cellulases. Activities were examined using Avicel as a pure microcrystalline cellulose substrate and pretreated cellulose-enriched wheat straw as a model substrate derived from a native source. All scaffoldin combinations yielded active trivalent designer cellulosome assemblies on both substrates that exceeded the levels of the free enzyme systems. A preferred modular arrangement for the trivalent designer scaffoldin was not observed for the three enzymes used in this study, indicating that they could be integrated at any position in the designer cellulosome without significant effect on cellulose-degrading activity. Designer cellulosomes assembled with the long-linker scaffoldins achieved higher levels of activity, compared to those assembled with short-and no-linker scaffoldins. CONCLUSIONS: The results demonstrate the robustness of the cellulosome system. Long intermodular scaffoldin linkers are preferable, thus leading to enhanced degradation of cellulosic substrates, presumably due to the increased flexibility and spatial positioning of the attached enzymes in the complex. These findings provide a general basis for improved designer cellulosome systems as a platform for bioethanol production

University centers for the study of public policy: Organizational viability

The central problems of creating and maintaining a university center for the study of public policy stem from the inherently interdisciplinary nature of the policy design process and the tensions in academic circles between “pure” and “applied” research.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45446/1/11077_2005_Article_BF01404904.pd

Quantitative principles of cis-translational control by general mRNA sequence features in eukaryotes.

BackgroundGeneral translational cis-elements are present in the mRNAs of all genes and affect the recruitment, assembly, and progress of preinitiation complexes and the ribosome under many physiological states. These elements include mRNA folding, upstream open reading frames, specific nucleotides flanking the initiating AUG codon, protein coding sequence length, and codon usage. The quantitative contributions of these sequence features and how and why they coordinate to control translation rates are not well understood.ResultsHere, we show that these sequence features specify 42-81% of the variance in translation rates in Saccharomyces cerevisiae, Schizosaccharomyces pombe, Arabidopsis thaliana, Mus musculus, and Homo sapiens. We establish that control by RNA secondary structure is chiefly mediated by highly folded 25-60 nucleotide segments within mRNA 5' regions, that changes in tri-nucleotide frequencies between highly and poorly translated 5' regions are correlated between all species, and that control by distinct biochemical processes is extensively correlated as is regulation by a single process acting in different parts of the same mRNA.ConclusionsOur work shows that general features control a much larger fraction of the variance in translation rates than previously realized. We provide a more detailed and accurate understanding of the aspects of RNA structure that directs translation in diverse eukaryotes. In addition, we note that the strongly correlated regulation between and within cis-control features will cause more even densities of translational complexes along each mRNA and therefore more efficient use of the translation machinery by the cell

Habitual wearers of colored lenses adapt more rapidly to the color changes the lenses produce

The visual system continuously adapts to the environment, allowing it to perform optimally in a changing visual world. One large change occurs every time one takes off or puts on a pair of spectacles. It would be advantageous for the visual system to learn to adapt particularly rapidly to such large, commonly occurring events, but whether it can do so remains unknown. Here, we tested whether people who routinely wear spectacles with colored lenses increase how rapidly they adapt to the color shifts their lenses produce. Adaptation to a global color shift causes the appearance of a test color to change. We measured changes in the color that appeared “unique yellow”, that is neither reddish nor greenish, as subjects donned and removed their spectacles. Nine habitual wearers and nine age-matched control subjects judged the color of a small monochromatic test light presented with a large, uniform, whitish surround every 5 s. Red lenses shifted unique yellow to more reddish colors (longer wavelengths), and greenish lenses shifted it to more greenish colors (shorter wavelengths), consistent with adaptation “normalizing” the appearance of the world. In controls, the time course of this adaptation contained a large, rapid component and a smaller gradual one, in agreement with prior results. Critically, in habitual wearers the rapid component was significantly larger, and the gradual component significantly smaller than in controls. The total amount of adaptation was also larger in habitual wearers than in controls. These data suggest strongly that the visual system adapts with increasing rapidity and strength as environments are encountered repeatedly over time. An additional unexpected finding was that baseline unique yellow shifted in a direction opposite to that produced by the habitually worn lenses. Overall, our results represent one of the first formal reports that adjusting to putting on or taking off spectacles becomes easier over time, and may have important implications for clinical management

Prevenção do câncer de colo uterino

O câncer do colo uterino constitui um grave problema de saúde pública, atingindo todas as camadas sociais e regiões geoeconômicas do país. Definido como afecção progressiva, o câncer de colo uterino é caracterizado por alterações intra-epiteliais cervicais, que podem se desenvolver para um estágio invasivo em longo prazo, tendo etapas bem definidas e de lenta evolução, sendo que este tipo de câncer permite sua interrupção a partir de um diagnóstico precoce e do tratamento oportuno que poderá apresentar custos reduzidos. Assim, as medidas de prevenção são consideradas de suma importância e envolvem o rastreamento de lesões na população sintomática e assintomática, podendo ser identificado o grau das mesmas e o tratamento ser adequado. Neste estudo foi realizado uma revisão narrativa, de trabalhos vinculados a Biblioteca Virtual de Saúde, realizados no período de 2000 a 2012 com o objetivo de discorrer sobre aspectos epidemiológicos, fisiopatológicos e de prevenção do câncer de colo uterino. O PSF se torna, cada vez mais, um instrumento de estratégia no combate ao câncer do colo do útero. Os profissionais devem aproveitar todas as oportunidades de contato com as mulheres para reforçar orientações, sanar dúvidas, conhecimentos, direitos em relação a sua saúde, sendo assim, atenção especial à educação em saúde. Há ainda muitas barreiras que impedem as mulheres ao acesso a educação e promoção da saúde, principalmente quanto ao câncer de colo de útero. Este fato mostra que as campanhas de prevenção e ou detecção precoce desta doença não têm sido bem sucedidas, apesar do amplo conhecimento que este tipo de câncer continua sendo uma séria ameaça para a população brasileira

Current european regulatory perspectives on insulin analogues

Insulin analogues are increasingly considered as an alternative to human insulin in the therapy of diabetes mellitus. Insulin analogues (IAs) are chemically different from human insulin and may have different pharmacokinetic or pharmacodynamic properties. The significance of the modifications of the insulin molecule for the safety profile of IAs must be considered. This review describes the regulatory procedure and the expectations for the scientific content of European marketing authorization applications for innovative IAs submitted to the European Medicines Agency. Particular consideration is given to a potential cancer hazard. Specific regulatory guidance on how to address a possible carcinogenic or tumor promoting effect of innovative IAs in non-clinical studies is available. After marketing authorization, the factual access of patients to the new product will be determined to great extent by health technology assessment bodies, reimbursement decisions and the price. Whereas the marketing authorization is a European decision, pricing and reimbursement are national or regional responsibilities. The assessment of benefit and risk by the European Medicines Agency is expected to influence future decisions on price and reimbursement on a national or regional level. Collaborations between regulatory agencies and health technology assessment bodies have been initiated on European and national level to facilitate the use of the European Medicines Agency's benefit risk assessment as basis on which to build the subsequent health technology assessment. The option for combined or joint scientific advice procedures with regulators and health technology assessment bodies on European level or on a national level in several European Member States may help applicants to optimize their development program and dossier preparation in regard of both European marketing authorization application and reimbursement decisions

Telomerase Efficiently Elongates Highly Transcribing Telomeres in Human Cancer Cells

RNA polymerase II transcribes the physical ends of linear eukaryotic chromosomes into a variety of long non-coding RNA molecules including telomeric repeat-containing RNA (TERRA). Since TERRA discovery, advances have been made in the characterization of TERRA biogenesis and regulation; on the contrary its associated functions remain elusive. Most of the biological roles so far proposed for TERRA are indeed based on in vitro experiments carried out using short TERRA-like RNA oligonucleotides. In particular, it has been suggested that TERRA inhibits telomerase activity. We have exploited two alternative cellular systems to test whether TERRA and/or telomere transcription influence telomerase-mediated telomere elongation in human cancer cells. In cells lacking the two DNA methyltransferases DNMT1 and DNMT3b, TERRA transcription and steady-state levels are greatly increased while telomerase is able to elongate telomeres normally. Similarly, telomerase can efficiently elongate transgenic inducible telomeres whose transcription has been experimentally augmented. Our data challenge the current hypothesis that TERRA functions as a general inhibitor of telomerase and suggest that telomere length homeostasis is maintained independently of TERRA and telomere transcription