Case analysis of complete uterine rupture in a tertiary health care center

Background: To determine the incidence, etiology, risk factors, complications, treatment strategies, maternal and fetal outcome associated with complete rupture uterus.Methods: This observational study was carried out in the Department of Obstetrics and Gynecology of Shriram Chandra Bhanj Medical College and Hospital, Cuttack, Odisha. The details of retrospective analysis of 52 cases of complete uterine rupture managed between July 2014 to April 2016 were reviewed.Results: The incidence of uterine rupture was 1 in 353 deliveries (0.28%). Most of the patients (61.5%) presented belonged to age group of 26-30 years. The most common cause of rupture uterus was rupture of previous caesarean scar in 30 cases (57.64%), whereas cepahalopelvic disproportion was predisposing factor in 18 cases (34.61%) and malpresentation in 4 cases. In majority 80.76 % of lower uterine segment was involved. Bladder injury was seen in 4 cases (7.69%) A most common form of management was rent repair in 53.84% cases. There were 2 maternal deaths with perinatal mortality rate being 100% associated with complete uterine rupture.Conclusions: Rupture of uterus is a dire emergency with high incidence of maternal and fetal mortality and morbidity. Most cases of rupture uterus are preventable with good antenatal and intrapartum care, and proper identification of high risk factors. Early diagnosis and active surgical management will go a long way in reducing the maternal and fetal mortality and morbidity.

Production of nuclei and antinuclei in pp and Pb-Pb collisions with ALICE at the LHC

We present first results on the production of nuclei and antinuclei such as (anti)deuterons, (anti)tritons, (anti)3He and (anti)4He in pp collisions at \s = 7 TeV and Pb-Pb collisions at \sNN = 2.76 TeV. These particles are identified using their energy loss (dE/dx) information in the Time Projection Chamber of the ALICE experiment. The Inner Tracking System gives a precise determination of the event vertex, by which primary and secondary particles are separated. The high statistics of over 360 million events for pp and 16 million events for Pb-Pb collisions give a significant number of light nuclei and antinuclei (Pb-Pb collisions: \sim30,000 anti-deuterons($\bar{d}$) and \sim4 anti-alpha($\bar{^4He}$)). The predictions of various particle ratios from the THERMUS model is also discussed.Comment: 4 pages, 5 figures, parallel talk at Quark Matter 2011, May 23rd-28th 2011, Annecy, Franc

Prioritizing Variants in Complete Hereditary Breast and Ovarian Cancer (HBOC) Genes in Patients Lacking known BRCA Mutations.

BRCA1 and BRCA2 testing for Hereditary breast and ovarian cancer (HBOC) does not identify all pathogenic variants. Sequencing of 20 complete genes in HBOC patients with uninformative test results (N = 287), including non-coding and flanking sequences of ATM, BARD1, BRCA1, BRCA2, CDH1, CHEK2, EPCAM, MLH1, MRE11A, MSH2, MSH6, MUTYH, NBN, PALB2, PMS2, PTEN, RAD51B, STK11, TP53, and XRCC2, identified 38,372 unique variants. We apply information theory (IT) to predict and prioritize non-coding variants of uncertain significance (VUS) in regulatory, coding, and intronic regions based on changes in binding sites in these genes. Besides mRNA splicing, IT provides a common framework to evaluate potential affinity changes in transcription factor (TFBSs), splicing regulatory (SRBSs), and RNA-binding protein (RBBSs) binding sites following mutation. We prioritized variants affecting the strengths of 10 splice sites (4 natural, 6 cryptic), 148 SRBS, 36 TFBS, and 31 RBBS. Three variants were also prioritized based on their predicted effects on mRNA secondary (2°) structure, and 17 for pseudoexon activation. Additionally, 4 frameshift, 2 in-frame deletions, and 5 stop-gain mutations were identified. When combined with pedigree information, complete gene sequence analysis can focus attention on a limited set of variants in a wide spectrum of functional mutation types for downstream functional and co-segregation analysis. This article is protected by copyright. All rights reserved

Missing sea level rise in southeastern Greenland during and since the Little Ice Age

The Greenland Ice Sheet has been losing mass at an accelerating rate over the past 2 decades. Understanding ice mass and glacier changes during the preceding several hundred years prior to geodetic measurements is more difficult because evidence of past ice extent in many places was later overridden. Salt marshes provide the only continuous records of relative sea level (RSL) from close to the Greenland Ice Sheet that span the period of time during and since the Little Ice Age (LIA) and can be used to reconstruct ice mass gain and loss over recent centuries. Salt marsh sediments collected at the mouth of Dronning Marie Dal, close to the Greenland Ice Sheet margin in southeastern Greenland, record RSL changes over the past ca. 300 years through changing sediment and diatom stratigraphy. These RSL changes record a combination of processes that are dominated by local and regional changes in Greenland Ice Sheet mass balance during this critical period that spans the maximum of the LIA and 20th-century warming. In the early part of the record (1725–1762 CE) the rate of RSL rise is higher than reconstructed from the closest isolation basin at Timmiarmiut, but between 1762 and 1880 CE the RSL rate is within the error range of the rate of RSL change recorded in the isolation basin. RSL begins to slowly fall around 1880 CE, with a total amount of RSL fall of 0.09±0.1 m in the last 140 years. Modelled RSL, which takes into account contributions from post-LIA Greenland Ice Sheet glacio-isostatic adjustment (GIA), ongoing deglacial GIA, the global non-ice sheet glacial melt fingerprint, contributions from thermosteric effects, the Antarctic mass loss sea level fingerprint and terrestrial water storage, overpredicts the amount of RSL fall since the end of the LIA by at least 0.5 m. The GIA signal caused by post-LIA Greenland Ice Sheet mass loss is by far the largest contributor to this modelled RSL, and error in its calculation has a large impact on RSL predictions at Dronning Marie Dal. We cannot reconcile the modelled RSL and the salt marsh observations, even when moving the termination of the LIA to 1700 CE and reducing the post-LIA Greenland mass loss signal by 30 %, and a “budget residual” of  mm yr−1 since the end of the LIA remains unexplained. This new RSL record backs up other studies that suggest that there are significant regional differences in the timing and magnitude of the response of the Greenland Ice Sheet to the climate shift from the LIA into the 20th century

Ethanol and Acetaminophen Synergistically Induce Hepatic Aggregation and TCH346-Insensitive Nuclear Translocation of GAPDH

The glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) signals during cellular stress via several post-translational modifications that change its folding properties, protein-protein interactions and sub-cellular localization. We examined GAPDH properties in acute mouse liver injury due to ethanol and/or acetaminophen (APAP) treatment. Synergistic robust and time-dependent nuclear accumulation and aggregation of GAPDH were observed only in combined, but not individual, ethanol/APAP treatments. The small molecule GAPDH-targeting compound TCH346 partially attenuated liver damage possibly via mitochondrial mechanisms, and independent of nuclear accumulation and aggregation of GAPDH. These findings provide a novel potential mechanism for hepatotoxicity caused by combined alcohol and acetaminophen exposure

A Unified Analytic Framework for Prioritization of Non-Coding Variants of Uncertain Significance in Heritable Breast and Ovarian Cancer

Background Sequencing of both healthy and disease singletons yields many novel and low frequency variants of uncertain significance (VUS). Complete gene and genome sequencing by next generation sequencing (NGS) significantly increases the number of VUS detected. While prior studies have emphasized protein coding variants, non-coding sequence variants have also been proven to significantly contribute to high penetrance disorders, such as hereditary breast and ovarian cancer (HBOC). We present a strategy for analyzing different functional classes of non-coding variants based on information theory (IT) and prioritizing patients with large intragenic deletions. Methods We captured and enriched for coding and non-coding variants in genes known to harbor mutations that increase HBOC risk. Custom oligonucleotide baits spanning the complete coding, non-coding, and intergenic regions 10 kb up- and downstream of ATM, BRCA1, BRCA2, CDH1, CHEK2, PALB2, and TP53 were synthesized for solution hybridization enrichment. Unique and divergent repetitive sequences were sequenced in 102 high-risk, anonymized patients without identified mutations in BRCA1/2. Aside from protein coding and copy number changes, IT-based sequence analysis was used to identify and prioritize pathogenic non-coding variants that occurred within sequence elements predicted to be recognized by proteins or protein complexes involved in mRNA splicing, transcription, and untranslated region (UTR) binding and structure. This approach was supplemented by in silico and laboratory analysis of UTR structure. Results 15,311 unique variants were identified, of which 245 occurred in coding regions. With the unified IT-framework, 132 variants were identified and 87 functionally significant VUS were further prioritized. An intragenic 32.1 kb interval in BRCA2 that was likely hemizygous was detected in one patient. We also identified 4 stop-gain variants and 3 reading-frame altering exonic insertions/deletions (indels). Conclusions We have presented a strategy for complete gene sequence analysis followed by a unified framework for interpreting non-coding variants that may affect gene expression. This approach distills large numbers of variants detected by NGS to a limited set of variants prioritized as potential deleterious changes

Automating dicentric chromosome detection from cytogenetic biodosimetry data.

We present a prototype software system with sufficient capacity and speed to estimate radiation exposures in a mass casualty event by counting dicentric chromosomes (DCs) in metaphase cells from many individuals. Top-ranked metaphase cell images are segmented by classifying and defining chromosomes with an active contour gradient vector field (GVF) and by determining centromere locations along the centreline. The centreline is extracted by discrete curve evolution (DCE) skeleton branch pruning and curve interpolation. Centromere detection minimises the global width and DAPI-staining intensity profiles along the centreline. A second centromere is identified by reapplying this procedure after masking the first. Dicentrics can be identified from features that capture width and intensity profile characteristics as well as local shape features of the object contour at candidate pixel locations. The correct location of the centromere is also refined in chromosomes with sister chromatid separation. The overall algorithm has both high sensitivity (85 %) and specificity (94 %). Results are independent of the shape and structure of chromosomes in different cells, or the laboratory preparation protocol followed. The prototype software was recoded in C++/OpenCV; image processing was accelerated by data and task parallelisation with Message Passaging Interface and Intel Threading Building Blocks and an asynchronous non-blocking I/O strategy. Relative to a serial process, metaphase ranking, GVF and DCE are, respectively, 100 and 300-fold faster on an 8-core desktop and 64-core cluster computers. The software was then ported to a 1024-core supercomputer, which processed 200 metaphase images each from 1025 specimens in 1.4 h

Chemostat culture systems support diverse bacteriophage communities from human feces

BACKGROUND: Most human microbiota studies focus on bacteria inhabiting body surfaces, but these surfaces also are home to large populations of viruses. Many are bacteriophages, and their role in driving bacterial diversity is difficult to decipher without the use of in vitro ecosystems that can reproduce human microbial communities. RESULTS: We used chemostat culture systems known to harbor diverse fecal bacteria to decipher whether these cultures also are home to phage communities. We found that there are vast viral communities inhabiting these ecosystems, with estimated concentrations similar to those found in human feces. The viral communities are composed entirely of bacteriophages and likely contain both temperate and lytic phages based on their similarities to other known phages. We examined the cultured phage communities at five separate time points over 24 days and found that they were highly individual-specific, suggesting that much of the subject-specificity found in human viromes also is captured by this culture-based system. A high proportion of the community membership is conserved over time, but the cultured communities maintain more similarity with other intra-subject cultures than they do to human feces. In four of the five subjects, estimated viral diversity between fecal and cultured communities was highly similar. CONCLUSIONS: Because the diversity of phages in these cultured fecal communities have similarities to those found in humans, we believe these communities can serve as valuable ecosystems to help uncover the role of phages in human microbial communities

Electronic and Structural Properties of a 4d-Perovskite: Cubic Phase of SrZrO3_3

First-principles density functional calculations are performed within the local density approximation to study the electronic properties of SrZrO$_3$, an insulating 4d-perovskite, in its high-temperature cubic phase, above 1400 K, as well as the generic 3d-perovskite SrTiO$_3$, which is also a d^0-insulator and cubic above 105 K, for comparison reasons. The energy bands, density of states and charge density distributions are obtained and a detailed comparison between their band structures is presented. The results are discussed also in terms of the existing data in the literature for both oxides.Comment: 5 pages, 2 figure

Association of chronic musculoskeletal pain with mortality among UK adults: A population-based cohort study with mediation analysis.

BACKGROUND: We aimed to quantify the association between chronic musculoskeletal pain and all-cause mortality, and to investigate the extent to which this association is mediated by physical activity, smoking status, alcohol consumption, and opioid use. METHODS: For this population-based cohort study, we used data from UK Biobank, UK between baseline visit (2006-2010) to 18th December 2020. We assessed the associations between chronic musculoskeletal pain and all-cause mortality using a Cox proportional hazards model. We performed causal mediation analyses to examine the proportion of the association between chronic musculoskeletal pain and all-cause mortality. FINDINGS: Of the 384,367 included participants, a total of 187,269 participants reported chronic musculoskeletal pain. Higher number of pain sites was associated with increased risk of all-cause mortality compared to having no pain (e.g., four sites vs no site of pain, Hazard Ratio [HR] 1.46, 95% Confidence Interval [CI] 1.35 to 1.57). The multiple mediator analyses showed that the mediating proportions of all four mediators ranged from 53.4% to 122.6%: among participants with two or more pain sites, the effect estimate reduced substantially, for example, HR reduced from 1.25 (95% CI: 1.21 to 1.30; two pain sites) to 1.07 (95% CI: 1.01 to 1.11; two pain sites). INTERPRETATION: We found that higher number of pain sites was associated with increased risk of all-cause mortality compared to having no pain, and at least half of the association of chronic musculoskeletal pain with increased all-cause mortality may be accounted for by four mediators. FUNDING: Twins Research Australia