Clinical Relevance of Baseline TCP in Transcatheter Aortic Valve Replacement

AIMS: To investigate the influence of baseline thrombocytopenia (TCP) on short-term and long-term outcomes after transcatheter aortic valve replacement (TAVR). METHODS AND RESULTS: A total of 732 consecutive patients with severe, symptomatic aortic stenosis undergoing TAVR from January 2012 to December 2015 were included. Primary outcomes of interest were the relationship of baseline TCP with 30-day and 1-year all-cause mortality. Secondary outcomes of interest were procedural complications and in-hospital mortality in the same subgroups. The prevalence of TCP (defined as platelet count <150 × 109/L) at baseline was 21.9%, of whom 4.0% had moderate/severe TCP (defined as platelet count <100 × 109/L). Compared to no or mild TCP, moderate/severe TCP at baseline was associated with a significantly higher 30-day mortality (23.3% vs 2.3% and 3.1%, respectively; P<.001) and 1-year mortality (40.0% vs 8.3% and 13.4%, respectively; P<.001). In Cox regression analysis, moderate/severe baseline TCP was an independent predictor of 30-day and 1-year mortality (hazard ratio [HR], 13.18; 95% confidence interval [CI], 4.49-38.64; P<.001 and HR, 5.90; 95% CI, 2.68-13.02; P<.001, respectively). CONCLUSIONS: In conclusion, baseline TCP is a strong predictor of mortality in TAVR patients, possibly identifying a specific subgroup of frail patients; therefore, it should be taken into account when addressing TAVR risk

Assessment of the Severity of Paravalvular Regurgitation and its Role on Survival After Transcatheter Aortic Valve Replacement

Background: To evaluate the impact of various measurements of paravalvular regurgitation (PVR) on survival after transcatheter aortic valve replacement (TAVR). PVR can be difficult to grade and both its incidence and impact on survival may be decreasing as TAVR evolves. Methods: This retrospective study included 911 patients undergoing TAVR in two institutions. PVR was graded according to the 3-grade scheme proposed by the guidelines (PVR grade), and subsequently grade 2 and 3, and grade 0 and 1 were lumped together. PVR was also graded as a composite score (PVR score), based on 6 commonly used metrics. PVR grade, PVR score and its six individual components were tested against the risk of both 1-year and longer term mortality after TAVR. Results: Patients with moderate/severe PVR had a higher Society of Thoracic Sugeons (STS) score, higher levels of serum creatinine and larger left atria compared to patients with none/mild PVR. Moderate/severe PVR was more frequent with self-expandable and larger valves. After adjusting for American College of Cardiology (ACC) TAVR risk score, neither PVR grade, PVR score nor its six components were associated with an increased risk of mortality at 1-year (severe PVR adjusted HR: 0.75, 95% Confidence Interval [CI]: 0.19, 3.01, p = 0.50). However, intervention for clinically severe PVR increased the risk of mortality by more than 7-fold (adjusted hazard ratio [HR]: 7.6, 95% CI: 2.4, 23.5, p < 0.0001). Conclusions: In the contemporary era, moderate-severe PVR is uncommon. However, re-intervention for PVR portends a poor prognosis. This highlights the crucial importance of clinical judgment over imaging alone

Approach to Perturbative Results in the N-Delta Transition

We show that constraints from perturbative QCD calculations play a role in the nucleon to Delta(1232) electromagnetic transition even at moderate momentum transfer scales. The pQCD constraints, tied to real photoproduction data and unseparated resonance response functions, lead to explicit forms for the helicity amplitudes wherein the E2/M1 ratio remains small at moderately large momentum transfer.Comment: 4 pages, 2 figures, ReVTe

Forcing the archive:Involuntary migrants ‘of Ceylon’ in the Indian Ocean World of the 18–19th centuries

Asian Studie

An integrated clinical program and crowdsourcing strategy for genomic sequencing and Mendelian disease gene discovery.

Despite major progress in defining the genetic basis of Mendelian disorders, the molecular etiology of many cases remains unknown. Patients with these undiagnosed disorders often have complex presentations and require treatment by multiple health care specialists. Here, we describe an integrated clinical diagnostic and research program using whole-exome and whole-genome sequencing (WES/WGS) for Mendelian disease gene discovery. This program employs specific case ascertainment parameters, a WES/WGS computational analysis pipeline that is optimized for Mendelian disease gene discovery with variant callers tuned to specific inheritance modes, an interdisciplinary crowdsourcing strategy for genomic sequence analysis, matchmaking for additional cases, and integration of the findings regarding gene causality with the clinical management plan. The interdisciplinary gene discovery team includes clinical, computational, and experimental biomedical specialists who interact to identify the genetic etiology of the disease, and when so warranted, to devise improved or novel treatments for affected patients. This program effectively integrates the clinical and research missions of an academic medical center and affords both diagnostic and therapeutic options for patients suffering from genetic disease. It may therefore be germane to other academic medical institutions engaged in implementing genomic medicine programs

Conditions of malaria transmission in Dakar from 2007 to 2010

Background: Previous studies in Dakar have highlighted the spatial and temporal heterogeneity of Anopheles gambiae s.l. biting rates. In order to improve the knowledge of the determinants of malaria transmission in this city, the present study reports the results of an extensive entomological survey that was conducted in 45 areas in Dakar from 2007 to 2010. Methods: Water collections were monitored for the presence of anopheline larvae. Adult mosquitoes were sampled by human landing collection. Plasmodium falciparum circumsporozoite (CSP) protein indexes were measured by ELISA (enzyme-linked immunosorbent assay), and the entomological inoculation rates were calculated. Results: The presence of anopheline larvae were recorded in 1,015 out of 2,683 observations made from 325 water collections. A water pH of equal to or above 8.0, a water temperature that was equal to or above 30 degrees C, the absence of larvivorous fishes, the wet season, the presence of surface vegetation, the persistence of water and location in a slightly urbanised area were significantly associated with the presence of anopheline larvae and/or with a higher density of anopheline larvae. Most of the larval habitats were observed in public areas, i.e., freely accessible. A total of 496,310 adult mosquitoes were caught during 3096 person-nights, and 44967 of these specimens were identified as An. gambiae s.l. The mean An. gambiae s.l. human-biting rate ranged from 0.1 to 248.9 bites per person per night during the rainy season. Anopheles arabiensis (93.14%), Anopheles melas (6.83%) and An. gambiae s.s. M form (0.03%) were the three members of the An. gambiae complex. Fifty-two An. arabiensis and two An. melas specimens were CSP-positive, and the annual CSP index was 0.64% in 2007, 0.09% in 2008-2009 and 0.12% in 2009-2010. In the studied areas, the average EIR ranged from 0 to 17.6 infected bites per person during the entire transmission season. Conclusion: The spatial and temporal heterogeneity of An. gambiae s.l. larval density, adult human-biting rate (HBR) and malaria transmission in Dakar has been confirmed, and the environmental factors associated with this heterogeneity have been identified. These results pave the way for the creation of malaria risk maps and for a focused anti-vectorial control strategy

Risk Factors for Cervical Precancer and Cancer in HIV-Infected, HPV-Positive Rwandan Women

Although cervical cancer is an AIDS-defining condition, infection with human immunodeficiency virus (HIV) may only modestly increase the risk of cervical cancer. There is a paucity of information regarding factors that influence the natural history of human papillomavirus (HPV) in HIV-infected women. We examined factors associated with cervical intraepithelial neoplasia grade 3 or cancer (CIN3+) in Rwandan women infected with both HIV and HPV (HIV+/HPV+).In 2005, 710 HIV+ Rwandan women ≥25 years enrolled in an observational cohort study; 476 (67%) tested HPV+. Each woman provided sociodemographic data, CD4 count, a cervical cytology specimen and cervicovaginal lavage (CVL), which was tested for >40 HPV genotypes by MY09/MY11 PCR assay. Logistic regression models calculated odds ratios (OR) and 95% confidence intervals (CI) of associations of potential risk factors for CIN3+ among HIV+/HPV+ women.Of the 476 HIV+/HPV+ women 42 (8.8%) were diagnosed with CIN3+. Factors associated with CIN3+ included ≥7 (vs. 0-2) pregnancies, malarial infection in the previous six months (vs. never), and ≥7 (vs. 0-2) lifetime sexual partners. Compared to women infected by non-HPV16 carcinogenic HPV genotypes, HPV16 infection was positively associated and non-carcinogenic HPV infection was inversely associated with CIN3+. CD4 count was significantly associated with CIN3+ only in analyses of women with non-HPV16 carcinogenic HPV (OR = 0.62 per 100 cells/mm(3), CI = 0.40-0.97).In this HIV+/HPV+ population, lower CD4 was significantly associated with CIN3+ only in women infected with carcinogenic non-HPV16. We found a trend for higher risk of CIN3+ in HIV+ women reporting recent malarial infection; this association should be investigated in a larger group of HIV+/HPV+ women

The Cotton Centromere Contains a Ty3-gypsy-like LTR Retroelement

The centromere is a repeat-rich structure essential for chromosome segregation; with the long-term aim of understanding centromere structure and function, we set out to identify cotton centromere sequences. To isolate centromere-associated sequences from cotton, (Gossypium hirsutum) we surveyed tandem and dispersed repetitive DNA in the genus. Centromere-associated elements in other plants include tandem repeats and, in some cases, centromere-specific retroelements. Examination of cotton genomic survey sequences for tandem repeats yielded sequences that did not localize to the centromere. However, among the repetitive sequences we also identified a gypsy-like LTR retrotransposon (Centromere Retroelement Gossypium, CRG) that localizes to the centromere region of all chromosomes in domestic upland cotton, Gossypium hirsutum, the major commercially grown cotton. The location of the functional centromere was confirmed by immunostaining with antiserum to the centromere-specific histone CENH3, which co-localizes with CRG hybridization on metaphase mitotic chromosomes. G. hirsutum is an allotetraploid composed of A and D genomes and CRG is also present in the centromere regions of other AD cotton species. Furthermore, FISH and genomic dot blot hybridization revealed that CRG is found in D-genome diploid cotton species, but not in A-genome diploid species, indicating that this retroelement may have invaded the A-genome centromeres during allopolyploid formation and amplified during evolutionary history. CRG is also found in other diploid Gossypium species, including B and E2 genome species, but not in the C, E1, F, and G genome species tested. Isolation of this centromere-specific retrotransposon from Gossypium provides a probe for further understanding of centromere structure, and a tool for future engineering of centromere mini-chromosomes in this important crop species