Performance and Reproducibility of Gynecologic Cytology Interpretation Using the FocalPoint System

Objectives: To assess whether automated screening in the cytologic examination of Papanicolaou smear slides results in smaller margins of error than manual screening. Methods: We compared cytotechnologists’ performance and reproducibility of manual and automated screening of 10,165 consecutive cervical cytology slides examined at Barretos Cancer Hospital using the FocalPoint system. Results: In total, 83% of atypical squamous cells of undetermined significance and greater were classified as quintiles 1 and 2; no high-grade squamous intraepithelial lesions and greater were observed in quintile 5. No statistically significant differences were found between manual and automated screening, using cervical biopsy specimens as the gold standard. Conclusions: FocalPoint safely screened high-grade lesions, which can be valuable for high-workload routines

The Pioneer Anomaly

Radio-metric Doppler tracking data received from the Pioneer 10 and 11 spacecraft from heliocentric distances of 20-70 AU has consistently indicated the presence of a small, anomalous, blue-shifted frequency drift uniformly changing with a rate of ~6 x 10^{-9} Hz/s. Ultimately, the drift was interpreted as a constant sunward deceleration of each particular spacecraft at the level of a_P = (8.74 +/- 1.33) x 10^{-10} m/s^2. This apparent violation of the Newton's gravitational inverse-square law has become known as the Pioneer anomaly; the nature of this anomaly remains unexplained. In this review, we summarize the current knowledge of the physical properties of the anomaly and the conditions that led to its detection and characterization. We review various mechanisms proposed to explain the anomaly and discuss the current state of efforts to determine its nature. A comprehensive new investigation of the anomalous behavior of the two Pioneers has begun recently. The new efforts rely on the much-extended set of radio-metric Doppler data for both spacecraft in conjunction with the newly available complete record of their telemetry files and a large archive of original project documentation. As the new study is yet to report its findings, this review provides the necessary background for the new results to appear in the near future. In particular, we provide a significant amount of information on the design, operations and behavior of the two Pioneers during their entire missions, including descriptions of various data formats and techniques used for their navigation and radio-science data analysis. As most of this information was recovered relatively recently, it was not used in the previous studies of the Pioneer anomaly, but it is critical for the new investigation.Comment: 165 pages, 40 figures, 16 tables; accepted for publication in Living Reviews in Relativit

IODP Expeditions 303 and 306 Monitor Miocene-Quaternary Climate in the North Atlantic

Introduction The IODP Expeditions 303 and 306 drilling sites were chosen for two reasons: (1) to capture Miocene-Quaternary millennial-scale climate variability in sensitive regions at the mouth of the Labrador Sea and in the North Atlantic icerafted debris (IRD) belt (Ruddiman et al., 1977), and (2) to provide the sedimentary and paleomagnetic attributes, including adequate sedimentation rates, for constructinghigh-resolution isotopic and magnetic stratigraphies.High accumulation rates, reaching 20 cm ky-1, permit the study of millennial-scale variations in climate and in the Earth's magnetic fi eld over the past several million years, when the amplitude and frequency of climate variability changed substantially. Shipboard logging and scanning data (magnetic susceptibility and remanence, density, natural gamma radiation, digital images and color refl ectance) and post-expedition x-ray fl uorescence (XRF) scanning datahave revealed that the sediment cores recovered on Expeditions 303 and 306 contain detailed histories of millennial-scale climate and geomagnetic fi eld variability throughout the late Miocene to Quaternary epochs. The climate proxies will be integrated with paleomagnetic data to place the records of millennial-scale climate change into a high resolution stratigraphy based on oxygen isotope andrelative paleomagnetic intensity (RPI). The paleomagnetic record of polarity reversals, excursions and RPI in these cores is central to the construction of the stratigraphic template and will provide detailed documentation of geomagnetic fi eld behavior

Phenotypic Characterization of EIF2AK4 Mutation Carriers in a Large Cohort of Patients Diagnosed Clinically With Pulmonary Arterial Hypertension.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a rare disease with an emerging genetic basis. Heterozygous mutations in the gene encoding the bone morphogenetic protein receptor type 2 (BMPR2) are the commonest genetic cause of PAH, whereas biallelic mutations in the eukaryotic translation initiation factor 2 alpha kinase 4 gene (EIF2AK4) are described in pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis. Here, we determine the frequency of these mutations and define the genotype-phenotype characteristics in a large cohort of patients diagnosed clinically with PAH. METHODS: Whole-genome sequencing was performed on DNA from patients with idiopathic and heritable PAH and with pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis recruited to the National Institute of Health Research BioResource-Rare Diseases study. Heterozygous variants in BMPR2 and biallelic EIF2AK4 variants with a minor allele frequency of <1:10 000 in control data sets and predicted to be deleterious (by combined annotation-dependent depletion, PolyPhen-2, and sorting intolerant from tolerant predictions) were identified as potentially causal. Phenotype data from the time of diagnosis were also captured. RESULTS: Eight hundred sixty-four patients with idiopathic or heritable PAH and 16 with pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis were recruited. Mutations in BMPR2 were identified in 130 patients (14.8%). Biallelic mutations in EIF2AK4 were identified in 5 patients with a clinical diagnosis of pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis. Furthermore, 9 patients with a clinical diagnosis of PAH carried biallelic EIF2AK4 mutations. These patients had a reduced transfer coefficient for carbon monoxide (Kco; 33% [interquartile range, 30%-35%] predicted) and younger age at diagnosis (29 years; interquartile range, 23-38 years) and more interlobular septal thickening and mediastinal lymphadenopathy on computed tomography of the chest compared with patients with PAH without EIF2AK4 mutations. However, radiological assessment alone could not accurately identify biallelic EIF2AK4 mutation carriers. Patients with PAH with biallelic EIF2AK4 mutations had a shorter survival. CONCLUSIONS: Biallelic EIF2AK4 mutations are found in patients classified clinically as having idiopathic and heritable PAH. These patients cannot be identified reliably by computed tomography, but a low Kco and a young age at diagnosis suggests the underlying molecular diagnosis. Genetic testing can identify these misclassified patients, allowing appropriate management and early referral for lung transplantation

Selling sex in unsafe spaces: sex work risk environments in Phnom Penh, Cambodia

<p>Abstract</p> <p>Background</p> <p>The risk environment framework provides a valuable but under-utilised heuristic for understanding environmental vulnerability to HIV and other sexually transmitted infections among female sex workers. Brothels have been shown to be safer than street-based sex work, with higher rates of consistent condom use and lower HIV prevalence. While entertainment venues are also assumed to be safer than street-based sex work, few studies have examined environmental influences on vulnerability to HIV in this context.</p> <p>Methods</p> <p>As part of the Young Women's Health Study, a prospective observational study of young women (15-29 years) engaged in sex work in Phnom Penh, we conducted in-depth interviews (n = 33) to explore vulnerability to HIV/STI and related harms. Interviews were conducted in Khmer by trained interviewers, transcribed and translated into English and analysed for thematic content.</p> <p>Results</p> <p>The intensification of anti-prostitution and anti-trafficking efforts in Cambodia has increased the number of women working in entertainment venues and on the street. Our results confirm that street-based sex work places women at risk of HIV/STI infection and identify significant environmental risks related to entertainment-based sex work, including limited access to condoms and alcohol-related intoxication. Our data also indicate that exposure to violence and interactions with the police are mediated by the settings in which sex is sold. In particular, transacting sex in environments such as guest houses where there is little or no oversight in the form of peer or managerial support or protection, may increase vulnerability to HIV/STI.</p> <p>Conclusions</p> <p>Entertainment venues may also provide a high risk environment for sex work. Our results indicate that strategies designed to address HIV prevention among brothel-based FSWs in Cambodia have not translated well to street and entertainment-based sex work venues in which increasing numbers of women are working. There is an urgent need for targeted interventions, supported by legal and policy reforms, designed to reduce the environmental risks of sex work in these settings. Future research should seek to investigate sex work venues as risk environments, explore the role of different business models in mediating these environments, and identify and quantify exposure to risk in different occupational settings.</p

Sex work and HIV in Cambodia: trajectories of risk and disease in two cohorts of high-risk young women in Phnom Penh, Cambodia

Objectives HIV prevalence among Cambodian female sex workers (FSW) is among the highest in Southeast Asia. We describe HIV prevalence and associated risk exposures in FSW sampled serially in Phnom Penh, Cambodia (Young Women's Health Study (YWHS)), before and after the implementation of a new law designed to combat human trafficking and sexual exploitation. Design Cross-sectional analysis of baseline data from two prospective cohorts. Setting Community-based study in Phnom Penh, Cambodia. Participants Women aged 15–29 years, reporting ≥2 sexual partners in the last month and/or engaged in transactional sex in the last 3 months, were enrolled in the studies in 2007 (N=161; YWHS-1), and 2009 (N=220; YWHS-2) following information sessions where 285 and 345 women attended. Primary outcomes HIV prevalence, sexual risk behaviour, amphetamine-type stimulant (ATS) and alcohol use, and work-related factors were compared in the two groups, enrolled before and after implementation of the new law. Results Participants in the two cohorts were similar in age (median 25 years), but YWHS-2 women reported fewer sex partners, more alcohol use and less ATS use. A higher proportion of YWHS-2 compared with YWHS-1 women worked in entertainment-based venues (68% vs 31%, respectively). HIV prevalence was significantly lower in the more recently sampled women: 9.2% (95% CI 4.5% to 13.8%) vs 23% (95% CI 16.5% to 29.7%). Conclusions Sex work context and risk have shifted among young FSW in Phnom Penh, following implementation of anti-prostitution and anti-trafficking laws. While both cohorts were recruited using the same eligibility criteria, more recently sampled women had lower prevalence of sexual risk and HIV infection. Women engaging more directly in transactional sex have become harder to sample and access. Future prevention research and programmes need to consider how new policies and demographic changes in FSW impact HIV transmission

Approximating A Dsm‐5 Diagnosis Of Ptsd Using Dsm‐Iv Criteria

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/111929/1/da22364.pd

Contact investigation for active tuberculosis among child contacts in Uganda.

BACKGROUND: Tuberculosis is a large source of morbidity and mortality among children. However, limited studies characterize childhood tuberculosis disease, and contact investigation is rarely implemented in high-burden settings. In one of the largest pediatric tuberculosis contact investigation studies in a resource-limited setting, we assessed the yield of contact tracing on childhood tuberculosis and indicators for disease progression in Uganda. METHODS: Child contacts aged &lt;15 years in Kampala, Uganda, were enrolled from July 2002 to June 2009 and evaluated for tuberculosis disease via clinical, radiographic, and laboratory methods for up to 24 months. RESULTS: Seven hundred sixty-one child contacts were included in the analysis. Prevalence of tuberculosis in our child population was 10%, of which 71% were culture-confirmed positive. There were no cases of disseminated tuberculosis, and 483 of 490 children (99%) started on isoniazid preventative therapy did not develop disease. Multivariable testing suggested risk factors including human immunodeficiency virus (HIV) status (odds ratio [OR], 7.90; P &lt; .001), and baseline positive tuberculin skin test (OR, 2.21; P = .03); BCG vaccination was particularly protective, especially among children aged ≤5 years (OR, 0.23; P &lt; .001). Adult index characteristics such as sex, HIV status, and extent or severity of disease were not associated with childhood disease. CONCLUSIONS: Contact tracing for children in high-burden settings is able to identify a large percentage of culture-confirmed positive tuberculosis cases before dissemination of disease, while suggesting factors for disease progression to identify who may benefit from targeted screening

Discrepancies in central review re-testing of patients with ER-positive and HER2-negative breast cancer in the OPTIMA prelim randomised clinical trial

Background:There is limited data on results of central re-testing of samples from patients with invasive breast cancer categorised in their local hospital laboratories as oestrogen receptor (ER) positive and human epidermal growth factor receptor homologue 2 (HER2) negative.Methods:The Optimal Personalised Treatment of early breast cancer usIng Multiparameter Analysis preliminary study (OPTIMA prelim) was the feasibility phase of a randomised controlled trial to validate the use of multiparameter assay-directed chemotherapy decisions in the UK National Health Service (NHS). Eligibility criteria included ER positivity and HER2 negativity. Central re-testing of receptor status was mandatory.Results:Of the 431 patients tested centrally, discrepant results between central and local laboratory results were identified in only 19 (4.4%; 95% confidence interval 2.5-6.3%) patients (with 21 tumours). On central review, seven patients had cancers that were ER-negative (1.6%) and 13 (3.0%) patients with 15 tumours had HER2-positive disease, including one tumour discrepant for both biomarkers.Conclusions:Central re-testing of receptor status of invasive breast cancers in the UK NHS setting shows a high level of reproducibility in categorising tumours as ER-positive and HER2-negative, and raises questions regarding the cost effectiveness and clinical value of central re-testing in this sub-group of breast cancers in this setting.</p

Measurement of the W+W− cross section in pp collisions at s√=7 TeV and limits on anomalous WWγ and WWZ couplings

A measurement of W+W− production in pp collisions at s√=7 TeV is presented. The data were collected with the CMS detector at the LHC, and correspond to an integrated luminosity of 4.92±0.11 fb−1. The W+W− candidates consist of two oppositely charged leptons, electrons or muons, accompanied by large missing transverse energy. The W+W− production cross section is measured to be 52.4±2.0 (stat.)±4.5 (syst.)±1.2 (lum.) pb. This measurement is consistent with the standard model prediction of 47.0±2.0 pb at next-to-leading order. Stringent limits on the WWγ and WWZ anomalous triple gauge-boson couplings are set