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Sexually transmitted infections (STIs) pose a serious public health threat with more than 1 million curable infections diagnosed every day. While these infections are prevalent globally, the approach to evaluation and treatment varies greatly based on the capacity to make an accurate diagnosis. In low-resource settings, a syndromic approach is often used over an etiologic-based evaluation and management. Syndromic treatment of STIs recognizes groups of symptoms and recommends a multidrug empiric treatment that will cover the most likely causative organisms. By definition, syndromic treatment cannot be used as a screening tool, leaving a large portion of asymptomatic infections untreated. This will lead to the persistence of infection and associated sequelae including pelvic inflammatory disease and infertility. Syndromic treatment also leads to the overtreatment of many infections, which contributes to antimicrobial resistance. The rising threat of Neisseria gonorrhoeae resistance to last-line antibiotics is of global concern. Rapid, accurate, affordable, and easy-to-use point-of-care testing needs to be made readily available to all corners of the world to provide better care to patients and address the growing threat of multidrug resistant organisms. An urgent and collaborative global effort is needed to address the looming threat of a dangerous STI that is resistant to last-line antibiotics.

Intrapartum stillbirths and early neonatal deaths remain stubbornly high in low income countries. Fetal monitoring in labour can reduce these poor outcomes, but limited progress is being achieved in these settings. Intermittent auscultation and continuous electronic fetal monitoring (CEFM) can both be employed to monitor a fetus during labour. There are challenges and limitations with both modalities. We used AI augmented fetal monitoring in a hospital in Malawi and demonstrated substantial reductions in both intrapartum stillbirths and early neonatal deaths with a small increase in the cesarean delivery rate. AI-CEFM should be studied further to achieve better perinatal outcomes.

Purpose: A clinical hurdle for dermatopathology is the accurate diagnosis of melanocytic neoplasms. While histopathologic assessment is frequently sufficient, high rates of diagnostic discordance are reported. The development and validation of a 35-gene expression profile (35-GEP) test that accurately differentiates benign and malignant pigmented lesions is described. Methods: Lesion samples were reviewed by at least three independent dermatopathologists and included in the study if 2/3 or 3/3 diagnoses were concordant. Diagnostic utility of 76 genes was assessed with quantitative RT-PCR; neural network modeling and cross-validation were utilized for diagnostic gene selection using 200 benign nevi and 216 melanomas for training. To reflect the complex biology of melanocytic neoplasia, the 35-GEP test was developed to include an intermediate-risk zone. Results: Validation of the 35-GEP was performed in an independent set of 273 benign and 230 malignant lesions. The test demonstrated 99.1% sensitivity, 94.3% specificity, 93.6% positive predictive value and 99.2% negative predictive value. 96.4% of cases received a differential result and 3.6% had intermediate-risk. Conclusions: The 35-GEP test was developed to refine diagnoses of melanocytic neoplasms by providing clinicians with an objective tool. A test with these accuracy metrics could alleviate uncertainty in difficult-to-diagnose lesions leading to decreased unnecessary procedures while appropriately identifying at-risk patients.

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Aims: To measure depression using the PHQ-9 over time and to identify characteristics associated with persistent depression. Methods: A database of women undergoing obstetric fistula repair was used to examine association of depression with variables such as general demographics, type of obstetric fistula, surgical outcome, and continence status at the time of discharge. Results: 797 patients completed the PHQ-9 upon initial pre-operative assessment. 365 (45.8%) had a PHQ-9 score of 5 or higher, indicating symptoms of depression. Pre-operatively, depression was associated with the 18-34 year old age group and women with no children. Post-operatively, worse incontinence was associated with depression, however, over time depression was rarely found among women returning for follow-up. Conclusions: The decrease of depression seen over time is either due to selection bias or due to improved adjustment to one’s circumstances. Either way, this study underscores the need for ongoing follow-up, perhaps especially for those not presenting. Further studies are needed to assess the mental health of women who do not present for follow-up visits.

Aims: To compare sling types as anti-incontinence procedure for women with obstetric fistulas at high-risk for residual incontinence.Methods: This is a multiple-site randomized controlled trial comparing autologous fascia slings to pubococcygeal (PC) slings at time of fistula repair. Participants with a Goh type 3 or 4 vesico-vaginal fistula (urethral length

Purpose: The development of a genetic signature for the identification of high-risk cutaneous melanoma tumors would provide a valuable prognostic tool with value for stage I and II patients who represent a remarkably heterogeneous group with a 3% to 55% chance of disease progression and death 5 years from diagnosis. Experimental Design: A prognostic 28-gene signature was identified by analysis of microarray expression data. Primary cutaneous melanoma tumor tissue was evaluated by RT-PCR for expression of the signature, and radial basis machine (RBM) modeling was performed to predict risk of metastasis. Results: RBM analysis of cutaneous melanoma tumor gene expression reports low risk (class 1) or high risk (class 2) of metastasis. Metastatic risk was predicted with high accuracy in development (ROC = 0.93) and validation (ROC = 0.91) cohorts of primary cutaneous melanoma tumor tissue. Kaplan–Meier analysis indicated that the 5-year disease-free survival (DFS) rates in the development set were 100% and 38% for predicted classes 1 and 2 cases, respectively (P < 0.0001). DFS rates for the validation set were 97% and 31% for predicted classes 1 and 2 cases, respectively (P < 0.0001). Gene expression profile (GEP), American Joint Committee on Cancer stage, Breslow thickness, ulceration, and age were independent predictors of metastatic risk according to Cox regression analysis. Conclusions: The GEP signature accurately predicts metastasis risk in a multicenter cohort of primary cutaneous melanoma tumors. Preliminary Cox regression analysis indicates that the signature is an independent predictor of metastasis risk in the cohort presented. Clin Cancer Res; 21(1); 175–83. ©2015 AACR.

Background A 15-gene expression profile test has been clinically validated and is widely utilized in newly diagnosed uveal melanoma (UM) patients to assess metastatic potential of the tumor. As most patients are treated with eye-sparing radiotherapy, there is limited tumor tissue available for testing, and technical reliability and success of prognostic testing are critical. This study assessed the analytical performance of the 15-gene expression test for UM and the correlation of molecular class with pathologic characteristics. Methods Inter-assay, intra-assay, inter-instrument/operator, and inter-site experiments were conducted, and concordance of the 15-gene expression profile test results and associated discriminant scores for matched tumor samples were evaluated. Technical success was determined from de-identified clinical reports from January 2010 - May 2016. Pathologic characteristics of enucleated tumors were correlated with molecular class results. Results Inter-assay concordance on 16 samples run on 3 consecutive days was 100%, and matched discriminant scores were strongly correlated (R2 = 0.9944). Inter-assay concordance of 46 samples assayed within a one year period was 100%, with an R2 value of 0.9747 for the discriminant scores. Intra-assay concordance of 12 samples run concurrently in duplicates was 100%; discriminant score correlation yielded an R2 of 0.9934. Concordance between two sites assessing the same tumors was 100% with an R2 of 0.9818 between discriminant scores. Inter-operator/instrument concordance was 96% for Class 1/2 calls and 90% for Class 1A/1B calls, and the discriminant scores had a correlation R2 of 0.9636. Technical success was 96.3% on 5516 samples tested since 2010. Increased largest basal diameter and thickness were significantly associated with Class 1B and Class 2 vs. Class 1A signatures. Conclusions These results show that the 15-gene expression profile test for UM has robust, reproducible performance characteristics. The technical success rate during clinical testing remains as high as first reported during validation. As molecular testing becomes more prevalent for supporting precision medicine efforts, high technical success and reliability are key characteristics when testing such limited and precious samples. The performance of the 15-gene expression profile test in this study should provide confidence to physicians who use the test’s molecular classification to inform patient management decisions. Electronic supplementary material The online version of this article (doi:10.1186/s13000-017-0650-3) contains supplementary material, which is available to authorized users.

To develop a risk score to identify women with vesicovaginal fistula at high risk of residual urinary incontinence after surgical repair.We conducted a prospective cohort study among 401 women undergoing their first vesicovaginal fistula repair at a referral fistula repair center in Lilongwe, Malawi, between September 2011 and December 2014, who returned for follow-up within 120 days of surgery. We used logistic regression to develop a risk score to identify women with a high likelihood of residual urinary incontinence, defined as incontinence grade 2-5 within 120 days of vesicovaginal fistula repair, based on preoperative clinical and demographic characteristics (age, number of years with fistula, human immunodeficiency virus status, body mass index, previous repair surgery at an outside facility, revised Goh classification, Goh vesicovaginal fistula size, circumferential fistula, vaginal scaring, bladder size, and urethral length). The sensitivity, specificity, and positive and negative predictive values of the risk score at each cut point were assessed.Overall, 11 (3%) women had unsuccessful fistula closure. Of those with successful fistula closure (n=372), 85 (23%) experienced residual incontinence. A risk score cut point of 20 had sensitivity of 82% (95% confidence interval [CI] 72-89%) and specificity 63% (95% CI 57-69%) to potentially identify women with residual incontinence. In our population, the positive predictive value for a risk score cut point of 20 or higher was 43% (95% CI 36-51%) and the negative predictive value was 91% (95% CI 86-94%). Forty-eight percent of our study population had a risk score 20 or greater and, therefore, would have been identified for further intervention.A risk score of 20 or higher was associated with an increased likelihood of residual incontinence with satisfactory sensitivity and specificity. If validated in alternative settings, the risk score could be used to refer women with a high likelihood of postoperative incontinence to more experienced surgeons.

The objective of this research study is to identify quality indicators of cesarean deliveries and determine their relationship to neonatal and maternal morbidity and mortality in one high volume maternity hospital in Lilongwe, Malawi. Demographic, perioperative, and postoperative data were collected on all cesarean deliveries over three months. Indicators of quality (antibiotic administration, use of oxytocin, decision-to-incision time, and uterine incision type) were compared to maternal morbidities (postpartum hemorrhage, fistula and wound infection) and neonatal mortality. Causes of delays in decision to incision time were identified. 513 cesarean deliveries were performed during the study period, with no maternal deaths and 39 neonatal deaths. Adherence to oxytocin and antibiotic administration was high but not complete, with greater adherence to the former (97.1% vs 82.6%). The decision to incision time between women with and without neonatal deaths was similar (1.62 hours vs 1.49 hours, p = 0.41). Most delays were attributed to a busy operating theatre (49.1%) and delayed transfer to the operating theatre (26.9%). Uterine rupture and cesarean hysterectomy were associated with an outcome of neonatal death (p0.001). Infrastructure and personnel limitations are major barriers to the improvement of quality of cesarean deliveries. Future endeavors towards quality improvement must address these deficiencies.

A molecular test performed using fresh-frozen tissue was proposed for use in the prognosis of patients with pleural mesothelioma. The accuracy of the test and its properties was assessed under Clinical Laboratory Improvement Amendments–approved guidelines using FFPE tissue from an independent multicenter patient cohort. Concordance studies were performed using matched frozen and FFPE mesothelioma samples. The prognostic value of the test was evaluated in an independent validation cohort of 73 mesothelioma patients who underwent surgical resection. FFPE-based classification demonstrated overall high concordance (83%) with the matched frozen specimens, on removal of cases with low confidence scores, showing sensitivity and specificity in predicting type B classification (poor outcome) of 43% and 98%, respectively. Concordance between research and clinical methods increased to 87% on removal of low confidence cases. Median survival times in the validation cohort were 18 and 7 months in type A and type B cases, respectively (P = 0.002). Multivariate classification adding pathologic staging information to the gene expression score resulted in significant stratification of risk groups. The median survival times were 52 and 14 months in the low-risk (class 1) and intermediate-risk (class 2) groups, respectively. The prognostic molecular test for mesothelioma can be performed on FFPE tissues to predict survival, and can provide an orthogonal tool, in combination with established pathologic parameters, for risk evaluation.

Objective To describe rates of improved knowledge following a structured 2-day emergency obstetrics training course. Methods Quantitative assessments to evaluate emergency obstetrics knowledge and practical skills were administered before, immediately after, and 3–9 months following the training course for 65 final-year medical students at the National University of Rwanda. A survey was administered during the final assessment. Results In total, 52 (80.0%) students demonstrated knowledge improvement after training. Fifty-seven (87.7%) students improved or maintained their scores from the post-training written test to the final assessment, and 32 (49.2%) retained practical skills. Twenty-one (32.3%) of the class demonstrated competency in both written and practical skills. According to multivariable logistic regression analysis, female gender was associated with overall competency (P = 0.01), and use of the internet for academic purposes more than 3–5 times per week tended toward competency (P = 0.11). Conclusion A 2-day emergency obstetrics training course increased knowledge among medical students. Because educational policies are tailored to address high rates of maternal mortality in resource-poor settings, workshops dedicated to emergency obstetrics should be promoted.

Objective To determine the knowledge, attitudes, and practices of obstetric care providers (OCPs) in Bugesera District, Rwanda, crucial to the delivery of safe motherhood services. Methods A quantitative descriptive survey in Kinyarwanda targeting all OCPs in the district was implemented in November 2010 to determine demographic characteristics, safe motherhood knowledge, obstetric practices, and attitudes toward additional training. Results The study captured 87% of OCPs, of whom 137 of 168 (82%) were A2 level nurses. Most expressed a need to improve their knowledge (60.6%) and skills confidence (72.2%) in safe motherhood. The mean percentage of correct answers of 50 questions assessing overall knowledge was 46.4%; sections on normal labor (39.3% correct) and obstetric complications (37.1% correct) were the weakest. Fundal pressure during vaginal delivery was practiced by 60.8%, and only 15.9% of providers practiced active management of the third stage of labor for all deliveries. Providers supported additional training, and 89.3% expressed willingness to participate in a 2-day workshop even if it were their day off. Conclusion The study has identified a need to improve safe motherhood knowledge and practices of OCPs in the Bugesera District of Rwanda. OCPs support additional training as an intervention to reduce maternal mortality.

Acute menorrhagia is a common gynecological disorder. Prevalence is high among women with inherited bleeding disorders and recent guidance for optimal management is lacking. Following a comprehensive review of the literature, an international expert panel in obstetrics, gynecology and hematology reached consensus on recommendations regarding the management of acute menorrhagia in women without a diagnosed bleeding disorder, as well as in patients with von Willebrand disease, platelet function disorders and other rare hemostatic disorders. The causes and predictors of acute menorrhagia are discussed and special consideration is given for the treatment of women on anticoagulation therapy. This review and accompanying recommendations will provide guidance for healthcare practitioners in the emergency management of acute menorrhagia.

Adolescent childbearing is most prevalent in Sub-Saharan Africa. Deliveries in adolescent primiparas at an Austrian and an East African tertiary referral centre were compared to reveal differences in obstetric outcome.A total of 186 primiparas delivering at an age of 17 or less between 1999 and 2005 at the Austrian centre were compared with 209 adolescent primiparas who delivered between 2005 and 2007 at the African centre. The type of delivery and complications were studied.Adolescent primiparas accounted for 1.2% of the overall obstetric population at the Austrian centre, as compared with 2.3% at the East African centre (p0.01). When comparing the adolescents' outcome at the Austrian centre with the outcome of 22-27 years old primiparas at the same institution, we noted that the rates of adverse obstetric outcomes were higher among the adult group. However, at the East African centre the opposite was observed.In contrast to the results of Africa, data from Austria show that the obstetric outcome in adolescent pregnancies can be favourable. However, socioeconomic considerations have to be taken into account. Education and health knowledge seem critical for young females particularly in low-resource settings like East Africa.

Objectives Hepatitis C virus (HCV) infection is commonly associated with cognitive dysfunction. Viral sequences and proteins were previously found in brain macrophage/microglia cells. The aim of the current study was to determine whether HCV infection affects the expression of key cytokines and chemokines in these cells. Methods Autopsy brain tissue from 15 patients was studied; 7 patients were HCV positive and 8 were HCV negative. Cryostat sections of frontal cortex and subcortical white matter were stained with monoclonal antibodies specific for microglia/macrophages (anti-CD68) and separated by laser capture microscopy. Transcripts representing 25 various cytokines and chemokines were measured by real-time quantitative PCR. Results Compared with HCV-negative controls, HCV-positive patients demonstrated significantly higher levels of proinflammatory cytokines interleukin 1α (IL-1α), IL-1β, tumour necrosis factor α (TNFα), IL-12 and IL-18. HCV infection was also associated with increased transcription of chemokines IL-8, IL-16 and interferon-inducible protein 10 (IP-10). Type 1 interferon (IFN) activation was suggested by increased concentrations of IFNβ and myxovirus resistance protein A (MxA) transcripts. Similar results were obtained when CD68-positive/HCV-positive cells were compared with CD68-positive/HCV-negative cells in each of the 7 HCV-infected patients. Conclusion Evidence was found for activation of brain macrophages/microglia cells in autopsy brain tissue from HCV-positive patients. These findings could relate to the common presence of neurocognitive dysfunction among patients with chronic hepatitis C.

Hepatitis C virus (HCV) infection often is associated with cognitive dysfunction and depression. HCV sequences and replicative forms were detected in autopsy brain tissue and cerebrospinal fluid from infected patients, suggesting direct neuroinvasion. However, the phenotype of cells harboring HCV in brain remains unclear. We studied autopsy brain tissue from 12 HCV-infected patients, 6 of whom were coinfected with human immunodeficiency virus. Cryostat sections of frontal cortex and subcortical white matter were stained with monoclonal antibodies specific for microglia/macrophages (CD68), oligodendrocytes (2′,3′-cyclic nucleotide 3′-phosphodiesterase), astrocytes (glial fibrillary acidic protein [GFAP]), and neurons (neuronal-specific nuclear protein); separated by laser capture microscopy (LCM); and tested for the presence of positive- and negative-strand HCV RNA. Sections also were stained with antibodies to viral nonstructural protein 3 (NS3), separated by LCM, and phenotyped by real-time PCR. Finally, sections were double stained with antibodies specific for the cell phenotype and HCV NS3. HCV RNA was detected in CD68-positive cells in eight patients, and negative-strand HCV RNA, which is a viral replicative form, was found in three of these patients. HCV RNA also was found in astrocytes from three patients, but negative-strand RNA was not detected in these cells. In double immunostaining, 83 to 95% of cells positive for HCV NS3 also were CD68 positive, while 4 to 29% were GFAP positive. NS3-positive cells were negative for neuron and oligodendrocyte phenotypic markers. In conclusion, HCV infects brain microglia/macrophages and, to a lesser extent, astrocytes. Our findings could explain the biological basis of neurocognitive abnormalities in HCV infection.

360 degrees video is emerging as a new way of experiencing immersive video due to the ready availability of powerful handheld devices such as smartphones. 360 degrees video enables immersive “real life”, “being there” experience for consumers by capturing the 360 degree view of the world. Users can change their viewpoint and dynamically view any part of the captured scene they desire. 360 degrees video requires higher bitrate than conventional video due to increased video resolution (4K and beyond) needed to support the wider field of view. Efficient compression of 360 degrees video is thus needed to provide high quality immersive video viewing experience to consumers. This paper provides an overview of 360 degrees video and presents a region adaptive video smoothing technique that exploits the unique characteristics of 360 degrees video to provide up to 20% bitrate savings with minimal perceptual quality degradation while requiring no modifications to the video decoder.

To evaluate whether a hospital-based mentoring program could significantly increase short- and longer-term emergency obstetrics and neonatal care (EmONC) knowledge and skills among health providers.In a prospective before-and-after study, 20 mentors were trained using a specially-created EmONC mentoring and training program at Bwaila Hospital in Lilongwe, Malawi. The mentors then trained an additional 114 providers as mentees in the curriculum. Mentors and mentees were asked to complete a test before initiation of the training (Pre-Test), immediately after training (Post-Test 1), and at least 6 months after training (Post-Test 2) to assess written and practical EmONC knowledge and skills. Mean scores were then compared.Scores increased significantly between the Pre-Test and Post-Test 1 for both written (n=134; difference 22.9%, P0.001) and practical (n=125; difference 29.5%, P0.001) tests. Scores were still significantly higher in Post-Test 2 than in the Pre-Test for written (n=111; difference 21.0%, P0.001) and practical (n=103; difference 29.3%, P0.001) tests.A hospital-based mentoring program can result in both short- and longer-term improvement in EmONC knowledge and skills. Further research is required to assess whether this leads to behavioral changes that improve maternal and neonatal outcomes.

Summary. Background: Hepatitis C virus (HCV) translation is initiated in a cap-independent manner by an internal ribosome entry site (IRES) located within the 5′ untranslated region (5′UTR). Sequence changes in this region could affect translation efficiency and presumably viral replication. Aim: To determine translation efficiency of 5′UTR variants developing during post-transfusion hepatitis C in two immunocompetent subjects and in two immunosuppressed liver recipients with recurrent HCV. Methods: Sequential samples were screened for 5′UTR changes by single-strand conformation polymorphism followed by cloning and sequencing whenever band pattern suggested sequence changes. 5′UTR variants were tested for IRES activity using a bicistronic dual luciferase expression plasmid transfected into HepG2 and Huh7 cell-lines. Results: In the transfused patients, translation efficiency of 5′UTR variants from early post-transfusion samples was 5.1- to 13.7-fold higher than that of predominant variants found in late follow-up samples. Post-transplant variants in the other two patients had 2.6- to 5.9-fold higher translation efficiency than those present only in pretransplant samples. Conclusion: In the immunocompetent host there may be selection of low translation efficiency HCV variants over the course of infection. However, in immunosuppressed subjects the opposite seems to be true as low translation efficiency variants are superseded by high translation efficiency variants.

Hepatitis C virus (HCV) infection is common among HIV-1–infected patients, with 50%–90% being coinfected [1]. Thus, HCV coinfection has emerged as a major public health problem that contributes to significant morbidity and mortality in HIV-1–infected patients. HIV-1 coinfection accelerates the development of severe liver disease attributable to HCV [1, 2], whereas HCV coinfection has been reported to accelerate the progression of HIV-1 disease [3, 4]. Since the introduction of effective measures to screen blood and blood products for HCV, injection drug use has become the predominant mode of HCV acquisition. However, exposure via injection drugs cannot account for up to 20% of new infections [5, 6]. Several reports have suggested that HCV may be transmitted through sexual intercourse [5, 7, 8], during childbirth [9, 10], and even during casual contacts between household members [11]. The probability of mother-to-child and female-to-male transmission appears to increase in the presence of coinfection with HIV-1 [10, 12–14]. Similar findings have been reported for HIV-1–positive men who engage in high-risk sexual behaviors (such as unprotected sex) with other men [15]. However, there are conflicting results with regard to female-to-male HCV transmission [16, 17]. The mechanism of increased HCV replication in HIV-1–infected patients has been attributed to immunosuppression, as evidenced by high viral loads in patients receiving immunosuppressive drugs after transplantation [18]. However, there is also evidence suggesting that HCV replication may be directly enhanced by the presence of HIV-1 [19]. Surprisingly, despite mounting evidence for the existence of female-to-male and mother-to-child transmission of HCV, very little is known about vaginal and cervical shedding of HCV in HIV-1–positive and HIV-1–negative women. Very few studies have assessed HCV RNA in vaginal secretions. Furthermore, HCV load and quasispecies distribution in the genital tract compartment has not been analyzed previously [20–22]. This could be explained by the difficulties of obtaining cervicovaginal specimens, the methods for which have only recently been standardized in HIV-1 settings [23]. In this article, we present our findings on HCV detection, viral load, and quasispecies composition in the female genital tract using cervicovaginal lavage (CVL) fluid from HCV/HIV-1–coinfected women.

It has been reported that hepatitis C virus (HCV) infection is associated with cognitive dysfunction, fatigue and depression, which do not correlate with the severity of liver disease and cannot be accounted for by hepatic encephalopathy or drug abuse. There is also emerging evidence that HCV infection can have negative neurocognitive effects in HIV-infected cohorts. Magnetic resonance spectroscopy has suggested the likely existence of a biological basis for these effects. HCV replicative forms have recently been detected in autopsy brain tissue and the infected cells have been identified as CD68-positive (macrophages/microglia). These findings raise the possibility that HCV infection of the brain could be directly related to the reported neuropsychological and cognitive changes. HCV is not strictly hepatotropic, as it can also replicate in leukocytes, including monocytes/macrophages. The latter cells could provide access of HCV into the central nervous system ('Trojan horse' mechanism) in a process similar to that postulated for HIV-1. In support of this hypothetical mechanism come reports showing a close relationship between HCV sequences present in the brain and cerebrospinal fluid and sequences found in lymph nodes and peripheral blood mononuclear cells. However, despite some similarities there is a fundamental difference between HIV-1 and HCV infection as the latter does not progress into AIDS-type dementia.

Background & Aims: Studies on hepatitis C virus (HCV) quasispecies dynamics in the natural course of infection are rare owing to difficulties in obtaining samples from the early phase of infection. Methods: We studied 15 patients from the Transfusion-Transmitted Viruses Study who seroconverted to anti-HCV after receiving infected blood. Follow-up serum samples were collected every 2–3 weeks for 6 months, at 10 months, and at 11–16 years. Viral quasispecies in the second envelope hypervariable region 1 (E2/HVR1) and 5′ untranslated region (5′UTR) were analyzed with single-strand conformation polymorphism (SSCP) and heteroduplex mobility assay (HMA). Results: Seven patients cleared infection within 7–24 weeks (mean, 14.0 wk) and 3 patients eventually became anti-HCV negative. In 6 patients with resolving hepatitis the SSCP band pattern remained stable, whereas in one patient minor changes appeared before clearance. In contrast, in all 8 patients progressing to chronicity, major changes in the E2/HVR1 quasispecies developed at 8–22 weeks (mean, 13.1 wk). Shannon entropy and medium mobility shift values derived from HMA gels remained stable in patients with resolving hepatitis but changed in those who developed chronic infection. Only 2 patients showed minor changes in 5′UTR. A decrease in E2/HVR1 complexity at the time of transmission (bottleneck) was found in 5 patients altogether. Conclusions: Changes in E2/HVR1 quasispecies 8–22 weeks after infection, likely caused by mounting immune pressure, were predictive of ensuing chronic infection, whereas stability was associated with resolution. Our study also showed that composition of HCV quasispecies may be preserved during transmission from host to host.

When hepatitis C virus (HCV) infection recurs after liver transplantation, it is unclear whether the liver graft is colonized by virions present in the circulation or by those associated with peripheral blood mononuclear cells (PBMC). In 6 HCV-infected transplant recipients, HCV sequences were analyzed by the single-strand conformational polymorphism (SSCP) assay and direct sequencing in pretransplant-paired PBMC and serum samples and in posttransplant follow-up serum samples. In 2 patients, SSCP patterns for pretransplant PBMC-serum pairs were identical, while in 4 patients they were different. In 3 patients from the latter group, the posttransplant viral sequences resembled those found in pretransplant serum samples, whereas in the other patient from that group, viral sequences after transplantation were transiently identical to those found in pretransplant PBMC. In HCV-positive liver transplant recipients, the liver graft is colonized primarily by liver-derived virus remaining in the circulation. However, virus variants of likely extrahepatic origin can be detected in serum early after transplantation.

Pregnant women with obstetric fistula are at high risk for obstetric complications and present a unique challenge in management.A young, HIV-positive woman with a history of rectovaginal and vesicovaginal fistulae after a prior delivery presented in premature labor. Upon cesarean delivery, fecal matter entered the uterus. The uterus was irrigated, closed, and a sigmoid colostomy was created. Subsequently, she underwent repair of both fistulae with bilateral ureteral reimplantation, hysterectomy, primary rectal repair, and colostomy reversal. She remains continent of urine and stool at 6 months'follow-up.Obstetric fistula patients who conceive must be followed closely for obstetric complications and offered timely cesarean delivery.

A gene expression profile (GEP) test able to accurately identify risk of metastasis for patients with cutaneous melanoma has been clinically validated.We aimed for assessment of the prognostic accuracy of GEP and sentinel lymph node biopsy (SLNB) tests, independently and in combination, in a multicenter cohort of 217 patients.Reverse transcription polymerase chain reaction (RT-PCR) was performed to assess the expression of 31 genes from primary melanoma tumors, and SLNB outcome was determined from clinical data. Prognostic accuracy of each test was determined using Kaplan-Meier and Cox regression analysis of disease-free, distant metastasis-free, and overall survivals.GEP outcome was a more significant and better predictor of each end point in univariate and multivariate regression analysis, compared with SLNB (P.0001 for all). In combination with SLNB, GEP improved prognostication. For patients with a GEP high-risk outcome and a negative SLNB result, Kaplan-Meier 5-year disease-free, distant metastasis-free, and overall survivals were 35%, 49%, and 54%, respectively.Within the SLNB-negative cohort of patients, overall risk of metastatic events was higher (∼30%) than commonly found in the general population of patients with melanoma.In this study cohort, GEP was an objective tool that accurately predicted metastatic risk in SLNB-eligible patients.

BACKGROUND: Hepatitis C virus (HCV) coinfection was reported to negatively affect HIV disease and HIV infection has a deleterious effect on HCV-related liver disease. However, despite common occurrence of HCV/HIV coinfection little is known about the mechanisms of interactions between the two viruses. METHODS: We studied CD4+ and CD8+ T cell and CD19+ B cell apoptosis in 104 HIV-positive patients (56 were also HCV-positive) and in 22 HCV/HIV-coinfected patients treated for chronic hepatitis C with pegylated interferon and ribavirin. We also analyzed HCV/HIV coinfection in a Daudi B-cell line expressing CD4 and susceptible to both HCV and HIV infection. Apoptosis was measured by AnnexinV staining. RESULTS: HCV/HIV coinfected patients had lower CD4+ and CD8+ T cell apoptosis and higher CD19+ B cell apoptosis than those with HIV monoinfection. Furthermore, anti-HCV treatment of HCV/HIV coinfected patients was followed by an increase of CD4+ and CD8+ T cell apoptosis and a decrease of CD19+ B cell apoptosis. In the Daudi CD4+ cell line, presence of HCV infection facilitated HIV replication, however, decreased the rate of HIV-related cell death. CONCLUSION: In HCV/HIV coinfected patients T-cells were found to be destroyed at a slower rate than in HIV monoinfected patients. These results suggest that HCV is a molecular-level determinant in HIV disease.

The aim of this work was to study the impact of anemia on surgical outcomes and the impact of instituting appropriate workup and treatment of anemia on surgical outcomes. We conducted a case–control retrospective chart review of all hernia repair, hydrocele repair, and hysterectomy cases at the SEARCH Hospital in Gadchiroli, India, from January 2008 to April 2010, and included 340 male and 112 female surgical patients. We also performed a prospective assessment of the impact of the institution of appropriate workup and treatment of anemia on the surgical outcomes for all hernia repair, hydrocele repair, and hysterectomy cases at SEARCH from May 2010 to May 2011 and included 138 male and 76 female surgical patients. The retrospective arm of the study included 340 males and 112 females with a median age of 39 and 41 years, respectively. The mean hemoglobin values were 12.50 (range = 8.8–15.4) for men and 10.39 (range = 5.2–14.8) for women. Patients with anemia had (1) increased incidence of spinal headache after inguinal hernia repair (p = 0.0266) and (2) increased incidence of fever after total hysterectomy (p = 0.0070). There was no statistically significant correlation between anemia and other outcomes (all p > 0.05). The prospective arm of the study included 138 males and 76 females with a median age of 35 and 40, respectively. The mean hemoglobin values were 11.8 (range = 6.4–14.8) for men and 10.6 (range = 6.9–12.8) for women. There was no statistically significant correlation between anemia and any surgical outcomes (p > 0.05). The incidence of complications in both the retrospective and the prospective arm was compared according to increasing severity of anemia across genders. Overall, there was no statistically significant increase in complication rates with increasing severity of anemia (p > 0.05). In the retrospective arm of this study, anemia was associated with increased incidence of spinal headache and fever. In the prospective arm of this study, there was no statistically significant correlation between anemia and any surgical outcome. The incidence of complications did not increase with the severity of anemia in either arm of the study. Further investigation is needed into the optimal management and treatment of anemia prior to surgery in resource-poor settings.

The purpose of this report is to provide a literature review of the cognitive and learning science research that is relevant to defining an effective after action review (AAR) process. The goal of this review is to assemble research sources that apply to the design and conduct of after action reviews. Therefore, this report provides a synopsis of research that exists, identifies notable researchers who have addressed the problem, presents results of both military and non-military investigations or implementations of the AAR technique, highlights existing theories that may contribute to the advancement of AARs, and isolates specific areas that demand further work. The findings are a distillation of what is known about the AAR process. As such, they would be of interest to researchers who wish to acquire or update their knowledge of the area. The findings would also be of interest to those who train AAR facilitators as a comprehensive foundation of AAR research.

Adolescence in girls is marked by a host of physical and psychological changes, including those associated with menstruation. Abnormal uterine bleeding (AUB) is one of the most commonly encountered medical problems in this transition from childhood to maturity. Although common, this problem is likely underreported and population-derived prevalence rates are not well described for adolescents. Small studies, however, suggest that the problem transcends ethnic and geographic boundaries. In Nigeria, 12.1% of adolescents experienced heavy menstrual bleeding which affected their work or school performance. In Hong Kong, 17.9% of girls at a mean age of 15 reported heavy menstrual bleeding. In Sweden, 37% of girls with an average age of 16.7 reported heavy menstruations. Similar rates have been reported in Malaysia and Turkey. Abnormal uterine bleeding includes a number of different types of bleeding patterns. In the medical literature, different terminologies have been used to describe the symptoms of AUB and the underlying disorders including dysfunctional uterine bleeding, menorrhagia, metrorrhagia, menometrorrhagia, etc. However, confusion and lack of agreement over the use of these terminologies have been demonstrated. Therefore, a study group established by the International Federation of Gynecology and Obstetrics recommended that these terminologies should be replaced by simple descriptive terms which specify

Ethical decision making in women's health presents a series of unique challenges that are exacerbated considerably in under-resourced settings. Severe constraints on both autonomy and resources highlight limitations of principle-based ethics for addressing ethical dilemmas. Other useful ethical "tools" are considered in the context of 2 cases that emphasize the challenges to ethical decision making in under-resourced settings. The cases confront traditional notions of patient autonomy, highlight pervasive issues with regard to allocation of resources, and demonstrate the difficulties encountered in the careful application of medical ethics.

The purpose of this paper is to evaluate the results of sling procedures for stress incontinence after repair of vesicovaginal fistulae at the National Hospital in Niamey, Niger. This study is a retrospective chart review of 701 women surgically treated for vesicovaginal fistulae. One hundred forty women subsequently underwent a sling procedure for stress incontinence after fistula repair. The demographics among the groups were similar. No significant difference was seen in results between the sling types except the risk of erosion was significantly greater in the synthetic sling group. There was a trend towards greater sling success in the fascia lata group. Correction of incontinence is a common and difficult challenge following repair of obstetric vesicovaginal fistula. Compared to published studies on sling procedures, these patients have higher rates of continued incontinence. This is likely due to the frequent loss of a urethral sphincter as well as high prevalence of detrusor overactivity and decreased bladder capacity.

This study investigated the relationship between two dimensions of anger-hostility--the expression of anger-hostility and the experience of anger-hostility--and cardiovascular reactivity in provoked and angered men. A serial subtraction task was administered to 41 male undergraduates who were provoked and angered. A measure of the expression of anger-hostility correlated positively and significantly with systolic and diastolic blood pressure (BP) reactivity. There were no significant correlations between a measure of the experience of anger-hostility and cardiovascular reactivity. The two types of anger-hostility were also found to relate differentially to life-style variables that have been identified as risk factors for coronary heart disease (CHD), with only the expression of anger-hostility showing positive relationships with these life-style CHD risk factors. These findings are discussed within the context of a similar differential relationship between the two dimensions of anger-hostility and CAD and CHD. Finally, significant negative relationships were obtained between the experience of anger-hostility and resting BP and heart rate levels. These findings are discussed within the context of other data suggesting that trait anxiety-neuroticism may have protective properties.

Vesicovaginal fistulas from obstructed labor no longer exist in wealthy industrialized countries. In the impoverished countries of sub-Saharan Africa and south Asia obstetric fistulas continue to be a prevalent clinical problem. As many as 3.5 million women may suffer from this condition and few centers exist that can provide them with competent and compassionate surgical repair of their injuries. As this situation has become more widely known in the industrialized world, increasing numbers of surgeons have begun traveling to poor countries to perform fistula operations. To date, these efforts have been carried out largely by well-intentioned individuals, acting alone. An international community of fistula surgeons who share common goals and values is still in the process of being created. To help facilitate the development of a common ethos and to improve the quality of care afforded to women suffering from obstetric fistulas, we propose a Code of Ethics for fistula surgeons that embraces the fundamental principles of beneficence, non-maleficence, respect for personal autonomy, and a dedication to the pursuit of justice.

9066 Background: A GEP has been validated as an independent predictor of DM, distant metastasis free survival (DMFS) and overall survival (OS) (Gerami, CCR 2015; Gerami JAAD, 2015). This abstract c...

Hepatitis C virus (HCV) is a positive-strand RNA virus that replicates through a negative-strand intermediary. Although hepatocytes are the primary sites for HCV replication, there is evidence of negative-strand HCV RNA in peripheral blood mononuclear cells (PBMCs), and the HCV genomic sequences present in PBMCs have been found to differ from those found in serum and the liver [1–6]. HCV RNA has also been detected in PBMCs and hematopoietic progenitor cells by means of in situ hybridization [7]. The presence of HCV replication has been documented in lymph nodes from patients with AIDS [8] and, recently, also in lymph nodes from HIV-negative liver transplant recipients [9]. Importantly, the same minor quasi-species variants of HCV strain H77, which were selected in lymphoblastoid cells in vitro, were found to be replicating in vivo in the PBMCs of chimpanzees inoculated with the same parental strain [10]. HCV is common among persons infected with HIV, because both pathogens share similar routes of transmission. In the United States and Europe, 13%–43% of HIV-infected persons are also infected with HCV [11], and this proportion of persons with HIV/HCV coinfection is even higher among injection drug users. HIV coinfection has important implications for HCV infection. First, it is likely to facilitate the spread of HCV. Mothers who are coinfected with HIV and HCV have been reported to transmit HCV to their infants at a much higher rate than mothers infected with HCV only [12–14]. Similarly, horizontal, possibly sexual, transmission of HCV is more common among HIV/HCV-coinfected persons than among HCV-monoinfected persons [15]. Second, HIV accelerates the development of HCV-associated severe liver disease [16–19]. Paradoxically, the reduction in mortality and morbidity among HIV-infected patients after the introduction of highly active antiretroviral therapy (HAART) may have contributed to the emergence of HCV as a significant pathogen in this population [20]. There is emerging evidence that HIV facilitates HCV replication in vivo, not only in the liver but also at extrahepatic sites [8, 21–23]. However, the prevalence of this phenomenon and the factors associated with its occurrence need further investigation. We addressed these questions in a cohort study of anti-HCV–positive/HIV-infected women enrolled in the Women’s Interagency HIV Study (WIHS).

Objective The purpose of this study was to evaluate the histories of women with urinary incontinence caused by vesicovaginal fistulae in Niger. This is an exploratory analysis to investigate possible contributing factors to the development of vesicovaginal fistulae. Study Design From September 2005 to January 2006, 58 women who were treated for vesicovaginal fistulae at the National Hospital Fistula Center, Niamey, Niger, were interviewed. Results The average age of marriage was 15.6 years and of first pregnancy was 17.3 years; 44.9% of the women were primigravid; and 94.8% of the women began labor at home. By delivery, 91.4% of the women sought additional care. The average labor lasted 2.61 days. An average of 1.61 days passed before further assistance was sought; 91.4% of infants were stillborn. Conclusion Early marriage, young age at first pregnancy, and labor length are common findings in our population of women with vesicovaginal fistulae. Most women who experienced fistulae also had poor obstetric outcomes. Increasing access to emergency obstetric care is of paramount importance to prevent fistula formation.