Vogt-Koyanagi-Harada Syndrome in a 10 Years Old Child

The Vogt-Koyanagi-Harada (VKH) syndrome is a rare systemic disorder of uveitis, dysacousia, vitiligo, premature graying of the hair, eyebrows and eyelashes, and meningoencephalitis. Although frequently unrecognised,VKH may affect children. We report a case of a 10 year old girl who presented with headache and dimness of vision and was diagnosed as papillitis on the basis of bilateral disc edema. However over the course of time developed skin changes (poliosis, vitiligo over lower back) and depigmented patches in inferior fundus suggesting diagnosis of VKH disease. Thus the diagnosis is difficult in the absence of extraocular manifestations. In such cases the diagnosis is based on clinical evolution of the disease

Concomitant CIS on TURBT does not impact oncological outcomes in patients treated with neoadjuvant or induction chemotherapy followed by radical cystectomy

© Springer-Verlag GmbH Germany, part of Springer Nature 2018Background: Cisplatin-based neoadjuvant chemotherapy (NAC) for muscle invasive bladder cancer improves all-cause and cancer specific survival. We aimed to evaluate whether the detection of carcinoma in situ (CIS) at the time of initial transurethral resection of bladder tumor (TURBT) has an oncological impact on the response to NAC prior to radical cystectomy. Patients and methods: Patients were identified retrospectively from 19 centers who received at least three cycles of NAC or induction chemotherapy for cT2-T4aN0-3M0 urothelial carcinoma of the bladder followed by radical cystectomy between 2000 and 2013. The primary and secondary outcomes were pathological response and overall survival, respectively. Multivariable analysis was performed to determine the independent predictive value of CIS on these outcomes. Results: Of 1213 patients included in the analysis, 21.8% had concomitant CIS. Baseline clinical and pathologic characteristics of the ‘CIS’ versus ‘no-CIS’ groups were similar. The pathological response did not differ between the two arms when response was defined as pT0N0 (17.9% with CIS vs 21.9% without CIS; p = 0.16) which may indicate that patients with CIS may be less sensitive to NAC or ≤ pT1N0 (42.8% with CIS vs 37.8% without CIS; p = 0.15). On Cox regression model for overall survival for the cN0 cohort, the presence of CIS was not associated with survival (HR 0.86 (95% CI 0.63–1.18; p = 0.35). The presence of LVI (HR 1.41, 95% CI 1.01–1.96; p = 0.04), hydronephrosis (HR 1.63, 95% CI 1.23–2.16; p = 0.001) and use of chemotherapy other than ddMVAC (HR 0.57, 95% CI 0.34–0.94; p = 0.03) were associated with shorter overall survival. For the whole cohort, the presence of CIS was also not associated with survival (HR 1.05 (95% CI 0.82–1.35; p = 0.70). Conclusion: In this multicenter, real-world cohort, CIS status at TURBT did not affect pathologic response to neoadjuvant or induction chemotherapy. This study is limited by its retrospective nature as well as variability in chemotherapy regimens and surveillance regimens.Peer reviewedFinal Accepted Versio

The burden of diabetes mellitus during pregnancy in low- and middle-income countries : a systematic review

Peer reviewedPublisher PD

Chemoinformatic-guided engineering of polyketide synthases

Polyketide synthase (PKS) engineering is an attractive method to generate new molecules such as commodity, fine and specialty chemicals. A central challenge in PKS design is replacing a partially reductive module with a fully reductive module through a reductive loop exchange, thereby generating a saturated β-carbon. In this work, we sought to establish an engineering strategy for reductive loop exchanges based on chemoinformatics, a field traditionally used in drug discovery. We first introduced a set of donor reductive loops of diverse genetic origin and chemical substrate structures into the first extension module of the lipomycin PKS (LipPKS1). These results demonstrated that chemical similarity between the substrate of the donor loops and recipient LipPKS1 correlated with product titers. Consequently, we identified donor loops with substrates chemically similar to LipPKS1 for further reductive loop exchanges, and we observed a statistically significant correlation with production. Reductive loops with the highest chemical similarity resulted in production of branched, short-chain fatty acids reaching a titer of 165 mg/L in Streptomyces albus J1074. Collectively, our work formulizes a new chemoinformatic paradigm for de novo PKS biosynthesis which may accelerate the production of valuable bioproducts

Оценка надежности высоконадежных систем с учетом ЗИП

Предложены приближенные верхние и нижние оценки коэффициента готовности высоконадежной восстанавливаемой системы со структурной избыточностью. Полученные расчетные соотношения могут использоваться для оценки надежности высоконадежных систем с учетом различных стратегий пополнения ЗИП

Data Stream Clustering for Real-Time Anomaly Detection: An Application to Insider Threats

Insider threat detection is an emergent concern for academia, industries, and governments due to the growing number of insider incidents in recent years. The continuous streaming of unbounded data coming from various sources in an organisation, typically in a high velocity, leads to a typical Big Data computational problem. The malicious insider threat refers to anomalous behaviour(s) (outliers) that deviate from the normal baseline of a data stream. The absence of previously logged activities executed by users shapes the insider threat detection mechanism into an unsupervised anomaly detection approach over a data stream. A common shortcoming in the existing data mining approaches to detect insider threats is the high number of false alarms/positives (FPs). To handle the Big Data issue and to address the shortcoming, we propose a streaming anomaly detection approach, namely Ensemble of Random subspace Anomaly detectors In Data Streams (E-RAIDS), for insider threat detection. E-RAIDS learns an ensemble of p established outlier detection techniques [Micro-cluster-based Continuous Outlier Detection (MCOD) or Anytime Outlier Detection (AnyOut)] which employ clustering over continuous data streams. Each model of the p models learns from a random feature subspace to detect local outliers, which might not be detected over the whole feature space. E-RAIDS introduces an aggregate component that combines the results from the p feature subspaces, in order to confirm whether to generate an alarm at each window iteration. The merit of E-RAIDS is that it defines a survival factor and a vote factor to address the shortcoming of high number of FPs. Experiments on E-RAIDS-MCOD and E-RAIDS-AnyOut are carried out, on synthetic data sets including malicious insider threat scenarios generated at Carnegie Mellon University, to test the effectiveness of voting feature subspaces, and the capability to detect (more than one)-behaviour-all-threat in real-time. The results show that E-RAIDS-MCOD reports the highest F1 measure and less number of false alarm = 0 compared to E-RAIDS-AnyOut, as well as it attains to detect approximately all the insider threats in real-time

Attitudes to and management of fertility among primary health care physicians in Turkey: An epidemiological study

BACKGROUND: The subject of infertility has taken its place in the health sector at the top level. Since primary health care services are insufficient, most people, especially women, keep on suffering from it all over the world, namely in underdeveloped or developing countries. The aim of this study was to determine primary care physicians' opinions about the approach to infertility cases and their place within primary health care services (PHCSs). METHODS: The study was conducted between October 2003 and April 2004. The study group comprised 748 physicians working in PHCSs. They were asked to fill in a questionnaire with questions pertaining to infertility support, laboratory and treatment algorithms, as well as the demographic characteristics. The data was evaluated using the chi square test, percentage rates and a logistic regression model. RESULTS: The multivariate analyses showed that having a previous interest in infertility and having worked for a postgraduate period of between 5–9 years and ≥10 years were the variables that most positively influenced them in their approach to cases of infertility (p < 0.05, each one). Just 28.7% of the physicians indicated that they believed cases of infertility could be evaluated at the primary care level. The most frequently proposed reason for indicating 'difficulty in practice' (n = 533) was inadequate provision of equipment in PHCSs (55.7%). The physicians reported that they were able to perform most of the supportive treatments and proposals (between 64.6%–87.7%). The most requested laboratory investigations were the instruction of patients in taking basal body temperatures and semen analysis (89.7% and 88.7%, respectively). The most preferential course of treatment was that of sexually transmitted diseases (95.5%). CONCLUSION: It is clear that not enough importance is attached to the provision of care to infertile couples within PHCSs. This leads us to conclude that an integration of infertility services in primary care would be appropriate after strengthening the PHCSs

A new family of periplasmic-binding proteins that sense arsenic oxyanions

Arsenic contamination of drinking water affects more than 140 million people worldwide. While toxic to humans, inorganic forms of arsenic (arsenite and arsenate), can be used as energy sources for microbial respiration. AioX and its orthologues (ArxX and ArrX) represent the first members of a new sub-family of periplasmic-binding proteins that serve as the first component of a signal transduction system, that's role is to positively regulate expression of arsenic metabolism enzymes. As determined by X-ray crystallography for AioX, arsenite binding only requires subtle conformational changes in protein structure, providing insights into protein-ligand interactions. The binding pocket of all orthologues is conserved but this alone is not sufficient for oxyanion selectivity, with proteins selectively binding either arsenite or arsenate. Phylogenetic evidence, clearly demonstrates that the regulatory proteins evolved together early in prokaryotic evolution and had a separate origin from the metabolic enzymes whose expression they regulate

High prevalence of obesity, central obesity and abnormal glucose tolerance in the middle-aged Finnish population

<p>Abstract</p> <p>Background</p> <p>There is a worldwide increase in the prevalence of obesity and disturbances in glucose metabolism. The aim of this study was to assess the current prevalence of obesity, central obesity and abnormal glucose tolerance in Finnish population, and to investigate the associations between body mass index (BMI), waist circumference and abnormal glucose tolerance.</p> <p>Methods</p> <p>A cross-sectional population-based survey was conducted in Finland during October 2004 and January 2005. A total of 4500 randomly selected individuals aged 45–74 years were invited to a health examination that included an oral glucose tolerance test. The participation rate was 62% in men and 67% in women.</p> <p>Results</p> <p>The prevalence of obesity was 23.5% (95% Confidence Interval (CI) 21.1–25.9) in men, and 28.0% (95% CI 25.5–30.5) in women. The overall prevalence of abnormal glucose tolerance (including type 2 diabetes, impaired glucose tolerance, or impaired fasting glucose) was 42.0% (95% CI 39.2–44.8) in men and 33.4% (95% CI 30.9–36.0) in women. The prevalence of previously unknown, screen-detected type 2 diabetes was 9.3% (95% CI 7.7–11.0) in men and 7.3% (95% CI 5.9–8.7) in women. Central obesity was associated with abnormal glucose tolerance within each of the three BMI categories normal (< 25 kg/m²), overweight (25–29 kg/m²), and obese (≥ 30 kg/m²).</p> <p>Conclusion</p> <p>In a population-based random sample of Finnish population, prevalences of obesity, central obesity and abnormal glucose tolerance were found to be high. A remarkably high number of previously undetected cases of type 2 diabetes was detected. Waist circumference is a predictor of abnormal glucose tolerance in all categories of obesity.</p