Changing patterns of malaria during 1996-2010 in an area of moderate transmission in Southern Senegal

<p>Abstract</p> <p>Background</p> <p>Malaria is reportedly receding in different epidemiological settings, but local long-term surveys are limited. At Mlomp dispensary in south-western Senegal, an area of moderate malaria transmission, year-round, clinically-suspected malaria was treated with monotherapy as per WHO and national policy in the 1990s. Since 2000, there has been a staggered deployment of artesunate-amodiaquine after parasitological confirmation; this was adopted nationally in 2006.</p> <p>Methods</p> <p>Data were extracted from clinic registers for the period between January 1996 and December 2010, analysed and modelled.</p> <p>Results</p> <p>Over the 15-year study period, the risk of malaria decreased about 32-times (from 0.4 to 0.012 episodes person-year), while anti-malarial treatments decreased 13-times (from 0.9 to 0.07 treatments person-year) and consultations for fever decreased 3-times (from 1.8 to 0.6 visits person-year). This was paralleled by changes in the age profile of malaria patients so that the risk of malaria is now almost uniformly distributed throughout life, while in the past malaria used to concern more children below 16 years of age.</p> <p>Conclusions</p> <p>This study provides direct evidence of malaria risk receding between 1996-2010 and becoming equal throughout life where transmission used to be moderate. Infection rates are no longer enough to sustain immunity. Temporally, this coincides with deploying artemisinin combinations on parasitological confirmation, but other contributing causes are unclear.</p

Efficacy and safety of single 40 mg/kg oral praziquantel in the treatment of schistosomiasis in preschool-age versus school-age children:An individual participant data meta-analysis

Better knowledge of the efficacy and safety of single 40 mg/kg oral praziquantel in preschool-age children is required, should preventive chemotherapy programs for schistosomiasis be expanded to include this age group.; We analyzed individual participant-level data from 16 studies (13 single-arm or cohort studies and three randomized trials), amounting to 683 preschool-age children (aged <6 years) and 2,010 school-age children (aged 6-14 years). Children had a documented Schistosoma mansoni or S. haematobium infection, were treated with single 40 mg/kg oral praziquantel, and assessed between 21 and 60 days post-treatment. Efficacy was expressed as arithmetic mean and individual egg reduction rate (ERR) and meta-analyzed using general linear models and mixed models. Safety was summarized using reported adverse events (AEs).; Preschool-age children had significantly lower baseline Schistosoma egg counts and more losses to follow-up compared to school-age children. No difference in efficacy was found between preschool- and school-age children using a general linear model of individual-participant ERR with baseline log-transformed egg count as covariate and study, age, and sex as fixed variables, and a mixed model with a random effect on the study. Safety was reported in only four studies (n = 1,128 individuals); few AEs were reported in preschool-age children 4 and 24 hours post-treatment as well as at follow-up. Three severe but not serious AEs were recorded in school-age children during follow-up.; There is no indication that single 40 mg/kg oral praziquantel would be less efficacious and safe in preschool-age children compared to school-age children, with the caveat that only few randomized comparisons exist between the two age groups. Preventive chemotherapy might therefore be extended to preschool-age children, with proper monitoring of its efficacy and safety

Statistical M-Estimation and Consistency in Large Deformable Models for Image Warping

The problem of defining appropriate distances between shapes or images and modeling the variability of natural images by group transformations is at the heart of modern image analysis. A current trend is the study of probabilistic and statistical aspects of deformation models, and the development of consistent statistical procedure for the estimation of template images. In this paper, we consider a set of images randomly warped from a mean template which has to be recovered. For this, we define an appropriate statistical parametric model to generate random diffeomorphic deformations in two-dimensions. Then, we focus on the problem of estimating the mean pattern when the images are observed with noise. This problem is challenging both from a theoretical and a practical point of view. M-estimation theory enables us to build an estimator defined as a minimizer of a well-tailored empirical criterion. We prove the convergence of this estimator and propose a gradient descent algorithm to compute this M-estimator in practice. Simulations of template extraction and an application to image clustering and classification are also provided

PENGARUH TEKANAN KETAATAN DAN KOMPLEKSITAS TUGAS TERHADAP AUDIT JUDGMENT (Survey Terhadap Lima Kantor AkuntanPublik di Kota Bandung)

ABSTRAK Seperti yang kita ketahui bahwa seorang auditor dalam melakukan tugasnya membuat audit judgment dipengaruhi banyak faktor, baik bersifat teknis dan non teknis. Salah satu faktor non teknis adalah aspek perilaku individual. Aspek perilaku individu, sebagai salah satu faktor yang banyak mempengaruhi pembuatan audit judgment. Pada penelitian ini ada beberapa faktor yang mempengaruhi audit judgment yaitu tekanan ketaatan dan kompleksitas tugas. Dalam penelitian ini penullis ingin mengetahui sejauh mana “tekanan ketaatan dan kompleksitas tugas terhadap audit judgment”. Sedangkan tujuan dari penelitian ini adalah untuk mengetahui dan mempelajari tekanan ketaatan dan kompleksitas tugas terhadap audit judgment. Hipotesis yang diuji dalam penelitian ini adalah “ jika tekanan ketaatan dan kompleksitas tugas baik, maka audit judgment akan meningkat ( baik pula)”. Hipotesis ini berdasarkan asumsi bahwa tekanan ketaatan dan kompleksitas tugas berpengaruh terhadap audit judgment.dalam penelitian ini penulis menggunakan metode deskriptif asosiatif dengan pendekatan survey dan tes statistik. Penelitian ini terdiri dari atas variabel X1 dan X2 dan audit judgment sebagai veriabel Y atau variabel independen. Uji statistik dilakukan dengan mengolah data dari hasil jawaban kuesioner. Dalam penelitian ini, peulis menyebarkan angket kepada 5 Kantor Akuntan Publik di Kota Bandung khusunya untuk para auditor. Pengumpulan data dilakukan dengan cara penyebaran kuesioner yang telah diuji validitasnya dan reabilitasnya. Penelitian ini dilakukan di 5 KAP di Kota Bandung. Pengambilan sampel ini menggunakan purposive sampling berukuran 28 orang responden. Untuk uji hipotesis penelitian, penulis melakukannya dengan uji t untuk masing-masing variabel X1,X2, dan Y. Dari hasil uji tHitung tekanan ketaatan terhadap audit judgment tHitung =4,178>ttabel = 1.705 kompleksitas tugas terhadap audit judgment 5 tHitung = 3.364 > ttabel = 1,705. Maka, dari hasil uji hipotesis tersebut penulis menyimpulkan bahwa hipotesis penelitian diterima (Ho ditolak, Ha diterima) artinya terdapat pengaruh antara terkanan ketaatan terhadap audit judgment dan kompleksitas tugas terhadap audit judgment Untuk mencari besarnya pengaruh Tekanan ketaatan dan Kompleksitas Tugas terhadap Audit Judgment secara simultan penulis melakukannya dengan uji f dengan koefisien determinasi (KD). Dari hasil uji fhitung dan > f table yaitu 16,182>3,370. Kata kunci : Tekanan Ketaatan dan Kompleksitas tugas Terhadap Audit Judgmen

Analysis of KLF transcription factor family gene variants in type 2 diabetes

<p>Abstract</p> <p>Background</p> <p>The Krüppel-like factor (<it>KLF</it>) family consists of transcription factors that can activate or repress different genes implicated in processes such as differentiation, development, and cell cycle progression. Moreover, several of these proteins have been implicated in glucose homeostasis, making them candidate genes for involvement in type 2 diabetes (T2D).</p> <p>Methods</p> <p>Variants of nine <it>KLF </it>genes were genotyped in T2D cases and controls and analysed in a two-stage study. The first case-control set included 365 T2D patients with a strong family history of T2D and 363 normoglycemic individuals and the second set, 750 T2D patients and 741 normoglycemic individuals, all of French origin. The SNPs of six <it>KLF </it>genes were genotyped by Taqman^®SNP Genotyping Assays. The other three <it>KLF </it>genes (KLF2, -15 and -16) were screened and the identified frequent variants of these genes were analysed in the case-control studies.</p> <p>Results</p> <p>Three of the 28 SNPs showed a trend to be associated with T2D in our first case-control set (P < 0.10). These SNPs, located in the <it>KLF2, KLF4 </it>and <it>KLF5 </it>gene were then analysed in our second replication set, but analysis of this set and the combined analysis of the three variants in all 2,219 individuals did not show an association with T2D in this French population. As the <it>KLF2</it>, -15 and -16 variants were representative for the genetic variability in these genes, we conclude they do not contribute to genetic susceptibility for T2D.</p> <p>Conclusion</p> <p>It is unlikely that variants in different members of the <it>KLF </it>gene family play a major role in T2D in the French population.</p

A Multicentre Randomized Controlled Trial of the Efficacy and Safety of Single-Dose Praziquantel at 40 mg/kg vs. 60 mg/kg for Treating Intestinal Schistosomiasis in the Philippines, Mauritania, Tanzania and Brazil

Control of urinary and intestinal schistosomiasis is based on mass administration of praziquantel at the World Health Organization (WHO) recommended dose of 40 mg/kg, though some countries use 60 mg/kg. This multi-country randomized clinical trial compared the efficacy (cure and egg reduction rates three weeks post-treatment) and safety of these two doses for treating intestinal schistosomiasis in 856 patients in Brazil, Mauritania and Tanzania (Schistosoma mansoni), and The Philippines (S. japonicum). Transmission and infection intensities varied across the sites, but there was no bias or heterogeneity in efficacy outcomes. The two doses are equally effective in curing intestinal schistosomiasis; the higher dose may be less well tolerated, though effects are generally mild and transient. In endemic areas people can be re-infected; one year post-treatment patients on 60 mg/kg had fewer re-infections but this finding is difficult to explain. This study was conducted to respond to the demand for evidence about the dose of praziquantel when deployed in endemic countries. The results, along with those of systematic reviews, support the current WHO recommendation for using praziquantel at 40 mg/kg and should inform policy decisions in countries. The Philippines has already changed from 60 to 40 mg/kg after this study

Effect of predicted low suspend pump treatment on improving glycaemic control and quality of sleep in children with type 1 diabetes and their caregivers: the QUEST randomized crossover study.

BACKGROUND: In attempting to achieve optimal metabolic control, the day-to-day management is challenging for a child with type 1 diabetes (T1D) and his family and can have a major negative impact on their quality of life. Augmenting an insulin pump with glucose sensor information leads to improved outcomes: decreased haemoglobin A1c levels, increased time in glucose target and less hypoglycaemia. Fear of nocturnal hypoglycaemia remains pervasive amongst parents, leading to chronic sleep interruption and lack of sleep for the parents and their children. The QUEST study, an open-label, single-centre randomized crossover study, aims to evaluate the impact on time in target, in hypoglycaemia and hyperglycaemia and the effect on sleep and quality of life in children with T1D, comparing a sensor-augmented pump (SAP) with predictive low glucose suspend and alerts to the use of the same insulin pump with a flash glucose measurement (FGM) device not interacting with the pump. METHODS/DESIGN: Subjects meeting the inclusion criteria are randomized to treatment with the SAP or treatment with an insulin pump and independent FGM for 5 weeks. Following a 3-week washout period, the subjects cross over to the other study arm for 5 weeks. During the week before and in the last week of treatment, the subjects and one of their caregivers wear a sleep monitor in order to obtain sleep data. The primary endpoint is the between-arm difference in percentage of time in glucose target during the final 6 days of each treatment arm, measured by a blinded continuous glucose measurement (CGM). Additional endpoints include comparison of quantity and quality of sleep as well as quality of life perception of the subjects and one of their caregivers in the two different treatment arms. Recruitment started in February 2017. A total of 36 patients are planned to be randomized. The study recruitment was completed in April 2018. DISCUSSION: With this study we will provide more information on whether insulin pump treatment combined with more technology (SmartGuard® feature and alerts) leads to better metabolic control. The inclusion of indicators on quality of sleep with less sleep interruption, less lack of sleep and perception of quality of life in both children and their primary caregivers is essential for this study and might help to guide us to further treatment improvement. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03103867 . Registered on 6 April 2017

The Luxembourg Parkinson’s Study: A Comprehensive Approach for Stratification and Early Diagnosis

While genetic advances have successfully defined part of the complexity in Parkinson’s disease (PD), the clinical characterization of phenotypes remains challenging. Therapeutic trials and cohort studies typically include patients with earlier disease stages and exclude comorbidities, thus ignoring a substantial part of the real-world PD population. To account for these limitations, we implemented the Luxembourg PD study as a comprehensive clinical, molecular and device-based approach including patients with typical PD and atypical parkinsonism, irrespective of their disease stage, age, comorbidities, or linguistic background. To provide a large, longitudinally followed, and deeply phenotyped set of patients and controls for clinical and fundamental research on PD, we implemented an open-source digital platform that can be harmonized with international PD cohort studies. Our interests also reflect Luxembourg-specific areas of PD research, including vision, gait, and cognition. This effort is flanked by comprehensive biosampling efforts assuring high quality and sustained availability of body liquids and tissue biopsies. We provide evidence for the feasibility of such a cohort program with deep phenotyping and high quality biosampling on parkinsonism in an environment with structural specificities and alert the international research community to our willingness to collaborate with other centers. The combination of advanced clinical phenotyping approaches including device-based assessment will create a comprehensive assessment of the disease and its variants, its interaction with comorbidities and its progression. We envision the Luxembourg Parkinson’s study as an important research platform for defining early diagnosis and progression markers that translate into stratified treatment approaches