Comparison of stochastic and deterministic models for gambiense sleeping sickness at different spatial scales : a health area analysis in the DRC

The intensification of intervention activities against the fatal vector-borne disease gambiense human African trypanosomiasis (gHAT, sleeping sickness) in the last two decades has led to a large decline in the number of annually reported cases. However, while we move closer to achieving the ambitious target of elimination of transmission (EoT) to humans, pockets of infection remain, and it becomes increasingly important to quantitatively assess if different regions are on track for elimination, and where intervention efforts should be focused. We present a previously developed stochastic mathematical model for gHAT in the Democratic Republic of Congo (DRC) and show that this same formulation is able to capture the dynamics of gHAT observed at the health area level (approximately 10,000 people). This analysis was the first time any stochastic gHAT model has been fitted directly to case data and allows us to better quantify the uncertainty in our results. The analysis focuses on utilising a particle filter Markov chain Monte Carlo (MCMC) methodology to fit the model to the data from 16 health areas of Mosango health zone in Kwilu province as a case study. The spatial heterogeneity in cases is reflected in modelling results, where we predict that under the current intervention strategies, the health area of Kinzamba II, which has approximately one third of the health zone’s cases, will have the latest expected year for EoT. We find that fitting the analogous deterministic version of the gHAT model using MCMC has substantially faster computation times than fitting the stochastic model using pMCMC, but produces virtually indistinguishable posterior parameterisation. This suggests that expanding health area fitting, to cover more of the DRC, should be done with deterministic fits for efficiency, but with stochastic projections used to capture both the parameter and stochastic variation in case reporting and elimination year estimations

Neonatal outcomes of extremely preterm infants from the NICHD Neonatal Research Network.

OBJECTIVE: This report presents data from the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network on care of and morbidity and mortality rates for very low birth weight infants, according to gestational age (GA). METHODS: Perinatal/neonatal data were collected for 9575 infants of extremely low GA (22-28 weeks) and very low birth weight (401-1500 g) who were born at network centers between January 1, 2003, and December 31, 2007. RESULTS: Rates of survival to discharge increased with increasing GA (6% at 22 weeks and 92% at 28 weeks); 1060 infants died at CONCLUSION: Although the majority of infants with GAs of \u3eor=24 weeks survive, high rates of morbidity among survivors continue to be observed

Research, evidence and policymaking: the perspectives of policy actors on improving uptake of evidence in health policy development and implementation in Uganda

<p>Abstract</p> <p>Background</p> <p>Use of evidence in health policymaking plays an important role, especially in resource-constrained settings where informed decisions on resource allocation are paramount. Several knowledge translation (KT) models have been developed, but few have been applied to health policymaking in low income countries. If KT models are expected to explain evidence uptake and implementation, or lack of it, they must be contextualized and take into account the specificity of low income countries for example, the strong influence of donors. The main objective of this research is to elaborate a Middle Range Theory (MRT) of KT in Uganda that can also serve as a reference for other low- and middle income countries.</p> <p>Methods</p> <p>This two-step study employed qualitative approaches to examine the principal barriers and facilitating factors to KT. Step 1 involved a literature review and identification of common themes. The results informed the development of the initial MRT, which details the facilitating factors and barriers to KT at the different stages of research and policy development. In Step 2, these were further refined through key informant interviews with policymakers and researchers in Uganda. Deductive content and thematic analysis was carried out to assess the degree of convergence with the elements of the initial MRT and to identify other emerging issues.</p> <p>Results</p> <p>Review of the literature revealed that the most common emerging facilitating factors could be grouped under institutional strengthening for KT, research characteristics, dissemination, partnerships and political context. The analysis of interviews, however, showed that policymakers and researchers ranked institutional strengthening for KT, research characteristics and partnerships as the most important. New factors emphasized by respondents were the use of mainstreamed structures within MoH to coordinate and disseminate research, the separation of roles between researchers and policymakers, and the role of the community and civil society in KT.</p> <p>Conclusions</p> <p>This study refined an initial MRT on KT in policymaking in the health sector in Uganda that was based on a literature review. It provides a framework that can be used in empirical research of the process of KT on specific policy issues.</p

The relationship between plasma lipid peroxidation products and primary graft dysfunction after lung transplantation is modified by donor smoking and reperfusion hyperoxia

BACKGROUND: Donor smoking history and higher fraction of inspired oxygen (FIO2) at reperfusion are associated with primary graft dysfunction (PGD) after lung transplantation. We hypothesized that oxidative injury biomarkers would be elevated in PGD, with higher levels associated with donor exposure to cigarette smoke and recipient hyperoxia at reperfusion. METHODS: We performed a nested case-control study of 72 lung transplant recipients from the Lung Transplant Outcomes Group cohort. Using mass spectroscopy, F2-isoprostanes and isofurans were measured in plasma collected after transplantation. Cases were defined in 2 ways: grade 3 PGD present at day 2 or day 3 after reperfusion (severe PGD) or any grade 3 PGD (any PGD). RESULTS: There were 31 severe PGD cases with 41 controls and 35 any PGD cases with 37 controls. Plasma F2-isoprostane levels were higher in severe PGD cases compared with controls (28.6 pg/ml vs 19.8 pg/ml, p = 0.03). Plasma F2-isoprostane levels were higher in severe PGD cases compared with controls (29.6 pg/ml vs 19.0 pg/ml, p = 0.03) among patients reperfused with FIO2 >40%. Among recipients of lungs from donors with smoke exposure, plasma F2-isoprostane (38.2 pg/ml vs 22.5 pg/ml, p = 0.046) and isofuran (66.9 pg/ml vs 34.6 pg/ml, p = 0.046) levels were higher in severe PGD compared with control subjects. CONCLUSIONS: Plasma levels of lipid peroxidation products are higher in patients with severe PGD, in recipients of lungs from donors with smoke exposure, and in recipients exposed to higher Fio2 at reperfusion. Oxidative injury is an important mechanism of PGD and may be magnified by donor exposure to cigarette smoke and hyperoxia at reperfusion

Kitozanski umetci za periodontitis: Utjecaj količine lijeka, plastifikatora i umrežavanja na oslobađanje metronidazola in vitro

Chitosan based metronidazole (MZ) inserts were fabricated by the casting method and characterized with respect to mass and thickness uniformity, metronidazole loading and in vitro metronidazole release kinetics. The fabricated inserts exhibited satisfactory physical characteristics. The mass of inserts was in the range of 5.63 ± 0.42 to 6.04 ± 0.89 mg. The thickness ranged from 0.46 ± 0.06 to 0.49 ± 0.08 mm. Metronidazole loading was in the range of 0.98 ± 0.09 to 1.07 ± 0.07 mg except for batch CM3 with MZ loading of 2.01 ± 0.08 mg. The inserts exhibited an initial burst release at the end of 24 h, irrespective of the drug to polymer ratio, plasticizer content or cross-linking. However, further drug release was sustained over the next 6 days. Cross-linking with 10% (m/m) of glutaraldehyde inhibited the burst release by ~30% and increased the mean dissolution time (MDT) from 0.67 to 8.59 days. The decrease in drug release was a result of reduced permeability of chitosan due to cross-linking.Umetci metronidazola na bazi kitozana napravljeni su kasting metodom. Proučavana je ujednačenost mase i debljine, količina ljekovite tvari i kinetika oslobađanja metronidazola in vitro. Fizičke karakteristike umetaka bile su zadovoljavajuće: masa je bila u rasponu 5,63 ± 0,42 – 6,04 ± 0,89 mg, debljina od 0.46 ± 0.06 – 0.49 ± 0.08 mm with, količina metronidazola od 0,98 ± 0,09 – 1,07 ± 0,07 mg. Nakon 24 h iz svih umetaka, neovisno o omjeru ljekovite tvari i polimera, količini plastifikatora ili umrežavanju, dio metronidazola se naglo oslobodio. Međutim, daljnje oslobađanje je bilo polagano tijekom 6 dana. Umrežavanje s 10% (m/m) otopinom glutaraldehida spriječilo je naglo oslobađanje za ~30% i povećalo je srednje vrijeme oslobađanja (MDT) s 0,67 na 8,59 dana. Smanjenje u oslobađanju ljekovite tvari posljedica je smanjenja permeabilnosti umreženog kitozana

Association of risk factors and drug resistance pattern in tuberculosis patients in North India

Context: India is one of the high tuberculosis (TB) burden countries in the world. Improper implementation in the guidelines for the management of TB and high rate of defaults on the part of the patients are most important risk factors for the development of multi-drug resistant TB. Aims: This study examines the drug resistance profile and the effect of demographic, clinical and behavioral risk factors on the prevalence of TB and multidrug resistance (MDR) in north India. Settings and Design: This was a prospective, observational study carried out from May 2012 to February 2014 in tertiary care hospital of Varanasi. Subjects and Methods: The study was performed on 721 pulmonary and extrapulmonary specimens of suspected TB patients based on history, was subjected for the Ziehl–Neelsen staining and culture on Lowenstein–Jensen (LJ) media. Statistical Analysis: The features of groups were compared by Chi-square (χ2) and odds ratio. Results: Out of 721 clinically suspected pulmonary and extrapulmonary TB patients, 222 (30.8%) patients were smear positive for acid-fast bacilli and 244 (38.3%) were positive for Mycobacterium species cultured on LJ medium. The prevalence of resistance to at least one anti-TB drug was 71.1% and MDR was 53.5%. Age, gender, HIV status, nature of TB, smoking, and alcohol consumption risk factors were significantly associated with TB prevalence; while prior history of TB infection, pervious household exposure, smoking, and alcohol consumption were significantly associated with MDR. Conclusion: This study showed a high prevalence of drug resistance TB in this region. It also provides evidence in our circumstance, of the role of prior history of TB infection, alcohol and smoking in increasing the risk of developing TB and MDR-TB. Therefore, it is necessary for the public health community to incorporate and strengthen alcohol and smoking nonparticipation interference in TB control program

Resputtering Effect on Nanocrystalline Ni-Ti Alloy Films

We report on the effect of resputtering on the properties of nanocrystalline Ni-Ti alloy thin films deposited using co-sputtering of Ni and Ti targets. In order to facilitate the formation of nanocrystalline phases, films were deposited at room temperature and 573 K (300 A degrees C) with substrate bias voltage of -100 V. The influence of substrate material on the composition, surface topography microstructure, and phase formations of nanocrystalline Ni-Ti thin films was also systematically investigated. The preferential resputtering of Ti adatoms was lesser for Ni-Ti films deposited on quartz substrate owing to high surface roughness of 4.87 nm compared to roughness value of 1.27 nm for Si(100) substrate

Effect of Pelvic Endometrial Implants on Overall Reproductive Functions of Female Rats

The effects of pelvic endometrial implants on the overall reproductive potential of female rats were investigated. After homologous transplantation in the peritoneum, the ectopic endometrium developed into highly vascularized nodes that gradually increased in mass until the 9th week postsurgery and then plateaued. In the presence of these implants, overall reproductive function was adversely affected. The effect was of greatest magnitude during 50–70 days posttransplantation. As compared with values in corresponding controls, ovulation was reduced by 43% (6 of 14) (p , 0.05), mating rate was reduced by 44% (12 of 27) (p , 0.025), and premature termination of pregnancy occurred in 34% (5 of 15) of rats. Wastage of pregnancy, which included complete termination or reduction of fetal number, occurred during the postimplantation course of gestation. Furthermore, 100% of the rats with transplants failed to respond to the copulomimetic stimulation for the induction of pseudopregnancy (p , 0.01, compared with corresponding controls). However, on exposure to vasectomized males, 46% (6 of 13) of these rats exhibited development of pseudopregnancy (p , 0.05, compared with corresponding group receiving copulomimetic stimulation). Increased rate of mating failure and differential pseudopregnancy rates after copulomimetic and natural cervical stimulation suggest that the rats with endometrial explants possibly had an absence or a short appearance of behavioral estrus. Hormonal assessment during the preovulatory phase showed a tendency toward lower mean levels of preovulatory estradiol and significantly lower LH (p , 0.01) and progesterone (p , 0.01) concentrations. The adversely affected reproductive functions may be a secondary consequence of these altered endocrine milieus

Mechanosignaling in the vasculature: emerging concepts in sensing, transduction and physiological responses

Cells are constantly exposed to mechanical forces that play a role in modulating cellular structure and function. The cardiovascular system experiences physical forces in the form of shear stress and stretch associated with blood flow and contraction, respectively. These forces are sensed by endothelial cells and cardiomyocytes and lead to responses that control vascular and cardiac homeostasis. This was highlighted at the Pan American Physiological Society meeting at Iguassu Falls, Brazil, in a symposium titled “Mechanosignaling in the Vasculature.” This symposium presented recent research that showed the existence of a vital link between mechanosensing and downstream redox sensitive signaling cascades. This link helps to transduce and transmit the physical force into an observable physiological response. The speakers showcased how mechanosensors such as ion channels, membrane receptor kinases, adhesion molecules, and other cellular components transduce the force via redox signals (such as reactive oxygen species and nitric oxide) to receptors (transcription factors, growth factors, etc.). Receptor activated pathways then lead to cellular responses including cellular proliferation, contraction, and remodeling. These responses have major relevance to the physiology and pathophysiology of various cardiovascular diseases. Thus an understanding of the complex series of events, from the initial sensing through the final response, is essential for progress in this field. Overall, this symposium addressed some important emerging concepts in the field of mechanosignaling and the eventual pathophysiological responses.Fil: Chatterjee, Shampa. University of Pennsylvania; Estados UnidosFil: Fujiwara, Keigi. University Of Texas; Estados UnidosFil: Perez, Nestor Gustavo. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnológico la Plata. Centro de Investigaciones Cardiovasculares "dr. Horacio Eugenio Cingolani"; Argentina. Universidad Nacional de la Plata. Facultad de Ciencias Médicas; ArgentinaFil: Ushio Fukai, Masuko. University Of Illinois; Estados UnidosFil: Fisher, Aron B.. University of Pennsylvania; Estados Unido