Substantial and sustained reduction in under-5 mortality, diarrhea, and pneumonia in Oshikhandass, Pakistan : Evidence from two longitudinal cohort studies 15 years apart

Funding Information: Study 1 was funded through the Applied Diarrheal Disease Research Program at Harvard Institute for International Development with a grant from USAID (Project 936–5952, Cooperative Agreement # DPE-5952-A-00-5073-00), and the Aga Khan Health Service, Northern Areas and Chitral, Pakistan. Study 2 was funded by the Pakistan US S&T Cooperative Agreement between the Pakistan Higher Education Commission (HEC) (No.4–421/PAK-US/HEC/2010/955, grant to the Karakoram International University) and US National Academies of Science (Grant Number PGA-P211012 from NAS to the Fogarty International Center). The funding bodies had no role in the design of the study, data collection, analysis, interpretation, or writing of the manuscript. Publisher Copyright: © 2020 The Author(s).Peer reviewedPublisher PD

Evaluation of appendicitis risk prediction models in adults with suspected appendicitis

Background Appendicitis is the most common general surgical emergency worldwide, but its diagnosis remains challenging. The aim of this study was to determine whether existing risk prediction models can reliably identify patients presenting to hospital in the UK with acute right iliac fossa (RIF) pain who are at low risk of appendicitis. Methods A systematic search was completed to identify all existing appendicitis risk prediction models. Models were validated using UK data from an international prospective cohort study that captured consecutive patients aged 16–45 years presenting to hospital with acute RIF in March to June 2017. The main outcome was best achievable model specificity (proportion of patients who did not have appendicitis correctly classified as low risk) whilst maintaining a failure rate below 5 per cent (proportion of patients identified as low risk who actually had appendicitis). Results Some 5345 patients across 154 UK hospitals were identified, of which two‐thirds (3613 of 5345, 67·6 per cent) were women. Women were more than twice as likely to undergo surgery with removal of a histologically normal appendix (272 of 964, 28·2 per cent) than men (120 of 993, 12·1 per cent) (relative risk 2·33, 95 per cent c.i. 1·92 to 2·84; P < 0·001). Of 15 validated risk prediction models, the Adult Appendicitis Score performed best (cut‐off score 8 or less, specificity 63·1 per cent, failure rate 3·7 per cent). The Appendicitis Inflammatory Response Score performed best for men (cut‐off score 2 or less, specificity 24·7 per cent, failure rate 2·4 per cent). Conclusion Women in the UK had a disproportionate risk of admission without surgical intervention and had high rates of normal appendicectomy. Risk prediction models to support shared decision‐making by identifying adults in the UK at low risk of appendicitis were identified

Rice Response to Phosphorus and Potassium in Fluvisol of Second Order Lowland in a Guinea Savanna Zone of Sub-Saharan Africa

Aims: Poor management of P- and K-fertilizers can affect Nitrogen effect in rice grain yield and nutritional quality as the most limiting nutrient for rice production in second order lowland of Guinea savanna in West Africa. For the development of best management strategy of N, P and K fertilizers in this agro-ecosystem, the response surface curve of rice to P- and K-fertilizer rates was assessed with the recommended rate of nitrogen. Study Design: An agronomic trial including eleven (11) treatments in three replications was laid out in a complete randomized blocks design. Place and Duration of the Study: During three successive cropping cycles of rice in 2012, the study was conducted in M’be II valley of the Centre Cote d’Ivoire, a Guinea savanna zone. Methodology: Three rates of P- Ca(H2PO4)2H2O [30, 60 and 90 kgPha-1] as well as three of K-KCl [25, 50 and 75kg Kha-1] and their recommended rates (13 kgPha-1 and 25 kgKha-1) in the humid forest zone were the treatments. A total of 80 kgNha-1(urea) was applied in three splits to each of the micro-plots except in the control including no fertilizer. The rice variety named NERICA L19 was transplanted. Results: The results showed a synergism between K- fertilization and N-nutrition of rice likewise for P-fertilizer which has limited effect on K-nutrition. Conclusion: The rates of 10 kgPha-1 and 75 kgKha-1 were recommended for the production of high grain yield and nutritional quality of rice when applying 80 kgNha-1. However, further assessments of K and N were suggested for sustaining rice production in the studied agro-ecology

Humoral immune response against epidermal growth factor encapsulated in dehydration rehydration vesicles of different phospholipid composition

We investigated the influence of dehydration-rehydration vesicles (DRV) phospholipid composition and the addition of other components on human recombinant epidermal growth factor (hrEGF) encapsulation efficiency and its release from liposomes. Encapsulation of EGF into DRV composed of phosphatidylcholine with different unsaturation levels was around 20-35%. The best result was obtained with dipalmitoyl phosphatidylcholine: cholesterol (DPPC:Ch) liposomes (35%) corresponding to the lowest hrEGF release during one month of storage. Even with this phospholipid composition, modification of the DRV procedure by including an extrusion step did not improve hrEGF encapsulation efficiency, rendering less stable particles. The inclusion of recombinant P64k from Neisseria meningitidis (rP64k), as such or conjugated to hrEGF, decreased the encapsulation efficiency of the latter protein into DRV or freeze and thaw multilamellar vesicles (FATMLV). The hrEGF release from liposomes could be related to the interaction between this polypeptide and the bilayer, as evidenced by increased carboxyfluorescein release from hrEGF-DRV; less susceptibility to fluorescence quenching by acrylamide in the presence of liposomes; and a measurable decrease of phospholipid phase transition Delta enthalpy (Delta H). DRV comprising saturated phospholipids (DPPC:Ch or distearoyl phosphatidylcholine [DSPC]:Ch) and containing the conjugate EGF-P64k induced a more efficient immune response against hrEGF than unsaturated phospholipid and alum in terms of total IgG, IgG(2a), and IgG(2b) subclasses and the ability of antibody to inhibit the interaction of the EGF receptor with hrEGF

Diagnostic Accuracy of 4 Commercially Available Semiautomatic Packages for Carotid Artery Stenosis Measurement on CTA

Semiautomatic measurement of ICA stenosis potentially increases observer reproducibility. In this study, we assessed the diagnostic accuracy and interobserver reproducibility of a commercially available semiautomatic ICA stenosis measurement on CTA and estimated the agreement among different software packages. We analyzed 141 arteries from 90 patients with TIA or ischemic stroke. Manual stenosis measurements were performed by 2 neuroradiologists. Semiautomatic measurements by using 4 methods (3mensio and comparable software from Philips, TeraRecon, and Siemens) were performed by 2 observers. Diagnostic accuracy was estimated by comparing semiautomatic with manual measurements. Interobserver reproducibility and agreement between different packages was assessed by calculation of the intraclass correlation coefficient and Bland-Altman 95% limits of agreement. False-negative classifications were retrospectively inspected by a neuroradiologist. There was no significant difference in the diagnostic performance of the 4 semiautomatic methods. The sensitivity for detecting ≥50% and ≥70% degree of stenosis was between 76% and 82% and 46% and 62%, respectively. Specificity and overall diagnostic accuracy were between 92% and 97% and 85% and 90%, respectively. The interobserver intraclass correlation coefficient was between 0.83 and 0.96 for semiautomatic measurements and 0.81 for manual measurement. The limits of agreement between each pair of semiautomatic packages ranged from -18%-24% to -33%-31%. False-negative classifications were caused by ulcerative plaques and observer variation in stenosis and reference measurements. Semiautomatic methods have a low-to-good sensitivity and a good specificity and overall diagnostic accuracy. The high interobserver reproducibility makes semiautomatic stenosis measurement valuable for clinical practice, but semiautomatic measurements should be checked by an experienced radiologis

Development of a diagnostic compatible BCG vaccine against Bovine tuberculosis

Bovine tuberculosis (BTB) caused by Mycobacterium bovis remains a major problem in both the developed and developing countries. Control of BTB in the UK is carried out by test and slaughter of infected animals, based primarily on the tuberculin skin test (PPD). Vaccination with the attenuated strain of the M. bovis pathogen, BCG, is not used to control bovine tuberculosis in cattle at present, due to its variable efficacy and because it interferes with the PPD test. Diagnostic tests capable of Differentiating Infected from Vaccinated Animals (DIVA) have been developed that detect immune responses to M. bovis antigens absent in BCG; but these are too expensive and insufficiently sensitive to be used for BTB control worldwide. To address these problems we aimed to generate a synergistic vaccine and diagnostic approach that would permit the vaccination of cattle without interfering with the conventional PPD-based surveillance. The approach was to widen the pool of M. bovis antigens that could be used as DIVA targets, by identifying antigenic proteins that could be deleted from BCG without affecting the persistence and protective efficacy of the vaccine in cattle. Using transposon mutagenesis we identified genes that were essential and those that were non-essential for persistence in bovine lymph nodes. We then inactivated selected immunogenic, but non-essential genes in BCG Danish to create a diagnostic-compatible triple knock-out ΔBCG TK strain. The protective efficacy of the ΔBCG TK was tested in guinea pigs experimentally infected with M. bovis by aerosol and found to be equivalent to wild-type BCG. A complementary diagnostic skin test was developed with the antigenic proteins encoded by the deleted genes which did not cross-react in vaccinated or in uninfected guinea pigs. This study demonstrates the functionality of a new and improved BCG strain which retains its protective efficacy but is diagnostically compatible with a novel DIVA skin test that could be implemented in control programmes

Intraplaque Hemorrhage and the Plaque Surface in Carotid Atherosclerosis: The Plaque At RISK Study (PARISK)

An important characteristic of vulnerable plaque, intraplaque hemorrhage, may predict plaque rupture. Plaque rupture can be visible on noninvasive imaging as a disruption of the plaque surface. We investigated the association between intraplaque hemorrhage and disruption of the plaque surface. We selected the first 100 patients of the Plaque At RISK study, an ongoing prospective noninvasive plaque imaging study in patients with mild-to-moderate atherosclerotic lesions in the carotid artery. In carotid artery plaques, disruption of the plaque surface (defined as ulcerated plaques and/or fissured fibrous cap) and intraplaque hemorrhage were assessed by using MDCTA and 3T MR imaging, respectively. We used a χ(2) test and multivariable logistic regression to assess the association between intraplaque hemorrhage and disrupted plaque surface. One hundred forty-nine carotid arteries in 78 patients could be used for the current analyses. Intraplaque hemorrhage and plaque ulcerations were more prevalent in symptomatic compared with contralateral vessels (hemorrhage, 38% versus 11%; P < .001; and ulcerations, 27% versus 7%; P = .001). Fissured fibrous cap was more prevalent in symptomatic compared with contralateral vessels (13% versus 4%; P = .06). After adjustment for age, sex, diabetes mellitus, and degree of stenosis, intraplaque hemorrhage was associated with disrupted plaque surface (OR, 3.13; 95% CI, 1.25-7.84) in all vessels. Intraplaque hemorrhage is associated with disruption of the plaque surface in patients with a carotid artery stenosis of <70%. Serial studies are needed to investigate whether intraplaque hemorrhage indeed increases the risk of plaque rupture and subsequent ischemic stroke during follow-u

Association between fibrinogen and fibrinogen gamma ' and atherosclerotic plaque morphology and composition in symptomatic carotid artery stenosis: Plaque-At-RISK study : Plaque-At-RISK study

INTRODUCTION: Von Willebrand Factor (VWF), ADAMTS13, fibrinogen and fibrinogen γ' are associated with an increased risk of ischemic stroke. Carotid atherosclerosis is an important risk factor for ischemic stroke. Characteristics of the vulnerable plaque; intraplaque hemorrhage (IPH), plaque ulceration and lipid-rich necrotic core (LRNC) can be visualized with imaging techniques. Since atherosclerosis might attribute to the association between coagulation factors and ischemic stroke risk, the aim of this study is to investigate the association between coagulation factors and atherosclerotic plaque characteristics in more detail. MATERIALS AND METHODS: In 182 patients of the Plaque-At-RISK study (prospective multicenter cohort study) with a recent transient ischemic attack (TIA) or ischemic stroke and a symptomatic mild-to-moderate carotid artery stenosis, we measured VWF antigen (VWF:Ag), ADAMTS13 activity, fibrinogen (Clauss), and fibrinogen γ'. Presence of plaque ulceration, IPH volume and LRNC volume were determined by Multidetector-Row Computed Tomography (MDCTA, n = 160) and Magnetic Resonance Imaging (MRI, n = 172). Linear regression analysis was used to assess the association between imaging biomarkers and coagulation factors. RESULTS: VWF:Ag or ADAMTS13 levels were not significantly associated with plaque ulceration, IPH and LRNC. We found an inverse association between fibrinogen and fibrinogen γ' and IPH volume (B = -23.40 mm3/g/L, p = 0.01 and B = -161.73 mm3/g/L, p = 0.01) and between fibrinogen and fibrinogen γ' and LRNC volume (B = -38.89 mm3 g/L, p < 0.01 and B = -227.06 mm3 g/L, p = 0.01). Additional adjustments for C-reactive protein (CRP) did not change the results. CONCLUSIONS: Fibrinogen and fibrinogen γ' are inversely associated with IPH volume and LRNC volume, independent of inflammation. CLINICAL TRIAL REGISTRATION: clinicaltrials.govNCT01208025