The local economic development processes in low-income countries: the case of the metropolis of Chegutu in Zimbabwe

Local authorities are widely regarded as catalysts accelerating localised processes of economic development in industrialised countries but in low-income countries they are perceived as dysfunctional, inefficient and ineffective in meeting and addressing societal demands. This abstract view is however, not grounded in empirical research. As such, utilising the case of the metropolis of Chegutu a survey was designed to empirically explicate the economic processes militating its economic development. The findings are useful to policy-makers, local government authorities and management scholars. The study's unique contribution lies in its examination of the processes of local economic development in a low-income country

A preliminary study of genetic factors that influence susceptibility to bovine tuberculosis in the British cattle herd

Associations between specific host genes and susceptibility to Mycobacterial infections such as tuberculosis have been reported in several species. Bovine tuberculosis (bTB) impacts greatly the UK cattle industry, yet genetic predispositions have yet to be identified. We therefore used a candidate gene approach to study 384 cattle of which 160 had reacted positively to an antigenic skin test (‘reactors’). Our approach was unusual in that it used microsatellite markers, embraced high breed diversity and focused particularly on detecting genes showing heterozygote advantage, a mode of action often overlooked in SNP-based studies. A panel of neutral markers was used to control for population substructure and using a general linear model-based approach we were also able to control for age. We found that substructure was surprisingly weak and identified two genomic regions that were strongly associated with reactor status, identified by markers INRA111 and BMS2753. In general the strength of association detected tended to vary depending on whether age was included in the model. At INRA111 a single genotype appears strongly protective with an overall odds ratio of 2.2, the effect being consistent across nine diverse breeds. Our results suggest that breeding strategies could be devised that would appreciably increase genetic resistance of cattle to bTB (strictly, reduce the frequency of incidence of reactors) with implications for the current debate concerning badger-culling

Theoretical framework and methodological development of common subjective health outcome measures in osteoarthritis: a critical review

Subjective measures involving clinician ratings or patient self-assessments have become recognised as an important tool for the assessment of health outcome. The value of a health outcome measure is usually assessed by a psychometric evaluation of its reliability, validity and responsiveness. However, psychometric testing involves an accumulation of evidence and has recognised limitations. It has been suggested that an evaluation of how well a measure has been developed would be a useful additional criteria in assessing the value of a measure. This paper explored the theoretical background and methodological development of subjective health status measures commonly used in osteoarthritis research. Fourteen subjective health outcome measures commonly used in osteoarthritis research were examined. Each measure was explored on the basis of their i) theoretical framework (was there a definition of what was being assessed and was it part of a theoretical model?) and ii) methodological development (what was the scaling strategy, how were the items generated and reduced, what was the response format and what was the scoring method?). Only the AIMS, SF-36 and WHOQOL defined what they were assessing (i.e. the construct of interest) and no measure assessed was part of a theoretical model. None of the clinician report measures appeared to have implemented a scaling procedure or described the rationale for the items selected or scoring system. Of the patient self-report measures, the AIMS, MPQ, OXFORD, SF-36, WHOQOL and WOMAC appeared to follow a standard psychometric scaling method. The DRP and EuroQol used alternative scaling methods. The review highlighted the general lack of theoretical framework for both clinician report and patient self-report measures. This review also drew attention to the wide variation in the methodological development of commonly used measures in OA. While, in general the patient self-report measures had good methodological development, the clinician report measures appeared less well developed. It would be of value if new measures defined the construct of interest and, that the construct, be part of theoretical model. By ensuring measures are both theoretically and empirically valid then improvements in subjective health outcome measures should be possible

Cutpoints for mild, moderate and severe pain in patients with osteoarthritis of the hip or knee ready for joint replacement surgery

<p>Abstract</p> <p>Background</p> <p>Cutpoints (CPs) for mild, moderate and severe pain are established and used primarily in cancer pain. In this study, we wanted to determine the optimal CPs for mild, moderate, and severe pain in joint replacement surgery candidates with osteoarthritis (OA) of the hip or knee, and to validate the different CPs.</p> <p>Methods</p> <p>Patients (n = 353) completed the Brief Pain Inventory (BPI), the WOMAC Arthritis Index, and the SF-36 health status measure. Optimal CPs for categorizing average pain with three severity levels were derived using multivariate analysis of variance, using different CP sets for average pain as the independent variable and seven interference items from the BPI as the dependent variable. To validate the CPs, we assessed if patients in the three pain severity groups differed in pain as assessed with WOMAC and SF-36, and if BPI average pain with the optimal CPs resulted in higher correlation with pain dimensions of the WOMAC and SF-36 than other CPs.</p> <p>Results</p> <p>The optimal CPs on the 0–10 point BPI scale were CP (4,6) among hip patients and CP (4,7) among knee patients. The resulting pain severity groups differed in pain, as assessed with other scales than those used to derive the CPs. The optimal CPs had the highest association of average pain with WOMAC pain scores.</p> <p>Conclusion</p> <p>CPs for pain severity differed somewhat for patients with OA of the hip and knee. The association of BPI average pain scores categorized according to the optimal CPs with WOMAC pain scores supports the validity of the derived optimal CPs.</p

Methods for specifying the target difference in a randomised controlled trial : the Difference ELicitation in TriAls (DELTA) systematic review

Peer reviewedPublisher PD

CD209 Genetic Polymorphism and Tuberculosis Disease

BACKGROUND: Tuberculosis causes significant morbidity and mortality worldwide, especially in sub-Saharan Africa. DC-SIGN, encoded by CD209, is a receptor capable of binding and internalizing Mycobacterium tuberculosis. Previous studies have reported that the CD209 promoter single nucleotide polymorphism (SNP)-336A/G exerts an effect on CD209 expression and is associated with human susceptibility to dengue, HIV-1 and tuberculosis in humans. The present study investigates the role of the CD209 -336A/G variant in susceptibility to tuberculosis in a large sample of individuals from sub-Saharan Africa. METHODS AND FINDINGS: A total of 2,176 individuals enrolled in tuberculosis case-control studies from four sub-Saharan Africa countries were genotyped for the CD209 -336A/G SNP (rs4804803). Significant overall protection against pulmonary tuberculosis was observed with the -336G allele when the study groups were combined (n = 914 controls vs. 1262 cases, Mantel-Haenszel 2 x 2 chi(2) = 7.47, P = 0.006, odds ratio = 0.86, 95%CI 0.77-0.96). In addition, the patients with -336GG were associated with a decreased risk of cavitory tuberculosis, a severe form of tuberculosis disease (n = 557, Pearson's 2x2 chi(2) = 17.34, P = 0.00003, odds ratio = 0.42, 95%CI 0.27-0.65). This direction of association is opposite to a previously observed result in a smaller study of susceptibility to tuberculosis in a South African Coloured population, but entirely in keeping with the previously observed protective effect of the -336G allele. CONCLUSION: This study finds that the CD209 -336G variant allele is associated with significant protection against tuberculosis in individuals from sub-Saharan Africa and, furthermore, cases with -336GG were significantly less likely to develop tuberculosis-induced lung cavitation. Previous in vitro work demonstrated that the promoter variant -336G allele causes down-regulation of CD209 mRNA expression. Our present work suggests that decreased levels of the DC-SIGN receptor may therefore be protective against both clinical tuberculosis in general and cavitory tuberculosis disease in particular. This is consistent with evidence that Mycobacteria can utilize DC-SIGN binding to suppress the protective pro-inflammatory immune response

Maternal Arterial Stiffness in Women Who Subsequently Develop Pre-Eclampsia

BACKGROUND/OBJECTIVES: Pre-eclampsia (PE) is associated with profound changes in the maternal cardiovascular system. The aim of the present study was to assess whether alterations in the maternal arterial stiffness precede the onset of PE in at risk women. METHODOLOGY/PRINCIPAL FINDINGS: This was a cross sectional study involving 70 pregnant women with normal and 70 women with abnormal uterine artery Doppler examination at 22-24 weeks of gestation. All women had their arterial stiffness (augmentation index and pulse wave velocity of the carotid-femoral and carotid-radial parts of the arterial tree) assessed by applanation tonometry in the second trimester of pregnancy, at the time of the uterine artery Doppler imaging. Among the 140 women participating in the study 29 developed PE (PE group) and 111 did not (non-PE group). Compared to the non-PE group, women that developed PE had higher central systolic (94.9 ± 8.6 mmHg vs 104.3 ± 11.1 mmHg; p  =  < 0.01) and diastolic (64.0 ± 6.0 vs 72.4 ± 9.1; p < 0.01) blood pressures. All the arterial stiffness indices were adjusted for possible confounders and expressed as multiples of the median (MoM) of the non-PE group. The adjusted median augmentation index was similar between the two groups (p  =  0.84). The adjusted median pulse wave velocities were higher in the PE group compared to the non-PE group (carotid-femoral: 1.10 ± 0.14 MoMs vs 0.99 ± 0.11 MoMs; p < 0.01 and carotid-radial: 1.08 ± 0.12 MoMs vs 1.0 ± 0.11 MoMs; p < 0.01). CONCLUSIONS/SIGNIFICANCE: Increased maternal arterial stiffness, as assessed by pulse wave velocity, predates the development of PE in at risk women

Essential versus accessory aspects of cell death: recommendations of the NCCD 2015

Cells exposed to extreme physicochemical or mechanical stimuli die in an uncontrollable manner, as a result of their immediate structural breakdown. Such an unavoidable variant of cellular demise is generally referred to as ‘accidental cell death’ (ACD). In most settings, however, cell death is initiated by a genetically encoded apparatus, correlating with the fact that its course can be altered by pharmacologic or genetic interventions. ‘Regulated cell death’ (RCD) can occur as part of physiologic programs or can be activated once adaptive responses to perturbations of the extracellular or intracellular microenvironment fail. The biochemical phenomena that accompany RCD may be harnessed to classify it into a few subtypes, which often (but not always) exhibit stereotyped morphologic features. Nonetheless, efficiently inhibiting the processes that are commonly thought to cause RCD, such as the activation of executioner caspases in the course of apoptosis, does not exert true cytoprotective effects in the mammalian system, but simply alters the kinetics of cellular demise as it shifts its morphologic and biochemical correlates. Conversely, bona fide cytoprotection can be achieved by inhibiting the transduction of lethal signals in the early phases of the process, when adaptive responses are still operational. Thus, the mechanisms that truly execute RCD may be less understood, less inhibitable and perhaps more homogeneous than previously thought. Here, the Nomenclature Committee on Cell Death formulates a set of recommendations to help scientists and researchers to discriminate between essential and accessory aspects of cell death

The Intensive Diet and Exercise for Arthritis (IDEA) trial: design and rationale

Background: Obesity is the most modifiable risk factor, and dietary induced weight loss potentially the best nonpharmacologic intervention to prevent or to slow osteoarthritis (OA) disease progression. We are currently conducting a study to test the hypothesis that intensive weight loss will reduce inflammation and joint loads sufficiently to alter disease progression, either with or without exercise. This article describes the intervention, the empirical evidence to support it, and test-retest reliability data. Methods/Design: This is a prospective, single-blind, randomized controlled trial. The study population consists of 450 overweight and obese (BMI = 27-40.5 kg/m2) older (age greater than or equal to 55 yrs) adults with tibiofemoral osteoarthritis. Participants are randomized to one of three 18-month interventions: intensive dietary restriction-plus-exercise; exercise-only; or intensive dietary restriction-only. The primary aims are to compare the effects of these interventions on inflammatory biomarkers and knee joint loads. Secondary aims will examine the effects of these interventions on function, pain, and mobility; the dose response to weight loss on disease progression; if inflammatory biomarkers and knee joint loads are mediators of the interventions; and the association between quadriceps strength and disease progression. Results: Test-retest reliability results indicated that the ICCs for knee joint load variables were excellent, ranging from 0.86 - 0.98. Knee flexion/extension moments were most affected by BMI, with lower reliability with the highest tertile of BMI. The reliability of the semi-quantitative scoring of the knee joint using MRI exceeded previously reported results, ranging from a low of 0.66 for synovitis to a high of 0.99 for bone marrow lesion size. Discussion: The IDEA trial has the potential to enhance our understanding of the OA disease process, refine weight loss and exercise recommendations in this prevalent disease, and reduce the burden of disability. Originally published BMC Musculoskeletal Disorders, Vol. 10, No. 93, July 200

Knee disorders in primary care: design and patient selection of the HONEUR knee cohort.

BACKGROUND: Knee complaints are a frequent reason for consultation in general practice. These patients constitute a specific population compared to secondary care patients. However, information to base treatment decisions on is generally derived from specialistic settings. Our cohort study is aimed at collecting knowledge about prognosis and prognostic factors of knee complaints presented in a primary care setting. This paper describes the methods used for data collection, and discusses potential selectiveness of patient recruitment. METHODS: This is a descriptive prospective cohort study with one-year follow-up. 40 Dutch GPs recruited consecutive patients with incident knee complaints aged 12 years and above from October 2001 to October 2003. Patients were assessed with questionnaires and standardised physical examinations. Additional measurements of subgroups included MRI for recent knee traumas and device assessed function measurements for non-traumatic patients. After the inclusion period we retrospectively searched the computerized medical files of participating GPs to obtain a sample to determine possible selective recruitment. We assessed differences in proportions of gender, traumatic onset of injury and age groups between participants and non-participants using Odds Ratios (OR) and 95% confidence intervals. RESULTS: We recruited 1068 patients. In a sample of 310 patients visiting the GP, we detected some selective recruitment, indicating an underrepresentation of patients aged 12 to 35 years (OR 1.70; 1.15-2.77), especially among men (OR 2.16; 1.12-4.18). The underrepresentation of patients with traumatic onset of injury was not statistically significant. CONCLUSION: This cohort is unique in its size, setting, and its range of both age and type of knee complaints. We believe the detected selective recruitment is unlikely to introduce significant bias, as the cohort will be divided into subgroups according to age group or traumatic onset of injury for future analyses. However, the underrepresentation of men in the age group of 12 to 35 years of age warrants caution. Based on the available data, we believe our cohort is an acceptable representation of patients with new knee complaints consulting the GP, and we expect no problems with extrapolation of the results to the general Dutch population