Corporate community relations and development: engagement with indigenous peoples

Purpose – The purpose of this paper is to increase knowledge about community relations and development (CRD) activities done in conjunction with mining activities of multinational companies affecting indigenous peoples and thus help improve relationships between them, despite continuing bad consequences the people continue to endure. It is through such better relationships that these consequences may be redressed and mitigated, and greater sharing of benefits of mining may occur, bearing in mind what constitutes benefits may differ from the perspectives of the indigenous peoples and the miners. Design/methodology/approach – A qualitative approach is taken, including interviews with company officials responsible for CRD activities, elaborated with observations, company and public documents and previous literature about these mining operations and the peoples. Findings – The CRD activities have gradually increased compared with their absence previously. They are officially labelled social investment in community development programmes, and are funded from profits and couched in terms of human development, human rights, preservation of culture and physical development of infrastructure. Dissatisfied with programme quality and relevance, company officials now relate with indigenous people, their leaders and representatives in ways called engagement and partnerships. Practical implications – The findings can inform policies and practices of the parties to CRD, which in this West Papua case would be the miners and their company, CRD practitioners, the indigenous peoples and the civil authorities at the local and national level and aid industry participants. Social implications – The study acknowledges and addresses social initiatives to develop the indigenous peoples affected by mining. Originality/value – The study extends older studies in the same territory before CRD had matured, and corroborates and elaborates other studies of CRD in different territories

Neurofilament light protein in blood as a potential biomarker of neurodegeneration in Huntington's disease: a retrospective cohort analysis

BACKGROUND: Blood biomarkers of neuronal damage could facilitate clinical management of and therapeutic development for Huntington's disease. We investigated whether neurofilament light protein NfL (also known as NF-L) in blood is a potential prognostic marker of neurodegeneration in patients with Huntington's disease. METHODS: We did a retrospective analysis of healthy controls and carriers of CAG expansion mutations in HTT participating in the 3-year international TRACK-HD study. We studied associations between NfL concentrations in plasma and clinical and MRI neuroimaging findings, namely cognitive function, motor function, and brain volume (global and regional). We used random effects models to analyse cross-sectional associations at each study visit and to assess changes from baseline, with and without adjustment for age and CAG repeat count. In an independent London-based cohort of 37 participants (23 HTT mutation carriers and 14 controls), we further assessed whether concentrations of NfL in plasma correlated with those in CSF. FINDINGS: Baseline and follow-up plasma samples were available from 97 controls and 201 individuals carrying HTT mutations. Mean concentrations of NfL in plasma at baseline were significantly higher in HTT mutation carriers than in controls (3·63 [SD 0·54] log pg/mL vs 2·68 [0·52] log pg/mL, p<0·0001) and the difference increased from one disease stage to the next. At any given timepoint, NfL concentrations in plasma correlated with clinical and MRI findings. In longitudinal analyses, baseline NfL concentration in plasma also correlated significantly with subsequent decline in cognition (symbol-digit modality test r=–0·374, p<0·0001; Stroop word reading r=–0·248, p=0·0033), total functional capacity (r=–0·289, p=0·0264), and brain atrophy (caudate r=0·178, p=0·0087; whole-brain r=0·602, p<0·0001; grey matter r=0·518, p<0·0001; white matter r=0·588, p<0·0001; and ventricular expansion r=–0·589, p<0·0001). All changes except Stroop word reading and total functional capacity remained significant after adjustment for age and CAG repeat count. In 104 individuals with premanifest Huntington's disease, NfL concentration in plasma at baseline was associated with subsequent clinical onset during the 3-year follow-up period (hazard ratio 3·29 per log pg/mL, 95% CI 1·48–7·34, p=0·0036). Concentrations of NfL in CSF and plasma were correlated in mutation carriers (r=0·868, p<0·0001). INTERPRETATION: NfL in plasma shows promise as a potential prognostic blood biomarker of disease onset and progression in Huntington's disease

Huntington disease: natural history, biomarkers and prospects for therapeutics

Huntington disease (HD) can be seen as a model neurodegenerative disorder, in that it is caused by a single genetic mutation and is amenable to predictive genetic testing, with estimation of years to predicted onset, enabling the entire range of disease natural history to be studied. Structural neuroimaging biomarkers show that progressive regional brain atrophy begins many years before the emergence of diagnosable signs and symptoms of HD, and continues steadily during the symptomatic or 'manifest' period. The continued development of functional, neurochemical and other biomarkers raises hopes that these biomarkers might be useful for future trials of disease-modifying therapeutics to delay the onset and slow the progression of HD. Such advances could herald a new era of personalized preventive therapeutics. We describe the natural history of HD, including the timing of emergence of motor, cognitive and emotional impairments, and the techniques that are used to assess these features. Building on this information, we review recent progress in the development of biomarkers for HD, and potential future roles of these biomarkers in clinical trials

Cerebrospinal fluid total tau concentration predicts clinical phenotype in Huntington's disease

Huntington's disease (HD) is a hereditary neurodegenerative condition with no therapeutic intervention known to alter disease progression, but several trials are ongoing and biomarkers of disease progression are needed. Tau is an axonal protein, often altered in neurodegeneration, and recent studies pointed out its role on HD neuropathology. Our goal was to study whether cerebrospinal fluid (CSF) tau is a biomarker of disease progression in HD. After informed consent, healthy controls, pre-symptomatic and symptomatic gene expansion carriers were recruited from two HD clinics. All participants underwent assessment with the Unified HD Rating Scale '99 (UHDRS). CSF was obtained according to a standardized lumbar puncture protocol. CSF tau was quantified using enzyme-linked immunosorbent assay. Comparisons between two groups were tested using ANCOVA. Pearson's correlation coefficients were calculated for disease progression. Significance level was defined as p<0.05. Seventy-six participants were included in this cross-sectional multicentre international pilot study. Age-adjusted CSF tau was significantly elevated in gene expansion carriers compared with healthy controls (p=0.002). UHDRS total functional capacity was significantly correlated with CSF tau (r=-0.29, p=0.004) after adjustment for age, and UHDRS total motor score was significantly correlated with CSF tau after adjustment for age (r=0.32, p=0.002). Several UHDRS cognitive tasks were also significantly correlated with CST total tau after age-adjustment. This study confirms that CSF tau concentrations in HD gene mutation carriers are increased comparing with healthy controls and reports for the first time that CSF tau concentration is associated with phenotypic variability in HD. These conclusions strengthen the case for CSF tau as a biomarker in HD. This article is protected by copyright. All rights reserved

Grifonin-1: A Small HIV-1 Entry Inhibitor Derived from the Algal Lectin, Griffithsin

Background: Griffithsin, a 121-residue protein isolated from a red algal Griffithsia sp., binds high mannose N-linked glycans of virus surface glycoproteins with extremely high affinity, a property that allows it to prevent the entry of primary isolates and laboratory strains of T- and M-tropic HIV-1. We used the sequence of a portion of griffithsin's sequence as a design template to create smaller peptides with antiviral and carbohydrate-binding properties. Methodology/Results: The new peptides derived from a trio of homologous β-sheet repeats that comprise the motifs responsible for its biological activity. Our most active antiviral peptide, grifonin-1 (GRFN-1), had an EC50 of 190.8±11.0 nM in in vitro TZM-bl assays and an EC50 of 546.6±66.1 nM in p24gag antigen release assays. GRFN-1 showed considerable structural plasticity, assuming different conformations in solvents that differed in polarity and hydrophobicity. Higher concentrations of GRFN-1 formed oligomers, based on intermolecular β-sheet interactions. Like its parent protein, GRFN-1 bound viral glycoproteins gp41 and gp120 via the N-linked glycans on their surface. Conclusion: Its substantial antiviral activity and low toxicity in vitro suggest that GRFN-1 and/or its derivatives may have therapeutic potential as topical and/or systemic agents directed against HIV-1

Huntington's disease

Huntington’s disease is devastating to patients and their families — with autosomal dominant inheritance, onset typically in the prime of adult life, progressive course and combination of motor, cognitive and behavioural features. The disease is caused by an expanded CAG trinucleotide repeat (of variable length) in HTT, the gene which encodes the protein huntingtin. In mutation carriers, huntingtin is produced with abnormally long polyglutamine sequences that confers toxic gains of function and predispose the protein to fragmentation, resulting in neuronal dysfunction and death. In this Primer, we review the epidemiology of Huntington’s disease, noting that prevalence is higher than previously thought, geographically variable and increasing. We describe the relationship between CAG repeat length and clinical phenotype and the concept of genetic modifiers of the disease. We discuss normal huntingtin protein function, evidence for differential toxicity of mutant huntingtin variants, theories of huntingtin aggregation and the many different mechanisms of Huntington’s disease pathogenesis. We describe the genetic and clinical diagnosis of the condition, its clinical assessment and the multidisciplinary management of symptoms, given the absence of effective disease-modifying therapies. We review past and present clinical trials and therapeutic strategies under investigation, including impending trials of targeted huntingtin-lowering drugs and the progress in development of biomarkers that will support the next generation of trials

Neurofilament light protein in blood predicts regional atrophy in Huntington disease

Objective: Neurofilament light (NfL) protein in blood plasma has been proposed as a prognostic biomarker of neurodegeneration in a number of conditions, including Huntington disease (HD). This study investigates the regional distribution of NfL-associated neural pathology in HD gene expansion carriers. / Methods: We examined associations between NfL measured in plasma and regionally specific atrophy in cross-sectional (n = 198) and longitudinal (n = 177) data in HD gene expansion carriers from the international multisite TRACK-HD study. Using voxel-based morphometry, we measured associations between baseline NfL levels and both baseline gray matter and white matter volume; and longitudinal change in gray matter and white matter over the subsequent 3 years in HD gene expansion carriers. / Results: After controlling for demographics, associations between increased NfL levels and reduced brain volume were seen in cortical and subcortical gray matter and within the white matter. After also controlling for known predictors of disease progression (age and CAG repeat length), associations were limited to the caudate and putamen. Longitudinally, NfL predicted subsequent occipital gray matter atrophy and widespread white matter reduction, both before and after correction for other predictors of disease progression. / Conclusions: These findings highlight the value of NfL as a dynamic marker of brain atrophy and, more generally, provide further evidence of the strong association between plasma NfL level, a candidate blood biomarker, and pathologic neuronal change

Health-related quality of life in diabetic patients and controls without diabetes in refugee camps in the Gaza strip: a cross-sectional study

BACKGROUND: Prevalence of diabetes mellitus is increasing in developed and developing countries. Diabetes is known to strongly affect the health-related quality of life (HRQOL). HRQOL is also influenced by living conditions. We analysed the effects of having diabetes on HRQOL under the living conditions in refugee camps in the Gaza strip. METHODS: We studied a sample of 197 diabetic patients who were recruited from three refugee camps in the Gaza strip and 197 age- and sex-matched controls living in the same camps. To assess HRQOL, we used the World Health Organization Quality of Life questionnaire (WHOQOL-BREF) including four domains (physical health, psychological, social relations and environment). Domain scores were compared for cases (diabetic patients) and controls (persons without diabetes) and the impact of socio-economic factors was evaluated in both groups. RESULTS: All domains were strongly reduced in diabetic patients as compared to controls, with stronger effects in physical health (36.7 vs. 75.9 points of the 0–100 score) and psychological domains (34.8 vs. 70.0) and weaker effects in social relationships (52.4 vs. 71.4) and environment domains (23.4 vs. 36.2). The impact of diabetes on HRQOL was especially severe among females and older subjects (above 50 years). Low socioeconomic status had a strong negative impact on HRQOL in the younger age group (<50 years). CONCLUSION: HRQOL is strongly reduced in diabetic patients living in refugee camps in the Gaza strip. Women and older patients are especially affected

In-reach specialist nursing teams for residential care homes : uptake of services, impact on care provision and cost-effectiveness

Background: A joint NHS-Local Authority initiative in England designed to provide a dedicated nursing and physiotherapy in-reach team (IRT) to four residential care homes has been evaluated.The IRT supported 131 residents and maintained 15 'virtual' beds for specialist nursing in these care homes. Methods: Data captured prospectively (July 2005 to June 2007) included: numbers of referrals; reason for referral; outcome (e.g. admission to IRT bed, short-term IRT support); length of stay in IRT; prevented hospital admissions; early hospital discharges; avoided nursing home transfers; and detection of unrecognised illnesses. An economic analysis was undertaken. Results: 733 referrals were made during the 2 years (range 0.5 to 13.0 per resident per annum)resulting in a total of 6,528 visits. Two thirds of referrals aimed at maintaining the resident's independence in the care home. According to expert panel assessment, 197 hospital admissions were averted over the period; 20 early discharges facilitated; and 28 resident transfers to a nursing home prevented. Detection of previously unrecognised illnesses accounted for a high number of visits. Investment in IRT equalled £44.38 per resident per week. Savings through reduced hospital admissions, early discharges, delayed transfers to nursing homes, and identification of previously unrecognised illnesses are conservatively estimated to produce a final reduction in care cost of £6.33 per resident per week. A sensitivity analysis indicates this figure might range from a weekly overall saving of £36.90 per resident to a 'worst case' estimate of £2.70 extra expenditure per resident per week. Evaluation early in implementation may underestimate some cost-saving activities and greater savings may emerge over a longer time period. Similarly, IRT costs may reduce over time due to the potential for refinement of team without major loss in effectiveness. Conclusion: Introduction of a specialist nursing in-reach team for residential homes is at least cost neutral and, in all probability, cost saving. Further benefits include development of new skills in the care home workforce and enhanced quality of care. Residents are enabled to stay in familiar surroundings rather than unnecessarily spending time in hospital or being transferred to a higher dependency nursing home setting

Prevalence and correlates of inadequate glycaemic control: results from a nationwide survey in 6,671 adults with diabetes in Brazil

Diabetes is a significant public health burden on the basis of its increased incidence, morbidity, and mortality. This study aimed to estimate the prevalence of inadequate glycaemic control and its correlates in a large multicentre survey of Brazilian patients with diabetes. A cross-sectional study was conducted in a consecutive sample of patients aged 18 years or older with either type 1 or type 2 diabetes, attending health centres located in ten large cities in Brazil (response rate = 84%). Information about diabetes, current medications, complications, diet, and satisfaction with treatment were obtained by trained interviewers, using a standardized questionnaire. Glycated haemoglobin (HbA1c) was measured by high-performance liquid chromatography in a central laboratory. Patients with HbA1c ≥ 7 were considered to have inadequate glycaemic control. Overall 6,701 patients were surveyed, 979 (15%) with type 1 and 5,692 (85%) with type 2 diabetes. The prevalence of inadequate glycaemic control was 76%. Poor glycaemic control was more common in patients with type 1 diabetes (90%) than in those with type 2 (73%), P < 0.001. Characteristics significantly associated with improved glycaemic control included: fewer years of diabetes duration, multi professional care, participation in a diabetes health education program, and satisfaction with current diabetes treatment. Despite increased awareness of the benefits of tight glycaemic control, we found that few diabetic patients in Brazil met recommended glycaemic control targets. This may contribute to increased rates of diabetic complications, which may impact health care costs. Our data support the public health message of implementation of early, aggressive management of diabetes