940 research outputs found
Policy opportunities to enhance the role of smallholder livestock systems in Limpopo Province of South Africa
Post-apartheid administrations in South Africa were faced with redressing the legacy of multifaceted poverty and social inequalities created by apartheid politics. The entrance of smallholder farmers into the mainstream economy became a government priority and policy aim. Institutional efforts in Limpopo Province provided infrastructure to establish poultry and vegetable producing enterprises. Very few livestock projects were funded. The success rate of institutional interventions was low. We argue that smallholder livestock systems offer policy opportunities to realise post-apartheid reform goals in the smallholder livestock sector. The premises are; there are more livestock in communal smallholder sector than in the commercial sector. This indicates there is a substantial level of natural, human and social capital existing within smallholder livestock systems. Secondly, commercial livestock systems are increasingly converted to game and wildlife enterprises necessitating imports of large numbers of livestock from Namibia to account for the shortfall in red-meat in South Africa. It is possible that the low off-take characterising smallholder livestock and the Cattle Complex Philosophy probably deterred past efforts to recognise the potential of smallholder livestock systems for rural and agricultural development. The Cattle Complex Philosophy claims that African smallholders have an attitudinal resistance to sell livestock. Data from a survey amongst 193 households in ten villages of Sekhukhune District of Limpopo Province illustrates that low livestock sales relates to the dysfunctional composition, sub-optimal reproductive potential and high calf mortality of smallholder herds. Conclusions and policy recommendations are offered.Keywords: Smallholder, Livestock, Limpopo Provinc
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Evidence of association with type 1 diabetes in the SLC11A1 gene region
BackgroundLinkage and congenic strain analyses using the nonobese diabetic (NOD) mouse as a model for human type 1 autoimmune diabetes (T1D) have identified several NOD mouse Idd (insulin dependent diabetes) loci, including Slc11a1 (formerly known as Nramp1). Genetic variants in the orthologous region encompassing SLC11A1 in human chromosome 2q35 have been reported to be associated with various immune-related diseases including T1D. Here, we have conducted association analysis of this candidate gene region, and then investigated potential correlations between the most T1D-associated variant and RNA expression of the SLC11A1 gene and its splice isoform.MethodsNine SNPs (rs2276631, rs2279015, rs1809231, rs1059823, rs17235409 (D543N), rs17235416 (3'UTR), rs3731865 (INT4), rs7573065 (-237 C → T) and rs4674297) were genotyped using TaqMan genotyping assays and the polymorphic promoter microsatellite (GT)n was genotyped using PCR and fragment length analysis. A maximum of 8,863 T1D British cases and 10,841 British controls, all of white European descent, were used to test association using logistic regression. A maximum of 5,696 T1D families were also tested for association using the transmission/disequilibrium test (TDT). We considered P ≤ 0.005 as evidence of association given that we tested nine variants in total. Upon identification of the most T1D-associated variant, we investigated the correlation between its genotype and SLC11A1 expression overall or with splice isoform ratio using 42 PAXgene whole blood samples from healthy donors by quantitative PCR (qPCR).ResultsUsing the case-control collection, rs3731865 (INT4) was identified to be the variant most associated with T1D (P = 1.55 × 10-6). There was also some evidence of association at rs4674297 (P = 1.57 × 10-4). No evidence of disease association was obtained at any of the loci using the family collections (PTDT ≥ 0.13). We also did not observe a correlation between rs3731865 genotypes and SLC11A1 expression overall or with splice isoform expression.ConclusionWe conclude that rs3731685 (INT4) in the SLC11A1 gene may be associated with T1D susceptibility in the European ancestry population studied. We did not observe a difference in SLC11A1 expression at the RNA level based on the genotypes of rs3731865 in whole blood samples. However, a potential correlation cannot be ruled out in purified cell subsets especially monocytes or macrophages
THE TREATMENT OF COCCIDIOIDOMYCOSIS
SUMMARYTherapy of coccidioidomycosis continues to evolve. For primary pulmonary disease, antifungal therapy is frequently not required while prolonged courses of antifungals are generally needed for those in whom extrathoracic disseminated has occurred. Intravenous amphotericin B should be reserved for those with severe disease. Oral triazole antifungals have had a great impact on the management of coccidioidomycosis. Both fluconazole and itraconazole at 400 mg daily have been effective for various forms of coccidioidomycosis, including meningitis, although relapse after therapy is discontinued is a problem. Individuals with suppressed cellular immunity are at increased risk for symptomatic coccidioidomycosis and they include those with HIV infection, those on immunosuppressive medications, and those who have received a solid organ transplant. Pregnant women and African-American men have been identified as two other groups who are at an increased risk for symptomatic and severe infection
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Theories of behaviour change synthesised into a set of theoretical groupings: Introducing a thematic series on the Theoretical Domains Framework
Behaviour change is key to increasing the uptake of evidence into healthcare practice. Designing behaviour-change interventions first requires problem analysis, ideally informed by theory. Yet the large number of partly overlapping theories of behaviour makes it difficult to select the most appropriate theory. The need for an overarching theoretical framework of behaviour change was addressed in research in which 128 explanatory constructs from 33 theories of behaviour were identified and grouped. The resulting Theoretical Domains Framework (TDF) appears to be a helpful basis for investigating implementation problems. Research groups in several countries have conducted TDF-based studies. It seems timely to bring together the experience of these teams in a thematic series to demonstrate further applications and to report key developments. This overview article describes the TDF, provides a brief critique of the framework, and introduces this thematic series.
In a brief review to assess the extent of TDF-based research, we identified 133 papers that cite the framework. Of these, 17 used the TDF as the basis for empirical studies to explore health professionals’ behaviour. The identified papers provide evidence of the impact of the TDF on implementation research. Two major strengths of the framework are its theoretical coverage and its capacity to elicit beliefs that could signify key mediators of behaviour change. The TDF provides a useful conceptual basis for assessing implementation problems, designing interventions to enhance healthcare practice, and understanding behaviour-change processes. We discuss limitations and research challenges and introduce papers in this series
Networks link antigenic and receptor-binding sites of influenza hemagglutinin: Mechanistic insight into fitter strain propagation
Influenza viral passaging through pre-vaccinated mice shows that emergent antigenic site mutations on the viral hemagglutinin (HA) impact host receptor-binding affinity and, therefore, the evolution of fitter influenza strains. To understand this phenomenon, we computed the Significant Interactions Network (SIN) for each residue and mapped the networks of antigenic site residues on a representative H1N1 HA. Specific antigenic site residues are ‘linked’ to receptor-binding site (RBS) residues via their SIN and mutations within “RBS-linked” antigenic residues can significantly influence receptor-binding affinity by impacting the SIN of key RBS residues. In contrast, other antigenic site residues do not have such “RBS-links” and do not impact receptor-binding affinity upon mutation. Thus, a potential mechanism emerges for how immunologic pressure on RBS-linked antigenic residues can contribute to evolution of fitter influenza strains by modulating the host receptor-binding affinity
Discovery of mating in the major African livestock pathogen Trypanosoma congolense
The protozoan parasite, Trypanosoma congolense, is one of the most economically important pathogens of livestock in Africa and, through its impact on cattle health and productivity, has a significant effect on human health and well being. Despite the importance of this parasite our knowledge of some of the fundamental biological processes is limited. For example, it is unknown whether mating takes place. In this paper we have taken a population genetics based approach to address this question. The availability of genome sequence of the parasite allowed us to identify polymorphic microsatellite markers, which were used to genotype T. congolense isolates from livestock in a discrete geographical area of The Gambia. The data showed a high level of diversity with a large number of distinct genotypes, but a deficit in heterozygotes. Further analysis identified cryptic genetic subdivision into four sub-populations. In one of these, parasite genotypic diversity could only be explained by the occurrence of frequent mating in T. congolense. These data are completely inconsistent with previous suggestions that the parasite expands asexually in the absence of mating. The discovery of mating in this species of trypanosome has significant consequences for the spread of critical traits, such as drug resistance, as well as for fundamental aspects of the biology and epidemiology of this neglected but economically important pathogen
International criteria for acute kidney injury: advantages and remaining challenges
• Acute Kidney Injury (AKI) is defined using widely accepted international criteria that are based on changes in serum creatinine concentration and degree of oliguria.
• AKI, when defined in this way, has a strong association with poor patient outcomes, including high mortality rates and longer hospital admissions with increased resource utilisation and subsequent chronic kidney disease.
• The detection of AKI using current criteria can assist with AKI diagnosis and stratification of individual patient risk.
• The diagnosis of AKI requires clinical judgement to integrate the definition of AKI with the clinical situation, to determine underlying cause of AKI, and to take account of factors that may affect performance of current definitions
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Sequencing and association analysis of the type 1 diabetes - linked region on chromosome 10p12-q11
Background: In an effort to locate susceptibility genes for type I diabetes (TID) several genome-wide linkage scans have been undertaken. A chromosomal region designated IDDM10 retained genome-wide significance in a combined analysis of the main linkage scans. Here, we studied sequence polymorphisms in 23 Mb on chromosome 10p12-q11, including the putative IDDM10 region, to identify genes associated with TID. Results: Initially, we resequenced the functional candidate genes, CREM and SDF1, located in this region, genotyped 13 tag single nucleotide polymorphisms (SNPs) and found no association with TID. We then undertook analysis of the whole 23 Mb region. We constructed and sequenced a contig tile path from two bacterial artificial clone libraries. By comparison with a clone library from an unrelated person used in the Human Genome Project, we identified 12,058 SNPs. We genotyped 303 SNPs and 25 polymorphic microsatellite markers in 765 multiplex TID families and followed up 22 associated polymorphisms in up to 2,857 families. We found nominal evidence of association in six loci (P = 0.05-0.0026), located near the PAPDI gene. Therefore, we resequenced 38.8 kb in this region, found 147 SNPs and genotyped 84 of them in the TID families. We also tested 13 polymorphisms in the PAPDI gene and in five other loci in 1,612 TID patients and 1,828 controls from the UK. Overall, only the D10S193 microsatellite marker located 28 kb downstream of PAPDI showed nominal evidence of association in both TID families and in the case-control sample (P = 0.037 and 0.03, respectively). Conclusion: We conclude that polymorphisms in the CREM and SDFI genes have no major effect on TID. The weak TID association that we detected in the association scan near the PAPDI gene may be either false or due to a small genuine effect, and cannot explain linkage at the IDDM10 region
Differences between <i>Trypanosoma brucei gambiense</i> groups 1 and 2 in their resistance to killing by Trypanolytic factor 1
<p><b>Background:</b> The three sub-species of <i>Trypanosoma brucei</i> are important pathogens of sub-Saharan Africa. <i>T. b. brucei</i> is unable to infect humans due to sensitivity to trypanosome lytic factors (TLF) 1 and 2 found in human serum. <i>T. b. rhodesiense</i> and <i>T. b. gambiense</i> are able to resist lysis by TLF. There are two distinct sub-groups of <i>T. b. gambiense</i> that differ genetically and by human serum resistance phenotypes. Group 1 <i>T. b. gambiense</i> have an invariant phenotype whereas group 2 show variable resistance. Previous data indicated that group 1 <i>T. b. gambiense</i> are resistant to TLF-1 due in-part to reduced uptake of TLF-1 mediated by reduced expression of the TLF-1 receptor (the haptoglobin-hemoglobin receptor (<i>HpHbR</i>)) gene. Here we investigate if this is also true in group 2 parasites.</p>
<p><b>Methodology:</b> Isogenic resistant and sensitive group 2 <i>T. b. gambiense</i> were derived and compared to other T. brucei parasites. Both resistant and sensitive lines express the <i>HpHbR</i> gene at similar levels and internalized fluorescently labeled TLF-1 similar fashion to <i>T. b. brucei</i>. Both resistant and sensitive group 2, as well as group 1 <i>T. b. gambiense</i>, internalize recombinant APOL1, but only sensitive group 2 parasites are lysed.</p>
<p><b>Conclusions:</b> Our data indicate that, despite group 1 <i>T. b. gambiense</i> avoiding TLF-1, it is resistant to the main lytic component, APOL1. Similarly group 2 <i>T. b. gambiense</i> is innately resistant to APOL1, which could be based on the same mechanism. However, group 2 <i>T. b. gambiense</i> variably displays this phenotype and expression does not appear to correlate with a change in expression site or expression of <i>HpHbR</i>. Thus there are differences in the mechanism of human serum resistance between <i>T. b. gambiense</i> groups 1 and 2.</p>
Risk factors for incident falls in older men and women:The English longitudinal study of ageing
Background: falls are a major cause of disability and death in older people, particularly women. Cross-sectional surveys suggest that some risk factors associated with a history of falls may be sex-specific, but whether risk factors for incident falls differ between the sexes is unclear. We investigated whether risk factors for incident falls differ between men and women.Methods: participants were 3298 people aged ≥60 who took part in the Waves 4-6 surveys of the English Longitudinal Study of Ageing. At Wave 4, they provided information about sociodemographic, lifestyle, behavioural and medical factors and had their physical and cognitive function assessed. Data on incident falls during the four-year follow-up period was collected from them at Waves 5 and 6. Poisson regression with robust variance estimation was used to derive relative risks (RR) for the association between baseline characteristics and incident falls.Results: in multivariable-adjusted models that also controlled for history of falls, older age was the only factor associated with increased risk of incident falls in both sexes. Some factors were only predictive of falls in one sex, namely more depressive symptoms (RR (95% CI) 1.03 (1.01,1.06)), incontinence (1.12 (1.00,1.24)) and never having married in women (1.26 (1.03,1.53)), and greater comorbidity (1.04 (1.00,1.08)), higher levels of pain (1.10 (1.04,1.17) and poorer balance, as indicated by inability to attempt a full-tandem stand, (1.23 (1.04,1.47)) in men. Of these, only the relationships between pain, balance and comorbidity and falls risk differed significantly by sex.Conclusions: there were some differences between the sexes in risk factors for incident falls. Our observation that associations between pain, balance and comorbidity and incident falls risk varied by sex needs further investigation in other cohorts. <br/
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