The potential to control Haemonchus contortus in indigenous South African goats with copper oxide wire particles

The high prevalence of resistance of Haemonchus contortus to all major anthelmintic groups has prompted investigations into alternative control methods in South Africa, including the use of copper oxide wire particle (COWP) boluses. To assess the efficacy of COWP against H. contortus in indigenous South African goats, 18 male faecal egg-count-negative goats were each given ca.1200 infective larvae of H. contortus three times per week during weeks 1 and 2 of the experiment. These animals made up an “established” infection group (ESTGRP). At the start of week 7, six goats were each given a 2-g COWP bolus orally; six goats received a 4-g COWP bolus each and six animals were not treated. A further 20 goats constituted a “developing” infection group (DEVGRP). At the beginning of week 1, seven of the DEVGRP goats were given a 2-g COWP bolus each; seven goats were treated with a 4-g COWP bolus each and no bolus was given to a further six animals. During weeks 1–6, each of these DEVGRP goats was given ca. 400 H. contortus larvae three times per week. All 38 goats were euthanized for worm recovery from the abomasa and small intestines in week 11. In the ESTGRP, the 2-g and 4-g COWP boluses reduced the worm burdens by 95% and 93%, respectively compared to controls (mean burden ± standard deviation, SD: 23 ± 33, 30 ± 56 and 442 ± 518 worms, P = 0.02). However, in the DEVGRP goats, both the 2-g and 4-g COWP treatments were ineffective in reducing the worm burdens relative to the controls (mean burdens ± SD: 1102 ± 841, 649 ± 855, 1051 ± 661 worms, P = 0.16). Mean liver copper levels did not differ between the ESTGRP goats treated with 2-g COWP, 4-g COWP or no COWP (mean ± standard error of the mean, SEM, in ppm: 93.7 ± 8.3; 101.5 ± 8.3; 71.8 ± 8.3, P = 0.07) nor did they differ between the DEVGRP goats (mean ± SEM, in ppm: 74.1 ± 9.1; 75.4 ± 9.1; 74.9 ± 10.0, P > 0.99). The copper values were considered adequate, but not high, for goats. The COWP boluses have the potential to be used in the place of conventional anthelmintics for the control of established H. contortus infections in indigenous South African goats, but their use as part of an integrated approach to control H. contortus in the field must be fully investigated

Effectiveness of the inclusive design wheel in practice: Lessons from five pilot projects

The Inclusive Design Wheel (IDW) is an established inclusive con-cept design process, emphasizing iteration and early-stage evaluation. However, a structured evaluation of its effectiveness in practice has not been previously conducted. This paper describes how the IDW process was adapted for use in the design of digital mobility services. It was then trialled on five pilot projects in Italy, Spain, Belgium and the Netherlands. Questionnaires were completed by participants (both pilot partners and end-users) and interviews were held with pilot partners at the end of the project. Initial insights from the pilot experiences and the evaluation are described. The pilot teams found the IDW helpful and particularly valued its help in structuring the design process and offering clear steps and tools. Insights for improving the IDW focus on the importance and role of co-creation, issues with recording iteration and the balance between structure and flexibility. Implications are highlighted for improving the Inclusive Design Wheel and for inclusive design processes more generally.Peer ReviewedPreprin

Persistence of the efficacy of copper oxide wire particles against Haemonchus contortus in grazing South African goats

A study was conducted to examine the duration of anthelmintic effect of copper oxide wire particles (COWP) in grazing goats, as data for the persistence of efficacy of COWP in this host species is limited. Forty-eight indigenous male goats were infected naturally by grazing them on Haemonchus contortus-infected pasture. When the faecal egg count (FEC) in the goats was 3179 ± 540 eggs per gram of faeces (mean ± standard error), half the animals were treated with 4 g COWP (day 0; mean live weight = 25.5 ± 0.8 kg). Eight treated (COWP) and eight non-treated (CONTROL) goats were removed from the pasture on each of days 7, 28 and 56, maintained for 27 or 29 days in concrete pens and then humanely slaughtered for nematode recovery. Mean liver copper levels were in the high range in the goats removed from pasture at day 7 (treated: 191 ± 19.7 ppm; untreated: 120 ± 19.7 ppm; P = 0.022), but had dropped to normal levels at days 28 and 56. The mean H. contortus burdens of the treated versus the non-treated goats were, respectively, 184 ± 48 and 645 ± 152 for the goats removed from pasture at day 7 (71% reduction; P = 0.004), 207 ± 42 and 331 ± 156 at day 28 (37% reduction; P = 0.945) and 336 ± 89 and 225 ± 53 at day 56 (−49% reduction; P = 0.665). Weekly monitoring of FECs after treatment until slaughter indicated that the COWP-treated goats had lower FECs than the controls, the treatment main effect being significant at days 7, 28 and 56 (P < 0.01). The day main effect and the treatment × day interaction were only significant for the goats removed from pasture at day 28 (P ≤ 0.001). Packed cell volumes increased during the course of the experiment (day, P < 0.001), but the treatment main effect was significant only for the goats removed from pasture at day 28 (CONTROL 28 d, 28.65 ± 0.52% < COWP 28 d, 31.31 ± 0.52%; P < 0.001). No differences in live weight between groups were considered to be of any practical significance. The study indicated that persistence of efficacy of COWP is limited in goats, extending at most to 28 days after treatment. However, repeated COWP administration at three-month intervals may be safe, given that liver copper levels return to normal two to three months after COWP treatment

Combined FUS+ basophilic inclusion body disease and atypical tauopathy presenting with an ALS/MND-plus phenotype

AIMS: Amyotrophic lateral sclerosis / motor neurone disease (ALS/MND) is characterised by the presence of inclusions containing TDP-43 within motor neurones. In rare cases, ALS/MND may be associated with inclusions containing other proteins, such as fused in sarcoma (FUS), whilst motor system pathology may rarely be a feature of other neurodegenerative disorders. We here have investigated the association of FUS and tau pathology. METHODS: We report a case with an ALS/MND-plus clinical syndrome which pathologically demonstrated both FUS pathology and an atypical tauopathy. RESULTS: Clinical motor involvement was predominantly upper motor neurone, and was accompanied by extrapyramidal features and sensory involvement, but with only minimal cognitive impairment. The presentation was sporadic and gene mutation screening was negative. Post-mortem study demonstrated inclusions positive for FUS, including basophilic inclusion bodies. This was associated with 4R-tauopathy, largely as non-fibrillary diffuse phospho-tau in neurones, with granulovacuolar degeneration in a more restricted distribution. Double-staining revealed that neurones contained both types of protein pathology. CONCLUSION: FUS-positive basophilic inclusion body disease is a rare cause of ALS/MND, but in this case was associated with an unusual atypical tauopathy. The coexistence of two such rare neuropathologies raises the question of a pathogenic interaction

The Green, Green Grass of Home: an archaeo-ecological approach to pastoralist settlement in central Kenya

© 2016 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. This paper considers the ecological residues of pastoralist occupation at the site of Maili Sita in Laikipia, central Kenya, drawing links with the archaeological record so as to contribute a fresh approach to the ephemeral settlement sites of mobile herding communities, a methodological aspect of African archaeology that remains problematic. Variations in the geochemical and micromorphological composition of soils along transects across the site are compared with vegetation distributions and satellite imagery to propose an occupation pattern not dissimilar to contemporary Cushitic-speaking groups further north. We argue that Maili Sita exemplifies the broad migratory and cultural exchange networks in place during the mid- to late second millennium AD, with pastoralist occupants who were both physically and culturally mobile.British Academy (2002-5 Funding) European Union - Marie Curie Initiatives (EXT grant 2007-11

Tactical treatment with copper oxide wire particles and symptomatic levamisole treatment using the FAMACHA © system in indigenous goats in South Africa

Haemonchosis is considered to be the most economically important gastrointestinal disease of small ruminants in the tropics and subtropics. However, chemical anthelmintics, which were the mainstay of control, have been compromised by a high prevalence of resistance worldwide. Copper oxide wire particles (COWP) have been shown to have anthelmintic effects, but few studies have examined their use under field conditions. The use of COWP was therefore evaluated as a tactical anthelmintic treatment in indigenous goats raised under communal farming conditions in Bergville, KwaZulu-Natal Province, South Africa. At the beginning of the summer rainfall season (October 2007), the faecal egg counts of 172 female goats belonging to 15 farmers were determined and this sampling continued every four weeks until the second week of January 2008. The goats within each of the 15 herds were ranked according to their faecal egg counts for this week. The goats were sequentially paired off within each ranking starting with those goats with the highest counts. One goat from each pair was randomly allocated to a treated or control group. Two weeks later, a 4 g COWP bolus was randomly administered to each goat in the treated group. Faecal egg counts were carried out on the goats two weeks following treatment, and the sampling of the goats then proceeded every four weeks until October 2008. Except for the six-week period prior to the administration of the COWP, the goats were examined according to the FAMACHA© system and symptomatically treated with 12 mg/kg levamisole when anaemic. The percentage reduction in faecal egg count due to the COWP treatment was 89.0%. Mean pre- and post-treatment faecal egg counts for the COWP-treated group (n = 73) were 2347 eggs per gram of faeces (epg) and 264 epg, respectively. The corresponding values for the untreated controls (n = 66) were 2652 epg and 2709 epg. The prevalence of Haemonchus spp. larvae in pre- and post-treatment faecal cultures was 72% and 46%, respectively. Symptomatic anthelmintic treatments in combination with mid-summer tactical treatments with COWP appear to be useful strategies for the control of Haemonchus contortus in indigenous goats in this farming system and this approach could have application in other similar agro-ecological zones.This project was funded by The Wellcome Trust project number 075812/A/04/7, Onderstepoort Veterinary Institute (OVI), South Africa and KwaZulu-Natal Department of Agriculture, Environmental Affairs and Rural Development (KZN DoAEA&RD), South Africa.www.elsevier.com/locate/vetparhb2013ab201

Establishing mRNA and microRNA interactions driving disease heterogeneity in amyotrophic lateral sclerosis patient survival

Amyotrophic lateral sclerosis is a fatal neurodegenerative disease, associated with the degeneration of both upper and lower motor neurons of the motor cortex, brainstem and spinal cord. Death in most patients results from respiratory failure within 3–4 years from symptom onset. However, due to disease heterogeneity some individuals survive only months from symptom onset while others live for several years. Identifying specific biomarkers that aid in establishing disease prognosis, particularly in terms of predicting disease progression, will help our understanding of amyotrophic lateral sclerosis pathophysiology and could be used to monitor a patient’s response to drugs and therapeutic agents. Transcriptomic profiling technologies are continually evolving, enabling us to identify key gene changes in biological processes associated with disease. MicroRNAs are small non-coding RNAs typically associated with regulating gene expression, by degrading mRNA or reducing levels of gene expression. Being able to associate gene expression changes with corresponding microRNA changes would help to distinguish a more complex biomarker signature enabling us to address key challenges associated with complex diseases such as amyotrophic lateral sclerosis. The present study aimed to investigate the transcriptomic profile (mRNA and microRNA) of lymphoblastoid cell lines from amyotrophic lateral sclerosis patients to identify key signatures that are distinguishable in those patients who suffered a short disease duration (6 years) (n = 20). Transcriptional profiling of microRNA–mRNA interactions from lymphoblastoid cell lines in amyotrophic lateral sclerosis patients revealed differential expression of genes involved in cell cycle, DNA damage and RNA processing in patients with longer survival from disease onset compared with those with short survival. Understanding these particular microRNA–mRNA interactions and the pathways in which they are involved may help to distinguish potential therapeutic targets that could exert neuroprotective effects to prolong the life expectancy of amyotrophic lateral sclerosis patients

Measurement of the partial widths of the Z into up- and down-type quarks

Using the entire OPAL LEP1 on-peak Z hadronic decay sample, Z -> qbarq gamma decays were selected by tagging hadronic final states with isolated photon candidates in the electromagnetic calorimeter. Combining the measured rates of Z -> qbarq gamma decays with the total rate of hadronic Z decays permits the simultaneous determination of the widths of the Z into up- and down-type quarks. The values obtained, with total errors, were Gamma u = 300 ^{+19}_{-18} MeV and Gamma d = 381 ^{+12}_{-12} MeV. The results are in good agreement with the Standard Model expectation.Comment: 22 pages, 5 figures, Submitted to Phys. Letts.