102 research outputs found
Investigation of rheumatoid arthritis susceptibility genes identifies association of AFF3 and CD226 variants with response to anti-tumour necrosis factor treatment
No full textBackground Anti-tumour necrosis factor (anti-TNF) therapy has proved to be highly successful in treating rheumatoid arthritis (RA), although 30-40% of patients have little or no response. The authors hypothesise that this may be genetically determined. In other complex diseases, susceptibility genes have been shown to influence treatment response. The aim of the current study was to investigate the association of markers within confirmed RA susceptibility loci with the response to anti-TNF treatment. Methods Eighteen single nucleotide polymorphisms (SNPs) mapping to 11 genetic loci were genotyped in 1012 patients with RA receiving treatment with etanercept, infliximab or adalimumab. Multivariate linear regression analyses were performed using the absolute change in 28 joint count disease activity score (DAS28) between baseline and 6-month follow-up as the outcome variable, adjusting for confounders. p Values <0.05 were considered statistically significant and associated markers were genotyped in an additional 322 samples. Analysis was performed in the combined cohort of 1334 subjects with RA treated with anti-TNF. Results In the combined analysis, SNPs mapping to AFF3 and CD226 had a statistically significant association with the response to anti-TNF treatment under an additive model. The G allele at rs10865035, mapping to AFF3, was associated with an improved response to anti-TNF treatment (coefficient -0.14 (95% CI -0.25 to -0.03), p = 0.015). At the CD226 SNP rs763361, the C allele conferred reduced response to treatment (coefficient 0.11 (95% CI 0.00 to 0.22), p = 0.048). Conclusion These results suggest that AFF3 and CD226, two confirmed RA susceptibility genes, have an additional role in influencing the response to anti-TNF treatment
The use of specialisation indices to predict vulnerability of coral-feeding butterflyfishes to environmental change
No full textAuthor Posting. © The Author(s), 2011. This is the author's version of the work. It is posted here by permission of John Wiley & Sons for personal use, not for redistribution. The definitive version was published in Oikos 121 (2012): 191-200, doi:10.1111/j.1600-0706.2011.19409.x.In the absence of detailed assessments of extinction risk, ecological specialisation is often used as a proxy of vulnerability to environmental disturbances and extinction risk. Numerous indices can be used to estimate specialisation; however, the utility of these different indices to predict vulnerability to future environmental change is unknown. Here we compare the performance of specialisation indices using coral-feeding butterflyfishes as a model group. Our aims were to (i) quantify the dietary preferences of 3 butterflyfish species across habitats with differing levels of resource availability; (ii) investigate how estimates of dietary specialisation vary with the use of different specialisation indices; (iii) determine which specialisation indices best inform predictions of vulnerability to environmental change; and (iv) assess the utility of resource selection functions to inform predictions of vulnerability to environmental change. The relative level of dietary specialisation estimated for all three species varied when different specialisation indices were used, indicating that the choice of index can have a considerable impact upon estimates of specialisation. Specialisation indices that do not consider resource abundance may fail to distinguish species that primarily use common resources from species that actively target resources disproportionately more than they are available. Resource selection functions provided the greatest insights into the potential response of species to changes in resource availability. Examination of resource selection functions, in addition to specialisation indices, indicated that Chaetodon trifascialis was the most specialised feeder, with highly conserved dietary preferences across all sites, suggesting that this species is highly vulnerable to the impacts of climate-induced coral loss on reefs. Our results indicate that vulnerability assessments based on some specialisation indices may be misleading and the best estimates of dietary specialisation will be provided by indices which incorporate resource availability measures, as well as assessing responses of species to changes in resource availability.This research was funded in part by a Queensland Government Smart State PhD Scholarship and a Wildlife Preservation Society of Australia grant to RJL and a Sir Keith Murdoch Fellowship from the American Australian Association to MLB.2012-07-1
Crime and imprisonment in South Africa with particular reference to prison labour
No full textIn this thesis, which records research into prisoner employment practices in various countries and makes certain recommendations for the development of correctional treatment in South Africa, the author has started from the premise that, justifiably or not, imprisonment as a major penal sanction will be with us for the foreseeable future. Furthermore, it is probable that the average length of time being served by prisoners will increase as greater use is made of non-custodial methods of treatment. The treatment of juvenile offenders has been deliberately excluded throughout. Assuming that the aim of imprisonment is to reform/rehabilitate offenders, in addition to keeping them in safe custody, then everything practicable should be done to enhance the possibility of achieving this goal
Effects of selective digestive decontamination (SDD) on the gut resistome
No full textObjectives: Selective digestive decontamination (SDD) is an infection prevention measure for critically ill patients in intensive care units (ICUs) that aims to eradicate opportunistic pathogens from the oropharynx and intestines, while sparing the anaerobic flora, by the application of non-absorbable antibiotics. Selection for antibioticresistant bacteria is still a major concern for SDD. We therefore studied the impact of SDD on the reservoir of antibiotic resistance genes (i.e. the resistome) by culture-independent approaches. Methods: We evaluated the impact of SDD on the gut microbiota and resistome in a single ICU patient during and after an ICU stay by several metagenomic approaches. We also determined by quantitative PCR the relative abundance of two common aminoglycoside resistance genes in longitudinally collected samples from 12 additional ICU patients who received SDD. Results: The patientmicrobiotawas highly dynamic during the hospital stay. The abundance of antibiotic resistance genes more than doubled during SDD use, mainly due to a 6.7-fold increase in aminoglycoside resistance genes, in particular aph(2â 3)-Ib and an aadE-like gene.We show that aph(2â 3)-Ib is harboured by anaerobic gut commensals and is associated with mobile genetic elements. In longitudinal samples of 12 ICU patients, the dynamics of these two genes ranged from a ~104 fold increase to a ~10-10 fold decrease in relative abundance during SDD. Conclusions: ICU hospitalization and the simultaneous application of SDD has large, but highly individualized, effects on the gut resistome of ICU patients. Selection for transferable antibiotic resistance genes in anaerobic commensal bacteria could impact the risk of transfer of antibiotic resistance genes to opportunistic pathogens. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved
Unexplained macrocytosis
No full textOBJECTIVES: Macrocytosis is a relatively common finding in adult patients undergoing blood cell counting. Approximately 10percent of patients will have unexplained macrocytosis after laboratory evaluation. Data on the approach to patients with unexplained macrocytosis are limited. METHODS: To investigate this topic and help delineate an approach to this condition, the records of 9779 patients diagnosed in our institution between 1995 and 2005 as having macrocytosis were reviewed. Patients with evidence of liver disease, alcohol abuse, hypothyroidism, folate or vitamin B12 deficiency, hemolysis, or use of any drugs known to cause macrocytosis were excluded. RESULTS: Forty-three patients were found to have unexplained macrocytosis. The median follow-up was 4 years. A total of 11.6percent patients developed a primary bone marrow disorder (two B-cell lymphomas, two with myelodysplastic syndrome, one plasma cell disorder), 16.3percent developed worsening cytopenias, 69.7percent had stable disease, and 2.3percent resolved. The median time to first cytopenia was 18 months, and the mean time to diagnosis of bone marrow disorder was 31.6 months. The outcomes were not significantly different when comparing patients with or without anemia upon diagnosis. The probability of a bone marrow biopsy to establish a diagnosis of a primary disorder was 33.3percent in patients with macrocytosis without anemia compared with 75percent in patients with macrocytosis with anemia. CONCLUSIONS: Patients with unexplained macrocytosis still require close follow-up. We suggest a strategy of follow-up with blood cell counting every 6 months. Bone marrow biopsy should be performed when cytopenias are present because this approach may provide a higher yield of diagnosis and aid with therapeutic decisions.Copyright © 2013 The Southern Medical Association.ANTTILA P, 1995, BRIT J HAEMATOL, V90, P797, DOI 10.1111-j.1365-2141.1995.tb05198.x; BREEDVELD FC, 1981, ACTA MED SCAND, V209, P319; COLONOTERO G, 1992, MED CLIN N AM, V76, P581; DAVIDSON RJL, 1978, J CLIN PATHOL, V31, P493, DOI 10.1136-jcp.31.5.493; DONOFRIO G, 1995, BLOOD, V85, P818; HATTERSL.PG, 1971, AM J CLIN PATHOL, V55, P442; Hoffbrand V, 1997, BRIT MED J, V314, P430; Horstman AL, 2005, EUR J HAEMATOL, V75, P146, DOI 10.1111-j.1600-0609.2005.00441.x; Khalife MA, 2010, BLOOD, V116, P1925; LINDENBAUM J, 1983, BLOOD, V61, P624; Ma X, 2007, CANCER, V109, P1536, DOI 10.1002-cncr.22570; Mahmoud MY, 1996, AGE AGEING, V25, P310, DOI 10.1093-ageing-25.4.310; National Cancer Institute, SEER CANC STAT REV 1; WYMER A, 1990, J GEN INTERN MED, V5, P192, DOI 10.1007-BF02600531; YOUNG M, 1975, J CLIN PATHOL, V28, P12, DOI 10.1136-jcp.28.1.1211
The prospect of providing low-income medium density housing in developing countries : problems and opportunities with special reference to Cape Town, South Africa
No full textIncludes bibliography.It is thus proposed in this thesis that low-income medium-density developments, located appropriately in inner city areas to kick-start settlements that are integrated, compact and promote mixed land uses, as well as aspiring towards sustainable urban development, are needed in the cities of developing countries. A typical example of such a housing development is Springfield Terrace Woodstock, Cape Town. This pilot project, demonstrating how the provision oflow-income medium-density housing (in the fonn of three- to four-storey walk-up blocks of flats) can be provided in central Cape Town and how these benefit from the existing bulk infrastructure. It further demonstrates how this housing type could be located and utilised to encourage a shift away from low-density to medium-density housing, particularly with regard to lowincome earners
a systematic review and individual patient data meta-analysis
No full textFunding Information: RJC, BEB, MJG, RJL, JAS, and RNP are supported by Australian National Health and Medical Research Council (NHMRC) Investigator Grants (1194702, 2016792, 2017436, 1173210, 1196068, and 2008501). CSC works at Shoklo Malaria Research Unit, which is supported by the Wellcome Trust (220211). LC is supported by a US National Institutes of Health grant (U19 AI089672). MJG was supported by grants from the Malaysian Ministry of Health (BP00500420) and AusAID (108-07). NJW is a Wellcome Trust Principal Fellow (093956/Z/10/C). JH receives salary support from the US President's Malaria Initiative. This research was supported by grants from Medicines for Malaria Venture (MMV PO21/00478) and Bill & Melinda Gates Foundation (BMGF 024389). We thank all patients and staff who participated in these clinical trials at all the sites, and the WWARN team for technical and administrative support. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the US Centers for Disease Control and Prevention nor President's Malaria Initiative. Publisher Copyright: © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licenseBackground: Primaquine, the only widely available treatment to prevent relapsing Plasmodium vivax malaria, is produced as 15 mg tablets, and new paediatric formulations are being developed. To inform the optimal primaquine dosing regimen for children, we aimed to determine the efficacy and safety of different primaquine dose strategies in children younger than 15 years. Methods: We undertook a systematic review (Jan 1, 2000–July 26, 2024) for P vivax efficacy studies with at least one treatment group that was administered primaquine over multiple days, that enrolled children younger than 15 years, that followed up patients for at least 28 days, and that had data available for inclusion by June 30, 2022. Patients were excluded if they were aged 15 years or older, presented with severe malaria, received adjunctive antimalarials within 14 days of diagnosis, commenced primaquine more than 7 days after starting schizontocidal treatment, had a protocol violation in the original study, or were missing data on age, sex, or primaquine dose. Available individual patient data were collated and standardised. To evaluate efficacy, the risk of recurrent P vivax parasitaemia between days 7 and 180 was assessed by time-to-event analysis for different total mg/kg primaquine doses (low total dose of ∼3·5 mg/kg and high total dose of ∼7 mg/kg). To evaluate tolerability and safety, the following were assessed by daily mg/kg primaquine dose (low daily dose of ∼0·25 mg/kg, intermediate daily dose of ∼0·5 mg/kg, and high daily dose of ∼1 mg/kg): gastrointestinal symptoms (vomiting, anorexia, or diarrhoea) on days 5–7, haemoglobin decrease of at least 25% to less than 7g/dL (severe haemolysis), absolute change in haemoglobin from day 0 to days 2–3 or days 5–7, and any serious adverse events within 28 days. This study is registered with PROSPERO, CRD42021278085. Findings: In total, 3514 children from 27 studies and 15 countries were included. The cumulative incidence of recurrence by day 180 was 51·4% (95% CI 47·0–55·9) following treatment without primaquine, 16·0% (12·4–20·3) following a low total dose of primaquine, and 10·2% (8·4–12·3) following a high total dose of primaquine. The hazard of recurrent P vivax parasitaemia in children younger than 15 years was reduced following primaquine at low total doses (adjusted hazard ratio [HR] 0·17, 95% CI 0·11–0·25) and high total doses (0·09, 0·07–0·12), compared with no primaquine. In 525 children younger than 5 years, the relative rates of recurrence were also reduced, with an adjusted HR of 0·33 (95% CI 0·18–0·59) for a low total dose and 0·13 (0·08–0·21) for a high total dose of primaquine compared with no primaquine. The rate of recurrence following a high total dose was reduced compared with a low dose in children younger than 15 years (adjusted HR 0·54, 95% CI 0·35–0·85) and children younger than 5 years (0·41, 0·21–0·78). Compared with no primaquine, children treated with any dose of primaquine had a greater risk of gastrointestinal symptoms on days 5–7 after adjustment for confounders, with adjusted risks of 3·9% (95% CI 0–8·6) in children not treated with primaquine, 9·2% (0–18·7) with a low daily dose of primaquine, 6·8% (1·7–12·0) with an intermediate daily dose of primaquine, and 9·6% (4·8–14·3) with a high daily dose of primaquine. In children with 30% or higher glucose-6-phosphate dehydrogenase (G6PD) activity, there were few episodes of severe haemolysis following no primaquine (0·4%, 95% CI 0·1–1·5), a low daily dose (0·0%, 0·0–1·6), an intermediate daily dose (0·5%, 0·1–1·4), or a high daily dose (0·7%, 0·2–1·9). Of 15 possibly drug-related serious adverse events in children, two occurred following a low, four following an intermediate, and nine following a high daily dose of primaquine. Interpretation: A high total dose of primaquine was highly efficacious in reducing recurrent P vivax parasitaemia in children compared with a low dose, particularly in children younger than 5 years. In children treated with high and intermediate daily primaquine doses compared with low daily doses, there was no increase in gastrointestinal symptoms or haemolysis (in children with 30% or higher G6PD activity), but there were more serious adverse events. Funding: Medicines for Malaria Venture, Bill & Melinda Gates Foundation, and Australian National Health and Medical Research Council.publishersversionpublishe
Stiffness in human joints
No full textArticular stiffness is an important symptom in most arthritic diseases and appears to be a useful marker of disease activity in rheumatoid arthritis. Attempts to obtain a reliable objective measure of articular stiffness span the last 30 years but a meaningful measure
of this symptom remains elusive. A number of reasons have been suggested to explain the discrepancy between objective and subjective stiffness in arthritis and these can be
summarised as: a semeiological confusion, aberrant mechano-receptor thresholds and concurrent muscle wasting. This thesis examines each of these hypotheses.
Some patients may confuse pain and stiffness or may wish to use other words to describe their joint symptoms. A questionnaire was developed which enabled patients
to express their joint symptomatology using a wide range of descriptors. No differences were found between health professionals and patients in their definition of each of the descriptors. The questionnaire discriminated clearly between groups of patients with rheumatoid arthritis, ankylosing spondylitis and non-articular rheumatism.
Movement perception threshold was measured in the finger but it was found that subjects relied on cutaneous information. Vibration perception threshold was used as
an alternative measure of mechano-receptor thresholds: no abnormalities were found in 50 patients with rheumatoid arthritis.
Muscle cross-sectional area was calculated from anthropometric data and the results compared with measurements obtained from computed tomographic scans. A
significant decrease in forearm muscle cross-sectional area was found in rheumatoid arthritis but the decrease was not sufficient to explain the reduction in grip strength
observed, some of the variation being explained by deformity and pain in the joints. From this study it was possible to make a correction for muscle wasting in previously published stiffness data, revealing significant increases in metacarpo-phalangeal joint stiffness in rheumatoid arthritis. This result was confirmed in new data based on the resonant frequency of the wrist. Further data on the qualitative aspects of muscle were obtained by relating dynamic angular wrist stiffness to level of contraction of forearm muscles. Although arthritic subjects differed significantly from normals at maximum activation, when the results were expressed in terms of absolute grip strength no differences were found, suggesting inhibition of muscle activation in rheumatoid arthritis.
It is concluded that symptomatic stiffness is objectively quantifiable in arthritis providing measurements are made in relationship to the equilibrium position of the joint
and providing a correction is made for muscle wasting
Cyrtopogon martini Lavigne & Dennis 2019, sp. nov.
No full textCyrtopogon martini Lavigne & Dennis sp. nov. Holotype male: Length 11 mm. Head: black; face and frons densely golden tomentose, gray pollinose spot laterally at base antennae; occiput golden pollinose at eye margins fading to gray; palpi and proboscis black. Mystax black with few brownish white setae in center; setae of frons, ocellar tubercle, upper occiput, entire eye margin, first two antennal segmenss, and second palpal segment black; beard, setae of proboscis and first palpal segment white. First two antennal segments and style black; third orange; first segment 1 1/5 times longer than second; third 1 1/3 times length first two segments together; style with apical spine one fourth length third; two strong black bristles subapically below on second point, slender third bristle also present. Thorax: largely shining black, brown pollinose; spots of golden tomentum at base postpronotal lobe, below on notopleura, below supraalar bristles, parallel to midline behind transverse suture and centrally at apex of mesonotum; pair central stripes light brown pollinose bisected by narrow golden tomentose median stripe Setae and bristles mesonotum and scutellum black; 2 notopleurals, 5–6 supraalars, and 4 postalars. Scutellum largely shining black with spot of golden tomentum at base. Pleura and coxae grayish-yellow tomentose; setae pro-thorax and coxae white, those meso- and katepisternum black, merals partly black, those below brownish white. Wings: infuscated with gray cloud covering apical half subcostal cell, discal cell largely hyaline; macrotrichia on costal vein black, veins dark brown, anterior cross vein 3/11 lengthdiscal cell. Base and stem of halteres brown, knob yellow. Legs: femora black; tibiae excepting apical one-sixth black, reddish brown; the tarsi reddish brown except fore tarsi yellowish and tarsal joints mid and hind legs black above; basal third of claws reddish brown, black apically; empodium brown, pulvilli straw white. Bristles black; femora with long white setae posteriorly, long white setae below on fore femora and brownish white setae below on other femora, basal third hind femora with long white setae anteriorly and short black setae apically; setae of tibiae black except those apical 1/3 and apical 1/4 mid tarsi of fore tibiae white anteriorly; tarsal bristles black; tarsal setae black except as follows: joints 1–5 fore tarsi with narrow crest of silvery white setae dorsally, parted on all joints; joints 1 and 2 mid tarsi white setae dorsally; fore tibiae and tarsi anteriorly, hind tibiae at apex and metatarsi posteriorly with usual short golden pile. Abdomen: shining black, tergites 2–3 with posterior gray tomentose fasciae complete, narrowly interrupted on tergite 4, small spot of gray pollen posterior corner fifth tergite; brown pollinose dorsocentral areas anteriorly tergites 2–5; tergites 6–7 shining black. Setae laterally segment 1 long, straw white, dorsum, short, straw white; segment 2 with long brown setae laterally, subequal to those first segment, short brown pile dorsally fading into white posteriorly; segment 3 with black setae laterally shorter and not so dense as on preceding segments, and short black setae fading into brown dorsocentrally; short black setae dorsocentrally in two separate rows middle and apex tergites 5–7, most distinct on sixth tergite; setae of sternite 1–3 white, 4–6 black. Genitalia: shining black with short black setae except those apex of cercus brown. Holotype, male: Carbon County, Wyoming: Bottle Creek Campground, Sierra Madres Mtns., 6 July 1963 / R.J. Lavigne (deposited in USNM). Paratypes, males: Carbon County, Wyoming: Bottle Creek Campground, Sierra Madres Mtns., 6 July 1963 / R.J. Lavigne (one specimen deposited in CAS and the other in the collection of the senior author). This new species runs to couplet 19 in Wilcox & Martin’s (1936) key. It is easily differentiated from both C. glarealis Melander and C. pulcher Back by the presence of the infuscated cloud at the apex of the wings of the male C. martini. This species is named in honor of Dr. Charles Martin (deceased), eminent authority on the family Asilidae, whose patience and understanding in training beginning dipterists is greatly appreciated. Distribution: CARBON: Bottle Creek Campground, Sierra Madres Mtns., 6 July 1963 (RJL). Habitat: Douglas fir forest and sagebrush steppe shrub and grassland vegetation types. Ethology: Nothing known. Prey: None known.Published as part of Lavigne, Robert J. & Dennis, Steve, 2019, Robber flies (Insecta: Diptera: Asilidae) of Wyoming, USA with keys to genera and species, pp. 1-126 in Zootaxa 4662 (1) on pages 69-70, DOI: 10.11646/zootaxa.4662.1.1, http://zenodo.org/record/338344
- …
