Delayed dislocation following metal-on-polyethylene hip replacement due to “silent” trunnion corrosion

AimsWe present a case series of ten metal-on-polyethylene total hip arthroplasties (MoP THAs) with delayed dislocation associated with unrecognised adverse local tissue reaction due to corrosion at the trunnion and pseudotumour formation.MethodsThe diagnosis was not suspected in nine of the ten patients (six female/four male; mean age 66 years), despite treatment in a specialist unit (mean time from index surgery to revision was 58 months, 36 to 84). It was identified at revision surgery and subsequently confirmed by histological examination of resected tissue. Pre-operative assessment and culture results ruled out infection. A variety of treatment strategies were used, including resection of the pseudotumour and efforts to avoid recurrent dislocation.ResultsThe rate of complications was high and included three deep infections, two patients with recurrent dislocation, and one recurrent pseudotumour.ConclusionThis series (mean follow-up of 76 months following index procedure and 19 months following revision THA) demonstrates that pseudotumour is an infrequent but important contributor to delayed instability following MoP THA. It is easy to overlook in the differential diagnosis, especially if the alignment of the components is less than optimal, leading to an assumption that malalignment is the cause of the dislocation. The instability is likely to be multifactorial and the revision surgery is complex. Take home message: Due to the high complication rate associated with revision in this cohort, the diagnosis should be borne in mind when counselling patients regarding the risks of revision surgery. Cite this article: Bone Joint J 2016;98-B:187–93.</jats:sec

Malaria vector control at crossroads: public health entomology and the drive to elimination

Vector control has been at the core of successful malaria control. However, a dearth of field-oriented vector biologists threatens to undermine global reductions in malaria burden. Skilled cadres are needed to manage insecticide resistance, to maintain coverage with current interventions, to develop new paradigms for tackling ‘residual' transmission, and to target interventions as transmission becomes increasingly heterogeneous. Recognising this human resource crisis, in September 2013, WHO Global Malaria Programme issued guidance for capacity building in entomology and vector control, including recommendations for countries and implementing partners. Ministries were urged to develop long-range strategic plans for building human resources for public health entomology and vector control (including skills in epidemiology, geographic information systems, operational research and programme management) and to set in place the requisite professional posts and career opportunities. Capacity building and national ownership in all partner projects and a clear exit strategy to sustain human and technical resources after project completion were emphasised. Implementing partners were urged to support global and regional efforts to enhance public health entomology capacity. While the challenges inherent in such capacity building are great, so too are the opportunities to establish the next generation of public health entomologists that will enable programmes to continue on the path to malaria eliminatio

Prenatal factors contribute to the emergence of kwoshiorkor or marasmus in severe undernutrition: evidence for the predictive adaptation model

Severe acute malnutrition in childhood manifests as oedematous (kwashiorkor, marasmic kwashiorkor) and non-oedematous (marasmus) syndromes with very different prognoses. Kwashiorkor differs from marasmus in the patterns of protein, amino acid and lipid metabolism when patients are acutely ill as well as after rehabilitation to ideal weight for height. Metabolic patterns among marasmic patients define them as metabolically thrifty, while kwashiorkor patients function as metabolically profligate. Such differences might underlie syndromic presentation and prognosis. However, no fundamental explanation exists for these differences in metabolism, nor clinical pictures, given similar exposures to undernutrition. We hypothesized that different developmental trajectories underlie these clinical-metabolic phenotypes: if so this would be strong evidence in support of predictive adaptation model of developmental plasticity

Antithymocyte Globulin Plus G-CSF Combination Therapy Leads to Sustained Immunomodulatory and Metabolic Effects in a Subset of Responders With Established Type 1 Diabetes.

Low-dose antithymocyte globulin (ATG) plus pegylated granulocyte colony-stimulating factor (G-CSF) preserves β-cell function for at least 12 months in type 1 diabetes. Herein, we describe metabolic and immunological parameters 24 months following treatment. Patients with established type 1 diabetes (duration 4-24 months) were randomized to ATG and pegylated G-CSF (ATG+G-CSF) (N = 17) or placebo (N = 8). Primary outcomes included C-peptide area under the curve (AUC) following a mixed-meal tolerance test (MMTT) and flow cytometry. "Responders" (12-month C-peptide ≥ baseline), "super responders" (24-month C-peptide ≥ baseline), and "nonresponders" (12-month C-peptide &lt; baseline) were evaluated for biomarkers of outcome. At 24 months, MMTT-stimulated AUC C-peptide was not significantly different in ATG+G-CSF (0.49 nmol/L/min) versus placebo (0.29 nmol/L/min). Subjects treated with ATG+G-CSF demonstrated reduced CD4+ T cells and CD4+/CD8+ T-cell ratio and increased CD16+CD56hi natural killer cells (NK), CD4+ effector memory T cells (Tem), CD4+PD-1+ central memory T cells (Tcm), Tcm PD-1 expression, and neutrophils. FOXP3+Helios+ regulatory T cells (Treg) were elevated in ATG+G-CSF subjects at 6, 12, and 18 but not 24 months. Immunophenotyping identified differential HLA-DR expression on monocytes and NK and altered CXCR3 and PD-1 expression on T-cell subsets. As such, a group of metabolic and immunological responders was identified. A phase II study of ATG+G-CSF in patients with new-onset type 1 diabetes is ongoing and may support ATG+G-CSF as a prevention strategy in high-risk subjects

The C-Band All-Sky Survey: Instrument design, status, and first-look data

The C-Band All-Sky Survey (C-BASS) aims to produce sensitive, all-sky maps of diffuse Galactic emission at 5 GHz in total intensity and linear polarization. These maps will be used (with other surveys) to separate the several astrophysical components contributing to microwave emission, and in particular will allow an accurate map of synchrotron emission to be produced for the subtraction of foregrounds from measurements of the polarized Cosmic Microwave Background. We describe the design of the analog instrument, the optics of our 6.1 m dish at the Owens Valley Radio Observatory, the status of observations, and first-look data.Comment: 10 pages, 11 figures, published in Proceedings of SPIE MIllimeter, Submillimeter, and Far-Infrared Detectors and Instrumentation for Astronomy V (2010), Vol. 7741, 77411I-1 - 77411I-1

Surface expression, peptide repertoire, and thermostability of chicken class I molecules correlate with peptide transporter specificity.

The chicken major histocompatibility complex (MHC) has strong genetic associations with resistance and susceptibility to certain infectious pathogens. The cell surface expression level of MHC class I molecules varies as much as 10-fold between chicken haplotypes and is inversely correlated with diversity of peptide repertoire and with resistance to Marek's disease caused by an oncogenic herpesvirus. Here we show that the average thermostability of class I molecules isolated from cells also varies, being higher for high-expressing MHC haplotypes. However, we find roughly the same amount of class I protein synthesized by high- and low-expressing MHC haplotypes, with movement to the cell surface responsible for the difference in expression. Previous data show that chicken TAP genes have high allelic polymorphism, with peptide translocation specific for each MHC haplotype. Here we use assembly assays with peptide libraries to show that high-expressing B15 class I molecules can bind a much wider variety of peptides than are found on the cell surface, with the B15 TAPs restricting the peptides available. In contrast, the translocation specificity of TAPs from the low-expressing B21 haplotype is even more permissive than the promiscuous binding shown by the dominantly expressed class I molecule. B15/B21 heterozygote cells show much greater expression of B15 class I molecules than B15/B15 homozygote cells, presumably as a result of receiving additional peptides from the B21 TAPs. Thus, chicken MHC haplotypes vary in several correlated attributes, with the most obvious candidate linking all these properties being molecular interactions within the peptide-loading complex (PLC).This work was originally supported by core funding to the Basel Institute for Immunology (which was founded and supported by F. Hoffmann-La Roche & Co. Ltd., CH-4005 Basel, Switzerland), then by core funding to the Institute for Animal Health [now re-branded the Pirbright Institute, sponsored by the Biotechnology and Biological Sciences Research Council (BBSRC) of the UK] and finally by programme grant 089305 from the Wellcome Trust to JK.This is the author accepted manuscript. The final version is available from PNAS via http://dx.doi.org/10.1073/pnas.151185911

A VSA search for the extended Sunyaev-Zel'dovich Effect in the Corona Borealis Supercluster

We present interferometric imaging at 33 GHz of the Corona Borealis supercluster, using the extended configuration of the Very Small Array. A total area of 24 deg^2 has been imaged, with an angular resolution of 11 arcmin and a sensitivity of 12 mJy/beam. The aim of these observations is to search for Sunyaev-Zel'dovich (SZ) detections from known clusters of galaxies in this supercluster and for a possible extended SZ decrement due to diffuse warm/hot gas in the intercluster medium. We measure negative flux values in the positions of the ten richest clusters in the region. Collectively, this implies a 3.0-sigma detection of the SZ effect. In the clusters A2061 and A2065 we find decrements of approximately 2-sigma. Our main result is the detection of two strong and resolved negative features at -70+-12 mJy/beam (-157+-27 microK) and -103+-10 mJy/beam (-230+-23 microK), respectively, located in a region with no known clusters, near the centre of the supercluster. We discuss their possible origins in terms of primordial CMB anisotropies and/or SZ signals related to either unknown clusters or to a diffuse extended warm/hot gas distribution. Our analyses have revealed that a primordial CMB fluctuation is a plausible explanation for the weaker feature (probability of 37.82%). For the stronger one, neither primordial CMB (probability of 0.33%) nor SZ can account alone for its size and total intensity. The most reasonable explanation, then, is a combination of both primordial CMB and SZ signal. Finally, we explore what characteristics would be required for a filamentary structure consisting of warm/hot diffuse gas in order to produce a significant contribution to such a spot taking into account the constraints set by X-ray data.Comment: 16 pages, 10 figures. Accepted in MNRA

Identification of platform-independent gene expression markers of cisplatin nephrotoxicity.

Within the International Life Sciences Institute Committee on Genomics, a working group was formed to focus on the application of microarray technology to preclinical assessments of drug-induced nephrotoxicity. As part of this effort, Sprague-Dawley rats were treated with the nephrotoxicant cisplatin at doses of 0.3-5 mg/kg over a 4- to 144-hr time course. RNA prepared from these animals was run on a variety of microarray formats at multiple sites. A set of 93 differentially expressed genes associated with cisplatin-induced renal injury was identified on the National Institute of Environmental Health Sciences (NIEHS) custom cDNA microarray platform using quadruplicate measurements of pooled animal RNA. The reproducibility of this profile of statistically significant gene changes on other platforms, in pooled and individual animal replicate samples, and in an independent study was investigated. A good correlation in response between platforms was found among the 48 genes in the NIEHS data set that could be matched to probes on the Affymetrix RGU34A array by UniGene identifier or sequence alignment. Similar results were obtained with genes that could be linked between the NIEHS and Incyte or PHASE-1 arrays. The degree of renal damage induced by cisplatin in individual animals was commensurate with the number of differentially expressed genes in this data set. These results suggest that gene profiles linked to specific types of tissue injury or mechanisms of toxicity and identified in well-performed replicated microarray experiments may be extrapolatable across platform technologies, laboratories, and in-life studies

The autoimmune disease-associated SNP rs917997 of IL18RAP controls IFNγ production by PBMC

AbstractType 1 Diabetes (T1D) is an autoimmune disorder characterized by aberrant T cell responses. Innate immune activation defects may facilitate a T helper 1 (Th1) phenotype. The cytokine IL-18 synergizes with IL-12 to induce IFNγ production and Th1 differentiation. The IL-18R subunit (IL18RAP) SNP rs917997 has been linked to decreased IL18RAP gene expression. Prior reports link rs917997 allele A with protection from T1D, and conversely with susceptibility to Celiac disease. However, few studies have investigated the IL-18 pathway in T1D. In this study, we analyzed responsiveness to IL-18 in T1D, and the effect of rs917997 genotype on IL18RAP gene expression post-activation. Upon IL-12 and IL-18 treatment, peripheral blood mononuclear cells from subjects carrying susceptibility alleles at rs917997 produced higher levels of IFNγ than those with protective genotypes. Additionally, the SNP modified IL18RAP surface protein expression by NK cells and gene expression in activated T cells. Taken together, these data suggest that the disease-associated rs917997 allele G permits hyperresponsiveness to IL-18, providing a novel target for therapeutic intervention in T1D