Anti-CTLA-4 (CD 152) monoclonal antibody-induced autoimmune interstitial nephritis

Targeted immune-modulating agents are entering clinical practice in many specialties, providing novel therapeutic possibilities but introducing new potential toxicities. We present the first reported case, to our knowledge, of immune-mediated nephritis following the administration of Tremelimumab (CP-675, 206), an anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) monoclonal antibody. High-dose steroid therapy led to a rapid improvement in renal function, avoiding the need for renal replacement therapy.Peer reviewe

A comparative study of blood endotoxin detection in haemodialysis patients

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Wong et al Journal of Inflammation (2016) 13:24, the version of record is available online at doi: 10.1186/s12950-016-0132-5BACKGROUND: Endotoxemia is commonly reported in patients receiving haemodialysis and implicated in the pathogenesis of systemic inflammation. The Limulus Amoebocyte Lysate (LAL) assay is the most commonly used blood endotoxin detection assay. Two kinetic variations of the assay are commercially available - the turbidimetric and chromogenic assay, it is unknown which assay is superior for endotoxin detection in uremic patients. Selection of the optimum LAL technique for endotoxin detection in haemodialysis patients is important to further understanding of the sequela of endotoxemia and development of endotoxin-lowering strategies in this population. METHOD: A turbidimetric and chromogenic LAL assay from the same manufacturer were directly compared. We investigated the ability of both LAL assays to detect endotoxin in uremic plasma. Plasma samples from haemodialysis patients and healthy controls were spiked with endotoxin and percentage spike recovery for the chromogenic and turbidimetric assay was determined. Assay accuracy and precision were compared between both LAL assays. RESULTS: The turbidimetric assay had greater accuracy than the chromogenic assay. Spike recovery was 113.8 % vs. 53.8 % for the turbidimetric and chromogenic assay respectively. Assay bias was higher in the chromogenic assay (-0.384EU/mL vs. 0.011EU/mL). The turbidimetric assay demonstrated greater precision compared to the chromogenic assay. Coefficient of variation ranged from 4.5 to 24.1 % for the turbidimetric assay and 25.8-26.5 % for the chromogenic assay. CONCLUSION: The study findings suggest that the kinetic turbidimetric LAL assay has greater accuracy and precision than the chromogenic assay and is the optimum LAL technique for endotoxin detection in haemodialysis patients, though these findings should be verified using LAL reagents from other sources.Peer reviewe

Interdisciplinary Pedagogy, Integrated Curriculum, and Professional Development

The challenges involved in facing and solving the most pressing global problems of the 21st century will involve collaboration and critical engagement from multiple disciplines. Interdisciplinary education and the critical skills it can teach—innovation, team-based collaboration, and effective communication, among many others—are crucial to preparing current students for their futures as professional problem-solvers. We introduce an integrated pedagogical approach between three introductory courses at Purdue University: Design Thinking in Technology (Tech 120), English Composition (English 106), and Fundamentals of Speech Communication (Com 114). Instructors and administrators in all three of these programs are working together to reinforce the valuable and important connections between STEM and Humanities work. Along with an overview of the development and implementation of this integration, we present a summary of findings from our ongoing assessment of the program. The integration has the most beneficial effects on students’ sense of community, which in turn significantly impacts their performance on team projects. When STEM and Humanities instructors and faculty share goals and spend time innovating together, the potential benefits to students and to the future of engineering education overall are clear

Development and application of environmental DNA surveillance for the threatened crucian carp (Carassius carassius)

The crucian carp (Carassius carassius ) is one of few fish species associated with small ponds in the UK. These populations contain genetic diversity not found in Europe and are important to conservation efforts for the species which has declined across its range in Europe. Detection and monitoring of extant crucian carp populations are crucial for conservation success. Environmental DNA (eDNA) analysis could be very useful in this respect as a rapid, cost‐efficient monitoring tool. We developed a species‐specific quantitative polymerase chain reaction (qPCR) assay for eDNA surveillance of crucian carp to enable non‐invasive, large‐scale distribution monitoring. We compared fyke netting and eDNA analysis at ponds with (n = 10) and without (n = 10) crucian carp for presence–absence detection. We examined biotic (crucian carp density represented by catch‐per‐unit‐effort [CPUE] estimate) and abiotic influences on eDNA detection probability using a hierarchical occupancy model, and eDNA quantification using a mixed‐effects model. eDNA analysis achieved 90% detection for crucian carp (n = 10), failing in only one pond where presence was known. CPUE estimate and conductivity had positive and negative influences on eDNA detection probability in qPCR replicates respectively. Similarly, conductivity had a negative effect on DNA copy number, whereas copy number increased with CPUE estimate. Our results demonstrate that eDNA analysis could enable detection of crucian carp populations in ponds and benefit ongoing conservation efforts, but imperfect species detection in relation to biotic and abiotic factors and eDNA workflow requires further investigation. Nonetheless, we have established an eDNA framework for the crucian carp as well as sources of imperfect detection which future investigations can build upon

The consequences of traumatic brain injury from the classroom to the courtroom: understanding pathways through structural equation modelling

Purpose: Paediatric traumatic brain injury (TBI) can have resultant ongoing significant impairments which can impact life outcomes. The primary aim of this research was to explore whether TBI contributes to the relationship between poor educational outcomes and offending trajectories. Materials and methods: Through analysis of a dataset consisting of self-reported health, educational, and offending histories of 70 incarcerated young males, structural equation modelling was used to explore the mediation of educational outcomes and patterns in offending behaviour by chronic symptoms following TBI. Results: Symptoms related to TBI significantly mediated the relationship between decreased educational attainment and more frequent convictions. It did not mediate any relationships involving age at first conviction. Conclusions: Traumatic brain injury appears to have more influence over frequency of offending patterns than age at first conviction. However, TBI remains a pervasive factor in both higher rates of offending and poorer educational attainment. In order to tackle this effect on adverse social outcomes, greater attention to the impact of TBI is required in education and criminal justice systems. IMPLICATIONS FOR REHABILITATION Highlights traumatic brain injury as a contributory factor in some education to offending pathways, suggesting that greater focus on rehabilitation within the education and criminal justice systems is required. Reinforces that greater understanding of educational pathways post-injury is needed to better facilitate rehabilitation within the school system

The ABC130 barrel module prototyping programme for the ATLAS strip tracker

For the Phase-II Upgrade of the ATLAS Detector, its Inner Detector, consisting of silicon pixel, silicon strip and transition radiation sub-detectors, will be replaced with an all new 100 % silicon tracker, composed of a pixel tracker at inner radii and a strip tracker at outer radii. The future ATLAS strip tracker will include 11,000 silicon sensor modules in the central region (barrel) and 7,000 modules in the forward region (end-caps), which are foreseen to be constructed over a period of 3.5 years. The construction of each module consists of a series of assembly and quality control steps, which were engineered to be identical for all production sites. In order to develop the tooling and procedures for assembly and testing of these modules, two series of major prototyping programs were conducted: an early program using readout chips designed using a 250 nm fabrication process (ABCN-25) and a subsequent program using a follow-up chip set made using 130 nm processing (ABC130 and HCC130 chips). This second generation of readout chips was used for an extensive prototyping program that produced around 100 barrel-type modules and contributed significantly to the development of the final module layout. This paper gives an overview of the components used in ABC130 barrel modules, their assembly procedure and findings resulting from their tests.Comment: 82 pages, 66 figure

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements