Characterization of irradiated RD53A pixel modules with passive CMOS sensors

We are investigating the feasibility of using CMOS foundries to fabricate silicon detectors, both for pixels and for large-area strip sensors. The availability of multi-layer routing will provide the freedom to optimize the sensor geometry and the performance, with biasing structures in poly-silicon layers and MIM-capacitors allowing for AC coupling. A prototyping production of strip test-structures and RD53A compatible pixel sensors was recently completed at LFoundry in a 150$\,$nm CMOS process. This paper will focus on the characterization of irradiated and non-irradiated pixel modules, composed by a CMOS passive sensor interconnected to a RD53A chip. The sensors are designed with a pixel cell of $25\times100\,\mu \mathrm{m}^2$ in case of DC coupled devices and $50\times50\,\mu \mathrm{m}^2$ for the AC coupled ones. Their performance in terms of charge collection, position resolution, and hit efficiency was studied with measurements performed in the laboratory and with beam tests. The RD53A modules with LFoundry silicon sensors were irradiated to fluences up to $1.0\times10^{16}\,\frac{\mathrm{n}_\mathrm{eq}}{\mathrm{cm}^2}$

Oxygen isotopic ratios in galactic clouds along the line of sight towards Sagittarius B2

As an independent check on previous measurements of the isotopic abundance of oxygen through the Galaxy, we present a detailed analysis of the ground state rotational lines of 16OH and 18OH in absorption towards the giant molecular cloud complex, Sagittarius B2. We have modelled the line shapes to separate the contribution of several galactic clouds along the line of sight and calculate 16OH/18OH ratios for each of these features. The best fitting values are in the range 320-540, consistent with the previous measurements in the Galactic Disk but slightly higher than the standard ratio in the Galactic Centre. They do not show clear evidence for a gradient in the isotopic ratio with galactocentric distance. The individual 16OH column densities relative to water give ratios of [H2O/OH]=0.6-1.2, similar in magnitude to galactic clouds in the sight lines towards W51 and W49. A comparison with CH indicates [OH/CH] ratios higher than has been previously observed in diffuse clouds. We estimate OH abundances of 10^-7 - 10^-6 in the line of sight features.Comment: 10 pages, 6 figures, accepted for publication in A&

The German version of the Bath Body Perception Disturbance Scale (BBPDS-D): Translation, cultural adaptation and linguistic validation on patients with complex regional pain syndrome

© 2018, Deutsche Schmerzgesellschaft e.V. Published by Springer Medizin Verlag GmbH, ein Teil von Springer Nature - all rights reserved. Background: Besides the classical clinical manifestations, body perception disturbances are common among patients with complex regional pain syndrome (CRPS). The Bath Body Perception Disturbance Scale (BBPDS) represents auseful tool to assess these changes in CRPS patients; however, to date no validated German version is available. Objective: The aim of this study was to translate the BBPDS into German, to perform across-cultural adaptation and linguistic validation in patients with acute (symptom

Bevacizumab continuation versus no continuation after first-line chemotherapy plus bevacizumab in patients with metastatic colorectal cancer: a randomized phase III non-inferiority trial (SAKK 41/06)

In this trial, stopping bevacizumab after completion of induction chemotherapy was associated with a shorter time to progression, but no statistically significant difference in overall survival compared with the bevacizumab continuation strategy. Non-inferiority could not be demonstrated. Treatment costs are substantially higher for continuous bevacizumab treatmen

Deflating the deep brain stimulation causes personality changes bubble: the authors reply

To conclude that there is enough or not enough evidence demonstrating that deep brain stimulation (DBS) causes unintended postoperative personality changes is an epistemic problem that should be answered on the basis of established, replicable, and valid data. If prospective DBS recipients delay or refuse to be implanted because they are afraid of suffering from personality changes following DBS, and their fears are based on unsubstantiated claims made in the neuroethics literature, then researchers making these claims bear great responsibility for prospective recipients' medical decisions and subsequent well-being. Our article “Deflating the ‘DBS causes personality’ bubble” reported an increase in theoretical neuroethics publications suggesting putative DBS-induced changes to personality, identity, agency, autonomy, authenticity and/or self (PIAAAS) and a critical lack of supporting primary empirical studies. This special issue of Neuroethics brings together responses to our initial publication, with our own counter-responses organized according to common themes. We provide a brief summary for each commentary and its main criticisms as well as a discussion of the way in which these responses can: 1) help clarify the meaning of PIAAAS, suggesting supplementary frameworks for understanding the impact of DBS on PIAAAS; 2) provide further empirical evidence of PIAAAS by presenting results from the researchers’ own work; and/or 3) offer a critique of our research approach and/or findings. Unintended postoperative putative changes to PIAAAS remain a critical ethical concern. It is beyond dispute that we need to develop reliable empirical and conceptual instruments able to measure complex cognitive, affective, and behavioural changes in order to investigate whether they are attributable to DBS alone

The use of thermographic imaging to evaluate therapeutic response in human tumour xenograft models

YesNon-invasive methods to monitor tumour growth are an important goal in cancer drug development. Thermographic imaging systems offer potential in this area, since a change in temperature is known to be induced due to changes within the tumour microenvironment. This study demonstrates that this imaging modality can be applied to a broad range of tumour xenografts and also, for the first time, the methodology’s suitability to assess anti-cancer agent efficacy. Mice bearing subcutaneously implanted H460 lung cancer xenografts were treated with a novel vascular disrupting agent, ICT-2552, and the cytotoxin doxorubicin. The effects on tumour temperature were assessed using thermographic imaging over the first 6 hours post-administration and subsequently a further 7 days. For ICT-2552 a significant initial temperature drop was observed, whilst for both agents a significant temperature drop was seen compared to controls over the longer time period. Thus thermographic imaging can detect functional differences (manifesting as temperature reductions) in the tumour response to these anti-cancer agents compared to controls. Importantly, these effects can be detected in the first few hours following treatment and therefore the tumour is observable non-invasively. As discussed, this technique will have considerable 3Rs benefits in terms of reduction and refinement of animal use.University of Bradfor

Neoadjuvant chemoradiotherapy with or without panitumumab in patients with wild-type KRAS, locally advanced rectal cancer (LARC): a randomized, multicenter, phase II trial SAKK 41/07

Background We conducted a randomized, phase II, multicenter study to evaluate the anti-epidermal growth factor receptor (EGFR) mAb panitumumab (P) in combination with chemoradiotherapy (CRT) with standard-dose capecitabine as neoadjuvant treatment for wild-type KRAS locally advanced rectal cancer (LARC). Patients and methods Patients with wild-type KRAS, T3-4 and/or N+ LARC were randomly assigned to receive CRT with or without P (6 mg/kg). The primary end-point was pathological near-complete or complete tumor response (pNC/CR), defined as grade 3 (pNCR) or 4 (pCR) histological regression by Dworak classification (DC). Results Forty of 68 patients were randomly assigned to P + CRT and 28 to CRT. pNC/CR was achieved in 21 patients (53%) treated with P + CRT [95% confidence interval (CI) 36%-69%] versus 9 patients (32%) treated with CRT alone (95% CI: 16%-52%). pCR was achieved in 4 (10%) and 5 (18%) patients, and pNCR in 17 (43%) and 4 (14%) patients. In immunohistochemical analysis, most DC 3 cells were not apoptotic. The most common grade ≥3 toxic effects in the P + CRT/CRT arm were diarrhea (10%/6%) and anastomotic leakage (15%/4%). Conclusions The addition of panitumumab to neoadjuvant CRT in patients with KRAS wild-type LARC resulted in a high pNC/CR rate, mostly grade 3 DC. The results of both treatment arms exceeded prespecified thresholds. The addition of panitumumab increased toxicit

Comparison of the Gene Expression Profiles from Normal and Fgfrl1 Deficient Mouse Kidneys Reveals Downstream Targets of Fgfrl1 Signaling

Fgfrl1 (fibroblast growth factor receptor-like 1) is a transmembrane receptor that is essential for the development of the metanephric kidney. It is expressed in all nascent nephrogenic structures and in the ureteric bud. Fgfrl1 null mice fail to develop the metanephric kidneys. Mutant kidney rudiments show a dramatic reduction of ureteric branching and a lack of mesenchymal-to-epithelial transition. Here, we compared the expression profiles of wildtype and Fgfrl1 mutant kidneys to identify genes that act downstream of Fgfrl1 signaling during the early steps of nephron formation. We detected 56 differentially expressed transcripts with 2-fold or greater reduction, among them many genes involved in Fgf, Wnt, Bmp, Notch, and Six/Eya/Dach signaling. We validated the microarray data by qPCR and whole-mount in situ hybridization and showed the expression pattern of candidate genes in normal kidneys. Some of these genes might play an important role during early nephron formation. Our study should help to define the minimal set of genes that is required to form a functional nephron

A systematic review of non-antibiotic measures for the prevention of urinary tract infections in pregnancy

Background: Urinary tract infections (UTIs) are common in pregnancy and account for the highest proportion of primary care antibiotic prescriptions issued to pregnant women in the UK. It is well known that antibiotic use is associated with increased antimicrobial resistance and therefore measures to minimise antibiotic use for UTI prevention have been studied. The efficacy and safety of these measures in pregnancy have not been addressed and therefore the aim of this study was to systematically review the literature to identify and evaluate potential measures to prevent UTIs in pregnant women. Methods: Ten databases (EMBASE, AMED, BNI, CINAHL, Medline, PubMed, PsycINFO, Cochrane Trials, Scopus and Science Direct) were systematically searched in July 2017 for studies reporting non-antibiotic measures to prevent UTIs in pregnancy. The terms (“urinary tract infection”or UTI or bacteriuria or cystitis) AND (prevention) AND (pregnan*) were used. The quality of the publications was appraised using the Critical Appraisal Skills Programme (CASP) checklists for cohort study, case-control study and randomised controlled trial. The results were synthesised using a textual narrative approach. Results: Search results yielded 3276 publications and after reviewing titles and removing duplicates, 57 full text articles were assessed for eligibility and eight were included in the review. Five different approaches (hygiene measures, cranberry juice, immunisation, ascorbic acid and Canephron® N) have been identified, all of which are reported to be safe in pregnancy. Conclusion: The quality of the evidence varied considerably and only hygiene measures were supported by evidence to be recommended in practice. Future work needs to concentrate on strengthening the evidence base through improved design and reporting of studies with a focus on immunisation, ascorbic acid and Canephron® N

Stress-induced decreases in local cerebral glucose utilization in specific regions of the mouse brain

BACKGROUND: Restraint stress in rodents has been reported to activate the hypothalamic-pituitary-adrenocortical (HPA) axis and to increase c-fos expression in regions that express components of the corticotropin-releasing factor (CRF) system. We have previously reported that acute central administration of CRF increased a measure of relative local cerebral glucose utilization (LCGU), a measure of neuronal activity in specific brain regions, and activated the HPA axis in mice. It was hypothesized that the involvement of the CRF system in the stress response would lead to similar changes in relative LCGU after restraint stress. In the present studies the effect of restraint stress on relative LCGU and on the HPA axis in C57BL/6N mice were examined. FINDINGS: Restraint stress activated the HPA axis in a restraint-duration dependent manner, but in contrast to the reported effects of CRF, significantly decreased relative LCGU in frontal cortical, thalamic, hippocampal and temporal dissected regions. These findings support evidence that stressors enforcing limited physical activity reduce relative LCGU, in contrast to high activity stressors such as swim stress. CONCLUSIONS: In conclusion, the present studies do not support the hypothesis that stress-induced changes in relative LCGU are largely mediated by the CRF system. Further studies will help to delineate the role of the CRF system in the early phases of the relative LCGU response to stress and investigate the role of other neurotransmitter systems in this response