The Role of The Fictitious Narrator in Heinrich Boll\u27s Gruppenbild Mit Dame

This thesis attempts to analyze the role of the fictitious narrator in the 1972 Nobel prize-winning novelist Heinrich Boll’s novel, Gruppenbild Mit Dame. The novel consists of a fictitious report about Leni Pfeiffer composed by the fictitious narrator who is referred to only as “the Author.” The report is a collection of information and opinions gathered by the Author from various witnesses to events in Leni’s life. The first topic to be considered is the Author’s purpose in writing the report. He maintains that his purpose is purely existential, and the reader must accept this reason. The next topic dealt with is the Author’s style. He claims to be writing a factual report, but it is apparent that he uses many devices to influence the reader’s opinions. The Author’s relationship to the reader for whom he is writing is then examined. The Author develops as a character within the novel, and this development is the fourth topic of the thesis. Finally the Author’s relationship to Leni is considered. It is concluded that the Author has composed a portrait of life as it is—the major issues are riddled with mundane triviality

Development of a Process Parameter Selection Guideline for Additively Manufacturing New Materials Via Laser Powder Bed Fusion

As new materials are designed for metal additive manufacturing (AM), there is a need to develop a systematic approach to optimize process parameters. The purpose of this research is to develop a guideline for laser-based powder bed fusion (LPBF) operators that will minimize computational and experimental trial and error. The guideline illustrates a two-step optimization problem based on the following four process parameters: laser power, scan speed, layer thickness, and hatch distance. The first step focuses on optimizing laser power and scan speed parameters in order to achieve desirable melt pool dimensions. The Eagar-Tsai model was employed as an aid to predict the width and depth of the melt pool. The second step optimizes the latter two parameters by considering the melt pool geometry from step one and calculating the optimal hatch distance while mitigating lack of fusion. Characterization of single tracks and cubes is performed to explore the relationship between process parameters and porosity and differential evaporation of a binary nickel alloy

Teaching higher education staff to understand and support autistic students: evaluation of a novel training program

BackgroundAutistic students are particularly vulnerable to stressors within a university environment and are more likely to experience poor mental health than their non-autistic peers. Students’ experiences of stigma from staff and peers, and the masking behaviors they deploy to minimize it, can also result in worsening mental health. Despite these concerns, there is a lack of tailored support for autistic students at university. The current project assesses a co-created training course for university staff focused on debunking stereotypes, educating about the autistic experience at university, mental health presentation among autistic individuals, and practical strategies to improve interactions with autistic students.MethodsThe Autism Stigma and Knowledge Questionnaire [ASK-Q] was administered before and after the training, to examine changes in trainees’ understanding and acceptance of autism and autistic people. Post-training interviews and surveys were also conducted with trainees, covering the impact the training has had on their perceptions of autism, the strategies they found beneficial, and how they will use the materials in future.ResultsThere were no statistically significant differences between pre- and post-training scores on the ASK-Q, likely due to ceiling effects as pre-training scores were high. Thematic analysis of interviews identified five themes: value of lived experience; developing nuanced, in-depth knowledge of autism; training as acceptable and feasible; links to professional practice; and systemic barriers.ConclusionAlthough ceiling effects meant there were no changes to participant’s knowledge about autism and autistic people statistically, the qualitative data reveals the extensive benefits they gained from taking part in the training programs. Scoring highly on the ASK-Q did not mean that people could not learn important new information and benefit from the course. This more nuanced understanding of autism led to practical changes in their practice. Listening to and learning from autistic people was seen as particularly important, highlighting the value of co-production. Our results also emphasize the need for varied approaches to evaluating training effectiveness, as reliance on quantitative data alone would have missed the subtler, but impactful, changes our participants experienced. This has important implications for professional practice, both within higher education and more broadly

Shifts in the size and distribution of marine trophy fishing world records

The extensive nature of recreational angling makes it difficult to explore trends in global catches. However, trophy fishing world records may provide an insight into recreational fishing pressure on the largest species and size classes. Trophy fishing is promoted and recorded by the International Game Fish Association (IGFA), who manage an 80-year database on the largest individuals of a species caught – called all-tackle records (ATRs) – with information on the size and location of each record catch. We analyse these data to explore temporal trends in the size of record-setting fishes, determine how past and present ATR catches are distributed globally, and examine trends in records for International Union for Conservation of Nature (IUCN) threatened species. The number of ATRs, and the number of species awarded an ATR, have increased significantly over the past 80 years. New records are for increasingly smaller maximum-sized species of fish, with the average sized record shifting from 167.7 kg in the 1950s to 8.1 kg in the 2010s. ATRs for species listed as threatened (Vulnerable or higher) on the IUCN Red List have also declined by approximately 66% over the past two decades. Records were unevenly distributed around the world but have spread globally over time. Historically, ATRs were concentrated around the coastline of the USA but in recent decades more were reported in areas such as Japan and New Zealand. These data either reflect a shift away from mainly targeting large taxa to targeting a wider variety of smaller species, or that there are now limited larger specimens and so fewer ATRs are being set. Additionally, the scarcity of new records for threatened species appears to support IUCN assessments of their poor stock status. The spread of ATRs suggests a growing pressure on the largest size classes in regions with previously little trophy fishing pressure. We encourage the greater use of catch-and-release initiatives and mandatory data collection for all near records to better quantify trophy fishing pressure and ensure sustainable practices

Intravenous sodium nitrite in acute ST-elevation myocardial infarction: a randomized controlled trial (NIAMI).

AIM: Despite prompt revascularization of acute myocardial infarction (AMI), substantial myocardial injury may occur, in part a consequence of ischaemia reperfusion injury (IRI). There has been considerable interest in therapies that may reduce IRI. In experimental models of AMI, sodium nitrite substantially reduces IRI. In this double-blind randomized placebo controlled parallel-group trial, we investigated the effects of sodium nitrite administered immediately prior to reperfusion in patients with acute ST-elevation myocardial infarction (STEMI). METHODS AND RESULTS: A total of 229 patients presenting with acute STEMI were randomized to receive either an i.v. infusion of 70 μmol sodium nitrite (n = 118) or matching placebo (n = 111) over 5 min immediately before primary percutaneous intervention (PPCI). Patients underwent cardiac magnetic resonance imaging (CMR) at 6-8 days and at 6 months and serial blood sampling was performed over 72 h for the measurement of plasma creatine kinase (CK) and Troponin I. Myocardial infarct size (extent of late gadolinium enhancement at 6-8 days by CMR-the primary endpoint) did not differ between nitrite and placebo groups after adjustment for area at risk, diabetes status, and centre (effect size -0.7% 95% CI: -2.2%, +0.7%; P = 0.34). There were no significant differences in any of the secondary endpoints, including plasma troponin I and CK area under the curve, left ventricular volumes (LV), and ejection fraction (EF) measured at 6-8 days and at 6 months and final infarct size (FIS) measured at 6 months. CONCLUSIONS: Sodium nitrite administered intravenously immediately prior to reperfusion in patients with acute STEMI does not reduce infarct size

Calcium-sensing receptor residues with loss- and gain-of-function mutations are located in regions of conformational change and cause signalling bias

The calcium-sensing receptor (CaSR) is a homodimeric G-protein-coupled receptor that signals via intracellular calcium (Ca2+i) mobilisation and phosphorylation of extracellular signal-regulated kinase 1/2 (ERK) to regulate extracellular calcium (Ca2+e) homeostasis. The central importance of the CaSR in Ca2+e homeostasis has been demonstrated by the identification of loss- or gain-of-function CaSR mutations that lead to familial hypocalciuric hypercalcaemia (FHH) or autosomal dominant hypocalcaemia (ADH), respectively. However, the mechanisms determining whether the CaSR signals via Ca2+i or ERK have not been established, and we hypothesised that some CaSR residues, which are the site of both loss- and gain-of-function mutations, may act as molecular switches to direct signalling through these pathways. An analysis of CaSR mutations identified in >300 hypercalcaemic and hypocalcaemic probands revealed five 'disease-switch' residues (Gln27, Asn178, Ser657, Ser820 and Thr828) that are affected by FHH and ADH mutations. Functional expression studies using HEK293 cells showed disease-switch residue mutations to commonly display signalling bias. For example, two FHH-associated mutations (p.Asn178Asp and p.Ser820Ala) impaired Ca2+i signalling without altering ERK phosphorylation. In contrast, an ADH-associated p.Ser657Cys mutation uncoupled signalling by leading to increased Ca2+i mobilization while decreasing ERK phosphorylation. Structural analysis of these five CaSR disease-switch residues together with four reported disease-switch residues revealed these residues to be located at conformationally active regions of the CaSR such as the extracellular dimer interface and transmembrane domain. Thus, our findings indicate that disease-switch residues are located at sites critical for CaSR activation and play a role in mediating signalling bias

Trichuris muris infection drives cell-intrinsic IL4R alpha independent colonic RELMα+ macrophages

From PLOS via Jisc Publications RouterHistory: received 2021-02-23, accepted 2021-06-29, collection 2021-07, epub 2021-07-30Publication status: PublishedFunder: Medical Research Council; funder-id: http://dx.doi.org/10.13039/501100000265; Grant(s): MR/N022661/1Funder: wellcome trust; funder-id: http://dx.doi.org/10.13039/100004440; Grant(s): 106898/A/15/ZThe intestinal nematode parasite Trichuris muris dwells in the caecum and proximal colon driving an acute resolving intestinal inflammation dominated by the presence of macrophages. Notably, these macrophages are characterised by their expression of RELMα during the resolution phase of the infection. The RELMα+ macrophage phenotype associates with the presence of alternatively activated macrophages and work in other model systems has demonstrated that the balance of classically and alternatively activated macrophages is critically important in enabling the resolution of inflammation. Moreover, in the context of type 2 immunity, RELMα+ alternatively activated macrophages are associated with the activation of macrophages via the IL4Rα. Despite a breadth of inflammatory pathologies associated with the large intestine, including those that accompany parasitic infection, it is not known how colonic macrophages are activated towards an alternatively activated phenotype. Here, we address this important knowledge gap by using Trichuris muris infection, in combination with transgenic mice (IL4Rαfl/fl.CX3CR1Cre) and IL4Rα-deficient/wild-type mixed bone marrow chimaeras. We make the unexpected finding that education of colonic macrophages towards a RELMα+, alternatively activated macrophage phenotype during T. muris infection does not require IL4Rα expression on macrophages. Further, this independence is maintained even when the mice are treated with an anti-IFNγ antibody during infection to create a strongly polarised Th2 environment. In contrast to RELMα, PD-L2 expression on macrophages post infection was dependent on IL4Rα signalling in the macrophages. These novel data sets are important, revealing a surprising cell-intrinsic IL4R alpha independence of the colonic RELMα+ alternatively activated macrophage during Trichuris muris infection

Standardised clinical data from patients with primary ciliary dyskinesia:FOLLOW-PCD

Clinical data on primary ciliary dyskinesia (PCD) are limited, heterogeneous and mostly derived from retrospective chart reviews, leading to missing data and unreliable symptoms and results of physical examinations. We need standardised prospective data collection to study phenotypes, severity and prognosis and improve standards of care.A large, international and multidisciplinary group of PCD experts developed FOLLOW-PCD, a standardised clinical PCD form and patient questionnaire. We identified existing forms for clinical data collection via the Better Experimental Approaches to Treat PCD (BEAT-PCD) COST Action network and a literature review. We selected and revised the content items with the working group and patient representatives. We then revised several drafts in an adapted Delphi process, refining the content and structure.FOLLOW-PCD has a modular structure, to allow flexible use based on local practice and research focus. It includes patient-completed versions for the modules on symptoms and lifestyle. The form allows a comprehensive standardised clinical assessment at baseline and for annual reviews and a short documentation for routine follow-up. It can either be completed using printable paper forms or using an online REDCap database.Data collected in FOLLOW-PCD version 1.0 is available in real-time for national and international monitoring and research. The form will be adapted in the future after extensive piloting in different settings and we encourage the translation of the patient questionnaires to multiple languages. FOLLOW-PCD will facilitate quality research based on prospective standardised data from routine care, which can be pooled between centres, to provide first-line and real-time evidence for clinical decision-making