Cryptococcosis: a proteomic investigation of an emerging fungal disease

Fungal infections are increasing in frequency throughout the world. The development of new diagnostic and treatment strategies has not kept pace with this increase. The result is a high incidence of infection recurrence and high mortality rates. The pathogenic yeasts Cryptococcus neoformans and Cryptococcus gattii provide an excellent system for determining the spectrum of fungal growth and infection, from environmental saprotrophic growth, to self-limiting infection and through to severe primary infection. Cryptococcus cells obtained from pulmonary infection, and infected rat lung tissue, represented technically challenging sample types that required significant protocol development prior to comparative analysis. This subjected the obtained data to a number of experimental caveats. Despite the significant impediments to experimentation, the advances made in protocol development by this study allowed for the first in vivo analysis of intracellular Cryptococcus protein expression. This result provided proof of concept for global "–omics" analysis of Cryptococcus from an in vivo sample. In addition, qualitative data were obtained that offered insights into fungal pathogenesis at the protein level and highlighted a number of Cryptococcus proteins that could be exploited as drug targets. Furthermore, the identification of host lung proteins and systemic cytokines of biological relevance to pulmonary cryptococcosis provides proof of the ability of comparative proteomics to elucidate future drug targets, biomarkers and diagnostic markers from in vivo mammalian infection models. The studies’ most significant achievement has been the advances made in protocol development. It is hoped that these advances will lead to further, potentially quantitative, analysis of fungal pathogens under in vivo conditions, along with continued development of novel therapeutic and diagnostic options for pathogenic fungi

Freinet Pedagogy: Enduring Impact Over an Individual Career

This article presents an individual perspective on the impact of Freinet Pedagogy across the career of one English language teacher and teacher educator. With special attention to language instruction, I will highlight a number perennially important Freinet dimensions that gradually came to my attention over the years. My admiration for Freinet Pedagogy first arose in relation to two very hands-on techniques: free writing and classroom printing. Later, my interest took a more theoretical turn, through recognition of illuminating consistencies between Freinet Pedagogy and two other more recent developments: broadly, van Lier’s (2004) influential ecological perspective on language learning may be taken as a backdrop against which to highlight the coherence of Freinet Pedagogy both with the flexibly system-based style of planning now advocated by such authorities as Reason (2008), and with the present-day connectionist psychological approach to opportunities for language teaching and learning that has been metaphorically represented in back-to-the-well terms (Sivell & Sivell, 2012)

Normative Democratic Deliberation and the Role of Argumentation in the Canadian Mandatory Minimum Sentence Debate

This paper explores the role of argumentation within the debates on Bill C-10, the Safe Streets and Communities Act, that came into force in 2012. Through examining Hansard transcripts, this paper aims to investigate how argumentation on mandatory minimums was utilized in this political decision making setting to legitimize and accomplish this policy initiative. I draw upon the concepts of normative democratic deliberation, new right ideology and the punitive turn to explore the Harper government’s use of argumentation strategies and discuss their implications for the Canadian political process and the current direction of the administration of justice in Canada. This paper’s goal is to contribute to literature on mandatory minimums and policy making through an exploration of the political deliberative process through which the C-10 provisions on mandatory minimums were adopted

The preferences and perspectives of family caregivers towards place of care for their relatives at the end-of-life. A systematic review and thematic synthesis of the qualitative evidence

Background Home is often reported as the preferred place of care for patients at the end-of-life. The support of family caregivers is crucial if this is to be realised. However, little is known about their preferences; a greater understanding would identify how best to support families at the end-of-life, ensuring more patients are cared for in their preferred location. Objectives To systematically search and synthesise the qualitative literature exploring the preferences and perspectives of family caregivers towards place of care for their relatives at the end-of-life. Methods Ten databases (MEDLINE, PsycINFO, EMBASE, AMED, ASSIA, CINAHL, Social Care Online, Cochrane Database, Scopus, Web of Science) and reference lists of key journals were searched up to January 2014. Included studies were appraised for quality and data thematically synthesised. Results Eighteen studies were included; all were of moderate or high quality. Two main themes were identified: (1) Preferences and perspectives: most family caregivers preferred home care, although a range of perspectives were reported. Both positive and negative perspectives of home, hospices and hospitals emerged. At times, family caregivers reported feeling obligated to provide home care. (2) Impact of facilitating home care; both positive and negative effects on family caregivers were reported. Conclusions Many family caregivers reported home as the preferred place of care; other places of care were infrequently considered. Healthcare professionals and service providers should be aware of these preferences and provide support where needed to enable family caregivers to successfully care at home, thus improving end-of-life experiences for families as a whole

Managing, making sense of and finding meaning in advanced illness: a qualitative exploration of the coping and wellbeing experiences of patients with lung cancer

Coping plays an essential role in maintaining the wellbeing of patients with cancer. A number of different coping responses and strategies have been identified in the literature. The value and relevance of meaning based coping theory has also been emphasised, including Antonovosky’s (1979) Sense of Coherence (SoC) theory. Ten patients with advanced lung cancer were interviewed up to three times. A total of twenty in depth interviews were carried out, fully transcribed and data were analysed following a methodology of Interpretative Phenomenological Analysis. Three broad domains were identified to categorise the core life concerns of participants; making sense of and managing one’s illness; maintaining daily life and relationships and confronting the future. Within these domains multiple coping themes are identified, which to varying degrees help to maintain patient wellbeing and quality of life. This paper considers the relevance of SoC theory for understanding the coping experiences of patients with advanced cancer, and identifies resources and factors likely to support patient coping, with implications for health and social care services

Symptom management, nutrition and hydration at end-of-life: a qualitative exploration of patients', carers' and health professionals' experiences and further research questions

Background Symptom management is an essential aspect of palliative and end-of-life care, but evidence suggests that patients’ symptoms may not always be relieved, causing significant harm to patients and magnifying their relatives’ distress. A growing body of evidence focuses on symptom management at the end-of-life, but research funding for palliative care remains disproportionately low. It is therefore crucial that research funding is targeted at areas of importance to patients and relatives. The Palliative and end-of-life care Priority Setting Partnership (PeolcPSP) undertook a UK-wide free-text survey to establish research priorities within palliative and end-of-life care and disseminated its results in 2015. Much of the data were related more broadly to personal perceptions and experiences rather than specific research questions. The aim of this article is to report on a supplementary analysis exploring the experiences and questions of PeolcPSP survey respondents regarding symptoms, hydration and nutrition. Methods The PeolcPSP data (n=1403) were coded by a team of qualitative researchers in a supplementary analysis. There were 190 responses that related to symptoms, nutrition and hydration. The data were analysed thematically using Braun and Clarke’s approach. Results Five themes were identified: pain, breathlessness, agitation, nutrition and hydration. The majority of responses related to symptoms that were sub-optimally managed, in particular pain. Nutrition and hydration were of significant concern, particularly for carers. Overall, respondents consistently asked about the most effective, evidence-based methods for managing symptoms and suggested areas where further research is necessary. Conclusions This study highlights the perceptions and experiences of patients, families and professionals within palliative care, highlighting the need for improved care, communication and further research to establish which treatments are most effective within a palliative care population. This is essential to reduce harm and distress for patients and families

'I didn't really understand it, I just thought it'd help': exploring the motivations, understandings and experiences of patients with advanced lung cancer participating in a non-placebo clinical IMP trial

BACKGROUND: Few studies have explored in depth the experiences of patients with advanced cancer who are participating in clinical investigational medicinal product trials. However, integrated qualitative studies in such trials are needed to enable a broader evaluation of patient experiences in the trial, with important ethical and practical implications for the design and conduct of similar trials and treatment regimes in the future. METHODS: Ten participants were recruited from the control and intervention arms of FRAGMATIC: a non-placebo trial for patients with advanced lung cancer. Participants were interviewed at up to three time points during their time in the trial. Interviews were analysed using Interpretive Phenomenological Analysis. RESULTS: Patients were motivated to join the trial out of hope of medical benefit and altruism. Understanding of randomisation was mixed and in some cases poor, as was appreciation of trial purpose and equipoise. The trial was acceptable to and evaluated positively by most participants; participants receiving the intervention focused on the potential treatment benefits they hoped they would receive, whilst participants in the control arm found alternative reasons, such as altruism, personal fulfilment and positive attention, to commit to and perceive benefits from the trial. However, whilst experiences were generally very positive, poor understanding, limited engagement with trial information and focus on treatment benefits amongst some participants give cause for concern. CONCLUSIONS: By exploring longitudinally the psychological, emotional and cognitive domains of trial participation, we consider potential harms and benefits of participation in non-placebo trials amongst patients with advanced lung cancer and identify several implications for future research with and care for patients with advanced cancer. TRIAL REGISTRATION: ISRCTN80812769. Registered on 8 July 2005

The genome sequence of the cinnabar moth, Tyria jacobaeae (Linnaeus, 1758)

We present a genome assembly from an individual male Tyria jacobaeae (the Cinnabar Moth; Arthropoda; Insecta; Lepidoptera; Erebidae). The genome sequence is 589.7 megabases in span. Most of the assembly is scaffolded into 31 chromosomal pseudomolecules, including the Z sex chromosome. The mitochondrial genome has also been assembled and is 15.74 kilobases in length

The three-item ALERT-B questionnaire provides a validated screening tool to detect chronic gastrointestinal symptoms after pelvic radiotherapy in cancer survivors

Aims: Although pelvic radiotherapy is an effective treatment for various malignancies, around half of patients develop significant gastrointestinal problems. These symptoms often remain undetected, despite the existence of effective treatments. This study developed and refined a simple screening tool to detect common gastrointestinal symptoms in outpatient clinics. These symptoms have a significant effect on quality of life. This tool will increase detection rates and so enable access to specialist gastroenterologists, which will in turn lead to improved symptom control and quality of life after treatment. Materials and methods: A literature review and expert consensus meeting identified four items for the ALERT-B (Assessment of Late Effects of RadioTherapy - Bowel) screening tool. ALERT-B was face tested for its usability and acceptability using cognitive interviews with 12 patients experiencing late gastrointestinal symptoms after pelvic radiotherapy. Thematic analysis and probe category were used to analyse interview transcripts. Interview data were presented to a group of experts to agree on the final content and format of the tool. ALERT-B was assessed for reliability and tested for validity against the Gastrointestinal Symptom Rating Scale in a clinical study (EAGLE). Results: Overall, the tool was found to be acceptable in terms of wording, response format and completion time. Participant-reported experiences, including lifestyle modifications and the psychological effect of the symptoms, led to further modifications of the tool. The refined tool includes three questions covering rectal bleeding, incontinence, nocturnal bowel movements and impact on quality of life, including mood, relationships and socialising. ALERT-B was successfully validated against the Gastrointestinal Symptom Rating Scale in the EAGLE study with the tool shown broadly to be internally consistent (Cronbach’s alpha=0.61 and all item-subscale correlation [Spearman] coefficients are > 0.6). Conclusion: The ALERT-B screening tool can be used in clinical practice to improve post-treatment supportive care by triggering the clinical assessment of patients suitable for referral to a gastroenterologist