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A five year old girl with life-long TPN dependence for short gut syndrome presented with two episodes of non-fatal Mucor indicus central line associated blood stream infection (CLABSI). Each episode occurred fifteen months apart, without any evidence of ongoing mould infection whilst off antifungal therapy in the intervening time period. Both episodes were treated with removal of the infected central venous catheter (CVC) and 6 weeks of intravenous liposomal amphotericin B and/or posaconazole, with good clinical, microbiological, and radiological response. The possibility of gut translocation is supported by the repeated isolation of Mucor indicus in cases of intestinal mucormycosis. To our knowledge, this is the first case of recurrent episodes of blood culture positive mucormycosis in a single patient. Mucor indicus blood stream infection may differ significantly from invasive mucormycosis caused by other species.

Summary: Human physiology is highly susceptible to frameshift mutations within coding regions, and many hereditary diseases and cancers are caused by such indels. Presently, therapeutic options to counteract them are limited and, in the case of direct genome editing, risky. Here, we show that release factor 1 (eRF1) from Euplotes, an aquatic protist known for frequent +1 frameshifts in its coding regions, can enhance +1 ribosomal frameshifting at slippery heptameric sequences in human cells without an apparent requirement for an mRNA secondary structure. We further show an increase in frameshifting rate at the premature termination sequence found in the HEXA gene of Tay-Sachs disease patients, or a breast cancer cell line that harbors a tumor-driving frameshift mutation in GATA3. Although the overall increase in frameshifting would need further improvement for clinical applications, our results underscore the potential of exogenous factors, such as Eu eRF1, to increase frameshifting in human cells.

Abstract Despite existing wellbeing services, university students remain particularly vulnerable to mental health difficulties. Therefore, this study was designed to provide a comprehensive assessment of the prevalence of psychiatric symptoms by using well validated scales with robust psychometric properties. More specifically, the current data provides crucial information concerning the prevalence of anxiety, depression, mania, insomnia, stress, suicidal ideation, psychotic experiences and loneliness amongst a sample of N = 1408 UK university students. A cross-sectional online questionnaire-based study was implemented. Online recruitment for this dataset began on September 17th, 2018, and ended on the 30th July 2019. Eight validated measures were used: Generalized Anxiety Disorder Scale; Patient Health Questionnaire; The Mood Disorder Questionnaire; The Sleep Condition Indicator; The Perceived Stress Scale; Suicidal Behaviours Questionnaire-Revised; The Prodromal Questionnaire 16 (PQ-16); and the University of California Loneliness Scale. The dataset is available to other researchers and is provided on figshare. Information concerning the data records, usage notes, code availability and technical validation are presented. Finally, we present demographic information concerning psychiatric symptom prevalence.

This study examined the extent to which the dimensions of the five-factor model, Type-D personality, and multidimensional perfectionism were associated with a diurnal preference in the general population. A sample of (N = 864) individuals completed the measures of diurnal preference, multidimensional perfectionism, Type-D personality, and the Big Five traits. A correlational analysis determined that agreeableness, conscientiousness, emotional stability, organization, and personal standards were independently related to morningness. In contrast, negative affect, social inhibition, Type-D personality, and perfectionistic doubts and concerns, as well as an increased perception of critical parental evaluation, were independently related to eveningness. After accounting for the shared variance amongst the personality traits, only negative affect, conscientiousness, organization, personal standards, and parental perception were significantly associated with diurnal preference. The current outcomes offer further insight into the relationship between personality and diurnal preference. Here, we observed greater reports of adaptive personality traits in relation to morningness, whereas negative affect and perceived parental evaluation and criticism were related to eveningness. As the first study to examine the relationship between Type-D personality, multidimensional perfectionism, and diurnal preference, the current outcomes should be considered preliminary.

Background Locally advanced/recurrent head and neck squamous cell carcinoma (HNSCC) is associated with significant morbidity and mortality. To target upregulated ErbB dimer expression in this cancer, we developed an autologous CD28-based chimeric antigen receptor T-cell (CAR-T) approach named T4 immunotherapy. Patient-derived T-cells are engineered by retroviral transduction to coexpress a panErbB-specific CAR called T1E28ζ and an IL-4-responsive chimeric cytokine receptor, 4αβ, which allows IL-4-mediated enrichment of transduced cells during manufacture. These cells elicit preclinical antitumor activity against HNSCC and other carcinomas. In this trial, we used intratumoral delivery to mitigate significant clinical risk of on-target off-tumor toxicity owing to low-level ErbB expression in healthy tissues.Methods We undertook a phase 1 dose-escalation 3+3 trial of intratumoral T4 immunotherapy in HNSCC (NCT01818323). CAR T-cell batches were manufactured from 40 to 130 mL of whole blood using a 2-week semiclosed process. A single CAR T-cell treatment, formulated as a fresh product in 1–4 mL of medium, was injected into one or more target lesions. Dose of CAR T-cells was escalated in 5 cohorts from 1×107−1×109 T4+ T-cells, administered without prior lymphodepletion.Results Despite baseline lymphopenia in most enrolled subjects, the target cell dose was successfully manufactured in all cases, yielding up to 7.5 billion T-cells (67.5±11.8% transduced), without any batch failures. Treatment-related adverse events were all grade 2 or less, with no dose-limiting toxicities (Common Terminology Criteria for Adverse Events V.4.0). Frequent treatment-related adverse events were tumor swelling, pain, pyrexias, chills, and fatigue. There was no evidence of leakage of T4+ T-cells into the circulation following intratumoral delivery, and injection of radiolabeled cells demonstrated intratumoral persistence. Despite rapid progression at trial entry, stabilization of disease (Response Evaluation Criteria in Solid Tumors V.1.1) was observed in 9 of 15 subjects (60%) at 6 weeks post-CAR T-cell administration. Subsequent treatment with pembrolizumab and T-VEC oncolytic virus achieved a rapid complete clinical response in one subject, which was durable for over 3 years. Median overall survival was greater than for historical controls. Disease stabilization was associated with the administration of an immunophenotypically fitter, less exhausted, T4 CAR T-cell product.Conclusions These data demonstrate the safe intratumoral administration of T4 immunotherapy in advanced HNSCC.

Abstract Background Social (or physical) distancing is an important transmission-prevention behaviour that has been endorsed to minimize COVID-19 transmission. This qualitative study explores the facilitators of and barriers to social distancing for young people during the COVID-19 pandemic, with recognition that young people represent a unique demographic group, with differing psychosocial needs and experiences to other age cohorts. Methods Qualitative data was collected as part of a larger Qualtrics survey between July 28th 2020 and August 24th 2020. Eligible participants were young people living on the Island of Ireland, aged 16-25 years. The survey design was underpinned by the Capability, Opportunity, and Motivation model of behaviour change (COM-B). Semi-inductive thematic analysis was used to analyse comments collected via three free-text survey items. The COM-B model provided a thematic framework to organise subthemes extracted. Results A total of N = 477 young people completed the survey, of which N = 347 provided comments for at least one of three free-text survey items. The majority of respondents lived in Northern Ireland (96%), the average age was 21 years, and most respondents were female (73%) and were students (81%). Key barriers identified included lack of environmental support for social distancing (lack of physical Opportunity to social distance), observing other people not social distancing (lack of social Opportunities supporting social distancing), and missing physical interaction from others (relating to the dissuading influence of automatic Motivational factors i.e. the influence of loneliness). Key facilitators included presence of clear and consistent environmental cues and availability of space to support social distancing (increasing physical Opportunity to social distance), increasing awareness and perceived consequences of risk of transmission (enhancing reflective Motivational factors i.e. perceived benefits (versus costs) of social distancing), and increasing opportunities to observe others’ adhering to guidelines (increasing social Opportunities supporting social distancing). Conclusions These findings suggest that the actions and endorsement of peers and the physical design of environments have a key role in influencing social distancing behaviour among young people living in NI. The COM-B factors identified in this study can inform the development of tailored interventions using models such as the Behaviour Change Wheel. The findings of this study suggest that intervention functions based on peer modelling and physical environmental restructuring and enablement should be priortitised, however it is imperative that interventions are co-designed with young people to foster collaboration and empowerment.

Rates of intimate partner violence (IPV) and substance use have risen during the COVID-19 pandemic, with potentially enduring effects on women’s health. A rapid review was conducted on IPV and women’s substance use in the context of the COVID-19 pandemic. The rapid review explored two separate research questions with a view to integrate the literature related to: (1) containment, social isolation, pandemics, disasters, lockdowns, and IPV; and (2) the relationships between substance use and IPV. Two different searches for each question were conducted between May and October 2020 and n = 47 articles were included. Women experience multiple physical and mental health consequences related to IPV that can be exacerbated by public health crises such as pandemics and disasters. Perpetrators may use these events as a tactic to threaten, isolate, or use coercive control. Similar tactics are reported in the complex relationship between IPV and substance use, where substance use can accompany IPV and/or be used as a coping mechanism for survivors. The findings highlight long standing women’s health concerns made further visible during the COVID-19 pandemic. Additional research is needed to identify actions required to reduce gender inequities and harms associated with IPV and substance use, and to adequately tailor and prepare effective responses in the context of future public health crises.

Abstract Objective To explore socioeconomic status (SES) differences in patterns of doctor‐patient communication within head and neck cancer clinics and why such differences exist. Methods Thirty‐six head and neck cancer review appointments with five Physicians were observed and audio‐taped, along with follow‐up interviews involving 32 patients. Data were analysed using Thematic Analysis, and compared by patient SES (education, occupation and Indices of Multiple Deprivation). Results Three main themes were identified: (a) Physicians used more humour and small talk in their consultations with high SES patients; (b) Low SES patients were more passive in their participation, engaged in less agenda setting and information‐seeking, and framed their clinical experience differently; (c) Low SES patients had different preferences for involvement, defining involvement differently to high SES patients and were seen to take a more stoical approach. Conclusion Low SES patients take a more passive role in medical consultations, engage in less relational talk and are less likely to raise concerns, but were satisfied with this. Physicians may adapt their communication behaviour in response to low SES patients’ expectations and preferences. Practice Implications A question prompt list may help low SES patients to raise concerns during their consultations. This may reduce inequalities in communication and health.

Abstract Resource managers face mounting challenges when it comes to the implementation of climate change adaptation strategies. Novel adaptation strategies, such as managed relocation, frequently entail embracing substantial risk of unintended harm to the focal ecosystems, in an effort to alleviate serious threats to biological diversity (e.g. extinction). Assessing ecological risks associated with different adaptation strategies is consistently called for, but the process for doing so is often undefined. Here, we describe a collaboration amongst university researchers, agency scientists and resource managers to create a set of ecological risk assessment protocols for managed relocation decision support. These protocols are designed to foster a rigorous assessment of ecological risk, while simultaneously being flexible and easy to use. We describe a collaborative process through which we developed a structure for assessing risk that includes a suite of 17 risk categories aggregated into six overarching groups, which is placed within a broader decision context for managed relocation (e.g. evaluating feasibility, social acceptability). Our risk scoring includes both scaled estimates of risk and perceived confidence in those estimates. Because of differences in the importance of risk categories, we do not recommend a quantitative summary across risk areas, but suggest decision makers make decisions based on three criteria: overall confidence that a proposed action can be confidently evaluated; low overall level or risk across categories; and no single risk category that is highly likely to result in severe adverse outcomes.

Abstract Background The degree to which patients participate in their care can have a positive impact on health outcomes. This review aimed to map the current literature on patient participation behaviours in interactions with physicians and the extent to which differences in these behaviours can be explained by socio‐economic status (SES). Search strategy Four electronic databases were searched from 1980 onwards using key words related to socio‐economic status and patient participation behaviours. Study selection Titles, abstracts and full texts were screened by two reviewers, with the second reviewer screening 20% of all entries. Data extraction Data on year of publication, country, patient population, setting, patient participation behaviour studied, and SES measure used were extracted. Main results Forty‐nine studies were included in the review. Most studies were conducted in the United States, and the most commonly studied patient participation behaviour was involvement in decision making. Most studies measured SES using education as an indicator, with very few studies using occupation as a measure. Many studies did not report on participants’ medical condition or study setting. Patient participation in their health‐care appointment increased with increasing SES in 24 studies, although in 27 studies no significant association was found. Discussion and conclusions Current literature was found to be mainly US‐centric. Many studies did not specify participants’ medical condition or in what setting the study was undertaken. More studies are needed on less commonly studied patient participation behaviours. It would be helpful for further studies to also include a wider range of SES indicators.

Research exploring the relationship between mental health difficulties and insomnia amongst students in the UK remains limited. This study further examined the extent of potential relationships between insomnia, anxiety and depression symptoms amongst university students in the UK. A sample of 487 students from four northern universities completed The Insomnia Severity Index, SLEEP-50, and Hospital Anxiety and Depression Scales. Approximately one fifth of students experienced mild to severe levels of depressive symptoms, and two thirds reported anxious symptoms. One quarter of students indicated insomnia symptoms in the clinical range, however the prevalence of sleep-disorders other than insomnia remained low (< 5%). Finally, symptoms of insomnia and apnoea were significantly related to depression, after controlling for co-morbid anxiety. The current outcomes highlight the high prevalence of depressive and insomnia symptoms amongst university students in the UK. Considering the relationship between insomnia and depression, student-focused mental health services should explore the possibility of treating insomnia to circumvent depression.

Evidence demonstrates increased vulnerability to thoughts and behaviors related to suicide (i.e., suicidal ideation) in students. This study examined the interaction between insomnia-symptoms and student-status (students vs. non-students) on reports of suicidal thoughts of behaviors. A total of 363 (N = 363) university students and 300 (N = 300) members of the general population provided complete data on measures of insomnia-symptoms and suicidal ideation. Students indicated greater reports of both total and lifetime ideation while also considering suicidal behavior within the past year. However, no differences were observed in reports of possible future attempt(s) and the disclosure of suicidal thoughts and behaviors to another person. Moreover, students presenting concurrent symptoms of insomnia reported significantly elevated levels of suicidal ideation relative to nonstudents. These outcomes highlight the possible role of insomnia symptoms in accentuating suicidal thoughts and behaviors in the student population.

This study examined the relationship between dark triad personality traits and chronotype disposition, whilst incorporating the mediating role of anxiety and/or depression after excluding individuals presenting insomnia and/or physiological sleep-disorder symptoms. Members of the general population (N = 453) completed online measures of dark triad personality traits, chronotype, and anxious and depressive symptoms. Psychopathy and Machiavellianism were independently related to an evening chronotype disposition. However, after accounting for age, sex, anxiety and depression, psychopathy and depression remained the only significant predictors of chronotype. Therefore, whilst psychopathy was the strongest predictor of an evening chronotype preference, this relationship is partially mediated by depression. Individuals presenting an evening disposition may display increased psychopathic traits due to greater emotion dysregulation. This is potentially perpetuated by depressive symptoms stemming from a delayed or blunted affective rhythm. Interacting factors (e.g. reduced light exposure) may also contribute to alterations in the biological rhythm amongst evening-types, resulting in a negative feedback cycle. Targeting chronotype and depressive symptoms amongst individuals presenting psychopathic tendencies could increase the efficacy of existing sleep-based interventions for hostile behaviour.

This study examined the relationship between the Big Five personality traits and insomnia symptoms in the general population. Additionally, the mediating role of anxiety and depression was examined. Participants (N = 625) completed online measures of the big five personality traits and insomnia severity. Insomnia symptoms were independently related to extroversion, agreeableness, conscientiousness, emotional stability, anxiety and depression in univariate analysis. Linear regression determined conscientiousness and emotional stability to be the only traits predicting insomnia symptoms. However, these relationships were at least partially mediated by anxiety and depression. Whilst reduced levels of conscientiousness and emotional stability has previously associated with poor sleep and insomnia, the current outcomes shed light on the mechanisms which serve to mediate this relationship.

This article maps the rise of the water-energy-food 'nexus' as a research, policy and project agenda in mainland Southeast Asia. We argue that introducing the concept of environmental justice into the nexus, especially where narratives, trade-offs and outcomes are contested, could make better use of how the nexus is framed, understood and acted upon. With funding from high-income country donors, it is found to have diffused from a global policy arena into a regional one that includes international and regional organisations, academic networks, and civil society, and national politicians and government officials. The nexus is yet to be extensively grounded, however, into national policies and practices, and broad-based local demand for nexus-framed policies is currently limited. The article contends that if the nexus is to support stated aspirations for sustainable development and poverty reduction, then it should engage more directly in identifying winners and losers in natural resource decision-making, the politics involved, and ultimately with the issue of justice. In order to do so, it links the nexus to the concept of environmental justice via boundary concepts, namely: sustainable development; the green economy; scarcity and addressing of trade-offs; and governance at, and across, the local, national and transnational scale.

Evidence-based veterinary medicine (EBVM) is the conscientious, explicit and judicious use of the current best evidence, when making decisions about the individual patient. Despite being shown to improve patient outcomes, the application of EBVM in equine practice remains seriously hampered by the lack of reliable data, even for the most common conditions.This poster won second place, which was presented at the Veterinary Evidence Today conference, Edinburgh November 1-3, 2016. Find out more about Sarah.

Cholangiocarcinoma (CCA) is a highly lethal malignant tumor arising from the biliary tract epithelium. Interleukin-6 (IL-6) is a major mediator of inflammation and contributor to carcinogenesis within the biliary tree. Previous studies suggested that enforced IL-6 contributes to cholangiocarcinogenesis through hypermethylation of several genes implicated in CCA. However, the precise mechanisms of IL-6 effects in CCA remain unclear. We now demonstrate that microRNA (miR)-370 is underexpressed in a large cohort of human CCA vs. normal liver tissues. In addition, we show that IL-6 induces a time-dependent silencing of miR-370. In addition, demethylation of CCA cells results in upregulation of miR-370. Furthermore, we demonstrate that miR-370 is imprinted, and that the Intergenic Differentially Methylated Region (IG-DMR) responsible for imprinting regulation of this genomic locus is hypermethylated in response to IL-6 treatment. In addition, the IG-DMR is hypermethylated in human CCA specimens compared to normal matched controls, in the same location as the IL-6 induced hypermethylation. Finally, miR-370 was found to regulate WNT10B in luciferase as well as western blotting experiments. Our data indicate that the paternal allele of miR-370 is normally silenced through genomic imprinting and that the overexpression of IL-6 in CCA effectively suppresses the expression of miR-370 from the maternal allele, lending support to the theory that miR-370 silencing in human CCA follows a classic two-hit mechanism.

One of the major factors in the promotion of paternal commitment is the ability of organizations and their representatives to contact fathers and offer them activities, services, resources or programs. Thanks to a 2003 survey of over 1000 Canadian organizations, we are in a position to describe the extent of interventions made available to fathers and the obstacles and results that were noted. We are also able to describe changes in such practices, via a sample group of respondents who took part in a similar survey four years earlier. Although we have observed an increase in services offered to fathers, there still remain a number of obstacles to improved access. However, this comparison over time shows that the continuance of services to fathers has lessened certain difficulties and, more especially, has made it easier to contact more fathers with problems.

Despite efforts to democratize horse/human relations, conceptions of harmony between horses and humans continue to privilege the human’s will, even in more progressive models of horsemanship. Using the tenets of Object-Oriented Ontology, this paper explores the ways in which nonhuman animal autonomy might condition cross-species connections and make harmony possible. While Object-Oriented Ontology acknowledges that all things withdraw from all things, this paper shows how touch is an access mode that can allude to and create out of the withdrawnness of the beings engaged in negotiation. In these processes of allusion and creation, we humans might simultaneously co-create and be immersed in harmonious, multispecies worlds.