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Abstract Mutations in the TP53 tumor suppressor gene occur in >80% of the triple-negative or basal-like breast cancer. To test whether neomorphic functions of specific TP53 missense mutations contribute to phenotypic heterogeneity, we characterized phenotypes of non-transformed MCF10A-derived cell lines expressing the ten most common missense mutant p53 proteins and observed a wide spectrum of phenotypic changes in cell survival, resistance to apoptosis and anoikis, cell migration, invasion and 3D mammosphere architecture. The p53 mutants R248W, R273C, R248Q, and Y220C are the most aggressive while G245S and Y234C are the least, which correlates with survival rates of basal-like breast cancer patients. Interestingly, a crucial amino acid difference at one position—R273C vs. R273H—has drastic changes on cellular phenotype. RNA-Seq and ChIP-Seq analyses show distinct DNA binding properties of different p53 mutants, yielding heterogeneous transcriptomics profiles, and MD simulation provided structural basis of differential DNA binding of different p53 mutants. Integrative statistical and machine-learning-based pathway analysis on gene expression profiles with phenotype vectors across the mutant cell lines identifies quantitative association of multiple pathways including the Hippo/YAP/TAZ pathway with phenotypic aggressiveness. Further, comparative analyses of large transcriptomics datasets on breast cancer cell lines and tumors suggest that dysregulation of the Hippo/YAP/TAZ pathway plays a key role in driving the cellular phenotypes towards basal-like in the presence of more aggressive p53 mutants. Overall, our study describes distinct gain-of-function impacts on protein functions, transcriptional profiles, and cellular behaviors of different p53 missense mutants, which contribute to clinical phenotypic heterogeneity of triple-negative breast tumors.

Category: Bunion; Other Introduction/Purpose: Minimally invasive techniques for surgical treatment of hallux valgus has gained popularity over the past few years. Most published reports involve combined minimally invasive Chevron and Akin osteotomies (MICA) performed by a single surgeon. This study reports radiographic and clinical results on patients who underwent minimally invasive transverse distal 1st metatarsal and Akin osteotomies by 3 fellowship trained Foot & Ankle orthopedic surgeons. A minimally invasive transverse distal 1st metatarsal osteotomy has advantages over MIS chevron osteotomy as it is less technically demanding and in theory, the surgeon can control 1st metatarsal head rotation to improve sesamoid position. Methods: Ninety-five consecutive patients between 2019 and 2021 with symptomatic Hallux valgus without 1st tarsometatarsal or metatarsal phalangeal joint arthritis or TMT joint instability were followed for at least one year. Primary radiographic outcomes include pre and postoperative hallux valgus and 1-2 intermetatarsal angles. Pain relief was measured by VAS scores. Patient Reported Outcomes (PROMS) used were Foot and Ankle Mobility (FAAM) scores in the dimension of activities of daily living (ADL) and sports. PROMS measured at one year follow-up. Radiographic recurrence was defined as a change in HVA >2.6 degrees between any 2 postoperative radiographs and an HVA >15 degrees. Z-Scores were calculated depending on the patient's demographics based on normative values to assess the deviation from a normal population FAAM scores. Results: Demographics and preoperative bunion classification of all patients included in this study can be found in table 1. Average pre-op HVA and IMA were 24.9 and 12.2 degrees respectively and improved to 8.43 and 5.86 degrees (p < 0.01) at 3 months. From the 3 months to 12 months, the patients’ HVA and IMA average was 9.39 and 6.85, but this change was not statistically significant (p = 0.35). VAS scores improved from 5.37 preoperatively to 1.9 at final follow up (p < 0.01). The average postoperative FAAM ADL score was (86.34 +/- 17.18) and z-score was (-0.08 +/- 1.16). The average postoperative FAAM sport score was (66.12 +/- 30.93) and z-score was (-0.26 +/- 1.94). Conclusion: Overall, the results of the study affirm the literature that third generation MIS hallux valgus surgery remains a good option. This study showed no infections in patients undergoing MIS hallux valgus surgery and the correction of the hallux valgus angles that persisted at 12 months with low recurrence rates. At this time, the results show a trend toward lower FAAM scores postoperatively at one year follow-up that was significant in the sports subscore but the difference from a normal population is not significant in the ADL subscore. Longer follow-up is needed to evaluate the trend further.

Purpose: Trauma centres have been proven to provide better outcomes in developed countries for overall trauma, but there is limited literature on the systematic factors that describe any discrepancies in outcomes for trauma laparotomies in these centres. This study was conducted to examine and interrogate the effect of systematic factors on patients undergoing a trauma laparotomy in a developed country, intending to identify potential discrepancies in the outcome. Methods: This was a retrospective study of all laparotomies performed for trauma at a level 1 trauma centre in New Zealand. All adult patients who had undergone an index laparotomy for trauma between February 2012 and November 2020 were identified and laparotomies for both blunt and penetrating trauma were included. Repeat laparotomies and trauma laparotomies in children were excluded. The primary clinical outcomes reviewed included morbidity, length of hospital stay, and mortality. All statistical analysis was performed using R v.4.0.3. Results: During the 9-year study period, 204 trauma laparotomies were performed at Waikato hospital. The majority (83.3%) were performed during office hours (170/204), and the remaining 16.7% were performed after hours (34/204). And 61.3% were performed on a weekday (125/204), whilst 38.7% were performed on the weekend/public holiday (79/204). Most of the parameters in office hours and after hours groups had no statistically significant difference, except lactate (p = 0.026). Most of the variables in weekday and weekend groups had no statistically significant difference, except pH, lactate, length of stay, and gastrointestinal complications (p = 0.012, p

Introduction: Blunt colonic injury (BCI) is relatively rare, and literature on the topic is sparse. This study reviews our contemporary experience in its management at a level-one trauma centre in New Zealand. Materials and Methods: This was a retrospective study (January 2012 to December 2020) that included all patients who sustained a BCI managed at Waikato Hospital, New Zealand. Results: Of the total of 1181 patients with blunt abdominal trauma, 69 (6%) of them sustained a BCI (49% male, mean age: 36 years). 78 separate colonic injuries were identified in the 69 cases. The most commonly injured segment was the ascending colon 49% (38/78). Eighty percent (55/69) underwent a CT scan, with only 16 showing definite evidence of a colonic injury. AAST Grade 1 was the most common (81%). Fifteen patients underwent damage control surgery. All 11 grade 1 injuries were repaired primarily, whilst the other four grade 4 and 5 colonic injuries were resected, with 3 having a subsequent stoma formation and one delayed anastomosis. There were four mortalities. Patients who had negative or equivocal admission CT findings for colonic injury had delays to the operating theatre and had poorer outcomes. Conclusion: BCI is rare but is associated with a prolonged hospital stay. The treatment of BCI is similar to that of penetrating colonic injury. CT appeared inaccurate in many cases.

Transgender (trans) and gender diverse (TGD) populations continue to experience significant inequities in social and health outcomes, often in connection with the systemic exposure of these groups to violence, stigma, and discrimination. Despite the promising role of peer support in mitigating adverse impacts of marginalization, this phenomenon remains under-examined. In this study, which is informed methodologically by an abductive approach to grounded theory and anchored theoretically in scholarship on critical resilience and intersectionality, we draw on individual semi-structured interviews with 35 TGD individuals located in two major cities in Canada (Toronto and Vancouver) to examine experiences of peer support. We also consider the role of peer support in building resilience among participants. Our findings are organized into four interrelated themes that both represent the constituent parts of peer support, and that explicate the connections between peer support and resilience. These include: (1) becoming visible to connect with similar others, (2) sharing embodiment, experience, and space, (3) constructing possibilities of being and collectivizing, and (4) surviving and thriving (at a cost). We leverage our findings to consider implications for research, policy, and practice, one of which includes the need for ongoing inquiry to substantiate the critical role of peer support in promoting health across diverse TGD communities.

Background: The literature has suggested that acceptable outcomes in elective general surgery can be achieved with registrars operating but is less clear with trauma surgery. Methods: This was a retrospective study of all laparotomies performed for adult trauma between 2012 and 2020 at a Level 1 Trauma Centre in New Zealand to identify potential differences in clinical outcomes between primary operators. The primary operator of each operation was identified, along with the presence or absence of a consultant and the clinical outcome. Results: During the 9-year study period, a total of 204 trauma laparotomies were performed at Waikato Hospital. The groups of the primary operators were: a registrar with a consultant present (27%), a registrar without a consultant present (22%), a registrar assisting a consultant (48%), and a consultant who operated without a registrar (3%). Direct comparison was made between the three groups where registrars were involved in the laparotomy. There was no significant difference in the clinical outcomes, whether a consultant was present or not. Conclusions: Surgical registrars have acceptable outcomes for trauma laparotomy in the appropriate patients. A consultant surgeon should still operate on patients with more significant physiological derangements.

Ankle arthrodesis (AA) represents an effective, dependable procedure for the treatment of end-stage osteoarthritis of the ankle. While AA offers the benefits of pain relief and some preservation of function, it sacrifices ankle motion which over time may lead to progressive degeneration of the adjacent joints of the hindfoot. Historically, salvage options for failed or painful AA included revisional AA, tibiotalocalcaneal arthrodesis, pantalar arthrodesis, and amputation. More recently the conversion of AA to total ankle arthroplasty (TAA) has been shown to be a viable salvage option which, unlike early salvage options, restores motion and function to the ankle and may help to avoid the need for periarticular arthrodesis. A unique challenge faced with AA conversion to TAA includes instances where fibular resection was performed during the primary procedure. Previous studies have evaluated the viability of conversion to TAA in patients with AA and prior fibular resection, with most authors stating that the absence of the lateral malleolus is an absolute contraindication to TAA. In contrast, newer studies have reported success with various techniques to restore the lateral fibular strut and perform the conversion of AA to TAA. This case report describes a unique approach of AA conversion to TAA utilizing a custom, fibular prosthesis to restore lateral stability following prior AA with fibular resection.

Aim: The management of abdominal stab wounds (SW) has continued to evolve. The use of CT and laparoscopy has been advocated to reduce the rate of laparotomy. This study reviews our experience with SW in a high income, low volume setting. Methods: A retrospective study was undertaken from 2006 to 2020 at Waikato Hospital, New Zealand. All adult patients age > 16 years that were admitted following trauma were included. Results: Seventy three cases of SW were included. Thirty two cases had indications for immediate laparotomy (peritonitis in 15, hemodynamic instability in 13, evisceration in 4). Twenty two underwent immediate laparotomy. Overall, 43 had a positive laparotomy. One had a negative laparotomy. Thirty seven cases had a CT. Laparoscopy was performed in 24 cases, with 23 demonstrating peritoneal breach. Subsequently 9 were converted to laparotomy whilst 15 had full laparoscopic exploration. Conclusion: The relative rarity of abdominal SW in our environment has resulted in a considerable degree of heterogeneity in our approach to this clinical dilemma. The simplified algorithm we have developed will hopefully facilitate clinical decision making in our institution.

Introduction: The objective of this study was to review the experience of surgical registrars in performing trauma laparotomies at a level 1 trauma centre in New Zealand, and to benchmark this exposure against the current literature on the topic. Methods: A cohort study was conducted retrospectively at a level 1 trauma centre, Waikato Hospital, Hamilton, New Zealand. All patients (>15 years) who underwent a laparotomy for trauma between 2012 and 2020 were included. These patients were stratified by the study conductors retrospectively, according to each case's primary operator and compared the experience of each respective operator according to the time of day and by the mechanism of injury. Results: During the 9-year study period, a total of 204 trauma laparotomies were performed at Waikato Hospital. Of these 204 laparotomies, a consultant was present in 78% (160/204). In 27% of cases, a registrar was the primary operator with a consultant present (55/204), and in 22% of cases, the registrar was the primary operator with no consultant present (44/204). In 48%, a registrar assisted a consultant (98/204), and in 3%, a consultant performed the operation without a registrar assisting (7/204). Based on there being four registrars rotating through Waikato Hospital each 6-month cycle, this would imply that each registrar would be exposed to three trauma laparotomies each cycle. Conclusions: Despite significant institutional volumes, the exposure of individual New Zealand surgical registrars to trauma laparotomy is limited. In addition, most trauma laparotomies were performed by registrars as assistants rather than as primary operators. It is hoped that the newly launched Post Fellowship Education and Training (PFET) in trauma in Australasia will provide greater exposure to surgeons who will be managing trauma in the future.

We analyze the MOA-2020-BLG-208 gravitational microlensing event and present the discovery and characterization of a new planet, MOA-2020-BLG-208Lb, with an estimated sub-Saturn mass. With a mass ratio $q={3.17}_{-0.26}^{+0.28}\times {10}^{-4}$ , the planet lies near the peak of the mass-ratio function derived by the MOA collaboration and near the edge of expected sample sensitivity. For these estimates we provide results using two mass-law priors: one assuming that all stars have an equal planet-hosting probability, and the other assuming that planets are more likely to orbit around more massive stars. In the first scenario, we estimate that the lens system is likely to be a planet of mass ${m}_{\mathrm{planet}}={46}_{-24}^{+42}\,{M}_{\oplus }$ and a host star of mass ${M}_{\mathrm{host}}={0.43}_{-0.23}^{+0.39}\,{M}_{\odot }$ , located at a distance ${D}_{L}={7.49}_{-1.13}^{+0.99}\,\mathrm{kpc}$ . For the second scenario, we estimate ${m}_{\mathrm{planet}}={69}_{-34}^{+37}\,{M}_{\oplus }$ , ${M}_{\mathrm{host}}={0.66}_{-0.32}^{+0.35}\,{M}_{\odot }$ , and ${D}_{L}={7.81}_{-0.93}^{+0.93}\,\mathrm{kpc}$ . The planet has a projected separation as a fraction of the Einstein ring radius $s={1.3807}_{-0.0018}^{+0.0018}$ . As a cool sub-Saturn-mass planet, this planet adds to a growing collection of evidence for revised planetary formation models.

Abstract Background Adult T-cell leukemia lymphoma (ATLL) is a chemotherapy-resistant malignancy with a median survival of less than one year that will afflict between one hundred thousand and one million individuals worldwide who are currently infected with human T-cell leukemia virus type 1. Recurrent somatic mutations in host genes have exposed the T-cell receptor pathway through nuclear factor κB to interferon regulatory factor 4 (IRF4) as an essential driver for this malignancy. We sought to determine if IRF4 represents a therapeutic target for ATLL and to identify downstream effectors and biomarkers of IRF4 signaling in vivo. Results ATLL cell lines, particularly Tax viral oncoprotein-negative cell lines, that most closely resemble ATLL in humans, were sensitive to dose- and time-dependent inhibition by a next-generation class of IRF4 antisense oligonucleotides (ASOs) that employ constrained ethyl residues that mediate RNase H-dependent RNA degradation. ATLL cell lines were also sensitive to lenalidomide, which repressed IRF4 expression. Both ASOs and lenalidomide inhibited ATLL proliferation in vitro and in vivo. To identify biomarkers of IRF4-mediated CD4 + T-cell expansion in vivo, transcriptomic analysis identified several genes that encode key regulators of ATLL, including interleukin 2 receptor subunits α and β, KIT ligand, cytotoxic T-lymphocyte-associated protein 4, and thymocyte selection-associated high mobility group protein TOX 2. Conclusions These data support the pursuit of IRF4 as a therapeutic target in ATLL with the use of either ASOs or lenalidomide.

Police records, held in the Crash Analysis System (CAS) by the New Zealand Transport Agency (NZTA), and hospital admission data held in the Midland Trauma System (MTS) trauma registry, were linked using probabilistic methods. A total of 1,331 casualties resulting from motorcycle crashes on roads in the Midland Region during 2012-2016 were recorded by police. During the same period, and occurring within the same geographical area, a total of 689 on-road motorcycle related crash casualties were admitted to hospital as trauma patients. Linkage of these two datasets revealed substantial under reporting to police of motorcycle crash casualties resulting in hospitalisation. Approximately 56% (386) of hospital trauma admission records could be linked with police CAS records with an additional 303 (44%) patient admission records which could not be linked to any police records. Linkage rates were significantly associated with crash severity as recorded by police, patient injury severity recorded in the trauma registry, patient age, rurality of crash location, and self-presentation to hospital. In particular, younger motorcyclists aged under 45 years were significantly more likely to self-present to hospital with the odds of linkage for self-presenters seventeen times lower than those who did not self-present. The merging of these two datasets has highlighted several sources of bias underlying reporting of motorcycle crashes to police. An understanding of these biases may help to inform policymakers when planning wider preventive strategies designed to reduce the burden of motorcycle crashes in New Zealand.

The COVID-19 pandemic has significantly affected all aspects of social work education, including field education. The Transforming the Field Education Landscape (TFEL) partnership conducted two national online surveys to determine the impacts of the pandemic on social work field education. The first survey explored the perspectives of students and received responses from 367 Bachelor of Social Work (BSW) and Master of Social Work (MSW) students. The second survey was designed to gather the perspectives of field instructors, with 73 field instructors completing the survey. The article examines the impacts of the pandemic on social work practice, field supervision, practicum flexibility and accommodations in placement, the shift to remote learning, perceptions of future career prospects and the effects on wellness and mental health. This article contributes to an increased understanding of the strengths and challenges facing social work field education, and informs field planning and responses in a pandemic. The findings will be of interest to social work field education programmes, field education coordinators and directors, field instructors, field agencies and undergraduate and graduate social work students. Recommendations for social work field education are offered.

Background and Objectives: Now more than ever, there is an obvious need to reduce the overall burden of disease and risk of premature mortality that are associated with mental health and substance use disorders among young people. However, the current state of research and evidence-based clinical care for high-risk substance use among youth is fragmented and scarce. The objective of the study is to establish consensus for the prevention, treatment, and management of high-risk substance use and overdose among youth (10 to 24 years old). Materials and Methods: A modified Delphi technique was used based on the combination of scientific evidence and clinical experience of a group of 31 experts representing 10 countries. A semi-structured questionnaire with five domains (clinical risks, target populations, intervention goals, intervention strategies, and settings/expertise) was shared with the panelists. Based on their responses, statements were developed, which were subsequently revised and finalized through three iterations of feedback. Results: Among the five major domains, 60 statements reached consensus. Importantly, experts agreed that screening in primary care and other clinical settings is recommended for all youth, and that the objectives of treating youth with high-risk substance use are to reduce harm and mortality while promoting resilience and healthy development. For all substance use disorders, evidence-based interventions should be available and should be used according to the needs and preferences of the patient. Involuntary admission was the only topic that did not reach consensus, mainly due to its ethical implications and resulting lack of comparable evidence. Conclusions: High-risk substance use and overdoses among youth have become a major challenge. The system’s response has been insufficient and needs substantial change. Internationally devised consensus statements provide a first step in system improvement and reform.

Due to the COVID-19 pandemic, cities and states adopted social distancing, social isolation, or quarantine measurements to slow the transmission of the disease. Negative mental health outcomes including depression and anxiety have been associated with social distancing or social isolation. The purpose of the present study was to examine changes in psychological health and physical activity over an 8 week period under social distancing policies during the COVID-19 pandemic.Methods: Ninety (73.3% female; age 32.04 ± 11.33) individuals participated in this study. Qualifying participants answered questions using an online survey regarding their loneliness, depressive symptoms, anxiety symptoms, mood state, and physical activity over four time points each lasting two weeks.Results: Symptoms of depression and state anxiety were increased in the population when compared to nationwide statistics from before the COVID-19 pandemic. Time point 2, ~1 month into social isolation, showed the most significant effects on mental health. During this time point, 100% of the participants showed symptoms of depression. There were no significant changes in physical activity over the 8 weeks. Loneliness, depressive symptoms, fatigue, and mood state were negatively associated with participation in physical activity. Vigor and state anxiety were associated with participation in physical activity.Conclusion: Social isolation and social distancing practices have had a negative effect on depression, anxiety, and mood over time. It appeared that depressive symptoms and total mood disturbance was elevated during time point two. Depressive symptoms were much higher than average compared to previous epidemiological data. Physical activity amount did not change over time but was associated with poor mental health.

Introduction Haemorrhage causes most preventable prehospital trauma deaths and about a third of in-hospital trauma deaths. Tranexamic acid (TXA), administered soon after hospital arrival in certain trauma systems, is an effective therapy in preventing or managing acute traumatic coagulopathy. However, delayed administration of TXA appears to be ineffective or harmful. The effectiveness of prehospital TXA, incidence of thrombotic complications, benefit versus risk in advanced trauma systems and the mechanism of benefit remain uncertain.Methods and analysis The Pre-hospital Anti-fibrinolytics for Traumatic Coagulopathy and Haemorrhage (The PATCH-Trauma study) is comparing TXA, initiated prehospital and continued in hospital over 8 hours, with placebo in patients with severe trauma at risk of acute traumatic coagulopathy. We present the trial protocol and an overview of the statistical analysis plan. There will be 1316 patients recruited by prehospital clinicians in Australia, New Zealand and Germany. The primary outcome will be the eight-level Glasgow Outcome Scale Extended (GOSE) at 6 months after injury, dichotomised to favourable (GOSE 5–8) and unfavourable (GOSE 1–4) outcomes, analysed using an intention-to-treat (ITT) approach. Secondary outcomes will include mortality at hospital discharge and at 6 months, blood product usage, quality of life and the incidence of predefined adverse events.Ethics and dissemination The study was approved by The Alfred Hospital Research and Ethics Committee in Victoria and also approved in New South Wales, Queensland, South Australia, Tasmania and the Northern Territory. In New Zealand, Northern A Health and Disability Ethics Committee provided approval. In Germany, Witten/Herdecke University has provided ethics approval. The PATCH-Trauma study aims to provide definitive evidence of the effectiveness of prehospital TXA, when used in conjunction with current advanced trauma care, in improving outcomes after severe injury.Trial registration number NCT02187120.

Abstract Background The Hessian fly response genes, Hfr-1 and Hfr-2, have been reported to be significantly induced in a Hessian fly attack. Nothing is known about the allelic variants of these two genes in susceptible (S) and resistant (R) wheat cultivars. Results Basic local alignment search tool (BLAST) analysis of Hessian fly response genes have identified three alleles of Hessian fly response gene 1 (Hfr-1) on chromosome 4AL and 7DS, and 10 alleles of Hessian fly response gene 2 (Hfr-2) on chromosome 2BS, 2DL, 4BS, 4BL, 5AL and 5BL. Resequencing exons of Hfr-1 and Hfr-2 have identified a single nucleotide polymorphism (SNP) in the lectin domain of each gene that segregates some R sources from S cultivars. Two SNP assays have been developed. The SNP883_Hfr-1 assay characterizes a ‘G/A’ SNP in Hfr-1, which differentiates 14 Hessian fly R cultivars from S ones. The SNP1294_Hfr-2 assay differentiates 12 R cultivars from S ones. Each of the two SNPs identified in Hfr-1 and Hfr-2 is ‘G/A’ and resulted in an amino acid change from isoleucine to valine in the lectin domain of the proteins of the alleles in the R cultivars. In addition to the genotype profiles of Hfr-1 and Hfr-2, generated for a set of 249 wheat cultivars which included a set of 39 R cultivars, this study has genotyped the Hessian fly response gene, HfrDrd, and the H32 gene for the wheat germplasm. Resistant cultivars from different origins with one, two, three or four resistance (R) genes in various combinations/permutations have been identified. Conclusion This study has identified allelic differences in two Hessian fly response genes, Hfr-1 and Hfr-2, between S and R cultivars and developed one SNP assay for each of the genes. These two SNP assays for Hfr-1 and Hfr-2, together with the published assays for HfrDrd and the H32 gene, can be used for the selection and incorporation of one or more of these 4 R genes identified in the different R sources in wheat breeding programs.

Prostate cancer affects men and their loved ones; consequently, survivors and their wives can gain from social support throughout the illness experience. After observing meetings of a support group for prostate cancer survivors and their partners, the authors used the constant comparison method to draw conclusions about the types of support generated in the men's and women's divisions of the group. The authors concluded that both divisions served as sites of information but not as scenes of practical assistance. The authors also found that the discursive practices of the groups and the structural elements of the group meetings inhibited emotional support through topic turning, comparisons between members, and the role of group facilitators. The authors consider the study's implications for support group leaders and scholars. [ABSTRACT FROM AUTHOR]

Introduction: A continuing policy and practice challenge in New Zealand has been how to reduce fragmentation and achieve more integrated care – co-ordinated care that provides a smooth and continuous transition between services, as patients receive health, rehabilitation and vocational services. The aim of this research is to explore injured patients’ experiences of care to identify areas for improvement in service delivery. Methods: Qualitative study drawing on 17 in-depth, semi-structured interviews, conducted from 1 October 2017 to 31 November 2017, with trauma patients (and patient-nominated key support people and health or social care professionals) registered by the Midland Trauma System Registry (New Zealand). Results: Patients perceived their pre-hospital and emergency care as high quality and highly valued the kindness of staff, although expressed concerns regarding access to psychosocial services to manage ongoing psychological trauma, the high level of reliance on key support people, inadequate information provision about what to expect in relation to the journey through the health system and a lack of preparedness for discharge. Trauma patients also perceived the need for a single point of contact for coordination of post-discharge care. Discussion: Surviving a traumatic event resulting in serious injury is a time of chaos and confusion for patients and their key support people. Inadequate communication from interprofessional health and social care professionals about what to expect in relation to the patient journey through the health and social care systems adds to this predicament significantly. Key support people are the single largest factor in facilitating patients’ recovery from serious injury yet are left significantly unsupported. Conclusion: This study identified several possible areas for improvement to service delivery following serious injury; specifically: (1) the review of service provider communication and service delivery processes and practices in co-design with former patients and key support people, including information sharing and discharge planning checklists; (2) screening for psychological trauma and facilitation of early engagement with psychological and counselling services; and (3) the review of outpatient clinic appointment booking practices and the use of virtual clinics. Lessons learned: These findings provide the opportunity to implement system changes, co-designed in partnership with patients, key support people, service and compensation providers, to support improved health and vocational outcomes following serious injury. Although undertaken in the Midland region, opportunities for improvement may apply to other healthcare contexts. Limitations: Complete exclusion of AIS body region one (head/neck) limited the number of eligible participants. Service provider perspectives were not fully explored as only a single participant from this group was nominated, which reinforced patient perceptions regarding lack of coordination of post-discharge care. Suggestions for future research: The size of this study limited the ability to explore the potential opportunities for improvement identified in smaller patient subgroups, including perceptions regarding cultural responsiveness. A larger study would provide the opportunity to explore more thoroughly additional opportunities for improvement.

There is a dearth of research on student-to-student abuse in Canada’s Indian Residential School System despite the fact that the legacy of this violence continues to negatively impact Indigenous communities. This paper proposes an approach to dealing with this difficult subject matter by using creative practice as a means of working collectively with community leaders, scholars, artists and students to develop shared understandings of the abuse and its continued legacy. This paper outlines the rationale for work in this area and the beginnings of the development of hybrid Indigenous and non-Indigenous methodology that brings survivors’ stories to audiences through a series of collectively authored theatrical performances that promote understanding and dialog. This paper is of interest to scholars, artists, playwrights, community leaders, and front line social workers who are working to bridge academic research and community engagement, particularly as it relates to artistic practice.

Pospiviroid species are transmitted through capsicum and tomato seeds. Trade in these seeds represents a route for the viroids to invade new regions, but the magnitude of this hazard has not been adequately investigated. Since 2012, tomato seed lots sent to Australia have been tested for pospiviroids before they are released from border quarantine, and capsicum seed lots have been similarly tested in quarantine since 2013. Altogether, more than 2000 seed lots have been tested. Pospiviroids were detected in more than 10% of the seed lots in the first years of mandatory testing, but the proportion of lots that were infected declined in subsequent years to less than 5%. Six pospiviroid species were detected: Citrus exocortis viroid, Columnea latent viroid, Pepper chat fruit viroid, Potato spindle tuber viroid, Tomato chlorotic dwarf viroid and Tomato apical stunt viroid. They were detected in seed lots exported from 18 countries from every production region. In many seed lots, the detectable fraction (prevalence) of infected seeds was estimated to be very small, as low as 6 × 10−5 (~1 in 16,000; CI 5 × 10−6 to 2.5 × 10−4) for some lots. These findings raise questions about seed production practices, and the study indicates the geographic distributions of these pathogens are uncertain, and there is a continuing threat of invasion.

This study explores the negotiation of care between a young carer and her parent experiencing mental illness and addiction. The bulk of research on young carers explores children’s caring work and the associated risks for carrying out caring work. Usually overlooked are the highly complex relationships between disabled or ill parents and their children who care for them. Using contextual action theory to frame this case study, we examine how a young carer and her mother negotiated care across a period of several months.

Tilletia indica causes the disease Karnal bunt in wheat. The disease is under international quarantine regulations. Comparative mitochondrial (mt) genome analysis of T. indica (KX394364 and DQ993184) and T. walkeri (EF536375) has found 325 to 328 SNPs, 57 to 60 short InDels (from 1 to 13 nt), two InDels (30 and 61 nt) and five (>200 nt) presence/absence variations (PAVs) between the two species. The mt genomes of both species have identical gene order. The numbers of SNPs and InDels between the mt genomes of the two species are approximately nine times of the corresponding numbers between the two T. indica isolates. There are eight SNPs between T. indica and T. walkeri that resulted in amino acid substitutions in the mt genes of cob, nad2 and nad5. In contrast, there is no amino acid substitution in the mt genes of the T. indica isolates from the SNPs found. The five PAVs present in T. indica (DQ993184) are absent in T. walkeri. Four PAVs are more than 1 kb and are not present in every T. indica isolate. Analysis of their presence and absence separates a collection of T. indica isolates into 11 subgroups. Two PAVs have ORFs for the LAGLIDAG endonuclease and two have ORFs for the GIY-YIG endonuclease family, which are representatives of homing endonuclease genes (HEGs). These intron- encoded HEGs confer intron mobility and account for their fluid distribution in T. indica isolates. The small PAV of 221 bp, present in every T. indica isolate and unique to the species, was used as the genetic fingerprint for the successful development of a rapid, highly sensitive and specific loop mediated isothermal amplification (LAMP) assay. The simple procedure of the LAMP assay and the easy detection formats will enable the assay to be automated for high throughput diagnosis.

BACKGROUND: Helicobacter pylori is a WHO class I carcinogen also associated with nonmalignant gastrointestinal diseases. Effective treatment exists, and all persons infected with H pylori should receive treatment. However, data regarding the rates of treatment prescription in clinical practice are lacking.

Abstract Background Prophages of enteric bacteria are frequently of key importance for the biology, virulence, or host adaptation of their host. Some C. jejuni isolates carry homologs of the CJIE1 (CMLP 1) prophage that carry cargo genes potentially involved in virulence. Possible role(s) of CJIE1 homologs in the biology and virulence of C. jejuni were therefore investigated by using in vitro cell culture assays and by assessing the association of C. jejuni isolates with and without these prophages with patients’ symptoms, with source, and with clonal lineages within the C. jejuni population. Results Four C. jejuni isolates, three carrying the CJIE1-like prophage and one without, were tested in cell culture assays for adherence and invasion. Both adherence and invasion of C. jejuni to cells in culture were increased by the presence of the CJIE1-family prophage. Differences in motility and growth rate did not appear to be responsible. The CJIE1 prophage was present in 23% of isolates from human and non-human sources combined that were obtained through sentinel-site surveillance, and the distribution of CJIE1 in this population showed modest clonal associations. There was no correlation between the presence of the CJIE1 prophage in C. jejuni and patient symptoms, although there was some statistical support for lower rates of abdominal pain and fever when the prophage was present. Little evidence was found for a role of the prophage in host adaptation or host specificity. Conclusion These biological effects suggest that the presence of the prophage may be a marker for differential virulence of some C. jejuni isolates. Ongoing research into the effects of the prophage on protein expression may provide additional insights into the roles the prophage may play in the biology of its host bacterium.

Abstract Background The alphaproteobacterium Wolbachia pipientis, the most common endosymbiont in eukaryotes, is found predominantly in insects including many Drosophila species. Although Wolbachia is primarily vertically transmitted, analysis of its genome provides evidence for frequent horizontal transfer, extensive recombination and numerous mobile genetic elements. The genome sequence of Wolbachia in Drosophila simulans Riverside (wRi) is available along with the integrated bacteriophages, enabling a detailed examination of phage genes and the role of these genes in the biology of Wolbachia and its host organisms. Wolbachia is widely known for its ability to modify the reproductive patterns of insects. One particular modification, cytoplasmic incompatibility, has previously been shown to be dependent on Wolbachia density and inversely related to the titer of lytic phage. The wRi genome has four phage regions, two WORiBs, one WORiA and one WORiC. Results In this study specific primers were designed to distinguish between these four prophage types in wRi, and quantitative PCR was used to measure the titer of bacteriophages in testes, ovaries, embryos and adult flies. In all tissues tested, WORiA and WORiB were not found to be present in excess of their integrated prophages; WORiC, however, was found to be present extrachromosomally. WORiC is undergoing extrachromosomal replication in wRi. The density of phage particles was found to be consistent in individual larvae in a laboratory population. The WORiC genome is organized in conserved blocks of genes and aligns most closely with other known lytic WO phages, WOVitA and WOCauB. Conclusions The results presented here suggest that WORiC is the lytic form of WO in D. simulans, is undergoing extrachromosomal replication in wRi, and belongs to a conserved family of phages in Wolbachia.

Abstract Background The control of gene expression in eukaryotic cells occurs both transcriptionally and post-transcriptionally. Although many genes are now known to be regulated at the translational level, in general, the mechanisms are poorly understood. We have previously presented polysomal gradient and array-based evidence that translational control is widespread in a significant number of genes when yeast cells are exposed to a range of stresses. Here we have re-examined these gene sets, considering the role of UTR sequences in the translational responses of these genes using recent large-scale datasets which define 5' and 3' transcriptional ends for many yeast genes. In particular, we highlight the potential role of 5' UTRs and upstream open reading frames (uORFs). Results We show a highly significant enrichment in specific GO functional classes for genes that are translationally up- and down-regulated under given stresses (e.g. carbohydrate metabolism is up-regulated under amino acid starvation). Cross-referencing these data with the stress response data we show that translationally upregulated genes have longer 5' UTRs, consistent with their role in translational regulation. In the first genome-wide study of uORFs in a set of mapped 5' UTRs, we show that uORFs are rare, being statistically under-represented in UTR sequences. However, they have distinct compositional biases consistent with their putative role in translational control and are more common in genes which are apparently translationally up-regulated. Conclusion These results demonstrate a central regulatory role for UTR sequences, and 5' UTRs in particular, highlighting the significant role of uORFs in post-transcriptional control in yeast. Yeast uORFs are more highly conserved than has been suggested, lending further weight to their significance as functional elements involved in gene regulation. It also suggests a more complex and novel mechanism of control, whereby uORFs permit genes to escape from a more general attenuation of translation under conditions of stress. However, since uORFs are relatively rare (only ~13% of yeast genes have them) there remain many unanswered questions as to how UTR elements can direct translational control of many hundreds of genes under stress.

The relationship between socioeconomic deprivation and health is inequitable. Chronic kidney disease (CKD) is an archetypal disease of inequality, being more common amongst those living in deprivation. The prevalence of CKD is rising driven by an increase in lifestyle-related conditions. This narrative review describes deprivation and its association with adverse outcomes in adults with non-dialysis-dependent CKD including disease progression, end-stage kidney disease, cardiovascular disease and all-cause mortality. We explore the social determinants of health and individual lifestyle factors to address whether patients with CKD who are socioeconomically deprived have poorer outcomes than those of higher socioeconomic status. We describe whether observed differences in outcomes are associated with income, employment, educational attainment, health literacy, access to healthcare, housing, air pollution, cigarette smoking, alcohol use or aerobic exercise. The impact of socioeconomic deprivation in adults with non-dialysis-dependent CKD is complex, multi-faceted and frequently under-explored within the literature. There is evidence that patients with CKD who are socioeconomically deprived have faster disease progression, higher risk of cardiovascular disease and premature mortality. This appears to be the result of both socioeconomic and individual lifestyle factors. However, there is a paucity of studies and methodological limitations. Extrapolation of findings to different societies and healthcare systems is challenging, however, the disproportionate effect of deprivation in patients with CKD necessitates a call to action. Further empirical study is warranted to establish the true cost of deprivation in CKD to patients and societies., Competing Interests: The authors declare no conflicts of interest. Unrelated to this work, K.I.S. has received personal lectureship honorarium from Bayer and Boehringer Ingelheim. K.I.S. is member of the CKJ editorial board. J.S.L. has received personal lectureship honorarium from Pfizer, AstraZeneca and Bristol Myers Squibb. The results presented in this paper have not been published previously in whole or part., (© The Author(s) 2023. Published by Oxford University Press on behalf of the ERA.)

Background: Lung cancer is the most common cause of cancer related death worldwide and survival is poor. Patients with lung cancer may develop a critical illness, but it is unclear what features are associated with an Intensive Care Unit (ICU) admission., Methods: This retrospective, observational, population-based study of linked cancer registration, ICU, hospital discharge and mortality data described the factors associated with ICU admission in patients with lung cancer. The cohort comprised all incident cases of adult lung cancer diagnosed between 1st January 2000 and 31st December 2009 in the West of Scotland, UK, who were subsequently admitted to an ICU within 2 years of cancer diagnosis. Multiple logistic regression was used to determine factors associated with admission., Results: 26,731 incident cases of lung cancer were diagnosed with 398 (1.5%) patients admitted to an ICU. Patients were most commonly admitted with respiratory conditions and there was a high rate of invasive mechanical ventilation. ICU, in-hospital and six-month survival were 58.5, 42.0 and 31.2%, respectively. Surgical treatment of lung cancer increased the odds of ICU admission (OR 7.23 (5.14-10.2)). Odds of admission to ICU were reduced with older age (75-80 years OR 0.69 (0.49-0.94), > 80 years OR 0.21 (0.12-0.37)), female gender (OR 0.73 (0.59-0.90)) and radiotherapy (OR 0.54 (0.39-0.73)) or chemotherapy treatment (OR 0.52 (0.38-0.70))., Conclusion: 1.5% of patients diagnosed with lung cancer are admitted to an ICU but both short term and long term survival was poor. Factors associated with ICU admission included age < 75 years, male gender and surgical treatment of cancer.

Background: Proton pump inhibitors (PPIs) are associated with acute tubulointerstitial nephritis and there are reports associating their use with the development of chronic kidney disease (CKD)., Aim: To determine if PPI use is associated with major adverse renal events (MARE) in patients with CKD., Design: Observational cohort study comprising patients with CKD attending secondary care renal clinics from 1 January 2006 until 31 December 2016., Methods: We collated baseline clinical, socio-demographic and biochemical data at start of PPI (PPI group) or study inception (control group). MARE was considered a composite of doubling of creatinine or end-stage renal disease. Association between PPI exposure and progression to MARE was assessed by cause-specific hazards competing risk survival analysis., Results: There were 3824 patients with CKD included in the analyses of whom 1195 were prescribed a PPI. The PPI group was younger (64.8 vs. 67.0 years, P < 0.001), with lower estimated glomerular filtration rate (eGFR) (30 vs. 35 ml/min, P < 0.001) and more proteinuria (64 vs. 48 mg/mmol, P < 0.001). PPI use was associated with progression to MARE on multivariable adjustment (hazard ratio 1.13 [95% confidence interval 1.02-1.25], P = 0.021). Other factors significantly associated with progression to MARE were higher systolic blood pressure, lower eGFR, greater proteinuria, congestive cardiac failure and diabetes. Hypomagnesaemia was more common in the PPI group (39.5 vs. 18.9%, P < 0.001)., Conclusion: PPI use was associated with progression to MARE, but not death in patients with CKD after adjusting for factors known to predict declining renal function, including lower eGFR, proteinuria and comorbidities. A prospective cohort study is required to validate these findings., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Prolonged antibiotic therapy is associated with antimicrobial resistance and increased mortality in preterm infants. We evaluated the impact of an automatic stop order (ASO) and C-reactive protein (CRP) on the duration of antibiotics and level of intervention in infants screened for early-onset sepsis who had negative cultures. We introduced an ASO for low-risk infants, then, consequently, for all infants treated for suspected sepsis. We subsequently introduced a single CRP measurement at 36 hours. Between 2011 and 2014, 4 time periods were studied, at baseline and after each intervention. The proportion of infants receiving ≤48 hours of antibiotics increased from 19% to 72.5% ( P < .0001), whereas that of infants receiving avoidable doses (>48 hours and <5 days) fell from 50% to 0.8% ( P < .0001). The use of an ASO decreased the proportion receiving avoidable doses from 26/92 (28.3%) to 9/293 (3.1%); P < .0001. There was a reduction in lumbar punctures performed, from 35% to 20%; P = .015.

Background: Exercise improves physical capacity in patients with end-stage renal disease on haemodialysis (HD), but few patients engage in it. Whole-body vibration exercise (WBVE) is a novel protocol that has been shown to benefit frail elderly patients' rehabilitation. We assessed the utility of WBVE before HD sessions and tested methods to inform the design of a randomized controlled trial (RCT)., Methods: Physical condition and quality of life were assessed at enrolment and repeated 2 weeks later in a pilot study of 49 patients undergoing regular HD. All patients then undertook 8 weeks of WBVE, thrice weekly for 3 min, after which the assessments were repeated and results compared (paired t -tests). Further assessments were made after a 4-week layoff. Patients completed a post-study questionnaire about their experiences of using WBVE. The reproducibility of WBVE and effects on measures of functionality, muscle strength, indirect exercise capacity, nutritional status, bone health and quality of life were recorded to undertake a power calculation for an RCT., Results: Of 49 patients enrolled, 25 completed all assessments. The dropout rate was high at 49%, but overall, WBVE was an acceptable form of exercise. Functionality as assessed by the 60-s sit-to-stand test (STS-60) improved significantly by 11% (P = 0.002). Some quality of life domains also improved significantly. All improvements were maintained 4 weeks after discontinuing WBVE., Conclusions: WBVE was acceptable, safe, easily incorporated into the routine of HD and was associated with useful improvements in physical function sufficient to justify a RCT.

Objective: This study explored National Health Service (NHS) pharmacists' perceptions and experiences of pharmacist-led research in the workplace., Design: Semistructured, face-to-face discussions continued until distinct clusters of opinion characteristics formed. Verbatim transcripts of audio-recordings were subjected to framework analysis., Setting: Interviews were carried out with 54 pharmacists with diverse backgrounds and roles from general practices and secondary care in the UK's largest health authority., Results: The purpose and potential of health services research (HSR) was understood and acknowledged to be worthwhile by participants, but a combination of individual and system-related themes tended to make participation difficult, except when this was part of formal postgraduate education leading to a qualification. Lack of prioritisation was routinely cited as the greatest barrier, with motivation, confidence and competence as additional impediments. System-related themes included lack of practical support and pharmacy professional issues. A minority of highly motivated individuals managed to embed research participation into routine activity., Conclusions: Most pharmacists realised the desirability and necessity of research to underpin pharmacy service expansion, but a combination of individual and professional level changes is needed to increase activity. Our findings provide a starting point for better understanding the mindset of hospital-based and general practice-based pharmacists towards research, as well as their perceived barriers and supports., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

The purpose of this study was to examine the relations among patients' perceptions of their physicians' communicative behavior during the informed consent interview, the patient's feeling of being confirmed by the physician and satisfied with care delivered by the physician, and the patient's decision to participate in a clinical trial or not. Respondents included 130 cancer patients who were eligible for a clinical trial and who had recently discussed trial participation with their physicians. Results indicated that a linear combination of the variables physician affiliative style, physician dominant or controlling style, patient satisfaction, patient confirmation, patient preference for decision making, patient desire for information, and patient age discriminate between patients who agree to participate in clinical trials and patients who refuse to participate. Physicians' affiliative communicative behaviors and patient satisfaction were clearly important to patients who agreed to participate. Motivations for patients who declined to participate in trials were less clear. Implications for physicians who offer clinical trials to their patients are that specific communication skills may enhance their patients' satisfaction and may help increase enrollment in clinical trials.