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Background: In Australia, university clinical programs rely heavily on external healthcare professionals to provide a range of authentic clinical training and professional development opportunities for students. There is, however, a limited understanding of the factors that motivate these professionals to be educators and whether this varies across different healthcare disciplines within Australia. As the demand for clinical placements continues to increase, it is critical for the ongoing success of these programs that universities identify both the barriers associated with teaching and the benefits that enhance job satisfaction., Methods: A two-part questionnaire was emailed to 849 external healthcare educators teaching predominantly in Medicine, Medical Imaging, and Optometry programs at Deakin University. Part-one surveyed the socio-demographics, perceived benefits, and barriers to teaching, plus the utilisation of entitlements offered by the university. Part-two was modelled on Dybowski and Harendza's validated Physician Teaching Motivation Questionnaire (PTMQ) and adapted to an Australian audience., Results: Overall, 776 out of the 849 questionnaires were considered in the final participant pool. The response rate for part-one was 19.7% (n = 153/776) and 18.3% (n = 142/776) for part-two. Across all professions, altruism was the primary source of motivation for teaching in Deakin University's healthcare programs. Medical Imaging educators placed a higher value on career-related teaching aspects compared to those in Medicine and Optometry (p < 0.003). The resources and benefits associated with teaching were generally perceived to be of minimal importance. External healthcare educators most commonly reported that there were no barriers to teaching (41.3%, n = 78) however, increased workloads and time constraints were the next most likely factors to affect teaching participation (31.8%, n = 60)., Conclusion: Our validated adaptation of the PTMQ successfully targeted healthcare professions not focussed on by Dybowski and Harendza. Altruistic motivation was the overarching theme for why Australian external healthcare educators contribute to teaching with some differences in career-driven motivation additionally acknowledged. Despite there being no key benefits or barriers to teaching participation, universities must remain cognisant of the factors that influence the recruitment and retention of external healthcare educators and how to optimise these for the ongoing success and sustainability of their teaching programs., (© 2024. The Author(s).)

Abstract: Loss of long-term hematopoietic stem cell (LT-HSC) function ex vivo hampers the success of clinical protocols that rely on culture. However, the kinetics and mechanisms through which this occurs remain incompletely characterized. In this study, through time-resolved single-cell RNA sequencing, matched in vivo functional analysis, and the use of a reversible in vitro system of early G1 arrest, we defined the sequence of transcriptional and functional events that occur during the first ex vivo division of human LT-HSCs. We demonstrated that the sharpest loss in LT-HSC repopulation capacity happens early on, between 6 and 24 hours of culture, before LT-HSCs commit to cell cycle progression. During this time window, LT-HSCs adapt to the culture environment, limit the global variability in gene expression, and transiently upregulate gene networks involved in signaling and stress responses. From 24 hours, LT-HSC progression past early G1 contributes to the establishment of differentiation programs in culture. However, contrary to the current assumptions, we demonstrated that the loss of HSC function ex vivo is independent of cell cycle progression. Finally, we showed that targeting LT-HSC adaptation to culture by inhibiting the early activation of JAK/STAT signaling improves HSC long-term repopulating function ex vivo. Collectively, our study demonstrated that controlling early LT-HSC adaptation to ex vivo culture, for example, via JAK inhibition, is critically important to improve HSC gene therapy and expansion protocols., (© 2024 American Society of Hematology. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

To improve the provision of psychotherapy, many countries have now established clinical practice guidelines for the treatment of specific disorders and mental health concerns. These guidelines have typically been based on evidence from meta-analyses of randomized clinical trials with minimal consideration of findings from qualitative research designs. This said, there has been growing interest in incorporating qualitative research in guideline development processes from both stakeholders and guideline development bodies. In this international collaboration, 19 qualitative psychotherapy researchers from 10 countries articulated the benefits of including qualitative findings within the guideline development process and generated recommendations for guideline developers. The underlying question of this report was "Why and how should qualitative research be used in efforts to develop guidance for psychotherapy practice?" The advantages of reviewing qualitative findings included the ability to identify treatment patterns at the level of in-session dynamics, cultural contexts, interpersonal relationships, and internal experiences, thereby creating guidance that is responsive to clients' needs in the moment-to-moment therapy process. Recommendations are offered at the systemic level (e.g., guideline formation processes, methods of education, research funding priorities). Also, methodological advice is offered for guideline developers when selecting to incorporate qualitative research in the implementation of an expanded guideline development process. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Large-scale digitization of natural history collections requires automation of image acquisition and processing. Reflecting this fact, various approaches, some highly sophisticated, have been developed to support imaging of museum specimens. However, most of these systems are complex and expensive, restricting their deployment. Here we describe a simple, inexpensive technique for imaging arthropods larger than 5 mm. By mounting a digital SLR camera on a CNC (computer numerical control) motor-drive rig, we created a system that captures high-resolution z-axis stacked images (6960 × 4640 pixels) of 95 specimens in 30 minutes. This system can be assembled inexpensively ($1000 USD without a camera) and it is easy to set-up and maintain. By coupling low cost with high production capacity, it represents a solution for digitizing any natural history collection., Competing Interests: The authors have declared that no competing interests exist., (Dirk Steinke, Jaclyn T. A. McKeown, Allison Zyba, Joschka McLeod, Corey Feng, Paul D. N. Hebert.)

Background: In both routine practice contexts and research studies, evidence from standardized self-report symptom measures, administered pre- and post-treatment, is predominantly used to determine whether psychotherapy has been successful. Understanding the nature of unsuccessful psychotherapy requires an ability to evaluate the credibility of outcome data generated by such techniques. An important body of research has identified discrepancies between outcomes assessed through symptom measures and those obtained from other sources. However, not enough is known about the extent to which such paradoxical outcomes exist., Objective: This study analyzes the relationship between outcomes, as assessed by a standardized self-report measure, and as assessed by ratings of young people's descriptions of change at post-counseling interviews., Methods: Participants were 50 young people (13-16 years old) who had taken part in a trial of up to 10 weeks of school-based humanistic counseling. Our primary standardized measure was the Young Person's CORE (YP-CORE). To assess young people's experiences of counseling change, three independent raters scrutinized transcripts of post-counseling interviews, and scored levels of helpfulness on a 1 (Not at all helpful) to 10 (Extremely helpful) scale. Inter-rater reliabilities were 0.94 (Cronbach's Alpha) and 0.96 (McDonald's Omega). Sensitivity analyses were conducted to explore relationships between helpfulness ratings and other outcome measures, i.e., satisfaction with counseling (ESQ) and the Goal-Based-Outcome Tool (GBO), and process measures, i.e., the Working Alliance Inventory (WAI-S) and the Barret Lennard Relationship Inventory (BLRI)., Results: Multilevel analysis indicated that helpfulness ratings were not significantly associated with changes in YP-CORE scores. Analyzed categorically, 38% of those showing reliable improvement on the standardized measure were below the median for self-described helpfulness, and 47% of those not showing reliable change were at or above the median for self-described helpfulness. Sensitivity analyses demonstrated closer correlations between helpfulness ratings and other outcome measures (ESQ and GBO), and between helpfulness ratings and process measures (WAI-S and BLRI)., Discussion: Our results raise questions about reliance on symptom change outcome measures for defining treatment success and failure, given their disparity with clients' own descriptions of the helpfulness of therapy. Implications for practice and research are discussed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 McLeod, Stänicke, Oddli, Smith, Pearce and Cooper.)

Background: Partner notification (PN) is key to the control of sexually transmitted infections (STIs) and human immunodeficiency virus (HIV). Digital interventions have been used to facilitate PN. A scoping review was conducted to describe the interventions used, user preferences and acceptability of digital PN interventions from patient and partner perspectives., Methods: A systematic literature search was conducted of eight databases for articles published in English, available online with digital PN outcome data. Articles were assessed using the Mixed Methods Appraisal Tool. Quantitative and qualitative data were synthesised and analysed using thematic analysis., Results: Twenty-six articles met the eligibility criteria. Articles were heterogeneous in quality and design, with the majority using quantitative methods. Nine articles focused solely on bacterial STIs (five on syphilis; four on chlamydia), one on HIV, two on syphilis and HIV, and 14 included multiple STIs, of which 13 included HIV. There has been a shift over time from digital PN interventions solely focusing on notifying partners, to interventions including elements of partner management, such as facilitation of partner testing and treatment, or sharing of STI test results (between index patients and tested sex partners). Main outcomes measured were number of partners notified (13 articles), partner testing/consultation (eight articles) and treatment (five articles). Relationship type and STI type appeared to affect digital PN preferences for index patients with digital methods preferred for casual rather than established partner types. Generally, partners preferred face-to-face PN., Conclusion: Digital PN to date mainly focuses on notifying partners rather than comprehensive partner management. Despite an overall preference for face-to-face PN with partners, digital PN could play a useful role in improving outcomes for certain partner types and infections. Further research needs to understand the impact of digital PN interventions on specific PN outcomes, their effectiveness for different infections and include health economic evaluations., Competing Interests: Competing interests: CSE and JG report receiving NIHR funding to research digital sexual health (NIHR129157 (JG) and NIHR200856 (CSE, JG)). CSE is an associate editor and JG is on the Editorial Board for STI journal. No other conflicts to declare., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Complex motor skills can be acquired while observing a model without physical practice. Transcranial direct-current stimulation (tDCS) applied to the primary motor cortex (M1) also facilitates motor learning. However, the effectiveness of observational practice for bimanual coordination skills is debated. We compared the behavioural and brain causal connectivity patterns following three interventions: primary motor cortex stimulation (M1-tDCS), action-observation (AO) and a combined group (AO+M1-tDCS) when acquiring a bimanual, two-ball juggling skill. Thirty healthy young adults with no juggling experience were randomly assigned to either video observation of a skilled juggler, anodal M1-tDCS or video observation combined with M1-tDCS. Thirty trials of juggling were performed and scored after the intervention. Resting-state EEG data were collected before and after the intervention. Information flow rate was applied to EEG source data to measure causal connectivity. The two observation groups were more accurate than the tDCS alone group. In the AO condition, there was strong information exchange from (L) parietal to (R) parietal regions, strong bidirectional information exchange between (R) parietal and (R) occipital regions and an extensive network of activity that was (L) lateralized. The M1-tDCS condition was characterized by bilateral long-range connections with the strongest information exchange from the (R) occipital region to the (R) temporal and (L) occipital regions. AO+M1-tDCS induced strong bidirectional information exchange in occipital and temporal regions in both hemispheres. Uniquely, it was the only condition that was characterized by information exchange between the (R) frontal and central regions. This study provides new results about the distinct network dynamics of stimulating the brain for skill acquisition, providing insights for motor rehabilitation.

On December 5, 2022, an indirect drive fusion implosion on the National Ignition Facility (NIF) achieved a target gain G&#95;{target} of 1.5. This is the first laboratory demonstration of exceeding "scientific breakeven" (or G&#95;{target}>1) where 2.05 MJ of 351 nm laser light produced 3.1 MJ of total fusion yield, a result which significantly exceeds the Lawson criterion for fusion ignition as reported in a previous NIF implosion [H. Abu-Shawareb et al. (Indirect Drive ICF Collaboration), Phys. Rev. Lett. 129, 075001 (2022)PRLTAO0031-900710.1103/PhysRevLett.129.075001]. This achievement is the culmination of more than five decades of research and gives proof that laboratory fusion, based on fundamental physics principles, is possible. This Letter reports on the target, laser, design, and experimental advancements that led to this result.

Background: Partner notification (PN) is key to controlling sexually transmitted infections (STIs) and human immunodeficiency virus (HIV). Digital PN options (e.g. social media, short message service (SMS), emails) are promising in increasing PN behaviour. However, their implementation is often challenging and studies report varied levels of acceptability and uptake of PN, highlighting the need to optimise digital PN interventions., Methods: A systematic review of barriers and facilitators to digital PN interventions for STIs, including HIV, across eight research databases (from 2010 to 2023) identified eight relevant studies, two of which addressed HIV. Data extraction identified 98 barriers and 54 facilitators to the use of digital PN interventions. These were synthesised into 18 key barriers and 17 key facilitators that were each deemed amenable to change. We then used the Behaviour Change Wheel approach, the Acceptability, Practicability, Effectiveness, Affordability, Side-effects and Equity criteria, and multidisciplinary expert input, to systematically develop practical recommendations to optimise digital PN., Results: Thirty-two specific recommendations clustered around three themes. Digital PN interventions should: (1) empower and support the index patient by providing a range of notification options, accompanied by clear instructions; (2) integrate into users' existing habits and the digital landscape, meeting contemporary standards and expectations of usability; and (3) address the social context of PN both online and offline through normalising the act of PN, combating STI-related stigma and stressing the altruistic aspects of PN through consistent messaging to service users and the public., Conclusions: Our evidence-based recommendations should be used to optimise existing digital PN interventions and inform the co-production of new ones.

Understanding the long-term evolution of natural gas is critical in the context of long-term energy system transitions. Here, we explicitly represent traded pipeline and liquefied natural gas (LNG) infrastructure in the Global Change Analysis Model (GCAM). We find LNG to make up a dominant share of gas trade, as it can be flexibly shipped across regions. New global investments in LNG and pipeline export infrastructure respectively range from 230 to 840 and 70-620 million tons per annum (MTPA) by 2050 across scenarios; the lower end of this range is achieved through transitioning to low-carbon energy systems along with limited trade. Our results also highlight diverging implications for regions based on their gas trade profiles. For example, Russia, which produces gas largely for pipeline exports may experience greater production losses due to liquefaction and shipping improvements and geopolitical shifts than regions oriented more toward domestic and LNG markets, such as USA and Middle East., Competing Interests: The authors declare no competing interests., (© 2024 Battelle Memorial Institute.)

Purpose: The aim of this randomised controlled trial (RCT) was to explore whether a community nursing intervention for outpatients receiving systemic therapy reduced unplanned hospital presentations and improved physical and psychosocial health outcomes over the first three cycles of treatment compared to a control group receiving standard care., Methods: The number of and reasons for unplanned presentations were obtained for 170 intervention and 176 control group adult patients with solid tumours starting outpatient chemotherapy. Poisson regression was used to compare the number of presentations between the intervention and control groups. Patients self-completed the Hospital Anxiety and Depression Scale, the Cancer Behavior Inventory and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire core 30 (EORTC QLQ-C30) at the start of the first four cycles. Linear regression techniques were used to compare quality of life outcomes., Results: The reduction in unplanned presentations in the intervention group relative to the control group was 12% (95% CI, - 25%, 37%; P = 0.48). At the start of cycle 4, there was no difference in anxiety (difference = 0.47 (95% CI, - 0.28, 1.22; P = 0.22)), depression (difference = 0.57 (95% CI, - 0.18, 1.31; P = 0.13)) or EORTC QLQ-C30 summary score (difference = 0.16 (95% CI, - 2.67, 3.00; P = 0.91)). Scores for self-efficacy as measured by the Cancer Behavior Inventory were higher in the intervention group (difference = 4.3 (95% CI, 0.7, 7.9; P = 0.02))., Conclusion: This RCT did not demonstrate a benefit in reducing unplanned presentations to hospital. The trial identified improved cancer-based self-efficacy in patients receiving the intervention., Trial Registration: Registered at Australian and New Zealand Clinical Trials Registry: ACTRN12614001113640, registered 21/10/2014., (© 2024. The Author(s).)

Background: Hereditary angioedema (HAE) is a rare condition marked by swelling episodes in various body parts, including the extremities, upper airway, face, intestinal tract, and genitals. Long-term prophylaxis (LTP), prescribed to control recurring HAE attacks, is integral to its management. Previously, attenuated androgens (AAs) were the only oral LTP options. However, in 2020, berotralstat, an oral plasma kallikrein inhibitor, was approved in the United States. A 2018 survey of adults with HAE type I or type II showed that almost all the patients who used prophylactic HAE medication preferred oral treatment (98%) and felt that it fit their lifestyle better than injectable treatment (96%). Still, guidelines lack consensus on transitioning patients from AAs to alternative oral prophylactic therapy. Objective: This paper aims to share expert insights and patient feedback on transitioning from AAs to berotralstat, an alternative oral prophylactic therapy, from the perspective of clinicians with extensive experience in treating patients with HAE. Methods: A panel of five HAE specialists convened for a virtual half-day roundtable discussion in April 2023. Results: Discussions about transitioning from AAs to berotralstat were prompted by routine consultations, patient inquiries based on independent research, ineffective current treatment, or worsening AA-related adverse effects. For patients who switched from AAs, the physicians reported that the decision was influenced by the alternative therapy's ability to prevent HAE attacks, its safety, and the once-daily administration schedule. All expert panel members identified fewer AA-related adverse effects; better quality of life; and less severe, shorter, and less frequent HAE attacks as clinical or patient goals they hoped to achieve through the treatment switch. Conclusion: The emergence of new, highly specific LTP drugs for HAE calls for the development of comprehensive recommendations and guidelines for transitioning from AAs to alternative oral prophylactic therapy. The expert panel highlighted key factors to consider during the development of such guidelines.

Purpose: The aim of this study was to conduct a process evaluation of a whole-genome sequence report form (SRF) used to reduce nosocomial SARS-CoV-2 through changing infection prevention and control (IPC) behaviours within the COVID-19 pandemic., Methods: We used a three-staged design. Firstly, we described and theorized the purported content of the SRF using the behaviour change wheel (BCW). Secondly, we used inductive thematic analysis of one-to-one interviews (n = 39) to explore contextual accounts of using the SRF. Thirdly, further deductive analysis gauged support for the intervention working as earlier anticipated., Results: It was possible to theorize the SRF using the BCW approach and visualize it within a simple logic model. Inductive thematic analyses identified the SRF's acceptability, ease of use and perceived effectiveness. However, major challenges to embedding it in routine practice during the unfolding COVID-19 crisis were reported. Notwithstanding this insight, deductive analysis showed support for the putative intervention functions 'Education', 'Persuasion' and 'Enablement'; behaviour change techniques '1.2 Problem solving', '2.6 Biofeedback', '2.7 Feedback on outcomes of behaviour' and '7.1 Prompts and cues'; and theoretical domains framework domains 'Knowledge' and 'Behavioural regulation'., Conclusions: Our process evaluation of the SRF, using the BCW approach to describe and theorize its content, provided granular support for the SRF working to change IPC behaviours as anticipated. However, our complementary inductive thematic analysis highlighted the importance of the local context in constraining its routine use. For SRFs to reach their full potential in reducing nosocomial infections, further implementation research is needed., (© 2023 The Authors. British Journal of Health Psychology published by John Wiley & Sons Ltd on behalf of British Psychological Society.)

Background: COVID-19 outbreaks have disproportionately affected Residential Aged Care Facilities (RACFs) around the world, with devastating impacts for residents and their families. Many factors such as community prevalence, facility layout, and infection control practices have been linked to resident outcomes. At present, there are no scoring systems designed to quantify these factors and assess their level of association with resident attack rates and mortality rates., Methods: We constructed a novel Infection Prevention and Control (IPC) scoring system to quantify facility layout, ability to cohort residents, and IPC practices in RACFs. We conducted a retrospective observational cohort study of COVID-19 outbreaks, applying our IPC scoring system to all COVID-19 outbreaks occurring in RACFs in Sydney Local Health District during the Delta and Omicron waves of the COVID-19 pandemic in New South Wales, Australia., Results: Twenty-six COVID-19 outbreaks in 23 facilities in the Delta wave, and 84 outbreaks in 53 facilities in the Omicron wave were included in the study. A linear Generalised Estimating Equation model was fitted to the Omicron data. Higher IPC scores were associated with higher attack rates and mortality rates. Facilities with IPC scores greater than 75.0% had attack rates 19.6% higher [95% CI: 6.4%-32.8%] and mortality rates 1.7% higher [95% CI: 0.6%-2.7%] than facilities with an IPC score of less than 60.0%., Conclusions: The results of this study suggest the utility of the IPC scoring system for identifying facilities at greater risk of adverse outcomes from COVID-19 outbreaks. While further validation and replication of accuracy is required, the IPC scoring system could be used and adapted to improve planning, policy, and resource allocation for future outbreaks., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Peer support is widely assumed to help individuals with spinal cord injury (SCI) adjust, yet the evidence is mixed. We propose that peer support may be more likely to promote adjustment when informal support is lacking. To test this hypothesis, 135 individuals living with SCI receiving peer support (46.7% female; M age  = 42.36, SD = 14.83) completed an online survey assessing aspects of and satisfaction with the peer support and family/friend support that they were receiving as well as measures of adjustment. Although those reporting receiving more peer support were not any better adjusted than those reporting less, individuals who were more satisfied with the peer support they received reported better adjustment. Moreover, the relation of satisfaction with peer support with depressive symptoms was dependent on the level of family/friend support. These findings suggest that peer support is most effective among those lacking support from family and friends.

Primary hyperoxaluria (PH) is a family of ultra-rare, autosomal recessive, metabolic disorders associated with frequent kidney stones, chronic kidney disease and kidney failure, and serious complications due to systemic oxalosis, resulting in significant morbidity. We investigated the burden of PH among affected patients and caregivers. This cross-sectional, web-based survey was used to quantify the burden of PH, in terms of healthcare resource utilization, health-related quality of life, and work productivity and activity impairment among adults (≥ 18 years) with PH and caregivers of children (≤ 17 years) with PH in the US. Among the 20 respondents, there were 7 adults with PH and 13 caregivers of children with PH. Adherence to hyperhydration was noted as the most, or one of the most, difficult aspects of PH by 56% of respondents. Most patients (95%) had experienced painful kidney stone events, one-third had visited the emergency room, and 29% were hospitalized for complications due to PH. Of the 24% of patients on dialysis, all found the procedure burdensome. Adult patients' quality of life was negatively affected across several domains. Most respondents (81%) reported that PH had a negative effect on their finances. Employed adult patients and caregivers, and children with PH, had moderate impairment in work productivity, school attendance, and activity. Anxiety about future PH-related sequelae was moderate to high. These findings highlight the need for improvements in PH medical management. A plain language summary is available in the supplementary information., (© 2023. The Author(s).)

A major issue facing society is the extent to which the usability of the digital evidence base is at risk because, in the digital era, the concept of the record has been eroded. The nature and reality of a record are no longer agreed. Addressing the challenges that the digital presents for managing records and assuring their future usability is not one that records and archives scholars and professionals can tackle alone. This article argues that this is a 'grand challenge' which requires a broad range of perspectives and expertise and convergence research to resolve. It discusses findings from an international multidisciplinary research network established to critically explore, through a grounded theory approach, the nature of a digital record and the implications of the digital era for the usability and functionality of the future evidence base. A series of different visions of a digital record emerged alongside a wide-ranging set of research questions that form the basis of an agenda for future collaborative (convergence) research., (© The Author(s) 2023.)

An integrated design environment (IDE) has been developed that allows the capture of design ideas, virtual compounds, and design hypotheses for medicinal chemistry projects. Specific consideration for rational molecular design, including design strategy and tactics, as well as comparator reference compounds have been incorporated to more easily convey the proposed design idea. A hierarchical tree architecture and customizable layouts allow for facile browsing across multiple programs and rapid examination of both ongoing and newly designed virtual compounds enabling centralized team discussions to ensure the most efficient prosecution of a queue of these target compounds. Additionally, a "whiteboard" module was incorporated for the rapid evaluation of virtual compounds against a suite of computational models enabling real-time design and triage. Finally, aggregation of cross-project design data enables broader analyses that can indicate portfolio-wide design challenges., (© 2022 Wiley Periodicals LLC.)

Introduction: It is now 25 years since the Riverland health service began its partnership with Flinders University to create the Parallel Rural Community Curriculum (PRCC) in rural South Australia. What started as a workforce program quickly became a successful disruptive technology for broader pedagogy in medical education. Despite more graduates of the PRCC choosing rural practice compared with their urban rotation-based colleagues, local medical workforce crises have persisted., Methods: In February 2021, the Local Health Network decided to implement the National Rural Generalist Pathway in its local region. It created the Riverland Academy of Clinical Excellence (RACE) as its vehicle for taking responsibility for training its own health professional workforce., Results: RACE has increased the region's medical workforce by over 20% in 1 year. It gained accreditation as a provider of junior doctor and advanced skills training and recruited five interns (all of whom had previously undertaken 1-year rural clinical school placements), six second year and above doctors, and four advanced skills registrars. RACE has linked with GPEx Rural Generalist registrars and formed a Public Health Unit from those registrars who also have MPH qualifications. RACE and Flinders University are expanding teaching facilities in the region and enabling medical students to complete their MD in the region., Discussion: Health services can facilitate vertical integration of rural medical education, supporting a full pathway to rural practice. Providing length of training contracts is proving attractive for junior doctors who are interested in establishing a rural home base for their training.

Background: Barriers to rapid return of sequencing results can affect the utility of sequence data for infection prevention and control decisions., Aim: To undertake a mixed-methods analysis to identify challenges that sites faced in achieving a rapid turnaround time (TAT) in the COVID-19 Genomics UK Hospital-Onset COVID-19 Infection (COG-UK HOCI) study., Methods: For the quantitative analysis, timepoints relating to different stages of the sequencing process were extracted from both the COG-UK HOCI study dataset and surveys of study sites. Qualitative data relating to the barriers and facilitators to achieving rapid TATs were included from thematic analysis., Findings: The overall TAT, from sample collection to receipt of sequence report by infection control teams, varied between sites (median 5.1 days, range 3.0-29.0 days). Most variation was seen between reporting of a positive COVID-19 polymerase chain reaction (PCR) result to sequence report generation (median 4.0 days, range 2.3-27.0 days). On deeper analysis, most of this variability was accounted for by differences in the delay between the COVID-19 PCR result and arrival of the sample at the sequencing laboratory (median 20.8 h, range 16.0-88.7 h). Qualitative analyses suggest that closer proximity of sequencing laboratories to diagnostic laboratories, increased staff flexibility and regular transport times facilitated a shorter TAT., Conclusion: Integration of pathogen sequencing into diagnostic laboratories may help to improve sequencing TAT to allow sequence data to be of tangible value to infection control practice. Adding a quality control step upstream to increase capacity further down the workflow may also optimize TAT if lower quality samples are removed at an earlier stage., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Dance classes designed for people with Parkinson's are very popular and associated not only with increasing individuals' motor control abilities but also their mood; not least by providing a social network and the enjoyment of the music. However, quantitative evidence of the benefits is inconsistent and often lacks in power. For a better understanding of the contradictory findings between participants' felt experiences and existing quantitative findings in response to dance classes, we employed a mixed method approach that focussed on the effects of music. Participant experience of the dance class was explored by means of semi-structured interviews and gait changes were measured in a within-subjects design through the Timed Up and Go (TUG) test before and after class, with and without music. We chose the TUG test for its ecological validity, as it is a simple test that resembles movements done in class. We hypothesised that the music and the dance class would have a facilitating effect on the TUG performance. In line with existing research, we found that before class, the gait of 26 participants was significantly improved when accompanied by a soundtrack. However, after class, music did not have a significantly facilitating effect, yet gait without music significantly improved after class compared to before. We suggest that whilst the music acts as an external stimulator for movement before the dance class, after the dance class, participants have an internalised music or rhythm that supports their motor control. Thus, externally played music is of less relevance. The importance of music was further emphasised in the qualitative data alongside social themes. A better understanding of how music and dance affects Parkinson's symptoms and what aspects make individuals 'feel better' will help in the design of future interventions., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Jola et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Historically, research and practice of psychotherapy have been conducted within conceptual frameworks defined in terms of theoretical models. These models are in turn guided by meta-theories about the purpose of psychotherapy and its place in society. An image of psychotherapy that underpins much contemporary practice is the idea that therapy operates as an intervention that involves the implementation and application of a pre-existing theoretical model or set of empirically validated procedures. The present paper introduces the idea that it may be valuable to regard psychotherapy not as an intervention but instead as a process of making, in the sense of offering a cultural space for the co-construction of meaningful and satisfying ways of living that draw on shared cultural resources. We offer an overview of what a therapy of making might look like, followed by an account of theoretical perspectives, both within the psychotherapy literature and derived from wider philosophical and social science sources, that we have found valuable in terms of making sense of this way of thinking about practice. Our conclusion is that we need something in addition to theory-specific and protocol-driven therapies, in order to be able to incorporate the unexpected, the not-before-met perspective, event or practice of living, and to be open towards the radically new, the given, and the unknown., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 McLeod and Sundet.)

Background: Given the importance of the selection process, many medical schools are reviewing their selection criteria. The traditional pathway for post-graduate medicine has been from science-based undergraduate degrees, however some programs are expanding their criteria. In this study we investigated academic success across all years and themes of the Deakin University medical degree, based on the type of degree undertaken prior to admission. We evaluated whether the traditional pathway of biomedical science into medicine should remain the undergraduate degree of choice, or whether other disciplines should be encouraged., Methods: Data from 1159 students entering the degree from 2008 to 2016 was collected including undergraduate degree, grade point average (GPA), Graduate Medical Schools Admission Test (GAMSAT) score and academic outcomes during the 4 years of the degree. Z-scores were calculated for each assessment within each cohort and analysed using a one sample t-test to determine if they differed from the cohort average. Z-scores between groups were analysed by 1-way ANOVA with LSD post-hoc analysis correcting for multiple comparisons., Results: The majority of students had Science (34.3%) or Biomedical Science (31.0%) backgrounds. 27.9% of students had a Health-related undergraduate degree with smaller numbers of students from Business (3.5%) and Humanities (3.4%) backgrounds. At entry, GPA and GAMSAT scores varied significantly with Biomedical Science and Science students having significantly higher scores than Health students. Health students consistently outperformed students from other disciplines in all themes while Biomedical Science students underperformed., Conclusions: Our data suggest that a Health-related undergraduate degree results in the best performance throughout medical school, whereas a Biomedical Science background is associated with lower performance. These findings challenge the traditional Biomedical Science pathway into medicine and suggest that a health background might be more favourable when determining the selection criteria for graduate entry into medicine., (© 2022. The Author(s).)

For more than half a century, researchers around the world have been engaged in attempts to achieve fusion ignition as a proof of principle of various fusion concepts. Following the Lawson criterion, an ignited plasma is one where the fusion heating power is high enough to overcome all the physical processes that cool the fusion plasma, creating a positive thermodynamic feedback loop with rapidly increasing temperature. In inertially confined fusion, ignition is a state where the fusion plasma can begin "burn propagation" into surrounding cold fuel, enabling the possibility of high energy gain. While "scientific breakeven" (i.e., unity target gain) has not yet been achieved (here target gain is 0.72, 1.37 MJ of fusion for 1.92 MJ of laser energy), this Letter reports the first controlled fusion experiment, using laser indirect drive, on the National Ignition Facility to produce capsule gain (here 5.8) and reach ignition by nine different formulations of the Lawson criterion.

Purpose: This paper reports on patient participant experiences of a larger randomised controlled trial evaluating a shared-care pathway intervention designed to support outpatients at home during their first three cycles of systemic anti-cancer therapies delivered in two large tertiary hospitals in Sydney, Australia. This qualitative study explores the perspectives of patient participants who received the intervention, which involved targeted home visits by community nurses post treatment administration., Methods: A qualitative inductive thematic analysis was used to examine data from semi-structured interviews with patients who received the intervention., Results: Twenty-five patient participants were interviewed. We identified four themes: Stepping into the unknown; Impact of availability of health and social care support; Building confidence to manage self-care; Uncertainty, frailty and co-morbidities. Targeted support at home is seen to be effective and welcomed by patients as early stages of each treatment cycle can be extremely challenging, particularly for those who are elderly, frail or with co-morbidities, and for those with limited health and social support., Conclusion: Regular contact with community nursing services can, at least for some patients, support the development of patient self-efficacy in managing aspects of their own care. Some patients are sufficiently confident to self-manage some treatment side effects by treatment cycle four., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Inflammatory bowel disease (IBD) can lead to substantial impairments of quality-of-life. Clinical guidelines and quality indicators aid physicians in practice but may not reflect the perspectives and experiences of patients with IBD. To address this, the objectives of this study were to understand patient experiences with IBD care and to explore priorities., Methods: Based on a convenience sample of 36 participants, five focus groups were completed at four sites across Canada. Data were analyzed using a deductive thematic analysis approach to assess emergent themes and variability in participants' experiences., Results: Our results are organized by themes of structure, process and outcomes to illustrate common issues with respect to how care is organized in the healthcare system, how patients receive and experience care and how patients perceive the outcomes of their care. Our results frame a health systems quality approach that signal needed improvements in access to care, the need for innovation with respect to virtual medicine, the potential expansion of multidisciplinary team-based care and the importance of addressing the psychosocial dimensions for patients with IBD and their caregivers in order to better deliver patient-centred care., Conclusions: The issues identified have the potential to impact priority areas in the system, IBD care delivery, and how outcomes can be improved by focusing on 'lived experience' and patient-centred care. The differing values and perspectives of all those involved in caring for patients with IBD underscore the importance of good communication with patients, caregivers and family members, as well as staying responsive to evolving needs., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Canadian Association of Gastroenterology.)

We evaluated the effects of higher-load (HL) versus (lower-load) higher-volume (HV) resistance training on skeletal muscle hypertrophy, strength, and muscle-level molecular adaptations. Trained men ( n  = 15, age: 23 ± 3 years; training experience: 7 ± 3 years) performed unilateral lower-body training for 6 weeks (3× weekly), where single legs were randomly assigned to HV and HL paradigms. Vastus lateralis (VL) biopsies were obtained prior to study initiation (PRE) as well as 3 days (POST) and 10 days following the last training bout (POSTPR). Body composition and strength tests were performed at each testing session, and biochemical assays were performed on muscle tissue after study completion. Two-way within-subject repeated measures ANOVAs were performed on most dependent variables, and tracer data were compared using dependent samples t-tests. A significant interaction existed for VL muscle cross-sectional area (assessed via magnetic resonance imaging; interaction p  = 0.046), where HV increased this metric from PRE to POST (+3.2%, p  = 0.018) whereas HL training did not (-0.1%, p  = 0.475). Additionally, HL increased leg extensor strength more so than HV training (interaction p  = 0.032; HV < HL at POST and POSTPR, p  < 0.025 for each). Six-week integrated non-myofibrillar protein synthesis (iNon-MyoPS) rates were also higher in the HV versus HL condition, while no difference between conditions existed for iMyoPS rates. No interactions existed for other strength, VL morphology variables, or the relative abundances of major muscle proteins. Compared to HL training, 6 weeks of HV training in previously trained men optimizes VL hypertrophy in lieu of enhanced iNon-MyoPS rates, and this warrants future research., Competing Interests: CH was CEO of Fitomics, LLC while being involved with this study. However, Fitomics, LLC did not financially contribute toward study expenditures or any other aspect related to the study. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Vann, Sexton, Osburn, Smith, Haun, Rumbley, Mumford, Montgomery, Ruple, McKendry, Mcleod, Bashir, Beyers, Brook, Smith, Atherton, Beck, McDonald, Young, Phillips and Roberts.)

Central nervous system (CNS) dissemination of B-precursor acute lymphoblastic leukemia (B-ALL) has poor prognosis and remains a therapeutic challenge. Here we performed targeted DNA sequencing as well as transcriptional and proteomic profiling of paired leukemia-infiltrating cells in the bone marrow (BM) and CNS of xenografts. Genes governing mRNA translation were upregulated in CNS leukemia, and subclonal genetic profiling confirmed this in both BM-concordant and BM-discordant CNS mutational populations. CNS leukemia cells were exquisitely sensitive to the translation inhibitor omacetaxine mepesuccinate, which reduced xenograft leptomeningeal disease burden. Proteomics demonstrated greater abundance of secreted proteins in CNS-infiltrating cells, including complement component 3 (C3), and drug targeting of C3 influenced CNS disease in xenografts. CNS-infiltrating cells also exhibited selection for stemness traits and metabolic reprogramming. Overall, our study identifies targeting of mRNA translation as a potential therapeutic approach for B-ALL leptomeningeal disease. SIGNIFICANCE: Cancer metastases are often driven by distinct subclones with unique biological properties. Here we show that in B-ALL CNS disease, the leptomeningeal environment selects for cells with unique functional dependencies. Pharmacologic inhibition of mRNA translation signaling treats CNS disease and offers a new therapeutic approach for this condition. This article is highlighted in the In This Issue feature, p. 1 ., (©2021 American Association for Cancer Research.)

Goal: This study aims to evaluate the quality of online hepatocellular carcinoma (primary liver cancer) resources by using a validated tool to determine the strengths and limitations of hepatocellular carcinoma Web sites designed for patient education., Background: In recent years, online health information-seeking behavior has become more prevalent. Meanwhile, hepatocellular carcinoma incidence rates have also increased. However, there is currently limited literature assessing the quality of online hepatocellular carcinoma information., Materials and Methods: The term "hepatocellular carcinoma" was searched using the search engine Google and the meta-search engines Dogpile and Yippy. A validated rating tool was used to assign quality scores to 100 Web sites based on the domains of Web site affiliation, accountability, interactivity, structure and organization, readability, and content quality. Overall quality scores were tallied for all Web sites., Results: Noncommercial hepatocellular carcinoma Web sites received significantly higher overall quality scores compared with their commercial counterparts. Overall, 30% of the Web sites identified their author(s), 42% cited sources, and 33% were updated within the past 2 years. The majority of Web sites utilized at least 1 interactive feature and 4 structural tools. Average readability was at a grade 11.8 level using the Flesch-Kincaid grading system, which is significantly higher than the recommended grade 6 level. Definition and treatment were the most commonly covered topics, while prevention and prognosis were the least commonly covered., Conclusions: The quality of online hepatocellular carcinoma information is highly variable. Health care professionals should be aware of its limitations and be proactive in guiding patients to reliable resources., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

The adoption of a pluralistic perspective on research design, processes of data collection and analysis and dissemination of findings, has the potential to enable psychotherapy research to make a more effective contribution to building a just society. A review of the key features of the concept of pluralism is followed by a historical analysis of the ways in which research in counselling, psychotherapy and related disciplines has moved in the direction of a pluralistic position around knowledge creation. Core principles of a pluralistic approach to research are identified and explored in the context of a critical case study of contemporary research into psychotherapy for depression, examples of pluralistically oriented research practices, and analysis of a pluralistic conceptualisation of the nature of evidence. Implications of a pluralistic perspective for research training and practice are discussed. Pluralistic inquiry that emphasises dialogue, collaboration, epistemic justice and the co-existence of multiple truths, creates opportunities for individuals, families and communities from a wide range of backgrounds to co-produce knowledge in ways that support their capacities for active citizenship and involvement in open democratic decision-making. To fulfil these possibilities, it is necessary for psychotherapy research to be oriented towards social goals that are sufficiently relevant to both researchers and co-participants to harness their passion and work together for a common good., (Copyright © 2021 Smith, McLeod, Blunden, Cooper, Gabriel, Kupfer, McLeod, Murphie, Oddli, Thurston and Winter.)

Objective: This retrospective observational study aimed to compare the impact of the Prevent Alcohol and Risk-Related Trauma Youth (P.A.R.T.Y.) Program when delivered as In-hospital or Outreach models to rural and regional students., Methods: The study population were consented participants from regional areas between 2013 and 2017 who completed pre-programme, immediately post-programme and 3-5 months post-programme surveys. Responses from the metropolitan In-hospital programme participants and regional Outreach programme participants were analysed within groups across the three time points. The primary outcome variable was a change in self-reported perception of driving after drinking alcohol. Secondary outcome variables were designating a safe driver after drinking, perception of risk of injury if not wearing a seatbelt, risks of injury if undertaking physical risk-taking activities and likelihood of the programme changing perceptions., Results: There were 1314 participants invited to participate and 547 (42%) sets of complete surveys were received, of whom 296 (54%) were Outreach participants. Pre-programme, a significantly lower proportion of Outreach participants reported 'definitely not' to driving after drinking (84% vs 91%), and perceived a 'definite' likelihood of sustaining injury if not wearing a seatbelt (57% vs 66%). Outreach participants displayed improvements in likelihood to drive after drinking alcohol immediately post-programme and on follow up (P = 0.028). Responses to all other secondary outcome measures demonstrated some improvement., Conclusions: Although demographically similar, baseline perceptions toward alcohol, risk-taking and injury differed between groups. Improvements in perception were demonstrated across both models. These findings support P.A.R.T.Y. as an injury prevention initiative for regional youth., (© 2020 Australasian College for Emergency Medicine.)

Drug development is hampered by poor target selection. Phenotypic screens using neurons differentiated from patient stem cells offer the possibility to validate known and discover novel disease targets in an unbiased fashion. To identify targets for managing hyperexcitability, a pathological feature of amyotrophic lateral sclerosis (ALS), we design a multi-step screening funnel using patient-derived motor neurons. High-content live cell imaging is used to evaluate neuronal excitability, and from a screen against a chemogenomic library of 2,899 target-annotated compounds, 67 reduce the hyperexcitability of ALS motor neurons carrying the SOD1(A4V) mutation, without cytotoxicity. Bioinformatic deconvolution identifies 13 targets that modulate motor neuron excitability, including two known ALS excitability modulators, AMPA receptors and Kv7.2/3 ion channels, constituting target validation. We also identify D2 dopamine receptors as modulators of ALS motor neuron excitability. This screen demonstrates the power of human disease cell-based phenotypic screens for identifying clinically relevant targets for neurological disorders., Competing Interests: Declaration of interests The authors declare the following competing financial interests: K.C.D.R., K.E., and C.J.W. are founders of QurAlis; L.Z., A.B., A.P.B., A.B.J., J.K.M., K.L.L., F.V., H.Y., L.H.J., and A.J.C. are current or previous employees of Pfizer., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To better understand how therapists facilitate client goal attainment in therapy, we analyzed therapists' future-oriented actions in good outcome cases in which clients recorded high ratings on goal items in the Working Alliance Inventory-Short Revised., Method: We selected clients who were within the clinical range (OQ-45.2) at pretreatment, demonstrated reliable change at the end of treatment, and recorded high WAI client goals scores early in treatment. Qualitative analyses of transcripts of the initial three sessions and client posttreatment interviews were integrated into a combined analysis to identify themes across the two separate sets of findings., Results: Therapist future-oriented activity included: (1) Picking up explicit and implicit intentions; (2) using linguistic devices, such as meta-communication, action language, and hedging; (3) using evocative interventions; and (4) nudging the client into practicing change. Core finding: Therapists aligned with clients' directionality in a forward-driven, gradually evolving process., Conclusion: Conceptual and clinical implications are discussed., (© 2021 The Authors. Journal of Clinical Psychology published by Wiley Periodicals LLC.)

Continuous supply of immune cells throughout life relies on the delicate balance in the hematopoietic stem cell (HSC) pool between long-term maintenance and meeting the demands of both normal blood production and unexpected stress conditions. Here we identified distinct subsets of human long-term (LT)-HSCs that responded differently to regeneration-mediated stress: an immune checkpoint ligand CD112 lo subset that exhibited a transient engraftment restraint (termed latency) before contributing to hematopoietic reconstitution and a primed CD112 hi subset that responded rapidly. This functional heterogeneity and CD112 expression are regulated by INKA1 through direct interaction with PAK4 and SIRT1, inducing epigenetic changes and defining an alternative state of LT-HSC quiescence that serves to preserve self-renewal and regenerative capacity upon regeneration-mediated stress. Collectively, our data uncovered the molecular intricacies underlying HSC heterogeneity and self-renewal regulation and point to latency as an orchestrated physiological response that balances blood cell demands with preserving a stem cell reservoir.

Background: Poor nutrition is a major contributor to chronic disease, but the level of nutrition education in medical training is limited. Deakin University Medical School has been working to embed more nutrition into the curriculum since 2009., Aim: To assess the nutrition content of all summative examinations in the Bachelor of Medicine, Bachelor of Surgery over a 4-year period., Methods: The type, amount and scope of nutrition-related questions were assessed in all summative examinations delivered to all 4-year levels from 2013 to 2016. These were assessed independently and analysed for nutrition content. The amount of nutrition was quantified, and the nutrition topic areas and nutrition competencies addressed were documented., Results: Less than 10% of summative examination questions contained any nutrition content. For first-year and second-year students, these examinations included an average yearly total of 433 multiple choice questions (MCQs) (range 337-530) and 47 short answer questions (SAQs) (range 33-62). Third-year and fourth-year students had 150 MCQs on average per year and no SAQs. The percentage of nutrition-related questions across all 4 years ranged from 6% in 2013 to 10% in 2016. The proportion of SAQs with nutrition content ranged from 12% in 2013 to 19% in 2016. Basic nutritional sciences, accounted for 60% of nutrition content and, 25% addressed dietary strategies for prevention and treatment of disease, and skills-based nutrition competencies represented approximately 10% of all questions., Summary and Conclusions: Minimal nutrition was included in the summative examinations. There did not appear to be any consistent increase in the nutrition content of MCQs over the 4-year period but there was some indication of an increase in nutrition content in SAQs. Longer term evaluation is required to confirm this trend. Only a small number of nutrition questions were skills based, most focused on basic nutritional science. Examinations included few skills-based nutrition questions, and consideration of setting a minimum level of nutrition in examinations could assist in ensuring the development of appropriate nutrition competencies in medical graduates., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: We examined the patterns of hand hygiene compliance (HHC) among health care providers (HCP) as observed by trained nurse and patient auditors over time in an ambulatory care Canadian provincial cancer agency., Methods: Nurse and volunteer patient auditors completed separate standardized forms documenting hand-cleansing opportunities during clinic visits. HHC rates were compared over time by HCP group and by specialty teams. Observations from 10 calendar quarters were analyzed from April 2015 to September 2019., Results: Nurse audit HHC rates ranged from 84% to 96%, encompassing 7,213 opportunities with no significant time-dependent trends by linear regression (R 2  = 2.3E-005, P = .9895). The patient audit HHC rates ranged from 57% to 82%, encompassing 23,402 opportunities, were lower overall compared to the nurse audit (73.6% vs 89.2%, respectively, P < .0001), but displayed an increasing trend (R 2  = 0.5374, P = .0159) over the same 10 time periods. The relative risk ratio for the differences decreased over time (R 2  = .5101, P = .0203). Patients acknowledged the importance of HHC and the audit process, but were reticent to remind HCP to comply., Conclusions: The nurse audit measuring HCP HHC before entering and after exiting patient examination rooms showed persistently high compliance over time whereas the patient-driven audit measuring HHC within the examination room increased over time suggesting a training effect upon practice. These measures appeared complementary., (Copyright © 2020. Published by Elsevier Inc.)

Background: There are no national prevalence studies of Strongyloides stercoralis infection in Australia, although it is known to be endemic in northern Australia and is reported in high risk groups such as immigrants and returned travellers. We aimed to determine the seropositivity (number positive per 100,000 of population and percent positive of those tested) and geographical distribution of S. stercoralis by using data from pathology laboratories., Methodology: We contacted all seven Australian laboratories that undertake Strongyloides serological (ELISA antibody) testing to request de-identified data from 2012-2016 inclusive. Six responded. One provided positive data only. The number of people positive, number negative and number tested per 100,000 of population (Australian Bureau of Statistics data) were calculated including for each state/territory, each Australian Bureau of Statistics Statistical Area Level 3 (region), and each suburb/town/community/locality. The data was summarized and expressed as maps of Australia and Greater Capital Cities., Principal Findings: We obtained data for 81,777 people who underwent serological testing for Strongyloides infection, 631 of whom were from a laboratory that provided positive data only. Overall, 32 (95% CI: 31, 33) people per 100,000 of population were seropositive, ranging between 23/100,000 (95% CI: 19, 29) (Tasmania) and 489/100,000 population (95%CI: 462, 517) (Northern Territory). Positive cases were detected across all states and territories, with the highest (260-996/100,000 and 17-40% of those tested) in regions across northern Australia, north-east New South Wales and north-west South Australia. Some regions in Greater Capital Cities also had a high seropositivity (112-188/100,000 and 17-20% of those tested). Relatively more males than females tested positive. Relatively more adults than children tested positive. Children were under-represented in the data., Conclusions/significance: The study confirms that substantial numbers of S. stercoralis infections occur in Australia and provides data to inform public health planning., Competing Interests: The authors have declared that no competing interests exist.

Validated methods are needed to detect spoilage microbes present in low numbers in foods and ingredients prior to defect onset. We applied propidium monoazide combined with 16S rRNA gene sequencing, qPCR, isolate identification, and pilot-scale cheese making to identify the microorganisms that cause slit defects in industrially produced Cheddar cheese. To investigate milk as the source of spoilage microbes, bacterial composition in milk was measured immediately before and after high-temperature, short-time (HTST) pasteurization over 10-h periods on 10 days and in the resulting cheese blocks. Besides HTST pasteurization-induced changes to milk microbiota composition, a significant increase in numbers of viable bacteria was observed over the 10-h run times of the pasteurizer, including 68-fold-higher numbers of the genus Thermus However, Thermus was not associated with slit development. Milk used to make cheese which developed slits instead contained a lower number of total bacteria, higher alpha diversity, and higher proportions of Lactobacillus , Bacillus , Brevibacillus , and Clostridium Only Lactobacillus proportions were significantly increased during cheese aging, and Limosilactobacillus ( Lactobacillus ) fermentum , in particular, was enriched in slit-containing cheeses and the pre- and post-HTST-pasteurization milk used to make them. Pilot-scale cheeses developed slits when inoculated with strains of L. fermentum , other heterofermentative lactic acid bacteria, or uncultured bacterial consortia from slit-associated pasteurized milk, thereby confirming that low-abundance taxa in milk can negatively affect cheese quality. The likelihood that certain microorganisms in milk cause slit defects can be predicted based on comparisons of the bacteria present in the milk used for cheese manufacture. IMPORTANCE Food production involves numerous control points for microorganisms to ensure quality and safety. These control points (e.g., pasteurization) are difficult to develop for fermented foods wherein some microbial contaminants are also expected to provide positive contributions to the final product and spoilage microbes may constitute only a small proportion of all microorganisms present. We showed that microbial composition assessments with 16S rRNA marker gene DNA sequencing are sufficiently robust to detect very-low-abundance bacterial taxa responsible for a major but sporadic Cheddar cheese spoilage defect. Bacterial composition in the (pasteurized) milk and cheese was associated with slit defect development. The application of Koch's postulates showed that individual bacterial isolates as well as uncultured bacterial consortia were sufficient to cause slits, even when present in very low numbers. This approach may be useful for detection and control of low-abundance spoilage microorganisms present in other foods., (Copyright © 2021 Xue et al.)

Vaccination is central to controlling COVID-19. Its success relies on having safe and effective vaccines and also on high levels of uptake by the public over time. Addressing questions of population-level acceptability, stability of acceptance, and sub-population variation in acceptability are imperative. Using a prospective design, a repeated measures two-wave online survey was conducted to assess key sociodemographic variables and intention to accept a COVID-19 vaccine. The first survey (Time 1) was completed by 3436 people during the period of national lockdown in Scotland and the second survey (n = 2016) was completed two months later (Time 2) when restrictions had been eased. In the first survey, 74% reported being willing to receive a COVID-19 vaccine. Logistic regression analyses showed that there were clear sociodemographic differences in intention to accept a vaccine for COVID-19 with intention being higher in participants of white ethnicity as compared with Black, Asian, and minority ethnic (BAME) groups, and in those with higher income levels and higher education levels. Intention was also higher in those who had "shielding" status due to underlying medical conditions. Our results suggest that future interventions, such as mass media and social marketing, need to be targeted at a range of sub-populations and diverse communities.

Acute myeloid leukemia (AML) is a caricature of normal hematopoiesis, driven from leukemia stem cells (LSC) that share some hematopoietic stem cell (HSC) programs including responsiveness to inflammatory signaling. Although inflammation dysregulates mature myeloid cells and influences stemness programs and lineage determination in HSC by activating stress myelopoiesis, such roles in LSC are poorly understood. Here, we show that S1PR3, a receptor for the bioactive lipid sphingosine-1-phosphate, is a central regulator which drives myeloid differentiation and activates inflammatory programs in both HSC and LSC. S1PR3-mediated inflammatory signatures varied in a continuum from primitive to mature myeloid states across AML patient cohorts, each with distinct phenotypic and clinical properties. S1PR3 was high in LSC and blasts of mature myeloid samples with linkages to chemosensitivity, while S1PR3 activation in primitive samples promoted LSC differentiation leading to eradication. Our studies open new avenues for therapeutic target identification specific for each AML subset., Competing Interests: Conflict of interests J.E.D Celgene: research funding; Trillium Therapeutics: Advisory Board. All other authors declare no conflicts of interests.

The purpose of this study was to develop and evaluate a new, open-source MR-compatible device capable of assessing unipedal and bipedal lower extremity movement with minimal head motion and high test-retest reliability. To evaluate the prototype, 20 healthy adults participated in two magnetic resonance imaging (MRI) visits, separated by 2-6 months, in which they performed a visually guided dorsiflexion/plantar flexion task with their left foot, right foot, and alternating feet. Dependent measures included: evoked blood oxygen level-dependent (BOLD) signal in the motor network, head movement associated with dorsiflexion/plantar flexion, the test-retest reliability of these measurements. Left and right unipedal movement led to a significant increase in BOLD signal compared to rest in the medial portion of the right and left primary motor cortex (respectively), and the ipsilateral cerebellum (FWE corrected, p < .001). Average head motion was 0.10 ± 0.02 mm. The test-retest reliability was high for the functional MRI data (intraclass correlation coefficients [ICCs]: >0.75) and the angular displacement of the ankle joint (ICC: 0.842). This bipedal device can robustly isolate activity in the motor network during alternating plantarflexion and dorsiflexion with minimal head movement, while providing high test-retest reliability. Ultimately, these data and open-source building instructions will provide a new, economical tool for investigators interested in evaluating brain function resulting from lower extremity movement., (© 2020 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Performance accountability-also frequently referred to as quality improvement in the fields of medicine and public policy-is under growing scrutiny in mental and behavioral health care. As one high-profile example, psychologists and other mental health providers will be deemed "eligible clinicians" under the 2015 Medicare Access and Children's Health Insurance Program Reauthorization Act starting in 2019. This will incentivize psychologists to track their Medicare patients' clinical outcomes and report them in data registries, and those who do not will suffer a reimbursement penalty. However, many psychologists are not aware of these developments or prepared for this change. The goal of this article is to provide information to psychologists about quality improvement and clinical data registries from four distinct, though overlapping, vantage points: professional governance, quantitative research, qualitative research, and clinical practice. We review recent regulations and research in this area, with an emphasis on exploring both the potential benefits and challenges of quality improvement. We conclude by providing recommendations for the field of psychology. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

The leukemia stem cell (LSC) populations of acute myeloid leukemia (AML) exhibit phenotypic, genetic, and functional heterogeneity that contribute to therapy failure and relapse. Progress toward understanding the mechanistic basis for therapy resistance in LSCs has been hampered by difficulties in isolating cell fractions that enrich for the entire heterogeneous population of LSCs within individual AML samples. We previously reported that CD200 gene expression is upregulated in LSC-containing AML fractions. Here, we show that CD200 is present on a greater proportion of CD45dim blasts compared with more differentiated CD45high cells in AML patient samples. In 75% (49 of 65) of AML cases we examined, CD200 was expressed on ≥10% of CD45dim blasts; of these, CD200 identified LSCs within the blast population in 9 of 10 (90%) samples tested in xenotransplantation assays. CD200+ LSCs could be isolated from CD200+ normal HSCs with the use of additional markers. Notably, CD200 expression captured both CD34- and CD34+ LSCs within individual AML samples. Analysis of highly purified CD200+ LSC-containing fractions from NPM1-mutated AMLs, which are commonly CD34-, exhibited an enrichment of primitive gene expression signatures compared with unfractionated cells. Overall, our findings support CD200 as a novel LSC marker that is able to capture the entire LSC compartment from AML patient samples, including those with NPM1 mutation., (© 2020 by The American Society of Hematology.)

SARS-Cov-2 was identified in Wuhan, China in December 2019. The World Health Organization (WHO) declared it a pandemic in March of 2020. COVID-19 has now been reported on every continent. In the United States, the total number of confirmed reported cases of COVID-19 has exceeded 1.8 million with the total death exceeding 100,000 people. The most common investigational diagnostics of this disease are RT-PCR and serology testing. The objective of this work was to validate two commercial kits for the detection of IgM and IgG using lateral flow immunoassay tests and to study the effect of the combination of both serology kits for better detection of immunoglobulins. A total of 195 patients presenting with respiratory symptoms suggestive of infection with SARS-Cov-2 were subject to serology and molecular testing. Two lateral flow immunochromatographic assay kits were used: the Healgen Scientific for SARS-CoV-2 IgM/IgG and the Raybiotech for SARS-CoV-2 IgM/IgG. Sensitivity and specificity of each kit alone and in combination were determined and compared. The limit of detection, inter and intra test variations, as well interfering substances and cross reactivity were also studied for both kits. The results show sensitivities for IgM detection varying between 58.9 and 66.2% for the kits alone and 87.7% of the combination of both kits. IgG detection was not significantly affected by this combination. Both kits manifested high specificities (99.2-100%). Both kits showed high clinical performance in terms of cross reactivity and interfering substances. Our results suggest using combinatory testing for the serology of COVID-19 after a full evaluation study, assessing all the parameters affecting their clinical performance before deciding on this combination., (Copyright © 2020 Daoud, McLeod and Stockman.)

The biorecognition ability of hybridized toll-like receptors (TLRs) 2 and 6 proteins on electrode surfaces has been studied. TLR biosensors have been designed to be non-specific to particular bacterial strains but rather to provide broad spectrum detection of cells and toxins containing relevant pathogen-associated molecular patterns (PAMPs). Our electrochemical TLR2/6 biosensors demonstrated selective detection towards Gram-positive bacterial whole-cells and a synthetic diacylated lipopeptide (Pam2CSK4), a PAMP. Responses towards Bacillus licheniformis (B. licheniformis) and Enterococcus hirae (E. hirae) were obtained. The biosensor was able to differentiate signals between B. licheniformis and a Gram-negative bacterial cell (control) as low as 100 CFU mL-1. One challenge in developing protein-based biosensors is to improve the shelf-life of the biosensor chips and preserve the detection activity of the protein molecules, therefore we did our first exploration into storage conditions. The activity of stored biosensors was found to be strongly dependent on storage medium, and that effective 'shelf-life' was obtained makes an important step towards creating robust sensors for real-life applications.