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Background: Uptake of pre-exposure prophylaxis (PrEP) in the United States (US) remains below target, despite reported high efficacy in prevention of HIV infection and being considered as a strategy for ending new HIV transmissions. Here, we sought to investigate drivers for PrEP use and barriers to increased uptake using real-world data. Methods: Data were drawn from the Adelphi PrEP Disease Specific Programme ™ , a cross-sectional survey of PrEP users and PrEP non-users at risk for HIV and their physicians in the US between August 2021 and March 2022. Physicians reported demographic data, clinical characteristics, and motivations for prescribing PrEP. PrEP users and non-users reported reasons for or against PrEP use, respectively. Bivariate analyses were performed to compare characteris tics of users and non-users. Results: In total, 61 physicians reported data on 480 PrEP users and 121 non-users. Mean ± standard deviation of age of users and non-users was 35.3 ± 10.8 and 32.5 ± 10.8 years, respectively. Majority were male and men who have sex with men. Overall, 90.0% of users were taking PrEP daily and reported fear of contracting HIV (79.0%) and having at-risk behaviors as the main drivers of PrEP usage. About half of non-users (49.0%) were reported by physicians as choosing not to start PrEP due to not wanting long-term medication. PrEP stigma was a concern for both users (50.0%) and non-users (65.0%). More than half felt that remembering to take PrEP (57.0%) and the required level of monitoring (63.0%) were burdensome. Conclusions: Almost half of people at risk for HIV were not taking PrEP due to not wanting long-term daily medication and about half of current PrEP users were not completely adherent. The most common reason for suboptimal adherence was forgetting to take medication. This study highlighted drivers for PrEP uptake from physician, PrEP user, and non-user perspectives as well as the attributes needed in PrEP products to aid increased PrEP uptake.

Adherence to antiretroviral therapy (ART) is critical for people with HIV (PWH) to achieve and maintain virologic suppression and minimize drug resistance. This study aimed to use real-world data to characterize ART adherence and its effect on quality of life (QoL) in PWH. Data were drawn from the Adelphi HIV Disease Specific Programme™, a cross-sectional survey of physicians and PWH in the United States, conducted June-October 2021. Demographic and clinical characteristics, ART adherence and treatment satisfaction for PWH were reported by physicians. PWH completed standardized QoL questionnaires. Adherence level was categorized into completely, mostly and less adherent. Regression analysis was used to investigate factors associated with adherence and the association between adherence and QoL measures. Of 578 PWH, 189 (32.7%) were not completely adherent. Having AIDS-defining illnesses, anxiety/depression or being symptomatic was significantly associated with lower adherence. Reasons for poor adherence included forgetting, difficulties integrating into routine and side effects. QoL scores were significantly higher in the completely adherent group. These findings highlight the strong association between suboptimal adherence and QoL among PWH and key factors and PWH reasons that may lead to suboptimal adherence. Interventions aimed at improving the QoL of PWH by understanding these factors are warranted.

Artificial Intelligence (AI) is increasingly being adopted across many domains such as transport, healthcare, defence and sport, with football codes no exception. Though there is a range of potential benefits of AI, concern has also been expressed regarding potential risks. An important first step in ensuring that AI applications in football are usable, beneficial, safe and ethical is to understand the current range of applications, the AI models adopted and their proposed functions. This systematic review aimed to identify different applications of AI across football codes to synthesise current knowledge and determine whether potential risks are being considered. The systematic review included 190 peer-reviewed articles. Nine areas of application were found ranging from athlete evaluation and event detection to match outcome prediction and injury detection and prediction. In total, 27 different AI models were identified, with artificial neural networks the most frequently applied. Five AI assessment metrics were identified including specificity, recall, precision, accuracy and F1-score. Four potential risks were identified, concerning data security, usability, data biases and inappropriate athlete load management. It is concluded that, though a wide range of AI applications currently exist, further work is required to develop AI for football and identify and manage potential risks.

Competing Interests: Disclosure FS reports no conflicts of interest. CB reports institutional financial interest as an invited speaker for MSD Merck Sharp and Dohme AG. PS reports no conflicts of interest. LAJ reports institutional financial interest for expert testimony and as an invited speaker from Haute-Ecole Arc Santé, Neuchâtel. SD reports no conflicts of interest. NE reports no conflicts of interest. LG reports personal fees as an advisory board participant for Fidia and as a consultant for the Istituto a Carattere Scientifico IRCS-IRST Meldola (FC); royalties from Minerva Medica and Springer; non-remunerated roles as an officer of the World Psychiatric Association (WPA) and chair of the WPA Section on Psycho-Oncology and Palliative Care. YL reports no conflicts of interest. FV reports personal financial interests for a writing engagement for Verlag für Gesprächsführung bzw. Schattauer; non-remunerated roles as co-head of the Transplantation Medicine Working Group (WG), co-head of the Psychosomatic Consultation Liaison WG and member of the Deutsches Kollegium für Psychosomatische Medizin (DKPM); non-remunerated roles as co-head of the Transplantation Medicine Special Interest Group and member of the European Association of Psychosomatic Medicine; non-remunerated roles as co-head of the Communication WG and member of the German Cancer Society; personal fees for contribution to educational programmes from AIM, APP and Medical Council Bremen, University Hospital of Cologne; grants from German Cancer Aid, the German Pediatric Leucemia Society and the Innovation Committee (Innovationsausschuss) of the Federal Joint Committee (G-BA) (Berlin, TX, DE); employment as Head of the Department of Psychosomatic Medicine at Robert-Bosch-Krankenhaus Stuttgart and affiliated to the University Hospital of Cologne. DS reports no conflicts of interest. CIR reports no conflicts of interest.

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. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.

Objective: Chronic spontaneous urticaria (CSU) is a debilitating inflammatory skin condition, often impacting quality of life. International guidelines recommend omalizumab, an anti-immunoglobulin E antibody, for second-line treatment. Our objective was to understand patient characteristics associated with prescription of omalizumab, and assess real-world outcomes in patients with CSU treated with omalizumab., Methods: We analyzed data from the Adelphi Real World CSU Disease Specific Programme, a cross-sectional survey with retrospective data collection (December 2020-October 2021) from physicians and patients with CSU in the United States., Results: Data from allergists ( n  = 45), dermatologists ( n  = 51), and primary care physicians (PCPs; n  = 20) were included. At the time of data collection, one-third of patients were receiving omalizumab ( n  = 220) and 67% were eligible for but not receiving omalizumab ( n  = 455). Using logistic regression, the odds of receiving omalizumab were higher in patients whose entire bodies were affected by hives [odds ratio (OR) = 2.551; 95% confidence interval (CI) 1.502-4.333; p  < 0.001] or with deteriorating/unstable prognoses at treatment initiation [OR = 2.219; 95% CI 1.031-4.777; p  = 0.042], and lower in patients managed by PCPs [OR = 0.276; 95% CI 0.130-0.584; p  < 0.001]. Estimates from an inverse probability weighted regression adjustment model indicated that patients receiving omalizumab had higher treatment satisfaction, improvements in itching, hives, angioedema, insomnia, and anxiety, and lower impact on work productivity, compared with patients not receiving omalizumab., Conclusion: Around two-thirds of patients with CSU considered eligible for omalizumab were not receiving the guideline-recommended therapy. Patients receiving omalizumab had better real-world outcomes compared with patients not receiving omalizumab. Ensuring patients receive the most appropriate treatment could benefit patients with CSU.

Work Domain Analysis (WDA), the foundational phase in the Cognitive Work Analysis Framework (CWA), provides a platform for understanding and designing complex systems. Though it has been used extensively, there are few applications in healthcare, and model validation for different contexts is not always undertaken. The current study aimed to validate an Emergency Department (ED) WDA across three metropolitan hospitals that differ in the type and nature of services they provide, including the ED in which the original ED WDA was developed. A facilitated workshop was conducted at the first ED and interviews at two subsequent EDs to refine and validate the ED WDA. ED subject matter experts (SMEs) including nurses, doctors, administration, and allied health personnel provided feedback on the model. SME feedback resulted in modifications to the original ED WDA model including combining nodes to reduce duplication and amending five labels for clarity. The resulting WDA provides a valid representation of the EDs found in metropolitan districts within an Australian state and can be used by roles such as frontline ED clinicians, hospital managers, and policy developers to facilitate the design, testing, and sharing of solutions to local and shared problems. The findings also demonstrate the importance of validating WDA models across different contexts., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: The aim of this study was to evaluate six files on the pericervical dentin (PCD) and the smallest dentin thickness zones (SDTZ) in mesial root canals of mandibular molars., Materials and Methods: Sixty mandibular molars with two mesial canals and Vertucci configuration were aleatory allocated in 6 experimental groups of 10 molars and 20 root canals. Specimens were scanned before instrumentation using the SkyScan 1275 (Bruker microCT, Kontich, Belgium). Group 1 was treated with WaveOne Gold (WG), group 2 with Reciproc Blue (RB), group 3 with TRUShape (TS), group 4 with XP-endo Shaper (XP), group 5 with iRace (IR), and group 6 with TruNatomy (TN). After instrumentation, the molars were scanned again and the images recorded were reconstructed with the NRecon v.1.7 (Bruker micro-CT) and analyzed with CTAn v.1.20.8 software (Bruker micro-CT) quantifying the changes produced in the surface, volume, structure thickness, SMI, and centroids at the Pericervical Dentin area of the root canals (PCD) located from the root canal orifices at the floor of the pulp chamber to 4 mm in the apical direction, and the changes in the Smallest Dentin Thickness Zones (SDTZ) located (from the furcation to 4 mm and 7 mm in the apical direction. The data obtained were compared using Wilcoxon and ANOVA with a 5% significance level., Results: XP and TN were similar in all the parameters (P >.05) at the PCD, but TN showed significant differences from WG, RB, TS, and IR (P <.05), while XP showed significant differences from WG (P <.05) in volume, surface, and structure thickness. Regarding the changes in the SDTZ, the amount of dentin removed was similar between the groups in both canals at the middle 1/3, at the cervical 1/3 for MB canals, and in ML canals for RB, TS, XP, IR, and TN (P>.05). The action of WG was significantly different from that of XP and TN in the cervical 1/3 of the ML canal (P <.05)., Conclusions: XP and TN rotatory files with small taper and volume maintained better with minor changes at the PCD and SDTZ, while WG reciprocation file produced the largest change. All the files were maintained centered at the PCD, and their performances were safe with a minimal thickness higher 0.5 mm at the SDTZ, and without risk of perforation., Trial Registration: No clinical trials were indicated in this study., Clinical Relevance: The choice of endodontic files is a relevant factor in the conservative performance of root canal treatments., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Fracture burden has created a need to better understand bone repair processes under different pathophysiological states. Evaluation of structural and material properties of the mineralized callus, which is integral to restoring biomechanical stability is, therefore, vital. Microcomputed tomography (micro-CT) can facilitate noninvasive imaging of fracture repair, however, current methods for callus segmentation are only semiautomated, restricted to defined regions, time/labor intensive, and prone to user variation. Herein, we share a new automatic method for segmenting callus in micro-CT tomograms that will allow for objective, quantitative analysis of the bone fracture microarchitecture. Fractured and nonfractured mouse femurs were scanned and processed by both manual and automated segmentation of fracture callus from cortical bone after which microarchitectural parameters were analyzed. All segmentation and analysis steps were performed using CTAn (Bruker) with automatic segmentation performed using the software's image-processing plugins. Results showed automatic segmentation reliably and consistently segmented callus from cortical bone, demonstrating good agreement with manual methods with low bias: tissue volume (TV): -0.320 mm 3 , bone volume (BV): 0.0358 mm 3 , and bone volume/tissue volume (BV/TV): -3.52%, and was faster and eliminated user-bias and variation. Method scalability and translatability across rodent models were verified in scans of fractured rat femora showing good agreement with manual methods with low bias: TV: -3.654 mm 3 , BV: 0.830 mm 3 , and BV/TV: 7.81%. Together, these data validate a new automated method for segmentation of callus and cortical bone in micro-CT tomograms that we share as a fast, reliable, and less user-dependent tool for application to study bone callus in fracture, and potentially elsewhere., (© 2022 The Authors. Journal of Orthopaedic Research® published by Wiley Periodicals LLC on behalf of Orthopaedic Research Society.)

Despite many promising results obtained in previous preclinical studies, the clinical development of encapsulated cell technology (ECT) for the delivery of therapeutic proteins from macrocapsules is still limited, mainly due to the lack of an allogeneic cell line compatible with therapeutic application in humans. In our work, we generated an immortalized human myoblast cell line specifically tailored for macroencapsulation. In the present report, we characterized the immortalized myoblasts and described the engineering process required for the delivery of functional therapeutic proteins including a cytokine, monoclonal antibodies and a viral antigen. We observed that, when encapsulated, the novel myoblast cell line can be efficiently frozen, stored, and thawed, which limits the challenge imposed by the manufacture and supply of encapsulated cell-based therapeutic products. Our results suggest that this versatile allogeneic cell line represents the next step toward a broader development and therapeutic use of ECT., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper. E.C., A.E., and J.G. are employees of MaxiVAX SA. A.L. is a former employee of MaxiVAX SA and a current scientific advisor. N.M is founder and minority shareholder of MaxiVAX SA. MaxiVAX SA is a Geneva-based biotech company involved in cell encapsulation technology., (© 2022 The Authors.)

Purpose: Synchrotron radiation-based tomography yields microanatomical features in human and animal tissues without physical slicing. Recent advances in instrumentation have made laboratory-based phase tomography feasible. We compared the performance of three cutting-edge laboratory systems benchmarked by synchrotron radiation-based tomography for three specimens. As an additional criterion, the user-friendliness of the three microtomography systems was considered. Approach: The three tomography systems-SkyScan 2214 (Bruker-microCT, Kontich, Belgium), Exciscope prototype (Stockholm, Sweden), and Xradia 620 Versa (Zeiss, Oberkochen, Germany)-were given 36 h to measure three medically relevant specimens, namely, zebrafish larva, archaeological human tooth, and porcine nerve. The obtained datasets were registered to the benchmark synchrotron radiation-based tomography from the same specimens and selected ones to the SkyScan 1275 and phoenix nanotom m ® laboratory systems to characterize development over the last decade. Results: Next-generation laboratory-based microtomography almost reached the quality achieved by synchrotron-radiation facilities with respect to spatial and density resolution, as indicated by the visualization of the medically relevant microanatomical features. The SkyScan 2214 system and the Exciscope prototype demonstrated the complementarity of phase information by imaging the eyes of the zebrafish larva. The 3 - μ m thin annual layers in the tooth cementum were identified using Xradia 620 Versa. Conclusions: SkyScan 2214 was the simplest system and was well-suited to visualizing the wealth of anatomical features in the zebrafish larva. Data from the Exciscope prototype with the high photon flux from the liquid metal source showed the spiral nature of the myelin sheaths in the porcine nerve. Xradia 620 Versa, with detector optics as typically installed for synchrotron tomography beamlines, enabled the three-dimensional visualization of the zebrafish larva with comparable quality to the synchrotron data and the annual layers in the tooth cementum., (© 2022 The Authors.)

The link between smoking and lung cancer predisposes patients to feeling shame and guilt, which increases risk for depression. To test the hypothesis shame would have a stronger association with depressive symptoms than guilt, a hierarchical regression was conducted. Three regressions were run to examine the associations of self-compassion with shame, guilt, and depressive symptoms. The best model to explain depressive symptoms included shame, but not guilt. Greater self-compassion was associated with less shame and fewer depressive symptoms, but not guilt. Results point to interventions targeting shame via enhancing self-compassion among patients with lung cancer and histories of smoking.

Purpose Musculoskeletal (MSK) pain is a common cause of work absence. The recent SWAP (Study of Work And Pain) randomised controlled trial (RCT) found that a brief vocational advice service for primary care patients with MSK pain led to fewer days' work absence and provided good return-on-investment. The I-SWAP (Implementation of the Study of Work And Pain) initiative aimed to deliver an implementation test-bed of the SWAP vocational advice intervention with First Contact Practitioners (FCP). This entailed adapting the SWAP vocational advice training to fit the FCP role. This qualitative investigation explored the implementation potential of FCPs delivering vocational advice for patients with MSK pain. Methods Semi-structured interviews and focus groups were conducted with 10 FCPs and 5 GPs. Data were analysed thematically and findings explored using Normalisation Process Theory (NPT). Results I-SWAP achieved a degree of 'coherence' (i.e. made sense), with both FCPs and GPs feeling FCPs were well-placed to discuss work issues with these patients. However, for many of the FCPs, addressing or modifying psychosocial and occupational barriers to return-to-work was not considered feasible within FCP consultations, and improving physical function was prioritised. Concerns were also raised that employers would not act on FCPs' recommendations regarding return-to-work. Conclusion FCPs appear well-placed to discuss work issues with MSK patients, and signpost/refer to other services; however, because they often only see patients once they are less suited to deliver other aspects of vocational advice. Future research is needed to explore how best to provide vocational advice in primary care settings., (© 2021. The Author(s).)

Patient flow between the emergency department (ED) and hospital wards becomes problematic when bed availability is limited. To better understand the constraints that shape patient flow and everyday work in the ED, we applied Control Task Analysis (i.e. Contextual Activities Template, CAT) and Social Organisational Cooperation Analysis (SOCA) phases from the Cognitive Work Analysis framework to identify ways in which to optimise patient flow. The model and analysis were created through observations in the ED of clinicians (e.g. nurses, doctors), and professional staff (e.g. ward personnel, clerks). The CAT and SOCA-CAT models illustrate workspaces, patient journey phases, and patient volume within the department that are heavily loaded with tasks and human and non-human agents performing these tasks, while others are underutilised. The findings suggest that an ED's adaptive capacity could be strengthened through the integration of additional human and non-human agents allowing the redistribution of clinical and non-clinical tasks. Practitioner Summary: Workflow in EDs is constrained by uneven geographical distribution of activities, insufficient adaptive support during critical patient journey phases and periods of high patient volume. Adaptive capacity could be strengthened by additional human and non-human agents in combination with a redistribution of tasks, supporting seamless successful structural and behavioural adaptation in ED.

Competing Interests: Competing interests: All authors are coauthors of the Chartered Institute of Ergonomics and Human Factors white paper referred to in the manuscript. MS is a member of the Governing Council of the Chartered Institute of Ergonomics and Human Factors.

Background: Emergency departments (EDs) are complex socio-technical work systems that require staff to manage patients in an environment of fluctuating resources and demands. To better understand the purpose, and pressures and constraints for designing new ED facilities, we developed an abstraction hierarchy model as part of a work domain analysis (WDA) from the cognitive work analysis (CWA) framework. The abstraction hierarchy provides a model of the structure of the ED, encompassing the core objects, processes, and functions relating to key values and the ED's overall purpose., Methods: Reviews of relevant national and state policy, guidelines, and protocol documents applicable to care delivery in the ED were used to construct a WDA. The model was validated through focus groups with ED clinicians and subsequently validated using a series of WDA prompts., Results: The model shows that the ED system exhibits extremely interconnected and complex features. Heavily connected functions introduce vulnerability into the system with function performance determined by resource availability and prioritization, leading to a trade-off between time and safety priorities., Conclusions: While system processes (e.g., triage, fast-track) support care delivery in ED, this delivery manifests in complex ways due to the personal and disease characteristics of patients and the dynamic state of the ED system. The model identifies system constraints that create tension in care delivery processes (e.g., electronic data entry, computer availability) potentially compromising patient safety., Application: The model identified aspects of the ED system that could be leveraged to improve ED performance through innovative ED system design.

Objective: Few studies have explored the shared effects of Parkinson's disease (PD) within patient/caregiver dyads. To fill this gap, we compared stress-health outcomes of patients with those of caregiving-partners, examined individual stress-health associations, and explored stress-health associations within dyads., Method: A total of 18 PD patient/caregiving-partner dyads (N = 36) reported on disease-specific distress, anxiety, quality of life (QOL), and provided saliva samples for cortisol assessment. This cross-sectional, secondary analysis of a prospective pilot study used Actor-Partner Interdependence Models to test aims., Results: Patients reported greater anxiety, poorer QOL, and demonstrated flatter cortisol slopes and higher mean bedtime cortisol compared to caregiving-partners. Both patients and caregiving-partners with greater anxiety had elevated bedtime cortisol and poorer QOL. Greater disease-specific distress in an individual was associated with higher diurnal mean cortisol in their partner., Conclusions: Findings highlight the potential for psychosocial interventions at the dyadic level to reduce shared burden and promote coping among PD patient/caregiving-partner dyads., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

This study utilized a latent profile analysis approach to examine the relationship between mindfulness profiles and self-reported mental and physical health, as well as salivary cortisol levels in a sample of 85 undergraduate students. Consistent with theory, the Judgmentally Observing (high monitoring, low acceptance) reported poorer mental health and exhibited flatter diurnal cortisol slopes than the Unobservant Accepting (low monitoring, high acceptance) and Average Mindfulness profiles. No differences in self-reported physical health, cortisol response to awakening, or diurnal mean cortisol were observed among the profiles. Future directions are discussed.

Objective: This paper presents the Binary-Based Model (BBM), a new approach to Human Factors (HF) method selection. The BBM helps practitioners select the most appropriate HF methodology in relation to the complexity within the target system., Background: There are over 200 HF methods available to the practitioner and little guidance to help choose between them., Method: The BBM defines a HF "problem space" comprising three complexity attributes. HF problems can be rated against these attributes and located in the "problem space." In addition, a similar HF "approach space" in which 66 predictive methods are rated according to their ability to confront those attributes is defined. These spaces are combined into a "utility space" in which problems and methods coexist. In the utility space, the match between HF problems and methods can be formally assessed., Results: The method space is split into octants to establish broad groupings of methods distributed throughout the space. About 77% of the methods reside in Octant 1 which corresponds to problems with low levels of complexity. This demonstrates that most HF methods are suited to problems in low-complexity systems., Conclusion: The location of 77% of the rated methods in Octant 1 indicates that HF practitioners are underserved with methods for analysis of HF problems exhibiting high complexity., Application: The BBM can be used by multidisciplinary teams to select the most appropriate HF methodology for the problem under analysis. All the materials and analysis are placed in the public domain for modification and consensus building by the wider HF community.

Background: Teamwork in the operating theatre is a complex emergent phenomenon and is driven by cooperative relationships between staff. A foundational requirement for teamwork is the ability to communicate effectively, and in particular, knowing each other's name. Many operating theatre staff do not know each other's name, even after formal team introductions. The use of theatre caps to display a staff member's name and role has been suggested to improve communication and teamwork., Methods: We hypothesized that the implementation of scrub hats with individual team members' names and roles would improve the perceived quality and effectiveness of communication in the operating theatre. A pilot project was designed as a pre-/post-implementation questionnaire sent to 236 operating room staff members at a general hospital in suburban Melbourne, Victoria, Australia, between November 6 to December 18, 2018. Participants included medical practitioners (anaesthetists, surgeons, obstetricians and gynaecologists), nurses (anaesthetic, scrub/scout and paediatric nurses), midwives and theatre technicians. The primary outcome was a change in perceived teamwork score, measured using a five position Likert scale., Results: Of 236 enrolled participants, 107 (45%) completed both the pre and post intervention surveys. The median perceived teamwork response of four did not change after the intervention, though the number of low scores was reduced (p = 0.015). In a pre-planned subgroup analysis, the median perceived teamwork score rose for midwives from three to four (p < 0.001), while for other craft groups remained similar. The median number of staff members in theatre that a participant did not know the name of reduced from three to two (p < 0.001). Participants reported knowing the names of all staff members present in the theatre more frequently after the intervention (31% vs 15%, p < 0.001). The reported rate of formal team introductions was not significantly different after the intervention (34.7% vs 47.7% p = 0.058)., Conclusions: In this study, we found that wearing caps displaying name and role appeared to improve perceived teamwork and improve communication between staff members working in the operating theatre., (© 2021. The Author(s).)

Introduction: This research studies and compares the shaping ability of WaveOne Gold (WG; Dentsply Tulsa Dental Specialties, Tulsa, OK), the Reciproc Blue (RB; VDW, Munich, Germany), TRUShape (TS, Dentsply Tulsa Dental Specialties), XP-endo Shaper (XP; FKG, La Chaux-de-Fonds, Switzerland), iRace (IR, FKG), and TruNatomy (TN; Dentsply Sirona, Ballaigues, Switzerland) in the preparation of moderately curved canals and using micro-computed tomographic technology., Methods: Sixty lower molars with 2 mesial canals were randomly distributed into 6 groups of 10 molars and 20 canals per group (n = 20). Specimens were scanned before and after preparation using the SkyScan 1275 (Bruker microCT, Kontich, Belgium). Group 1 was treated with WG, group 2 with RB, group 3 with TS, group 4 with XP, group 5 with IR, and group 6 with TN. After instrumentation, researchers quantified the changes produced in the canal geometry in terms of surface, volume, structure thickness, surface convexity index, structure model index, percentage of surface touched, and centroids. Wilcoxon and analysis of variance tests were performed to compare the values before and after preparation and the differences between groups. The significance level was established at 5%., Results: There were no significant differences between WG and RB (P > .05) and between TN and XP (P > .05). TN had significant differences with WG, RB, TS, and IR (P < .05). All the files produced similar apical transportation (P > .05)., Conclusions: WG and RB and TN and XP had similar shaping effectivity. TS and WG touched the highest percentages of canal surfaces (81% and 73%, respectively) but produced the biggest changes in the canal anatomy. TN and XP better kept the canal anatomy, but TN touched the lowest percentage of canal surface (50%). All the files used were able to clean and to shape moderately curved canals with minimal apical transportation., (Copyright © 2021 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Background: Sustainable shifts in population behaviours require system-level implementation and embeddedness of large-scale health interventions. This paper aims to understand how different contexts of scaling up interventions affect mechanisms to produce intended and unintended scale up outcomes., Methods: A mixed method study combining a realist perspective and systems analysis (causal loop diagrams) of scaled-up physical activity and/or nutrition interventions implemented at a state/national level in Australia (2010-18). The study involved four distinct phases: Phase 1 expert consultation, database and grey literature searches to identify scaled-up interventions; Phase 2 generating initial Context-Mechanism-Outcome configurations (CMOs) from the WHO ExpandNet framework for scaling up; Phase 3 testing and refining CMOs via online surveys and realist interviews with academics, government and non-government organisations (NGOs) involved in scale up of selected interventions (Phase 1); and Phase 4 generating cross-case mid-range theories represented in systems models of scaling up; validated by member checking. Descriptive statistics were reported for online survey data and realist analysis for interview data., Results: Seven interventions were analysed, targeting nutrition (n = 1), physical activity (n = 1), or a combination (n = 5). Twenty-six participants completed surveys; 19 completed interviews. Sixty-three CMO pathways underpinned successful scale up, reflecting 36 scale up contexts, 8 key outcomes; linked via 53 commonly occurring mechanisms. All five WHO framework domains were represented in the systems models. Most CMO pathways included 'intervention attributes' and led to outcomes 'community sustainability/embeddedness' and 'stakeholder buy-in/perceived value'. Irrespective of interventions being scaled in similar contexts (e.g., having political favourability); mechanisms still led to both intended and unintended scale up outcomes (e.g., increased or reduced sustainability)., Conclusion: This paper provides the first evidence for mechanisms underpinning outcomes required for successful scale up of state or nationally delivered interventions. Our findings challenge current prerequisites for effective scaling suggesting other conditions may be necessary. Future scale up approaches that plan for complexity and encourage iterative adaptation throughout, may enhance scale up outcomes. Current linear, context-to-outcome depictions of scale up oversimplify what is a clearly a complex interaction between perceptions, worldviews and goals of those involved. Mechanisms identified in this study could potentially be leveraged during future scale up efforts, to positively influence intervention scalability and sustainability.

Development of new veterinary antibacterials is an important and challenging endeavor. Global recognition of antimicrobial resistance as a threat across human, animal, plant, food, and environmental sectors has increased the level of scrutiny on veterinary antibacterial use. Rigorous scientific evaluation of these products has and continues to be the underpinning of effectiveness evaluations and how hazards are identified, characterized, and ultimately used to make evidence-based and risk-based safety decisions. Some scientific factors commonly considered in the development of veterinary antibacterials include the pathogenesis and sequelae of the indicated disease, clinical and bacteriological improvement, dosage regimen (dose amount, route, duration, frequency), and antimicrobial-resistance qualitative risk assessments. Key discussion areas covered are how culture and susceptibility testing help determine if antibacterial effects are primarily responsible for clinical improvement and how pharmacokinetic and pharmacodynamic data can help predict success, aid in defining an adequate dosage regimen, and help minimize resistance emergence and spread., (Published 2019. This article is a U.S. Government work and is in the public domain in the USA.)

The medical and university department of biology pathology at Henri Mondor hospital in Créteil has been engaged in an NF EN ISO 15189 accreditation process since 2014. One of the elements of this process concerns the quality of handling of samples and their transportation to laboratories, including the implementation place requires fighting against pre-examination non-conformities, which are the source of many dysfunctions. The pre-examination group has implemented several actions in a targeted care service. Thanks to these, the rate of non-conformities has halved in 18 months. In parallel, a work project targeting student nurses on internship was born to follow up on the results of a statistical study carried out by the pre-examination group on non-conformities. The objective of the project was to include nursing students on internship in a full support course on good sampling practices and pre-analytical non-conformities. This was based on the realization of two knowledge quizzes (before and after training), theoretical training, and visits to several laboratories. This study lasted 10 months with the participation of 37 students. The results showed a marked improvement in knowledge of pre-analytics as well as total satisfaction of all students. Our approach has helped to better understand the needs of laboratories and demonstrates the usefulness of training students in good sampling practices in order to ensure better patient care as well as an improvement in their comfort and well-being.

Background: Emotional distress (defined as any negative mood state, including anxiety, depression, trauma symptoms and global distress) is common in people with multiple sclerosis (PwMS). To develop more integrated care for PwMS requires a better understanding of causal variables underlying persistent emotional distress. This systematic review critically appraised and synthesised the findings of prospective studies investigating predictors of emotional distress in PwMS., Method: CINAHL, Medline, and PsycINFO, were systematically searched for: i) prospective cohort studies with ≥1-month follow-up period, which; ii) evaluated baseline clinical and demographic, social and/or psychosocial predictors of emotional distress; iii) presented results for adults with MS; and iv) used validated measures to assess emotional distress. Risk of bias was assessed using an adapted version of the Newcastle-Ottawa Scale., Results: Thirteen studies, reported in 17 papers, were included. A wide range of outcome measures and statistical methods were used. The most reliable finding was that baseline emotional distress and stress-coping variables predicted emotional distress. Less robust support was found for income, negative cognitive illness appraisals and poor social support. No other variables often predicted emotional distress., Limitations: Lack of consistency across included studies may limit confidence in the results obtained., Conclusions: Little is currently known about how or why some people become and remain distressed following a diagnosis of MS, whilst others do not. However, psychological and social factors such as emotional distress and stress-coping variables appear to be important. A better understanding of the psychological factors underpinning distress in PwMS is needed., (Copyright © 2020. Published by Elsevier B.V.)

Erythropoietin (EPO), the hypoxia-inducible hematopoietic hormone, has well-established neuroprotective/neurotrophic roles in the developing central nervous system and the therapeutic potential of EPO has been widely explored in clinical studies for the treatment of perinatal hypoxic brain lesion, as well as prematurity. Here, we reveal that both EPO and Epo receptor (EPOR) are expressed in the developing rat somatosensory cortex during radial migration and laminar positioning of granular and supragranular neurons. Experimental deregulation of EPO signaling using genetic approaches results in aberrant migration, as well as permanent neuronal misplacement leading to abnormal network activity and protracted sensory behavioral deficits. We identify ERK as the downstream effector of the EPO signaling pathway for neuronal migration. These findings reveal a crucial role for endogenous EPO signaling in neuronal migration, and offer important insights for understanding how the temporary deregulation of EPO could result in migration defects that lead to abnormal behavior in the adult., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2020. Published by The Company of Biologists Ltd.)

The common cause hypothesis, as applied here, proposes that similar networks of influencing factors may contribute to both adverse outcomes and near misses. This hypothesis has not been evaluated using a systems-thinking perspective. The aims of this study are to evaluate whether networks of contributory and protective factors exist within aviation serious near miss reports and to determine if the common cause hypothesis is applicable in this context. Sixteen incident reports from French civil aviation crash investigation bureau were analysed using the AcciMap method. Contributory and protective factors, and relationships between both were identified via coding of the reports. The results indicate that considering protective factors support a richer picture of incidents and provide support for the common cause hypothesis as measured by similar mean factor volume and sociotechnical levels for both contributory and protective factors. However, the findings also show the direction of relationships among protective and contributory factors may be indicative of a difference among adverse outcomes, near misses, and normal work. Future research should consider how a network of relationships may impact on the common contributory and protective factors found in near misses., Competing Interests: Declaration of competing interest None., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Purpose: Promoting health-related quality of life (HRQOL) is a primary goal of lung cancer treatment. Trauma history and distress can negatively impact HRQOL., Design: A cross-sectional design examined the associations of trauma history, cancer-specific distress, and HRQOL., Sample/method: Sixty lung cancer patients completed questionnaires on trauma history including the number and severity of traumatic events experienced. Cancer-specific distress, HRQOL, and depression were also reported., Findings: As hypothesized, trauma history and cancer-specific distress were negatively associated with HRQOL (all r's > -.27). Depression emerged as a confound in the association between cancer-specific distress and HRQOL., Conclusions: Retrospectively-reported trauma was linked with poorer HRQOL in lung cancer patients., Implications: Interventions aimed at improving lung cancer patients' HRQOL should consider the possible role of trauma history (both frequency and distress).

Previous meta-analyses conclude that psychological treatments are efficacious for emotional distress in breast cancer (BCa). However, the practical relevance of these meta-analyses is questionable; none focused specifically on clinically distressed patients or whether treatment effects were clinically significant. In a two-stage individual patient data (IPD) meta-analysis of 17 randomized controlled trials of manualized psychological treatments in BCa, we evaluated treatment efficacy in distressed BCa patients (n = 1591) using clinical significance and effect size analyses. Outcomes were anxiety, depression, and general distress, evaluated at post-treatment and follow-up. Moderators examined were treatment type, treatment format, therapists' profession, control condition, age, outcome measure, and trial quality. Treated patients were more likely than controls to recover from anxiety and general distress at post-treatment (14-15% more treated patients recovered), but not at mean 8-months follow-up. Overall recovery rates were low: across outcomes, at post-treatment, only 30-32% of treated patients and 15-25% of controls recovered; at follow-up, only 21-30% of treated patients and 18-35% of controls recovered. Small between-group effect sizes in favour of treatment were found across outcomes at post-treatment (g = 0.32-0.34) but not at follow-up. Across the different analysis methods, few moderator effects were found. More efficacious psychological treatments are needed for distressed BCa patients., Competing Interests: Declaration of competing interest None., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Animal models are essential tools for addressing fundamental scientific questions about skeletal diseases and for the development of new therapeutic approaches. Traditionally, mice have been the most common model organism in biomedical research, but their use is hampered by several limitations including complex generation, demanding investigation of early developmental stages, regulatory restrictions on breeding, and high maintenance cost. The zebrafish has been used as an efficient alternative vertebrate model for the study of human skeletal diseases, thanks to its easy genetic manipulation, high fecundity, external fertilization, transparency of rapidly developing embryos, and low maintenance cost. Furthermore, zebrafish share similar skeletal cells and ossification types with mammals. In the last decades, the use of both forward and new reverse genetics techniques has resulted in the generation of many mutant lines carrying skeletal phenotypes associated with human diseases. In addition, transgenic lines expressing fluorescent proteins under bone cell- or pathway- specific promoters enable in vivo imaging of differentiation and signaling at the cellular level. Despite the small size of the zebrafish, many traditional techniques for skeletal phenotyping, such as x-ray and microCT imaging and histological approaches, can be applied using the appropriate equipment and custom protocols. The ability of adult zebrafish to remodel skeletal tissues can be exploited as a unique tool to investigate bone formation and repair. Finally, the permeability of embryos to chemicals dissolved in water, together with the availability of large numbers of small-sized animals makes zebrafish a perfect model for high-throughput bone anabolic drug screening. This review aims to discuss the techniques that make zebrafish a powerful model to investigate the molecular and physiological basis of skeletal disorders., (Copyright © 2020 Tonelli, Bek, Besio, De Clercq, Leoni, Salmon, Coucke, Willaert and Forlino.)

Transplantation of appropriate neuronal precursors after injury is a promising strategy to reconstruct cortical circuits, but the efficiency of these approaches remains limited. Here, we applied targeted apoptosis to selectively ablate layer II/III pyramidal neurons in the rat juvenile cerebral cortex and attempted to replace lost neurons with their appropriate embryonic precursors by transplantation. We demonstrate that grafted precursors do not migrate to replace lost neurons but form vascularized clusters establishing reciprocal synaptic contacts with host networks and show functional integration. These heterotopic neuronal clusters significantly enhance the activity of the host circuits without causing epileptic seizures and attenuate the apoptotic injury-induced functional deficits in electrophysiological and behavioral tests. Chemogenetic activation of grafted neurons further improved functional recovery, and the persistence of the graft was necessary for maintaining restored functions in adult animals. Thus, implanting neuronal precursors capable to form synaptically integrated neuronal clusters combined with activation-based approaches represents a useful strategy for helping long-term functional recovery following brain injury., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Bones adapt to mechanical forces according to strict principles predicting straight shape. Most bones are, however, paradoxically curved. To solve this paradox, we used computed tomography-based, four-dimensional imaging methods and computational analysis to monitor acute and chronic whole-bone shape adaptation and remodeling in vivo. We first confirmed that some acute load-induced structural changes are reversible, adhere to the linear strain magnitude regulation of remodeling activities, and are restricted to bone regions in which marked antiresorptive actions are evident. We make the novel observation that loading exerts significant lasting modifications in tibial shape and mass across extensive bone regions, underpinned by (re)modeling independent of local strain magnitude, occurring at sites where the initial response to load is principally osteogenic. This is the first report to demonstrate that bone loading stimulates nonlinear remodeling responses to strain that culminate in greater curvature adjusted for load predictability without sacrificing strength., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY).)

The validity of methods is an ongoing issue in ergonomics. Inconsistent definitions and approaches to evaluation exacerbate this challenge. In this study, the construct and criterion-referenced validity of a new near miss reporting form was evaluated to determine the extent to which it comprehensively captures near miss incidents and is aligned with the systems thinking approach to accident causation. Interview data were used as the reference standard in the evaluation. Using signal detection theory (SDT), a high average hit rate (HR), predictive value (PV) and sensitivity index (SI) were found, with an almost perfect ranking for the index of concordance. The findings show that the reporting form has strong construct and criterion-referenced validity. It is proposed that the approach used in this study could be used by researchers and practitioners when testing the validity of incident data collection tools. Practitioner summary: The validity of methods is a key issue in ergonomics. In this study, we test the validity of a near miss reporting form using interview data as a standard. This approach could be used by practitioners when testing the validity of other ergonomics methods.

We appraise the role of screening for distress as part of health psychology assessment of patients newly diagnosed with cancer. We reviewed records of consecutive patients who accepted a health psychologist's assessment over 4 years, examining convergence and divergence of the result of screening (whether patients reached threshold as 'cases') with the psychologist's clinical judgment of need for intervention. Of 261 patients, 88 (33.7%) were 'cases'. Of these, need for psychological intervention was identified in 70 (79.5%). Of the 173 (66.3%) 'non-cases', need was identified in 59 (34.1%). Examination of cases where the psychologist's judgment diverged from screening showed that 'caseness' can arise from distress that patients can manage themselves and, conversely, that psychological needs arise in the absence of overt distress. Formal screening may not identify need for psychological intervention. The psychologist's role is to make expert judgments of patients' current and future needs. Dialogue with patients should be the vehicle for assessment.

Background: The scalp presents unique surgical challenges, and specialized techniques are sometimes required to achieve optimal results. Tumors arising on the scalp may also be at increased risk of complications such as in-transit metastasis and perineural invasion., Objective: To review challenges to Mohs micrographic surgery on the scalp and techniques for successful tumor extirpation and reconstruction., Methods and Materials: This article reviews our experience with tumors of the scalp including techniques that we have found helpful both for tumor removal and for reconstruction., Conclusion: Familiarity with the anatomy of the scalp as well as common challenges encountered during Mohs surgery may help improve outcomes and impart increase confidence to the practicing surgeon.

Aim: The aim of the present study was to utilise a systems thinking approach to explore the perceived responsibilities for identifying and treating concussion held by different actors across the community rugby system (e.g., players, coaches, parents, medics, referees, and management), as well as their role-specific concussion management strategies., Methods: A systems approach was taken to assess what different stakeholders within rugby systems perceive their roles to be regarding concussion identification and treatment. Through an online survey, 118 members of the amateur (community) rugby union system were asked about their role-specific concussion management responsibilities and strategies. Respondents included players, parents, medics, coaches, club managers, administrators, and volunteers., Results: The majority of respondents indicated that they were able to identify the symptoms of rugby-related concussion, however, only medics stated their responsibility to use formal concussion assessments (e.g., SCAT2). A smaller number of the respondents indicated that they were involved in treating concussion within their current role/s (majority of which were medics)., Conclusions: This study illustrated that the current challenges in the identification and treatment of rugby-related concussion in community sport may be due to role/responsibility confusion and possible overreliance on field-side medics. These findings offer insight into the possible limitations of the current concussion management guidelines and may offer empirically based direction for future revisions., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Purpose: Parkinson's disease (PD) patients and their caregivers experience significant distress that impacts physical, emotional and social functioning in the patient, and in turn, has a significant impact on the caregiver. Lower levels of stress have been associated with a better prognosis in PD. The quality of dispositional mindfulness-innate present moment, non-judgmental awareness-has consistently been associated with less perceived stress, greater well-being, and better physical health in both clinical and healthy populations. To date, associations of mindfulness with distress, depression, sleep problems, and other variables that define health-related quality of life have not been examined in the context of PD patient/caregiver dyads., Methods: We investigated the impact of dispositional mindfulness in a stress-health model among eighteen dyads consisting of PD patients and their caregivers., Results: Multilevel linear modeling (actor-partner interdependence models) revealed significant associations between dispositional mindfulness and stress appraisal, interpersonal support, depressive symptoms, sleep, and health-related quality of life (HRQOL) within both dyadic partners. As expected, results demonstrated significant associations of distress with interpersonal support, depressive symptoms, sleep and HRQOL for both PD patients and caregivers., Conclusions: Dispositional mindfulness was associated with reduced distress and its downstream clinical consequences. These results support an ameliorative role for dispositional mindfulness among PD patients and caregivers, as a protective factor against psychosocial burdens imposed on couples related to disease and caregiving. Findings suggest future studies should explore mindfulness training as a therapeutic option.

Objective: To identify call handlers' key experiences of providing telephone help on a cancer helpline., Methods: Semi-structured qualitative interviews with 30 call handlers from three UK-based cancer helplines. Transcribed interview data were analysed thematically., Results: Thematic analysis identified three themes: (a) call handlers' perceptions of their role on the helpline, (b) challenges of working on a helpline and (c) the need for training/keeping up with competencies. Call handlers reported satisfaction with their experience. However, there are tensions: whilst advice is formally not part of the remit of the helpline, in practice the boundary between giving advice and giving information can be blurred. No follow-up with callers could be difficult and experienced as a lost opportunity to help. Managing patient expectations could be challenging, and interviewees described particular difficulties with distressed callers. Training for the role was commonplace, but there was sometimes a desire for more opportunities., Conclusion: There are challenges faced by helpline staff, and it can be difficult to manage callers' distress and expectations of what they might get from a call experience. Recognising the skill and complexity of the call handler role is important, as it is meeting call handlers' support and training needs. Support is important to minimise the risk to their own emotional well-being., (© 2019 John Wiley & Sons Ltd.)

Objective: Shared decision-making exists to reconcile healthcare practitioners' responsibilities to respect patients' autonomy whilst ensuring well-made decisions. Patients sometimes make unprompted requests for procedures that carry medical and other risks, such as risk-reducing mastectomy (RRM). Faced with pre-formed decisions into which they have had little input, it is unclear how practitioners can reconcile respecting autonomy with ensuring well-made decisions., Methods: Qualitative study of linked patient-practitioner interviews in a breast unit in North-West England. We examined how 10 practitioners addressed 19 patients' unprompted requests for RRM., Results: Practitioners empathised with patients' distress about cancer risk, regarded RRM as legitimate to help, but were wary of choices made 'emotionally'. Practitioners did not seek to establish whether choices were well-made but, instead, 'warranted' patients by satisfying themselves that patients were 'sensible' and 'informed' decision-makers, and thus their decisions could be trusted. Practitioners provided information, and tested patients' resolve by delaying decisions and presenting 'what if' scenarios depicting failure or harm from RRM., Conclusion: Patients who present emotionally and with resolution can receive RRM without evidence of a well-made decision., Practice Implications: Argumentation theory proposes an ethically robust and clinically practicable approach, whereby practitioners elicit, examine and, where appropriate, challenge arguments underpinning patients' decisions., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Background Psychological distress is prevalent among patients with cardiovascular disease and is linked to increased risk of future cardiac events. Cardiac rehabilitation (CR) is widely recommended for treating psychological distress but has been of limited benefit. This study aims to understand how distressed cardiac patients describe their emotional needs and the response of CR. Methods and Results A qualitative descriptive study was conducted with 46 patients who screened positively for anxiety and/or depression. Semi-structured interviews were held, and data were analyzed using a constant comparative approach. Patients described low mood and diverse concerns, including threat of another cardiac event, restrictions on their lives, and problems unrelated to their health. Patients described worrying constantly about these concerns, worrying about their worry, and feeling that worry was uncontrollable and harmful. Patients wanted to "get back to normal" but lacked any sense of how to achieve this and were reluctant to discuss their worries with CR staff. They hoped to recover over time, meanwhile seeking reassurance that they were responding "normally." Patients were mostly dismissive of psychological techniques used in CR. Conclusions These findings expose a conundrum. Distressed CR patients have diverse worries but do not generally want to discuss them, so they invest hopes for feeling better in time passing and reassurance. An intervention acceptable to CR patients would allow them to address diverse worries but without having to share the content of worries, would have "face validity," and would address patients' worry about worry. Metacognitive therapy is an intervention that might be suitable. Clinical Trial Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT02420431.

Shared decision making (SDM) evolved to resolve tension between patients' entitlement to make health-care decisions and practitioners' responsibility to protect patients' interests. Implicitly assuming that patients are willing and able to make "good" decisions, SDM proponents suggest that patients and practitioners negotiate decisions. In practice, patients often do not wish to participate in decisions, or cannot make good decisions. Consequently, practitioners sometimes lead decision making, but doing so risks the paternalism that SDM is intended to avoid. We argue that practitioners should take leadership when patients cannot make good decisions, but practitioners will need to know: (a) when good decisions are not being made; and (b) how to intervene appropriately and proportionately when patients cannot make good decisions. Regarding (a), patients rarely make decisions using formal decision logic, but rely on informal propositions about risks and benefits. As propositions are idiographic and their meanings context-dependent, normative standards of decision quality cannot be imposed. Practitioners must assess decision quality by making subjective and contextualized judgements as to the "reasonableness" of the underlying propositions. Regarding (b), matched to judgements of reasonableness, we describe levels of leadership distinguished according to how directively practitioners act; ranging from prompting patients to question unreasonable propositions or consider new propositions, to directive leadership whereby practitioners recommend options or deny requested procedures. In the context of ideas of relational autonomy, the objective of practitioner leadership is to protect patients' autonomy by supporting good decision making, taking leadership in patients' interests only when patients are unwilling or unable to make good decisions., (© 2018 The Authors Health Expectations published by John Wiley & Sons Ltd.)

Ionizing radiation constitutes a health risk to imaging scientists and study animals. Both PET and CT produce ionizing radiation. CT doses in pre-clinical in vivo imaging typically range from 50 to 1,000 mGy and biological effects in mice at this dose range have been previously described. [ 18 F]FDG body doses in mice have been estimated to be in the range of 100 mGy for [ 18 F]FDG. Yearly, the average whole body doses due to handling of activity by PET technologists are reported to be 3-8 mSv. A preclinical PET/CT system is presented with design features which make it suitable for small animal low-dose imaging. The CT subsystem uses a X-source power that is optimized for small animal imaging. The system design incorporates a spatial beam shaper coupled with a highly sensitive flat-panel detector and very fast acquisition (<10 s) which allows for whole body scans with doses as low as 3 mGy. The mouse total-body PET subsystem uses a detector architecture based on continuous crystals, coupled to SiPM arrays and a readout based in rows and columns. The PET field of view is 150 mm axial and 80 mm transaxial. The high solid-angle coverage of the sample and the use of continuous crystals achieve a sensitivity of 9% (NEMA) that can be leveraged for use of low tracer doses and/or performing rapid scans. The low-dose imaging capabilities of the total-body PET subsystem were tested with NEMA phantoms, in tumor models, a mouse bone metabolism scan and a rat heart dynamic scan. The CT imaging capabilities were tested in mice and in a low contrast phantom. The PET low-dose phantom and animal experiments provide evidence that image quality suitable for preclinical PET studies is achieved. Furthermore, CT image contrast using low dose scan settings was suitable as a reference for PET scans. Total-body mouse PET/CT studies could be completed with total doses of <10 mGy.

Background: Preliminary evidence suggests that metacognitive therapy (MCT), a brief, process-focused psychological intervention, alleviates distress in cancer survivors. In a longitudinal qualitative study nested in an open trial of MCT for cancer survivors, we explored how patients understood, experienced and applied MCT., Methods: Patients received six MCT sessions. Consenting patients provided semi-structured interviews post-intervention ( n = 19), and at 3- and 6-months follow-up ( n = 14 and 10 respectively). Interviews were audio-recorded and transcribed. Analysis followed a constant comparison approach., Results: Participants felt "overwhelmed" by worry before starting MCT and doubted that such brief therapy could help. Their accounts focused on feeling "challenged" to think differently by the psychologist. Those completing therapy were enthusiastic about it. They described having learned that thoughts are "only thoughts," that feelings of worry or sadness are a normal part of life, and that they were in control of whether and how they engaged with thoughts. Consequently, most described a sense of freedom to live free from worry. A minority described being unable to apply MCT to certain thoughts. Two patients who withdrew before completing MCT did not describe having learned what MCT was intended to achieve., Conclusion: MCT is an acceptable brief intervention for distressed cancer survivors. Feeling challenged to understand the processes maintaining their distress was central to their enthusiasm for it, irrespective of their presenting difficulties., Implications for Cancer Survivors: The complexity of emotional distress in cancer survivors can potentially be addressed using a transdiagnostic model which focuses on the psychological processes which maintain distress.