DISP1 deficiency: monoallelic and biallelic variants cause a spectrum of midline craniofacial malformations.

PURPOSE: DISP1 encodes a transmembrane protein that regulates the secretion of the morphogen, Sonic hedgehog (SHH), a deficiency of which is a major cause of holoprosencephaly (HPE). This disorder covers a spectrum of brain and midline craniofacial malformations. The objective of the present study was to better delineate the clinical phenotypes associated with DISP1 variants. METHODS: This study was based on the identification of at least one pathogenic variant of the DISP1 gene in individuals for whom detailed clinical data were available. RESULTS: A total of 23 DISP1 variants were identified in heterozygous, compound heterozygous or homozygous states in 25 individuals with midline craniofacial defects. Most cases were minor forms of HPE, with craniofacial features such as orofacial cleft, solitary median maxillary central incisor (SMMCI), and congenital nasal pyriform aperture stenosis (CNPAS). These individuals had either monoallelic loss-of-function variants or biallelic missense variants in DISP1. In individuals with severe HPE, the DISP1 variants were commonly found associated with a variant in another HPE-linked gene (i.e. oligogenic inheritance). CONCLUSION: The genetic findings we have acquired demonstrate a significant involvement of DISP1 variants in the phenotypic spectrum of midline defects. This underlines its importance as a crucial element in the efficient secretion of SHH. We also demonstrated that the very rare SMMCI-CNPAS combination is part of the DISP1-related phenotype. The present study highlights the clinical risks to be flagged up during genetic counseling after the discovery of a pathogenic DISP1 variant.

Improving access to exome sequencing in a medically underserved population through the Texome Project.

PURPOSE: Genomic medicine can end diagnostic odysseys for patients with complex phenotypes; however, limitations in insurance coverage and other systemic barriers preclude individuals from accessing comprehensive genetics evaluation and testing. METHODS: The Texome Project is a 4-year study that reduces barriers to genomic testing for individuals from underserved and underrepresented populations. Participants with undiagnosed, rare diseases who have financial barriers to obtaining exome sequencing (ES) clinically are enrolled in the Texome Project. RESULTS: We highlight the Texome Project process and describe the outcomes of the first 60 ES results for study participants. Participants received a genetic evaluation, ES, and return of results at no cost. We summarize the psychosocial or medical implications of these genetic diagnoses. Thus far, ES provided molecular diagnoses for 18 out of 60 (30%) of Texome participants. Plus, in 11 out of 60 (18%) participants, a partial or probable diagnosis was identified. Overall, 5 participants had a change in medical management. CONCLUSION: To date, the Texome Project has recruited a racially, ethnically, and socioeconomically diverse cohort. The diagnostic rate and medical impact in this cohort support the need for expanded access to genetic testing and services. The Texome Project will continue reducing barriers to genomic care throughout the future study years.

When tomorrow comes: A prospective risk assessment of a future artificial general intelligence-based uncrewed combat aerial vehicle system.

There are concerns that Artificial General Intelligence (AGI) could pose an existential threat to humanity; however, as AGI does not yet exist it is difficult to prospectively identify risks and develop requisite controls. We applied the Work Domain Analysis Broken Nodes (WDA-BN) and Event Analysis of Systemic Teamwork-Broken Links (EAST-BL) methods to identify potential risks in a future 'envisioned world' AGI-based uncrewed combat aerial vehicle system. The findings suggest five main categories of risk in this context: sub-optimal performance risks, goal alignment risks, super-intelligence risks, over-control risks, and enfeeblement risks. Two of these categories, goal alignment risks and super-intelligence risks, have not previously been encountered or dealt with in conventional safety management systems. Whereas most of the identified sub-optimal performance risks can be managed through existing defence design lifecycle processes, we propose that work is required to develop controls to manage the other risks identified. These include controls on AGI developers, controls within the AGI itself, and broader sociotechnical system controls.

Applying a systems thinking lens to anti-doping: A systematic review identifying the contributory factors to doping in sport.

The use of performance enhancing substances and methods (known as "doping") in sport is an intractable issue, with current anti-doping strategies predominantly focused on the personal responsibility and strict liability of individual athletes. This is despite an emerging understanding that athletes exist as part of a broader complex sports system that includes governance, policymakers, media, sponsors, clubs, team members, and athlete support staff, to name a few. As such, there is a need to examine the broader systemic factors that influence doping in sport. The aim of this systematic review was to identify and synthesise the factors contributing to doping and doping behaviours, attitudes, and beliefs and the extent to which this knowledge extends beyond the athlete to consider broader sports systems. The review followed PRISMA guidelines with risk of bias and study quality assessed by the Mixed Methods Appraisal Tool, and identified contributory factors synthesised and mapped onto a systems thinking-based framework. Overall, the included studies were determined to be of high quality. Support personnel, the coach, and the coach-athlete relationship represent key influences on the athletes' decisions to dope. From the evidence presented, doping is an emergent property of sport systems and represents a complex systemic problem that will require whole-of-system interventions. The implications for this and the focus of future research are discussed.

What Enables Child Sexual Abuse in Sport? A Systematic Review.

Sporting environments provide opportunities for perpetrators to commit child sexual abuse (CSA). While awareness of CSA in sport and preventative interventions are increasing, CSA in sport still occurs at alarming rates. A systematic review was conducted to identify and synthesize the extant literature on the enabling factors for CSA in sport. The 34 included articles were peer-reviewed and were primary sources; had full-text versions in English; included the individual, situational, environmental, or systemic antecedent factors and characteristics which enable CSA in organized sport (clubs, schools, universities, and representative teams); and focused on abuse in children (0-18 years old), and included retrospective incidents. The enabling factors from across the broader sports system were identified and mapped using a systems thinking-based approach, the Risk Management Framework (RMF) and the associated AcciMap method. The results indicated that enabling factors for CSA in sport were identified at multiple levels of the sporting system hierarchy. The results show that 24.1% (n = 46) of the enabling factors identified in the literature relate to the hierarchical level of the Athlete, teammates, opponents, and fans levels, and 52.9% (n = 101) of the enabling factors relate to the level of Direct supervisors, management, medical, and performance personnel level. However, only 13% (n = 25) of enabling factors to CSA in sport were identified at the combined top four hierarchical levels. Results indicate that the problem of CSA in sport is a systems issue, and future research is required to explore how these factors interact to enable CSA in sport.

Champions of democracy or agents of professionalization? The extension era at the universities of Toronto, Queen's, and McMaster.

I narrate a historical sociology of extension work undertaken at Queen's University, McMaster University, and the University of Toronto from the late 1800s through the early 1960s. University administrators positioned extension work as dedicated to the democratization of higher education. However, a critical analysis of archival data reveals that the rise and fall of extension reflected these universities' material interests and organizational goals relating to public relations, government relations, and enrollment growth. Further, extension programs at these universities were primarily oriented to providing alternative credential pathways to those seeking professional status as schoolteachers, accountants, bankers, and business managers. Indeed, extension leaders demonstrated substantial agency in the professionalization of these fields. Contributing to the historical sociology of higher education and the professions, I argue that the extension era in Ontario resulted in partial democratization of higher education whilst helping to construct mechanisms of social closure rooted in credentialism and professionalization.

Dans cet article, je raconte une sociologie historique des programmes de vulgarisation entrepris à l'Université Queen's, à l'Université McMaster et à l'Université de Toronto de la fin des années 1800 jusqu'au début des années 1960. Les administrateurs des universités ont présenté le travail de vulgarisation comme étant dédié à la démocratisation de l'enseignement supérieur. Cependant, une analyse critique des données d'archives révèle que l'essor et le déclin de la vulgarisation reflètent les intérêts matériels et les objectifs organisationnels de ces universités en matière de relations publiques, de relations avec le gouvernement et d'augmentation des inscriptions. En outre, les programmes de vulgarisation de ces universités étaient principalement axés sur la délivrance de diplômes alternatifs à ceux qui cherchaient à obtenir un statut professionnel en tant qu'enseignants, comptables, banquiers et chefs d'entreprise. En effet, les responsables de la vulgarisation ont joué un rôle important dans la professionnalisation de ces domaines. Contribuant à la sociologie historique de l'enseignement supérieur et des professions, je soutiens que l'ère de l'extension en Ontario a entraîné une démocratisation partielle de l'enseignement supérieur tout en aidant à construire des mécanismes de fermeture sociale enracinés dans le crédentisme et la professionnalisation.

Use of neuromuscular blockade for neck dissection and association with iatrogenic nerve injury.

BACKGROUND: Cranial nerve injury is an uncommon but significant complication of neck dissection. We examined the association between the use of intraoperative neuromuscular blockade and iatrogenic cranial nerve injury during neck dissection. METHODS: This was a single-center, retrospective, electronic health record review. Study inclusion criteria stipulated patients > 18 years who had ≥ 2 neck lymphatic levels dissected for malignancy under general anesthesia with a surgery date between 2008 - 2018. Use of neuromuscular blockade during neck dissection was the primary independent variable. This was defined as any use of rocuronium, cisatracurium, or vecuronium upon anesthesia induction without reversal with sugammadex prior to surgical incision. Univariate tests were used to compare variables between those patients with, and those without, iatrogenic cranial nerve injury. Multivariable logistic regression determined predictors of cranial nerve injury and was performed incorporating Firth's estimation given low prevalence of the primary outcome. RESULTS: Our cohort consisted of 925 distinct neck dissections performed in 897 patients. Neuromuscular blockade was used during 285 (30.8%) neck dissections. Fourteen instances (1.5% of surgical cases) of nerve injury were identified. On univariate logistic regression, use of neuromuscular blockade was not associated with iatrogenic cranial nerve injury (OR: 1.73, 95% CI: 0.62 - 4.86, p = 0.30). There remained no significant association on multivariable logistic regression controlling for patient age, sex, weight, ASA class, paralytic dose, history of diabetes, stroke, coronary artery disease, carotid atherosclerosis, myocardial infarction, and cardiac arrythmia (OR: 1.87, 95% CI: 0.63 - 5.51, p = 0.26). CONCLUSIONS: In this study, use of neuromuscular blockade intraoperatively during neck dissection was not associated with increased rates of iatrogenic cranial nerve injury. While this investigation provides early support for safe use of neuromuscular blockade during neck dissection, future investigation with greater power remains necessary.

Neoadjuvant Immune Checkpoint Inhibition in Metastatic Conjunctival Melanoma.

The development of immune checkpoint inhibitors (ICI) has transformed the treatment of advanced-stage cutaneous melanoma; however, most trials did not include patients with conjunctival melanoma. Herein the authors describe a patient with recurrent conjunctival melanoma who developed locally advanced, b-raf and v-raf murine sarcoma viral oncogene homolog B1-negative melanoma in her nasal cavity and extensive, metabolically active, bilateral lymphadenopathy in her thorax. Her nasal mass measured 4.3 × 1.7 cm and was determined to be unresectable. She was treated with 4 cycles of combination ipilimumab and nivolumab therapy followed by maintenance nivolumab. She experienced a dramatic treatment response with a reduction in the size of her nasal mass to 3.0 × 1.1 cm and a complete resolution of her adenopathy. She then underwent complete surgical resection of her residual mass (approximately 75% of her original tumor size) and remains melanoma-free at 1 year of follow-up. Given the underlying genetic similarities of conjunctival melanoma to cutaneous melanoma, providers should consider the use of neoadjuvant immune checkpoint inhibitors for patients with locally advanced or limited metastatic disease.

From Anti-doping-I to Anti-doping-II: Toward a paradigm shift for doping prevention in sport.

Doping remains an intractable issue in sport and occurs in a complex and dynamic environment comprising interactions between individual, situational, and environmental factors. Anti-doping efforts have previously predominantly focused on athlete behaviours and sophisticated detection methods, however, doping issues remain. As such, there is merit in exploring an alternative approach. The aim of this study was to apply a systems thinking approach to model the current anti-doping system for four football codes in Australia, using the Systems Theoretic Accident Model and Processes (STAMP). The STAMP control structure was developed and validated by eighteen subject matter experts across a five-phase validation process. Within the developed model, education was identified as a prominent approach anti-doping authorities use to combat doping. Further, the model suggests that a majority of existing controls are reactive, and hence that there is potential to employ leading indicators to proactively prevent doping and that new incident reporting systems could be developed to capture such information. It is our contention that anti-doping research and practice should consider a shift away from the current reactive and reductionist approach of detection and enforcement to a proactive and systemic approach focused on leading indicators. This will provide anti-doping agencies a new lens to look at doping in sport.

Defining and quantifying fatigue in the rugby codes.

The rugby codes (i.e., rugby union, rugby league, rugby sevens [termed 'rugby']) are team-sports that impose multiple complex physical, perceptual, and technical demands on players which leads to substantial player fatigue post-match. In the post-match period, fatigue manifests through multiple domains and negatively influences recovery. There is, however, currently no definition of fatigue contextualised to the unique characteristics of rugby (e.g., locomotor and collision loads). Similarly, the methods and metrics which practitioners consider when quantifying the components of post-match fatigue and subsequent recovery are not known. The aims of this study were to develop a definition of fatigue in rugby, to determine agreement with this common definition of fatigue, and to outline which methods and metrics are considered important and feasible to implement to quantify post-match fatigue. Subject matter experts (SME) undertook a two-round online Delphi questionnaire (round one; n = 42, round two; n = 23). SME responses in round one were analysed to derive a definition of fatigue, which after discussion and agreement by the investigators, obtained 96% agreement in round two. The SME agreed that fatigue in rugby refers to a reduction in performance-related task ability which is underpinned by time-dependent negative changes within and between cognitive, neuromuscular, perceptual, physiological, emotional, and technical/tactical domains. Further, there were 33 items in the neuromuscular performance, cardio-autonomic, or self-report domains achieved consensus for importance and/or feasibility to implement. Highly rated methods and metrics included countermovement jump force/power (neuromuscular performance), heart rate variability (cardio-autonomic measures), and soreness, mood, stress, and sleep quality (self-reported assessments). A monitoring system including highly-rated fatigue monitoring objective and subjective methods and metrics in rugby is presented. Practical recommendations of objective and subjective measures, and broader considerations for testing and analysing the resulting data in relation to monitoring fatigue are provided.

Intranasal Carbetocin Reduces Hyperphagia, Anxiousness, and Distress in Prader-Willi Syndrome: CARE-PWS Phase 3 Trial.

CONTEXT: Prader-Willi syndrome (PWS) is a rare genetic disorder characterized by endocrine and neuropsychiatric problems including hyperphagia, anxiousness, and distress. Intranasal carbetocin, an oxytocin analog, was investigated as a selective oxytocin replacement therapy. OBJECTIVE: To evaluate safety and efficacy of intranasal carbetocin in PWS. DESIGN: Randomized, double-blind, placebo-controlled phase 3 trial with long-term follow-up. SETTING: Twenty-four ambulatory clinics at academic medical centers. PARTICIPANTS: A total of 130 participants with PWS aged 7 to 18 years. INTERVENTIONS: Participants were randomized to 9.6 mg/dose carbetocin, 3.2 mg/dose carbetocin, or placebo 3 times daily during an 8-week placebo-controlled period (PCP). During a subsequent 56-week long-term follow-up period, placebo participants were randomly assigned to 9.6 mg or 3.2 mg carbetocin, with carbetocin participants continuing at their previous dose. MAIN OUTCOME MEASURES: Primary endpoints assessed change in hyperphagia (Hyperphagia Questionnaire for Clinical Trials [HQ-CT]) and obsessive-compulsive symptoms (Children's Yale-Brown Obsessive-Compulsive Scale [CY-BOCS]) during the PCP for 9.6 mg vs placebo, and the first secondary endpoints assessed these same outcomes for 3.2 mg vs placebo. Additional secondary endpoints included assessments of anxiousness and distress behaviors (PWS Anxiousness and Distress Behaviors Questionnaire [PADQ]) and clinical global impression of change (CGI-C). RESULTS: Because of onset of the COVID-19 pandemic, enrollment was stopped prematurely. The primary endpoints showed numeric improvements in both HQ-CT and CY-BOCS which were not statistically significant; however, the 3.2-mg arm showed nominally significant improvements in HQ-CT, PADQ, and CGI-C scores vs placebo. Improvements were sustained in the long-term follow-up period. The most common adverse event during the PCP was mild to moderate flushing. CONCLUSIONS: Carbetocin was well tolerated, and the 3.2-mg dose was associated with clinically meaningful improvements in hyperphagia and anxiousness and distress behaviors in participants with PWS. CLINICAL TRIALS REGISTRATION NUMBER: NCT03649477.

Using systems thinking-based risk assessment methods to assess hazardous manual tasks: a comparison of Net-HARMS, EAST-BL, FRAM and STPA.

Formal risk assessment is a component of safety management relating to hazardous manual tasks (HMT). Systems thinking approaches are currently gaining interest for supporting safety management. Existing HMT risk assessment methods have been found to be limited in their ability to identify risks across the whole work system; however, systems thinking-based risk assessment (STBRA) methods were not designed for the HMT context and have not been tested in this area. The aim of this study was to compare the performance of four state-of-the-art STBRA methods: Net-HARMS, EAST-BL, FRAM and STPA to determine which would be most useful for identifying HMT risks. Each method was independently applied by one of four analysts to assess the risks associated with a hypothetical HMT system. The outcomes were assessed for alignment with a benchmark analysis. Using signal detection theory (SDT), overall STPA was found to be the best performing method having the highest hit rate, second lowest false alarm rate and highest Matthews Correlation Coefficient of the four methods.Practitioner summary: A comparison of four systems thinking risk assessment methods found that STPA had the highest level of agreement with the benchmark analysis and is the most suitable for practitioners to use to identify the risks associated with HMT systems.

Patterns of co-occurring birth defects in children with anotia and microtia.

Many infants with anotia or microtia (A/M) have co-occurring birth defects, although few receive syndromic diagnoses in the perinatal period. Evaluation of co-occurring birth defects in children with A/M could identify patterns indicative of undiagnosed/unrecognized syndromes. We obtained information on co-occurring birth defects among infants with A/M for delivery years 1999-2014 from the Texas Birth Defects Registry. We calculated observed-to-expected ratios (OER) to identify birth defect combinations that occurred more often than expected by chance. We excluded children diagnosed with genetic or chromosomal syndromes from analyses. Birth defects and syndromes/associations diagnosed ≤1 year of age were considered. We identified 1310 infants with non-syndromic A/M, of whom 38% (N = 492) were diagnosed with co-occurring major defects. Top combinations included: hydrocephalus, ventricular septal defect, and spinal anomalies (OER 58.4); microphthalmia and anomalies of the aorta (OER 55.4); and cleft lip with or without cleft palate and rib or sternum anomalies (OER 32.8). Some combinations observed in our study may represent undiagnosed/atypical presentations of known A/M associations or syndromes, or novel syndromes yet to be described in the literature. Careful evaluation of infants with multiple birth defects including A/M is warranted to identify individuals with potential genetic or chromosomal syndromes.

Patient Perceptions of Wearable and Smartphone Technologies for Remote Outcome Monitoring in Total Knee Arthroplasties.

While there is enthusiasm for wearables and smartphone technologies in evaluating clinical outcomes among clinicians, less is known about the willingness of patients who have osteoarthritis (OA) to consent for remote outcome monitoring. We developed an Institutional Review Board-approved questionnaire to assess patient perceptions of remote monitoring technologies in a high-volume orthopaedic clinical center. Fifty total knee arthroplasty (TKA) patients (56% female; mean age: 61 years, range: 23-89) and fifty nonoperative OA knee patients (54% female; mean age: 58 years, range: 25-89) routinely consulted in the clinic as part of their OA treatment and consented to participate in the study. Patient perceptions were compared using Pearson's chi-square analyses with a significance threshold of p < 0.05. We found that TKA patients were more receptive to the use of smartphone apps (84 vs. 60%, p = 0.008) and wearable sensors (80 vs. 48%, p < 0.001) and learning to use custom wearables (72 vs. 38%, p = 0.002) than nonoperative OA knee patients as part of their treatment. Likewise, the majority of TKA patients were willing to use the global positioning system in their postoperative technology (54 vs. 18%, p < 0.001), especially if they were only active during certain circumstances (62 vs. 24%, p < 0.001). TKA patients also expressed willingness to have their body movement (68%), balance (70%), sleep (76%), and cardiac output (80%) tracked using remote technologies. Overall, we found that TKA patients were highly receptive to using wearable technology in their treatments, whereas nonoperative OA knee patients were generally unreceptive. Our study challenges the concept that current wearable technology approaches will be generally effective as a tool to remotely monitor all patients across the OA severity landscape.

Patient Perceptions of Wearable and Smartphone Technologies for Remote Outcome Monitoring in Patients Who Have Hip Osteoarthritis or Arthroplasties.

BACKGROUND: Although there is interest in wearables and smartphone technologies for remote outcome monitoring, little is known regarding the willingness of hip osteoarthritis (OA) and/or total hip arthroplasty (THA) patients to authorize and adhere to such treatment. METHODS: We developed an Institutional Review Board-approved questionnaire to evaluate patient perceptions of remote monitoring technologies in a high-volume orthopedic center. Forty-seven THA patients (60% female; mean age: 66 years) and 50 nonoperative OA hip patients (52% female; mean age: 63 years) participated. Patient perceptions were compared using Pearson's chi-squared analyses. RESULTS: THA patients were similarly interested in the use of smartphone apps (91% vs 94%, P = .695) in comparison to nonoperative hip OA patients. THA patients were more receptive to using wearable sensors (94% vs 44%, P < .001) relative to their nonoperative counterparts. THA patients also expressed stronger interest in learning to use custom wearables (87% vs 32%, P < .001) vs nonoperative patients. Likewise, the majority of THA patients were willing to use Global Positioning System technology (74% vs 26%, P < .001). THA patients also expressed willingness to have their body movement (89%), balance (89%), sleep (87%), and cardiac output (91%) tracked using remote technology. CONCLUSION: Overall, we found that THA patients were highly receptive to using wearable technology in their treatments. Nonoperative OA hip patients were generally unreceptive to using smart technologies, with the exception of smartphone applications. This information may be useful as utilization of these technologies for patient care continues to evolve.

Incident reporting in the outdoors: a systems-based analysis of injury, illness, and psychosocial incidents in led outdoor activities in Australia.

Incident reporting systems are a fundamental component of safety management, however, most systems used in practice are not aligned with contemporary accident causation models. This article presents an analysis of a National Incident Dataset (NID) for adverse incidents occurring in the Australian Led Outdoor Activity (LOA) sector. The aim was to investigate the adverse Injury, Illness, and Psychosocial incidents reported to the NID. In total, 1657 injuries, 532 illnesses, and 146 psychosocial incidents were analysed from 357,691 program participation days. The findings show that the rate of incidents per 1000 program participant days in LOAs was 4.6 for injury, 1.5 for illness, and 0.04 for psychosocial incidents, and incident severity was predominately minor. The analysis of systemic contributory factors demonstrates that incidents in LOA are systemic in nature, with multiple levels of the LOA system identified as contributing to adverse incidents. For example, contributory factors were identified across local government (facilities), schools (communication), parents (communication), LOA management (policies and procedures), people involved in the incidents (mental and physical condition), and the environment (terrain) and equipment (clothing). This study presents an assessment of the current state of safety in the Australian LOA sector and demonstrates the utility of applying systems ergonomics methods in practice. Practitioner summary: This article presents an analysis of 1657 injury, 532 illness, and 146 psychosocial incidents occurring in the Australian Led Outdoor Activity (LOA) sector, using a systems ergonomics method. The findings demonstrate the incident charactersitics and how decisions and actions from across the system contribute to adverse incidents in LOAs.

The cultural logic of precariousness and the marginalization of the sociological imagination: Signs from Mexican self-help books.

In recent decades, precariousness has become an increasingly prominent feature of life in many countries. At the same time as precarious forms of social relations have proliferated, self-help books have become tremendously popular. This article examines five best-selling self-help books in Mexico - two promoting mental wellness, one providing financial advice, one about romantic relationships, and one sharing inspirational lessons regarding success - to explore how self-help texts reflect the cultural logic of precariousness. While encouraging readers to overcome challenges, think positively, and transform bad habits into good ones, the texts present visions of human agency free from social constraint. Self-help books in Mexico reproduce a cultural logic that corresponds to material realities of precariousness in work and family life. This logic helps account for the expanding popularity of the genre and encourages a marginalization of the sociological imagination in popular culture - a marginalization that sociologists should contest through greater public engagement.

Au cours des dernières décennies, la précarité est devenue une caractéristique de plus en plus importante de la vie dans de nombreux pays. Parallèlement à la prolifération des formes précaires de relations sociales, les livres d'auto-assistance sont devenus extrêmement populaires. Cet article examine cinq livres d'auto-assistance les plus vendus au Mexique - deux promouvant le bien-être mental, un fournissant des conseils financiers, un sur les relations amoureuses, et un partageant des leçons inspirantes sur le succès - pour explorer comment les textes d'auto-assistance reflètent la logique culturelle de la précarité. Tout en encourageant les lecteurs à surmonter les difficultés, à penser de manière positive et à transformer les mauvaises habitudes en bonnes habitudes, les textes présentent des visions de l'agence humaine libérée des contraintes sociales. Les livres d'auto-assistance au Mexique reproduisent une logique culturelle qui correspond aux réalités matérielles de la précarité dans la vie professionnelle et familiale. Cette logique contribue à expliquer la popularité croissante du genre et encourage la marginalisation de l'imaginaire sociologique dans la culture populaire - une marginalisation que les sociologues devraient contester en s'engageant davantage auprès du public.

Isolation of circulating tumor cells to diagnose melanoma and evaluate the efficacy of surgical resection using melanoma-specific microsystem.

Melanoma is one of the most aggressive skin cancers due to its potential to metastasize widely in the body. The risk of metastasis is increased with later detection and increased thickness of the primary lesion, thus early identification and surgical removal is critical for higher survival rates for patients. However, even with appropriate treatment, some patients will develop recurrence which may be difficult to identify until advanced or causing symptoms. Recent advances in liquid biopsy have proposed less-invasive alternatives for cancer diagnosis and monitoring using minimal/zero invasion at sample collection, and circulating tumor cells(CTCs) have been considered a promising blood-based surrogate marker of primary tumors. However, previous CTC technologies relying on epithelial-cell adhesion molecules have limited to epithelial cells, thus hampering use of CTCs for non-epithelial cancers such as melanoma. Here, we used the Melanoma-specific OncoBean platform(MelanoBean) conjugated with melanoma specific antibodies(MCAM and MCSP). The device was used in comprehensive studies for diagnosing melanoma and evaluating surgery efficacy based on change in the number and characteristics of CTCs and CTC-clusters pre- and post-surgical treatment. Our study demonstrated that melanoma patients(n=45) at all stages(I-IV) have a noticeable number of MCTCs as well as MCTC-clusters compared to healthy donors(n=9)(P=0.0011), and surgical treatment leads to a significant decrease in the number of CTCs(P<0.0001). The CTCs recovered from the device underwent molecular profiling for melanoma-associated genes expression using multiplexed qRT-PCR, demonstrating the ability to monitor molecular signature through treatment. The presented MelanoBean and the comprehensive approach will empower prognostic value of CTCs in melanoma in much larger cohort studies.

Evaluation of a systems ergonomics-based incident reporting system.

INTRODUCTION: Incident reporting and learning systems are a fundamental component of safety management. The purpose of this study was to evaluate a novel incident reporting system specific to the Australian Led Outdoor Activity (LOA) sector. The Understanding and Preventing Led Outdoor Accidents Data System (UPLOADS), is a recently introduced systems thinking-based incident reporting and learning system that utilises contemporary safety theory and methods. METHOD: The implementation of UPLOADS was evaluated using the RE-AIM framework based on the following dimensions: Reach, Efficacy, Adoption, Implementation, and Maintenance. A pragmatic evaluation approach was used in which evaluation data were collected through the triangulation of multiple sources including different LOA stakeholders from both the individual organisational level (LOA providers) and LOA sector governance level (LOA industry representatives), incident data collected through the UPLOADS National Incident Dataset, and the online and physical presence of UPLOADS. RESULTS: The findings show that a key strength of UPLOADS is its effectiveness as incident reporting tool for improving safety in the LOA sector. However, a weakness of UPLOADS is that it is not being implemented appropriately by the LOA providers. CONCLUSION: Overall, the current findings suggest that UPLOADS incident reporting tool is perceived by SMEs as an effective tool for improving safety in LOA. However, further work is required for UPLOADS to have a greater impact on the LOA sector. Specifically, Implementation of the UPLOADS system requires improvement, as well as additional training and education may be required to upskill and empower LOA providers to improve reporting and enhance the value placed on safety by LOA stakeholders. The RE-AIM framework was an appropriate evaluation framework for understanding the effectiveness of UPLOADS as a LOA sector specific incident reporting and learning system. PRACTICAL APPLICATIONS: The current findings have practical implications for ergonomics researchers applying evaluation frameworks in the real world, and LOA providers for implementing safety interventions. Lastly, contemporary systems-based incident reporting and learning systems have the capability to enhance the safety practices of the LOA sector.