A hexagonal planar transition-metal complex.

Transition-metal complexes are widely used in the physical and biological sciences. They have essential roles in catalysis, synthesis, materials science, photophysics and bioinorganic chemistry. Our understanding of transition-metal complexes originates from Alfred Werner's realization that their three-dimensional shape influences their properties and reactivity1, and the intrinsic link between shape and electronic structure is now firmly underpinned by molecular-orbital theory2-5. Despite more than a century of advances in this field, the geometries of transition-metal complexes remain limited to a few well-understood examples. The archetypal geometries of six-coordinate transition metals are octahedral and trigonal prismatic, and although deviations from ideal bond angles and bond lengths are frequent6, alternative parent geometries are extremely rare7. The hexagonal planar coordination environment is known, but it is restricted to condensed metallic phases8, the hexagonal pores of coordination polymers9, or clusters that contain more than one transition metal in close proximity10,11. Such a geometry had been considered12,13 for [Ni(PtBu)6]; however, an analysis of the molecular orbitals suggested that this complex is best described as a 16-electron species with a trigonal planar geometry14. Here we report the isolation and structural characterization of a simple coordination complex in which six ligands form bonds with a central transition metal in a hexagonal planar arrangement. The structure contains a central palladium atom surrounded by three hydride and three magnesium-based ligands. This finding has the potential to introduce additional design principles for transition-metal complexes, with implications for several scientific fields.

Acceptability of digital vending machines to access STI and HIV tests in two UK cities.

OBJECTIVES: Prompt HIV and STI diagnosis and treatment is a public health priority and relies on accessible testing. Technology-based approaches to distribute test kits have the potential to increase access to testing. We evaluated the acceptability and uptake of vending machines in publicly available settings in Brighton and Hove (BH) and Bristol, North Somerset and South Gloucestershire (BNSSG), to distribute HIV rapid self-test and STI self-sample kits. METHODS: Seven machines were installed in BH and four in BNSSG. User characteristics, proportion of kits returned and test results, taken from the machine database and clinic records, combined with online questionnaires completed by self-recruited users and analysed using Stata and SPSS. RESULTS: 2536 kits were dispensed over 12 months (April 2022 to March 2023). The STI self-sample kits were most popular (74% of vends). 78% of kits dispensed were among users aged 16-35 years and 56% identified as male. 68% and 59% of users had either not tested in the last 12 months or never tested for HIV and STIs, respectively. 51% of STI kits were returned via post, lower than the local online service (65%). 208 users completed questionnaires. Convenience, desire for instant access and increased confidentiality were the most common reasons for using machines. 92% of respondents thought the machines were user-friendly and 97% would recommend the service. Concerns about safety and privacy while using the machine were reported by 42% and 66% of respondents. CONCLUSIONS: This study demonstrates that vending machines are an acceptable and effective means of accessing infrequent or never testers in the general population and can act as a horizontal intervention to tackle HIV and STIs. Research is needed to understand optimal machine locations to assure privacy and safety along with the long-term impact on sexual health services.

Genome-wide pleiotropy analysis identifies novel blood pressure variants and improves its polygenic risk scores.

Systolic and diastolic blood pressure (S/DBP) are highly correlated modifiable risk factors for cardiovascular disease (CVD). We report here a bidirectional Mendelian Randomization (MR) and horizontal pleiotropy analysis of S/DBP summary statistics from the UK Biobank (UKB)-International Consortium for Blood Pressure (ICBP) (UKB-ICBP) BP genome-wide association study and construct a composite genetic risk score (GRS) by including pleiotropic variants. The composite GRS captures greater (1.11-3.26 fold) heritability for BP traits and increases (1.09- and 2.01-fold) Nagelkerke's R2 for hypertension and CVD. We replicated 118 novel BP horizontal pleiotropic variants including 18 novel BP loci using summary statistics from the Million Veteran Program (MVP) study. An additional 219 novel BP signals and 40 novel loci were identified after a meta-analysis of the UKB-ICBP and MVP summary statistics but without further independent replication. Our study provides further insight into BP regulation and provides a novel way to construct a GRS by including pleiotropic variants for other complex diseases.

Greater male variability in daily energy expenditure develops through puberty.

There is considerably greater variation in metabolic rates between men than between women, in terms of basal, activity and total (daily) energy expenditure (EE). One possible explanation is that EE is associated with male sexual characteristics (which are known to vary more than other traits) such as musculature and athletic capacity. Such traits might be predicted to be most prominent during periods of adolescence and young adulthood, when sexual behaviour develops and peaks. We tested this hypothesis on a large dataset by comparing the amount of male variation and female variation in total EE, activity EE and basal EE, at different life stages, along with several morphological traits: height, fat free mass and fat mass. Total EE, and to some degree also activity EE, exhibit considerable greater male variation (GMV) in young adults, and then a decreasing GMV in progressively older individuals. Arguably, basal EE, and also morphometrics, do not exhibit this pattern. These findings suggest that single male sexual characteristics may not exhibit peak GMV in young adulthood, however total and perhaps also activity EE, associated with many morphological and physiological traits combined, do exhibit GMV most prominently during the reproductive life stages.

A critical review and analysis of the context, current burden, and application of policy to improve cancer equity in Ghana.

BACKGROUND: Cancer causes a major disease burden worldwide. This is increasingly being realised in low and middle-income countries, which account disproportionately for preventable cancer deaths. Despite the World Health Organization calling for governments to develop policies to address this and alleviate cancer inequality, numerous challenges in executing effective cancer policies remain, which require consideration of the country-specific context. As this has not yet been considered in Ghana, the aim of this review was to bring together and critique the social-environmental, health policy and system factors to identifying opportunities for future health policies to reduce cancer burden in the Ghanian context. A critical policy-focused review was conducted to bring together and critique the current health systems context relating to cancer in Ghana, considering the unmet policy need, health system and social factors contributing to the burden and policy advances related to cancer. CONCLUSION: The findings highlight the changing burden of cancer in Ghana and the contextual factors within the socio-ecosystem that contribute to this. Policies around expanding access to and coverage of services, as well as the harmonization with medical pluralism have potential to improve outcomes and increase equity but their implementation and robust data to monitor their impact pose significant barriers.

Variability in energy expenditure is much greater in males than females.

In mammals, trait variation is often reported to be greater among males than females. However, to date, mainly only morphological traits have been studied. Energy expenditure represents the metabolic costs of multiple physical, physiological, and behavioral traits. Energy expenditure could exhibit particularly high greater male variation through a cumulative effect if those traits mostly exhibit greater male variation, or a lack of greater male variation if many of them do not. Sex differences in energy expenditure variation have been little explored. We analyzed a large database on energy expenditure in adult humans (1494 males and 3108 females) to investigate whether humans have evolved sex differences in the degree of interindividual variation in energy expenditure. We found that, even when statistically comparing males and females of the same age, height, and body composition, there is much more variation in total, activity, and basal energy expenditure among males. However, with aging, variation in total energy expenditure decreases, and because this happens more rapidly in males, the magnitude of greater male variation, though still large, is attenuated in older age groups. Considerably greater male variation in both total and activity energy expenditure could be explained by greater male variation in levels of daily activity. The considerably greater male variation in basal energy expenditure is remarkable and may be explained, at least in part, by greater male variation in the size of energy-demanding organs. If energy expenditure is a trait that is of indirect interest to females when choosing a sexual partner, this would suggest that energy expenditure is under sexual selection. However, we present a novel energetics model demonstrating that it is also possible that females have been under stabilizing selection pressure for an intermediate basal energy expenditure to maximize energy available for reproduction.

Genetic and stress influences on the prevalence of hypertension among hispanics/latinos in the hispanic community health study/study of latinos (HCHS/SOL).

PURPOSE: The current study examined the effects of chronic stress and a genetic risk score on the presence of hypertension and elevated systolic blood pressure and diastolic blood pressure among Hispanics/Latinos in the target population of Hispanic Community Health Study/Study of Latinos. MATERIALS AND METHODS: Of the participants (N = 11,623) assessed during two clinic visits (Visit 1 2008-2013 & Visit 2 2014-2018), we analysed data from 7,429 adults (50.4% female), aged 18-74, who were genotyped and responded to chronic stress questionnaires. We calculated an unweighted genetic risk score using blood pressure increasing single nucleotide polymorphisms (SNPs) found to be generalisable to Hispanics/Latinos (10 SNPs). Linear and logistic regression models were used to estimate associations between chronic stress and genetic risk score and their interaction, with prevalent Visit 2 SBP or DBP, and hypertension, respectively. Models accounted for sampling weights, stratification, and cluster design. RESULTS: Chronic stress (adjusted OR = 1.18, 95%CI:1.15,1.22) and hypertension genetic risk score (adjusted OR = 1.04, 95%CI:1.01,1.07) were significantly associated with prevalent hypertension, but there was no significant interaction between the chronic stress and genetic risk score on hypertension (p = .49). genetic risk score (b = .32, 95%CI:.08, .55, R2 = .02) and chronic stress (b = .45, 95%CI:.19, .72, R2 = .11) were related to DBP, with no significant interaction (p = .62). Genetic risk score (b = .42, 95%CI:.08, .76, R2 = .01) and chronic stress (b = .80, 95%CI:.34,1.26, R2 = .11) were also related to SBP, with no significant interaction (p = .51). CONCLUSION: Results demonstrate the utility of a genetic risk score for blood pressure and are consistent with literature suggesting chronic stress has a strong, direct association with elevated blood pressure among U.S. Hispanics/Latinos.

Left, right, left, right: 24-36-months-olds' planning and execution of simple alternating actions.

This study investigated toddlers' ability to control simple alternating pattern actions, and how this relates to motor competence and executive functions. 70 toddlers between 24 and 36 months of age were instructed to sort coins in an alternating pattern into two boxes; left, right, left, right etc. Executive functions and memory competence performance were assessed in additional small games. The results showed that the ability to plan and execute actions according to a simple extended alternating pattern improved over toddlerhood. Furthermore, working memory and motor competence scores were both independent predictors of the ability to plan and execute simple alternating actions. These findings underscore the fact that between 24 and 36 months of age is a period in which the ability to string together multiple actions in a sequence to achieve a distal goal is still developing.

The Continuum Between Hexagonal Planar and Trigonal Planar Geometries.

New heterometallic hydride complexes that involve the addition of {Mg-H} and {Zn-H} bonds to group 10 transition metals (Pd, Pt) are reported. The side-on coordination of a single {Mg-H} to Pd forms a well-defined σ-complex. In contrast, addition of three {Mg-H} or {Zn-H} bonds to Pd or Pt results in the formation of planar complexes with subtly different geometries. We compare their structures through experiment (X-ray diffraction, neutron diffraction, multinuclear NMR), computational methods (DFT, QTAIM, NCIPlot), and theoretical analysis (MO diagram, Walsh diagram). These species can be described as snapshots along a continuum of bonding between ideal trigonal planar and hexagonal planar geometries.

Use of Racial and Ethnic Categories in Medical Testing and Diagnosis: Primum Non Nocere.

BACKGROUND: Use of race and ethnicity is common in medical tests and procedures, even though these categories are defined by sociological, historical, and political processes, and vary considerably in their definitions over time and place. Because all societies organize themselves around these constructs in some way, they are undeniable facets of the human experience, with myriad health consequences. In the biomedical literature, they are also commonly interpreted as representing biological heterogeneity that is relevant for health and disease. CONTENT: We review the use of race and ethnicity in medical practice, especially in the USA, and provide 2 specific examples to represent a large number of similar instances. We then critique these uses along a number of different dimensions, including limitations in measurement, within- versus between-group variance, and implications for informativeness of risk markers for individuals, generalization from arbitrary or nonrepresentative samples, perpetuation of myths and stereotypes, instability in time and place, crowding out of more relevant risk markers, stigmatization, and the tainting of medicine with the history of oppression. We conclude with recommendations to improve practice that are technical, ethical, and pragmatic. SUMMARY: Medicine has evolved from a mystical healing art to a mature science of human health through a rigorous process of quantification, experimentation, and evaluation. Folkloric traditions, such as race- and ethnic-specific medicine will fade from use as we become increasingly critical of outdated and irrational clinical practices and replace these with personalized, evidenced-based tests, algorithms, and procedures that privilege patients' individual humanity over obsolete and misleading labels.

Science with Duplo: Multilevel goal management in preschoolers' toy house constructions.

Executing goal-directed action sequences is fundamental to our behavior. Planning and controlling these action sequences improves greatly over the preschool years. In this study, we examined preschoolers' ability to plan action sequences. A total of 69 3- to 5-year-olds were assessed on an action sequence planning task with a hierarchical goal structure and on several executive function tasks. Planning abilities improved with age. Improvements in inhibition were related to avoidance of actions irrelevant to the goal hierarchy. Updating skill appears to be associated with executing actions relevant to different subgoals. Using optical motion capture, we showed that children who followed the subgoals displayed less movement with their nonreaching hand within a subgoal. This effect was enhanced in children with better inhibitory skills, suggesting that such skills allow greater focus on executing the current subgoal. Thus, we provide evidence that structuring of subgoals in action sequence planning emerges during the preschool years and that improvements in performance in action sequence planning are related to executive functions.

Patients' and clinicians' perceptions of oral anticoagulants in atrial fibrillation: a systematic narrative review and meta-analysis.

BACKGROUND: Atrial fibrillation (AF) increases the risk of developing a stroke by 20%. AF related strokes are associated with greater morbidity. Historically, warfarin was the anticoagulant of choice for stroke prevention in patients with AF but lately patients are being switched or started on direct oral anticoagulants (DOACs). DOACs are promoted as safer alternatives to warfarin and it is expected that they will be associated with fewer challenges both for patients and healthcare professionals. This systematic narrative review aimed to explore perspectives of patients and professionals on medicines optimisation of oral anticoagulation with vitamin K antagonists and DOACs in atrial fibrillation. METHODS: Prospero registration CRD42018091591. Systematic searches undertaken of research studies (qualitative and quantitative), published February 2018 to November 2020 from several databases (Web of Science, Scopus, Medline Via Ovid, CINHAL via Ebsco, and PubMED via NCBI) following PRISMA methodology. Data were organised using Covidence software. Two reviewers independently assessed the quality of the included studies and synthesized the findings (thematic analysis approach). RESULTS: Thirty-four studies were included. Studies were critically appraised using established critical appraisal tools (Qualsyst) and a risk of bias was assigned. Clinicians considered old age and the associated complexities such as co-morbidities and the increased potential for bleeding as potential barriers to optimising anticoagulation. Whereas patients' health and medication beliefs influenced adherence. Notably, structured patient support was important in enhancing safety and effective anticoagulation. For both patients and clinicians, confidence and experience of safe anticoagulation was influenced by the presence of co-morbidities,  poor knowledge and understanding of AF and the purpose of anticoagulation. CONCLUSION: Age, complex multimorbidity and polypharmacy influence prescribing, with DOACs being perceived to be safer than warfarin. This systematic narrative review suggests that interventions are needed to support patient self-management. There are residual anxieties associated with long term anticoagulation in the context of complexities. TRIAL REGISTRATION: Not applicable.

Molecular analysis of the blood meals and bacterial communities of bed bugs (Cimex lectularius L.) to assess interactions with alternative hosts.

Common bed bugs (Cimex lectularius L.) are hematophagous pests present in urban environments across the globe. It is widely established that they have a strong host preference for humans. However, there are records of C. lectularius feeding upon a range of mammalian and avian hosts, including rodents, in the field. There is little information available about how frequently common bed bugs feed on alternative hosts in residential settings, but understanding this phenomenon has implications for both management of infestations and public health. Here, we examined cohorts of C. lectularius collected from 13 different dwellings in the state of New Jersey, USA, that were known to be simultaneously infested with house mice (Mus musculus domesticus). Host-specific quantitative polymerase chain reaction (qPCR) was used to determine if blood meals were taken from mice, while 16S rRNA gene amplicon sequencing was used to screen the bed bugs for the presence of zoonotic bacterial pathogens. We found no evidence that any of the bed bugs we collected fed on mice. Furthermore, the insects harbored depauperate bacterial communities that did not include known human pathogens. However, host-specific qPCR detected feline DNA in a pool of bed bugs from one dwelling, suggesting that interaction with domestic pets should be further investigated. Although sampling in this study was limited, the approach described herein will be useful for additional studies of the interactions between bed bugs and alternative blood meal hosts.

Potential Cardiovascular Disease Events Prevented with Adoption of the 2017 American College of Cardiology/American Heart Association Blood Pressure Guideline.

BACKGROUND: Over 10 years, achieving and maintaining 2017 ACC/AHA guideline goals could prevent 3.0 million (UR, 1.1-5.1 million), 0.5 million (UR, 0.2-0.7 million), and 1.4 million (UR, 0.6-2.0 million) cardiovascular disease (CVD) events compared with maintaining current blood pressure (BP) levels, achieving 2003 Seventh Joint National Committee Report goals, and achieving 2014 Eighth Joint National Committee goals, respectively. We estimated the number of cardiovascular disease events prevented and treatment-related serious adverse events incurred over 10 years among US adults with hypertension by achieving 2017 ACC/AHA guideline-recommended BP goals compared with (1) current BP levels, (2) achieving 2003 Seventh Joint National Committee Report BP goals, and (3) achieving 2014 Eighth Joint National Committee panel member report BP goals. METHODS: US adults aged ≥45 years with an indication for BP treatment were grouped according to recommendations for antihypertensive drug therapy in the 2017 ACC/AHA guideline, 2003 Seventh Joint National Committee Report, and 2014 Eighth Joint National Committee. Population sizes were estimated from the 2011 to 2014 National Health and Nutrition Examination Surveys. Rates for fatal and nonfatal CVD events (stroke, coronary heart disease, or heart failure) were estimated from the REGARDS (REasons for Geographic And Racial Differences in Stroke) study, weighted to the US population. CVD risk reductions with treatment to BP goals and risk for serious adverse events were obtained from meta-analyses of BP-lowering trials. CVD events prevented and treatment-related nonfatal serious adverse events over 10 years were calculated. Uncertainty surrounding main data inputs was expressed in uncertainty ranges (UR). RESULTS: Over ten years, achieving and maintaining 2017 ACC/AHA guideline goals compared with current BP levels, achieving 2003 Seventh Joint National Committee Report goals, or achieving 2014 Eighth Joint National Committee goals could prevent 3.0 million (UR, 1.1-5.1 million), 0.5 million (UR, 0.2-0.7 million), or 1.4 million (UR, 0.6-2.0 million) CVD events, respectively. Compared with current BP levels, achieving and maintaining 2017 goals could prevent 71.9 (UR, 26.6-122.3) CVD events per 1000 treated. Achieving 2017 guideline BP goals compared with current BP levels could also lead to nearly 3.3 million more serious adverse events over 10 years (UR, 2.2-4.4 million). CONCLUSIONS: Achieving and maintaining 2017 ACC/AHA BP goals could prevent a greater number of CVD events than achieving 2003 Seventh Joint National Committee Report or 2014 Eighth Joint National Committee BP goals but could also lead to more serious adverse events.

Detecting fitness epistasis in recently admixed populations with genome-wide data.

BACKGROUND: Fitness epistasis, the interaction effect of genes at different loci on fitness, makes an important contribution to adaptive evolution. Although fitness interaction evidence has been observed in model organisms, it is more difficult to detect and remains poorly understood in human populations as a result of limited statistical power and experimental constraints. Fitness epistasis is inferred from non-independence between unlinked loci. We previously observed ancestral block correlation between chromosomes 4 and 6 in African Americans. The same approach fails when examining ancestral blocks on the same chromosome due to the strong confounding effect observed in a recently admixed population. RESULTS: We developed a novel approach to eliminate the bias caused by admixture linkage disequilibrium when searching for fitness epistasis on the same chromosome. We applied this approach in 16,252 unrelated African Americans and identified significant ancestral correlations in two pairs of genomic regions (P-value< 8.11 × 10- 7) on chromosomes 1 and 10. The ancestral correlations were not explained by population admixture. Historical African-European crossover events are reduced between pairs of epistatic regions. We observed multiple pairs of co-expressed genes shared by the two regions on each chromosome, including ADAR being co-expressed with IFI44 in almost all tissues and DARC being co-expressed with VCAM1, S1PR1 and ELTD1 in multiple tissues in the Genotype-Tissue Expression (GTEx) data. Moreover, the co-expressed gene pairs are associated with the same diseases/traits in the GWAS Catalog, such as white blood cell count, blood pressure, lung function, inflammatory bowel disease and educational attainment. CONCLUSIONS: Our analyses revealed two instances of fitness epistasis on chromosomes 1 and 10, and the findings suggest a potential approach to improving our understanding of adaptive evolution.

Reducing Cardiovascular Disparities Through Community-Engaged Implementation Research: A National Heart, Lung, and Blood Institute Workshop Report.

Cardiovascular disparities remain pervasive in the United States. Unequal disease burden is evident among population groups based on sex, race, ethnicity, socioeconomic status, educational attainment, nativity, or geography. Despite the significant declines in cardiovascular disease mortality rates in all demographic groups during the last 50 years, large disparities remain by sex, race, ethnicity, and geography. Recent data from modeling studies, linked micromap plots, and small-area analyses also demonstrate prominent variation in cardiovascular disease mortality rates across states and counties, with an especially high disease burden in the southeastern United States and Appalachia. Despite these continued disparities, few large-scale intervention studies have been conducted in these high-burden populations to examine the feasibility of reducing or eliminating cardiovascular disparities. To address this challenge, on June 22 and 23, 2017, the National Heart, Lung, and Blood Institute convened experts from a broad range of biomedical, behavioral, environmental, implementation, and social science backgrounds to summarize the current state of knowledge of cardiovascular disease disparities and propose intervention strategies aligned with the National Heart, Lung, and Blood Institute mission. This report presents the themes, challenges, opportunities, available resources, and recommended actions discussed at the workshop.

An international survey of airway management education in 61 countries†.

BACKGROUND: Deficiencies in airway management skills and judgement contribute to poor outcomes. Airway management practice guidelines emphasise the importance of education. Little is known about the global uptake of guidelines, availability of equipment, provision of training, assessment of skills, and confidence with procedures. METHODS: We devised a survey to examine these issues. Initially, 24 127 anaesthetists were questioned in New Zealand, Canada, South Africa, UK, India, and Germany, representing the home countries of the members of the Worldwide Airway Meeting (2015) Education Group; however, the survey could be forwarded to others. The survey was open for a maximum of 90 days. RESULTS: We received 4948 fully or partially completed surveys from 61 countries: 33 high-income and 28 middle- or low-income countries. Most respondents were consultants (77.2%, n=4948), and the remainder trainees, with a male/female ratio of 1.8:1 (3105 males, n=4866). Of those responding, 1358 (76.6%, n=1798) were members of an airway interest group. Most respondents (91.3% of 2910) agreed with assessment of airway skills, fewer (2237; 59.7%, n=3750) reported requiring airway training for completion of training, and only 810 (33.6%, n=2408) reported it as a requirement for continuing medical education. Reported confidence was lowest for awake tracheal intubation, front-of-neck access, and retrograde intubation. CONCLUSIONS: Global training is variable in its delivery and necessity. Confidence is limited in potentially life-saving techniques. The desire for assessment appears universal and may improve standards, but in resource- or time-limited environments this will be challenging.

Direct versus indirect laryngoscopy using a Macintosh video laryngoscope: a mannequin study comparing applied forces.

PURPOSE: Upper airway injury and sympathetic activation may be related to the forces applied during laryngoscopy. We compared the applied forces during laryngoscopy using direct and indirect visualization of a standardized mannequin glottis. METHODS: Force transducers were applied to the concave surface of a GlideScope T-MAC Macintosh-style video laryngoscope that can also be used as a conventional direct-view laryngoscope. Thirty-four anesthesiologists performed four laryngoscopies (two direct and two indirect views) on an Ambu mannequin in a randomized sequence. During each laryngoscopy, participants were instructed to obtain views corresponding to > 80% and 50% of the glottic opening aperture. Peak and impulse forces were measured for each view. RESULTS: To achieve a 50% glottic opening view, the top 10th percentile force was higher with direct vs indirect laryngoscopy in terms of peak (difference, 9.1 newton; 99% confidence interval [CI], 7.4 to 13.9) and impulse (difference, 56.4 newton·sec; 99% CI, 49.0 to 81.7) forces. To achieve >80% view of the glottic opening, median force was higher with direct vs indirect laryngoscopy in terms of peak (difference, 3.6 newton; 99% CI, 1.6 to 7.3) and impulse (difference, 20.4 newton·sec; 99% CI, 11.7 to 35.1) forces. CONCLUSIONS: In this mannequin study, lower forces applied during indirect vs direct laryngoscopy may reflect an advantage of video laryngoscopy, but additional studies using patients are required to confirm the clinical implications of these findings.

RéSUMé: OBJECTIF: Les lésions aux voies aériennes supérieures et l'activation du système sympathique pourraient être dues aux forces appliquées pendant la laryngoscopie. Nous avons comparé les forces appliquées pendant une laryngoscopie avec visualisation directe vs indirecte d'une glotte standardisée sur mannequin. MéTHODE: Des transducteurs ont été appliqués à la surface concave d'un vidéolaryngoscope de type Macintosh GlideScope T-MAC, un dispositif qui peut également être utilisé comme laryngoscope conventionnel avec visualisation directe. Trente-quatre anesthésiologistes ont chacun réalisé quatre laryngoscopies (deux visualisations directes et deux indirectes) sur un mannequin Ambu en suivant une séquence randomisée. Pendant chaque laryngoscopie, les participants avaient pour consigne d'obtenir des vues correspondant à > 80 % et 50 % de l'ouverture glottique. Les forces maximales et impulsions ont été mesurées pour chaque visualisation. RéSULTATS: Pour obtenir une visualisation à 50 % de l'ouverture glottique, le 10e percentile maximal était plus élevé en cas de laryngoscopie directe qu'en cas de laryngoscopie indirecte tant au maximum de la force (différence, 9,1 newton; intervalle de confiance [IC] 99 %, 7,4 à 13,9) qu'à l'impulsion (différence, 56,4 newton·sec; IC 99 %, 49,0 à 81,7). Pour obtenir une visualisation à > 80 % de l'ouverture glottique, la médiane était également plus élevée en cas de laryngoscopie directe qu'en cas de laryngoscopie indirecte, tant au maximum de la force (différence, 3,6 newton; intervalle de confiance [IC] 99 %, 1,6 à 7,3) qu'à l'impulsion (différence, 20,4 newton·sec; IC 99 %, 11,7 à 35,1). CONCLUSION: Dans cette étude sur mannequin, les forces et impulsions moins prononcées appliquées pendant la laryngoscopie indirecte plutôt que directe pourraient refléter un avantage de la vidéolaryngoscopie, mais des études supplémentaires sur patient sont nécessaires afin de confirmer les implications cliniques de ces résultats.

Role of patients' organizations in Health Technology Assessment: a Habermasian system and lifeworld perspective.

Patient and public involvement in Health Technology Assessment (HTA) is gaining increased interest among research and policy communities. Patients' organizations represent an important link between individual patients and the health system. Social theories are increasingly being used to explain doctor-patient-system interactions, expanding understanding beyond the mere clinical perspective. In this sense, patient involvement in HTA can also be considered through the Habermas's theory of communicative action. From a Habermasian perspective, HTA as part of the instrumental rationality contributes to an increased efficiency of resource use within the system; however, such rationalization threatens to colonize the lifeworld by making it "increasingly state administered with attenuated possibilities for communicative action as a result of the commercialization and rationalization in terms of immediate returns." Using Habermasian system/lifeworld framework, this paper explores opportunities and obstacles to patient involvement in HTA, whereby trying to understand current and possible roles of patients' organizations as a mediating force between HTA as a function of the system and the lifeworld represented by patients.

Discovery and fine-mapping of adiposity loci using high density imputation of genome-wide association studies in individuals of African ancestry: African Ancestry Anthropometry Genetics Consortium.

Genome-wide association studies (GWAS) have identified >300 loci associated with measures of adiposity including body mass index (BMI) and waist-to-hip ratio (adjusted for BMI, WHRadjBMI), but few have been identified through screening of the African ancestry genomes. We performed large scale meta-analyses and replications in up to 52,895 individuals for BMI and up to 23,095 individuals for WHRadjBMI from the African Ancestry Anthropometry Genetics Consortium (AAAGC) using 1000 Genomes phase 1 imputed GWAS to improve coverage of both common and low frequency variants in the low linkage disequilibrium African ancestry genomes. In the sex-combined analyses, we identified one novel locus (TCF7L2/HABP2) for WHRadjBMI and eight previously established loci at P < 5×10-8: seven for BMI, and one for WHRadjBMI in African ancestry individuals. An additional novel locus (SPRYD7/DLEU2) was identified for WHRadjBMI when combined with European GWAS. In the sex-stratified analyses, we identified three novel loci for BMI (INTS10/LPL and MLC1 in men, IRX4/IRX2 in women) and four for WHRadjBMI (SSX2IP, CASC8, PDE3B and ZDHHC1/HSD11B2 in women) in individuals of African ancestry or both African and European ancestry. For four of the novel variants, the minor allele frequency was low (<5%). In the trans-ethnic fine mapping of 47 BMI loci and 27 WHRadjBMI loci that were locus-wide significant (P < 0.05 adjusted for effective number of variants per locus) from the African ancestry sex-combined and sex-stratified analyses, 26 BMI loci and 17 WHRadjBMI loci contained ≤ 20 variants in the credible sets that jointly account for 99% posterior probability of driving the associations. The lead variants in 13 of these loci had a high probability of being causal. As compared to our previous HapMap imputed GWAS for BMI and WHRadjBMI including up to 71,412 and 27,350 African ancestry individuals, respectively, our results suggest that 1000 Genomes imputation showed modest improvement in identifying GWAS loci including low frequency variants. Trans-ethnic meta-analyses further improved fine mapping of putative causal variants in loci shared between the African and European ancestry populations.