The mediating roles of workplace support and ethical work environment in associations between leadership and moral distress: a longitudinal study of Canadian health care workers during the COVID-19 pandemic.

Introduction: The COVID-19 pandemic has resulted in heightened moral distress among health care workers (HCWs) worldwide. Past research has shown that effective leadership may mitigate potential for the development of moral distress. However, no research to date has considered the mechanisms by which leadership might have an influence on moral distress. We sought to evaluate longitudinally whether Canadian HCWs' perceptions of workplace support and ethical work environment would mediate associations between leadership and moral distress. Methods: A total of 239 French- and English-speaking Canadian HCWs employed during the COVID-19 pandemic were recruited to participate in a longitudinal online survey. Participants completed measures of organizational and supervisory leadership at baseline and follow-up assessments of workplace support, perceptions of an ethical work environment, and moral distress. Results: Associations between both organizational and supervisory leadership and moral distress were fully mediated by workplace supports and perceptions of an ethical work environment. Discussion: To ensure HCW well-being and quality of care, it is important to ensure that HCWs are provided with adequate workplace supports, including manageable work hours, social support, and recognition for efforts, as well as an ethical workplace environment.

Faculty-Wide Peer-Support Program During the COVID-19 Pandemic: Design and Preliminary Results.

BACKGROUND: Physicians experience higher rates of burnout relative to the general population. Concerns of confidentiality, stigma, and professional identities as health care providers act as barriers to seeking and receiving appropriate support. In the context of the COVID-19 pandemic, factors that contribute to burnout and barriers to seeking support have been amplified, elevating the overall risks of mental distress and burnout for physicians. OBJECTIVE: This paper aimed to describe the rapid development and implementation of a peer support program within a health care organization located in London, Ontario, Canada. METHODS: A peer support program leveraging existing infrastructures within the health care organization was developed and launched in April 2020. The "Peers for Peers" program drew from the work of Shapiro and Galowitz in identifying key components within hospital settings that contributed to burnout. The program design was derived from a combination of the peer support frameworks from the Airline Pilot Assistance Program and the Canadian Patient Safety Institute. RESULTS: Data gathered over 2 waves of peer leadership training and program evaluations highlighted a diversity of topics covered through the peer support program. Further, enrollment continued to increase in size and scope over the 2 waves of program deployments into 2023. CONCLUSIONS: Findings suggest that the peer support program is acceptable to physicians and can be easily and feasibly implemented within a health care organization. The structured program development and implementation can be adopted by other organizations in support of emerging needs and challenges.

Estimating infant upper extremities motion with an RGB-D camera and markerless deep neural network tracking: A validation study.

Quantitative biomarkers of infant motion may be predictive of the development of movement disorders. This study presents and validates a low cost, markerless motion tracking method for the estimation of upper body kinematics of infants from which proper biomarkers may be extracted. The method requires a single RGB-D camera, a 2D motion tracking software publicly available (DeepLabCut) and an algorithm generating 3D point coordinates from the 2D tracked points, dealing with missing data, originating from various sources, for estimating joint kinematics. The proposed method is validated using known point kinematics obtained from a doll, with size and shape of an infant, lying on a turntable rotating at 33⅓ rpm. Two camera image plane orientations are tested: parallel to the turntable motion plane and forming a 45° angle with respect to the motion plane. The latter enhances the occurrence of body parts occlusions during motion as expected in live infant motion recordings. The length of upper body segments, elbow and shoulder joint angles and the linear point velocity determined with the proposed method are evaluated against reference values obtained from the known motion of the turntable. The relevant Mean Absolute Errors (MAE) found indicate the margin of error to expect when processing live infant motion. The proposed method may be improved if enhanced hardware and tracking software are employed, therefore reducing the above-mentioned margin of error. Clinical Relevance - The validation of the proposed method carried out in this study allows clinicians to select proper quantitative biomarkers obtained from infants upper body motion that may be useful for predicting movement disorders.

Which Aspects of the CanMEDS Competencies are Most Valued in Radiologists? Perspectives of Trainees From Other Specialties.

PURPOSE: Radiologists work primarily in collaboration with other healthcare professionals. As such, these stakeholder perspectives are of value to the development and assessment of educational outcomes during the transition to competency-based medical education. Our aim in this study was to determine which aspects of the Royal College CanMEDS competencies for diagnostic radiology are considered most important by future referring physicians. METHODS: Institutional ethics approval was obtained. After pilot testing, an anonymous online survey was sent to all residents and clinical fellows at our university. Open-ended questions asked respondents to describe the aspects of radiologist service they felt were most important. Thematic analysis of the free-text responses was performed using a grounded theory approach. The resulting themes were mapped to the 2015 CanMEDS Key Competencies. RESULTS: 115 completed surveys were received from residents and fellows from essentially all specialties and years of training (out of 928 invited). Major themes were 1) timeliness and accessibility of service, 2) quality of reporting, and 3) acting as a valued team member. The competencies identified as important by resident physicians were largely consistent with the CanMEDS framework, although not all key competencies were covered in the responses. CONCLUSIONS: This study illustrates how CanMEDS roles and competencies may be exemplified in a concrete and specialty-specific manner from the perspective of key stakeholders. Our survey results provide further insight into specific objectives for teaching and assessing these competencies in radiology residency training, with the ultimate goal of improving patient care through strengthened communication and working relationships.

Cross-sectional evaluation of visuomotor tracking performance following subconcussive head impacts.

BACKGROUND: Repeated mild traumatic brain injury (mTBI) has been associated with increased risk of degenerative neurological disorders. While the effects of mTBI and repeated injury are known, studies have only recently started examining repeated subconcussive impacts, impacts that do not result in a clinically diagnosed mTBI. In these studies, repeated subconcussive impacts have been connected to cognitive performance and brain imaging changes. OBJECTIVE: Recent research suggests that performance on a visuomotor tracking (VMT) task may help improve the identification of mTBI. The goal of this study was to investigate if VMT performance is sensitive to the cumulative effect of repeated subconcussive head impacts in collegiate men's lacrosse players. METHODS: A cross-sectional, prospective study was completed with eleven collegiate men's lacrosse players. Participants wore helmet-mounted sensors and completed VMT and reaction time assessments. The relationship between cumulative impact metrics and VMT metrics were investigated. RESULTS: In this study, VMT performance correlated with repeated subconcussive head impacts; individuals approached clinically diagnosed mTBI-like performance as the cumulative rotational velocity they experienced increased. CONCLUSION: This suggests that repeated subconcussive impacts can result in measurable impairments and indicates that visuomotor tracking performance may be a useful tool for monitoring the effects of repeated subconcussive impacts.

Meditation and vacation effects have an impact on disease-associated molecular phenotypes.

Meditation is becoming increasingly practiced, especially for stress-related medical conditions. Meditation may improve cellular health; however, studies have not separated out effects of meditation from vacation-like effects in a residential randomized controlled trial. We recruited healthy women non-meditators to live at a resort for 6 days and randomized to either meditation retreat or relaxing on-site, with both groups compared with 'regular meditators' already enrolled in the retreat. Blood drawn at baseline and post intervention was assessed for transcriptome-wide expression patterns and aging-related biomarkers. Highly significant gene expression changes were detected across all groups (the 'vacation effect') that could accurately predict (96% accuracy) between baseline and post-intervention states and were characterized by improved regulation of stress response, immune function and amyloid beta (Aß) metabolism. Although a smaller set of genes was affected, regular meditators showed post-intervention differences in a gene network characterized by lower regulation of protein synthesis and viral genome activity. Changes in well-being were assessed post intervention relative to baseline, as well as 1 and 10 months later. All groups showed equivalently large immediate post-intervention improvements in well-being, but novice meditators showed greater maintenance of lower distress over time compared with those in the vacation arm. Regular meditators showed a trend toward increased telomerase activity compared with randomized women, who showed increased plasma Aß42/Aß40 ratios and tumor necrosis factor alpha (TNF-α) levels. This highly controlled residential study showed large salutary changes in gene expression networks due to the vacation effect, common to all groups. For those already trained in the practice of meditation, a retreat appears to provide additional benefits to cellular health beyond the vacation effect.

Extracting insights from the shape of complex data using topology.

This paper applies topological methods to study complex high dimensional data sets by extracting shapes (patterns) and obtaining insights about them. Our method combines the best features of existing standard methodologies such as principal component and cluster analyses to provide a geometric representation of complex data sets. Through this hybrid method, we often find subgroups in data sets that traditional methodologies fail to find. Our method also permits the analysis of individual data sets as well as the analysis of relationships between related data sets. We illustrate the use of our method by applying it to three very different kinds of data, namely gene expression from breast tumors, voting data from the United States House of Representatives and player performance data from the NBA, in each case finding stratifications of the data which are more refined than those produced by standard methods.

Hepatitis B virus infection and immunization status in a new generation of injection drug users in San Francisco.

Hepatitis B virus (HBV) infection is common among injection drug users (IDU). Younger IDU, however, may be less susceptible to infection due to the implementation of public health interventions, such as universal immunization programs and syringe exchange programs. To investigate the current epidemiology of HBV infection and control among a new generation of drug users in the United States, we conducted interviews and examined HBV serologic markers in a cross-section of street-recruited IDU under age 30 in San Francisco, CA. Of the 831 persons studied, 21% showed serologic evidence of current or past infection; 22% had isolated antibodies to hepatitis B surface antigen consistent with vaccine-mediated immunity; and 56% had no HBV markers. In multivariate analyses, HBV infection was associated with drug use behaviour in heterosexual males; sexual behaviour in males who have sex with males; and both drug use and sexual behaviour in females. Vaccine-mediated immunity was independently associated with female sex and younger age. In conclusion, HBV transmission persists among young IDU in San Francisco. Few young injectors show evidence of successful immunization and the majority remains susceptible to disease. Until the broad effects of universal vaccination are seen, targeted and innovative approaches to immunizing young IDU in the US are needed to prevent a substantial number of new HBV infections.

An inward-facing conformation of a putative metal-chelate-type ABC transporter.

The crystal structure of a putative metal-chelate-type adenosine triphosphate (ATP)-binding cassette (ABC) transporter encoded by genes HI1470 and HI1471 of Haemophilus influenzae has been solved at 2.4 angstrom resolution. The permeation pathway exhibits an inward-facing conformation, in contrast to the outward-facing state previously observed for the homologous vitamin B12 importer BtuCD. Although the structures of both HI1470/1 and BtuCD have been solved in nucleotide-free states, the pairs of ABC subunits in these two structures differ by a translational shift in the plane of the membrane that coincides with a repositioning of the membrane-spanning subunits. The differences observed between these ABC transporters involve relatively modest rearrangements and may serve as structural models for inward- and outward-facing conformations relevant to the alternating access mechanism of substrate translocation.

An integrative genomics approach to the reconstruction of gene networks in segregating populations.

The reconstruction of genetic networks in mammalian systems is one of the primary goals in biological research, especially as such reconstructions relate to elucidating not only common, polygenic human diseases, but living systems more generally. Here we propose a novel gene network reconstruction algorithm, derived from classic Bayesian network methods, that utilizes naturally occurring genetic variations as a source of perturbations to elucidate the network. This algorithm incorporates relative transcript abundance and genotypic data from segregating populations by employing a generalized scoring function of maximum likelihood commonly used in Bayesian network reconstruction problems. The utility of this novel algorithm is demonstrated via application to liver gene expression data from a segregating mouse population. We demonstrate that the network derived from these data using our novel network reconstruction algorithm is able to capture causal associations between genes that result in increased predictive power, compared to more classically reconstructed networks derived from the same data.

Molecular requirements of the human nucleoside transporters hCNT1, hCNT2, and hENT1.

Concentrative nucleoside transporters (CNTs) and equilibrative nucleoside transporters (ENTs) are important in physiological and pharmacological activity and disposition of nucleosides and nucleoside drugs. A better understanding of the structural requirements of inhibitors for these transporters will aid in designing therapeutic agents. To define the relative and unified structural requirements of nucleoside analogs for interaction with hCNT1, hCNT2, and hENT1, we applied an array of structure-activity techniques. Unique pharmacophore models for each respective nucleoside transporter were generated. These models reveal that hCNT2 affinity is dominated by hydrogen bonding features, whereas hCNT1 and hENT1 displayed mainly electrostatic and steric features. Hydrogen bond formation over 3'-OH is essential for all nucleoside transporters. Inhibition of nucleoside transporters by a series of uridine and adenosine analogs and a variety of drugs was analyzed by comparative molecular field analysis. Cross-validated r2 (q2) values were 0.65, 0.52, and 0.74 for hCNT1, hCNT2, and hENT1, respectively. The predictive quality of the models was further validated by successful prediction of the inhibition of a set of test compounds. Addition of a hydroxyl group around the 2-position of purine (or 3-position of pyrimidine) may increase inhibition to hCNT2 transporter; addition of hydroxyl group around the 2,7-position of purine (or the 3,5-position of pyrimidine) would increase the inhibition to hENT1 transporter. Utilization of these models should assist the design of high-affinity nucleoside transporter inhibitors and substrates for both anticancer and antiviral therapy.

Clustering of hepatotoxins based on mechanism of toxicity using gene expression profiles.

Microarray technology, which allows one to quantitate the expression of thousands of genes simultaneously, has begun to have a major impact on many different areas of drug discovery and development. The question remains of whether microarray analysis and gene expression signature profiles can be applied to the field of toxicology. To date, there are very few published studies showing the use of microarrays in toxicology and important questions remain regarding the predictability and accuracy of applying gene expression profiles to toxicology. To begin to address these questions, we have treated rats with 15 different known hepatotoxins, including allyl alcohol, amiodarone, Aroclor 1254, arsenic, carbamazepine, carbon tetrachloride, diethylnitrosamine, dimethylformamide, diquat, etoposide, indomethacin, methapyrilene, methotrexate, monocrotaline, and 3-methylcholanthrene. These agents cause a variety of hepatocellular injuries including necrosis, DNA damage, cirrhosis, hypertrophy, and hepatic carcinoma. Gene expression analysis was done on RNA from the livers of treated rats and was compared against vehicle-treated controls. The gene expression results were clustered and compared to the histopathology findings and clinical chemistry values. Our results show strong correlation between the histopathology, clinical chemistry, and gene expression profiles induced by the agents. In addition, genes were identified whose regulation correlated strongly with effects on clinical chemistry parameters. Overall, the results suggest that microarray assays may prove to be a highly sensitive technique for safety screening of drug candidates and for the classification of environmental toxins.

Hepatitis C virus infection and needle exchange use among young injection drug users in San Francisco.

Young injection drug users (IDUs) in San Francisco may be at high risk for hepatitis C virus (HCV) infection despite access to several needle exchange venues. The authors conducted a cross-sectional study from 1997 to 1999 in San Francisco to estimate the prevalence and incidence of antibody to HCV (anti-HCV) among street-recruited IDUs under age 30, and to examine risk behaviors and sources of sterile needles. Among 308 participants, the prevalence of anti-HCV was 45%. Using statistical modeling, incidence of HCV infection was estimated to be 11 per 100 person years. Independent risk factors for anti-HCV included age (odds ratio [OR], 1.17 per year; 95% confidence interval [CI], 1.05-1.30), years injecting (OR, 1.21 per year; 95% CI, 1.10-1.34), years in San Francisco (OR, 1.06 per year; 95% CI, 1.00-1.14), first injected by a sex partner (OR, 4.06; 95% CI, 1.74-9.52), injected daily (OR, 3.85; 95% CI, 2.07-7.17), ever borrowed a needle (OR, 2.56; 95% CI, 1.18-5.53), bleached last time a needle was borrowed (OR, 0.50; 95% CI, 0.24-1.02), snorted or smoked drugs in the prior year (OR, 0.48; 95% CI, 0.26-0.89), and injected by someone else in the prior month (OR, 0.50; 95% CI, 0.25-0.99). In the prior month, 88% used at least 1 of several needle exchange venues, and 32% borrowed a needle. We conclude that anti-HCV prevalence is lower than in previous studies of older IDUs, but 11% incidence implies high risk of HCV infection in a long injecting career. Despite access to sterile needles, borrowing of needles persisted.

Investigation of a secondary syringe exchange program for homeless young adult injection drug users in San Francisco, California, U.S.A.

This study investigated an HIV prevention program for homeless young adult injection drug users (IDUs) that combined a secondary syringe exchange program (SEP) with community-level activities. Homeless young IDUs were recruited from street-based settings in San Francisco, and a structured questionnaire was administered. The secondary SEP operated in a circumscribed geographic area, and for analytic purposes respondents were assigned to the intervention site group if they primarily spent time in this area (n = 67), or the comparison site group if they primarily spent time elsewhere (n = 55). Almost all (96%) intervention site youth had used the secondary SEP in the past 30 days and were significantly more likely to regularly use SEP. In bivariate analysis, comparison site IDUs were more likely to share syringes, reuse syringes, share the cotton used to filter drugs, and use condoms with casual sex partners only inconsistently. In multivariate analysis, comparison site remained positively associated with sharing syringes (adjusted odds ratio [AOR], 3.748; 95% confidence interval [CI], 1.406-9.988), reusing syringes (AOR, 2.769; 95% CI,1.120-6.847), and inconsistent condom use with casual sex partners (AOR, 4.825; 95% CI, 1.392- 16.721). This suggests that the intervention was effective in delivering SEP services to homeless young adult IDUs, and that IDUs who frequented the intervention site had a lower HIV risk than comparison group IDUs.

Cell-wall-deficient bacteria and culture-negative febrile episodes in bone-marrow-transplant recipients.

BACKGROUND: Although about 75-80% of neutropenic fevers are thought to be caused by infections, a causal organism can be confirmed microbiologically or suspected clinically in only 30-50%, and even fewer of these cases (16%) have a documented bacteraemia. The cause of neutropenic fever in the remaining cases remains elusive. We investigate the role of cell-wall-deficient bacteria in bone-marrow transplantation (BMT). METHODS: Blood cultures were obtained from bone-marrow-transplant recipients and were inoculated into an aerobic bottle with resin, an anaerobic bottle, and a bottle to isolate cell-wall deficient bacteria. When growth was detected in the blood-culture bottle for cell-wall-deficient bacteria, 20 microL of the broth was subcultured and the isolate identified by standard biochemical methods. The microbiological findings were correlated with the clinical characteristics of the patients. FINDINGS: From the 86 BMT recipients enrolled into the study, 798 sets of blood cultures were sent for laboratory analysis. 55 blood cultures were positive in the aerobic bottle, and the same isolates were also detected in 52 blood-culture bottles for cell-wall-deficient forms. For 20 sets of blood cultures, the isolates were detected only in the bottle for cell-wall-deficient forms. Blood for 13 (65%) of these 20 sets were sampled in the pre-engraftment neutropenic period, three (15%) during conditioning when the absolute neutrophil count was above 0.5 x 10(3)/L, and four (20%) in the post-engraftment period. 17 (85%) of the isolates were gram positive: four (20%) were Staphylococcus spp and ten (50%) were Bacillus spp. Antibiotic treatment was successful in 19 (95%) of 20 episodes. INTERPRETATION: Bacteraemia due to cell-wall-deficient forms causes a significant proportion of so-called culture-negative febrile episodes in BMT recipients.

Experimental annotation of the human genome using microarray technology.

The most important product of the sequencing of a genome is a complete, accurate catalogue of genes and their products, primarily messenger RNA transcripts and their cognate proteins. Such a catalogue cannot be constructed by computational annotation alone; it requires experimental validation on a genome scale. Using 'exon' and 'tiling' arrays fabricated by ink-jet oligonucleotide synthesis, we devised an experimental approach to validate and refine computational gene predictions and define full-length transcripts on the basis of co-regulated expression of their exons. These methods can provide more accurate gene numbers and allow the detection of mRNA splice variants and identification of the tissue- and disease-specific conditions under which genes are expressed. We apply our technique to chromosome 22q under 69 experimental condition pairs, and to the entire human genome under two experimental conditions. We discuss implications for more comprehensive, consistent and reliable genome annotation, more efficient, full-length complementary DNA cloning strategies and application to complex diseases.

Leukocytoclastic vasculitis complicating Klebsiella pneumoniae bacteremia.

A 79-year old woman, with a history of hypertension, presented with clinical features of congestive heart failure, fever, a purpuric rash, and left lower quadrant abdominal tenderness. Contrast computed tomography scan of the abdomen showed features of acute diverticulitis, and blood culture was subsequently positive for Klebsiella pneumoniae. Histological examination of a biopsy of the rash confirmed a diagnosis of leukocytoclastic vasculitis (LCV). The bacteremia responded to intravenous amoxycillin/clavulanic acid and gentamicin and the rash subsided. This case represents the first case of LCV complicating K. pneumoniae bacteremia in the English literature. The English literature on bacteria-associated LCV is reviewed. Taking aside organisms such as Rickettsia that cause endothelial invasion, the associated bacterial species tends to be subacute or chronic pathogens e.g. Mycoplasma pneumoniae, Mycobacterium tuberculosis, and Yersinia enterocolitica; or the disease process is of a subacute or chronic nature e.g. endocarditis, bronchiectesis, and cystic fibrosis, leading to prolonged exposure to pathogens that apparently cause acute pyogenic infections, such as K. pneumoniae.

Identification of Mycobacterium neoaurum isolated from a neutropenic patient with catheter-related bacteremia by 16S rRNA sequencing.

A rapidly growing pigmented mycobacterial strain with an ambiguous biochemical profile was isolated from the blood culture taken through the Hickman catheter of a 9-year-old girl with acute lymphoblastic leukemia. Whole-cell fatty acid analysis showed that the best match profile was that of Mycobacterium aurum, but the similarity index was only 0.217, meaning that there were no good matches between the isolate and the organisms in the database of the Microbial Identification System. The 16S rRNA gene of the mycobacterial strain was amplified, agarose gel purified, and sequenced. There were 44 base differences between the gene sequence of the isolate and that of M. aurum but only one base difference between the sequence of the isolate and that of Mycobacterium neoaurum, showing that the isolate was indeed a strain of M. neoaurum by using this "gold standard." This represents the first case of M. neoaurum infection documented by 16S rRNA sequencing.

Functional discovery via a compendium of expression profiles.

Ascertaining the impact of uncharacterized perturbations on the cell is a fundamental problem in biology. Here, we describe how a single assay can be used to monitor hundreds of different cellular functions simultaneously. We constructed a reference database or "compendium" of expression profiles corresponding to 300 diverse mutations and chemical treatments in S. cerevisiae, and we show that the cellular pathways affected can be determined by pattern matching, even among very subtle profiles. The utility of this approach is validated by examining profiles caused by deletions of uncharacterized genes: we identify and experimentally confirm that eight uncharacterized open reading frames encode proteins required for sterol metabolism, cell wall function, mitochondrial respiration, or protein synthesis. We also show that the compendium can be used to characterize pharmacological perturbations by identifying a novel target of the commonly used drug dyclonine.