Gender Disparities in Mentorship and Career Outcomes in Ophthalmology.

Background: Gender disparities in the field of ophthalmology have been increasingly recognized. Although mentorship has been proposed as a contributing factor, there are limited data on the differences in mentorship experiences by gender among ophthalmologists. Objective: The purpose of this study was to evaluate gender disparities in mentorship experiences among ophthalmologists, and the impact of mentorship disparities on career outcomes. Design: Prospective, cross-sectional study. Setting: Web-based survey distributed through ophthalmology listservs. Participants: Ophthalmologists and ophthalmologists-in-training who completed the survey. Exposure: Training and practicing in the field of ophthalmology. Main Outcome Measures: Mentorship score based on 10 items from a previously published scale of mentorship quality and self-reported career outcomes (income, job satisfaction, achievement of career goals, and support to achieve future career goals). Results: We received survey responses from 202 male and 245 female ophthalmologists. Female ophthalmologists reported significantly lower mentorship satisfaction and worse quality of mentorship (p < 0.03). Female ophthalmologists also reported significantly lower income, worse job satisfaction, and lower rates of goal achievement and support to achieve future goals; all of these career outcomes, except income level, were partly mediated by mentorship score (mediation effect ranged from 29% to 68%, p < 0.014). Conclusions and Relevance: Gender-based inequities in achievement of career goals and job satisfaction are partly mediated by disparities in mentorship. Therefore, focused mentorship of women in ophthalmology at all career stages is imperative to reduce these inequities.

Informing care pathways and policies for children and youth with Indigenous perspectives to advance Canada's National Autism Strategy.

In Canada, most services for Autistic people are provided by provincial and territorial governments. However, support for Indigenous Peoples (First Nations, Inuit, and Métis) are under federal responsibility and are outlined by a set of treaties and agreements with the Crown and a few regional governments. This patchwork results in barriers in service access and navigation challenges in many under-resourced communities, including under-diagnosis and potentially life-threatening outcomes. Designing equitable policy structures and processes would reduce harms and meaningfully interface with Indigenous and other racialized communities. The objective of this Policy Practice Review is to provide a framework for the discovery of appropriate care strategies addressing the conceptualization of autism in Indigenous Peoples and to understand the interactions between racialized Autistic peoples and the Criminal Justice System. First, we conducted environmental scans of publicly-accessible government services available in Canada pertaining to autism in Indigenous communities and the justice system, and explored the dissonance with beliefs and perceptions of autism in Northern Indigenous communities. Second, we focused on the interactions of Indigenous and other racialized populations, with an emphasis on Autistic children and youth with the justice system, an interaction that is often life-altering, downstream, and detrimental to health and wellbeing. The implications of this work include identifying the need for Indigenous-led knowledge and policy recommendations for Canada's upcoming National Autism Strategy, informing the need for culturally appropriate multidisciplinary care and facilitating the coordination between health and social services for these communities.

Multilingual toddlers' vocabulary development in two languages: Comparing bilinguals and trilinguals.

Many children grow up hearing multiple languages, learning words in each. How does the number of languages being learned affect multilinguals' vocabulary development? In a pre-registered study, we compared productive vocabularies of bilingual (n = 170) and trilingual (n = 20) toddlers aged 17-33 months growing up in a bilingual community where both French and English are spoken. We hypothesized that because trilinguals have reduced input in French and English due to time spent hearing their third language, they would have smaller French-English vocabulary sizes than bilinguals. Trilinguals produced on average 2/3 of the number of words in these languages that bilinguals did: however, this difference was not statistically robust due to large levels of variability. Follow-up analyses did, however, indicate a relationship between input quantity and vocabulary size. Our results indicate that similar factors contribute to vocabulary development across toddlers regardless of the number of languages being acquired.

Interrater Reliability among Novice Raters in the Assessment of Pelvic Floor Muscle Tone Using the Reissing Tone Scale.

Purpose: The authors sought to determine the interrater reliability among novice raters of intra-vaginal manual assessment of pubococcygeus muscle tone in women using the Reissing tone scale (RTS). Method: Three graduating physiotherapy students (novice raters) and one experienced pelvic floor physiotherapist assessed 31 female participants (aged 20-66 y). Assessors gave RTS scores for pubococcygeus tone at three intra-vaginal locations (6:00, 9:00, and 3:00). Interrater reliability was determined for the novice raters using a two-way random single-measures absolute agreement intra-class correlation coefficient (ICC). Spearman rank correlation (SRC) analysis determined the correlation between the novice and expert scores. Results: The ICC values for the novice raters were 0.523, 0.274, and 0.336 at 6:00, 9:00, and 3:00, and the SRC values between the novice and expert raters were 0.580, 0.320, and 0.340. Conclusions: The novice raters demonstrated low to moderate interrater reliability for intra-vaginal manual assessment of pubococcygeus tone. This result indicates that manual assessment of pelvic floor muscle tone is not reliable enough to use as a stand-alone test to guide treatment, at least for physiotherapists with limited clinical experience.

Objectif : déterminer la fiabilité interévaluateur des évaluateurs novices qui procèdent à l'évaluation intravaginale manuelle du tonus musculaire pubo-coccygien au moyen du score de tonus de Reissing (STR). Méthodologie : trois étudiants en physiothérapie finissants (les évaluateurs novices) et un physiothérapeute périnéal d'expérience ont évalué 31 participantes (âgées de 20 à 66 ans). Ils ont attribué un STR au tonus pubo-coccygien à trois foyers intravaginaux (à 6, 9 et 3 heures). Les chercheurs ont déterminé la fiabilité interévaluateur des évaluateurs novices au moyen d'un coefficient intraclasse de corrélation (CIC) à concordance absolue des mesures simples bidirectionnelles randomisées. Les chercheurs ont analysé la corrélation de Spearman (CdS) pour établir le lien entre les scores des novices et de l'expert. Résultats : la CIC des évaluateurs novices s'élevait à 0,523, 0,274 et 0,336 à 6, 9 et 3 heures, respectivement, et la CdS entre les évaluateurs novices et expert s'établissait à 0,580, 0,320 et 0,340. Conclusion : les évaluateurs novices ont démontré une fiabilité interévaluateur faible à modérée lors de l'évaluation intravaginale manuelle du tonus pubo-coccygien. Ainsi, l'évaluation manuelle du tonus périnéal n'est pas assez fiable si elle est utilisée seule pour orienter le traitement, du moins chez les physiothérapeutes ayant une expérience clinique limitée.

A single mutation in the mammalian orthoreovirus S1 gene is responsible for increased interferon sensitivity in a virus mutant selected in Vero cells.

In a previous study, a mammalian orthoreovirus mutant was isolated based on its increased ability to infect interferon-defective Vero cells and was referred to as Vero-cells-adapted virus (VeroAV). This virus exhibits reduced ability to resist the antiviral effect of interferon. In the present study, the complete genome sequence of VeroAV was first determined. Reverse genetics was then used to identify a unique mutation on the S1 gene, overlapping the σ1 and σ1 s reading frame, resulting in increased sensitivity to interferon. A virus lacking σ1 s expression consecutive to mutation of its initiation codon was then shown to exhibit a further increase in sensitivity to interferon, supporting the idea that σ1 s is the viral protein responsible. This identification of a new determinant of reovirus sensitivity to interferon gives credentials to the idea that multiple reovirus genes are responsible for the level of interferon induction and susceptibility to the interferon-induced antiviral activities.

Gonioscopy-Assisted Transluminal Trabeculotomy (GATT) in Postpenetrating Keratoplasty Steroid-induced Glaucoma: A Case Report.

Glaucoma following penetrating keratoplasty (PKP) remains the leading cause of blindness following PKP. Patients with post-PKP glaucoma can be managed medically and surgically. Evidence studying glaucoma surgical techniques following PKP is limited, but suggests the possibility for high-risk complications, including graft failure. Minimally invasive glaucoma surgeries offer an alternative. We report the first case of post-PKP glaucoma managed with gonioscopy-assisted transluminal trabeculotomy (GATT). The patient was a 33-year-old man with a history of keratoconus who underwent PKP in his right eye. On presentation, his visual acuity was 20/60 and intraocular pressure was 48 mm Hg OD. He underwent GATT and cataract phacoemulsification. Following 22 months of follow-up, the patient's visual acuity was 20/30 and intraocular pressure 13 mm Hg, off all glaucoma medications. This case demonstrates GATT may be a good surgical option for post-PKP glaucoma, given the ability to perform future incisional surgery and avoidance of high-risk complications associated with traditional glaucoma surgeries.

Disinfection of the Goldman applanation tonometer: a systematic review.

OBJECTIVES: The Goldmann applanation tonometer is the gold standard for measuring intraocular pressure and a possible vector for the transmission of infectious diseases. The purpose of this study is to consolidate the evidence pertaining to the disinfection of Goldmann tonometers in an effort to facilitate an informed discussion regarding public policy in this important area. DESIGN: Systematic review. METHODS: An exhaustive literature review was undertaken to identify primary-level research that assesses the effectiveness of different agents used in the disinfection of Goldmann applanation tonometer prisms. Seven discrete databases were reviewed by 2 independent researchers, and a symmetrical screening process was used to identify and review all pertinent studies. RESULTS: Our review identified only 19 primary-level studies that relate specifically to the disinfection of Goldmann tonometer prisms. These studies are largely heterogeneous with regard to the pathogens and disinfectants that were tested and the experimental protocols that were employed. Accordingly, definitive conclusions as to the optimal agent cannot be made on this basis. Furthermore, the results of our review reinforce previous suggestions that only adenovirus has been transmitted between patients via the Goldmann tonometer. CONCLUSIONS: The present state of the literature does not permit a definitive conclusion regarding optimal disinfection agent for Goldmann applanation tonometer prisms. Further well-constructed studies are required to better delineate the effectiveness of disinfectants in the specific context of tonometer prisms.

First case report of an adrenocortical carcinoma caused by a BRCA2 mutation.

BACKGROUND: Adrenocortical carcinoma (ACC) may rarely be a component of inherited cancer syndromes such as Li-Fraumeni syndrome and Beckwith-Wiedemann syndrome. ACC caused by a BRCA2 mutation has never been reported. METHODS: Nucleotide sequencing of BRCA2 in lymphocyte and tumoral DNA of a 50-year-old male who presented with an androgen-secreting ACC and a strong family history of breast, ovarian, and pancreatic cancers. RESULTS: A germline BRCA2 2 bp heterozygous deletion at nucleotide 8765 (8765delAG) leading to a frameshift mutation (p.Glu2846GlyfsX23) was detected. Only the BRCA2 deleted allele was retained in the ACC tumoral DNA compared with the control DNA supporting a loss of heterozygosity in the tumor. CONCLUSION: This is the first reported case of a patient with ACC associated with a BRCA2 germline mutation. Loss of heterozygosity in ACC DNA suggests a causal link with the BRCA2 8765delAG mutation.

[BETWEEN USAGE AND POLEMIC, AN ARGUMENT IN FAVOUR OF CLARIFYING THE TERMINOLOGY FOR PREIMPLANTATION GENETIC DIAGNOSIS]. / ENTRE USAGES ET POLÉMIQUES, UN ARGUMENT EN FAVEUR D'UNE CLARIFICATION TERMINOLOGIQUE POUR LE DIAGNOSTIC PRÉIMPLANTATOIRE.

Over 30 years ago, preimplantation genetic diagnosis (PGD) was developed to help couples at risk of transmitting a serious genetic disease to their offspring. Today, the range of medical and non-medical uses of PGD has expanded considerably and some raise much controversy. This is the case, for example, with In-Vitro Fertilization to select embryos as 'saviour siblings' or to screen for susceptibility and predisposition to late onset diseases or conditions of variable penetrance. The situation is even more problematic in the case of sex selection or selection of traits that are culturally valued or discredited (such as deafness, behavioral traits, or height). The debate surrounding PGD has been employing terms to describe these particular uses that have contributed to a focus on the negative effects, thus preventing a distinction between the abuses and the benefits of this reproductive technology. In this context, this paper proposes a terminological clarification that would allow distinguishing medical and non-medical use and, therefore, the issues relevant to each. A more accurate and less generic nomenclature could prevent a conflation of different levels of ethical, clinical and social issues under the single term 'PGD'. For the vast majority of medical uses, we propose to keep: 'preimplantation genetic diagnosis (PGD)', which emphasizes that it is a genetic diagnosis. For non-medical uses, we suggest: 'preimplantation genetic trait selection (PGTS)'.

Posthumous reproduction with surplus in vitro fertilization embryos: a study exploring users' choices.

OBJECTIVE: To report results of analysis of in vitro fertilization (IVF) users' choices regarding the potential use of their surplus cryopreserved embryos for posthumous assisted reproduction (PAR). DESIGN: Examination of signed consent forms. SETTING: Public IVF clinic. PATIENT(S): A total of 498 individuals who had signed consent forms for cryopreservation of surplus embryos. INTERVENTION(S): Content analysis of consent form. MAIN OUTCOME MEASURE(S): Agreement to PAR; importance of appropriate counseling within the consent process. RESULT(S): Approximately 68% of individuals consented to the use of surplus embryos for embryologist training and improvement of assisted reproductive techniques, and 56% consented to the use of surplus embryos in a research project; 73.5% of men and 61.8% of women agreed to leave their cryopreserved embryos to their partners for reproductive use in the event of their death. CONCLUSION(S): Our results demonstrate that a majority of both men and women agree to leave their frozen embryos to their partners for PAR in a "real life" context, i.e., in which they were required to provide consent for this prospective option. PAR involves complex issues, including the psychologic aspects of initiating a pregnancy while mourning the loss of a loved one or the effect on the prospective child. We argue that in light of the acceptability of PAR-as demonstrated by our results-further research is required regarding how to best counsel and inform IVF users about the choices they are making in this context, to ensure that their consent for PAR is in fact well informed.

The BRCA2 c.9004G>A (E2002K) [corrected] variant is likely pathogenic and recurs in breast and/or ovarian cancer families of French Canadian descent.

Specific BRCA1 and BRCA2 mutations recur in French Canadian breast and/or ovarian cancer families because of common ancestors, facilitating carrier detection in this population. We recently reported a BRCA2 c.9004G>A variant of unknown clinical significance in two French Canadian breast cancer families. It confers a E3002K alteration in the conserved C-terminus domain of BRCA2, and has been reported in non-French Canadian cancer families. Seven variant positive French Canadian families have since been identified by mutation screening of referrals to hereditary cancer clinics. In this article, we describe the cancer phenotypes of these families and further assess the contribution of this variant in the French Canadian population. We screened index breast cancer cases from 58 cancer families with at least three confirmed cases of breast and/or ovarian cancer and 960 breast cancer cases (48 years mean age) not selected for family history of cancer that were previously found not to carry the most common BRCA1 and BRCA2 mutations reported in this population. The index variant-positive cases from each family had breast cancer between the ages of 35-55 years (43 years mean age); and reported close relatives with breast cancer diagnoses between the ages of 28-84 years (57 years mean age). Three families had ovarian or peritoneal cancers. BRCA2-associated cancers, such as bladder, esophagus, pancreas, prostate, and thyroid cancers also occurred in these families. One c.9004G>A carrier also harbored the PALB2 c.2323C>T (Q775X) mutation found to recur in French Canadian breast cancer cases. No new BRCA2 variant carriers were identified in mutation screens. The absence of BRCA2 c.9004G>A carriers in the breast cancer cases not selected for family history contrasts with familial cases, supporting a pathogenic status for this variant and addition to the existing common BRCA1 and BRCA2 mutation-screening panel for French Canadian breast and/or ovarian cancer families.

[Development of a tool to analyze the menus provided in early childhood daycare centres]. / Développement d'une grille d'analyse des menus en services de garde à la petite enfance.

A review of the literature reveals that there are currently no tools available to analyze the quality of the menus provided in daycare centres. An analysis grid has been developed for this purpose, specifically targeting the food served to preschool children aged 18 months and over. The tool was produced on the basis of findings from recent scientific research. The final version of the grid features 25 statements that cover types of menus, the food groups and recommendations of Canada's Food Guide, sources of protein, the supply of beverages,processed foods, cariogenic products, nutritional variety,allergens and sensory properties of foods. The data gathered using this grid will help establish recommendations for daycare administrators and kitchen managers with respect to various considerations that are key to promoting healthy eating habits in early childhood. The limitations to its use stem from the need to complement these recommendations by conducting an analysis of the recipes and ingredients used, the beverages served and the portion sizes offered.

Disruption of AP1S1, causing a novel neurocutaneous syndrome, perturbs development of the skin and spinal cord.

Adaptor protein (AP) complexes regulate clathrin-coated vesicle assembly, protein cargo sorting, and vesicular trafficking between organelles in eukaryotic cells. Because disruption of the various subunits of the AP complexes is embryonic lethal in the majority of cases, characterization of their function in vivo is still lacking. Here, we describe the first mutation in the human AP1S1 gene, encoding the small subunit sigma1A of the AP-1 complex. This founder splice mutation, which leads to a premature stop codon, was found in four families with a unique syndrome characterized by mental retardation, enteropathy, deafness, peripheral neuropathy, ichthyosis, and keratodermia (MEDNIK). To validate the pathogenic effect of the mutation, we knocked down Ap1s1 expression in zebrafish using selective antisens morpholino oligonucleotides (AMO). The knockdown phenotype consisted of perturbation in skin formation, reduced pigmentation, and severe motility deficits due to impaired neural network development. Both neural and skin defects were rescued by co-injection of AMO with wild-type (WT) human AP1S1 mRNA, but not by co-injecting the truncated form of AP1S1, consistent with a loss-of-function effect of this mutation. Together, these results confirm AP1S1 as the gene responsible for MEDNIK syndrome and demonstrate a critical role of AP1S1 in development of the skin and spinal cord.

Influenzavirus infection is a primary cause of febrile respiratory illness in HIV-infected adults, despite vaccination.

BACKGROUND: There are, to our knowledge, no prospective studies of respiratory tract infections in human immunodeficiency virus (HIV)-infected adults in the highly active antiretroviral therapy (HAART) era. We performed a surveillance study of outpatients who presented with fever and respiratory symptoms to examine the role of viral pathogens in these patients. METHODS: Consecutive patients with a temperature of >38.0 degrees C and respiratory symptoms were recruited from a tertiary care HIV clinic during the period 2003-2006. Nasal pharyngeal samples were tested for influenzavirus A and B, respiratory syncytial virus, and human metapneumovirus using real-time multiplex polymerase chain reaction assays. Paired acute- and convalescent-phase serum samples were tested for respiratory viruses by complement fixation. RESULTS: Fifty patients (90% of whom were receiving HAART) were included in the study (median CD4(+) T cell count, 325 cells/microL; median HIV RNA level, <50 copies/mL). A causative pathogen was identified in 25 patients (50%). Even though 76% of subjects had received influenza vaccine, viral infections were diagnosed in 21 patients (42%), as follows: influenza A, 10 patients; influenza B, 10; and parainfluenza virus type 3 infection, 1. Patients with and those without viral infection had similar demographic characteristics and HIV statuses. No patients with influenza and 23% of patients with other conditions had radiography-confirmed pneumonia (P=.07). Antibiotic prescriptions were common: 70% of patients received antibiotics. No patients with influenza required hospitalization, compared with 21% of other patients (P=.03). CONCLUSIONS: Although illness was mild, influenza accounted for a large proportion of unscheduled visits to a health care provider for respiratory illness and was associated with unnecessary antibiotic prescriptions that may contribute to antimicrobial resistance. Vaccination alone was insufficient to prevent infection. Thus, specific identification and management of influenza should be performed in HIV-infected outpatients who present with fever and respiratory symptoms.

Antibiotic use in children is not influenced by the result of rapid antigen detection test for the respiratory syncytial virus.

BACKGROUND: Rapid antigen detection test (RADT) for respiratory syncytial virus (RSV) is widely used in children hospitalized with acute respiratory tract infection (ARTI), but its influence on antibiotic (AB) use is uncertain. OBJECTIVE: To evaluate if confirmation of RSV infection by RADT modified AB use and elucidate others factors associated with the continuation of antibiotics. STUDY DESIGN: Charts of children hospitalized with viral ARTI aged 0-35 months were reviewed. Modification of antibiotics according to RSV RADT results was compared using Kaplan-Meier estimates and multivariate Cox regression. RESULTS: Of children receiving antibiotics when the RSV RADT result was available, RSV RADT was positive in 144 and negative in 54. Positive RSV RADT results did not lead to modification of antibiotic use. Factors independently associated with cessation of intravenous antibiotics were age > or = 3 months (HR 2.44 [1.41-4.21]) and absence of pneumonia (HR 1.50 [1.03-2.19]). Absence of otitis was associated with cessation of oral antibiotics (HR 9.16 [95% CI, 2.35-35.76]). CONCLUSION: Confirmed presence of RSV by RADT did not influence antibiotic use in young children with ARTI. Except with pneumonia, the risk of bacterial superinfection of RSV infected children is minimal and confirmation of RSV infection should prompt treating physicians to interrupt antibiotics.

An outbreak of severe respiratory tract infection due to human metapneumovirus in a long-term care facility.

BACKGROUND: Human metapneumovirus (hMPV) is a newly described paramyxovirus that is mainly associated with bronchiolitis in children. We sought to describe the epidemiological, virological, and histopathological findings associated with a large outbreak of hMPV infection in a long-term care facility. METHODS: An investigation of the outbreak was performed by public health authorities, who used standardized questionnaires to collect relevant clinical information from all residents of the facility. Nasopharyngeal samples were obtained from a subset of patients who had influenza-like illnesses for testing by viral culture and reverse-transcriptase polymerase chain reaction. Lung tissue samples from a patient whose case was fatal were available for molecular, histopathological, and immunohistochemical testing. RESULTS: A total of 96 (27%) of 364 residents of a long-term care facility presented with respiratory or constitutional symptoms between 1 January 2006 and 15 February 2006. The attack rate in the most affected ward was 72% (31 of 43 patients), which included 4 of the 6 polymerase chain reaction-confirmed cases of hMPV infection. In contrast, viral culture results were positive for hMPV in only 2 of the 5 polymerase chain reaction-positive samples tested. The most reported diagnosis was an upper respiratory tract infection or an influenza-like illness, although 21% of residents in 1 of the 3 wards that had confirmed cases of hMPV infection had lower respiratory tract infections. The fatality rate was 50% (3 of 6 patients) among confirmed cases and 9.4% (9 of 96 patients) among patients with possible cases. A patient with a fatal case had histopathological findings that confirmed the presence of hMPV RNA and proteins in the bronchiolar epithelium of affected lobes. Phylogenetic analysis revealed the presence of 2 distinct strains of hMPV circulating simultaneously on different wards. CONCLUSION: hMPV can be associated with important outbreaks of acute respiratory tract infection in elderly institutionalized persons.

Infections by human coronavirus-NL in hospitalized children.

BACKGROUND: A new human coronavirus (HCoV), HCoV-NL, was recently reported for Dutch patients with acute respiratory tract infections (ARTI). Little information is available on the incidence, clinical manifestations and epidemiologic features of HCoV-NL infections. METHODS: We performed a prospective study of symptomatic (case subjects with ARTI) and asymptomatic (control subjects undergoing elective surgery) children,

Analysis of replication kinetics of the human metapneumovirus in different cell lines by real-time PCR.

Human metapneumovirus (hMPV) is associated with acute respiratory tract disease especially in young children. Using a quantitative real-time TaqMan PCR, we analyzed the replication kinetics of hMPV in different cell lines. Our results indicate that hMPV replicates slightly more efficiently in LLC-MK2 than in Vero cells and poorly in HEp-2 cells.