Neurotransmitter classification from electron microscopy images at synaptic sites in Drosophila melanogaster.

High-resolution electron microscopy of nervous systems has enabled the reconstruction of synaptic connectomes. However, we do not know the synaptic sign for each connection (i.e., whether a connection is excitatory or inhibitory), which is implied by the released transmitter. We demonstrate that artificial neural networks can predict transmitter types for presynapses from electron micrographs: a network trained to predict six transmitters (acetylcholine, glutamate, GABA, serotonin, dopamine, octopamine) achieves an accuracy of 87% for individual synapses, 94% for neurons, and 91% for known cell types across a D. melanogaster whole brain. We visualize the ultrastructural features used for prediction, discovering subtle but significant differences between transmitter phenotypes. We also analyze transmitter distributions across the brain and find that neurons that develop together largely express only one fast-acting transmitter (acetylcholine, glutamate, or GABA). We hope that our publicly available predictions act as an accelerant for neuroscientific hypothesis generation for the fly.

The oral nucleoside prodrug GS-5245 is efficacious against SARS-CoV-2 and other endemic, epidemic, and enzootic coronaviruses.

Despite the wide availability of several safe and effective vaccines that prevent severe COVID-19, the persistent emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) that can evade vaccine-elicited immunity remains a global health concern. In addition, the emergence of SARS-CoV-2 VOCs that can evade therapeutic monoclonal antibodies underscores the need for additional, variant-resistant treatment strategies. Here, we characterize the antiviral activity of GS-5245, obeldesivir (ODV), an oral prodrug of the parent nucleoside GS-441524, which targets the highly conserved viral RNA-dependent RNA polymerase (RdRp). We show that GS-5245 is broadly potent in vitro against alphacoronavirus HCoV-NL63, SARS-CoV, SARS-CoV-related bat-CoV RsSHC014, Middle East respiratory syndrome coronavirus (MERS-CoV), SARS-CoV-2 WA/1, and the highly transmissible SARS-CoV-2 BA.1 Omicron variant. Moreover, in mouse models of SARS-CoV, SARS-CoV-2 (WA/1 and Omicron B1.1.529), MERS-CoV, and bat-CoV RsSHC014 pathogenesis, we observed a dose-dependent reduction in viral replication, body weight loss, acute lung injury, and pulmonary function with GS-5245 therapy. Last, we demonstrate that a combination of GS-5245 and main protease (Mpro) inhibitor nirmatrelvir improved outcomes in vivo against SARS-CoV-2 compared with the single agents. Together, our data support the clinical evaluation of GS-5245 against coronaviruses that cause or have the potential to cause human disease.

Connectome-driven neural inventory of a complete visual system.

Vision provides animals with detailed information about their surroundings, conveying diverse features such as color, form, and movement across the visual scene. Computing these parallel spatial features requires a large and diverse network of neurons, such that in animals as distant as flies and humans, visual regions comprise half the brain's volume. These visual brain regions often reveal remarkable structure-function relationships, with neurons organized along spatial maps with shapes that directly relate to their roles in visual processing. To unravel the stunning diversity of a complex visual system, a careful mapping of the neural architecture matched to tools for targeted exploration of that circuitry is essential. Here, we report a new connectome of the right optic lobe from a male Drosophila central nervous system FIB-SEM volume and a comprehensive inventory of the fly's visual neurons. We developed a computational framework to quantify the anatomy of visual neurons, establishing a basis for interpreting how their shapes relate to spatial vision. By integrating this analysis with connectivity information, neurotransmitter identity, and expert curation, we classified the ~53,000 neurons into 727 types, about half of which are systematically described and named for the first time. Finally, we share an extensive collection of split-GAL4 lines matched to our neuron type catalog. Together, this comprehensive set of tools and data unlock new possibilities for systematic investigations of vision in Drosophila, a foundation for a deeper understanding of sensory processing.

Infant antibody and B-cell responses following confirmed pediatric GII.17 norovirus infections functionally distinguish GII.17 genetic clusters.

Genogroup II (GII) noroviruses are a major cause of diarrheal disease burden in children in both high- and low-income countries. GII.17 noroviruses are composed of distinct genetic clusters (I, II, IIIa, and IIIb) and have shown potential for replacing historically more prevalent GII.4 strains, but the serological basis for GII.17 antigenic diversity has not been studied in children. Utilizing samples from a birth cohort, we investigated antibody and B-cell responses to GII.17 cluster variants in confirmed GII.17 infections in young children as well as demonstrated that the distinct genetic clusters co-circulate. Polyclonal serum antibodies bound multiple clusters but showed cluster-specific blockade activity in a surrogate virus neutralization assay. Antibodies secreted by immortalized memory B cells (MBCs) from an infant GII.17 case were highly specific to GII.17 and exhibited blockade activity against this genotype. We isolated an MBC-derived GII.17-specific Immunoglobulin A (IgA) monoclonal antibody called NVA.1 that potently and selectively blocked GII.17 cluster IIIb and recognized an epitope targeted in serum from cluster IIIb-infected children. These data indicate that multiple antigenically distinct GII.17 variants co-circulate in young children, suggesting retention of cluster diversity alongside potential for immune escape given the existence of antibody-defined cluster-specific epitopes elicited during infection.

Efficacy of the oral nucleoside prodrug GS-5245 (Obeldesivir) against SARS-CoV-2 and coronaviruses with pandemic potential.

Despite the wide availability of several safe and effective vaccines that can prevent severe COVID-19 disease, the emergence of SARS-CoV-2 variants of concern (VOC) that can partially evade vaccine immunity remains a global health concern. In addition, the emergence of highly mutated and neutralization-resistant SARS-CoV-2 VOCs such as BA.1 and BA.5 that can partially or fully evade (1) many therapeutic monoclonal antibodies in clinical use underlines the need for additional effective treatment strategies. Here, we characterize the antiviral activity of GS-5245, Obeldesivir (ODV), an oral prodrug of the parent nucleoside GS-441524, which targets the highly conserved RNA-dependent viral RNA polymerase (RdRp). Importantly, we show that GS-5245 is broadly potent in vitro against alphacoronavirus HCoV-NL63, severe acute respiratory syndrome coronavirus (SARS-CoV), SARS-CoV-related Bat-CoV RsSHC014, Middle East Respiratory Syndrome coronavirus (MERS-CoV), SARS-CoV-2 WA/1, and the highly transmissible SARS-CoV-2 BA.1 Omicron variant in vitro and highly effective as antiviral therapy in mouse models of SARS-CoV, SARS-CoV-2 (WA/1), MERS-CoV and Bat-CoV RsSHC014 pathogenesis. In all these models of divergent coronaviruses, we observed protection and/or significant reduction of disease metrics such as weight loss, lung viral replication, acute lung injury, and degradation in pulmonary function in GS-5245-treated mice compared to vehicle controls. Finally, we demonstrate that GS-5245 in combination with the main protease (Mpro) inhibitor nirmatrelvir had increased efficacy in vivo against SARS-CoV-2 compared to each single agent. Altogether, our data supports the continuing clinical evaluation of GS-5245 in humans infected with COVID-19, including as part of a combination antiviral therapy, especially in populations with the most urgent need for more efficacious and durable interventions.

Cardiopulmonary, Functional, Cognitive and Mental Health Outcomes Post-COVID-19, Across the Range of Severity of Acute Illness, in a Physically Active, Working-Age Population.

BACKGROUND: The COVID-19 pandemic has led to significant morbidity and mortality, with the former impacting and limiting individuals requiring high physical fitness, including sportspeople and emergency services. METHODS: Observational cohort study of 4 groups: hospitalised, community illness with on-going symptoms (community-symptomatic), community illness now recovered (community-recovered) and comparison. A total of 113 participants (aged 39 ± 9, 86% male) were recruited: hospitalised (n = 35), community-symptomatic (n = 34), community-recovered (n = 18) and comparison (n = 26), approximately five months following acute illness. Participant outcome measures included cardiopulmonary imaging, submaximal and maximal exercise testing, pulmonary function, cognitive assessment, blood tests and questionnaires on mental health and function. RESULTS: Hospitalised and community-symptomatic groups were older (43 ± 9 and 37 ± 10, P = 0.003), with a higher body mass index (31 ± 4 and 29 ± 4, P < 0.001), and had worse mental health (anxiety, depression and post-traumatic stress), fatigue and quality of life scores. Hospitalised and community-symptomatic participants performed less well on sub-maximal and maximal exercise testing. Hospitalised individuals had impaired ventilatory efficiency (higher VE/V̇CO2 slope, 29.6 ± 5.1, P < 0.001), achieved less work at anaerobic threshold (70 ± 15, P < 0.001) and peak (231 ± 35, P < 0.001), and had a reduced forced vital capacity (4.7 ± 0.9, P = 0.004). Clinically significant abnormal cardiopulmonary imaging findings were present in 6% of hospitalised participants. Community-recovered individuals had no significant differences in outcomes to the comparison group. CONCLUSION: Symptomatically recovered individuals who suffered mild-moderate acute COVID-19 do not differ from an age-, sex- and job-role-matched comparison population five months post-illness. Individuals who were hospitalised or continue to suffer symptoms may require a specific comprehensive assessment prior to return to full physical activity.

Immune Imprinting Drives Human Norovirus Potential for Global Spread.

Understanding the complex interactions between virus and host that drive new strain evolution is key to predicting the emergence potential of variants and informing vaccine development. Under our hypothesis, future dominant human norovirus GII.4 variants with critical antigenic properties that allow them to spread are currently circulating undetected, having diverged years earlier. Through large-scale sequencing of GII.4 surveillance samples, we identified two variants with extensive divergence within domains that mediate neutralizing antibody binding. Subsequent serological characterization of these strains using temporally resolved adult and child sera suggests that neither candidate could spread globally in adults with multiple GII.4 exposures, yet young children with minimal GII.4 exposure appear susceptible. Antigenic cartography of surveillance and outbreak sera indicates that continued population exposure to GII.4 Sydney 2012 and antigenically related variants over a 6-year period resulted in a broadening of immunity to heterogeneous GII.4 variants, including those identified here. We show that the strongest antibody responses in adults exposed to GII.4 Sydney 2012 are directed to previously circulating GII.4 viruses. Our data suggest that the broadening of antibody responses compromises establishment of strong GII.4 Sydney 2012 immunity, thereby allowing the continued persistence of GII.4 Sydney 2012 and modulating the cycle of norovirus GII.4 variant replacement. Our results indicate a cycle of norovirus GII.4 variant replacement dependent upon population immunity. Young children are susceptible to divergent variants; therefore, emergence of these strains worldwide is driven proximally by changes in adult serological immunity and distally by viral evolution that confers fitness in the context of immunity. IMPORTANCE In our model, preepidemic human norovirus variants harbor genetic diversification that translates into novel antigenic features without compromising viral fitness. Through surveillance, we identified two viruses fitting this profile, forming long branches on a phylogenetic tree. Neither evades current adult immunity, yet young children are likely susceptible. By comparing serological responses, we demonstrate that population immunity varies by age/exposure, impacting predicted susceptibility to variants. Repeat exposure to antigenically similar variants broadens antibody responses, providing immunological coverage of diverse variants but compromising response to the infecting variant, allowing continued circulation. These data indicate norovirus GII.4 variant replacement is driven distally by virus evolution and proximally by immunity in adults.

A Multitrait Locus Regulates Sarbecovirus Pathogenesis.

Infectious diseases have shaped the human population genetic structure, and genetic variation influences the susceptibility to many viral diseases. However, a variety of challenges have made the implementation of traditional human Genome-wide Association Studies (GWAS) approaches to study these infectious outcomes challenging. In contrast, mouse models of infectious diseases provide an experimental control and precision, which facilitates analyses and mechanistic studies of the role of genetic variation on infection. Here we use a genetic mapping cross between two distinct Collaborative Cross mouse strains with respect to severe acute respiratory syndrome coronavirus (SARS-CoV) disease outcomes. We find several loci control differential disease outcome for a variety of traits in the context of SARS-CoV infection. Importantly, we identify a locus on mouse chromosome 9 that shows conserved synteny with a human GWAS locus for SARS-CoV-2 severe disease. We follow-up and confirm a role for this locus, and identify two candidate genes, CCR9 and CXCR6, that both play a key role in regulating the severity of SARS-CoV, SARS-CoV-2, and a distantly related bat sarbecovirus disease outcomes. As such we provide a template for using experimental mouse crosses to identify and characterize multitrait loci that regulate pathogenic infectious outcomes across species. IMPORTANCE Host genetic variation is an important determinant that predicts disease outcomes following infection. In the setting of highly pathogenic coronavirus infections genetic determinants underlying host susceptibility and mortality remain unclear. To elucidate the role of host genetic variation on sarbecovirus pathogenesis and disease outcomes, we utilized the Collaborative Cross (CC) mouse genetic reference population as a model to identify susceptibility alleles to SARS-CoV and SARS-CoV-2 infections. Our findings reveal that a multitrait loci found in chromosome 9 is an important regulator of sarbecovirus pathogenesis in mice. Within this locus, we identified and validated CCR9 and CXCR6 as important regulators of host disease outcomes. Specifically, both CCR9 and CXCR6 are protective against severe SARS-CoV, SARS-CoV-2, and SARS-related HKU3 virus disease in mice. This chromosome 9 multitrait locus may be important to help identify genes that regulate coronavirus disease outcomes in humans.

Comprehensive clinical assessment identifies specific neurocognitive deficits in working-age patients with long-COVID.

INTRODUCTION: There have been more than 425 million COVID-19 infections worldwide. Post-COVID illness has become a common, disabling complication of this infection. Therefore, it presents a significant challenge to global public health and economic activity. METHODS: Comprehensive clinical assessment (symptoms, WHO performance status, cognitive testing, CPET, lung function, high-resolution CT chest, CT pulmonary angiogram and cardiac MRI) of previously well, working-age adults in full-time employment was conducted to identify physical and neurocognitive deficits in those with severe or prolonged COVID-19 illness. RESULTS: 205 consecutive patients, age 39 (IQR30.0-46.7) years, 84% male, were assessed 24 (IQR17.1-34.0) weeks after acute illness. 69% reported ≥3 ongoing symptoms. Shortness of breath (61%), fatigue (54%) and cognitive problems (47%) were the most frequent symptoms, 17% met criteria for anxiety and 24% depression. 67% remained below pre-COVID performance status at 24 weeks. One third of lung function tests were abnormal, (reduced lung volume and transfer factor, and obstructive spirometry). HRCT lung was clinically indicated in <50% of patients, with COVID-associated pathology found in 25% of these. In all but three HRCTs, changes were graded 'mild'. There was an extremely low incidence of pulmonary thromboembolic disease or significant cardiac pathology. A specific, focal cognitive deficit was identified in those with ongoing symptoms of fatigue, poor concentration, poor memory, low mood, and anxiety. This was notably more common in patients managed in the community during their acute illness. CONCLUSION: Despite low rates of residual cardiopulmonary pathology, in this cohort, with low rates of premorbid illness, there is a high burden of symptoms and failure to regain pre-COVID performance 6-months after acute illness. Cognitive assessment identified a specific deficit of the same magnitude as intoxication at the UK drink driving limit or the deterioration expected with 10 years ageing, which appears to contribute significantly to the symptomatology of long-COVID.

A Multitrait Locus Regulates Sarbecovirus Pathogenesis.

Infectious diseases have shaped the human population genetic structure, and genetic variation influences the susceptibility to many viral diseases. However, a variety of challenges have made the implementation of traditional human Genome-wide Association Studies (GWAS) approaches to study these infectious outcomes challenging. In contrast, mouse models of infectious diseases provide an experimental control and precision, which facilitates analyses and mechanistic studies of the role of genetic variation on infection. Here we use a genetic mapping cross between two distinct Collaborative Cross mouse strains with respect to SARS-CoV disease outcomes. We find several loci control differential disease outcome for a variety of traits in the context of SARS-CoV infection. Importantly, we identify a locus on mouse Chromosome 9 that shows conserved synteny with a human GWAS locus for SARS-CoV-2 severe disease. We follow-up and confirm a role for this locus, and identify two candidate genes, CCR9 and CXCR6 that both play a key role in regulating the severity of SARS-CoV, SARS-CoV-2 and a distantly related bat sarbecovirus disease outcomes. As such we provide a template for using experimental mouse crosses to identify and characterize multitrait loci that regulate pathogenic infectious outcomes across species.

Antigenic Site Immunodominance Redirection Following Repeat Variant Exposure.

Human norovirus is a leading cause of acute gastroenteritis, driven by antigenic variants within the GII.4 genotype. Antibody responses to GII.4 vaccination in adults are shaped by immune memory. How children without extensive immune memory will respond to GII.4 vaccination has not been reported. Here, we characterized the GII.4 neutralizing antibody (nAb) landscape following natural infection using a surrogate assay and antigenic site chimera virus-like particles. We demonstrate that the nAb landscape changes with age and virus exposure. Among sites A, C, and G, nAbs from first infections are focused on sites A and C. As immunity develops with age/exposure, site A is supplemented with antibodies that bridge site A to sites C and G. Cross-site nAbs continue to develop into adulthood, accompanied by an increase in nAb to site G. Continued exposure to GII.4 2012 Sydney correlated with a shift to co-dominance of sites A and G. Furthermore, site G nAbs correlated with the broadening of nAb titer across antigenically divergent variants. These data describe fundamental steps in the development of immunity to GII.4 over a lifetime, and illustrate how the antigenicity of one pandemic variant could influence the pandemic potential of another variant through the redirection of immunodominant epitopes.

The effect of medium-term recovery status after COVID-19 illness on cardiopulmonary exercise capacity in a physically active adult population.

A failure to fully recover following coronavirus disease 2019 (COVID-19) may have a profound impact on high-functioning populations ranging from frontline emergency services to professional or amateur/recreational athletes. The aim of the study is to describe the medium-term cardiopulmonary exercise profiles of individuals with "persistent symptoms" and individuals who feel "recovered" after hospitalization or mild-moderate community infection following COVID-19 to an age, sex, and job-role matched control group. A total of 113 participants underwent cardiopulmonary functional tests at a mean of 159 ± 7 days (∼5 mo) following acute illness; 27 hospitalized with persistent symptoms (hospitalized-symptomatic), 8 hospitalized and now recovered (hospitalized-recovered); 34 community managed with persistent symptoms (community-symptomatic); 18 community managed and now recovered (community-recovered); and 26 controls. Hospitalized groups had the least favorable body composition (body mass, body mass index, and waist circumference) compared with controls. Hospitalized-symptomatic and community-symptomatic individuals had a lower oxygen uptake (V̇o2) at peak exercise (hospitalized-symptomatic, 29.9 ± 5.0 mL/kg/min; community-symptomatic, 34.4 ± 7.2 mL/kg/min; vs. control 43.9 ± 3.1 mL/kg/min, both P < 0.001). Hospitalized-symptomatic individuals had a steeper V̇e/V̇co2 slope (lower ventilatory efficiency) (30.5 ± 5.3 vs. 25.5 ± 2.6, P = 0.003) versus. controls. Hospitalized-recovered had a significantly lower oxygen uptake at peak (32.6 ± 6.6 mL/kg/min vs. 43.9 ± 13.1 mL/kg/min, P = 0.015) compared with controls. No significant differences were reported between community-recovered individuals and controls in any cardiopulmonary parameter. In conclusion, medium-term findings suggest that community-recovered individuals did not differ in cardiopulmonary fitness from physically active healthy controls. This suggests their readiness to return to higher levels of physical activity. However, the hospitalized-recovered group and both groups with persistent symptoms had enduring functional limitations, warranting further monitoring, rehabilitation, and recovery.NEW & NOTEWORTHY At 5 mo postinfection, community-treated individuals who feel recovered have comparable cardiopulmonary exercise profiles to the physically trained and active controls, suggesting a readiness to return to higher intensity/volumes of exercise. However, both symptomatic groups and the hospital-recovered group have persistent functional limitations when compared with active controls, supporting the requirement for ongoing monitoring, rehabilitation, and recovery.

Therapeutic treatment with an oral prodrug of the remdesivir parental nucleoside is protective against SARS-CoV-2 pathogenesis in mice.

The coronavirus disease 2019 (COVID-19) pandemic remains uncontrolled despite the rapid rollout of safe and effective severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines, underscoring the need to develop highly effective antivirals. In the setting of waning immunity from infection and vaccination, breakthrough infections are becoming increasingly common and treatment options remain limited. In addition, the emergence of SARS-CoV-2 variants of concern, with their potential to escape neutralization by therapeutic monoclonal antibodies, emphasizes the need to develop second-generation oral antivirals targeting highly conserved viral proteins that can be rapidly deployed to outpatients. Here, we demonstrate the in vitro antiviral activity and in vivo therapeutic efficacy of GS-621763, an orally bioavailable prodrug of GS-441524, the parent nucleoside of remdesivir, which targets the highly conserved virus RNA-dependent RNA polymerase. GS-621763 exhibited antiviral activity against SARS-CoV-2 in lung cell lines and two different human primary lung cell culture systems. GS-621763 was also potently antiviral against a genetically unrelated emerging coronavirus, Middle East respiratory syndrome CoV (MERS-CoV). The dose-proportional pharmacokinetic profile observed after oral administration of GS-621763 translated to dose-dependent antiviral activity in mice infected with SARS-CoV-2. Therapeutic GS-621763 administration reduced viral load and lung pathology; treatment also improved pulmonary function in COVID-19 mouse model. A direct comparison of GS-621763 with molnupiravir, an oral nucleoside analog antiviral that has recently received EUA approval, proved both drugs to be similarly efficacious in mice. These data support the exploration of GS-441524 oral prodrugs for the treatment of COVID-19.

Dysautonomia following COVID-19 is not associated with subjective limitations or symptoms but is associated with objective functional limitations.

BACKGROUND: Individuals who contract coronavirus disease 2019 (COVID-19) can suffer with persistent and debilitating symptoms long after the initial acute illness. Heart rate (HR) profiles determined during cardiopulmonary exercise testing (CPET) and delivered as part of a post-COVID recovery service may provide insight into the presence and impact of dysautonomia on functional ability. OBJECTIVE: Using an active, working-age, post-COVID-19 population, the purpose of this study was to (1) determine and characterize any association between subjective symptoms and dysautonomia; and (2) identify objective exercise capacity differences between patients classified "with" and those "without" dysautonomia. METHODS: Patients referred to a post-COVID-19 service underwent comprehensive clinical assessment, including self-reported symptoms, CPET, and secondary care investigations when indicated. Resting HR >75 bpm, HR increase with exercise <89 bpm, and HR recovery <25 bpm 1 minute after exercise were used to define dysautonomia. Anonymized data were analyzed and associations with symptoms, and CPET outcomes were determined. RESULTS: Fifty-one of the 205 patients (25%) reviewed as part of this service evaluation had dysautonomia. There were no associations between symptoms or perceived functional limitation and dysautonomia (P >.05). Patients with dysautonomia demonstrated objective functional limitations with significantly reduced work rate (219 ± 37 W vs 253 ± 52 W; P <.001) and peak oxygen consumption (V̇o2: 30.6 ± 5.5 mL/kg/min vs 35.8 ± 7.6 mL/kg/min; P <.001); and a steeper (less efficient) V̇e/V̇co2 slope (29.9 ± 4.9 vs 27.7 ± 4.7; P = .005). CONCLUSION: Dysautonomia is associated with objective functional limitations but is not associated with subjective symptoms or limitation.

Gastrocnemius Muscle Architecture in Elite Basketballers and Cyclists: A Cross-Sectional Cohort Study.

Eccentric and concentric actions produce distinct mechanical stimuli and result in different adaptations in skeletal muscle architecture. Cycling predominantly involves concentric activity of the gastrocnemius muscles, while playing basketball requires both concentric and eccentric actions to support running, jumping, and landing. The aim of this study was to examine differences in the architecture of gastrocnemius medialis (GM) and gastrocnemius lateralis (GL) between elite basketballers and cyclists. A trained sonographer obtained three B-mode ultrasound images from GM and GL muscles in 44 athletes (25 basketballers and 19 cyclists; 24 ± 5 years of age). The images were digitized and average fascicle length (FL), pennation angle (θ), and muscle thickness were calculated from three images per muscle. The ratio of FL to tibial length (FL/TL) and muscle thickness to tibial length (MT/TL) was also calculated to account for the potential scaling effect of stature. In males, no significant differences were identified between the athletic groups in all parameters in the GM, but a significant difference existed in muscle thickness in the GL. In basketballers, GL was 2.5 mm thicker (95% CI: 0.7-4.3 mm, p = 0.011) on the left side and 2.6 mm thicker (95% CI: 0.6-5.7 mm, p = 0.012) on the right side; however, these differences were not significant when stature was accounted for (MT/TL). In females, significant differences existed in the GM for all parameters including FL/TL and MT/TL. Female cyclists had longer FL in both limbs (MD: 11.2 and 11.3 mm), narrower θ (MD: 2.1 and 1.8°), and thicker muscles (MD: 2.1 and 2.5 mm). For the GL, female cyclists had significantly longer FL (MD: 5.2 and 5.8 mm) and narrower θ (MD: 1.7 and 2.3°) in both limbs; no differences were observed in absolute muscle thickness or MT/TL ratio. Differences in gastrocnemius muscle architecture were observed between female cyclists and basketballers, but not between males. These findings suggest that participation in sport-specific training might influence gastrocnemius muscle architecture in elite female athletes; however, it remains unclear as to whether gastrocnemius architecture is systematically influenced by the different modes of muscle activation between these respective sports.

Reliability of ultrasonographic measurement of muscle architecture of the gastrocnemius medialis and gastrocnemius lateralis.

Ultrasonography is widely used to measure gastrocnemius muscle architecture; however, it is unclear if values obtained from digitised images are sensitive enough to track architectural responses to clinical interventions. The purpose of this study was to explore the reliability and determine the minimal detectable change (MDC) of gastrocnemius medialis (GM) and gastrocnemius lateralis (GL) muscle architecture using ultrasound in a clinical setting. A trained sonographer obtained three B-mode images from each of the GM and GL muscles in 87 volunteers (44 males, 43 females; 22±9 years of age) on two separate occasions. Three independent investigators received training, then digitised the images to determine intra-rater, inter-rater, and test-retest reliability for fascicle length (FL), pennation angle (θ) and muscle thickness. Median FL, θ, and muscle thickness for GM and GL were 53.6-55.7 mm and 65.8-69.3 mm, 18.7-19.5° and 11.9-12.5°, and 12.8-13.2 mm and 15.9-16.9 mm, respectively. Intra- and inter-rater reliability of manual digitisation was excellent for all parameters. Test-retest reliability was moderate to excellent with intraclass correlation coefficient (ICC) values ≥0.80 for FL, ≥0.61 for θ, and ≥0.81 for muscle thickness, in both GM and GL. The respective MDC for GM and GL FL, θ, and muscle thickness was ≤12.1 mm and ≤18.00 mm, ≤6.4° and ≤4.2°, and ≤3.2 mm and ≤3.1 mm. Although reliable, the relatively large MDC suggest that clinically derived ultrasound measurements of muscle architecture in GM and GL are more likely to be useful to detect differences between populations than to detect changes in muscle architecture following interventions.

Does having a voice disorder hurt credibility?

OBJECTIVE: The purpose of the study was to determine whether listeners were less likely to believe a statement that is produced in an atypical voice, as compared to a typical voice. It was hypothesized that an atypical voice, characterized by abnormal roughness, strain, and pitch, would elicit increased skepticism. This hypothesis was based on previous evidence that there are negative stereotypes against individuals who have a voice disorder, and that increased difficulty processing an utterance can lead to disbelief. METHODS: In Experiment 1, 36 listeners rated obscure trivia statements (such as "the elephant is the only mammal that cannot jump" and "the first public library was opened in Vienna in 1745") as definitely false, probably false, probably true, or definitely true. The statements were produced by a speaker who used their typical voice and simulated an atypical voice (of severe deviance according to the CAPE-V), as well as two additional control speakers with typical voices. Experiment 2 was a replication of Experiment 1 with a new set of 36 listeners and a new set of speakers. In addition, Experiment 2 examined whether reduced credibility was due to negative stereotypes and/or processing difficulty, through questionnaire data and correlation analyses. RESULTS: The results were largely consistent with the hypothesis that statements produced in an atypical voice would be perceived as less credible. In both experiments, the percentage of definitely false ratings was higher for the atypical voice than for the typical voice and control voices, with a large effect size in Experiment 1 and a medium effect size in Experiment 2. Further, Experiment 2 suggested that reduced credibility was due to negative stereotypes but not processing difficulty. CONCLUSION: The current study reveals a social consequence of having a voice disorder, i.e., decreased perceived credibility, with implications for job-related success.

Pair Scanning: Integrating the Student Sonographer Without Impacting Patient Care.

OBJECTIVES: Ultrasound departments in Canada frequently reduce patient bookings to support student training, which impacts not only patient care but also revenue generation. Therefore, physicians and employers are reluctant to host student sonographers, and educational programs struggle to find sufficient clinical placements for their students. Two research questions were investigated: (1) Can a pair scanning technique effectively integrate the student sonographer into the workplace without impacting patient volumes? (2) Does the pair scanning technique prepare the student sonographer for entry-level practice faster than traditional practice? METHODS: This research project was divided into 2 phases. The first phase used action research to develop the pair scanning protocol at a single site with a single preceptor and student. The second phase used a mixed methods approach to test the transferability of the pair scanning protocol across multiple sites, preceptors, and students. RESULTS: In phase 1, the student sonographer performed a greater number of total examinations than the rest of her cohort (who were at different placement sites), and the higher performance of independent examinations by the student sonographer under the pair scanning technique was statistically significant [H(4) = 36.297; P < .01]. In phase 2, the pair scanning group and the control group performed equally, with no statistically significant differences. CONCLUSIONS: The pair scanning protocol is effective at integrating the student sonographer into the work flow without impacting patient care. It prepares the student sonographer for entry-level practice equally with traditional practice and may be most effective with the weak to average student.

Mental health literacy among refugee communities: differences between the Australian lay public and the Iraqi and Sudanese refugee communities.

PURPOSE: This study investigated differences in mental health knowledge and beliefs between participants from the Iraqi and Sudanese refugee communities, and Australian-born individuals, in Sydney, Australia. METHODS: Ninety-seven participants were given vignettes of characters describing symptoms of major depressive disorder and posttraumatic stress. They were required to identify psychological symptoms as disorders, rate beliefs about the causes of and helpful treatments for these disorders, and rate attitude statements regarding the two characters. RESULTS: Australian participants recognized the presented symptoms as specific mental disorders significantly more than Iraqi and Sudanese participants did, and reported causal and treatment beliefs which were more congruent with expert beliefs as per the western medical model of mental disorder. The Sudanese group endorsed supernatural and religious causal beliefs regarding depression and posttraumatic stress symptoms most often; but both Sudanese and Iraqi participants strongly supported options from the supernatural and religious treatment items. However, evidence for pluralistic belief systems was also found. CONCLUSIONS: Although sampling was non-random, suggesting caution in the interpretation of results, it appears that the mental health literacy of lay Australians may be more aligned with the western medical model of mental disorder than that of Iraqi and Sudanese refugee communities. Mental health literacy support needs of Iraqi and Sudanese refugee communities resettled in western countries such as Australia might include education about specific symptoms and causes of mental disorder and the effectiveness of psychiatric treatments. These findings provide useful directions for the promotion of optimal service utilization among such communities.