Effects of Stimulus Type on 16-kHz Detection Thresholds.

OBJECTIVES: Audiometric testing typically does not include frequencies above 8 kHz. However, recent research suggests that extended high-frequency (EHF) sensitivity could affect hearing in natural communication environments. Clinical assessment of hearing often employs pure tones and frequency-modulated (FM) tones interchangeably regardless of frequency. The present study was designed to evaluate how the stimulus chosen to measure EHF thresholds affects estimates of hearing sensitivity. DESIGN: The first experiment used standard audiometric procedures to measure 8- and 16-kHz thresholds for 5- to 28-year olds with normal hearing in the standard audiometric range (250 to 8000 Hz). Stimuli were steady tones, pulsed tones, and FM tones. The second experiment tested 18- to 28-year olds with normal hearing in the standard audiometric range using psychophysical procedures to evaluate how changes in sensitivity as a function of frequency affect detection of stimuli that differ with respect to bandwidth, including bands of noise. Thresholds were measured using steady tones, pulsed tones, FM tones, narrow bands of noise, and one-third-octave bands of noise at a range of center frequencies in one ear. RESULTS: In experiment 1, thresholds improved with increasing age at 8 kHz and worsened with increasing age at 16 kHz. Thresholds for individual participants were relatively similar for steady, pulsed, and FM tones at 8 kHz. At 16 kHz, mean thresholds were approximately 5 dB lower for FM tones than for steady or pulsed tones. This stimulus effect did not differ as a function of age. Experiment 2 replicated this greater stimulus effect at 16 kHz than at 8 kHz and showed that the slope of the audibility curve accounted for these effects. CONCLUSIONS: Contrary to prior expectations, there was no evidence that the choice of stimulus type affected school-age children more than adults. For individual participants, audiometric thresholds at 16 kHz were as much as 20 dB lower for FM tones than for steady tones. Threshold differences across stimuli at 16 kHz were predicted by differences in audibility across frequency, which can vary markedly between listeners. These results highlight the importance of considering spectral width of the stimulus used to evaluate EHF thresholds.

Priority populations' experiences of isolation, quarantine and distancing for COVID-19: protocol for a longitudinal cohort study (Optimise Study).

INTRODUCTION: Longitudinal studies can provide timely and accurate information to evaluate and inform COVID-19 control and mitigation strategies and future pandemic preparedness. The Optimise Study is a multidisciplinary research platform established in the Australian state of Victoria in September 2020 to collect epidemiological, social, psychological and behavioural data from priority populations. It aims to understand changing public attitudes, behaviours and experiences of COVID-19 and inform epidemic modelling and support responsive government policy. METHODS AND ANALYSIS: This protocol paper describes the data collection procedures for the Optimise Study, an ongoing longitudinal cohort of ~1000 Victorian adults and their social networks. Participants are recruited using snowball sampling with a set of seeds and two waves of snowball recruitment. Seeds are purposively selected from priority groups, including recent COVID-19 cases and close contacts and people at heightened risk of infection and/or adverse outcomes of COVID-19 infection and/or public health measures. Participants complete a schedule of monthly quantitative surveys and daily diaries for up to 24 months, plus additional surveys annually for up to 48 months. Cohort participants are recruited for qualitative interviews at key time points to enable in-depth exploration of people's lived experiences. Separately, community representatives are invited to participate in community engagement groups, which review and interpret research findings to inform policy and practice recommendations. ETHICS AND DISSEMINATION: The Optimise longitudinal cohort and qualitative interviews are approved by the Alfred Hospital Human Research Ethics Committee (# 333/20). The Optimise Study CEG is approved by the La Trobe University Human Ethics Committee (# HEC20532). All participants provide informed verbal consent to enter the cohort, with additional consent provided prior to any of the sub studies. Study findings will be disseminated through public website (https://optimisecovid.com.au/study-findings/) and through peer-reviewed publications. TRIAL REGISTRATION NUMBER: NCT05323799.

The effect of increased collect pump rate on collection efficiency in hematopoietic progenitor cell collection by apheresis in allogeneic adult donors-A single center analysis.

BACKGROUND: Optimizing CD34 recovery while minimizing harm to hematopoietic progenitor cell donors by apheresis (HPC(A) donors) is critical to the success of allogeneic hematopoietic cell transplantation. We examined the efficacy and safety of starting allogeneic HPC(A) donors at a collect pump rate (CPR) of 2 mL/min on the Spectra Optia regardless of the inlet flow rate and/or pre-apheresis white blood cell (WBC) count (high CPR group). STUDY DESIGN AND METHODS: A single-center retrospective study was performed on allogeneic adult donors from 10/2020 to 12/2022. From 10/2020 to 6/19/2022, all donors had CPR of ~1 mL/min (historical group). High CPR group started 6/20/2022. RESULTS: During the study period, 412 donors were in historical group versus 196 (32.2%) in high CPR group. Median CD34 collection efficiency (CE) was higher and more consistent in high CPR group (55.1% vs. 53% in historical group, p < .0001) and remained significant in multivariate analysis. Although product volume was higher in high CPR group, WBC, hematocrit, and platelet concentrations were significantly lower. No difference in engraftment outcomes in patients receiving products from two groups was observed. Moreover, no differences occurred in a significant peri-procedural adverse event or percent decrease in platelets (6.87% decrease in platelets per 100 × 106 CD34 cells collected versus 6.66% in historical group, p = .89). Furthermore, high CPR group had ~26 min less in collection time for every 100 × 106 CD34 cells collected, resulting in less positive fluid balances. CONCLUSIONS: Starting allogeneic HPC(A) donor collection at a CPR of 2 mL/min is safe and effective.

I know what you did last summer: a cross-sectional study of personal COVID-19 risk reduction strategies used by Victorian adults, December 2021-January 2022.

OBJECTIVE: We describe COVID-19 risk reduction strategies adopted by Victorian adults during December 2021-January 2022, a period of high COVID-19 infection and limited government mandated public health measures. METHODS: In February 2022, participants of a Victorian-based cohort study (Optimise) completed a cross-sectional survey on risk reduction behaviours during December 2021-January 2022. Regression modelling estimated the association between risk reduction and demographics. RESULTS: A total of 556 participants were included (median age 47 years; 75% women; 82% in metropolitan Melbourne). Two-thirds (61%) adopted at least one risk reduction behaviour, with uptake highest among younger participants (18-34 years; adjusted relative risk (aRR): 1.20, 95% confidence interval [CI]: 1.01, 1.41) and those with a chronic health condition (aRR: 1.17, 95% CI: 1.02, 1.35). CONCLUSIONS: Participants adopted their own COVID-19 risk reduction strategies in a setting of limited government restrictions, with young people more likely to adopt a risk reduction strategy that did not limit social mobility. IMPLICATION FOR PUBLIC HEALTH: A public health response to COVID-19 that focusses on promoting personal risk reduction behaviours, as opposed to mandated restrictions, could be enhanced by disseminating information on and increasing availability of effective risk reduction strategies tailored to segments of the population.

Recruiting and retaining community-based participants in a COVID-19 longitudinal cohort and social networks study: lessons from Victoria, Australia.

BACKGROUND: Longitudinal studies are critical to informing evolving responses to COVID-19 but can be hampered by attrition bias, which undermines their reliability for guiding policy and practice. We describe recruitment and retention in the Optimise Study, a longitudinal cohort and social networks study that aimed to inform public health and policy responses to COVID-19. METHODS: Optimise recruited adults residing in Victoria, Australia September 01 2020-September 30 2021. High-frequency follow-up data collection included nominating social networks for study participation and completing a follow-up survey and four follow-up diaries each month, plus additional surveys if they tested positive for COVID-19 or were a close contact. This study compared number recruited to a-priori targets as of September 302,021, retention as of December 31 2021, comparing participants retained and not retained, and follow-up survey and diary completion October 2020-December 2021. Retained participants completed a follow-up survey or diary in each of the final three-months of their follow-up time. Attrition was defined by the number of participants not retained, divided by the number who completed a baseline survey by September 302,021. Survey completion was calculated as the proportion of follow-up surveys or diaries sent to participants that were completed between October 2020-December 2021. RESULTS: At September 302,021, 663 participants were recruited and at December 312,021, 563 were retained giving an overall attrition of 15% (n = 100/663). Among the 563 retained, survey completion was 90% (n = 19,354/21,524) for follow-up diaries and 89% (n = 4936/5560) for monthly follow-up surveys. Compared to participants not retained, those retained were older (t-test, p <  0.001), and more likely to be female (χ2, p = 0.001), and tertiary educated (χ2, p = 0.018). CONCLUSION: High levels of study retention and survey completion demonstrate a willingness to participate in a complex, longitudinal cohort study with high participant burden during a global pandemic. We believe comprehensive follow-up strategies, frequent dissemination of study findings to participants, and unique data collection systems have contributed to high levels of study retention.

Inclusion of Cultural and Linguistic Diversity in COVID-19 Public Health Research: Research Design Adaptations to Seek Different Perspectives in Victoria, Australia.

Participation of people from culturally and linguistically diverse (CALD) communities in public health research is often limited by challenges with recruitment, retention and second-language data collection. Consequently, people from CALD communities are at risk of their needs being marginalised in public health interventions. This paper presents intrinsic case analyses of two studies which were adapted to increase the cultural competence of research processes. Both cases were part of the Optimise study, a major mixed methods research study in Australia which provided evidence to inform the Victorian state government's decision-making about COVID-19 public health measures. Case study 1 involved the core Optimise longitudinal cohort study and Case study 2 was the CARE Victorian representative survey, an Optimise sub-study. Both case studies engaged cultural advisors and bilingual staff to adjust the survey measures and research processes to suit target CALD communities. Reflexive processes provided insights into the strengths and weaknesses of the inclusive strategies. Selected survey results are provided, demonstrating variation across CALD communities and in comparison to participants who reported speaking English at home. While in most cases a gradient of disadvantage was evident for CALD communities, some patterns were unexpected. The case studies demonstrate the challenge and value of investing in culturally competent research processes to ensure research guiding policy captures a spectrum of experiences and perspectives.

Estimating the proportion of Victorians infected with COVID-19 during the Omicron BA.1 epidemic wave of January 2022 in Australia.

OBJECTIVE: To estimate the proportion of Victorians infected with COVID-19 in January 2022. METHODS: Between 11-19 February 2022 we conducted a nested cross-sectional survey on experiences of COVID-19 testing, symptoms, test outcome and barriers to testing during January 2022 in Victoria, Australia. Respondents were participants of the Optimise Study, a prospective cohort of adults considered at increased risk of COVID-19 or the unintended consequences of COVID-19-related interventions. RESULTS: Of the 577 participants, 78 (14%) reported testing positive to COVID-19, 240 (42%) did not test in January 2022 and 91 of those who did not test (38%) reported COVID-19-like symptoms. Using two different definitions of symptoms, we calculated symptomatic (27% and 39%) and asymptomatic (4% and 11%) test positivity. We extrapolated these positivity rates to participants who did not test and estimated 19-22% of respondents may have had COVID-19 infection in January 2022. CONCLUSION: The proportion of Victorians infected with COVID-19 in January 2022 was likely considerably higher than officially reported numbers. IMPLICATIONS FOR PUBLIC HEALTH: Our estimate is approximately double the COVID-19 case numbers obtained from official case reporting. This highlights a major limitation of diagnosis data that must be considered when preparing for future waves of infection.

Non-invasive prenatal screening for fetal triploidy using single nucleotide polymorphism-based testing: Differential diagnosis and clinical management in cases showing an extra haplotype.

OBJECTIVE: An extra haplotype is infrequently encountered in single nucleotide polymorphism(SNP)-based non-invasive prenatal testing (NIPT) and is usually attributed to an undetected twin or triploidy. We reviewed a large series to establish relative frequencies of these outcomes and identify alternative causes. METHODS: In 515,804 women receiving NIPT from September 2017 through March 2019, all results with an extra haplotype were reviewed. Known viable and vanished twin pregnancies were excluded. For positive cases, pregnancy outcome information was sought. RESULTS: Of 1005 results with an extra haplotype (1 in 513), pregnancy outcome was available for 773 cases: 11% were confirmed or suspected triploidy; 65% to vanished twin; 10% with pregnancy loss. Rare explanations included complete mole, chimera, undisclosed donor egg pregnancy, maternal organ transplant and one instance of maternal neoplasm. Among triploid cases that were detected and independently confirmed, 23/27 (85%) were diandric. CONCLUSION: SNP-based NIPT, with detection of an extra haplotype, is 11% predictive of triploidy. For results with an extra haplotype, ultrasound is recommended to establish viability, evaluate for twins (viable or vanished), and detect findings consistent with triploidy. Review of patient history, serum screening, and ultrasound will reduce the number of CVS or amniocenteses necessary to confirm a diagnosis of triploidy.

Building point-of-care ultrasound capacity in rural emergency departments: An educational innovation.

INTRODUCTION: Point-of-care ultrasound (POCUS) use is the standard of care in emergency medicine (EM), but rural physicians face barriers to obtaining and retaining this skill and cite low confidence in their use of POCUS. Without access to high-quality educational opportunities, this important clinical tool may not be used to its full potential in rural hospitals. The Hands-On Ultrasound Education (HOUSE) programme, launched in 2015 by the University of British Columbia's (BC) Division of Rural Continuing Professional Development, is a rurally focused POCUS training and education programme that travels to rural and remote communities and aims to build a rural POCUS community of practice within BC. In this study, we present and evaluate the HOUSE programme. METHODS: The HOUSE programme is described. A comprehensive qualitative evaluation of semi-structured interviews pertaining to HOUSE was conducted in the 4th year of the programme to assess participant experience and programme outcomes. RESULTS: Results from 52 semi-structured interviews indicate that there is a significant increase in self-reported confidence on specific POCUS applications and increased POCUS use after completion of the course, and we report positive experiences with the HOUSE programme. CONCLUSION: By providing a customizable, accessible, hands-on training opportunity, the HOUSE programme removes barriers to POCUS training and education for physicians in rural and remote BC. The rurally focused elements have contributed to education for rural participants that demonstrates increased confidence and the use of POCUS as a clinical tool.

Résumé Introduction: L'échographie ciblée est la norme de soins en médecine d'urgence, mais les médecins des régions rurales ont de la difficulté à acquérir et à retenir cette compétence, et affirment avoir peu d'assurance à utiliser l'échographie ciblée. Privés d'activités d'apprentissage de bonne qualité, les médecins des hôpitaux ruraux n'utilisent pas pleinement cet important outil clinique. Le programme Hands-On Ultrasound Education (HOUSE), lancé en 2015 par la division de formation professionnelle continue en milieu rural de l'Université de la Colombie-Britannique, est un programme de formation axé sur la pratique rurale portant sur l'échographie ciblée. Le programme se déplace dans les communautés rurales et éloignées et il vise à créer une communauté de pratique rurale sur l'échographie ciblée en Colombie-Britannique. Dans cette étude, nous présentons et évaluons le programme HOUSE. Méthodes: Description du programme HOUSE. Une évaluation qualitative complète d'entrevues semi-structurées portant sur HOUSE a été réalisée durant la quatrième année du programme dans le but d'évaluer l'expérience des participants et les résultats du programme. Résultats: Les résultats de 52 entrevues semi-structurées indiquent que la confiance rapportée à l'égard de certaines applications d'échographie ciblée a significativement augmenté, et que l'utilisation de l'échographie ciblée a augmenté après le cours, et nous rapportons des expériences positives envers le programme HOUSE. Conclusion: En offrant des activités d'apprentissage personnalisables, accessibles et pratiques, le programme HOUSE fait tomber les obstacles à la formation sur l'échographie ciblée des médecins des régions rurales et éloignées de la C.-B. Les éléments axés sur les régions rurales ont contribué à l'éducation des participants ruraux qui démontrent une plus grande confiance et une plus grande utilisation de l'échographie ciblée comme outil clinique. Mots-clés: échographie ciblée, formation médicale, médecine d'urgence en milieu rural.

Comparing 2 Years of Empowering Families to Solve Real-World Problems with AI.

Over the course of 2 years a global technology education nonprofit engaged ~ 20,000 under-resourced 3rd-8th grade students, parents and educators from 13 countries in a multi-week AI competition. Families worked together with the help of educators to identify meaningful problems in their communities and developed AI-prototypes to address them. Key findings included: (1) Identifying a high level of interest in underserved communities to develop and apply AI-literacy skills; (2) Determining curricular and program implementation elements that enable families to apply AI knowledge and skills to real problems; (3) Identifying effective methods of engaging industry mentors to support participants; (4) Measuring and identifying changes in self-efficacy and ability to apply AI-based tools to real-world problems; (5) Determining effective curricula around value-sensitive design and ethical innovation.

Thumb-Rest Position and its Role in Neuromuscular Control of the Clarinet Task.

Musicians spend long hours of practice and performance to master their instrument. Clarinet players support their roughly 2-lb instrument on the right-hand thumb, which results in cumulative static loading of the arm. This posture in turn can cause discomfort and, in some cases, evolve into debilitating overuse injuries and pain throughout the right upper limb. Altering the thumb-rest position has been proposed as a way to alleviate this discomfort, although no quantitative research has been conducted on this issue. The purpose of this study was to address the impact of thumb-rest position on the neuromuscular control of holding the clarinet. Surface electromyographic recordings of superficial muscles that control the right thumb, wrist, and arm were taken during realistic playing tasks. Twenty clarinetists performed 10 held notes and 10 exercises on the three different thumb-rest positions. The notes and exercises were chosen to isolate specific elements of playing. We hypothesized that a high thumb-rest position would result in a significantly different balance of muscle activity than traditional and low thumb-rest positions. The patterns of muscle activity recorded among clarinetists were idiosyncratic, but for all players these patterns were influenced by the note(s) played and thumb-rest position, and thus the hypothesis was partially supported. Muscles that acted on the thumb and wrist were most influenced by thumb-rest position. These results support the notion that adjustment of thumb-rest position may be a useful way to alleviate discomfort in the supporting limb but must be evaluated for each individual.

Intraoperative passive knee kinematics during total knee arthroplasty surgery.

Surgical navigation systems for total knee arthroplasty (TKA) surgery are capable of capturing passive three-dimensional (3D) angular joint movement patterns intraoperatively. Improved understanding of patient-specific knee kinematic changes between pre and post-implant states and their relationship with post-operative function may be important in optimizing TKA outcomes. However, a comprehensive characterization of the variability among patients has yet to be investigated. The objective of this study was to characterize the variability within frontal plane joint movement patterns intraoperatively during a passive knee flexion exercise. Three hundred and forty patients with severe knee osteoarthritis (OA) received a primary TKA using a navigation system. Passive kinematics were captured prior to (pre-implant), and after prosthesis insertion (post-implant). Principal component analysis (PCA) was used to capture characteristic patterns of knee angle kinematics among patients, to identify potential patient subgroups based on these patterns, and to examine the subgroup-specific changes in these patterns between pre- and post-implant states. The first four extracted patterns explained 99.9% of the diversity within the frontal plane angle patterns among the patients. Post-implant, the magnitude of the frontal plane angle shifted toward a neutral mechanical axis in all phenotypes, yet subtle pattern (shape of curvature) features of the pre-implant state persisted.

What do medical trainees think is so difficult about communicating with patients?

OBJECTIVE: To identify the communication skills medical trainees perceive themselves to avoid or use during initial clinical encounters and the areas of communication learning need they identify. METHODS: 446 2nd year undergraduate medical students were invited to take part in the study. Details of four encounters with patients were entered into a web-based electronic logbook by the student. Details included perception of use, success and requests for further training from a list of communication process skills. RESULTS: 395 (89%) students took part. Factor analysis yielded three types of skills: those used to manage the flow of interaction; the emotional content of the interaction; and structuring the interaction. Skills perceived as being used least often and least successfully and identified by the students as requiring further training were primarily those that involved managing the emotional aspects of interactions with patients rather than managing the flow of information. CONCLUSION: Communication training should focus further on the emotional aspects of patient interactions in order to support students during early clinical encounters. PRACTICE IMPLICATIONS: Skills required to manage emotional encounters need to be made more explicit to students. Opportunities to obtain feedback and develop competency should be offered as part of the core curriculum.

Genetic manipulation of Campylobacter jejuni.

Molecular manipulation has been a limiting factor in C. jejuni research for many years. Recent advances in molecular techniques adapted for C. jejuni have furthered our understanding of the organism. This unit is dedicated to common molecular tools in bacterial research specifically tailored for C. jejuni. These include colony PCR, DNA isolation, and RNA isolation. The unit also reviews techniques for genetic manipulation, such as the use of plasmids, natural transformation, electroporation, conjugation, and transposition. In addition, a reporter system, the arylsulfatase assay, can be used to study gene expression.

Campylobacter jejuni: molecular biology and pathogenesis.

Campylobacter jejuni is a foodborne bacterial pathogen that is common in the developed world. However, we know less about its biology and pathogenicity than we do about other less prevalent pathogens. Interest in C. jejuni has increased in recent years as a result of the growing appreciation of its importance as a pathogen and the availability of new model systems and genetic and genomic technologies. C. jejuni establishes persistent, benign infections in chickens and is rapidly cleared by many strains of laboratory mouse, but causes significant inflammation and enteritis in humans. Comparing the different host responses to C. jejuni colonization should increase our understanding of this organism.

Biochemical characterization of the active heterodimer form of human heparanase (Hpa1) protein expressed in insect cells.

The mammalian endoglycosidase heparanase (Hpa1) is primarily responsible for cleaving heparan sulphate proteoglycans (HSPGs) present on the basement membrane of cells and its potential for remodelling the extracellular matrix (ECM) could be important in embryonic development and tumour metastasis. Elevated expression of this enzyme has been implicated in various pathological processes including tumour cell proliferation, metastasis, inflammation and angiogenesis. The enzyme therefore represents a potential therapeutic target. Hpa1 protein is initially synthesized as an inactive 65 kDa proenzyme that is then believed to be subsequently activated by proteolytic cleavage to generate an active heterodimer of 8 and 50 kDa polypeptides. By analysis of a series of Hpa1 deletion proteins we confirm that the 8 kDa subunit is essential for enzyme activity. We present here for the first time an insect cell expression system used for the generation of large amounts of recombinant protein of high specific activity. Individual subunits were cloned into baculoviral secretory vectors and co-expressed in insect cells. Active secreted heterodimer protein was recovered from the medium and isolated by a one-step heparin-Sepharose chromatography procedure to give protein of >90% purity. The recombinant enzyme behaved similarly to the native protein with respect to the size of HS fragments liberated on digestion, substrate cleavage specificity and its preference for acidic pH. A significant amount of activity, however, was also detectable at physiological pH values, as measured both by an in vitro assay and by in vivo degradation of cell-bound heparan sulphate.