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Summary: Background: In response to the COVID-19 pandemic, Victoria’s largest maternity service provider implemented a telehealth-integrated antenatal care (ANC) schedule for high- and low-risk pregnancies. The program has been maintained since March 2020. Given ever-increasing healthcare costs, economic evaluation is crucial to ensure value and guide ongoing use. Methods: The aim of the study was to perform a cost-minimisation analysis of telehealth integrated ANC compared to conventional in-person ANC, from the hospital and patient perspectives. We hypothesised that the costs associated with telehealth integrated ANC would be less than in-person ANC. We generated propensity score matched pre- and post-telehealth cohorts from women with a singleton pregnancy who received ANC and birthed at Monash Health from 1 Jan 2018–22 Mar 2020 (pre-telehealth), and 20 Apr 2020–31 Dec 2021 (post-telehealth). Data were extracted from electronic medical and finance records. We assigned costs for all Monash Health outpatient, inpatient, and emergency department episodes to calculate mean cost per birth. Patient travel costs were estimated based on distance residing from hospital. Findings: Matched pre- and post-telehealth cohorts of n = 13,534 each were created. There were no significant differences in stillbirth, pre-eclampsia, severe maternal morbidity, or death. There was a AU$133 (0.98%, 95% CI [−0.17%, 2.16%]) increase in cost per birth in the post-telehealth cohort. This was driven by increased hospital costs (AU$340 or 2.64% increase, [1.44%, 3.86%]), due to a 4.78% increase in antenatal inpatient episodes and 3.51% increase in outpatient appointments post-telehealth. Increased care complexity was noted in the post-telehealth period with increased rates of gestational diabetes, caesarean birth, and specialty-led care (p-values all

Circumcision is a common procedure performed since ancient times with an excellent safety profile and potential health benefits. In the United States, it is commonly performed in the neonatal period using devices such as the Gomco, Mogen, or Plastibell device. In the rare circumstance of a complication, it is often related to bleeding and usually managed conservatively. However, complications requiring surgical intervention can occur and remind practitioners of the importance of proper equipment and technique. Herein, we report a case in which extensive injuries to the penile skin after neonatal circumcision using a Gomco clamp required emergent intervention.

ABSTRACT Trypanosomatids are single-celled parasites responsible for human and animal disease. Typically, colonization of an insect host is required for transmission. Stable attachment of parasites to insect tissues via their single flagellum coincides with differentiation and morphological changes. Although attachment is a conserved stage in trypanosomatid life cycles, the molecular mechanisms are not well understood. To study this process, we elaborate upon an in vitro model in which the swimming form of the trypanosomatid Crithidia fasciculata rapidly differentiates following adhesion to artificial substrates. Live imaging of cells transitioning from swimming to attached shows parasites undergoing a defined sequence of events, including an initial adhesion near the base of the flagellum immediately followed by flagellar shortening, cell rounding, and the formation of a hemidesmosome-like attachment plaque between the tip of the shortened flagellum and the substrate. Quantitative proteomics of swimming versus attached parasites suggests differential regulation of cyclic adenosine monophosphate (cAMP)-based signaling proteins. We have localized two of these proteins to the flagellum of swimming C. fasciculata; however, both are absent from the shortened flagellum of attached cells. Pharmacological inhibition of cAMP phosphodiesterases increased cAMP levels in the cell and prevented attachment. Further, treatment with inhibitor did not affect the growth rate of either swimming or established attached cells, indicating that its effect is limited to a critical window during the early stages of adhesion. These data suggest that cAMP signaling is required for attachment of C. fasciculata and that flagellar signaling domains may be reorganized during differentiation and attachment.IMPORTANCETrypanosomatid parasites cause significant disease burden worldwide and require insect vectors for transmission. In the insect, parasites attach to tissues, sometimes dividing as attached cells or producing motile, infectious forms. The significance and cellular mechanisms of attachment are relatively unexplored. Here, we exploit a model trypanosomatid that attaches robustly to artificial surfaces to better understand this process. This attachment recapitulates that observed in vivo and can be used to define the stages and morphological features of attachment as well as conditions that impact attachment efficiency. We have identified proteins that are enriched in either swimming or attached parasites, supporting a role for the cyclic AMP signaling pathway in the transition from swimming to attached. As this pathway has already been implicated in environmental sensing and developmental transitions in trypanosomatids, our data provide new insights into activities required for parasite survival in their insect hosts.

ABSTRACT Introduction The Activating Lived Experience Leadership (ALEL) project was a South Australian participatory action research project that aimed to improve the ways lived experience is recognised, valued and integrated across mental health and social sector systems. ALEL was completed during 2019–2021, where it engaged 182 participants in generating community action and research knowledge. Objective Our paper discusses the project's processes of building a collective partnership among lived experience leaders and other leaders from within the sector, so that the actions and strategies identified through research could be implemented by systems‐level impact. We describe the collaborative process and key learnings that resulted in eight key action areas for transformative systems change in South Australia. Methods The project invited a diverse range of self‐identified lived experience and other leaders to be involved in a PAR process featuring formal qualitative research (focus groups, surveys and interviews) as well as community development activities (leaders' summit meetings, consultations, training and community of practice meetings). These processes were used to help us describe the purpose, achievements and potential of lived experience leadership. Project priorities and systems‐level analysis was also undertaken with lived experience sector leaders and project advisors across two leaders' summit meetings, integrating research outcomes with sector planning to define high‐level actions and a vision for transformational change. Results Participatory action research as informed by systems change and collective impact strategies assisted the project to generate detailed findings about the experiences and complexities of lived experience leadership, and collective responses of how systems could better support, be accountable to and leverage lived experience perspectives, experience and peer‐work approaches. Conclusion Systems change to define, value and embed lived experience leadership benefits from collective efforts in both formal research and sector development activities. These can be used to generate foundational understandings and guidance for working together in genuine ways for transforming mental health and social sector systems, experience and outcomes. Public Contribution Members of lived experience communities codesigned the project, and contributed to project governance and the development of all findings and project reports.

ABSTRACT Lyme disease is the most common tick-borne disease in North America. A vaccine for use in humans is not available. Here, we detail the development of two chimeric vaccine antigens, BAF and Chv2M. BAF elicits Abs that target proteins and protein variants produced by Borreliella species in ticks (OspB and OspA) and mammals (FtlA/B). OspB serves as the backbone structure for the BAF chimeric. Two OspA221-240 epitope-containing domain (ECD) variants (#A1 and #A15) were inserted into a loop in OspB. The N-terminal region of the FtlA protein was joined to the C-terminus of the chimeric. The second chimeric, Chv2M, consists of L5 (loop 5) and H5 (helix 5) ECDs derived from diverse OspC proteins. Borreliella species produce OspC upon exposure to the bloodmeal and during early infection in mammals. Here, we demonstrate that BAF and Chv2M are potent immunogens that elicit Abs that bind to each component protein (FtlA, FtlB, OspB, and multiple OspA and OspC variants). Anti-BAF and anti-Chv2M Abs kill Borreliella burgdorferi strains through Ab-mediated complement-dependent and complement-independent mechanisms. Eighty percent (32/40) of mice that received a three-dose vaccine regimen were protected from infection with B. burgdorferi B31. Efficacy increased to 90% (18/20) when the amount of Chv2M was increased in the third vaccine dose. Readouts for infection were flaB PCR and seroconversion to VlsE. This study establishes proof of principle for a chimeric immunogen vaccine formulation that elicits Abs to multiple targets on the B. burgdorferi cell surface produced during tick and mammalian stages of the enzootic cycle.IMPORTANCELyme disease is a growing public health threat across parts of the Northern Hemisphere. Regions that can support sustained tick populations are expanding, and the incidence of tick-borne diseases is increasing. In light of the increasing risk of Lyme disease, effective preventive strategies are needed. Most vaccine development efforts have focused on outer surface protein A, a Borreliella burgdorferi protein produced only in ticks. Herein, we describe the development of a novel vaccine formulation consisting of two multivalent chimeric proteins that are immunogenic and elicit antibodies with bactericidal activity that target several cell surface proteins produced by the Lyme disease spirochetes in feeding ticks and mammals. In a broader sense, this study advances efforts to develop custom-designed vaccinogens comprised of epitope-containing domains from multiple proteins.

The aim of this research was to establish prevalence estimates for aphantasia, hypophantasia, typical imagery ability, and hyperphantasia in a large multi-national cohort. In Study 1, the Vividness of Visual Imagery Questionnaire was completed by 3,049 participants. Results indicated prevalence estimates of 1.2% for aphantasia, 3% for hypophantasia, 89.9% for typical imagery ability, and 5.9% for hyperphantasia. In Study 2, to replicate these findings in a larger sample, the Study 1 data were combined with openly available data from previous prevalence studies to create a total sample of 9,063 participants. Re-analysis of this data confirmed prevalence estimates of 0.9% for aphantasia, 3.3% for hypophantasia, 89.7% for typical imagery ability, and 6.1% for hyperphantasia. These robust and up-to-date estimates provide enhanced clarity to researchers regarding the prevalence of differing visual imagery abilities and provide a platform for future studies exploring the role of visual imagery in various cognitive and behavioral tasks.

IntroductionInfants with congenital diaphragmatic hernia can suffer severe respiratory insufficiency and pulmonary hypertension after birth. Aerating the lungs before removing placental support (physiologically based cord clamping, PBCC) increases pulmonary blood flow (PBF) and reduces pulmonary vascular resistance (PVR) in lambs with a diaphragmatic hernia (DH). We hypothesized that these benefits of PBCC persist for at least 8 h after birth.MethodsAt ∼138 days of gestation age (dGA), 21 lambs with a surgically induced left-sided DH (∼86 dGA) were delivered via cesarean section. The umbilical cord was clamped either before ventilation onset (immediate cord clamping, ICC, n = 9) or after achieving a tidal volume of 4 ml/kg, with a maximum delay of 10 min (PBCC, n = 12). The lambs were ventilated for 8 h, initially with conventional mechanical ventilation, but were switched to high-frequency oscillatory ventilation after 30 min if required. Ventilatory parameters, cardiopulmonary physiology, and arterial blood gases were measured throughout the study.ResultsPBF increased after ventilation onset in both groups and was higher in the PBCC DH lambs than the ICC DH lambs at 8 h (5.2 ± 1.2 vs. 1.9 ± 0.3 ml/min/g; p

Cochlear implants (CIs) provide hundreds of thousands of users with increased access to sound, particularly speech, but experiences of music are more varied. Can greater engagement by CI users in the music mixing process mutually benefit them as well as audio engineers? This paper presents an exploratory mixed-methods study that leverages insights from CI users and professional audio engineers (AEs) in the investigation of techniques to enhance CI user music enjoyment and promote empathetic practices in AEs. Analysis of data collected over a multi-step process of surveys, interviews, and iterative cycles of sound mixing and feedback revealed two mixing strategies—namely essentializing and exaggeration of musical elements—common among mixes preferred by CI users. Participant responses also highlighted systemic ableism and audism in the music industry—an industry from which CI users report feeling excluded. Specifically, AEs felt inadequately trained around aural diversity considerations and experienced anxiety around their own aural diversity. In sum, this work contributes to insights into CI user music listening preferences; how AEs approach mixing for an aurally diverse audience; and discussion around the efficacy of CI simulation, user feedback, and AE peer feedback on mix enjoyment by CI users. Based on these findings, we offer several design insights that emphasize the need for customizable music listening tools centered around user agency and enjoyment.

The Children, Young People and Education Committee recently held an inquiry to scrutinise the Welsh Government’s progress in delivering its Programme for Government Commitment to ‘explore radical reform of current services for children looked after and care leavers’. A key observation highlighted in their report was that there was a lack of robust data collected about various aspects of the care system. Notably it was highlighted that there is a lack of data collected about permanent exclusions and suspensions from school amongst children looked after in out of home care (CLA). This study was therefore designed to fill this evidence gap. Using anonymised linked administrative data held in SAIL Databank to identify those receiving care and support (CRCS) from their local authority, rates of permanent exclusion and suspension have been determined for the different groups within the CRCS cohort (CLA, those on the child protection register (CPR) and those receiving support who are neither CLA nor CPR) which have then been compared to their peers without this experience. Factors such as phase of education, setting, free school meal entitlement, having additional learning needs, age and gender have also been considered along with the reason for the suspension or exclusion. In drawing comparisons with peers, an intersectional approach was adopted to identify disparity. It is hoped that findings from this student study will stimulate debate and contribute towards the development of changes in Welsh policy.

Objective To determine the prevalence of functional impairments in children with disabilities receiving care and support in Wales between 2016 and 2022, and to investigate risk factors associated with being placed in care amongst these children. Method This study used Children Receiving Care and Support (CRCS) Census records held in the Secure Anonymised Information Linkage Databank. We examined the proportion of children with specific impairments by their looked-after status, using bar charts and Upset plots. CRCS records were linked to demographic datasets to obtain information on area-level deprivation, and we conducted multivariable logistic regression analyses to model risk factors associated with being placed in care for children with disabilities. Results Of 38,165 children receiving care and support, 10,075 (26%) had a disability, and 3,360 (33%) of these children were placed in care. Older children were less likely to be placed in care than infants (e.g. for age group 1‒4: OR 0.37 (95% CI 0.24‒0.56)). Children of mixed ethnicity were more likely to be placed in care compared to White children (2.17 (1.65‒2.85)). Child mental health problems were associated with being placed in care (1.82 (1.60‒2.07)) as were parental mental health problems (1.44 (1.29‒1.60)), parental substance/alcohol misuse (3.16 (2.81‒3.56)), parental learning disability (2.92 (2.51‒3.38)), and domestic abuse (1.48 (1.31‒1.66)). Conclusions This new evidence may assist in the planning and provision of appropriate ongoing care and support for these children and their families to help prevent entry into the care system.

Abstract The mid‐latitude extreme weather disasters are often associated with explosively developing cyclones (ECs). Based on different vertical development characteristics, 4,608 ECs identified over the North Pacific in the cold season of 44 years of NCEP‐CFSR reanalyzes are divided into four types of upward development and four types of downward development categories. ECs with vertical upward (downward) development follow a northeastward (nearly eastward) path, mainly explosively developing over the Northwest Pacific (Asia continent and Pacific). Furthermore, utilizing the piecewise potential vorticity inversion method reveals the synergetic forcing of the turbulent heat transport and baroclinicity in the lower troposphere, the latent heat release in the middle levels, the upper‐level jet stream, and the downward intrusion of stratospheric potential vorticity on the ECs. Different configurations of these influences from the troposphere to the stratosphere result in the occurrences of eight types of ECs in the cold season over the North Pacific.

This publication is aimed to introduce “push-pull” technology and companion planting for pest management to high tunnel vegetable growers. It is also of interest to other crop producers wishing to improve their IPM practices.

Introduction:: Advice for women with pelvic organ prolapse (POP) often includes lying down to decrease the effects of gravity on the pelvic floor. The aim of this study was to compare pelvic floor morphometry before and after 30 min of supine lying in women with symptomatic POP. Methods:: Pelvic floor morphometry was assessed in vaginally parous, premenopausal women with symptomatic POP ≥ stage 1. The modified Pelvic Organ Prolapse Quantification system was used in supine to assess points Ba (anterior vaginal wall), Bp (posterior vaginal wall), and C (cervix). Transperineal ultrasound imaging was used in supine and standing to assess the following measures at rest and bearing down: bladder neck position, bladder position, rectal ampulla position, levator plate angle, anorectal angle, levator anteroposterior distance, and levator hiatal area. Measures taken before and after 30 min of supine lying were compared. Results:: Twenty-one women (median (range) age: 39 (29–50) years) with varied stages of POP (33% stage 1, 57% stage 2, and 10% stage 3) were included. Most measures of pelvic floor morphometry were unchanged after 30 min of supine lying compared to before lying. Participants had greater resting levator hiatal area in supine and levator anteroposterior distance at rest and bearing down in supine after lying down (p ≤ 0.001), suggesting reduced pelvic floor muscle activity. Conclusion:: Findings suggest that a 30-min period of supine lying does not improve support of the pelvic organs.

Traumatic brain injury (TBI) in military populations can cause disruptions in brain structure and function, along with cognitive and psychological dysfunction. Diffusion magnetic resonance imaging (dMRI) can detect alterations in white matter (WM) microstructure, but few studies have examined brain asymmetry. Examining asymmetry in large samples may increase sensitivity to detect heterogeneous areas of WM alteration in mild TBI. Through the Enhancing Neuroimaging Genetics Through Meta-Analysis Military-Relevant Brain Injury working group, we conducted a mega-analysis of neuroimaging and clinical data from 16 cohorts of Active Duty Service Members and Veterans (n = 2598). dMRI data were processed together along with harmonized demographic, injury, psychiatric, and cognitive measures. Fractional anisotropy in the cingulum showed greater asymmetry in individuals with deployment-related TBI, driven by greater left lateralization in TBI. Results remained significant after accounting for potentially confounding variables including posttraumatic stress disorder, depression, and handedness, and were driven primarily by individuals whose worst TBI occurred before age 40. Alterations in the cingulum were also associated with slower processing speed and poorer set shifting. The results indicate an enhancement of the natural left laterality of the cingulum, possibly due to vulnerability of the nondominant hemisphere or compensatory mechanisms in the dominant hemisphere. The cingulum is one of the last WM tracts to mature, reaching peak FA around 42 years old. This effect was primarily detected in individuals whose worst injury occurred before age 40, suggesting that the protracted development of the cingulum may lead to increased vulnerability to insults, such as TBI.

Accessibility to gifted programs is related to processes by which students are screened for eligibility and have knowledge of options for participation. Accessibility via websites is related to usability for all users, including those with limited technology or connectivity. The purpose of the present study was to evaluate accessibility and availability of information regarding gifted education for parents of gifted students from historically marginalized student populations. We conducted a content analysis of Florida's 74 district websites to determine accessibility and availability of gifted information. We found a disparity between accessibility based on number of clicks and availability based on embeddedness of information, although quantity of clicks was not necessarily correlated with the availability of information. Our findings led to practical implications and actionable items for educational institutions to address the potential impact of accessibility to gifted identification/program participation for students from underrepresented populations.

Abstract Background Randomized clinical trials (RCTs) are the gold standard for assessing treatment effectiveness; however, they have been criticized for generalizability issues such as how well trial participants represent those who receive the treatments in clinical practice. We assessed the representativeness of participants from eight RCTs for chronic spine pain in the U.S., which were used for an individual participant data meta-analysis on the cost-effectiveness of spinal manipulation for spine pain. In these clinical trials, spinal manipulation was performed by chiropractors. Methods We conducted a retrospective secondary analysis of RCT data to compare trial participants’ socio-demographic characteristics, clinical features, and health outcomes to a representative sample of (a) U.S. adults with chronic spine pain and (b) U.S. adults with chronic spine pain receiving chiropractic care, using secondary data from the National Health Interview Survey (NHIS) and Medical Expenditure Panel Survey (MEPS). We assessed differences between trial and U.S. spine populations using independent t-tests for means and z-tests for proportions, accounting for the complex multi-stage survey design of the NHIS and MEPS. Results We found the clinical trials had an under-representation of individuals from health disparity populations with lower percentages of racial and ethnic minority groups (Black/African American 7% lower, Hispanic 8% lower), less educated (No high school degree 19% lower, high school degree 11% lower), and unemployed adults (25% lower) with worse health outcomes (physical health scores 2.5 lower and mental health scores 5.3 lower using the SF-12/36) relative to the U.S. population with spine pain. While the odds of chiropractic use in the U.S. are lower for individuals from health disparity populations, the trials also under-represented these populations relative to U.S. adults with chronic spine pain who visit a chiropractor. Conclusions Health disparity populations are not well represented in spine pain clinical trials. Embracing key community-based approaches, which have shown promise for increasing participation of underserved communities, is needed.

Abstract Background Recent advancements in high-throughput genomics and targeted therapies have provided tremendous potential to identify and therapeutically target distinct mutations associated with cancers. However, to date the majority of targeted therapies are used to treat all functional mutations within the same gene, regardless of affected codon or phenotype. Results In this study, we developed a functional genomic analysis workflow with a unique isogenic cell line panel bearing two distinct hotspot PIK3CA mutations, E545K and H1047R, to accurately identify targetable differences between mutations within the same gene. We performed RNA-seq and ATAC-seq and identified distinct transcriptomic and epigenomic differences associated with each PIK3CA hotspot mutation. We used this data to curate a select CRISPR knock out screen to identify mutation-specific gene pathway vulnerabilities. These data revealed AREG as a E545K-preferential target that was further validated through in vitro analysis and publicly available patient databases. Conclusions Using our multi-modal genomics framework, we discover distinct differences in genomic regulation between PIK3CA hotspot mutations, suggesting the PIK3CA mutations have different regulatory effects on the function and downstream signaling of the PI3K complex. Our results demonstrate the potential to rapidly uncover mutation specific molecular targets, specifically AREG and a proximal gene regulatory region, that may provide clinically relevant therapeutic targets. The methods outlined provide investigators with an integrative strategy to identify mutation-specific targets for the treatment of other oncogenic mutations in an isogenic system.

Abstract The modification of fertile stamens into sterile staminodes has occurred independently many times in the flowering plant lineage. In the genus Aquilegia (columbine) and its closest relatives, the two stamen whorls closest to the carpels have been converted to staminodes. In Aquilegia, the only genetic analyses of staminode development have been reverse genetic approaches revealing that B-class floral identity genes are involved. A. jonesii, the only species of columbine where staminodes have reverted to fertile stamens, allows us to explore the genetic architecture of staminode development using a forward genetic approach. We performed QTL analysis using an outcrossed F2 population between A. jonesii and a horticultural variety that makes fully developed staminodes, A. coerulea ‘Origami’. Our results reveal a polygenic basis for staminode loss where the two staminode whorls are under some level of independent control. We also discovered that staminode loss in A. jonesii is not complete, in which staminode-like traits sometimes occur in the inner fertile stamens, potentially representing a fading boundary of gene expression. The QTLs identified in this study provide a map to guide future reverse genetic and functional studies examining the genetic basis and evolutionary significance of this trait.

Abstract Background This investigation evaluated the state of ultrasound imaging (USI) education in entry-level Doctor of Physical Therapy (DPT) program curricula in the USA, including faculty perceptions and qualifications regarding USI and identification of potential barriers to inclusion or expansion of USI education. A review of published literature reveals that the inclusion of USI education in entry-level DPT program curricula has not been systematically investigated and is largely unknown. Methods Investigators created an online survey developed in QualtricsXM and distributed through email an electronic link to the program chair/director at all 258 accredited entry-level DPT programs in the USA with instructions to complete and or share with faculty. Results The overall response rate was 24% (65/269) and represented 54 programs from 28 of the 50 states; 70% reported including USI education in their program’s curriculum, with 91% spending

Abstract Background Fabry disease (FD) is a rare lysosomal storage disease associated with glycolipid accumulation that impacts multiple physiological systems. We conducted a systematic literature review (SLR) to characterize the humanistic (quality of life [QoL]) and economic burden of FD. Methods Searches were conducted in the Embase, MEDLINE®, and MEDLINE® In-Process databases from inception to January 19, 2022. Conference abstracts of specified congresses were manually searched. Additional searches were performed in the Cochrane and ProQuest databases for the humanistic SLR and the National Health Service Economic Evaluations Database for the economic SLR. Studies of patients with FD of any sex, race, and age, and published in the English language were included. There was no restriction on intervention or comparator. For the humanistic SLR, studies that reported utility data, database/registry-based studies, questionnaires/surveys, and cohort studies were included. For the economic SLR, studies reporting economic evaluations or assessing the cost of illness and resource use were included. Results Of the 1363 records identified in the humanistic search, 36 studies were included. The most commonly used QoL assessments were the 36-item Short-Form Health Survey (n = 16), EQ-5D questionnaire descriptive system or visual analog scale (n = 9), and the Brief Pain Inventory (n = 8). Reduced QoL was reported in patients with FD compared with healthy populations across multiple domains, including pain, physical functioning, and depressive symptoms. Multiple variables—including sex, age, disease severity, and treatment status—impacted QoL. Of the 711 records identified in the economic burden search, 18 studies were included. FD was associated with high cost and healthcare resource use. Contributors to the cost burden included enzyme replacement therapy, healthcare, and social care. In the seven studies that reported health utility values, lower utility scores were generally associated with more complications (including cardiac, renal, and cerebrovascular morbidities) and with classical disease in males. Conclusion FD remains associated with a high cost and healthcare resource use burden, and reduced QoL compared with healthy populations. Integrating information from QoL and economic assessments may help to identify interventions that are likely to be of most value to patients with FD.

Objective: Anterior mitral anular calcification, particularly in radiation heart disease, and previous valve replacement with destroyed intervalvular fibrosa are challenging for prosthesis sizing and placement. The Commando procedure with intervalvular fibrosa reconstruction permits double-valve replacement in these challenging conditions. We referenced outcomes after Commando procedures to standard double-valve replacements. Methods: From January 2011 to January 2022, 129 Commando procedures and 1191 aortic and mitral double-valve replacements were performed at the Cleveland Clinic, excluding endocarditis. Reasons for the Commando were severe calcification after radiation (n = 67), without radiation (n = 43), and others (n = 19). Commando procedures were referenced to a subset of double-valve replacements using balancing-score methods (109 pairs). Results: Between balanced groups, Commando versus double-valve replacement had higher total calcium scores (median 6140 vs 2680 HU, P = .03). Hospital outcomes were similar, including operative mortality (12/11% vs 8/7.3%, P = .35) and reoperation for bleeding (9/8.3% vs 5/4.6%, P = .28). Survival and freedom from reoperation at 5 years were 54% versus 67% (P = .33) and 87% versus 100% (P = .04), respectively. Higher calcium score was associated with lower survival after double-valve replacement but not after the Commando. The Commando procedure had lower aortic valve mean gradients at 4 years (9.4 vs 11 mm Hg, P = .04). After Commando procedures for calcification, 5-year survival was 60% and 59% with and without radiation, respectively (P = .47). Conclusions: The Commando procedure with reconstruction of the intervalvular fibrosa destroyed by mitral anular calcification, radiation, or previous surgery demonstrates acceptable outcomes similar to standard double-valve replacement. More experience and long-term outcomes are required to refine patient selection for and application of the Commando approach.

ABSTRACT: Bunching behavior in cattle may occur for several reasons including enabling social interactions, a response to stress or danger, or due to shared interest in resources such as feeding or watering areas. There is evidence in pasture grazed cattle that bunching may occur more frequently at higher ambient temperatures, possibly due to sharing of fly-load or to seek shade from the direct sun under heat stress conditions. Here we demonstrate how bunching behavior is associated with higher ambient temperatures in a barn-housed UK dairy herd. A real-time local positioning system was used, as part of a precision livestock farming (PLF) approach, to track the spatial position and activity of a commercial dairy herd (∼100 cows) in a freestall barn continuously at high temporal resolution for 4 mo between August and November 2014. Bunching was determined using 4 different spatial measures determined on an hourly basis: herd full and core range size, mean herd intercow distance (ICD), and mean herd nearest-neighbor distance (NND). For hourly mean ambient temperatures above 20°C, the herd showed higher bunching behavior with increasing ambient temperature (i.e., reduced full and core range size, ICD, and NND). Aggregated space-use intensity was found to positively correlate with localized variations in temperature across the barn (as measured by animal-mounted sensors), but the level of correlation decreased at higher ambient barn temperatures. Bunching behavior may increase localized temperatures experienced by individuals and hence may be a maladaptive behavioral response in housed dairy cattle, which are known to suffer heat stress at higher temperatures. Our study is the first to use high-resolution positional data to provide evidence of associations between bunching behavior and higher ambient temperatures for a barn-housed dairy herd in a temperate region (UK). Further studies are needed to explore the exact mechanisms for this response to inform both welfare and production management.

Abstract Background The characteristics of optimal virtual pulmonary rehabilitation (PR) for individuals with post-COVID syndrome (PCS) have not been identified. This study aimed to assess the feasibility, safety, and satisfaction associated with a virtual PR program with the exercise component delivered through group or self-directed sessions. Methods Adults with PCS-respiratory symptoms were randomly assigned to the video conference (PRVC) or self-directed (PRSD) group and completed an exercise program (aerobic, strengthening, and breathing exercises) three times/week for eight weeks. PRVC sessions were led by a physiotherapist via Zoom, whereas the PRSD group exercised individually following a pre-recorded video. Both groups received personalized exercise recommendations, education related to the condition, and a weekly follow up call. Satisfaction was assessed through a patient survey. Lung function, dyspnea, fatigue, sit-to-stand capacity, health-related quality of life, and participation were assessed pre- and post-PR. Results Fourteen PCS individuals (49 ± 9 years, 86% females) completed 83% of the sessions. All participants were satisfied with information provided by the therapist and frequency of data submission, whereas most were satisfied with the frequency and duration of exercise sessions (88% in PRVC and 83% in PRSD). A higher proportion of participants in the PRVC (88%) were satisfied with the level of difficulty of exercises compared with the PRSD (67%), and 84% of the sample reported a positive impact of the program on their health. No adverse events were reported. Significant changes in sit-to-stand capacity (p = 0.012, Cohen’s r = 0.67) and questions related to fatigue (p = 0.027, Cohen’s r = 0.58), neurocognitive (p = 0.045, Cohen’s r = 0.53), and autonomic (p = 0.024, Cohen’s r = 0.60) domains of the DePaul Symptom Questionnaire short-form were also found between groups. Conclusion Virtual PR with exercises delivered via video conference or pre-recorded video were feasible, safe, and well-received by individuals with PCS. Trial registration NCT05003271 (first posted: 12/08/2021).

Abstract Background This case report is applicable to the field of ophthalmology because there is a paucity of medical literature related to the clinical presentation, diagnosis, and management of uveal effusion syndrome. This is an urgent concern because there are severe complications associated with this disease, including non-rhegmatogenous retinal detachment, angle closure glaucoma, and possible blindness. This report will fill clinical knowledge gaps using a patient example. Case presentation A 68-year-old white male with multiple cardiovascular risk factors initially presented to the Eye Institute Urgent Care Clinic with new onset visual symptoms, including eye pain, eye lid swelling, redness, and tearing of his left eye. He had experienced a foreign body sensation in the left eye and bilateral floaters weeks prior to his presentation. The patient was examined, and vision was 20/30 in both eyes, and intraocular pressure was 46 in the right eye and 36 in the left eye. After initial assessment, including compression gonioscopy, intermittent angle closure glaucoma was suspected. He received oral diamox 500 mg, one drop of alphagan in both eyes, one drop of latanoprost in both eyes, one drop of dorzolamide in both eyes, and one drop of 2% pilocarpine in both eyes. There was only slight response in intraocular pressure. Owing to the bilateral angle closure, he underwent laser peripheral iridotomy to decrease intraocular pressure and open the angle that was found closed on gonioscopy. The patient was discharged on oral and topical glaucoma drops and scheduled for the glaucoma clinic. When he presented for follow-up in the glaucoma clinic, he was evaluated and noted to have bilateral narrow angles and intraocular pressure in the mid-twenties. A brightness scan (B-scan) was performed and was noted to have bilateral choroidal effusions, confirmed by Optos fundus photos. He was started on prednisone at 60 mg once per day (QD) with taper, continuation of oral and topical glaucoma medications, and a retina evaluation. Evaluation with a retina specialist showed resolving choroidal effusion in the left eye. He continued the prednisone taper as well as glaucoma drops as prescribed. Follow-up in the glaucoma clinic revealed a grade 3 open angle. He continued the prednisone taper, cosopt twice per day in both eyes, and discontinued brimonidine. The magnetic resonance imaging (MRI) that was performed showed results that were remarkable. No hemorrhage or mass was present. Follow-up with the retina specialist found that the choroidal effusions had resolved completely. Conclusion This case report emphasizes the value in early detection, keen diagnostic evaluation, and cross-collaboration between multiple ophthalmology specialists to optimize healthcare outcomes for patients with uveal effusion syndrome.

Abstract Background Onchocerciasis is endemic in 14 of Sierra Leone's 16 districts with high prevalence (47–88.5%) according to skin snips at baseline. After 11 rounds of mass treatment with ivermectin with good coverage, an impact assessment was conducted in 2017 to assess the progress towards eliminating onchocerciasis in the country. Methods A cluster survey was conducted, either integrated with lymphatic filariasis (LF) transmission assessment survey (TAS) or standalone with the LF TAS sampling strategy in 12 (now 14) endemic districts. Finger prick blood samples of randomly selected children in Grades 1–4 were tested in the field using SD Bioline Onchocerciasis IgG4 rapid tests. Results In total, 17,402 children aged 4–19 years in 177 schools were tested, and data from 17,364 children aged 4–14 years (14,230 children aged 5–9 years) were analyzed. Three hundred forty-six children were confirmed positive for Ov-16 IgG4 antibodies, a prevalence of 2.0% (95% CI 1.8–2.2%) in children aged 4–14 years with prevalence increasing with age. Prevalence in boys (2.4%; 95% CI 2.1–2.7%) was higher than in girls (1.6%; 95% CI 1.4–1.9%). There was a trend of continued reduction from baseline to 2010. Using data from children aged 5–9 years, overall prevalence was 1.7% (95% CI 1.5–1.9%). The site prevalence ranged from 0 to 33.3% (median prevalence = 0.0%): 5%) was predicted in some focal areas, centered in Karene, Kailahun and Moyamba/Tonkolili. Conclusions Low Ov-16 IgG4 antibody prevalence was shown in most areas across Sierra Leone. In particular, low seroprevalence in children aged 5–9 years suggests that the infection was reduced to a low level after 11 rounds of treatment intervention. Sierra Leone has made major progress towards elimination of onchocerciasis. However, attention must be paid to those high prevalence focal areas. Graphical Abstract

Introduction:: Intra-abdominal pressure (IAP) and gravity may both challenge pelvic organ support and contribute to the development or worsening of pelvic organ prolapse (POP). This study aimed to assess whether pelvic floor morphometry differs between supine and standing positions in women with and without POP, at rest and with elevated IAP, and to compare the change in measures from the supine to standing position between groups. Methods:: Thirty premenopausal vaginally parous women with (n=15) and without (n=15) POP were included. Transperineal ultrasound was used to assess pelvic floor morphometry (bladder neck [BN], rectal ampulla [RA], levator plate angle [LPA], anorectal angle [ARA], levator anteroposterior distance [LAP], and levator hiatal area [LHA]) in supine and standing, at rest and bearing down. Measures were compared between positions (supine and standing) and groups (women with and without POP). Results:: At rest, BN and RA were lower and LPA was smaller in standing than supine for all participants (all p0.23). ARA was greater in women with POP than without POP in both positions at rest (p=0.002). During bearing down, BN and RA were lower, ARA and LPA were smaller, and LHA and LAP distance were larger in standing than in supine for all participants (all p

BackgroundHealth systems are increasingly interested in collaborative dementia care. Implementation challenges include the limited dementia specialist workforce, time pressures of high-volume care, increasing use of telemedicine, and inadequate reimbursement. The Care Ecosystem is a telephone-based collaborative dementia care model designed to augment existing healthcare services and be amenable to scale. Here we present the latest evidence for the Care Ecosystem, including the effects among subpopulations at risk for health disparities (rural and Hispanic/Latino), and facilitators from the early phase of Care Ecosystem implementation at 6 diverse health systems.MethodEffectiveness was evaluated in a single-blind, randomized clinical trial (N = 804). Persons with dementia (PWD)-caregiver dyads were randomized to receive 12 months of the intervention (N = 527) or usual care (N = 277). Outcomes were measured via telephone surveys at 6 and 12 months after randomization and medical record review. Subgroup analyses were performed for the 124 dyads who identified as Hispanic/Latino, and the 66 who lived in rural Nebraska or Iowa. The intervention was primarily delivered by an unlicensed, trained care team navigator, who provided education, support and care coordination with supervision and help from a dementia specialist team (advanced practice nurse, social worker, and pharmacist). Implementation facilitators were evaluated through observation and qualitative interviews with clinical teams at 6 health systems implementing the model.ResultsThe PWD-caregiver dyads lived in California (n = 476), Nebraska (n = 286), or Iowa (n = 42). Compared with usual care, the Care Ecosystem improved PWD quality of life, reduced emergency department visits, reduced the use of potentially inappropriate medications, and decreased caregiver depression and caregiver burden. Effect sizes were similar or greater in Hispanic/Latino and rural subgroups on most outcomes. Facilitators of Care Ecosystem implementation included open-access implementation tools (online training, care protocols), the adaptability of the care model, the care team navigator role, and remote care delivery.ConclusionEffective dementia care can be delivered by care team navigators via telephone to mitigate the burdens of dementia, including for underserved PWD living in rural areas or who identify as Hispanic/Latino. Implementation is a challenge although features of the care model appear to facilitate adoption.

BackgroundLifespace is a multidimensional construct that describes the geographic area in which a person lives and conducts their activities, and reflects mobility, health, and well-being. Traditionally, it has been measured by asking older people to self-report the length and frequency of trips taken and assistance required. Global Positioning System (GPS) sensors on smartphones have been used to measure Lifespace of older people, but not with people with Parkinson’s disease (PD). ObjectiveThe objective of this study was to investigate whether GPS data collected via smartphones could be used to indicate the Lifespace of people with PD. MethodsThe dataset was supplied via the Michael J Fox Foundation Data Challenge and included 9 people with PD and 7 approximately matched controls. Participants carried smartphones with GPS sensors over two months. Data analysis compared the PD group and the control group. The impact of symptom severity on Lifespace was also investigated. ResultsVisualization methods for comparing Lifespace were developed including scatterplots and heatmaps. Lifespace metrics for comparison included average daily distance, percentage of time spent at home, and number of trips into the community. There were no significant differences between the PD and the control groups on Lifespace metrics. Visual representations of Lifespace were organized based on the self-reported severity of symptoms, suggesting a trend of decreasing Lifespace with increasing PD symptoms. ConclusionsLifespace measured by GPS-enabled smartphones may be a useful concept to measure the progression of PD and the impact of various therapies and rehabilitation programs. Directions for future use of GPS-based Lifespace are provided.

There is a pressing need for prevention programs that address increasing rates of epidemics and pandemics, including noncommunicable diseases. However, many populations face substantial systemic barriers to accessing traditional prevention programs. To minimize persistent service utilization gaps for underserved populations, the field requires effective, efficient, and sustainable methods to increase accessibility and cultural relevance of prevention programming to multiple audiences. Cultural adaptation is one such strategy, but it can be daunting for many preventionists. Therefore, this paper presents a step-by-step guide to streamline the cultural adaptation of prevention programs through digitization and use of a novel application of storyboarding methodology, called "blueprint storyboarding." This innovative approach to cultural adaptation is designed to increase systematicity through manualization, efficiency, cost-effectiveness, and adaptability for multiple cultures and developmental stages. We illustrate this novel method by describing how we applied the blueprint storyboarding approach after digitization to culturally adapt the JUS Media? Programme, a food-focused media literacy program designed to buffer media-related obesity risks for diverse youth. [This paper was written with the JUS Media? Adaptation Team.]

The primary goal of the present systematic review was to examine the criteria and measures used for assessing students with "specific comprehension deficit" (SCD) who have adequate decoding skills but still perform poorly on reading comprehension assessments. From a systematic review of 32 studies, we found four predominant selection approaches for classifying students with SCD and a wide range of measurements of reading skills used to distinguish students with SCD from skilled readers. In addition, to develop a reading profile for students with SCD, we performed a meta-analysis to quantify the characteristics of SCD by comparing their reading skills to those of skilled readers. Results revealed that students with SCD demonstrated deficits in oral language (i.e., vocabulary and listening comprehension) and reading comprehension, despite adequate decoding and fluency skills. Their reading comprehension deficits (Hedges's "g" = -3.28) were also more severe than their oral language deficits (Hedges's "g" = -0.95). We provide recommendations and implications for future researchers and classroom teachers.

This exploratory study investigated the behaviors and content of onscreen calculator usage by a nationally representative sample of eighth-grade students who responded to items from the 2017 National Assessment of Educational Progress mathematics assessment. Meaningful features were generated from the process data to infer whether students spontaneously used calculators for mathematical problem solving, how frequently and when they used them, and the nature of the operations performed on calculators. Sequential pattern mining was applied on sequences of calculator keystrokes to obtain patterns of operations that were representative of students' problem-solving strategies or processes. Results indicated that higher scoring students not only were more likely to use calculators, but also used them in a more goal-driven manner than lower scoring students.

Patients with epilepsy face heightened risk of post-ictal cardiorespiratory suppression and sudden unexpected death in epilepsy (SUDEP). Studies have shown that neuroinflammation, mediated by the activation of microglia and astrocytes, may be a cause or consequence of seizure disorders. Kcnj16 (Kir5.1) knockout rats (SSkcnj16−/−) are susceptible to repeated audiogenic seizures and recapitulate features of human SUDEP, including post-ictal ventilatory suppression, which worsens with repeated seizures and seizure-induced mortality. In this study, we tested the hypothesis that repeated seizures cause neuroinflammation within key brainstem regions that contribute to the control of breathing. Audiogenic seizures were elicited once/day for up to 10 days in groups of adult male SSkcnj16−/− rats, from which frozen brainstem biopsies of the pre-Bötzinger complex/nucleus ambiguus (preBötC/NA), Bötzinger complex (BötC), and raphe magnus (RMg) regions were subjected to a cytokine array. Several cytokines/chemokines, including IL-1α and IL-1ß, were increased selectively in preBötC/NA after 3 or 5 days of seizures with fewer changes in other regions tested. In additional groups of male SSkcnj16−/− rats that underwent repeated seizures, we quantified microglial (IBA-1+) cell counts and morphology, specifically within the preBötC/NA region, and showed increased microglial cell counts, area, and volume consistent with microglial activation. To further test the role of inflammation in physiological responses to seizures and seizure-related mortality, additional groups of SSkcnj16−/− rats were treated with anakinra (IL-1R antagonist), ketoprofen (non-selective COX inhibitor), or saline for 3 days before and up to 10 days of seizures (1/day), and breathing was measured before, during, and after each seizure. Remarkably, IL-1R antagonism mitigated changes in post-ictal ventilatory suppression on days 7–10 but failed to prevent seizure-related mortality, whereas ketoprofen treatment exacerbated post-ictal ventilatory suppression compared to other treatment groups but prevented seizure-related mortality. These data demonstrate neuroinflammation and microglial activation within the key brainstem region of respiratory control following repeated seizures, which may functionally but differentially contribute to the pathophysiological consequences of repeated seizures.

One in three children in the United States is exposed to insecure housing conditions, including unaffordable, inconsistent, and unsafe housing. These exposures have detrimental impacts on youth mental health. Delineating the neurobehavioral pathways linking exposure to housing insecurity with children’s mental health has the potential to inform interventions and policy. However, in approaching this work, carefully considering the lived experiences of youth and families is essential to translating scientific discovery to improve health outcomes in an equitable and representative way. In the current paper, we provide an introduction to the range of stressful experiences that children may face when exposed to insecure housing conditions. Next, we highlight findings from the early-life stress literature regarding the potential neurobehavioral consequences of insecure housing, focusing on how unpredictability is associated with the neural circuitry supporting cognitive and emotional development. We then delineate how community-engaged research (CEnR) approaches have been leveraged to understand the effects of housing insecurity on mental health, and we propose future research directions that integrate developmental neuroscience research and CEnR approaches to maximize the impact of this work. We conclude by outlining practice and policy recommendations that aim to improve the mental health of children exposed to insecure housing.

Objective This study aimed to identify the primary sources of COVID-19 health information for adolescent girls in Sierra Leone and evaluate their perceived trustworthiness and influence on their behaviour.Design Using a convenience sampling strategy grounded in the social cognitive theory, the study explored adolescents' navigation and appraisal of health information sources, their understanding of COVID-19, and the impact of societal and observational influences on their health beliefs and actions. Data analysis involved thematic analysis using NVivo V.12 software, focusing on patterns within responses related to observational learning, trusted sources and behavioural outcomes.Setting Sierra Leone, July 2020.Participants 16 focus group discussions were conducted among 86 adolescents (6–8 per group) aged 15–19 years in Sierra Leone.Outcome measure Primary sources of COVID-19 information.Results Adolescent girls identified a diverse range of health information sources, including schools, social media, health workers and radio, with notable differences in trust and preference based on geographical and social contexts. A noteworthy finding was the significant trust placed in health workers, marking a stark contrast to fear and mistrust during the Ebola emergency only 5 years previously. This renewed trust in health professionals emerged as a critical factor influencing adolescents’ health behaviours and acceptance of COVID-19 preventive measures.Conclusion This study underscores the complexity of navigating health information among adolescent girls during the COVID-19 pandemic. It highlights the importance of tailored public health messaging that accounts for local cultural contexts, addresses misconceptions and builds on trusted information sources to foster effective health behaviours. Future interventions could prioritise enhancing educational resources, leveraging trusted community figures, and ensuring that health communication is scientifically accurate and culturally sensitive.

Intestinal disease is one of the earliest manifestations of cystic fibrosis (CF) in children and is closely tied to deficits in growth and nutrition, both of which are directly linked to future mortality. Patients are treated aggressively with pancreatic enzyme replacement therapy and a high-fat diet to circumvent fat malabsorption, but this does not reverse growth and nutritional defects. We hypothesized that defects in chylomicron production could explain why CF body weights and nutrition are so resistant to clinical treatments. We used gold standard intestinal lipid absorption and metabolism approaches, including mouse mesenteric lymph cannulation, in vivo chylomicron secretion kinetics, transmission electron microscopy, small intestinal organoids, and chylomicron metabolism assays to test this hypothesis. In mice expressing the G542X mutation in cystic fibrosis transmembrane conductance regulator (CFTR−/− mice), we find that defective FFA trafficking across the epithelium into enterocytes drives a chylomicron formation defect. Furthermore, G542X mice secrete small, triglyceride-poor chylomicrons into the lymph and blood. These defective chylomicrons are cleared into extraintestinal tissues at ∼10-fold faster than WT chylomicrons. This defect in FFA absorption resulting in dysfunctional chylomicrons cannot be explained by steatorrhea or pancreatic insufficiency and is maintained in primary small intestinal organoids treated with micellar lipids. These studies suggest that the ultrahigh-fat diet that most people with CF are counselled to follow may instead make steatorrhea and malabsorption defects worse by overloading the absorptive capacity of the CF small intestine.