Journal of Biomechanics

Modelling of hemodynamics in the circle of Willis (CoW) depends on vascular segmentation, which may vary based on imaging modality. Computed tomography angiography (CTA) is commonly used in clinic but involves radiation and injection of contrast agents, whereas magnetic resonance angiography (MRA) offers a non-invasive alternative. This study aims to compare CoW morphology and modelled cerebral perfusion pressure of CTA and MRA segmentations, validating if MRA can replace CTA in modelling workflows. CTA and time-of-flight MRA (TOF-MRA) of the CoW was performed in 19 patients undergoing elective aortic arch surgery (67{+/-}7 years, 8 women). The CoW was semi-automatically segmented based on signal intensity thresholding. A TOF-MRA threshold was optimized against the CTA segmentation, using the CTA as reference standard. Computational fluid dynamics (CFD) modelling with boundary conditions based on subject-specific flow rates from 4D flow MRI simulated cerebral perfusion pressure in the segmented geometries. A baseline simulation and a unilateral brain inflow simulation, i.e., occlusion of a carotid, were carried out. Linear mixed models indicated there was no effect of choice of modality on either average arterial lumen area (CTA - TOF-MRA: -0.2{+/-}1.3 mm2; p=0.762) or baseline pressure drops (0.2{+/-}1.9 mmHg; p=0.257). In the unilateral inflow simulation, we found no difference in pressure laterality (-6.6{+/-}18.4 mmHg; p=0.185) or collateral flow rate (10{+/-}46 ml/min; p=0.421). TOF-MRA geometries can with signal intensity thresholding be matched to produce similar morphology and modelled cerebral perfusion pressure to CTA geometries. The modelled pressure drops over the collateral arteries were sensitive to the segmentation regardless of modality.

Background | Angina with nonobstructive coronary arteries (ANOCA) is a heterogeneous condition encompassing distinct endotypes representing different underlying pathophysiological mechanisms. Endothelial dysfunction is considered a central hallmark of ANOCA. However, studying patient-derived endothelial cells (ECs) remains challenging due to the limited availability of disease-specific endothelial samples. We therefore aimed to assess the feasibility of isolating and culturing ECs from catheterization material obtained during routine coronary function testing in ANOCA patients. Methods | Catheterization material was collected from 79 ANOCA patients (84% female, age 58{+/-}10 years) undergoing coronary function testing. ECs were isolated, expanded and characterized using immunostaining, flow cytometry, gene expression profiling and functional assays. Results | EC isolation was successful in 43% of cases and resulted in 34 primary EC cultures that were expanded up to passage 10. Isolation success was independent of clinical or procedural characteristics. Isolated cells exhibited typical EC morphology and expressed EC markers confirmed by immunostaining, flow cytometry and gene expression analyses. EC marker gene expression remained largely stable over passages. However, stress- and defense-related gene expression programs increased over time, while proliferation-related processes decreased. Functional assays demonstrated that the coronary catheterization-derived ECs showed typical properties of wound healing, angiogenesis, activation responses upon stimuli and monocyte adhesion. Conclusions | This study demonstrates the feasibility of isolating and expanding ECs directly from catheterization material collected during routine coronary function testing in ANOCA patients. These patient-derived ECs retain characteristic endothelial features and functionality. This approach offers primary EC cultures to study the mechanisms underlying endothelial dysfunction in ANOCA.

Objectives: For suspected hip fractures, prehospital protocols directing patients to an orthopaedic centre rather than the nearest emergency department (ED) could reduce time-to-surgery but may impact EMS travel burden. This study evaluates the impact of transfer protocols by quantifying transport to hospitals from long term care (LTC) facilities across Ontario. Methods: A retrospective cross-sectional analysis of all Ontario LTC facilities and hospitals was performed. Two protocols were modeled: standard transfer to the nearest ED with subsequent transfer if required, and selective transfer based on Collingwood Hip Fracture Rule prehospital screening1 directly to the nearest orthopaedic services (orthoED). Median one-way travel distances were calculated from Google Maps. Results: In Ontario, 15.4% of LTC residents require hospital destination decisions because their nearest ED lacks orthopaedic services; for these facilities, median distances were 2.7km to the ED and 36.0km to the orthoED. Among the 52 LTC facilities where selective transfer was distance-optimal, it substantially reduced travel for patients with hip fracture (31.1km vs 49.6km; P<.01) while only modestly increasing travel for patients without hip fracture. Where standard transfer was distance-optimal, little travel difference was noted for patients with hip fracture, however false positive screened patients traveled significantly further to an orthoED. Greatest negative consequences of selective transfer lie in the 1.3% of residents living farthest (>100km) from an orthoED. Conclusions: EMS direct transportation to hospitals with orthopaedics may improve hip fracture care but can increase EMS burden due to patients identified falsely as having a hip fracture, particularly in remote communities.

Dystonia treatment evaluation in cerebral palsy (CP) is limited by the lack of clinician-assessed scales linking dystonia severity to functional impact. We asked 7 pediatric movement disorder specialists to review videos of 27 children with CP while performing an upper extremity task and while walking. Experts rated arm and leg dystonia severity using the Global Dystonia Severity Rating Scale (GDRS) and task-specific functional impact on a five-point scale adapted from the Dyskinetic Cerebral Palsy Functional Impact Scale. Arm GDRS scores correlated with functional impact on the upper extremity task (linear regression R^2=0.48, p=0.0005). Leg GDRS scores correlated with gait impact (R^2=0.43, p=0.001). A four-point increase in total GDRS corresponded to a one-point worsening in combined functional impact. By demonstrating how expert-rated limb dystonia severity correlates with task-specific functional impact in children with CP, these results could help clinically identify functionally-meaningful differences in dystonia severity.

Understanding how cells migrate through confined environments is crucial for elucidating fundamental biological processes, including cancer invasion, immune surveillance, and tissue morphogenesis. The nucleus, as the largest and stiffest cellular organelle, often limits cellular deformability, making it a key factor in migration through narrow pores or highly constrained spaces. In this work, we introduce a geometric surface partial differential equation (GS-PDE) model in which the cell plasma membrane and nuclear envelope are described as evolving energetic closed surfaces governed by force-balance equations. We replicate the results of a biophysical experiment, where a microfluidic device is used to impose compressive stresses on cells by driving them through narrow microchannels under a controlled pressure gradient. The model is validated by reproducing cell entry into the microchannels. A parametric sensitivity analysis highlights the dominant influence of specific parameters, whose accurate estimation is essential for faithfully capturing the experimental setup. We found that surface tension and confinement geometry emerge as key determinants of translocation efficiency. Although tailored to this specific setup for validation purposes, the framework is sufficiently general to be applied to a broad range of cell mechanics scenarios, providing a robust and flexible tool for investigating the interplay between cell mechanics and confinement. It also offers a solid foundation for future extensions integrating more complex biochemical processes such as active confined migration.

Background/Objective: Common measures of physical activity (PA) based on duration and intensity do not fully capture its complexity. Adding additional PA components of muscle strength, mechanical strain, and turning actions, can provide a more complete view of activity behavior. Furthermore, PA behaviors differ between men and women. Therefore, the goal of this study is to identify and cluster similar long-term PA patterns over time for each PA component, examined separately for men and women. Methods: We used data from 4963 participants (52% women; mean age 66 years, SD = 8.6) of the Longitudinal Aging Study Amsterdam (1992 to 2019). PA component scores were assigned to self-reported activities, and Sequence Analysis with Optimal Matching was used to identify and cluster similar activity patterns over a period of 10 years, separately for each component and stratified by sex. Results: PA components varied by sex and displayed a unique mix of trajectories, including predominately low, medium, or high activity, increasing or decreasing patterns, and trajectories characterized by early or late mortality. Importantly, trajectories remained independent, indicating that changes in one PA component were not linked to changes in others. Conclusion: Older men and women follow distinct and independent long term PA trajectories across components, underscoring that PA behaviour cannot be described by a single dimension. Significance/Implications: The observed independence and heterogeneity of trajectories suggest that muscle strength, mechanical strain, and turning actions capture meaningful and distinct aspects of PA that are not reflected by traditional measures alone. Future PA-strategies could incorporate these dimensions and acknowledge sex-specific patterns to better reflect natural movement. The independence of components suggests that future interventions should target multiple dimensions, as changes in one component may not translate to others. Such an approach may support more tailored and sustainable PA interventions in later life.

BACKGROUND: Guidelines recommend aortic valve replacement (AVR) in patients with severe aortic regurgitation (AR) based on progressive changes in left ventricular (LV) function or size. We aimed to reassess the clinical relevance of current guideline recommendations pertaining to traditional echocardiographic measurements in routine practice. METHODS: Retrospective analysis of patients with severe AR who underwent serial echocardiographic follow-up over at least 18 months. The composite outcome was symptom-driven AVR, acute heart failure hospitalization, or death. We used a joint modelling approach to handle within-subject correlation and censoring. RESULTS: The cohort consisted of 140 patients, with a median follow?up of 93 months (interquartile range 58?130). LV end-systolic (LVESD) and fractional shortening (FS) showed a small but statistically significant longitudinal trend, while LVEDD did not. Changes in all three parameters in parallel joint models adjusted for age and gender were consistently associated with increased risk of the composite event. Each 1?mm increase in LVESD and LVEDD was associated with a 6% and 5% increase in risk, respectively; each 1% decrease in FS corresponded to a 12% increase in risk. Only 8 (5.7%) of patients were predicted to exceed the guideline-recommended LVEDD threshold of 65 mm over 10 years. Age at onset was also a significant risk factor, with each decade increasing risk by 65% for each of the three parallel joint models. CONCLUSIONS: LV parameters show modest changes over time, despite holding strong prognostic value in patients with severe AR. LVEDD, while associated with overall risk, does not predictably or significantly dilate over time in most patients. AVR decisions should be based on comprehensive clinical and volumetric assessment rather than waiting for simple linear progression to guideline cutoffs.

Objective Cerebral palsy (CP) affects approximately 1 million Americans and 18 million individuals worldwide, yet contemporary US epidemiologic data remains limited. We aimed to use Cerebral Palsy Research Network (CPRN) clinical registry to describe demographics and clinical characteristics of individuals with CP across the US and determine associations with gross motor function and genetic etiology. Methods Registry subjects were included if they had clinician-confirmed CP and prospectively entered data for Gross Motor Function Classification System (GMFCS) Level, gestational age, genetic etiology, CP distribution, and tone/movement types. Logistic regression was used to determine which of these variables plus race, sex, ethnicity, and age were associated with GMFCS level and genetic etiology. Results A total of 9,756 children and adults with CP from 22 CPRN sites met inclusion criteria. Participants were predominantly White (73.0%), male (57.3%), non-Hispanic (87.8%), and younger than 18 years (73.7%). Most were classified as GMFCS levels I-III (55.6%), born preterm (52.8%), had spasticity (83.8%), and had quadriplegia (41.9%); 12.2% were identified as having a genetic etiology. Tone/movement types, CP distribution, and gestational age were significantly associated with both GMFCS level and genetic etiology (p<0.001). Compared to White individuals, Black individuals were more likely to have greater gross motor impairment (p<0.001). Conclusion In this large US cohort, clinical and demographic factors, including race, were associated with gross motor function and genetic etiology in CP. These findings highlight persistent disparities and demonstrate the value of a national clinical registry for informing prognostication, quality improvement efforts, and targeted genetic testing strategies.

Walking impairments in Parkinsons disease (PD), including reduced speed, cadence, and stride length, and increased variability, impair mobility and raise fall risk. Conventional treatments may fail to address these deficits, underscoring the need for complementary non-invasive alternatives. This study examined whether combining rhythmic auditory cueing with transcranial direct current stimulation (tDCS) over the supplementary motor area (SMA), a critical region for internally-generated movement, would enhance gait performance in PD. Thirty-three participants with PD and thirty-two healthy controls completed two sessions (anodal vs. sham tDCS) with gait assessed during stimulation, immediately after stimulation, and 15 minutes after stimulation under two auditory conditions: walking in silence and walking to music paced 10% faster than baseline cadence. Spatiotemporal, variability, and stability gait parameters were analyzed using linear mixed-effects models. Rhythmic auditory cueing significantly increased cadence and speed during, immediately after, and especially 15 minutes after stimulation, suggesting sustained effects of rhythmic entrainment. Anodal tDCS produced faster cadence, as well as lower stride time variability and stride width, particularly in individuals with PD. Although both music and anodal tDCS affected gait, no interaction was observed, indicating independent effects. Individuals with PD had greater gait variability overall, and adjusted temporal gait parameters less to music than healthy controls did. Anodal stimulation reduced walking variability in PD, reducing the group differences observed under sham conditions. These findings suggest that rhythmic cueing and SMA stimulation target complementary mechanisms, highlighting the promise of combined tDCS-music interventions for gait rehabilitation in PD.

Aims: Responses to remote pulmonary artery pressure data vary across programs. We evaluated SMART-HF, a structured pulmonary artery diastolic pressure (PAD)-guided workflow, in a community heart failure cohort. Methods: We retrospectively analysed adults with heart failure and an implanted pulmonary artery pressure sensor managed with SMART-HF. Pulmonary artery diastolic pressure (PAD) was calculated from prespecified 14-day windows at baseline, 90 days, and 6 months. Two hemodynamic management performance indices (HMPI) were prespecified: the 6-Month Delta HMPI (PAD reduction >2 mmHg from baseline) and the 90-Day Target HMPI (PAD [&le;]20 mmHg at 90 days). Exploratory analyses evaluated patients with baseline PAD >20 mmHg. Results: Of 37 patients, 36 had paired 90-day and 29 had paired 6-month windows. Mean PAD decreased from 18.3 +/- 7.0 to 16.1 +/- 6.3 mmHg at 90 days and from 18.8 +/- 6.8 to 15.5 +/- 5.8 mmHg at 6 months (both P < 0.001). The 90-Day Target HMPI was achieved in 26/36 (72.2%) and the 6-Month Delta HMPI in 19/29 (65.5%) [95% CI 45.7-82.1]. In the exploratory subgroup (baseline PAD >20 mmHg), mean PAD changes were -2.9 +/- 3.6 mmHg at 90 days (n = 19; P = 0.002) and -4.9 +/- 4.9 mmHg at 6 months (n = 15; P = 0.002). Conclusions: SMART-HF was associated with improved ambulatory pulmonary artery diastolic pressure control at 90 days and 6 months. Exploratory subgroup findings support further evaluation in patients with elevated baseline pulmonary artery diastolic pressure.

ObjectiveTo explore the interpretation of unexpected results from a randomized controlled trial (RCT). Study Design and SettingAdjunctive frequentist (power and type{square}M error) and Bayesian analyses were performed on a recently published RCT reporting a statistically significant relative risk reduction (p <0.01) for caffeinated coffee drinkers compared with abstinence on atrial fibrillation (AF) recurrence. Individual patient data for the Bayesian survival models were reconstructed from the RCT published material and priors informed by the RCT power calculations. ResultsThe original RCT design had limited power for realistic effect sizes, increasing susceptibility to type{square}M (magnitude) error. Bayesian analyses also tempered the benefit for caffeinated coffee implied by standard statistical analysis resulting in only modest probabilities of clinically meaningful risk reductions (e.g., hazard ratio < 0.9 of 88% or a risk difference > 2% of 82%). ConclusionsSupplemental frequentist and Bayesian approaches can provide robustness checks for unexpected RCT findings, providing contextualization, clarifying distinctions between statistical and clinical significance, and guiding replication needs. HighlightsO_LIRandomized controlled trial (RCT) results may be unexpected and challenge prior beliefs C_LIO_LISupplemental frequentist and Bayesian analyses can clarify interpretation of surprising findings C_LIO_LIPower and type{square}M error assessments help evaluate design adequacy for realistic effects C_LIO_LIBayesian posterior probabilities provide additional nuanced insights into contextulaization and clinical significance C_LI

Abstract Background: ST-elevation myocardial infarction (STEMI) is reported to be a leading cause of mortality worldwide. While cardiac troponins are the gold standard for myocardial injury detection but creatine kinase-MB (CK-MB) and total creatine phosphokinase (CPK) retain prognostic use in resource-limited settings. Objective: To evaluate the prognostic significance of admission CK-MB and CPK levels in STEMI patients and to assess their association with hematological parameters for integrated risk stratification. Methods: This cross-sectional study enrolled 15 consecutive STEMI patients from the Punjab Institute of Cardiology, Lahore, during January 2024. Comprehensive laboratory analysis including cardiac biomarkers (CK-MB, CPK, troponin-I, LDH), complete blood count, renal function, serum electrolytes, and metabolic parameters, was performed on admission. Pearson correlation and comparative statistical analyses were also conducted to assess the relationships between cardiac biomarkers and hematological indices. Results: The cohort includes 15 patients (mean age 50.1 +/- 12.2 years; 73.3% male). Cardiac biomarker elevation was prevalent: CK-MB was elevated in 12/15 (80%), CPK was elevated in 12/15 (80%), with concordant elevation in 11/15 (73.3%), which indicates extensive myocardial necrosis. Troponin-I showed the highest elevation rate at 13/15 (86.7%). Hematological abnormalities included anemia (60%), WBC elevation (53.3%), and RBC reduction (40%). Random glucose averaged 150.80 +/- 63.55 mg/dL, with 66.7% highlighted the hyperglycemia. Remarkably, electrolyte balance was preserved in all of the patients (0% sodium, potassium, and bicarbonate abnormalities), indicating maintained homeostasis. Pearson correlation analysis revealed a significant correlation between CK-MB and CPK (r = 0.615, p = 0.0126), while correlations between cardiac biomarkers and hematological parameters were weak (p > 0.05). Risk stratification identified 53.3% of patients as high-risk who required intensive management. Conclusions: CK-MB and CPK demonstrate significant concordance and retain prognostic value in STEMI patients, particularly in resource-limited settings where troponin access may be constrained. While troponin-I remains the most sensitive biomarker, combined assessment of conventional cardiac enzymes supports reliable evaluation of myocardial injury. Hematological parameters reflect systemic response but show limited correlation with cardiac biomarkers.

Background: Deep brain stimulation (DBS) is a treatment option for Parkinson disease (PD). However, the effect of DBS on the arterial pressure (AP) remains unexplored. We aimed to develop an artificial baroreflex system for treating orthostatic hypotension (OH) due to central baroreflex failure in patients with PD. To achieve this, we developed an appropriate algorithm after estimating the dynamic responses of the AP to DBS using a white noise system identification method. Methods: We randomly performed DBS while measuring the AP tonometrically in 3 trials involving 3 patients with PD treated with DBS. We calculated the frequency response of the AP to the DBS using a fast Fourier transform algorithm. Finally, the feedback correction factors were determined via numerical simulation. Results: The frequency responses of the systolic AP to random DBS were identifiable in all 3 trials, and the steady state gain was 8.24 mmHg/STM. Based on these results, the proportional correction factor was set to 0.12, and the integral correction factor was set to 0.018. The computer simulation revealed that the system could quickly and effectively attenuate a sudden AP drop induced by external disturbances such as head-up tilting. Conclusion: An artificial baroreflex system with DBS may be a novel therapeutic approach for OH caused by central baroreflex failure.

Purpose: Spatial distribution of coronary artery calcium (CAC) may provide additional prognostic value in patients undergoing SPECT and PET myocardial perfusion imaging (MPI). We aimed to automatically identify CAC in proximal segments from attenuation correction CT (CTAC) scans using artificial intelligence (AI) and to evaluate prognostic significance in two large international multicenter registries. Methods: From hybrid MPI/CT imaging (N=43,099) across 15 sites, we included 4,552 most relevant patients with 1) no prior coronary artery disease; 2) AI-derived mild CAC scores (1-99); and 3) normal perfusion (stress total perfusion deficit <5%). The independent associations between AI-identified proximal CAC and major adverse cardiovascular events (MACE) and all-cause mortality (ACM) were evaluated using multivariable Cox regression, likelihood ratio test (LRT), and continuous net reclassification index (NRI). Results: Among the patients with mild CAC and normal perfusion (mean age 65{+/-}12 years, 51% male), 1,730 (38%) had proximal CAC. Over 3.6 (inter-quartile interval 2.1, 5.2) years follow up, 599 (13%) and 444 (10%) patients had MACE or ACM, respectively. Proximal CAC was associated with an increased risk of MACE (adjusted hazard ratio [HR] 1.24, 95% CI 1.03-1.48, P=0.02) and ACM (adjusted HR 1.25, 95% CI 1.01-1.53, P=0.04) after the adjustment of CAC score and density, clinical risk factors, and perfusion deficit. Proximal CAC improved the risk stratification of MACE (LRT P=0.02; NRI 12%) and ACM (LRT P=0.04; NRI 12%). Conclusion: In patients with mild CAC and normal perfusion, AI detection of proximal CAC identified a higher-risk group for adverse outcomes, highlighting its prognostic utility.

BackgroundPatent ductus arteriosus (PDA) is a common and potentially serious cardiovascular condition in preterm infants, particularly those with low gestational age and birth weight. Its management remains controversial due to variability in screening, diagnostic criteria, and treatment strategies. This study aimed to evaluate risk factors, outcomes, and management strategies for PDA in preterm infants, and to identify predictors of clinical and echocardiographic response to therapy. MethodsWe conducted a retrospective cohort study over a 4-year period (2016-2019) in the neonatal intensive care unit (NICU) of a tertiary care center. All consecutive preterm infants admitted during the study period were eligible. Infants with echocardiographically confirmed PDA who received pharmacological treatment with intravenous paracetamol or ibuprofen were included in the analysis. Missing data were minimal and handled using available-case analysis. Statistical analyses included descriptive statistics, Pearsons chi-square test, and multivariable logistic regression. ResultsAmong 2154 preterm infants admitted to the NICU, 60 were diagnosed with PDA (incidence : 2.8%). The mean gestational age was 29 {+/-} 2.6 weeks, and the median birth weight was 1200 g. Respiratory distress occurred in 95% of cases, mainly due to hyaline membrane disease (86.7%). PDA was symptomatic in 80% of infants. First-line treatment resulted in clinical improvement in 77% and ductal closure in 83.3% of cases, most within 3 days. Predictors of successful closure included gestational age [&ge;] 28 weeks (OR = 5.9; 95% CI : 1.7-20.2) and antenatal corticosteroid exposure (OR = 1.2; 95% CI : 1.0-1.6). Overall mortality was 35% and was significantly higher in infants < 28 weeks (OR = 5.0; 95% CI : 2.4-10.3). Clinical improvement (OR = 3.7) and echocardiographic closure (OR = 4.5) after first-line treatment were associated with reduced mortality. ConclusionsPDA in preterm infants is associated with substantial morbidity and mortality, particularly in those born before 28 weeks of gestation. Early diagnosis, antenatal corticosteroid exposure, and timely pharmacological treatment may improve outcomes. Systematic echocardiographic screening in high-risk neonates should be considered.

Background: Dengue is rapidly emerging in parts of Europe. How households value vector control attributes, and whether inferences depend on decision models or message framing, is unclear. Methods: We conducted a split-ballot online experiment among adults in Italy and France, as well as a hotspot subsample from Marche, Italy. National samples included 1,505 respondents in Italy and 1,501 in France; 183 respondents were recruited in Marche. Participants were randomised to a discrete choice experiment (random utility maximisation) or a regret-based choice experiment (random regret minimisation) and to one of three pre-task messages (control, loss aversion, community values). Each respondent completed 12 choice tasks comparing two dengue control programmes and an opt-out. We estimated mixed logit and mixed random-regret models with random parameters and treatment effects. Results: Across frameworks, nearby cases and high mosquito prevalence were the dominant drivers of programme uptake, whereas cost and operational burden were secondary. In pooled analyses, loss-aversion messaging increased the weight on high mosquito prevalence in both models (from 0.483 to 0.547 in the utility model; from 0.478 to 0.557 in the regret model). Cost effects were small nationally but larger in the hotspot subsample. Conclusions: Risk salience dominates preferences for dengue vector control in these European settings. Random utility and random regret models yield consistent rankings of attributes but differ in behavioural interpretation and some secondary effects; messaging effects were modest and context dependent.

BackgroundFamily-based HIV index case testing identifies family members with unknown HIV status and links them to care. Data are limited in southern Ethiopia. MethodsA facility-based cross-sectional study was conducted among 377 adults on antiretroviral therapy (ART) in Wolaita Zone, Southern Ethiopia, from November 2022 to May 2023. Participants were selected using systematic random sampling. Data were collected via interviewer-administered semi-structured questionnaire. Multivariable logistic regression identified factors associated with index case family testing. Adjusted odds ratios (AOR) with 95% confidence intervals (CI) were calculated, and statistical significance was declared at p < 0.05. ResultsThe proportion of index case family testing for HIV was 84.9% (95% CI: 81.2- 88.6). In multivariable analysis, urban residence (AOR = 2.8; 95% CI: 1.16-6.75), duration on ART greater than 12 months (AOR = 13.0; 95% CI: 4.6-36.9), disclosure of HIV status to family members (AOR = 5.6; 95% CI: 1.9-16.5), discussion of HIV status with family members (AOR = 6.6; 95% CI: 1.9-23.2), and being counselled by health professionals to bring families for testing (AOR = 6.3; 95% CI: 2.1-19.0) were significantly associated with index case family testing. ConclusionThe prevalence of family-based HIV index case testing in Wolaita Zone was 84.9%, below the national 95% target. Health professionals should strengthen counselling on ART adherence, status disclosure, family discussion, and active referral to improve testing uptake among family members of people living with HIV.

Wastewater surveillance (WWS) is established as a vital tool for monitoring polio and SARS-CoV-2 with potential to improve surveillance for many other infectious diseases. This study evaluated the feasibility of detecting measles virus (MeV) RNA in wastewater as part of a national WS preparedness trial in Brisbane, Australia, from March to June 2025. Composite and passive sampling methods were employed in parallel at three wastewater treatment plants serving populations between 230,000 and 584,000. Nucleic acids were extracted and analyzed using RT-qPCR targeting MeV N and M genes to distinguish wild-type and vaccine strains. MeV RNA were detected in both 24-hour composite and passive samples on May 26 to 27, 2025 from the largest catchment of 584,000 which also included an international airport. No measles cases were reported in this city or region within 4 weeks of the WS detections. These were confirmed as vaccine-derived measles virus (MeVV) strain via specific RT-qPCR assay. Extraction recoveries varied (11.5% to 70.5%), with passive sampling showing higher efficiency. This is the first report of use of passive samples for detection of MeV. These findings are consistent with other studies reporting WWS results of both MeVV genotype A and wild type genotype B and/or D. It demonstrates the potential for sensitive MeV WWS with rapid differentiation of MeVV from wild type MeV shedding, including in airport transport hubs and with different sample types. Use of WWS could strengthen measles surveillance by enabling rapid detection of MeV RNA and supporting outbreak preparedness and response. This requires optimised methods which are specific to or differentiate wild-type MeV from MeVV. Furthermore, the successful detection of MeV using passive sampling in this study highlights its potential for deployment in diverse global contexts which may include non-sewered settings.

Study questionWhat are the characteristics and treatment outcomes of women who undertook planned egg freezing (PEF) in Australia and New Zealand between 2009 and 2023? Summary answerThere has been an average yearly increase in the uptake of PEF of 35%, with most women undergoing a single PEF procedure in their mid-thirties. Given ten years follow-up a little over one in four women return, with nearly half of those using donor sperm and one-third achieving a live birth. What is known alreadyPEF, where women freeze their eggs as a strategy to preserve fertility, has increased dramatically in high income countries in the last decade. Despite the rapid uptake of PEF, there remains limited information to guide women, clinicians and policy makers regarding the characteristics of women undertaking this procedure and treatment outcomes. Study design, size, durationA retrospective population-based cohort study of all women who undertook PEF in Australia and New Zealand between 2009 and 2023, including their subsequent return to thaw their eggs and treatment outcomes. Where women returned to utilise their eggs, all subsequent embryo transfer procedures were linked enabling calculation of live birth rates per woman. Participants/materials, setting, methods20,209 women who undertook PEF in Australia and New Zealand between 2009 and 2023 including 1,657 women who returned to thaw their eggs. Main results and the role of chanceThere has been a huge increase in uptake of PEF, from 55 women in 2009 to 4,919 in 2023. Women who freeze their eggs are typically aged 34-38 years (interquartile range) and nulliparous (98.6%). For women with at least 10 years follow-up (i.e. undertook PEF in 2009-13; N=514), 27.9% returned and thawed their frozen eggs (average time to return: 4.9 years). This reduced to 22.1% in those with at least 5 years follow-up (i.e. undertook PEF in 2009-2018; N=4,288). Of those who used their frozen eggs, 47% used donor sperm. After at least two years follow up, 33.9% had a live birth, rising over time to 37.8% for eggs thawed between 2019-2021. Limitations, reasons for cautionIn the timeframe 2009-2019 we did not have information on whether egg freezing occurred because of a cancer diagnosis, a cohort we wished to exclude from the study. As a result, for this timeframe we weighted observations by the probability that egg freezing occurred due to cancer, with the prediction model developed on the years 2020-2023. Wider implications of the findingsThis study provides recent and comprehensive data on PEF to guide prospective patients and clinicians and inform policy. The exponential growth in PEF in Australia and New Zealand mirrors trends in other high-income countries, suggesting a doubling time of 2-3 years. Study findings highlight the need for setting realistic expectations about the likelihood of returning to use frozen eggs and live birth rates. Study funding/competing interest(s)2020-2025 MRFF Emerging Priorities and Consumer Driven Research initiative: EPCD000014

BackgroundAccelerometer-derived behavioral phenotype captures multidimensional aspects of human behavior extending well beyond physical activity, encompassing light exposure, step counts, physical activity patterns, sleep, and circadian rhythms. Whether these five domains constitute a unified behavioral architecture underlying cancer risk and whether circadian organization and light exposure confer incremental predictive value beyond movement volume alone remains to be comprehensively established. MethodsWe conducted an accelerometer-wide association study (AWAS) encompassing the complete accelerometer-derived behavioral exposome across five behavioral domains in UK Biobank participants with valid wrist accelerometry data. Incident solid cancers were designated as the primary endpoint, with prespecified site-specific solid cancers and hematological malignancy as secondary outcomes. Cox proportional hazards models with age as the timescale were used. The minimal covariate set served as the primary reporting tier, followed by sensitivity analyses additionally adjusting for adiposity/metabolic factors, independent activity patterns, shift work history, and accelerometry measurement quality. Nominal statistical significance was defined as two-sided P < 0.05 ResultsAmong 89,080 participants, 6,598 incident solid cancer events were observed over a median follow-up of 8.39 years. In the minimally adjusted model, the pan-solid-tumor association atlas was dominated by signals from activity volume, inactivity fragmentation, and circadian rhythm. Higher overall acceleration (HR per SD: 0.91, 95% CI: 0.89-0.94) and higher daily step counts (HR: 0.93, 95% CI: 0.90-0.95) were independently associated with reduced solid cancer risk, while inactivity fragmentation metrics were consistently linked to higher risk. Notably, circadian rhythms, most prominently cosinor mesor (Midline Estimating Statistic of Rhythm under cosinor model), emerged as leading inverse risk signals, underscoring the independent contribution of circadian behavioral architecture. Site-specific analyses revealed pronounced heterogeneity across tumor sites. Lung cancer exhibited a robust inverse activity-risk gradient, while breast cancer showed reproducible associations with MVPA. Most strikingly, nocturnal light exposure demonstrated a tumor-site-specific association confined to pancreatic cancer, a signal absent across all other sites examined. Associations for uterine cancer were predominantly inactivity-related and substantially attenuated following adjustment for adiposity and metabolic factors. ConclusionsAcross five accelerometer-derived behavioral domains, solid cancers as a whole were most consistently associated with a high-movement, low-fragmentation, and circadian-coherent behavioral profile. While site-specific heterogeneity exists, the broad cancer risk landscape is dominated by movement volume, inactivity fragmentation, and circadian rhythmicity. Light exposure, although more localized in its contribution, demonstrates a potentially novel and specific association with pancreatic cancer risk. These findings support a five-domain behavioral exposome framework for cancer epidemiology and, importantly, position circadian rhythm integrity and nocturnal light exposure as critically understudied dimensions warranting dedicated mechanistic investigation.