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Development and validation of a gonadotropin dose selection model for optimized ovarian stimulation in IVF/ICSI: An individual participant data meta-Analysis
No full textBACKGROUND: The ovarian response to gonadotropin stimulation varies widely among women, and could impact the probability of live birth as well as treatment risks. Many studies have evaluated the impact of different gonadotropin starting doses, mainly based on predictive variables like ovarian reserve tests (ORT) including anti-Müllerian hormone (AMH), antral follicle count (AFC), and basal follicle-stimulating hormone (bFSH). A Cochrane systematic review revealed that individualizing the gonadotropin starting dose does not affect efficacy in terms of ongoing pregnancy/live birth rates, but may reduce treatment risks such as the development of ovarian hyperstimulation syndrome (OHSS). An individual patient data meta-analysis (IPD-MA) offers a unique opportunity to develop and validate a universal prediction model to help choose the optimal gonadotropin starting dose to minimize treatment risks without affecting efficacy. OBJECTIVE AND RATIONALE: The objective of this IPD-MA is to develop and validate a gonadotropin dose-selection model to guide the choice of a gonadotropin starting dose in IVF/ICSI, with the purpose of minimizing treatment risks without compromising live birth rates. SEARCH METHODS: Electronic databases including MEDLINE, EMBASE, and CRSO were searched to identify eligible studies. The last search was performed on 13 July 2022. Randomized controlled trials (RCTs) were included if they compared different doses of gonadotropins in women undergoing IVF/ICSI, presented at least one type of ORT, and reported on live birth or ongoing pregnancy. Authors of eligible studies were contacted to share their individual participant data (IPD). IPD and information within publications were used to determine the risk of bias. Generalized linear mixed multilevel models were applied for predictor selection and model development. OUTCOMES: A total of 14 RCTs with data of 3455 participants were included. After extensive modeling, women aged 39 years and over were excluded, which resulted in the definitive inclusion of 2907 women. The optimal prediction model for live birth included six predictors: age, gonadotropin starting dose, body mass index, AFC, IVF/ICSI, and AMH. This model had an area under the curve (AUC) of 0.557 (95% confidence interval (CI) from 0.536 to 0.577). The clinically feasible live birth model included age, starting dose, and AMH and had an AUC of 0.554 (95% CI from 0.530 to 0.578). Two models were selected as the optimal model for combined treatment risk, as their performance was equal. One included age, starting dose, AMH, and bFSH; the other also included gonadotropin-releasing hormone (GnRH) analog. The AUCs for both models were 0.769 (95% CI from 0.729 to 0.809). The clinically feasible model for combined treatment risk included age, starting dose, AMH, and GnRH analog, and had an AUC of 0.748 (95% CI from 0.709 to 0.787). WIDER IMPLICATIONS: The aim of this study was to create a model including patient characteristics whereby gonadotropin starting dose was predictive of both live birth and treatment risks. The model performed poorly on predicting live birth by modifying the FSH starting dose. On the contrary, predicting treatment risks in terms of OHSS occurrence and management by modifying the gonadotropin starting dose was adequate. This dose-selection model, consisting of easily obtainable patient characteristics, aids in the choice of the optimal gonadotropin starting dose for each individual patient to lower treatment risks and potentially reduce treatment costs
Regulatory data privacy concerns in proliferating IoT era of telecommunication data monetisation: a systematic literature review
No full textThe birth of the 5G telecommunication network laid a good foundation for driving the establishment of massive interconnectivity among IoT devices, which also coincided with the beginning of the Fourth Industrial Revolution (4IR). Such phenomena accelerated the creation of different innovative scenarios and deepen self-monitoring through smart algorithm analyses, as well as created high volume, high velocity, and high variety of data, further spurring relevant parties’ interest in monetising the data, especially the Telcos, where they see this as a new form of revenue through big data analytics. Through a systematic literature review following the PRISMA framework, this research represents one pioneer attempt to find out what impact Telco’s data monetisation of IoT systems has on data privacy regulation. It covers identifying potential data privacy regulatory challenges and potential solutions in the Telco IoT-based data monetisation scenario through PESTLE analysis, covering the literatures reviewed from 2014 to 2023 across three academic research bibliographic databases, namely Dimensions, Scopus and Google Scholar. Among the key findings indicated the challenges arising from the speed of various innovations in such a scenario outpacing the maturity of laws and regulations in regulating them. Further impacts, such as consistent re-evaluation of the data privacy boundary from data owners’ perspective, are compulsory from time to time, and the Privacy-by-Design concept becomes a critical evaluation factor (in both business and technologies) across all applicable laws and regulations. Furthermore, the outcome of this research also pointed out the future directions for more in-depth applied data analytics studies of the potential emergence of new Telco IoT-based data monetisation data privacy regulatory risks as the relevant technology innovations progress
Structural basis for the pore-forming activity of a complement-like toxin
No full textPore-forming proteins comprise a highly diverse group of proteins exemplified by the membrane attack complex/perforin (MACPF), cholesterol-dependent cytolysin (CDC), and gasdermin superfamilies, which all form gigantic pores (>150 angstroms). A recently found family of pore-forming toxins, called CDC-like proteins (CDCLs), are wide-spread in gut microbes and are a prevalent means of antibacterial antagonism. However, the structural aspects of how CDCLs assemble a pore remain a mystery. Here, we report the crystal structure of a proteolytically activated CDCL and cryo-electron microscopy structures of a prepore-like intermediate and a transmembrane pore providing detailed snapshots across the entire pore-forming pathway. These studies reveal a sophisticated array of regulatory features to ensure productive pore formation, and, thus, CDCLs straddle the MACPF, CDC, and gasdermin lineages of the giant pore superfamilies
An integrated framework to guide evidence-informed public health policymaking
No full textEvidence-informed policymaking emphasizes that policy decisions should be informed by the best available evidence from research and follow a systematic and transparent approach. For public health policymaking we can learn from existing practices of transparent, evidence-informed decision-making for clinical practice, medicines, and medical technology. We review existing evidence-to-decision frameworks, as well as frameworks and theories for policymaking to address the political dimension of policymaking, and use this analysis to propose an integrated framework to guide evidence-informed policymaking. The framework includes nine decision-making criteria and allows for the addition of other context-specific criteria. It also emphasizes elements of the decision-making process that can give greater legitimacy, fairness, and transparency to the policy decision, such as the use of deliberative processes and assessment of conflicts of interest. We offer the framework as a tool to help government policy makers use evidence in a structured and transparent way when making decisions about public health policy options
Randomized trial of same- versus opposite-arm coadministration of inactivated influenza and SARS-CoV-2 mRNA vaccines
No full textBACKGROUNDThe immunogenicity of current influenza vaccines needs improvement. Inactivated influenza and COVID-19 mRNA vaccines can be coadministered, but randomized controlled trial data are lacking on whether the 2 vaccines are more immunogenic if given in the same arm or opposite arms. Murine studies suggest mRNA vaccines can adjuvant influenza vaccines when coformulated and codelivered.METHODSWe randomly assigned 56 adults to receive the Afluria quadrivalent inactivated influenza and Moderna monovalent SARS-CoV-2 XBB.1.5 mRNA vaccines, either in opposite arms or both in the same arm at the same site. The primary endpoint was the difference in median combined serum hemagglutination inhibition titer to the H1, H3, and B-Vic vaccine influenza strains after vaccination.RESULTSWe found no significant difference in hemagglutination inhibition antibody levels between the groups (P = 0.30), with the same-arm group having a 1.26-fold higher titer than the opposite-arm group. There were no differences in analyses of antibodies against individual influenza strains or in nasal or saliva antibody levels. While both binding and neutralizing antibody titers against SARS-CoV-2 were not significantly different between groups postvaccination, there was a higher fold-change in BA.5 and ancestral strain neutralizing antibodies in the opposite-arm group.CONCLUSIONInfluenza vaccination is equivalently immunogenic if given in the same arm or opposite arms as the SARS-CoV-2 vaccine, but it may be preferable to administer the SARS-CoV-2 vaccine at a different site from influenza vaccines.TRIAL REGISTRATIONAustralian New Zealand Clinical Trials Registry ACTRN12624000445572.FUNDINGAustralian National Health and Medical Research Council, Australian Medical Research Future Fund, and National Institutes of Health (UH2AI176172)
Updating the diagnosis and management of elevated serum ferritin levels in the era of routine ferritin testing of blood donors by Australian Red Cross Lifeblood
No full textMy Milk, Your Fridge, Our Kitchen: Fragmented Consumption Within Shared Housing
No full text© 2025 Lu RenContemporary societies are increasingly characterised by precarity, uncertainty, and risk. In response, consumers have been relying on multiple modes of consumption to acquire and use resources, including ownership, access-based consumption, liquid consumption, and sharing. Prior research has theorised ownership and access-based consumption on a continuum, whereby consumers swiftly organise the things they own and the things they can access in their daily lives. This theorisation, however, conflates individual consumption with interpersonal consumption. As such, extant theories fall short in showing how consumers jointly negotiate arrangements about which resources are shared, which are individually owned, and which are merely accessible. Another stream of research closely connected with modes of consumption is space. Space has been seen as a resource consumed via multiple modes of consumption. Space, in turn, has its agency understood as affordances that shape consumption. Yet, there is a lack of comprehensive understanding of how consumer research on space and the body of work on modes of consumption coalesce. This dissertation adopts a qualitative research design within the context of Australian shared housing. It sets out to explore two research questions: (1) How do multiple consumers simultaneously navigate different modes of consumption? (2) How are space affordances actualised in interpersonal consumption when space is both a resource and an agent in consumption? I introduce the concept of fragmented consumption to answer these two research questions. I define fragmented consumption as a dynamic arrangement of modes of consumption for multiple resources, determined by multiple consumers and shaped by space. Fragmented consumption is inherently complex and often gives rise to tensions. I identify two recurring types of tension under fragmented consumption, namely, violation and misalignment. Violation arises when consumers fail to follow the established arrangement for the modes of consumption assigned to specific household resources. Misalignment is closely related to implicit arrangements for household resources, leading to differing perceptions of the consumption modes associated with them. I outline four coping strategies that consumers often adopt to manage these tensions: assertion, compromise, passive contestation, and resignation. Through these coping strategies, consumers either renegotiate or reframe ownership and access within the fragmented consumption system. My theorisation of fragmented consumption allows a re-examination of the relationships among modes of consumption and extends consumer research on space by accounting for how space affordances are actualised at the interpersonal level. Furthermore, it has implications for public policymaking, future housing design, product innovations, and offers actionable insights for consumers living in shared housing settings
Hepatitis B vaccination of preterm infants and risk of bronchopulmonary dysplasia: a cohort study, Australia
No full textOBJECTIVE: To determine whether hepatitis B virus (HBV) vaccination of extremely preterm infants (defined in our study as < 29 weeks gestation) within 24 hours of birth (birth-dose) increases the risk of developing bronchopulmonary dysplasia. METHODS: Using data from Australia, we conducted a population data linkage study using the Victorian Vaccine Safety Health Link. This platform links state-wide immunization and health outcomes from the Victorian Perinatal Data Collection and the Victorian Admitted Episodes Dataset. Our retrospective cohort study included all extremely preterm infants born alive during 2017-2020 (excluding data outliers). We investigated the relationship between birth-dose HBV vaccination and bronchopulmonary dysplasia diagnosis at 36 weeks postmenstrual age. We identified possible confounders using a directed acyclic graph, and included these confounders in a robust Poisson regression model. FINDINGS: Of the 818 extremely preterm infants meeting our inclusion criteria, 306 received birth-dose HBV vaccination: 50.7% (155/306) of the vaccinated and 61.9% (317/512) of the unvaccinated infants developed bronchopulmonary dysplasia. After accounting for measured confounders, the adjusted relative risk was 0.83 (95% confidence interval, CI: 0.68-1.00), suggesting no increased risk. However, residual confounding by indication may still be present as it is not known how clinician perception of the stability of the newborn affects the decision to vaccinate or not, potentially underestimating any association between vaccination and outcome. CONCLUSION: Our findings support existing World Health Organization recommendations to immunize all infants against HBV within 24 hours of birth, including those born prematurely
International practice patterns and perspectives on endovascular therapy for the treatment of cerebral venous thrombosis
No full textBACKGROUND: Cerebral venous thrombosis (CVT) accounts for 0.5-1% of all strokes. The role of endovascular therapy (EVT) in the management of CVT remains controversial and variations in practice patterns are not well known. AIMS: Here, we present a comprehensive, international characterization of practice patterns and perspectives on the use of EVT for CVT. METHODS: A comprehensive 42-question survey was distributed to stroke clinicians globally from May to October 2023, asking about practice patterns and perspectives on the use of EVT for CVT. RESULTS: The overall response rate was 31% (863 respondents of 2744 invited) across 61 countries. The majority of respondents (74%) supported the use of EVT for CVT in certain clinical situations. Key considerations for decision-making in using EVT favored clinical over radiographic/procedural factors and included worsening level of consciousness (86%) and worsening neurological deficits (76%). In the past 3 years, 56% of respondents used EVT for the treatment of CVT, with most (49.5%) involved in two to five cases. Among interventionalists, significant variability existed in the techniques used for EVT (p < 0.001), with aspiration thrombectomy (56%) and stent retriever (51%) being the most used overall. Regionally, interventionalists from China predominantly used intra-sinus heparin (56%), while this technique was most commonly ranked as "never indicated" throughout the rest of the world (23%). Post-procedure, low molecular weight heparin was the most used anticoagulant (83%), although North American respondents favored unfractionated heparin (37%), while imaging was primarily split between magnetic resonance (71.8%) and computed tomography (65.9%) arteriography or venography. CONCLUSION: Our survey reveals significant heterogeneity in approaches to EVT for CVT, and provides a comprehensive characterization of indications, techniques, and long-term management used by clinicians internationally. This resource will aid in optimizing patient selection and endovascular treatments for future trials
Molecular Methods Enhance the Detection of Pyoderma-Related Streptococcus pyogenes and emm-Type Distribution in Children
No full textBACKGROUND: Streptococcus pyogenes-related skin infections are increasingly implicated in the development of rheumatic heart disease (RHD) in lower-resource settings, where they are often associated with scabies. The true prevalence of S pyogenes-related pyoderma may be underestimated by bacterial culture. METHODS: A multiplex quantitative polymerase chain reaction (qPCR) assay for S pyogenes, Staphylococcus aureus, and Sarcoptes scabiei was applied to 250 pyoderma swabs from a cross-sectional study of children aged <5 years in The Gambia. Direct PCR-based emm-typing was used to supplement previous whole genome sequencing (WGS) of cultured isolates. RESULTS: Pyoderma lesions with S pyogenes increased from 51% (127/250) using culture to 80% (199/250) with qPCR. Compared to qPCR, the sensitivity of culture was 95.4% for S pyogenes (95% confidence interval {CI}, 77.2%-99.9%) in samples with S pyogenes alone (22/250 [9%]), but 59.9% (95% CI, 52.3%-67.2%) for samples with S aureus coinfection (177/250 [71%]). Direct PCR-based emm-typing was successful in 50% (46/92) of cases, identifying 27 emm-types, including 6 not identified by WGS (total 52 emm-types). CONCLUSIONS: Bacterial culture significantly underestimates the burden of S pyogenes in pyoderma, particularly with S aureus coinfection. Molecular methods should be used to enhance the detection of S pyogenes in surveillance studies and clinical trials of preventive measures in RHD-endemic settings