UKHCDO gene therapy taskforce: Guidance for implementation of haemophilia gene therapy into routine clinical practice for adults.

Introduction: 2022 was a landmark year with two adeno-associated viral vectors (AAVs) receiving conditional marketing authorization from EMA for the treatment of persons with severe haemophilia A and severe to moderately severe haemophilia B and a third in 2024. Gene therapy is a transformative, irreversible treatment with long-lasting effects, necessitating development of new clinical pathways to ensure optimal outcomes.

Aim: To develop a consensus framework and service specification for delivery of AAV gene therapy for haemophilia in adults within the UK using the hub-and-spoke model proposed by the European Association of Haemophilia and Allied Disorders and the European Haemophilia Consortium.

Mediating effects of inequitable gender norms on intimate partner violence and contraceptive use in a cluster randomized control trial in Niger.

Previous research has demonstrated that the Reaching Married Adolescents intervention (RMA) was associated with changes in inequitable gender norms, intimate partner violence (IPV), and modern contraceptive use. This study seeks to understand if changes in inequitable gender norms mediate the RMA intervention's effects on contraceptive use and intimate partner violence (IPV). A four-arm cluster randomized control trial was conducted to evaluate effects of the RMA intervention (household visits, small groups, combination, control) on married adolescent girls and their husbands in Dosso, Niger (baseline: 1042 dyads; 24m follow-up: 737 dyads; 2016-2019).

Speaker-independent speech inversion for recovery of velopharyngeal port constriction degreea).

For most of his illustrious career, Ken Stevens focused on examining and documenting the rich detail about vocal tract changes available to listeners underlying the acoustic signal of speech. Current approaches to speech inversion take advantage of this rich detail to recover information about articulatory movement. Our previous speech inversion work focused on movements of the tongue and lips, for which "ground truth" is readily available.

Computer-assisted syllable analysis of continuous speech as a measure of child speech disordera).

In this study, a computer-driven, phoneme-agnostic method was explored for assessing speech disorders (SDs) in children, bypassing traditional labor-intensive phonetic transcription. Using the SpeechMark® automatic syllabic cluster (SC) analysis, which detects sequences of acoustic features that characterize well-formed syllables, 1952 American English utterances of 60 preschoolers were analyzed [16 with speech disorder present (SD-P) and 44 with speech disorder not present (SD-NP)] from two dialectal areas. A four-factor regression analysis evaluated the robustness of seven automated measures produced by SpeechMark® and their interactions.

Physical, Sexual, and Intimate Partner Violence Among Transgender and Gender-Diverse Individuals.

Importance: Transgender and gender-diverse (TGD) communities experience disproportionate levels of violence, yet due to limitations in measuring TGD identity, few state-representative estimates are available.

Objective: To assess gender identity differences in experiences of violence among adults.

Design, Setting, And Participants: Cross-sectional data from the 2023 California Violence Experiences (CalVEX) survey, weighted to provide state-representative estimates, was used to assess associations between gender identity and past-year experiences of violence among adults 18 years and older.

Ubiquitin-specific protease 7 inhibitors reveal a differentiated mechanism of p53-driven anti-cancer activity.

The USP7 deubiquitinase regulates proteins involved in the cell cycle, DNA repair, and epigenetics and has been implicated in cancer progression. USP7 inhibition has been pursued for the development of anti-cancer therapies. Here, we describe the discovery of potent and specific USP7 inhibitors exemplified by FX1-5303.

"They Don't See Us": Asian Students' Perceptions of Sexual Violence and Sexual Harassment on Three California Public University Campuses.

Sexual violence and sexual harassment (SVSH) are prevalent among college and university students; however, the experiences of ethnic minority students, especially Asians, are understudied. This study aimed to reduce this gap by exploring Asian students' perceptions of SVSH on three public university campuses in Southern California. We examined their perceptions about the campus environment related to SVSH, attitudes, and behaviors toward help seeking, and utilization of on-campus resources.

Multi-Level Protective and Risk Factors Longitudinally Associated with Dating Violence Perpetration among Non-Urban Mexican-American Adolescents.

To assess the longitudinal relationship between individual and interpersonal risk and protective factors and dating violence perpetration among non-urban Mexican-American youth. With data from a 24-month prospective cohort study (2015-2019; baseline recruitment spanned from 2015-2017; four follow-up interviews every 6 months) of Mexican-American youth (8th grade at baseline) living in an agricultural region (Salinas, California), we utilized multivariable modified Poisson general estimating equations stratified by gender ( = 489) to assess the relationships of religiosity, non-violent problem-solving skills, school connectedness, family cohesion, and bullying victimization with dating violence perpetration. Among girls, but not boys, non-violent problem-solving skills [adjusted relative risk (ARR): 0.

Educational needs of patients, families, and healthcare professionals to support the patient journey in haemophilia gene therapy in the UK.

With the first gene therapies for haemophilia approved by the European Commission, the US Food and Drug Administration, and the Medicines and Healthcare products Regulatory Agency, it is important to consider the remaining unmet needs and challenges that may arise throughout patients' treatment journeys. We discuss existing unmet needs and important considerations prior to, during, and following haemophilia gene therapy treatment in the UK, and propose potential next steps. Key areas for attention are education, psychological support, and guidance on implementation.

Nutrition Education in Medical Schools: What do Medical Students Think?

Objective: To examine medical students' perceptions of the nutrition education received and their ability to apply that knowledge in clinical settings.

Methods: This is a qualitative study using a structured survey with free responses to solicit the perspective of US medical students regarding their nutrition education. A national online survey was distributed by the American Academy of Pediatrics, Section on Pediatric Trainees.

Effect of a gender-synchronized family planning intervention on inequitable gender norms in a cluster randomized control trial among husbands of married adolescent girls in Dosso, Niger.

Gender inequity is pervasive globally and has severe consequences for health and well-being, particularly for women and girls in Niger. The Reaching Married Adolescents in Niger (RMA) intervention aimed to promote equitable gender norms in order to increase modern contraceptive use and reduce intimate partner violence among married adolescent girls and their husbands in Niger. Using data from a 4-arm factorial cluster randomized control trial of the RMA intervention (2016-2019), the current study assesses effects of the RMA intervention on gender norms among husbands.

Effects of a clinic-based reproductive empowerment intervention on proximal outcomes of contraceptive use, self-efficacy, attitudes, and awareness and use of survivor services: a cluster-controlled trial in Nairobi, Kenya.

This study was undertaken to evaluate the effect of a reproductive empowerment contraceptive counselling intervention (ARCHES) adapted to private clinics in Nairobi, Kenya on proximal outcomes of contraceptive use and covert use, self-efficacy, awareness and use of intimate partner violence (IPV) survivor services, and attitudes justifying reproductive coercion (RC) and IPV. We conducted a cluster-controlled trial among female family planning patients ( = 659) in six private clinics non-randomly assigned to ARCHES or control in and around Nairobi, Kenya. Patients completed interviews immediately before (baseline) and after (exit) treatment and at three- and six-month follow-up.

Neural Changes in Children With Residual Speech Sound Disorder After Ultrasound Biofeedback Speech Therapy.

Purpose: Children with residual speech sound disorders (RSSD) have shown differences in neural function for speech production, as compared to their typical peers; however, information about how these differences may change over time and relative to speech therapy is needed. To address this gap, we used functional magnetic resonance imaging (fMRI) to examine functional activation and connectivity on adaptations of the syllable repetition task (SRT-Early Sounds and SRT-Late Sounds) in children with RSSD before and after a speech therapy program.

Method: Sixteen children with RSSD completed an fMRI experiment before (Time 1) and after (Time 2) a speech therapy program with ultrasound visual feedback for /ɹ/ misarticulation.

Measuring social norms of intimate partner violence to exert control over wife agency, sexuality, and reproductive autonomy: an item response modelling of the IPV-ASRA scale.

Background: The field of violence prevention research is unequivocal that interventions must target contextual factors, like social norms, to reduce gender-based violence. Limited research, however, on the social norms contributing to intimate partner violence or reproductive coercion exists. One of the driving factors is lack of measurement tools to accurately assess social norms.

Effects of the reaching married adolescents program on modern contraceptive use and intimate partner violence: results of a cluster randomized controlled trial among married adolescent girls and their husbands in Dosso, Niger.

Background: Niger has the highest rate of adolescent fertility in the world, with early marriage, early childbearing and high gender inequity. This study assesses the impact of Reaching Married Adolescents (RMA), a gender-synchronized social behavioral intervention designed to improve modern contraceptive use and reduce intimate partner violence (IPV) among married adolescent couples in rural Niger.

Methods: We conducted a four-armed cluster-randomized trial in 48 villages across three districts in Dosso region, Niger.

RNAi for the Treatment of People with Hemophilia: Current Evidence and Patient Selection.

Severe hemophilia is associated with spontaneous, prolonged and recurrent bleeding. Inadequate prevention and treatment of bleeding can lead to serious morbidity and mortality. Due to the limitations of intravenous clotting factor replacement, including the risk of inhibitory antibodies, innovative novel therapies have been developed that have dramatically changed the landscape of hemophilia therapy.

A Qualitative Analysis of Clinician Perspectives of Ultrasound Biofeedback for Speech Sound Disorders.

Purpose: Ultrasound biofeedback therapy (UBT) is a relatively new type of technology-assisted speech-language therapy and has shown promise in remediating speech sound disorders. However, there is a current lack of understanding of the barriers and benefits that may influence the usage behavior and clinical decision making for the implementation of UBT from a clinician perspective. In this qualitative study, we explore the perspectives of speech-language pathologists (SLPs) who have used ultrasound biofeedback in programs of speech sound therapy using the unified theory of acceptance and use of technology (UTAUT) model.

Hospital bed replacement for acute care of children at home during the COVID-19 pandemic through a Hospital-in-the-Home programme.

Objectives: During the COVID-19 pandemic, we expanded our Hospital-in-the-Home (HITH) programme to increase capacity and manage COVID-19-positive children. We aimed to assess impact on overall HITH activity and COVID-19-positive outcomes.

Design: Prospective comparative cohort study.

Malignant middle cerebral artery syndrome with thrombotic thrombocytopenia following vaccination against SARS-CoV-2.

Cases of thromboses at unusual sites with thrombocytopenia have been reported following vaccination against Sars-CoV-2. This new syndrome, christened vaccine-induced thrombotic thrombocytopenia (VITT), mainly results in venous thromboses. We report the case of a young woman with a right middle cerebral artery stroke following vaccination with ChAdOx1 nCoV-19.

Mediating effects of inequitable gender norms on intimate partner violence and contraceptive use in a cluster randomized control trial in Niger: A causal inference mediation analysis.

Background: Gender inequity, a deeply-rooted driver of poor health globally, is expressed in society through gender norms, the unspoken rules that govern gender-related roles and behavior. The development of public health interventions focused on promoting equitable gender norms are gaining momentum internationally, but there remain critical gaps in the evidence about how these interventions are working to change behavioral outcomes.

Methods: A four-arm cluster randomized control trial (cRCT) was conducted to evaluate the effects of the Reaching Married Adolescents in Niger (RMA) intervention on modern contraceptive use and intimate partner violence (IPV) among married adolescent girls and their husbands in Dosso, Niger (T1: 1042 dyads; 24 mos.

Little discrepancy between one-stage and chromogenic factor VIII (FVIII)/IX assays in a large international cohort of persons with nonsevere hemophilia A and B.

Background: Accurate measurements of coagulation factor activity form an essential part of hemophilia management and are performed by the one-stage or chromogenic assay. Current literature suggests that approximately one-third of persons with nonsevere hemophilia A exhibit assay discrepancy, albeit with a high variability between studies. Such data are scarce in nonsevere hemophilia B.

An improved human skin explant culture method for testing and assessing personal care products.

Background: Cultured human skin models have been widely used in the evaluation of dermato-cosmetic products as alternatives to animal testing and expensive clinical testing. The most common in vitro skin culture approach is to maintain skin biopsies in an airlifted condition at the interface of the supporting culture medium and the air phase. This type of ex vivo skin explant culture is not, however, adequate for the testing of cleansing products, such as shampoos and body washes.