Background: Deep brain stimulation (DBS) in Parkinson’s disease (PD) requires extensive trial-and-error programming, often taking over a year to optimize. An objective, rapid biomarker of stimulation success is needed. Our team developed a functional magnetic resonance imaging (fMRI)-based algorithm to identify optimal DBS settings. This study prospectively compared fMRI-guided programming with standard-of-care (SoC) clinical programming in a double-blind, crossover, non-inferiority trial. Methods: Twenty-two PD-DBS patients were prospectively enrolled for fMRI using a 30-sec DBS-ON/OFF cycling paradigm. Optimal settings were identified using our published classification algorithm. Subjects then underwent >1 year of SoC programming. Clinical improvement was assessed under SoC and fMRI-determined stimulation conditions. Results: fMRI optimization significantly reduced the time required to determine optimal settings (1.6 vs. 5.6 months, p<0.001). Unified Parkinson’s Disease Rating Scale (UPDRSIII) improved comparably with both approaches (23.8 vs. 23.6, p=0.9). Non-inferiority was demonstrated within a predefined margin of 5 points (p=0.0018). SoC led to greater tremor improvement (p=0.019), while fMRI showed greater bradykinesia improvement (p=0.040). Conclusions: This is the first prospective evaluation of an algorithm able to suggest stimulation parameters solely from the fMRI response to stimulation. It suggests that fMRI-based programming may achieve equivalent outcomes in less time than SoC, reducing patient burden while potentially enhancing bradykinesia response.

Background: X-linked dystonia-parkinsonism(XDP) is a rare movement disorder primarily affecting males of Filipino descent characterized by dystonia and parkinsonism. This case illustrates a patient with a novel gene variant responsive to deep brain stimulation (DBS). Methods: Case study of Filipino male with XDP followed for 15 years. Results: A 32-year-old Filipino male presented with oromandibular and cervical dystonia which later generalized. He went on to develop parkinsonism with significant gait impairment, incomprehensible speech, and required PEG tube placement. His symptoms were refractory to pharmacologic therapy. At age 43, he underwent bilateral globus pallidus internus (GPi) DBS placement with significant improvement of his symptoms as illustrated by videos accompanying this report. He had marked improvement of gait, speech, and pharyngeal dystonia resulting in removal of his PEG tube with return to full oral intake. He continues to benefit 3 years after DBS placement. Genetic testing identified a missense hemizygous non-coding transcript exon variant TAF1 n.5776C>T which is a novel gene variant of XDP not previously reported in the literature. Conclusions: This case illustrates a patient with a novel TAF1 gene variant associated with XDP not previously reported in the literature. This variant was responsive to bilateral GPi DBS placement.

Cardiometabolic pregnancy complications, including gestational diabetes mellitus (GDM), hypertensive disorders of pregnancy (HDP), intrauterine growth restriction (IUGR) and preterm birth (PTB) are prevalent pregnancy complications that adversely affect maternal and neonatal health during pregnancy, and increase women’s risk of future type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD)1–5. Pregnancy and postpartum, including intrapartum periods, are critical windows of opportunity to deliver care to support sustained behaviour change(6). There is currently a gap in lifestyle (diet and physical activity) interventions specific to cardiometabolic disease risk awareness and prevention during and following pregnancy(5,7). These are key life stages where early risk factors for cardiometabolic disease may present, women are actively engaged in the healthcare system and their health priorities are shifting as they transition into parenthood. Early intervention in pregnancy may enable commencement of pharmacological and/or lifestyle intervention to reduce the risk or severity of cardiometabolic pregnancy complications(8), whereas postpartum intervention may enable commencement of sustainable lifestyle change for reduction of long-term cardiometabolic risks(9). There are a range of settings where pregnant and postpartum women receive healthcare, including hospitals, primary care clinics, community health institutions and online platforms(8,10,11). The optimum timing and setting to deliver an intervention to these high-risk women is not known. Designing interventions to align with the needs and priorities of stakeholders is a critical first step in developing an acceptable intervention. The aims of this research were to explore stakeholder perspectives and prioritise the optimal timing and setting to deliver a lifestyle intervention to improve long-term cardiometabolic health amongst women at high-risk of or diagnosed with a cardiometabolic pregnancy complication. An embedded mixed-methods research design was utilised. Facilitator-led workshops were used to prioritise the preferred timing (pregnancy or postpartum) and setting (hospital, general practice, community health program, maternal and child health services or online) for an intervention. Women with prior GDM, HDP, IUGR and/or PTB (n = 9), and research partners (n = 15) (obstetricians, endocrinologists, community health representatives, researchers, midwife, general practitioner, dietitian) participated. Workshops were audio recorded, transcribed verbatim and thematically analysed using template analysis. Online polls were used to assess participants preferred timing and setting for an intervention. Women preferred a postpartum intervention delivered online, whereas research partners preferred a pregnancy intervention delivered via hospital antenatal care. Both groups suggested commencing interventions during pregnancy and continuing postpartum. Participants recommended ensuring interventions consider healthcare system barriers to intervention delivery, equity and sustainment, as well as consumer-specific barriers to intervention engagement and lifestyle change during pregnancy and postpartum. Commencing patient-centred interventions during pregnancy and continuing postpartum should be considered to support continuity of care and improve health outcomes across both life stages for this high-risk group of women.

Cardiometabolic pregnancy complications (gestational diabetes mellitus (GDM), hypertensive disorders of pregnancy (HDP), intrauterine growth restriction (IUGR), preterm birth (PTB)) present a unique sex-specific risk factor for future cardiometabolic disease(1–5). Lifestyle modifications and healthful behaviour change (diet and physical activity), which can be supported by the delivery of evidence-based lifestyle interventions, are important factors in modifying risks of cardiometabolic conditions(2,6,7). Pregnancy and postpartum present unique windows of opportunity to intervene and prevent or delay the onset of cardiometabolic pregnancy complications and future cardiometabolic disease(2,8). Co-design considers the end-users wants, needs, preferences, characteristics and abilities throughout the entirety of the design process(9,10). Co-design processes engage women with lived experience alongside other key stakeholders including; community organisations, healthcare professionals, primary healthcare and health promotion experts14. In line with patient-centred care it offers the opportunity to design lifestyle interventions that are adapted to suit end-users, in the hope of increasing uptake, engagement, implementation success and sustainability(11). This study aims to co-design and explore stakeholders’ perspectives of the acceptability and feasibility of a lifestyle and screening intervention to reduce cardiometabolic risk amongst women at risk of or diagnosed with a cardiometabolic pregnancy complication. A descriptive qualitative research design was utilised. Two 2-hour co-design group workshops and a series of one-on-one semi-structured interviews were conducted with women with prior GDM, HDP, IUGR and/or PTB (n = 11), and research partners (obstetricians, endocrinologists, community health representatives, researchers, midwives, general practitioners, dietitians) (n = 14). Participants were provided with an overview of a potential lifestyle intervention, discussed the acceptability of each intervention component (outlined by the TIDieR framework; brief name, why, what, who provided, how, where, when and how much, tailoring, modifications, how well(12)), and the feasibility of implementation (outlined by the Theoretical Framework of Acceptability(13) and the APEASE criteria for intervention design(14)). Workshops and interviews were audio recorded, transcribed and analysed using template analysis. Analysis highlighted 10 key themes. Participants recommended the intervention is holistic, user-friendly, empowering, empathetic, patient-centred and culturally sensitive. Participants highlighted the importance of good risk communication, focusing on a positive, healthy pregnancy as opposed to risk reduction. Participants recommended providing additional resources and access to health services to complement intervention content. Participants suggested the intervention be delivered by female healthcare professionals from a range of cultural backgrounds with expertise in cardiometabolic pregnancy complications and postpartum management. Participants discussed the importance and value of the proposed intervention in filling what was perceived as a current healthcare gap for women at risk and diagnosed with cardiometabolic conditions during and following pregnancy. Engaging stakeholders to co-design an intervention that aligns with women’s and the healthcare system’s preferences, needs and priorities will support the development of an acceptable intervention for implementation in a real-world setting.

Especially in the context of climate adaptation policy, creating support for hard policy instruments and convincing people that their individual contributions do matter are two significant challenges. In this study, we test the effect of an individually versus collectively framed gain-appeal infographic on the acceptance of hard policy instruments and this in the context of strictly private climate change adaptation behaviour. We used a mixed methods approach focussing on reducing private paving in domestic gardens in Belgium. Evidence from an online survey experiment (n = 3,389) showed that policy makers implementing a collectively framed infographic can increase the acceptance of a more strict permit policy and a yearly financial contribution, while simultaneously enhancing personal and collective self-efficacy and outcome expectancy beliefs. Complementary insights from qualitative data learned that perceived (in)equity is a crucial point of attention when designing climate policies addressing private paving. A collectively framed infographic may convey the message ‘yes, we ánd I can’. With these “findings, we want to trigger new opportunities in climate policies beyond the current policy scopes.

Objectives/Goals: Our goal is to enhance communication and documentation in collaborative biostatistics by refining data management and metadata processes. We aim to capture critical data collection and generation information, improve transparency and reproducibility, and foster stronger researcher partnerships for more effective collaborations. Methods/Study Population: Traditional statistical analysis plans (SAP) often miss essential contextual knowledge from collaborators, leading to gaps that hinder reproducibility and limit future data use. Biostatistics teams at the University of Kentucky have updated their strategies to better capture important details about data origins and collection processes. By focusing on clear, comprehensive documentation early in the research process, we aim to preserve foundational data insights and improve collaboration efficiency. Our Biostatistics, Epidemiology, and Research Design (BERD) team has established best practices for addressing data management structures with collaborators across medical and healthcare fields – covering all project stages, from initial data collection to metadata creation and dataset finalization. Results/Anticipated Results: We will detail the processes used to improve data management structures and the observed results of these processes. For example, initiating deeper discussions about data origins and collection processes as early as possible in the collaboration has resulted in a more comprehensive project narrative that lays the foundation for effective collaboration. By engaging with project leaders early in the process, we can confirm that critical details about how data were collected and processed are documented, improving both the transparency and reproducibility of research findings. Streamlining the processes of capturing this information makes it more accessible and useful for those with limited statistical backgrounds, which is particularly relevant for faculty and staff in BERD communities and Clinical and Translational Science Awards Programs. Discussion/Significance of Impact: Nuanced data documentation structures are crucial for transforming raw data into meaningful, reusable datasets. Our initiatives promote clear communication, enhanced efficiency, and streamlined workflows. Translational science researchers can benefit from improving data management and metadata to boost long-term collaborative success.

Objectives/Goals: The timing of neurosurgery is highly variable for post-hemorrhagic hydrocephalus (PHH) of prematurity. We sought to utilize microvascular imaging (MVI) in ultrasound (US) to identify biomarkers to discern the opportune time for intervention and to analyze the cerebrospinal fluid (CSF) characteristics as they pertain to neurosurgical outcome. Methods/Study Population: The inclusion criteria for the study are admission to the neonatal intensive care unit (NICU) with a diagnosis of Papile grade III or IV. Exclusion criteria are congenital hydrocephalus and hydrocephalus secondary to myelomeningocele/brain tumor/vascular malformation. We are a level IV tertiary referral center. Our current clinical care pathway utilizes brain US at admission and at weekly intervals. Patients who meet certain clinical and radiographic parameters undergo temporary or permanent CSF diversion. Results/Anticipated Results: NEL was implemented at our institution for PHH of prematurity in fall 2022. To date, we have had 20 patients who were diagnosed with grade III or IV IVH, of which 12 qualified for NEL. Our preliminary safety and feasibility results as well as the innovative bedside technique pioneered at our institution are currently in revision stages for publication. Preliminary results of the MVI data have yielded that hyperemia may confer venous congestion in the germinal matrix, which should then alert the neurosurgeon to delay any intervention to avoid progression of intraventricular blood. With regard to CSF characteristics, we anticipate that protein, cell count, hemoglobin, iron, and ferritin will decrease with NEL. Discussion/Significance of Impact: The timing of PHH of prematurity is highly variable. We expect that MVI will offer radiographic biomarkers to guide optimal timing of neurosurgical intervention. A better understanding of CSF characteristics could potentially educate the neurosurgeon with regard to optimal timing of permanent CSF diversion based on specific CSF parameters.

This article explores the causes of nationalist civil war, a subtype of ethnic civil war in which anti-state actors fight for greater communal autonomy. It presents a theoretical framework claiming that grievances over lost communal autonomy commonly motivate nationalist civil war, but that other conditions are needed to put this motive into action: Nationalist frames and expectations must make communities sensitive to lost autonomy, and mobilizational resources must be available so actors can organize nationalist movements. Nation-state building, in turn, commonly promotes reductions in communal autonomy, and British colonial pluralism frequently strengthened nationalist frames, expectations, and mobilizational resources, suggesting that nationalist civil war should be common in former British colonies after transitions from empire to nation-state. To test the framework, this article provides a comparative historical analysis of Zomia, a region that has the highest concentration of nationalist civil wars in the world and in which half of the countries are former British colonies. The analysis provides strong evidence supporting the theoretical framework.

Non-word repetition (NWR) is often utilized for the assessment of phonological short-term memory (PSTM) and as a clinical marker for language-related disorders. In this study, associations between children's language competence and their performance in language-specific NWR tasks as well as the relevance of NWR for the prediction of language development were scrutinized. German preschoolers (N = 1,801) were compared regarding their performance in NWR, German vocabulary, and articulation. For 141 children, results of a school enrolment test were available. Multilingual children performed as well as monolingual German-speaking children in NWR only under the condition of comparable German language skills. NWR performance depended on item length, children's vocabulary and articulation skills and was weakly associated with language-related medical issues. The predictive power of NWR for children's performance in the school enrolment test was minimal. To conclude, chosen German-based NWR tasks did not deliver convincing results as a clinical marker or predictor of language development.