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The Air Force Research Laboratory/Phillips Laboratory magnetically insulated transmission line oscillator (MILO) is a gigawatt-class, L-band, high-power microwave tube driven by a 500-kV, 60-kA electron beam. A previous version of this tube [1] generated 1.5 GW pulses, but with significant RF pulse shortening. This paper reports on improvements to the tube that have allowed us to increase the output power by 25% and to increase the RF pulse duration by a factor of two and a half. Index Terms - Crossed-field device, high-power microwave tube, magnetically insulated transmission line oscillator, MILO.

Samira Tatiyama Miyamoto,1 Dennis William Lendrem,2–4 Wan-Fai Ng,2–4 Katie Louise Hackett,2,4–5 Valéria Valim6,71Department of Integrated Education in Health, Universidade Federal do Espírito Santo, Vitória, Brazil; 2Musculoskeletal Research Group, Institute of Cellular Medicine, Newcastle University and NIHR Newcastle Biomedical Research Centre, Newcastle University, Newcastle upon Tyne, UK; 3NIHR Newcastle Biomedical Research Centre, Newcastle University, Newcastle upon Tyne, UK; 4Newcastle upon Tyne Hospitals NHS Trust, , Newcastle upon Tyne, UK; 5Department of Social Work, Education and Community Wellbeing, Northumbria University, Newcastle upon Tyne, UK; 6Department of Medical Clinic, Universidade Federal do Espírito Santo, Vitória, Brazil; 7Rheumatology Outpatient Clinic, Hospital Universitário Cassiano Antônio de Moraes (HUCAM), Vitória, BrazilAbstract: Primary Sjögren’s syndrome (pSS) patients identify fatigue as their most important symptom and the one most difficult to cope with, but there are still many challenges and few solutions to manage this debilitating symptom. Promising pharmacological treatments, such as rituximab, have failed in more stringent tests including randomized controlled trials (RCTs) and meta-analysis. While non-pharmacological interventions may be safer, less costly, and address other common comorbidities, to date only aerobic exercise seems to be effective at reducing fatigue in pSS. All interventions, pharmacological or not, need to be tested in high-quality RCTs. The aim of this review is to provide an overview of fatigue management in pSS and discuss potential opportunities for future research.Keywords: primary Sjögren’s syndrome, fatigue, treatment, review

Background: Current methods of monitoring cognition in older adults are insufficient to address the growing burden of Alzheimer disease and related dementias (AD/ADRD). New approaches that are sensitive, scalable, objective, and reflective of meaningful functional outcomes are direly needed. Mobility trajectories and geospatial life space patterns reflect many aspects of cognitive and functional integrity and may be useful proxies of age-related cognitive decline., Objective: We investigated the feasibility, acceptability, and preliminary validity of a 1-month smartphone digital phenotyping protocol to infer everyday cognition, function, and mood in older adults from passively obtained GPS data. We also sought to clarify intrinsic and extrinsic factors associated with mobility phenotypes for consideration in future studies., Methods: Overall, 37 adults aged between 63 and 85 years with healthy cognition (n=31, 84%), mild cognitive impairment (n=5, 13%), and mild dementia (n=1, 3%) used an open-source smartphone app (mindLAMP) to unobtrusively capture GPS trajectories for 4 weeks. GPS data were processed into interpretable features across categories of activity, inactivity, routine, and location diversity. Monthly average and day-to-day intraindividual variability (IIV) metrics were calculated for each feature to test a priori hypotheses from a neuropsychological framework. Validation measures collected at baseline were compared against monthly GPS features to examine construct validity. Feasibility and acceptability outcomes included retention, comprehension of study procedures, technical difficulties, and satisfaction ratings at debriefing., Results: All (37/37, 100%) participants completed the 4-week monitoring period without major technical adverse events, 100% (37/37) reported satisfaction with the explanation of study procedures, and 97% (36/37) reported no feelings of discomfort. Participants' scores on the comprehension of consent quiz were 97% on average and associated with education and race. Technical issues requiring troubleshooting were infrequent, though 41% (15/37) reported battery drain. Moderate to strong correlations (r≥0.3) were identified between GPS features and validators. Specifically, individuals with greater activity and more location diversity demonstrated better cognition, less functional impairment, less depression, more community participation, and more geospatial life space on objective and subjective validation measures. Contrary to predictions, greater IIV and less routine in mobility habits were also associated with positive outcomes. Many demographic and technology-related factors were not associated with GPS features; however, income, being a native English speaker, season of study participation, and occupational status were related to GPS features., Conclusions: Theoretically informed digital phenotypes of mobility are feasibly captured from older adults' personal smartphones and relate to clinically meaningful measures including cognitive test performance, reported functional decline, mood, and community activity. Future studies should consider the impact of intrinsic and extrinsic factors when interpreting mobility phenotypes. Overall, smartphone digital phenotyping is a promising method to unobtrusively capture relevant risk and resilience factors in the context of aging and AD/ADRD and should continue to be investigated in large, diverse samples., (©Katherine Hackett, Shiyun Xu, Moira McKniff, Lido Paglia, Ian Barnett, Tania Giovannetti. Originally published in JMIR Human Factors (https://humanfactors.jmir.org), 22.11.2024.)

Background: Sjögren's syndrome (SS) is the second most common autoimmune rheumatic disease, and the range of symptoms includes fatigue, dryness, sleep disturbances, and pain. Smartphone apps may help deliver a variety of cognitive and behavioral techniques to support self-management in SS. However, app-based interventions must be carefully designed to promote engagement and motivate behavior change., Objective: We aimed to explore self-management approaches and challenges experienced by people living with SS and produce a corresponding set of design recommendations that inform the design of an engaging, motivating, and evidence-based self-management app for those living with SS., Methods: We conducted a series of 8 co-design workshops and an additional 3 interviews with participants who were unable to attend a workshop. These were audio recorded, transcribed, and initially thematically analyzed using an inductive approach. Then, the themes were mapped to the Self-Determination Theory domains of competency, autonomy, and relatedness., Results: Participants experienced a considerable demand in the daily work required in self-managing their SS. The condition demanded unrelenting, fluctuating, and unpredictable mental, physical, and social efforts. Participants used a wide variety of techniques to self-manage their symptoms; however, their sense of competency was undermined by the complexity and interconnected nature of their symptoms and affected by interactions with others. The daily contexts in which this labor was occurring revealed ample opportunities to use digital health aids. The lived experience of participants showed that the constructs of competency, autonomy, and relatedness existed in a complex equilibrium with each other. Sometimes, they were disrupted by tensions, whereas on other occasions, they worked together harmoniously., Conclusions: An SS self-management app needs to recognize the complexity and overlap of symptoms and the complexities of managing the condition in daily life. Identifying techniques that target several symptoms simultaneously may prevent users from becoming overwhelmed. Including techniques that support assertiveness and communication with others about the condition, its symptoms, and users' limitations may support users in their interactions with others and improve engagement in symptom management strategies. For digital health aids (such as self-management apps) to provide meaningful support, they should be designed according to human needs such as competence, autonomy, and relatedness. However, the complexities among the 3 Self-Determination Theory constructs should be carefully considered, as they present both design difficulties and opportunities., (©Claire McCallum, Miglena Campbell, John Vines, Tim Rapley, Jason Ellis, Vincent Deary, Katie Hackett. Originally published in JMIR Human Factors (https://humanfactors.jmir.org), 17.04.2024.)

Background: Although whole-genome sequencing (WGS) is the preferred genotyping method for most genomic analyses, limitations are often experienced when studying genomes characterized by a high percentage of repetitive elements, high linkage, and recombination deserts. The Asian tiger mosquito (Aedes albopictus), for example, has a genome comprising up to 72% repetitive elements, and therefore we set out to develop a single-nucleotide polymorphism (SNP) chip to be more cost-effective. Aedes albopictus is an invasive species originating from Southeast Asia that has recently spread around the world and is a vector for many human diseases. Developing an accessible genotyping platform is essential in advancing biological control methods and understanding the population dynamics of this pest species, with significant implications for public health., Methods: We designed a SNP chip for Ae. albopictus (Aealbo chip) based on approximately 2.7 million SNPs identified using WGS data from 819 worldwide samples. We validated the chip using laboratory single-pair crosses, comparing technical replicates, and comparing genotypes of samples genotyped by WGS and the SNP chip. We then used the chip for a population genomic analysis of 237 samples from 28 sites in the native range to evaluate its usefulness in describing patterns of genomic variation and tracing the origins of invasions., Results: Probes on the Aealbo chip targeted 175,396 SNPs in coding and non-coding regions across all three chromosomes, with a density of 102 SNPs per 1 Mb window, and at least one SNP in each of the 17,461 protein-coding genes. Overall, 70% of the probes captured the genetic variation. Segregation analysis found that 98% of the SNPs followed expectations of single-copy Mendelian genes. Comparisons with WGS indicated that sites with genotype disagreements were mostly heterozygotes at loci with WGS read depth < 20, while there was near complete agreement with WGS read depths > 20, indicating that the chip more accurately detects heterozygotes than low-coverage WGS. Sample sizes did not affect the accuracy of the SNP chip genotype calls. Ancestry analyses identified four to five genetic clusters in the native range with various levels of admixture., Conclusions: The Aealbo chip is highly accurate, is concordant with genotypes from WGS with high sequence coverage, and may be more accurate than low-coverage WGS., (© 2024. The Author(s).)

Gene drive technology has been recognized for its potential to provide durable and cost-effective solutions for previously intractable problems in public health, conservation, and agriculture. In recognition of the rapid advances in this field, in 2016 the U.S. National Academies of Sciences, Engineering, and Medicine issued a report making several recommendations aimed at researchers, funders, and policymakers for the safe and responsible research and development of gene drive technology. Subsequently, in 2017 sixteen global organizations self-identifying as sponsors and supporters of gene drive research became public signatories committed to the 'Principles for Gene Drive Research' which were inspired by the report's recommendations. Herein we reflect on the progress of gene drive research in relation to the ethical principles laid out and committed to by the signatories to the Principles. Our analysis indicates high levels of alignment with the Principles in the field of gene drive research. The manuscript also discusses the Gene Drive Research Forum, which had its genesis in the publication of the Principles. Discussions between participants at the latest meeting of the Forum point to the work that lies ahead for gene drive research in line with the Principles. Going forward the gene drive research community can productively focus on: i) safety and efficacy criteria for open release, ii) risk assessment frameworks and methods, iii) more downstream technical, regulatory and policy considerations for field evaluations and implementation, iv) continued transparency and developing mechanisms of accountability, and v) strengthening capacity in locales of potential release and expected drive spread., Competing Interests: No competing interests were disclosed., (Copyright: © 2024 Roberts AJ et al.)

Addressing global health crises requires a receptive and expedient policy environment to minimise delays in making available potentially life-saving technologies. Over time, the policy environment has adapted to ensure that communities have expedited access to promising technologies, such as vaccines, that can mitigate morbidity and mortality. Emergency authorisations are one such policy mechanism. While these have been employed successfully for several diseases, such as influenza, Ebola and COVID-19, the policy mechanism is tied to contexts where key bodies have designated the disease an 'emergency', whereas no equivalent mechanism exists for those failing to acquire the designation (eg, malaria and tuberculosis). In this paper, we examine ethical issues associated with emergency authorisations. We argue that there is no moral difference between those diseases considered emergencies and many that fail to be designated as such with respect to impact on affected communities. Thus, tying access to an expedient policy mechanism for approval to an emergency designation is ethically unjustified-it should be based on considerations of risks and benefits, the disease burden and the values of the communities that carry those risks and not contingent on if the disease is designated an emergency. We suggest the need to further enhance the policy environment to ensure access to similar expedited approval programmes irrespective of if a disease is an emergency. Levelling the field for access to expedited approval programmes across diseases can help in moving towards achieving global health equity but is not a panacea., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Background: Nurses play an essential role in patient safety. Inadequate nursing physical assessment and communication in handover practices are associated with increased patient deterioration, falls and pressure injuries. Despite internationally implemented rapid response systems, falls and pressure injury reduction strategies, and recommendations to conduct clinical handovers at patients' bedside, adverse events persist. This trial aims to evaluate the effectiveness, implementation, and cost-benefit of an externally facilitated, nurse-led intervention delivered at the ward level for core physical assessment, structured patient-centred bedside handover and improved multidisciplinary communication. We hypothesise the trial will reduce medical emergency team calls, unplanned intensive care unit admissions, falls and pressure injuries., Methods: A stepped-wedge cluster randomised trial will be conducted over 52 weeks. The intervention consists of a nursing core physical assessment, structured patient-centred bedside handover and improved multidisciplinary communication and will be implemented in 24 wards across eight hospitals. The intervention will use theoretically informed implementation strategies for changing clinician behaviour, consisting of: nursing executive site engagement; a train-the-trainer model for cascading facilitation; embedded site leads; nursing unit manager leadership training; nursing and medical ward-level clinical champions; ward nurses' education workshops; intervention tailoring; and reminders. The primary outcome will be a composite measure of medical emergency team calls (rapid response calls and 'Code Blue' calls), unplanned intensive care unit admissions, in-hospital falls and hospital-acquired pressure injuries; these measures individually will also form secondary outcomes. Other secondary outcomes are: i) patient-reported experience measures of receiving safe and patient-centred care, ii) nurses' perceptions of barriers to physical assessment, readiness to change, and staff engagement, and iii) nurses' and medical officers' perceptions of safety culture and interprofessional collaboration. Primary outcome data will be collected for the trial duration, and secondary outcome surveys will be collected prior to each step and at trial conclusion. A cost-benefit analysis and post-trial process evaluation will also be undertaken., Discussion: If effective, this intervention has the potential to improve nursing care, reduce patient harm and improve patient outcomes. The evidence-based implementation strategy has been designed to be embedded within existing hospital workforces; if cost-effective, it will be readily translatable to other hospitals nationally., Trial Registration: Australian New Zealand Clinical Trials Registry ID: ACTRN12622000155796. Date registered: 31/01/2022., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: There is limited evidence between contraceptive use, availability of commodities and distance to the facility in developing countries. Distance to the facility is an essential determinant of contraceptive use. Still, women may not seek family planning services from the nearest facility and may be prepared to travel the farthest distance to receive quality family planning services., Methods: We analyzed women's survey data linked to health facility data and applied an alternate specific conditional logit model to examine the distance a woman is prepared to travel and the quality of services offered by facilities in urban areas in Karachi, Pakistan., Results: This study analyzed data from 336 women and 28 facilities and identified that the mean distance to the nearest facility was 0.44 km; the chosen facility was, on average, 5 km away. Women preferred facilities that offered a range of contraceptive methods and additional services provided by female healthcare providers only. Furthermore, on average, women are willing to travel a further 1.7 km for a facility that offers more family planning methods, 1.4 km for a facility that offers additional health services and 11 km for a facility that offers services delivered by female healthcare providers., Conclusions: The findings highlight the quality measures women prioritize over distance and consider essential when choosing a family planning facility., (© The Author(s) 2022. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

As the global burden of dementia continues to plague our healthcare systems, efficient, objective, and sensitive tools to detect neurodegenerative disease and capture meaningful changes in everyday cognition are increasingly needed. Emerging digital tools present a promising option to address many drawbacks of current approaches, with contexts of use that include early detection, risk stratification, prognosis, and outcome measurement. However, conceptual models to guide hypotheses and interpretation of results from digital tools are lacking and are needed to sort and organize the large amount of continuous data from a variety of sensors. In this viewpoint, we propose a neuropsychological framework for use alongside a key emerging approach-digital phenotyping. The Variability in Everyday Behavior (VIBE) model is rooted in established trends from the neuropsychology, neurology, rehabilitation psychology, cognitive neuroscience, and computer science literature and links patterns of intraindividual variability, cognitive abilities, and everyday functioning across clinical stages from healthy to dementia. Based on the VIBE model, we present testable hypotheses to guide the design and interpretation of digital phenotyping studies that capture everyday cognition in vivo. We conclude with methodological considerations and future directions regarding the application of the digital phenotyping approach to improve the efficiency, accessibility, accuracy, and ecological validity of cognitive assessment in older adults., (©Katherine Hackett, Tania Giovannetti. Originally published in JMIR Aging (https://aging.jmir.org), 07.09.2022.)

Plant breeding plays a crucial role for the EU to live up to its values and promises of sustainability, innovation and diversity and inclusion. The current regulations, however, make it de facto impossible to use new breeding technologies., (© 2022 The Authors.)

Social relationships change across the lifespan as social networks narrow and motivational priorities shift to the present. Interestingly, aging is also associated with changes in executive function, including decision-making abilities, but it remains unclear how age-related changes in both domains interact to impact financial decisions involving other people. To study this problem, we recruited 50 human participants (N younger  = 26, ages 18-34; N older  = 24, ages 63-80) to play an economic trust game as the investor with three partners (friend, stranger, and computer) who played the role of investee. Investors underwent functional magnetic resonance imaging (fMRI) during the trust game while investees were seated outside of the scanner. Building on our previous work with younger adults showing both enhanced striatal responses and altered default-mode network (DMN) connectivity as a function of social closeness during reciprocated trust, we predicted that these relations would exhibit age-related differences. We found that striatal responses to reciprocated trust from friends relative to strangers and computers were blunted in older adults relative to younger adults, thus supporting our primary pre-registered hypothesis regarding social closeness. We also found that older adults exhibited enhanced DMN connectivity with the temporoparietal junction (TPJ) during reciprocated trust from friends compared to computers while younger adults exhibited the opposite pattern. Taken together, these results advance our understanding of age-related differences in sensitivity to social closeness in the context of trusting others., Competing Interests: Conflict of interest statement The authors have no conflicts to disclose., (Copyright © 2022. Published by Elsevier Inc.)