Transcriptional regulators with broad expression in the zebrafish spinal cord.

BACKGROUND: The spinal cord is a crucial part of the vertebrate CNS, controlling movements and receiving and processing sensory information from the trunk and limbs. However, there is much we do not know about how this essential organ develops. Here, we describe expression of 21 transcription factors and one transcriptional regulator in zebrafish spinal cord. RESULTS: We analyzed the expression of aurkb, foxb1a, foxb1b, her8a, homeza, ivns1abpb, mybl2b, myt1a, nr2f1b, onecut1, sall1a, sall3a, sall3b, sall4, sox2, sox19b, sp8b, tsc22d1, wdhd1, zfhx3b, znf804a, and znf1032 in wild-type and MIB E3 ubiquitin protein ligase 1 zebrafish embryos. While all of these genes are broadly expressed in spinal cord, they have distinct expression patterns from one another. Some are predominantly expressed in progenitor domains, and others in subsets of post-mitotic cells. Given the conservation of spinal cord development, and the transcription factors and transcriptional regulators that orchestrate it, we expect that these genes will have similar spinal cord expression patterns in other vertebrates, including mammals and humans. CONCLUSIONS: Our data identify 22 different transcriptional regulators that are strong candidates for playing different roles in spinal cord development. For several of these genes, this is the first published description of their spinal cord expression.

Revealing spatio-temporal dynamics with long-term trypanosomatid live-cell imaging.

Trypanosoma brucei, the causative agent of human African trypanosomiasis, is highly motile and must be able to move in all three dimensions for reliable cell division. These characteristics make long-term microscopic imaging of live T. brucei cells challenging, which has limited our understanding of important cellular events. To address this issue, we devised an imaging approach that confines cells in small volumes within cast agarose microwells that can be imaged continuously for up to 24 h. Individual T. brucei cells were imaged through multiple rounds of cell division with high spatial and temporal resolution. We developed a strategy that employs in-well "sentinel" cells to monitor potential imaging toxicity during loss-of-function experiments such as small-molecule inhibition and RNAi. Using our approach, we show that the asymmetric daughter cells produced during T. brucei division subsequently divide at different rates, with the old-flagellum daughter cell dividing first. The flagellar detachment phenotype that appears during inhibition of the Polo-like kinase homolog TbPLK occurs in a stepwise fashion, with the new flagellum initially linked by its tip to the old, attached flagellum. We probe the feasibility of a previously proposed "back-up" cytokinetic mechanism and show that cells that initiate this process do not appear to complete cell division. This live-cell imaging method will provide a novel avenue for studying a wide variety of cellular events in trypanosomatids that have previously been inaccessible.

Investigating the association between nitrate dosing and nitrite generation by the human oral microbiota in continuous culture.

The generation of nitrite by the oral microbiota is believed to contribute to healthy cardiovascular function, with oral nitrate reduction to nitrite associated with systemic blood pressure regulation. There is the potential to manipulate the composition or activities of the oral microbiota to a higher nitrate-reducing state through nitrate supplementation. The current study examined microbial community composition and enzymatic responses to nitrate supplementation in sessile oral microbiota grown in continuous culture. Nitrate reductase (NaR) activity and nitrite concentrations were not significantly different to tongue-derived inocula in model biofilms. These were generally dominated by Streptococcus spp., initially, and a single nitrate supplementation resulted in the increased relative abundance of the nitrate-reducing genera Veillonella, Neisseria, and Proteus spp. Nitrite concentrations increased concomitantly and continued to increase throughout oral microbiota development. Continuous nitrate supplementation, over a 7-day period, was similarly associated with an elevated abundance of nitrate-reducing taxa and increased nitrite concentration in the perfusate. In experiments in which the models were established in continuous low or high nitrate environments, there was an initial elevation in nitrate reductase, and nitrite concentrations reached a relatively constant concentration over time similar to the acute nitrate challenge with a similar expansion of Veillonella and Neisseria. In summary, we have investigated nitrate metabolism in continuous culture oral biofilms, showing that nitrate addition increases nitrate reductase activity and nitrite concentrations in oral microbiota with the expansion of putatively NaR-producing taxa.IMPORTANCEClinical evidence suggests that blood pressure regulation can be promoted by nitrite generated through the reduction of supplemental dietary nitrate by the oral microbiota. We have utilized oral microbiota models to investigate the mechanisms responsible, demonstrating that nitrate addition increases nitrate reductase activity and nitrite concentrations in oral microbiota with the expansion of nitrate-reducing taxa.

Genomic variation in pepper vein yellows viruses in Australia, including a new putative variant, PeVYV-10.

Since the first identification and full sequence of the polerovirus pepper vein yellows virus in Australia in 2016, virus surveys of crops and weeds have sporadically identified PeVYV in different hosts and locations. Genomic comparisons of 14 PeVYV-like isolates using RT-PCR products spanning the 3' end of the RdRp region (ORF 2), the intergenic region, ORF 3a, ORF 4, and ORF 3 (1388 nt) showed that four of the PeVYV isolates might be a new variant or PeVYV-like virus. From six PeVYV-positive plants, eight PeVYV-like sequences were obtained by high-throughput sequencing, as two hosts, 5352 and 5634, contained two slightly different PeVYV-like isolates. Three of the PeVYV-like isolates were most closely related to PeVYV-6 and PeVYV-5, and two isolates were closely related to PeVYV-9 and PeVYV-2. The other three isolates shared only 69-74% nucleotide sequence identity across the whole genome with any of the other PeVYVs, despite sharing 73-98%, 87-91%, and 84-87% amino acid sequence identity in ORF 3a, ORF 3, and the RdRp (ORF 2), respectively, suggesting that this virus is a new PeVYV-like virus, which we have tentatively called PeVYV-10. This is also the first report of a PeVYV-like virus infecting garlic.

Molecular characterisation of a novel sadwavirus infecting cattleya orchids in Australia.

The complete genome sequence of a novel sadwavirus infecting cattleya orchids in South East Queensland is described. Isometric virions of c. 27 nm diameter were observed in sap extracts viewed under a transmission electron microscope, and the genome sequence of this virus was determined by high-throughput sequencing. The viral genome consists of two RNA components, 5,910 and 4,435 nucleotides (nt) in length, each encoding a long polyprotein, with predicted cleavage sites at H/Y, E/G, Q/S, and Q/G for the RNA1 and T/G for the RNA2 translation products, respectively. RNA2 has an additional small ORF of 684 nt near the 3' untranslated region. Phylogenetic analysis based on an amino acid sequence alignment of the Pro-Pol region suggested that this virus is most closely related to pineapple secovirus A, a member of the subgenus Cholivirus, but warrants classification as a member of a new species because it exhibited no more than 64% amino acid identity in pairwise sequence comparisons. Because of the prominent purple ringspots that were observed on the leaves of some of the plants, we propose the name "cattleya purple ringspot virus" for this virus (suggested species name: "Sadwavirus cattleyacola").

"We have to change our mindsets": a qualitative study of barriers and facilitators in research collaboration across integrated care system organisations.

The introduction of Integrated Care Systems (ICS) in England aimed to increase joint planning and delivery of health and social care, and other services, to better meet the needs of local communities. There is an associated duty to undertake collaborative research across ICS partners to inform this new integrated approach, which might be challenging given that organisations span health, local authority, voluntary and community sector, and research. This study aimed to explore the appetite for collaborative Research and Innovation (R&I) across ICSs, potential barriers and solutions. This qualitative study involved semi-structured interviews with 24 stakeholders who held senior positions within organisations across two ICS areas (Staffordshire and Stoke-on-Trent; Shropshire, Telford and Wrekin). Interview transcripts were analysed using inductive and deductive analysis, first mapping to the Theoretical Domains Framework (TDF), then considering key influences on organisational behaviour in terms of Capability, Opportunity and Motivation from the COM-B Behaviour Change Wheel. There were fundamental limitations on organisational opportunities for collaborative R&I: a historical culture of competition (rather than collaboration), a lack of research culture and prioritisation, compounded by a challenging adverse economic environment. However, organisations were motivated to undertake collaborative R&I. They recognised the potential benefits (e.g., skill-sharing, staff development, attracting large studies and funding), the need for collaborative research that mirrors integrated care, and subsequent benefits for care recipients. Related barriers included negative experiences of collaboration, fear of failing and low confidence. Capability varied across organisations in terms of research skills and confidence, which reflected the range of partners (from local authorities to NHS Trusts, primary care, and academic institutions). These findings indicate a need to shift from a culture of competition to collaboration, and to help organisations across ICS to prioritise research, and share resources and skills to mitigate the limiting effects of a constrained economic environment. This could be further explored using a systems change approach, to develop the collaborative research efforts alongside the overarching move towards integrated care.

Comparison of health-care utilization, costs and health-related quality of life across the subgroups defined by the Keele STarT MSK Tool.

OBJECTIVES: The aim of this study was to describe and compare health economic outcomes [health-care utilization and costs, work outcomes, and health-related quality of life (EQ-5D-5L)] in patients classified into different levels-of-risk subgroups by the Keele STarT MSK Tool. METHODS: Data on health-care utilization, costs and EQ-5D-5L were collected from a health-care perspective within a primary care prospective observational cohort study. Patients presenting with one (or more) of the five most common musculoskeletal pain presentations were included: back, neck, shoulder, knee or multi-site pain. Participants at low, medium and high risk of persistent disabling pain were compared in relation to mean health-care utilization and costs, health-related quality of life, and employment status. Regression analysis was used to estimate costs. RESULTS: Over 6 months, the mean (s.d.) total health-care (National Health Service and private) costs associated with the low, medium, and high-risk subgroups were £132.92 (167.88), £279.32 (462.98) and £476.07 (716.44), respectively. Mean health-related quality of life over the 6-month period was lower and more people changed their employment status in the high-risk subgroup compared with the medium- and low-risk subgroups. CONCLUSIONS: This study demonstrates that subgroups of people with different levels of risk for poor musculoskeletal pain outcomes also have different levels of health-care utilization, health-care costs, health-related quality of life, and work outcomes. The findings show that the STarT MSK Tool not only identifies those at risk of a poorer outcome, but also those who will have more health-care visits and incur higher costs.

Distinct microbiome profiles in convergent wisdom tooth impactions.

AIMS: Long-term retention of impacted third molars (wisdom teeth) is associated with plaque stagnation and the development of caries on the adjacent surface of the neighboring second molar. While caries and tooth loss are common outcomes of impaction, there is currently insufficient evidence to support the pre-emptive removal of asymptomatic wisdom teeth. Emerging evidence suggests that convergently growing impactions are associated with caries. We have therefore investigated the composition of dental plaque on the distal surface of the mandibular second molar at various impaction angles. METHODS AND RESULTS: We have compared the microbiome of these surfaces at four impaction angulations using short-read sequencing of the bacterial 16S rRNA gene: two convergent (horizontal and mesial) and two divergent (distal and vertical) angulations, and in cases where the wisdom tooth is missing. Horizontal angulations exhibited lower microbial diversity than mesial impactions. Amplicon Sequence Variants (ASVs) associated with Veillonella were significantly more abundant at impactions with angulations toward the midline. Using machine learning, a random forest classifier trained to distinguish microbiome profiles was used to predict the native angulations for a subset of samples, with samples from the two convergent impactions estimated with the greatest accuracy. CONCLUSIONS: Differences in microbial diversity were apparent between caries-associated convergent (horizontal and mesial) impacted wisdom teeth, as well as greater abundances of Veillonella ASVs at horizontal impactions.

A comparison of rapid weight loss practices within international, national and regional powerlifters.

Background: Rapid weight loss (RWL) practices are common amongst strength-sport athletes to 'make weight' for a chosen weight class. Aim: This study compared the RWL practices of International Powerlifting Federation (IPF) powerlifters from Great Britain. Methods: Participants (n = 69, male = 36, female = 33) were recruited from IPF lifting populations (mandatory <2-hour competition weigh-in). Participants were categorised based on highest level of competition (regional, national and international) and also sex (male and female). The previously validated 'Rapid Weight Loss Questionnaire' established RWL practices, however also included an open-ended question regarding thoughts, feeling and mood during RWL. Results: Nearly all participants (97%) had purposely acutely reduced body mass to compete, with an average typical pre-competition loss of 4.2%. Regional competitors reported a higher 'typical' body mass loss compared to international competitors (5.5% vs 3.3%, p = 0.004). Females reported a greater 'highest' body mass loss than males (6.7% vs 5.3%, p = 0.028). Fluid restriction (86.5%), water loading (67.2%) and increased exercise (49.2%) were the RWL methods most commonly used 'always' or 'sometimes'. Content analysis revealed a predominance of negative perceptions during RWL with the emergence of codes; fatigue, sensations, anxiety, low mood and irritation, accounting for ∼70% of responses. Conclusion: Prevalence of RWL is high amongst competitive powerlifters, with many competitors attributing negative perceptions during the weight-cutting process. The magnitude of reported acute RWL within regional lifters was beyond where performance decrements are commonly seen (>5%), this should be cautioned against given the IPF's mandatory <2-hour competition weigh-in.

Rapid Weight Loss Practices Within Olympic Weightlifters.

ABSTRACT: Gee, TI, Campbell, P, Bargh, MJ, and Martin, D. Rapid weight loss practices within Olympic weightlifters. J Strength Cond Res 37(10): 2046-2051, 2023-Rapid weight loss (RWL) practices are common among athletes to "make weight" for a chosen bodyweight class. This study's purpose was to investigate RWL prevalence, magnitude, and methods within Olympic weightlifters from Great Britain. Subjects (n = 39, male = 22, female = 17) were recruited from International Weightlifting Federation lifting populations (mandatory two-hour competition weigh-in). Subjects were categorized into competitive groups based on Sinclair coefficient total (high, mid, low) and also gender (male, female). The validated Rapid Weight Loss Questionnaire was used to establish RWL magnitude and practices. Of respondents, 33 of 39 (84.6%) had purposely acutely reduced body mass to compete, a higher proportion present within females (94.1%) than males (77.3%). The cohort's mean habitual precompetition acute body mass loss was 3.8 ± 1.7% and the "rapid weight loss score" (RWLS) was 23.6 ± 9.5. Across competitive groups there were no significant differences in habitual or highest precompetition body mass loss, postcompetition body mass gain or RWLS (p > 0.05). However, females attributed a significantly greater "highest" relative precompetition body mass loss compared with males (7.4 vs 4.9%, p = 0.045). For RWL methods used, frequencies of "always" and "sometimes" were reported highest for "restricting fluid ingestion" (81.8%), "gradual dieting" (81.8%), and "water loading" (54.5%). The prevalence of RWL is high among competitive Olympic weightlifters, and especially within the sampled female athletes. Magnitude of RWL was similar across different standards of athlete; however, female lifters demonstrated a higher maximum precompetition RWL.

Comparative genomics and genomic diversity of Pseudomonas syringae clade 2b-a in Australia.

BACKGROUND: A zucchini disease outbreak with unusual symptoms associated with Pseudomonas syringae clade 2b was identified in Bundaberg, Australia during autumn 2016. To investigate the genetic diversity of the 11 Australian isolates obtained from the outbreak, the genomes were compared to the publicly available P. syringae strains in phylogroup 2. RESULTS: Average nucleotide identity refined the P. syringae clade 2b-a into four clusters (Cluster A, B, C1 and C2), an expansion from the previously identified A, B and C. Australian isolates were in Cluster A, C1 and C2. Genomic analyses highlighted several key factors that may contribute to the virulence of these isolates. Six orthologous groups, including three virulence factors, were associated with P. syringae phylogroup 2 cucurbit-infecting strains. A region of genome plasticity analysis identified a type VI secretion system pathway in clade 2b-a strains which could also contribute to virulence. Pathogenicity assays on isolates KL004-k1, KFR003-1 and 77-4C, as representative isolates of Cluster A, C1 and C2, respectively, determined that all three isolates can infect pumpkin, squash, watermelon and zucchini var. Eva with different levels of disease severity. Subsequently, type III effectors were investigated and four type III effectors (avrRpt2, hopZ5, hopC1 and hopH1) were associated with host range. The hopZ effector family was also predicted to be associated with disease severity. CONCLUSIONS: This study refined the taxonomy of the P. syringae clade 2b-a, supported the association between effector profile and pathogenicity in cucurbits established in a previous study and provides new insight into important genomic features of these strains. This study also provided a detailed and comprehensive resource for future genomic and functional studies of these strains.

Bermuda grass latent virus in Australia: genome sequence, sequence variation, and new hosts.

Bermuda grass latent virus (BGLV; genus Panicovirus) is identified for the first time in Australia and in only the second country after the USA. A full-length genome sequence was obtained, which has 97% nucleotide sequence identity to that of the species exemplar isolate. Surveys for BGLV, utilising a newly designed universal panicovirus RT-PCR assay for diagnosis, demonstrated widespread infection by this virus in a broad variety of Bermuda grass cultivars (Cynodon dactylon and C. dactylon × C. transvaalensis) grown in both New South Wales and Queensland. The virus was also detected in Rhodes grass (Chloris gayana) and Kikuyu grass (Cenchrus clandestinus), which are both important pasture grasses in subtropical Australia, and the latter is also grown as turf. Furthermore, the Rhodes grass plant, which had strong mosaic symptoms, was also infected with sugarcane mosaic virus, warranting further investigations as to whether synergistic interactions occur between these two viruses.

Acceptability of, and preferences for, remote consulting during COVID-19 among older patients with two common long-term musculoskeletal conditions: findings from three qualitative studies and recommendations for practice.

BACKGROUND: Guidance for choosing face-to-face vs remote consultations (RCs) encourages clinicians to consider patient preferences, however, little is known about acceptability of, and preferences for RCs, particularly amongst patients with musculoskeletal conditions. This study aimed to explore the acceptability of, and preferences for, RC among patients with osteoporosis and rheumatoid arthritis. METHODS: Three UK qualitative studies, exploring patient experiences of accessing and receiving healthcare, undertaken during the pandemic, with people with osteoporosis and rheumatoid arthritis. Study team members agreed a consistent approach to conduct rapid deductive analysis using the Theoretical Framework of Acceptability (TFA) on transcripts from each data set relating to RC, facilitated by group meetings to discuss interpretations. Findings from the three studies were pooled. RESULTS: Findings from 1 focus group and 64 interviews with 35 people were included in the analysis. Participants' attitudes to RC, views on fairness (ethicality) and sense-making (intervention coherence) varied according to their needs within the consultation and views of the pandemic. Some participants valued the reduced burden associated with RC, while others highly valued non-verbal communication and physical examination associated with face-to-face consults (opportunity costs). Some participants described low confidence (self-efficacy) in being able to communicate in RCs and others perceived RCs as ineffective, in part due to suboptimal communication. CONCLUSIONS: Acceptability of, and preferences for RC appear to be influenced by societal, healthcare provider and personal factors and in this study, were not condition-dependant. Remote care by default has the potential to exacerbate health inequalities and needs nuanced implementation.

Simultaneous inhibition of PFKFB3 and GLS1 selectively kills KRAS-transformed pancreatic cells.

Activating mutations of the oncogenic KRAS in pancreatic ductal adenocarcinoma (PDAC) are associated with an aberrant metabolic phenotype that may be therapeutically exploited. Increased glutamine utilization via glutaminase-1 (GLS1) is one such feature of the activated KRAS signaling that is essential to cell survival and proliferation; however, metabolic plasticity of PDAC cells allow them to adapt to GLS1 inhibition via various mechanisms including activation of glycolysis, suggesting a requirement for combinatorial anti-metabolic approaches to combat PDAC. We investigated whether targeting the glycolytic regulator 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-3 (PFKFB3) in combination with GLS1 can selectively prevent the growth of KRAS-transformed cells. We show that KRAS-transformation of pancreatic duct cells robustly sensitizes them to the dual targeting of GLS1 and PFKFB3. We also report that this sensitivity is preserved in the PDAC cell line PANC-1 which harbors an activating KRAS mutation. We then demonstrate that GLS1 inhibition reduced fructose-2,6-bisphosphate levels, the product of PFKFB3, whereas PFKFB3 inhibition increased glutamine consumption, and these effects were augmented by the co-inhibition of GLS1 and PFKFB3, suggesting a reciprocal regulation between PFKFB3 and GLS1. In conclusion, this study identifies a novel mutant KRAS-induced metabolic vulnerability that may be targeted via combinatorial inhibition of GLS1 and PFKFB3 to suppress PDAC cell growth.

Indicators of dementia disease progression in primary care: An electronic health record cohort study.

BACKGROUND AND PURPOSE: The objectives were to assess the feasibility and validity of using markers of dementia-related health as indicators of dementia progression in primary care, by assessing the frequency with which they are recorded and by testing the hypothesis that they are associated with recognised outcomes of dementia. The markers, in 13 domains, were derived previously through literature review, expert consensus, and analysis of regional primary care records. METHODS: The study population consisted of patients with a recorded dementia diagnosis in the Clinical Practice Research Datalink, a UK primary care database linked to secondary care records. Incidence of recorded domains in the 36 months after diagnosis was determined. Associations of recording of domains with future hospital admission, palliative care, and mortality were derived. RESULTS: There were 30,463 people with diagnosed dementia. Incidence of domains ranged from 469/1000 person-years (Increased Multimorbidity) to 11/1000 (Home Pressures). An increasing number of domains in which a new marker was recorded in the first year after diagnosis was associated with hospital admission (hazard ratio for ≥4 domains vs. no domains = 1.24; 95% confidence interval = 1.15-1.33), palliative care (1.87; 1.62-2.15), and mortality (1.57; 1.47-1.67). Individual domains were associated with outcomes with varying strengths of association. CONCLUSIONS: Feasibility and validity of potential indicators of progression of dementia derived from primary care records are supported by their frequency of recording and associations with recognised outcomes. Further research should assess whether these markers can help identify patients with poorer prognosis to improve outcomes through stratified care and targeted support.

Are psychological symptoms a risk factor for musculoskeletal pain in adolescents?

Adolescent musculoskeletal pain is common and is associated with musculoskeletal pain in adulthood. Psychological symptoms, also common in adolescence, have been shown to be associated with musculoskeletal pain, but the current evidence is mixed and may be dependent on effect modifiers. This study investigated whether adolescents with psychological symptoms (internalizing and externalizing constructs) at age 13 years were at higher odds for musculoskeletal pain at age 17 years and whether the associations were modified by pubertal status and sex. A prospective cohort design examined data on 3865 adolescents from the Avon Longitudinal Study of Parents and Children (ALSPAC). Associations between baseline (aged 13 years) internalizing and externalizing symptoms and musculoskeletal pain at follow-up (aged 17 years) were investigated using logistic regression producing odds ratios (OR) and 95% confidence intervals (95% CI). In total 43.1% of adolescents reported musculoskeletal pain at follow-up. Externalizing symptoms at baseline increased the odds of musculoskeletal pain (OR 1.68, 95% CI 1.28, 2.20), and internalizing symptoms demonstrated a non-significant increase (OR 1.26, 95% CI 0.98, 1.62). Effect modification analysis showed an increased effect dependent on pubertal status.Conclusion: Adolescents with externalizing symptoms, and to some extent internalizing symptoms, are at increased odds of later musculoskeletal pain. Future research is now required to understand the reasons for these associations. What is Known: • Current evidence regarding the association between internalizing symptoms and externalizing symptoms and future musculoskeletal pain in adolescents is mixed. What is New: • This study found that adolescents with externalizing symptoms, and to some extent internalizing symptoms, are at increased odds for musculoskeletal pain, with an increased influence dependent on pubertal status. • These results are of interest for the development of timely preventative interventions designed to reduce the risk of musculoskeletal pain.

Mesenteric Vascular Injury in Trauma: An NTDB Study.

BACKGROUND: Although abdominal trauma remains a major cause of morbidity and mortality, there has not been a large-scale multicenter study regarding outcomes in patients who incur mesenteric vascular injuries. The goal of this retrospective analysis was to investigate the factors associated with outcomes in patients with trauma diagnosed with mesenteric vascular injuries. METHODS: A retrospective database analysis was performed on patients who sustained a mesenteric vascular injury (MVI, ICD-9 902.20-902.29) identified by the 2012 National Trauma Data Bank. Data were analyzed to identify differences in hospital length of stay, emergency room (ER) and final hospital disposition, and mortality based on patient age, gender, race, Injury Severity Score (ISS), and injury type (blunt or penetrating). RESULTS: Of the 1,133 total patients included, blunt trauma accounted for 740 (65%) of the injuries, whereas penetrating trauma accounted for 364 of the injuries (32%). Patients with penetrating injuries were 1.43 times more likely to die from their injuries than those suffering from blunt trauma (95% CI 1.04-1.98, P < 0.05). Patients with a higher ISS (>16) were 5.39 times more likely to die from their injuries than those with a lower ISS (95% CI 1.89-15.4, P = 0.002); if ISS was >25, the patient was 15.1 times more likely to die (95% CI 5.5-41.7, P < 0.001). Men were more likely to suffer from penetrating injuries than women (37% vs. 13%, P < 0.001), and African Americans were nearly 4 times more likely to present with penetrating injuries (69% vs 17%, P < 0.001). Age was also associated with mortality as patients >65 years and between 21 and 44 years were more likely to die from their injuries than patients in other age categories. Of the 740 patients with blunt MVIs, 326 (44%) were taken directly from the ER to the operating room (OR) and 306 (41%) to the intensive care unit (ICU), whereas with penetrating MVIs, 311 (85%) were taken to the OR from the emergency department and 18 (5%) to the intensive care unit. Of the 740 blunt MVIs, 115 died (16%), compared with 76 (21%) of the penetrating MVIs (P < 0.001). Injuries to the hepatic and superior mesenteric arteries were associated with higher mortality, with OR 2.03 and 3.03, respectively (P < 0.001). CONCLUSIONS: The presence of mesenteric arterial injury warrants rapid identification and management as these injuries are associated with significant morbidity and mortality, with penetrating mechanism, injury to large mesenteric vessels, and increased ISS associated with increased mortality.

Developing a framework for cash transfer programs that foster sustained economic empowerment to reduce sexual risk among adolescent girls and young women: a qualitative study.

BACKGROUND: Transactional sexual relationships contribute to a high incidence of HIV infection among adolescent girls and young women (AGYW) living in low-resource settings. Cash transfers (CT) are a structural approach to reduce sexual risk behaviors, but their positive economic effects frequently fade after the program ends. We aimed to understand AGYW's decision-making processes related to sexual, relationship, and financial decisions, in order to design a framework for a CT program that could lead to long-term financial independence and reduced transactional sex among AGYW. METHODS: We conducted qualitative research with AGYW participating in a CT program in Tanzania. Phase one was formative research to understand the context and experiences of AGYW regarding sexual behavior, relationships, and finances. Participants included 36 AGYW (15-23 years old), 15 influencers of AGYW (mothers and male partners) and 10 financially empowered women (FEW - women aged 20-30 with a sustained, reliable source of income independent of their partner). Decisions and decision-making contexts of AGYW that we identified in phase one informed the content of phase two. In phase two we simulated scenarios for decision-making and economic goals with 80 AGYW and 40 FEW, in order to identify key principles or intervention opportunities to guide development of a CT program framework. RESULTS: Through phases one and two of our research we identified three key themes in AGYW's vision of their desired future economic state: 1) positive social image, 2) power balance and respect, and 3) emotional and economic security. An important theme distinguishing AGYW from FEW was that AGYW lacked a vision to build self-agency. CONCLUSIONS: Our findings suggest that providing economic resources to AGYW through CT without ensuring self-agency is unlikely to be an effective long-term intervention for economic empowerment. Using these findings we developed a framework for CT programs with three key pillars for developing self-agency: 1) emotional efficacy, to increase AGYW's perception of rewards associated with developing self-agency; 2) social efficacy, to build constructive relationships and exit negative relationships that inhibit self-agency, and 3) economic efficacy, to help AGYW build a resilient stream of financial resources.

Markers of dementia-related health in primary care electronic health records.

OBJECTIVES: Identifying routinely recorded markers of poor health in patients with dementia may help treatment decisions and evaluation of earlier outcomes in research. Our objective was to determine whether a set of credible markers of dementia-related health could be identified from primary care electronic health records (EHR). METHODS: The study consisted of (i) rapid review of potential measures of dementia-related health used in EHR studies; (ii) consensus exercise to assess feasibility of identifying these markers in UK primary care EHR; (iii) development of UK EHR code lists for markers; (iv) analysis of a regional primary care EHR database to determine further potential markers; (v) consensus exercise to finalise markers and pool into higher domains; (vi) determination of 12-month prevalence of domains in EHR of 2328 patients with dementia compared to matched patients without dementia. RESULTS: Sixty-three markers were identified and mapped to 13 domains: Care; Home Pressures; Severe Neuropsychiatric; Neuropsychiatric; Cognitive Function; Daily Functioning; Safety; Comorbidity; Symptoms; Diet/Nutrition; Imaging; Increased Multimorbidity; Change in Dementia Drug. Comorbidity was the most prevalent recorded domain in dementia (69%). Home Pressures were the least prevalent domain (1%). Ten domains had a statistically significant higher prevalence in dementia patients, one (Comorbidity) was higher in non-dementia patients, and two (Home Pressures, Diet/Nutrition) showed no association with dementia. CONCLUSIONS: EHR captures important markers of dementia-related health. Further research should assess if they indicate dementia progression. These markers could provide the basis for identifying individuals at risk of faster progression and outcome measures for use in research.

Stabilization of Liner Implosions via a Dynamic Screw Pinch.

Magnetically driven implosions are susceptible to magnetohydrodynamic instabilities, including the magneto-Rayleigh-Taylor instability (MRTI). To reduce MRTI growth in solid-metal liner implosions, the use of a dynamic screw pinch (DSP) has been proposed [P. F. Schmit et al., Phys. Rev. Lett. 117, 205001 (2016)PRLTAO0031-900710.1103/PhysRevLett.117.205001]. In a DSP configuration, a helical return-current structure surrounds the liner, resulting in a helical magnetic field that drives the implosion. Here, we present the first experimental tests of a solid-metal liner implosion driven by a DSP. Using the 1-MA, 100-200-ns COBRA pulsed-power driver, we tested three DSP cases (with peak axial magnetic fields of 2 T, 14 T, and 20 T) and a standard z-pinch (SZP) case (with a straight return-current structure and thus zero axial field). The liners had an initial radius of 3.2 mm and were made from 650-nm-thick aluminum foil. Images collected during the experiments reveal that helical MRTI modes developed in the DSP cases, while nonhelical (azimuthally symmetric) MRTI modes developed in the SZP case. Additionally, the MRTI amplitudes for the 14-T and 20-T DSP cases were smaller than in the SZP case. Specifically, when the liner had imploded to half of its initial radius, the MRTI amplitudes for the SZP case and for the 14-T and 20-T DSP cases were, respectively, 1.1±0.3 mm, 0.7±0.2 mm, and 0.3±0.1 mm. Relative to the SZP, the stabilization obtained using the DSP agrees reasonably well with theoretical estimates.