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High-spatial-resolution HI observations have led to the realisation that the nearby (within few hundreds of parsecs) Galactic atomic filamentary structures are aligned with the ambient magnetic field. Enabled by the high quality data from the Australian Square Kilometre Array Pathfinder (ASKAP) radio telescope for the Galactic ASKAP HI (GASKAP-HI) survey, we investigate the potential magnetic alignment of the $\gtrsim 10\,{\rm pc}$-scale HI filaments in the Small Magellanic Cloud (SMC). Using the Rolling Hough Transform (RHT) technique that automatically identifies filamentary structures, combined with our newly devised ray-tracing algorithm that compares the HI and starlight polarisation data, we find that the HI filaments in the northeastern end of the SMC main body ("Bar" region) and the transition area between the main body and the tidal feature ("Wing" region) appear preferentially aligned with the magnetic field traced by starlight polarisation. Meanwhile, the remaining SMC volume lacks starlight polarisation data of sufficient quality to draw any conclusions. This suggests for the first time that filamentary HI structures can be magnetically aligned across a large spatial volume ($\gtrsim\,{\rm kpc}$) outside of the Milky Way. In addition, we generate maps of the preferred orientation of HI filaments throughout the entire SMC, revealing the highly complex gaseous structures of the galaxy likely shaped by a combination of the intrinsic internal gas dynamics, tidal interactions, and star formation feedback processes. These maps can further be compared with future measurements of the magnetic structures in other regions of the SMC., Comment: 24 pages, MNRAS accepted

The OSIRIS-REx spacecraft completed the first part of the primary objective by successfully sampling the surface of asteroid (101955) Bennu and storing the acquired sample in the re-entry capsule. The sampling ‘Touch-And-Go’ (TAG) maneuver was performed nominally at the primary sampling site, Nightingale, in Bennu’s Northern hemisphere. As a consequence of the TAG, material at the sampling site was mobilized and the morphology of the area was altered. This event offered a unique opportunity to investigate, in detail, the subsurface of asteroid Bennu giving access to fine grained and less altered material from Nightingale crater. We performed a detailed study on the infrared spectrum in the Nightingale region to search for modification resulting from the sampling event by analysing different features: slope, the H2O–OH− related absorption band in the $2.7\ \mu {\rm m}$ region, and other possible features. Our results show that, despite visible alteration of the TAG location detected by cameras, no strong variations are observed in the near-infrared bands and their quantitative evaluation is not possible beyond all the instrumental effects, although some changes may have occurred. We confirm that the infrared spectrum of the sampling site becomes redder with respect to the pre-TAG observations, conceivably due to fine material mobilization and exposure of less altered material, as confirmed by decreased spectral convexity. We identify possible modification of hydrated band at $2.7\ \mu {\rm m}$ but with some concerns due to data quality. However, our results place new constraints on the nature of Bennu’s subsurface material and the sample collected by OSIRIS-REx.

Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants continue to emerge, and effective tracking requires rapid return of results. Surveillance of variants is typically performed by whole genome sequencing (WGS), which can be financially prohibitive and requires specialized equipment and bioinformatic expertise. Genotyping approaches are rapid methods for monitoring SARS-CoV-2 variants but require continuous adaptation. Fragment analysis may represent an approach for improved SARS-CoV-2 variant detection. Methods A multiplex fragment analysis approach (CoVarScan) was validated using PCR targeting variants by size and fluorescent color. Eight SARS-CoV-2 mutational hot spots in variants of concern (VOCs) were targeted. Three primer pairs (recurrently deleted region [RDR] 1, RDR2, and RDR3–4) flank RDRs in the S-gene. Three allele-specific primers target recurrent spike receptor binding domain mutants. Lastly, 2 primer pairs target recurrent deletions or insertions in ORF1A and ORF8. Fragments were resolved and analyzed by capillary electrophoresis (ABI 3730XL), and mutational signatures were compared to WGS results. Results We validated CoVarScan using 3544 clinical respiratory specimens. The assay exhibited 96% sensitivity and 99% specificity compared to WGS. The limit of detection for the core targets (RDR1, RDR2, and ORF1A) was 5 copies/reaction. Variants were identified in 95% of samples with cycle threshold (CT) Conclusions Multiplex fragment analysis is adaptable and rapid and has similar accuracy to WGS to classify SARS-CoV-2 variants.

Background/Aims Fibroblasts isolated by traditional explant culture from skin biopsies in systemic sclerosis (SSc) have a profibrotic and “migratory” phenotype. Single cell RNAseq (scRNAseq) studies suggest other fibroblast subpopulations may be important in SSc pathogenesis. We have isolated a second fibroblast population termed “resident” from whole skin in SSc. We used bulk and scRNAseq to further characterise these populations. Methods Forearm skin from dcSSc (n = 3) and HC (n = 3) was biopsied. “Migratory” fibroblasts were isolated by standard explant culture. The remaining biopsy fragments underwent collagenase digestion to yield a second “resident” fibroblast population. Functional characterization included 3-D collagen gel contraction, migratory scratch-wound assays and western blot comparing expression of pro-collagen I, CTGF and αSMA. Significant difference in gene expression was defined by fold change≥1.5, and adjusted p-value Results Both SSc fibroblast populations showed a fibrotic phenotype with overexpression of COL1, CTGF and αSMA compared to HC, but with reduced expression αSMA in resident compared to migratory SSc fibroblasts (p Conclusion We have isolated for the first time two distinct profibrotic fibroblast populations from SSc skin with altered expression of key genes associated with SSc pathogenesis. Future work will define their role in SSc pathogenesis, potentially facilitating a more targeted treatment approach. Disclosure K.E. Clark: None. S. Xu: None. V.H. Ong: None. C.D. Buckley: None. C. Denton: None.

Background/Aims Preclinical studies suggest that the S100A4, a Damage Associated Molecular Pattern (DAMP) protein upregulated upon stress or injury, may be a target for antifibrotic therapy. We have studied expression and function of S100A4 in systemic sclerosis (SSc) to further explore its relevance as a driver of fibroblast activation. Methods S100A4 protein concentration was measured by ELISA (Cusabio, USA) in serum of SSc (n = 94) and healthy controls (n = 15). Association of serum level with major organ complications and skin score (mRSS) was determined. S100A4 protein expression in supernatant and cell layer of skin fibroblast cultures from diffuse cutaneous SSc (SScF, n = 6) and healthy controls (NF, n = 6) was assessed. Recombinant S100A4 and a high affinity anti-S100A4 neutralising monoclonal antibody (AX-202) were used to investigate activation of profibrotic molecular and functional phenotype in SSc and control fibroblasts. Results Median [range] S100A4 (ng/ml) was higher in serum of SSc (89.9 [15.0-240.0]) than healthy controls (71.4 [7.9-131.8]; p = 0.027). There was significant association with SSc-ILD (p = 0.025, n = 55), scleroderma renal crisis (p = 0.026, n = 4) and trend of increase in pulmonary hypertension (p = 0.075, n = 7). There was a trend for S100A4 to fall in longer disease duration (r=-0.18, p = 0.09) and a weak (r = 0.28, p = 0.07) correlation with current mRSS but not peak mRSS in dcSSc. Median [range] S100A4 (ng/ml) was higher in culture supernatants of SScF (4.19 [0.52-8.42]) than NF controls (0.28 [0.02-3.29]; p 1.5) induced in NF by S100A4 were also constitutively overexpressed in SScF, and significantly downregulated by AX-202. Pathway mapping of these S100A4 dependent transcripts in SSc showed the most significant enriched Kegg® pathways (FDR Conclusion Our findings provide compelling evidence supporting a profibrotic role for S100A4 in fibroblast activation in SSc and suggest that serum level may be a biomarker of major organ manifestations and disease severity. Studies to elucidate the therapeutic potential of targeting S100A4 in SSc are warranted. Disclosure C.P. Denton: None. S. Xu: None. R.H. Maclean: None. K.E. Clark: None. S. Borchert: Corporate appointments; Employee of ARXX Therapeutics. R. Hussain: Corporate appointments; Employee of ARXX Therapeutics. J. Klingelhöfer: Corporate appointments; Employee of ARXX Therapeutics. J. Hallén: Corporate appointments; Employee of ARXX Therapeutics. V.H. Ong: None.

Background Polysubstance use is a common, problematic behavior that increases risk of harm to self and others. Research suggests that rates may vary based on gender, sex and sexuality. Understanding the current state of this literature may inform prevention and treatment of polysubstance use, leading to reduced public health burden. Objectives This review aimed to synthesize research on gender, sex and sexuality differences in polysubstance use in adults and adolescents. Methods A scoping review was conducted using all EBSCO databases, PubMed and Google Scholar to identify articles examining the effects of gender, sex and sexuality on polysubstance use. Polysubstance use was defined broadly as the use of any combination of substances over any time period and included licit (alcohol, tobacco) and illicit substances, concurrent and simultaneous use, from lifetime to daily use and use at any frequency. Studies were considered if they were published in peer-reviewed journals between January 1990 and October 2020 and were written in English. Publicly available data sources were also utilized to fully capture prevalence data that has not been published elsewhere. Results Findings were mostly inconsistent and often conflicting. Only two findings were generally consistent: adult men were overall more likely to report polysubstance use than adult women, and sexual and gender minorities report more frequent polysubstance use than non-minorities. Conclusions Research has been unable to clearly elucidate differences in polysubstance use prevalence and patterns according to gender, sex and sexuality. Several recommendations are offered to advance future research and address limitations of current research.

The factors contributing to the rapid emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) BA.4 and BA.5 subvariants in populations that experienced recent surges of BA.2 and BA.2.12.1 infections are not understood. Neutralizing antibodies (NAbs) are likely to protect against severe disease if present in sufficient quantity. We found that after BA.2 or BA.2.12.1 infection, NAb responses were largely cross-neutralizing but were much less effective against BA.5. In addition, individuals who were infected and treated early with nirmatrelvir/ritonavir (Paxlovid) had lower NAb levels than untreated individuals.

To facilitate the delivery of accurate and timely care to patients in complex environments, process improvement methodologies such as Lean can be very effective. Lean is a quality improvement methodology that seeks to add value for patients and employees by continuously improving processes and eliminating waste. At our institution, Lean principles were applied to improve efficiency and minimize waste in the diagnostic breast imaging reading room. This paper describes how we applied Lean principles, including plan-do-study-act testing, level-loading (heijunka), and visual management, to level the workload of the diagnostic radiologists in our practice. Implementation of these principles to improve the diagnostic workflow in breast imaging is described along with examples from our practice, including challenges and future opportunities.

Objective Research suggests families whose infants are admitted to the Neonatal Intensive Care Unit (NICU) experience elevated distress and may have pre-existing risk factors for maladjustment. This study sought to validate the newly developed Psychosocial Assessment Tool (PAT-NICU/Cardiac Intensive Care Unit [CICU]), a comprehensive screening measure for family psychosocial risk in the NICU. Methods The sample included 171 mothers, who completed the PAT-NICU/CICU and other related measures within 2 weeks of their infant’s NICU admission at a level 4 unit within a large pediatric hospital. PAT-NICU/CICU scores were compared to a companion risk survey completed by NICU social workers. Test–retest reliability was assessed through repeated measures at 2-month follow-up. Results Analyses suggest the PAT-NICU/CICU is effective in classifying psychosocial risk. This is supported by statistically significant correlations between the PAT-NICU/CICU and validated measures, in addition to elevated scores on concurrent measures by risk classification. Internal consistency, test–retest reliability, and acceptability for the PAT-NICU/CICU were satisfactory. Conclusions This preliminary study demonstrates the validity, reliability, and acceptability of the PAT-NICU/CICU as a psychosocial screening tool to aid identification of families who may benefit from supportive services during NICU admission. This new measure is a more comprehensive tool that assesses a wide variety of risk factors and stress responses. However, future studies of this measure are needed with more diverse samples. Prompt screening of NICU parents may facilitate earlier linkage with appropriate levels of resources or intervention. This research is crucial in improving risk assessment and psychosocial care for families in the NICU.

Objective This review synthesizes the literature on benefit-finding and growth (BFG) among youth with medical illnesses and disabilities and their parents. Specifically, we summarized: (a) methods for assessing BFG; (b) personal characteristics, personal, and environmental resources, as well as positive outcomes, associated with BFG; (c) interventions that have enhanced BFG; and (d) the quality of the literature. Methods A medical research librarian conducted the search across PubMed, Scopus, PsycInfo, Google Scholar, and Cochrane Library. Studies on BFG among children ages 0–18 with chronic illnesses and disabilities, or the parents of these youth were eligible for inclusion. Articles were uploaded into Covidence; all articles were screened by two reviewers, who then extracted data (e.g., study characteristics and findings related to BFG) independently and in duplicate for each eligible study. The review was based on a systematic narrative synthesis framework and adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PROSPERO registration number: CRD42020189339). Results In total, 110 articles were included in this review. Generally, BFG capabilities were present across a range of pediatric health conditions and disabilities. Correlates of both youth and parent BFG are presented, including personal and environmental resources, coping resources, and positive outcomes. In addition, studies describing interventions aimed at enhancing BFG are discussed, and a quality assessment of the included studies is provided. Conclusions Recommendations are provided regarding how to assess BFG and with whom to study BFG to diversify and extend our current literature.

Economic insecurity has attracted growing attention, but there is no consensus as to its definition. We characterize a class of individual economic-insecurity measures based on the time profile of economic resources. We apply this economic-insecurity measure to political-preference data in the USA, UK, and Germany. Conditional on current economic resources, economic insecurity is associated with both greater political participation (support for a party or the intention to vote) and more support for conservative parties. In particular, economic insecurity predicts greater support for both Donald Trump before the 2016 US Presidential election and the UK leaving the European Union in the 2016 Brexit referendum.

Undergraduate students participating in the UCLA Undergraduate Research Consortium for Functional Genomics (URCFG) have conducted a two-phased screen using RNA interference (RNAi) in combination with fluorescent reporter proteins to identify genes important for hematopoiesis in Drosophila. This screen disrupted the function of approximately 3500 genes and identified 137 candidate genes for which loss of function leads to observable changes in the hematopoietic development. Targeting RNAi to maturing, progenitor, and regulatory cell types identified key subsets that either limit or promote blood cell maturation. Bioinformatic analysis reveals gene enrichment in several previously uncharacterized areas, including RNA processing and export and vesicular trafficking. Lastly, the participation of students in this course-based undergraduate research experience (CURE) correlated with increased learning gains across several areas, as well as increased STEM retention, indicating that authentic, student-driven research in the form of a CURE represents an impactful and enriching pedagogical approach.

This article examines the local legal histories of two “liberty of contract” constitutional disputes prior to Lochner in the South and West: Allgeyer v. Louisiana (1897) and Holden v. Hardy (1898). Drawing inspiration from the new history of American capitalism literature that has recently rethought the genesis of the modern American economy through a Southern and Western lens, this article argues that we have yet to fully grasp the relationship between uneven state development politics and economic rights jurisprudence under American constitutional law. In so doing, I build a new narrative that takes into account development politics, Louisiana lawyers with roots in the Confederacy, and Western Populist constitution-makers to rethink the origins and development of a doctrine that arguably continues to shape the modern world.

Despite an historical connection between the arts and sciences, in the past century, the two disciplines have been greatly siloed. However, there is a renewed interest in collaboration across the arts and sciences to support conservation practice by understanding and communicating complex environmental, social, and cultural challenges in novel ways. 6&6 was created as a transdisciplinary art–science initiative to promote a deeper appreciation of the Sonoran Desert. Six artists and six scientists were paired to create work that explored conservation issues in the Sonoran Desert and the Gulf of California. In-depth interviews were conducted with the artists and scientists throughout the 4-year initiative to understand the impact of 6&6 on their personal and professional behaviors and outlook. The findings from this case study reveal the role that intensive, place-based, and transdisciplinary art–science programs can play in shaping narratives to better communicate the patterns and processes of nature and human–environment interactions.

BackgroundTwenty-five germline variants are associated with adult diffuse glioma, and some of these variants have been shown to be associated with particular subtypes of glioma. We hypothesized that additional germline variants could be identified if a genome-wide association study (GWAS) were performed by molecular subtype.MethodsA total of 1320 glioma cases and 1889 controls were used in the discovery set and 799 glioma cases and 808 controls in the validation set. Glioma cases were classified into molecular subtypes based on combinations of isocitrate dehydrogenase (IDH) mutation, telomerase reverse transcriptase (TERT) promoter mutation, and 1p/19q codeletion. Logistic regression was applied to the discovery and validation sets to test for associations of variants with each of the subtypes. A meta-analysis was subsequently performed using a genome-wide P-value threshold of 5 × 10−8.ResultsNine variants in or near D-2-hydroxyglutarate dehydrogenase (D2HGDH) on chromosome 2 were genome-wide significant in IDH-mutated glioma (most significant was rs5839764, meta P = 2.82 × 10−10). Further stratifying by 1p/19q codeletion status, one variant in D2HGDH was genome-wide significant in IDH-mutated non-codeleted glioma (rs1106639, meta P = 4.96 × 10−8). Further stratifying by TERT mutation, one variant near FAM20C (family with sequence similarity 20, member C) on chromosome 7 was genome-wide significant in gliomas that have IDH mutation, TERT mutation, and 1p/19q codeletion (rs111976262, meta P = 9.56 × 10−9). Thirty-six variants in or near GMEB2 on chromosome 20 near regulator of telomere elongation helicase 1 (RTEL1) were genome-wide significant in IDH wild-type glioma (most significant was rs4809313, meta P = 2.60 × 10−10).ConclusionsPerforming a GWAS by molecular subtype identified 2 new regions and a candidate independent region near RTEL1, which were associated with specific glioma molecular subtypes.

A growing literature has concluded that terrorism affects the economy, yet less is known about its impact on individual welfare. This article estimates the impact of the 2013 Boston marathon bombing on well-being, exploiting representative daily data from the American Time Use Survey and Well-Being Supplement. Using a combined regression discontinuity and differences-in-differences design, with the 2012 Boston marathon as a counterfactual, we find an immediate reduction in well-being of a third of a standard deviation. In particular, happiness declined sharply and negative emotions rose significantly. While the effects do not persist beyond one week, they may entail adverse health and economic consequences.

Background/Aims Despite the considerable impact axial spondyloarthritis (axSpA) has on quality of life, condition-specific group education programmes are not routinely offered. Many people with axSpA report feeling isolated and often have never met anyone else with the condition. In 2020, the National Axial Spondyloarthritis Society (NASS) worked with patients and rheumatology departments to co-produce a pilot self-management programme (SMP) to explore demand from and assess the impact on patients and healthcare professionals (HCPs). Methods NASS identified six NHS centres to host the pilot SMP sessions. These centres represented a range of axSpA services. HCPs invited their axSpA cohort to attend by post or e-mail and NASS invited local NASS members. Attendees booked online via private URL. NASS developed content following consultation with rheumatology HCPs and people living with axSpA. The first session covered pain, flares, fatigue and emotional wellbeing. Following attendee feedback, three centres hosted a second session on medication and exercise. One centre held a third session covering night pain, sleep and stress. Sessions were delivered via online meeting software and included teaching, group discussions, polls and exercise. HCPs of the host rheumatology departments led these sessions in tandem with NASS staff, one of whom has lived experience of axSpA. Content and format were continually reviewed and improved using feedback from attendees and HCPs (Table 1); feedback was gathered by email, informal focus groups and anonymous surveys. Results A total of 266 patients attended. 55% were female and 27% were aged under 45. 10% were diagnosed within the past year; 26% within the last 5 years; >50% more than 10 years ago. No attendees had previously attended a hospital axSpA SMP session. Conclusion There is demand from patients and HCPs for an axSpA virtual patient SMP. Co-producing the programme can be effective for: engaging with a range of patients; educating and empowering patients to self-manage their condition; building relationships between HCPs and patients; reducing patient isolation; enabling appropriate self-referral to rheumatology services. This pilot has informed our next steps to expand the online sessions to new centres and explore co-producing an e-learning programme. Disclosure Z.E. Clark: Grants/research support; National Axial Spondyloarthritis Society receives grant funding from AbbVie, Biogen, Eli Lilly, Janssen, Novartis, UCB. W. Gregory: Honoraria; Speaker, conference registration and advisory board fees from AbbVie, Pfizer, Novartis, UCB. A. Chan: Member of speakers’ bureau; UCB, Novartis, Sanofi, AbbVie, Jannsen. A. Coy: None. Z. Cox: None. S. Dickinson: Grants/research support; National Axial Spondyloarthritis Society receives grant funding from AbbVie, Biogen, Eli Lilly, Janssen, Novartis, UCB. K. Gaffney: Shareholder/stock ownership; SpA Academy. Honoraria; Novartis, AbbVie, UCB, Lilly, Pfizer, Biogen. Member of speakers’ bureau; Celltrion, Novartis, UCB, AbbVie. Grants/research support; NASS, AbbVie, Pfizer, UCB, Novartis, Lilly, Jannsen, Gilead, Biogen. Other; Meeting expenses: AbbVie, Lilly, Roche, Novartis, Pfizer, UCB. B. Harrison: None. H. Herbert: None. C. Lewis: None. C. McCoy: None. K. Noel: None. K. Porthouse: None. K. Rigler: None. K. Weight: None. T. Williams: None. D. Webb: Grants/research support; National Axial Spondyloarthritis Society receives grant funding from AbbVie, Biogen, Eli Lilly, Janssen, Novartis, UCB. L. Dunkley: Honoraria; Honoraria with UCB, AbbVie, Pfizer.

A variety of genetic techniques have been devised to determine cell lineage relationships during tissue development. Some of these systems monitor cell lineages spatially and/or temporally without regard to gene expression by the cells, whereas others correlate gene expression with the lineage under study. The GAL4 Technique for Real-time and Clonal Expression (G-TRACE) system allows for rapid, fluorescent protein-based visualization of both current and past GAL4 expression patterns and is therefore amenable to genome-wide expression-based lineage screens. Here we describe the results from such a screen, performed by undergraduate students of the University of California, Los Angeles (UCLA) Undergraduate Research Consortium for Functional Genomics (URCFG) and high school summer scholars as part of a discovery-based education program. The results of the screen, which reveal novel expression-based lineage patterns within the brain, the imaginal disc epithelia, and the hematopoietic lymph gland, have been compiled into the G-TRACE Expression Database (GED), an online resource for use by the Drosophila research community. The impact of this discovery-based research experience on student learning gains was assessed independently and shown to be greater than that of similar programs conducted elsewhere. Furthermore, students participating in the URCFG showed considerably higher STEM retention rates than UCLA STEM students that did not participate in the URCFG, as well as STEM students nationwide.

Background As public health responds to evolving challenges around the globe, it is critical to draw on community-level evidence to inform decisions on emerging needs. There are existing tools for assessing the quality of research evidence, but none that explicitly focus on quality assessment of evidence from community sources, including local health status and ever-changing community and political preferences and actions. Methods The National Collaborating Centre for Methods and Tools (NCCMT) in Canada has developed new tools, called Quality Assessment of Community Evidence (QACE), to help public health decision makers assess the quality of community evidence. The QACE tools were drafted through extensive review of existing frameworks, tools and measures for appraising population health and community evidence, and diverse key informants. We identified three consistent themes that became the core dimensions in these tools. By using the QACE tools, practitioners can answer the question: “Is the quality of this evidence about local context, community needs and political preferences good enough to influence decision making?” Results The QACE tools provide probing questions for each of three dimensions: relevant, trustworthy and equity-informed. Supplementary resources help users delve more deeply into different aspects of quality assessment. The QACE tools are intended for public health practitioners who provide and use evidence to support or make decisions about public health practice and policy, including public health practitioners, senior leaders, policy makers and funders. Conclusions The QACE tool is a new addition to the public health toolbox for evidence-informed decision making, providing questions to ask about evidence from community sources. By using the tool as part of a decision-making process, public health practitioners can be assured that their decisions are based on the best-available evidence for their communities. Key messages The new Quality Assessment of Community Evidence (QACE) tools fill the gap in assessing quality of community-level evidence for public health decision-makers. Community evidence, including local health status and needs and community and political preferences and actions, should be assessed for quality in three critical domains.

Issue In 2019, the government of the Canadian province of Ontario announced major changes to the structure, governance and funding of public health services. Throughout these changes, publicly funded local and regional public health organizations are still expected to provide effective, evidence-informed programming to their communities. The National Collaborating Centre for Methods and Tools (NCCMT) has facilitated collaborations to support Ontario public health through this transition. Description of the problem In order to support evidence-informed public health in Ontario during this transition, the NCCMT reached out to current and potential partners, within and beyond the public health sector for a multidisciplinary approach. We conducted a needs assessment for an evidence review repository, which would allow public health practitioners to share and build upon each other's work. Finally, demonstrating the value of public health to policymakers can be inherently challenging as the return on investment in public health is often very long term. We partnered with health units in varying capacities to find and synthesize evidence to advocate for continued investment in public health. Results This initiative has provided important lessons in developing and maintaining strong partnerships. Looking beyond the public health sector can establish mutually beneficial partners and allies in other disciplines. A key finding was the need to establish infrastructure to support collaboration and resource sharing. Finally, we learned that big picture questions like demonstrating the value of public health require many different perspectives, inputs and areas of expertise. Lessons Through this initiative, we have developed a multidisciplinary, collaborative approach to supporting evidence-informed public health through times of major restructuring. This approach can be applied to future changes to public health on smaller or larger scales, or within other geographic regions. Key messages Multidisciplinary approaches can support collaboration, unity and advocacy in times of change. Establishing infrastructure to support collaboration and sharing of resources is valuable.

Issue It is well accepted that public health decision makers should use the best available research evidence in their decision-making process. However, research evidence alone is insufficient to inform public health decision making. Description of the problem As new challenges to public health emerge, there can be a paucity of high quality research evidence to inform decisions on new topics. Public health decision makers must combine various sources of evidence with their public health expertise to make evidence-informed decisions. The National Collaborating Centre for Methods and Tools (NCCMT) has developed a model which combines research evidence with other critical sources of evidence that can help guide decision makers in evidence-informed decision making. Results The NCCMT's model for evidence-informed public health combines findings from research evidence with local data and context, community and political preferences and actions and evidence on available resources. The model has been widely used across Canada and worldwide, and has been integrated into many public health organizations' decision-making processes. The model is also used for teaching an evidence-informed public health approach in Masters of Public Health programs around the globe. The model provides a structured approach to integrating evidence from several critical sources into public health decision making. Use of the model helps ensure that important research, contextual and preference information is sought and incorporated. Lessons Next steps for the model include development of a tool to facilitate synthesis of evidence across all four domains. Although Indigenous knowledges are relevant for public health decision making and should be considered as part of a complete assessment the current model does not capture Indigenous knowledges. Key messages Decision making in public health requires integrating the best available evidence, including research findings, local data and context, community and political preferences and available resources. The NCCMT’s model for evidence-informed public health provides a structured approach to integrating evidence from several critical sources into public health decision making.

Background There are few longitudinal studies of seasonal influenza-associated neurological disease (IAND) and none from the Southern Hemisphere. Methods We extracted prospectively acquired Australian surveillance data from 2 studies nested within the Paediatric Active Enhanced Disease Surveillance (PAEDS) network: the Influenza Complications Alert Network (FluCAN) study and the Australian Childhood Encephalitis (ACE) study between 2013 and 2015. We described the clinical features and severity of IAND in children, including influenza-associated encephalitis/encephalopathy (IAE). We calculated the proportion of hospitalized influenza that is associated with IAND and IAE, and incidence of IAE. Results Over 3 influenza seasons, we identified 54 cases of IAND at 2 tertiary children's hospitals from Australia that accounted for 7.6% of hospitalized influenza. These included 10 cases of IAE (1.4% hospitalized influenza). The mean annual incidence of IAE among Australian children (aged ≤14 years) was 2.8 per 1000000. The spectrum of IAND was broad and included IAE (n = 10) including distinct acute encephalopathy syndromes, simple febrile seizures (n = 14), other seizures (n = 16), acute ataxia (n = 4), and other subacute syndromes (transverse myelitis [n = 1], opsoclonus myoclonus [n = 1]). Two-thirds of children with IAND were aged ≤4 years; less than half had preexisting neurological disease or other risk factors for severe influenza. IAE caused death or neurological morbidity in half of cases. Conclusions Seasonal influenza is an important cause of acute neurological disease in Australian children. The spectrum of seasonal IAND appears similar to that described during the 2009 H1N1 pandemic. IAE is associated with high morbidity and mortality.

Walking function is compromised with older age, particularly for cognitively demanding complex walking tasks. Frontal lobe brain networks are important to both complex walking and cognitive function. There is a need for interventions that target this brain region. This pilot study assessed a novel intervention to enhance both walking and executive function in older adults. The primary hypothesis was that eighteen sessions of frontal lobe tDCS combined with complex walking rehabilitation would be feasible, safe, and show preliminary efficacy for improvements in walking and cognition. Eighteen participants were randomized to one of three intervention groups: active tDCS and rehabilitation with complex walking tasks (Active/Complex); sham tDCS and rehabilitation with complex walking tasks (Sham/Complex); or sham tDCS and rehabilitation with typical walking (Sham/Typical). Outcome measures included multiple tests of walking function, executive function, and prefrontal activity during walking measured by functional near infrared spectroscopy. For the walking tests, effect sizes for Active/Complex were generally higher than for Sham/Complex. The Sham/Typical group exhibited walking test effect sizes that were often larger than either of the complex walking groups, possibly due to higher intervention step count. For the executive function tests, effect sizes were largest for the Active/Complex group. Improvements in prefrontal activity during walking were observed, as conceptualized by the Compensation Related Utilization of Neural Circuits Hypothesis. These preliminary findings support that tDCS combined with complex walking rehabilitation in older adults is feasible and may enhance both walking function and executive function.

This pilot study assessed a novel intervention to enhance both walking and executive function in older adults. The primary hypothesis was that eighteen sessions of frontal lobe tDCS combined with walking rehabilitation would be feasible, safe, and show preliminary efficacy. Eighteen participants were randomized to one of three intervention groups: active tDCS and rehabilitation with complex walking tasks (Active/Complex); sham tDCS and rehabilitation with complex walking tasks (Sham/Complex); or sham tDCS and rehabilitation with typical walking (Sham/Typical). Outcome measures included multiple tests of walking function, executive function, and prefrontal activity during walking as measured by functional near infrared spectroscopy (fNIRS). Of the three groups, the Active/Complex group demonstrated the broadest improvements across outcome measures including for prefrontal activity. The functional range of prefrontal activity in this group was increased considerably, as conceptualized by the Compensation Related Utilization of Neural Circuits Hypothesis. Frontal tDCS is a promising adjuvant to walking rehabilitation.

B chromosomes are extra chromosomes found in many species of plants, animals, and fungi. B chromosomes often manipulate common cellular processes to increase their frequency, sometimes to the detriment of organismal fitness. Here, we characterize B chromosomes in several species of Lake Malawi cichlid fish. Whole genome sequencing of Metriaclima zebra "Boadzulu" individuals revealed blocks of sequence with unusually high sequence coverage, indicative of increased copy number of those sequences. These regions of high sequence coverage were found only in females. SNPs unique to the high copy number sequences permitted the design of specific amplification primers. These primers amplified fragments only in Metriaclima lombardoi individuals that carried a cytologically identified B chromosome (B-carriers), indicating these extra copies are located on the B chromosome. These same primers were used to identify B-carrying individuals in additional species from Lake Malawi. Across 7 species, a total of 43 B-carriers were identified among 323 females. B-carriers were exclusively female; no B chromosomes were observed in the 317 males surveyed from these species. Quantitative analysis of the copy number variation of B-specific sequence blocks suggests that B-carriers possess a single B chromosome, consistent with previous karyotyping of M. lombardoi A single B chromosome in B-carriers is consistent with 2 potential drive mechanisms: one involving nondisjunction and preferential segregation in a mitotic division prior to the germ-line, and the other involving preferential segregation during meiosis I.

Objectives: We compared the utility of membrane-associated guanylate kinase, WW and PDZ domain-containing protein 2 (MAGI-2) and α-methylacyl CoA (AMACR) by immunohistochemistry in diagnosing prostatic adenocarcinoma. Methods: Seventy-eight radical prostatectomies were used to construct three tissue microarrays with 512 cores, including benign prostatic tissue, benign prostatic hyperplasia, high-grade prostatic intraepithelial neoplasia (HGPIN), and adenocarcinoma. AMACR and MAGI-2 immunohistochemistry were evaluated by visual and image analysis. Results: MAGI-2 and AMACR were significantly higher in adenocarcinoma and HGPIN compared with benign tissue. At H-score cutoffs of 300 and 200, MAGI-2 was more accurate in distinguishing benign from malignant glands than AMACR. Areas under the curve by image and visual analysis were 0.846 and 0.818 for MAGI-2 and 0.937 and 0.924 for AMACR, respectively. The accuracy of MAGI-2 in distinguishing benign from malignant glands on the same core was higher (95% vs 88%). Conclusions: MAGI-2 could represent a useful adjunct for diagnosis of prostatic adenocarcinoma, especially when AMACR is not discriminatory.

Wolbachia pipientis are obligate intracellular bacteria commonly found in many arthropods. They can induce various reproductive alterations in hosts, including cytoplasmic incompatibility, male-killing, feminization, and parthenogenetic development, and can provide host protection against some viruses and other pathogens. Wolbachia differ from many other primary endosymbionts in arthropods because they undergo frequent horizontal transmission between hosts and are well known for an abundance of mobile elements and relatively high recombination rates. Here, we compare the genomes of two closely related Wolbachia (with 0.57% genome-wide synonymous divergence) that differ in their reproductive effects on hosts. wVitA induces a sperm–egg incompatibility (also known as cytoplasmic incompatibility) in the parasitoid insect Nasonia vitripennis, whereas wUni causes parthenogenetic development in a different parasitoid, Muscidifurax uniraptor. Although these bacteria are closely related, the genomic comparison reveals rampant rearrangements, protein truncations (particularly in proteins predicted to be secreted), and elevated substitution rates. These changes occur predominantly in the wUni lineage, and may be due in part to adaptations by wUni to a new host environment, or its phenotypic shift to parthenogenesis induction. However, we conclude that the approximately 8-fold elevated synonymous substitution rate in wUni is due to a either an elevated mutation rate or a greater number of generations per year in wUni, which occurs in semitropical host species. We identify a set of genes whose loss or pseudogenization in the wUni lineage implicates them in the phenotypic shift from cytoplasmic incompatibility to parthenogenesis induction. Finally, comparison of these closely related strains allows us to determine the fine-scale mutation patterns in Wolbachia. Although Wolbachia are AT rich, mutation probabilities estimated from 4-fold degenerate sites are not AT biased, and predict an equilibrium AT content much less biased than observed (57–50% AT predicted vs. 76% current content at degenerate sites genome wide). The contrast suggests selection for increased AT content within Wolbachia genomes.

Background Many studies have documented lower vaccine efficacy among children in low-income countries, compared with their counterparts in high-income countries. This disparity is especially apparent with respect to oral vaccines such as rotavirus and oral polio vaccines. One potential contributing factor is the presence of maternal antenatal helminth infections, which can modulate the infant's developing immune system. Methods Using a multiplex immunoassay, we tested plasma immunoglobulin A (IgA) or immunoglobulin G (IgG) levels specific for antigens in 9 routinely administered childhood vaccines among 1639 children aged approximately 13 months enrolled in the ECUAVIDA (Ecuador Life) birth cohort study in Ecuador. We compared vaccine responses in 712 children of mothers who tested positive for helminth infections in the last trimester of pregnancy to responses in 927 children of mothers without helminth infection. Results Plasma IgA levels specific for antigens in rotavirus vaccine and oral polio vaccine containing poliovirus serotypes 1 and 3 were all significantly higher in children of helminth-infected mothers, compared with children of uninfected mothers. Plasma IgG levels specific for diphtheria, tetanus, pertussis, measles, rubella, and Haemophilus influenzae type b vaccine antigens were comparable between the 2 groups. Conclusions Antenatal maternal helminth infections were not associated with reduced antibody responses to infant vaccines, but rather with modestly increased IgA responses to oral vaccines.

The enzymatic processing of cellular RNA molecules requires selective recognition of unique chemical and topological features. The unusual 2′,5′-phosphodiester linkages in RNA lariats produced by the spliceosome must be hydrolyzed by the intron debranching enzyme (Dbr1) before they can be metabolized or processed into essential cellular factors, such as snoRNA and miRNA. Dbr1 is also involved in the propagation of retrotransposons and retroviruses, although the precise role played by the enzyme in these processes is poorly understood. Here, we report the first structures of Dbr1 alone and in complex with several synthetic RNA compounds that mimic the branchpoint in lariat RNA. The structures, together with functional data on Dbr1 variants, reveal the molecular basis for 2′,5′-phosphodiester recognition and explain why the enzyme lacks activity toward 3′,5′-phosphodiester linkages. The findings illuminate structure/function relationships in a unique enzyme that is central to eukaryotic RNA metabolism and set the stage for the rational design of inhibitors that may represent novel therapeutic agents to treat retroviral infections and neurodegenerative disease.

Objective. The primary aim of this study was to assess smoking characteristics and cessation motivation prior to and after initiation of multi- disciplinary chronic pain treatment. A secondary aim was to identify predictors of cessation motivation among smokers initiating treatment for chronic pain. Design. We used a prospective, nonrandomized, repeated measures design. Setting. The study was conducted in a multi- disciplinary specialty pain treatment program at a veterans hospital. Patients. Smokers (N = 90) referred to a multi- disciplinary pain program for the treatment of chronic pain. Measures. Patients completed questionnaires assessing pain-related and smoking-related factors prior to (baseline) and 8 weeks post (follow-up) spe- cialty pain treatment initiation. Primary outcome measures were the Contemplation Ladder and the Stages of Change (SOC) algorithm. Results. At baseline, patients reported moderate levels of cessation motivation, and 69% were in the contemplation stage or higher on the SOC. Motiva- tion to quit smoking was higher at follow-up com- pared with baseline on both continuous, t(89) = 2.11, P < 0.05, and stage-based, z = 3.69, P < 0.01, mea- sures. At follow-up, participants reported greater interest in receiving cessation interventions, and 7.8% of patients had quit smoking. Pain-related pre- dictors of motivation (e.g., pain intensity) were sub- sumed by more general predictors (e.g., nicotine dependence). Conclusions. Patients in this sample were more motivated to quit smoking a few weeks after, as compared with before initiating specialty pain treat- ment. Future research into pain-specific predictors of cessation motivation is warranted to inform the development of interventions that address pain patients' unique needs.

BACKGROUND Previous studies have established several meningioma genomic subgroups, defined by the mutually exclusive genomic drivers. However, we distinguished a small subset of meningiomas simultaneously harboring multiple drivers from different genomic subgroups, thus referred to as “multiple-driver meningiomas”, that has not been previously investigated. We aimed to characterize the genomic landscape and clinical features of multiple-driver meningiomas. METHODS We identified 42 cases of multiple-driver meningiomas from a cohort of 3,016 cases screened for genomic drivers via molecular inversion probe sequencing (MIPS) and/or whole-exome sequencing (WES) previously in our laboratory. All driver mutations were validated via Sanger sequencing and chromosome 22 loss was accessed with qPCR. Clinical information was collected and genome-to-clinical correlations were statistically analyzed. We selected 10 multiple-driver meningioma cases for tumor-normal WES for further characterization of genomic architecture. RESULTS Multiple-driver meningiomas were significantly enriched for NF2 alteration (p< 0.001), had significantly higher WHO grade (p= 0.005) and proportion of recurrent tumors (p= 0.007) when compared with “single-driver meningiomas”, i.e. harboring driver alterations from a single genomic subgroup. Among female cases, those with multiple drivers were nearly four times more likely to be high-grade (II or III) compared to single-driver female samples (48.6% vs. 12.6%, p< 0.001). Among tumors harboring NF2 alteration, multiple-driver meningiomas demonstrated skull base predilection compared with single-driver meningiomas (50.0% vs. 27.9%, p= 0.005). WES analysis of 10 multiple-driver meningiomas identified 1p and/or 14q loss in 60% of cases. Clonality analysis revealed the presence of sub-clonal cell populations in 9 cases with all driver mutations clustered into the founding clone in 7 cases, suggesting their acquisition in the early phase of tumor development. CONCLUSION Multiple-driver meningiomas demonstrate distinct genomic and clinical features that distinguish them as clinically aggressive. They frequently occur in surgically challenging skull base locations, and are more prevalent among high-grade and recurrent cases.

The development of more effective medical simulators requires a collaborative team effort where three kinds of expertise are carefully coordinated: (1) exceptional medical expertise focused on providing complete and accurate information about the medical challenges (i.e., critical skills and knowledge) to be simulated; (2) instructional expertise focused on the design of simulation-based training and assessment methods that produce maximum learning and transfer to patient care; and (3) software development expertise that permits the efficient design and development of the software required to capture expertise, present it in an engaging way, and assess student interactions with the simulator. In this discussion, we describe a method of capturing more complete and accurate medical information for simulators and combine it with new instructional design strategies that emphasize the learning of complex knowledge. Finally, we describe three different types of software support (Development/Authoring, Run Time, and Post Run Time) required at different stages in the development of medical simulations and the instructional design elements of the software required at each stage. We describe the contributions expected of each kind of software and the different instructional control authoring support required.

Myrmecochory is a facultative, mutualistic interaction in which ants receive a protein-rich food reward (elaiosome) in return for dispersing plant seeds. In North American northeastern hardwood forests, Aphaenogaster ants are the primary genus dispersing myrmecochorous plants. In these forests, myrmecochores occur in plant guilds of understory spring ephemerals or seasonal greens. This mutualism has been demonstrated for Aphaenogaster rudis (Emery) and individual plant species, but it has not been demonstrated for other Aphaenogaster species or guilds of myrmecochores as they naturally occur. Aphaenogaster picea (Wheeler) colonies were fed three treatments over 5 mo: 1) a mixture of only elaiosomes from an entire plant guild, 2) a diet of only insect protein and 3) a combination diet of both elaiosomes and insect protein. This experiment investigated two potential hypotheses through which elaiosomes can benefit ants: 1) elaiosome proteins can substitute for protein nutritional requirements when ants are prey-limited, and 2) elaiosome nutrition can supplement insect protein when prey is ample. First, a mixture of elaiosomes from four myrmecochorous plant species provided to A. picea colonies was sufficient to maintain worker production, larval growth, and fat stores when no other food was available. A. picea colonies consuming elaiosomes as their only protein source could be sustained for a growing season (5 mo). Second, colonies fed both elaiosomes and protein did not yield more productive colonies than a control diet of just insect protein. These results support the hypothesis that myrmecochory is indeed a facultative mutualism in which ants take advantage of the protein content of elaiosomes when it is favorable, but when they are not limited by insect prey they do not gain any additional benefit from elaiosomes.

A 2-yr study was conducted using a 3 × 2 factorial arrangement of treatments to evaluate the effects of feeding dried distillers grains throughout a beef production system on performance, carcass characteristics, and fatty acid profile of beef. Factors were wheat pasture supplement [no supplement (CON), dry-rolled corn (DRC), and dried distillers grains (DDG)] fed at 0.5% BW daily and finishing diet [steam-flaked corn based diet containing 0 (SFC) or 35% (35DDG) DDG]. Each year, 60 preconditioned Hereford steers (initial BW = 198 kg ± 3) grazed winter wheat pasture with or without supplement. Body weight gain was 8% greater for steers consuming DDG supplement compared with CON and DRC steers (P < 0.01). After the grazing period, pastures within supplement treatment were randomly assigned to SFC or 35DDG. There was no supplement by finishing diet interaction for any performance or carcass variable of interest (P ≥ 0.41). Previous supplementation on winter wheat affected BW at feedlot entry and adjusted G:F (P ≤ 0.05) but had no effect on finishing ADG or carcass traits (P ≥ 0.12). On a carcass-adjusted basis, steers consuming 35DDG had reduced final BW, ADG, G:F, and total BW gain throughout the system (P ≤ 0.04) compared with SFC. Additionally, steers consuming 35DDG had reduced HCW, dressing percent, and fat thickness (P ≤ 0.03) compared with SFC. There was a supplement by finishing diet interaction (P = 0.02) for 18:0, in which cattle supplemented with DRC and fed the SFC finishing diet had the lowest concentration of 18:0 but DRC supplemented steers fed the 35DDG diet had the greatest concentration. The interaction was not significant (P ≥ 0.18) for other fatty acids. Main effects of supplement and finishing diet affected (P ≤ 0.05) several other fatty acids of interest, particularly 18:2, which is associated with reduced flavor-stability of beef. The use of DDG as a supplement to wheat pasture resulted in greater ADG during wheat grazing and heavier BW at feedlot entry, but final BW was not different from CON or DRC groups. Feeding DDG at 35% DM in steam-flaked corn-based finishing diets reduced ADG, G:F, and HCW, and affected the fatty acid composition of beef.

Two experiments were conducted to determine the effects of wet distillers grain plus solubles (WDG; 0.14) for DRC compared with SFC. Ruminal and total tract starch digestibility were greater (P < 0.01) for SFC compared with DRC. Dry matter and OM intake were not different (P ≥ 0.43) among WDG treatments. Ruminal and total tract OM digestibility decreased linearly (P < 0.01) with increasing WDG concentration. Intake, ruminal digestibility, and total tract digestibility of NDF increased linearly (P < 0.01) with increasing WDG concentration. Starch intake decreased linearly (P < 0.01) with increasing WDG concentration. Ruminal starch digestibility increased (P = 0.01) with increasing concentration of WDG. Total tract starch digestibility decreased quadratically (P < 0.01) with increasing concentration of WDG. Feeding SFC improved steer performance compared with DRC. The concentration of WDG and corn processing method influences nutrient digestibility and ruminal fermentation. The addition of WDG in SFC-based diets appears to negatively affect animal performance by diluting the energy density of the diet.

Embryonic growth and development are impacted by environmental conditions. In avian systems, parents tightly control these environments through provisioning of nutrients to the egg and through incubation. Parents can influence embryonic development through egg size, eggshell conductance, hormones, or other substances deposited in eggs and through the onset and temperature of incubation. In addition to these parental influences, evidence suggests that avian embryos are able to perceive and actively respond to their environment during incubation and adjust their own development. Evolution of embryos' responses to developmental environments in birds can be understood in the context of parent-offspring conflicts. When parental investments favor future reproduction over current reproduction, current offspring pay fitness costs, which result in strong selection for offspring that can respond to developmental environments independent of their parents. Here, we review literature indicating that avian embryos actively respond to maternally derived components of the egg, vocalizations, and differences in day length, and we explore these responses in the context of three situations where the consequence of these environments to the fitnesses of offspring and parents differ: the degree of synchrony in hatching, the deposition of hormones in yolks, and seasonal timing of breeding. However, the adaptive significance of responses of embryos to developmental environments arising from parent-offspring conflict has not been adequately explored in birds.

Bacteriophage flux can cause the majority of genetic diversity in free-living bacteria. This tenet of bacterial genome evolution generally does not extend to obligate intracellular bacteria owing to their reduced contact with other microbes and a predominance of gene deletion over gene transfer. However, recent studies suggest intracellular coinfections in the same host can facilitate exchange of mobile elements between obligate intracellular bacteria—a means by which these bacteria can partially mitigate the reductive forces of the intracellular lifestyle. To test whether bacteriophages transfer as single genes or larger regions between coinfections, we sequenced the genome of the obligate intracellular Wolbachia strain wVitB from the parasitic wasp Nasonia vitripennis and compared it against the prophage sequences of the divergent wVitA coinfection. We applied, for the first time, a targeted sequence capture array to specifically trap the symbiont’s DNA from a heterogeneous mixture of eukaryotic, bacterial, and viral DNA. The tiled array successfully captured the genome with 98.3% efficiency. Examination of the genome sequence revealed the largest transfer of bacteriophage and flanking genes (52.2 kb) to date between two obligate intracellular coinfections. The mobile element transfer occurred in the recent evolutionary past based on the 99.9% average nucleotide identity of the phage sequences between the two strains. In addition to discovering an evolutionary recent and large-scale horizontal phage transfer between coinfecting obligate intracellular bacteria, we demonstrate that ‘‘targeted genome capture’’ can enrich target DNA to alleviate the problem of isolating symbiotic microbes that are difficult to culture or purify from the conglomerate of organisms inside eukaryotes.

Transferring endosymbiotic bacteria between different host species can perturb the coordinated regulation of the host and bacterial genomes. Here we use the most common maternally transmitted bacteria, Wolbachia pipientis, to test the consequences of host genetic background on infection densities and the processes underlying those changes in the parasitoid wasp genus Nasonia. Introgressing the genome of Nasonia giraulti into the infected cytoplasm of N. vitripennis causes a two-order-of-magnitude increase in bacterial loads in adults and a proliferation of the infection to somatic tissues. The host effect on W. pipientis distribution and densities is associated with a twofold decrease in densities of the temperate phage WO-B. Returning the bacteria from the new host species back to the resident host species restores the bacteria and phage to their native densities. To our knowledge, this is the first study to report a host–microbe genetic interaction that affects the densities of both W. pipientis and bacteriophage WO-B. The consequences of the increased bacterial density include a reduction in fecundity, an increase in levels of cytoplasmic incompatibility (CI), and unexpectedly, male-to-female transfer of the bacteria to uninfected females and an increased acceptance of densely infected females to interspecific mates. While paternal inheritance of the W. pipientis was not observed, the high incidence of male-to-female transfer in the introgressed background raises the possibility that paternal transmission could be more likely in hybrids where paternal leakage of other cytoplasmic elements is also known to occur. Taken together, these results establish a major change in W. pipientis densities and tissue tropism between closely related species and support a model in which phage WO, Wolbachia, and arthropods form a tripartite symbiotic association in which all three are integral to understanding the biology of this widespread endosymbiosis.

Waterfowl lay large clutches of eggs over many days, yet the offspring hatch synchronously, indicating regulatory mechanisms must aid in minimizing developmental differences among offspring. Understanding how embryos' metabolic rates vary with the sequence in which the egg is laid can provide insight into intrinsic mechanisms regulating the synchrony of hatching. Furthermore, developmental rates differing among offspring within a clutch likely have post-hatching consequences for offspring performance. We characterized variation in developmental rates within a clutch and the consequences for offspring performance in the Canada Goose (Branta canadensis maxima). We measured embryonic metabolic rates every 2 to 3 days, examined goslings' yolk reserves immediately after hatching, and conducted a cross-fostering experiment to assess plasticity in hatching synchrony and gosling survival in the 2 weeks after hatching. We found that embryonic O2 consumption rates increased with age in an S-shaped pattern...

To review the literature addressing the assessment and management of pain in patients with polytraumatic injuries including traumatic brain injury (TBI) and blast-related headache, and to identify patient, clinician and systems factors associated with pain-related outcomes.Systematic review.We conducted searches in MEDLINE of literature published from 1950 through July 2008. Due to a limited number of studies using controls or comparators, we included observational and rigorous qualitative studies. We systematically rated the quality of systematic reviews, cohort, and case-control design studies.One systematic review, 93 observational studies, and one qualitative research study met inclusion criteria. The literature search yielded no published studies that assessed measures of pain intensity or pain-related functional interference among patients with cognitive deficits due to TBI, that compared patients with blast-related headache with patients with other types of headache, or that assessed treatments for blast-related headache pain. Studies on the association between TBI severity and pain reported mixed findings. There was limited evidence that the following factors are associated with pain among TBI patients: severity, location, and multiplicity of injuries; insomnia; fatigue; depression; and post-traumatic stress disorder.Very little evidence is currently available to guide pain assessment and treatment approaches in patients with polytrauma. Further research employing systematic observational as well as controlled intervention designs is clearly indicated.

Prostate cancer (PCa) is one of the most common cancers in the world. Inflammation has been described as a risk factor for PCa and depends on the production of cytokines in response to tissue damage or the presence of stimuli that induces cellular stress. Interindividual variation in cytokine production is partially controlled by single-nucleotide polymorphisms (SNPs) that have been associated with differential production of cytokines. We have recently showed that SNP-SNP interactions of cytokine genes are associated with PCa risk. However, little is known about the association of cytokine SNPs and PCa aggressiveness. In this study, we evaluated the association of 15 SNPs in five cytokine genes and aggressiveness of PCa in African- and Caucasian-American individuals. Caucasian Americans with the genotypes IL10-1082GG or IL1B+3954TT had 2.31-fold [95% confidence interval (CI) = 1.13-4.72] and 3.11 (95% CI = 1.20-8.06)-fold risk, respectively, of developing aggressive PCa, as compared with individuals without those genotypes. We did not find any associations in the African-American group. Using Multivariate Adaptive Regression Splines modeling for exploratory SNP-SNP interactions, our results showed that more aggressive PCa in Caucasians Americans is associated with the CT genotype at IL8-47 [odds ratios (OR) = 3.50; 95% CI = 1.13-10.88] or combined genotypes of IL1B-511CC and IL10-1082GG (OR = 3.38; 95% CI = 1.70-6.71). Unfortunately, the same analysis could not be performed in the African-Americans due to limited number of individuals. With limited sample size, the results from this study suggest that SNPs in cytokine genes may be associated with PCa aggressiveness. More extensive studies are warranted to validate our findings.