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The European North West shelf seas (NWS) support economic and environmental interests of several adjacent populous countries. Forecasts of physical marine variables on the NWS for upcoming months – an important decision-making timescale – would be useful for many industries. However, currently there is no operational seasonal forecasting product deemed sufficient for capturing the high variability associated with shallow, dynamic shelf waters. Here, we identify the dominant sources of seasonal predictability on the shelf and quantify the extent to which empirical persistence relationships can produce skilful seasonal forecasts of the NWS at the lowest level complexity. We find that relatively skilful forecasts of the typically well-mixed Winter and Spring seasons are achievable via persistence methods at a one-month lead time. In addition, incorporating observed climate modes of variability, such as the North Atlantic Oscillation (NAO), can significantly boost persistence for some locations and seasons, but this is dependent on the strength of the climate mode index. However, even where high persistence skill is demonstrated, there are sizeable regions exhibiting poor predictability and skilful persistence forecasts are typically limited to ≈ one-month lead times. Summer and Autumn forecasts are generally less skilful owing largely to the effects of seasonal stratification which emphasises the influence of atmospheric variability on sea surface conditions. As such, we also begin incorporating knowledge of future atmospheric conditions to forecasting strategies. We assess the ability of an existing global coupled ocean-atmosphere seasonal forecasting system to exceed persistence skill and highlight areas where additional downscaling efforts may be needed.

To describe the perceived prevalence of zoological companion animal (ZCA) species being evaluated and treated by American College of Veterinary Emergency and Critical Care (ACVECC) diplomates and Emergency and Critical Care (ECC) residents in an emergency room (ER) setting and to assess potential interest in further training for the ACVECC community in the emergency treatment and stabilization of these species.Internet-based survey.One hundred and thirty-nine ACVECC diplomates and ECC residents.An online survey was designed and administered to assess the perceived prevalence of ZCA species that were evaluated and treated in the veterinary ER and to gauge potential interest in advanced training opportunities in the emergency treatment of these patients.One hundred and fifteen (83%) respondents reported that their hospital offered veterinary services to ZCA species during business hours and 120 (86%) reported that they offered veterinary services to ZCA species during off-hours. Ninety-one (65%) respondents reported that ZCA patients were evaluated and treated through their ER with small mammals (n = 60/91 [66%]) and small birds (n = 48/91 [53%]) being the most common species presented. In hospitals with an available ZCA specialist (80/139 [56%]), primary case responsibility was maintained by the ZCA specialist 24-7 in 11 of 91 (14%) hospitals. Seventy-three (53%) ACVECC diplomate and ECC resident survey respondents reported clinical training specific to ZCA species during veterinary school. A total of 84 of 139 (60%) survey respondents expressed interest in further training regarding ZCA species, with 73 of 84 (87%) those individuals specifying interest or potential interest in a formal ACVECC certificate or other type of advanced training.

Raised-bar guidance surfaces (GSs) are used internationally to help wayfinding by vision-disabled pedestrians, but they are little used in the United States. However, difficulties experienced by vision-disabled pedestrians in locating crosswalks and aligning to cross have been documented, and the installation of GSs with bars perpendicular to the crossing direction has been shown to improve locating the crosswalk and aligning to cross at noncorner crossings. The present research investigated the effect, for a total of 68 participants, of a raised-bar GS on locating crosswalks and aligning to cross at (primarily) corner crossings in three cities. Using 2- × 2-ft raised-bar GSs with bars oriented perpendicular to the crossing direction at corner crossings, and a 2-ft wide strip of GSs extending across the sidewalk at noncorner crossings, significant improvements in the accuracy of crossing starting position and alignment were observed. Accuracy in locating the crosswalk was quite good at corner crossings, and was not improved by the GS. Installation of a raised-bar GS with bars perpendicular to the crossing direction is recommended to help vision-disabled pedestrians align for crossing. At corner crossings, a 2- × 2-ft GS located beside the detectable warning surface at the bottom of curb ramps, on the side farthest from the intersection, is recommended. At noncorner crossings, a 2-ft wide strip of GS extending all the way across the sidewalk, with the bars oriented perpendicular to the crossing direction, is recommended.

DNA methylation-derived epigenetic clocks offer the opportunity to examine aspects of age acceleration (i.e., the difference between an individual’s biological age and chronological age), which vary among individuals and may better account for age-related changes in cognitive function than chronological age. Leveraging existing ambulatory cognitive assessments in daily life from a genetically diverse sample of 142 adults in midlife, we examined associations between five measures of epigenetic age acceleration and performance on tasks of processing speed and working memory. Covarying for chronological age, we used multilevel models to examine associations of epigenetic age acceleration (Horvath 1, Horvath 2, Hannum, PhenoAge, GrimAge clocks) with both average-level and variability of cognitive performance. Positive age acceleration (i.e., epigenetic age greater than chronological age) was associated with poorer mean processing speed (Horvath 1 and 2) and working memory (GrimAge). Higher chronological age was also associated with poorer mean processing speed and working memory performance. Further, positive age acceleration was generally associated with greater intraindividual variability in working memory and processing speed tasks, whereas being chronologically older was associated with less intraindividual variability. Although further work is needed, our results indicate age acceleration effects have comparable or greater size as those for chronological age differences, suggesting that epigenetic age acceleration may be a better marker of risk and interindividual variation in cognitive performance than chronological age.

IntroductionWhile there have been several literature reviews on the performance of digital sepsis prediction technologies and clinical decision-support algorithms for adults, there remains a knowledge gap in examining the development of automated technologies for sepsis prediction in children. This scoping review will critically analyse the current evidence on the design and performance of automated digital technologies to predict paediatric sepsis, to advance their development and integration within clinical settings.Methods and analysisThis scoping review will follow Arksey and O’Malley’s framework, conducted between February and December 2022. We will further develop the protocol using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews. We plan to search the following databases: Association of Computing Machinery (ACM) Digital Library, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Embase, Google Scholar, Institute of Electric and Electronic Engineers (IEEE), PubMed, Scopus and Web of Science. Studies will be included on children >90 days postnatal to Ethics and disseminationEthics approval for this scoping review study of the available literature is not required. We anticipate that the scoping review will identify the current evidence and design characteristics of digital prediction technologies for the timely and accurate prediction of paediatric sepsis and factors influencing clinical integration. We plan to disseminate the preliminary findings from this review at national and international research conferences in global and digital health, gathering critical feedback from multidisciplinary stakeholders.Scoping review registrationhttps://osf.io/veqha/?view_only=f560d4892d7c459ea4cff6dcdfacb086

The coral reefs of the Pitcairn Islands are in one of the most remote areas of the Pacific Ocean, and yet they are exposed to the impacts of anthropogenic climate change. The Pitcairn Islands Marine Protected Area was designated in 2016 and is one of the largest in the world, but the marine environment around these highly isolated islands remains poorly documented. Evidence collated here indicates that while the Pitcairn Islands' reefs have thus far been relatively sheltered from the effect of warming sea temperatures, there is substantial risk of future coral decalcification due to ocean acidification. The projected acceleration in the rate of sea level rise, and the reefs' exposure to risks from distant ocean swells and cold-water intrusions, add further uncertainty as to whether these islands and their reefs will continue to adapt and persist into the future. Coordinated action within the context of the Pitcairn Islands Marine Protected Area can help enhance the resilience of the reefs in the Pitcairn Islands. Options include management of other human pressures, control of invasive species and active reef interventions. More research, however, is needed in order to better assess what are the most appropriate and feasible options to protect these reefs.

Introduction Prior research assessing self-reported or nocturnal sleep suggested that specific sleep traits (sleep restriction in the laboratory; poor sleep quality, sleep disorders) are associated with both pro and anti-inflammatory cytokine and C-Reactive Protein (CRP) levels. To extend prior research, we investigated associations between multiple dimensions of objectively assessed sleep health with both circulating and stimulated inflammatory markers in a diverse sample of older adults. Methods Participants in the Einstein Aging Study (EAS) were included (N=218, Mage=77.5 years, 6% female; 46% White, 38% Black, 14% Hispanic/other). A confirmatory factor analysis using wrist actigraphy sleep variables over 16 days yielded 6-component multi-dimensional sleep health facets: Regularity, Alertness/Sleepiness (daytime), Timing, Efficiency, Duration, and Rhythmicity. Inflammatory markers collected in the morning included CRP and both circulating markers reflecting current systemic inflammation, and lipopolysaccharide (LPS)-stimulated levels of (IL-1β, IL-4, IL-6, IL-8, IL-10, TNF𝛼), which reflect responses to an inflammatory challenge, an index of immune reactivity. Associations between each inflammatory marker and each sleep health facet were examined using linear regression, controlling for BMI, gender, age, education, ethnicity/race, number of health conditions, nocturnal hypoxemia, Oxygen Desaturation Index (ODI)≥15. Results Participants with more daytime sleepiness (i.e., higher number and longer duration of naps and lower activity level) had higher circulating IL-6 and CRP levels. Lower sleep efficiency was associated with lower levels of the anti-inflammatory circulating cytokine IL-4 and higher levels of stimulated IL-8 and TNF𝛼. Longer sleep duration was associated with higher levels of circulating IL-1β and CRP. Less rhythmicity across days was associated with higher levels of circulating IL-6. Nocturnal hypoxemia was associated with higher levels of CRP and stimulated IL-4, IL-8, and TNFα. We found no association between sleep timing and regularity and any inflammatory marker. Conclusion We observed that various sleep health facets are related to markers of inflammation and immune reactivity in older adults. This research also demonstrates the value of using 24-hour, device-based estimates of different sleep health facets relevant for immune function. Associations between 24-h sleep and inflammation are particularly important for older adults, who evidence more daytime sleepiness and less rhythmic sleep/active patterns in daily life. Support (if any) R01AG062622, P01AG003949, RF1AG056331-04

Prospective memory (PM) refers to our memory for future intentions, such as attending an appointment or taking medication. Research suggests that PM deficits can distinguish healthy older adults from those in early stages of dementia. However, limited work has examined PM and biological markers associated with pathological memory decline. The current study addressed this gap and examined self-reported PM lapses using a two-week ecological momentary assessment (EMA) diary protocol via smartphone as well as levels of blood-based inflammation among older adults (n = 231, Mage = 76.85 years) enrolled in the Einstein Aging Study. Reporting more PM lapses across the two weeks was related to higher levels of basal interleukin (IL)-8, although this effect did not hold when controlling for covariates. Furthermore, gender moderated this link; specifically, higher levels of IL-8 were associated with reporting more PM lapses among men but not women. No other significant relationships between PM lapses and basal or stimulated (ex vivo) cytokine levels (IL-1β, IL-4, IL-6, IL-8, IL-10, tumor necrosis factor-alpha [TNF-]) or C-reactive protein (CRP) emerged. Elevated levels of IL-8 in older men may possibly be an early indicator of neurodegeneration that relates to PM performance. Future studies should continue to examine PM and inflammation across genders to identify possible mechanisms through which these constructs may affect neurodegeneration and dementia risk.

Potentially harmful cyanobacterial blooms are an emerging environmental concern in freshwater bodies worldwide. Cyanobacterial blooms are generally caused by high nutrient inputs and warm, still waters and have been appearing with increasing frequency in water bodies used for drinking water supply and recreation, a problem which will likely worsen with a warming climate. Cyanobacterial blooms are composed of genera with known biological pigments and can be distinguished and analyzed via hyperspectral image collection technology such as remote sensing by satellites, airplanes, and drones. Here, we utilize hyperspectral microscopy and imaging spectroscopy to characterize and differentiate several important bloom-forming cyanobacteria genera obtained in the field during active research programs conducted by US Geological Survey and from commercial sources. Many of the cyanobacteria genera showed differences in their spectra that may be used to identify and predict their occurrence, including peaks and valleys in spectral reflectance. Because certain cyanobacteria, such as Cylindrospermum or Dolichospermum, are more prone to produce cyanotoxins than others, the ability to differentiate these species may help target high priority waterbodies for sampling. These spectra may also be used to prioritize restoration and research efforts to control cyanobacterial harmful algal blooms (CyanoHABs) and improve water quality for aquatic life and humans alike.

Novel opportunities to examine how life experiences connect to health and mortality through biological aging have increased due to the affordability of genomic analysis. Although epidemiological studies suggest associations between stress and accelerated biological aging, most if not all measures in the past have been global, data cross-sectional, and from primarily white samples. As part of a completed measurement study, a diverse sample (n=140, 25-65 years, Mage=47, 65% Female) provided detailed stress measures, including EMA and lifetime stress assessments, and consented to future analysis of their blood samples. We successfully used decade-old blood samples to estimate methylation-based epigenetic clocks and examined them within the context of various stress measures as a preliminary phase of a future longitudinal study. Additional whole genome sequencing will also allow for future work that incorporate continuous measures of genomic ancestry when examining lifetime discrimination-related stress, rather than simply testing for demographic group differences.

Prospective memory (PM) refers to our memory for future intentions, such as attending an appointment or taking medication. Research suggests that PM deficits can distinguish healthy older adults from those in early stages of dementia. However, limited work has examined PM and biological markers associated with pathological memory decline. The current study examined older adults’ everyday PM lapses and inflammation. Older dementia-free adults (n =237, Mage=76.86 years), enrolled in the ongoing Einstein Aging Study, completed a two-week ecological momentary assessment (EMA) as part of the first wave of data collection. Participants provided two blood samples (pre/post EMA) and self-reported daily PM lapses during nightly surveys. Inflammatory levels quantified from blood were averaged and included in regression analyses predicting total number of PM lapses (covarying for: age, education, race, health, BMI, depressive symptoms). Reporting more PM lapses was associated with higher circulating levels of interleukin [IL]-8 (p=.007); no significant associations emerged with C-reactive protein or other circulating or stimulated (ex-vivo) cytokines (IL-1β, IL-4, IL-6, IL-8, IL-10, TNF-a). Gender moderated the observed link between IL-8 and PM lapses (p=.015); specifically, higher levels of IL-8 were associated with more PM lapses among men (95%CI=[0.54, 4.72]) but not women (95%CI=[-1.56, 1.25]). Other researchers that found poor cognitive performance in association with elevated IL-8 have suggested that this relation may be indicative of neurodegeneration and future pathology. Future studies should continue to examine daily PM lapses and inflammation across genders to identify mechanisms through which these constructs may relate to neurodegeneration and dementia risk.

The presence and diversity of marine non-native species, the number of new invasions, and the impact on native communities and habitats are important metrics used to assess the health of marine ecosystems. Monitoring for marine non-native species, using traditional approaches such as rapid assessment surveys (RASs), requires taxonomic expertise and may still fail to detect rare or inconspicuous species. This study reports a validation process for a quantitative PCR (qPCR) assay based on the cytochrome oxidase 1 gene, designed to detect highly invasive tunicate Didemnum vexillum by targeting environmental DNA (eDNA) present in water samples. The D. vexillum qPCR assay showed high sensitivity, with the threshold limit of detection (LOD) and modeled LOD3 (based on triplicate qPCR reactions) estimated as 9.187 and 1.117 copies reaction–1, respectively and the limit of quantification (LOQ) was calculated as 18 copies reaction–1. Analyses of water samples collected from selected Pacific oyster farms and recreational marinas in Scotland showed 100% concordance between the historical data on presence of D. vexillum from RASs and detection of D. vexillum eDNA. Consistency of detection of D. vexillum eDNA among different sampling points within each infected sampling site varied, ranging between 100% positive throughout the site to some sampling points testing “negative” or only as “suspected” for D. vexillum. Sites with lower within-site detection consistency included sites with a low density of D. vexillum as reported by RASs or were sites undergoing D. vexillum management. The present pilot monitoring program demonstrates the potential to generate important data on presence of D. vexillum. This program will be scaled up across large geographic regions and used in the first instance to focus and target the traditional RASs to D. vexillum eDNA-positive sites in a cost-effective way, with an aim to verify the species presence by visual observation and direct Sanger sequencing of positive qPCR products.

Conceptualizing physical pain and negative affect as potentially interactive, we hypothesized that higher levels of peripheral inflammatory markers would be observed consistently only among individuals with both higher negative affect and pain symptomatology. Participants were generally healthy midlife adults from the Bronx, NY (

Objective. The transition to parenthood is a common yet stressful experience faced by many young and midlife adults, and the risk of cardiometabolic conditions also begins to rise at this time. Consequently, parenthood represents an opportune time to intervene with adults to support their psychological and physical health. Methods. We examined whether the benefits of the Family Foundations (FF) program, a perinatal preventative intervention promoting positive coparenting, extend beyond documented mental health and family relationship outcomes to better cardiometabolic risk factors among parents. We analyzed data from 183 couples who, eight years prior, were randomly assigned to the 9-session FF program or a control condition. We collected dried blood spots to measure C-reactive protein (CRP), interleukin-6 (IL-6), and cholesterol; parents also reported on their self-rated health. Results. Randomization to the FF condition was associated with lower cholesterol (B=-.081, p=.049). Among parents who demonstrated more negative communication styles at pretest (during pregnancy), the intervention was further associated with better self-rated health (B=.181, p=.018). Participation in the FF program was also marginally associated with lower CRP (B=-.261, p=.077), particularly among mothers (B=-.428, p=.076). Conclusions. These findings indicate that coparenting-focused interventions, such as FF, can lead to benefits beyond psychosocial and behavioral outcomes, and suggest that FF may improve parents’ longer-term physical health, with potentially more benefits among couples who demonstrated more negative communication styles during pregnancy.

Inspired by the success of the California-based Family Independence Initiative (FII), we designed a field experiment to estimate the impact of an inexpensive program structured around goal-setting, small monetary incentives, and support groups on the achievement of business-related objectives. In collaboration with Medellin-based Bancos de las Opportunidades, we randomly assigned small business owners to one of four experimental groups that met regularly for six months and to two control groups. Our results show that the mere act of establishing a goal plays a large and significant role in individual outcomes. Yet, it was the full FII combination of goal-setting, monetary incentive, and group support that resulted in the highest level of total business sales, pointing to the existence of complementarities between economic, social, and psychological interventions. Our study contributes to the emerging literature demonstrating that low-cost interventions focused on the internal constraints of the poor can help facilitate pathways out of poverty.

This thesis focuses on the 19th century albums Photographic Views Taken in Egypt, which hold photographs and text by James Douglas, M.D. (1800-1886) and his son James Douglas Jr. (1837-1918). The albums are held in the collections of the Archive of Modern Conflict (AMC), Toronto, Canada, the British Library, London, England, The Brooklyn Museum’s Wilbour Library of Egyptology Special Collections in Brooklyn, New York City, and Université Laval in Quebec City, Quebec, Canada. The albums are also identified as Photographic Views Taken in Nubia and Photographic Views of Egypt & Nubia and include views of both Egypt and Nubia. Since the albums were privately printed for friends and family, little research and academic discussion has taken place on them. This thesis strives to resolve this gap in academic discussion and has begun a discourse on Photographic Views Taken in Egypt.

Identification of genomic mutations by molecular testing plays an important role in diagnosis, prognosis, and treatment of myeloid neoplasms. Next-generation sequencing (NGS) is an efficient method for simultaneous detection of clinically significant genomic mutations with high sensitivity. Various NGS based in-house developed and commercial myeloid neoplasm panels have been integrated into routine clinical practice. However, some genes frequently mutated in myeloid malignancies are particularly difficult to sequence with NGS panels (e.g., CEBPA, CARL, and FLT3). We report development and validation of a 48-gene NGS panel that includes genes that are technically challenging for molecular profiling of myeloid neoplasms including acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and myeloproliferative neoplasms (MPN). Target regions were captured by hybridization with complementary biotinylated DNA baits, and NGS was performed on an Illumina NextSeq500 instrument. A bioinformatics pipeline that was developed in-house was used to detect single nucleotide variations (SNVs), insertions/deletions (indels), and FLT3 internal tandem duplications (FLT3-ITD). An analytical validation study was performed on 184 unique specimens for variants with allele frequencies ≥5%. Variants identified by the 48-gene panel were compared to those identified by a 35-gene hematologic neoplasms panel using an additional 137 unique specimens. The developed assay was applied to a large cohort (n = 2,053) of patients with suspected myeloid neoplasms. Analytical validation yielded 99.6% sensitivity (95% CI: 98.9–99.9%) and 100% specificity (95% CI: 100%). Concordance of variants detected by the 2 tested panels was 100%. Among patients with suspected myeloid neoplasms (n = 2,053), 54.5% patients harbored at least one clinically significant mutation: 77% in AML patients, 48% in MDS, and 45% in MPN. Together, these findings demonstrate that the assay can identify mutations associated with diagnosis, prognosis, and treatment options of myeloid neoplasms even in technically challenging genes.

Loch Creran on the west coast of Scotland supports the most expansive reefs of the serpulid (Serpula vermicularis) in the world. It also supports flame shell (Limaria hians) and horse mussel (Modiolus modiolus) reefs, thereby ensuring this loch received designation as a European Special Area of Conservation in 2005. In 2015, environmental DNA of the invasive, non-native colonial tunicate Didemnum vexillum, which has a worldwide distribution, was detected in Loch Creran. Didemnum vexillum was confirmed as being present at an oyster farm in the sea loch, using the cytochrome oxidase I gene (COI), following rapid intertidal and dive surveys in early September 2016. The abundance and distribution range assessment carried out at the farm indicated an early-stage D. vexillum invasion. The follow up dive surveys and wider loch intertidal surveys carried out in 2017 and 2018 confirmed that the D. vexillum presence continues to be associated exclusively with the oyster farm. This is the first time that such a highly invasive species has been found within a protected area of global significance and it has significant biosecurity and policy implications regarding how to manage such invasive species.

The use of the DNA dyes Hoechst (HO) and chromomycin A3 (CA3) has become the preferred combination for the bivariate analysis of chromosomes from both human and animals. This analysis requires a flow cytometer equipped with lasers of specific wavelength and of higher power than is typical on a conventional bench top flow cytometer. In this study, we have investigated the resolution of chromosome peaks in a human cell line with normal flow karyotype using different combinations of DNA dyes on a number of flow cytometers available in a flow cytometry core facility. Chromosomes were prepared from the human cell line using a modified polyamine isolation buffer. The bivariate flow karyotypes of different DNA dyes combination; 4′‐6‐diamidino‐2‐phenylindole (DAPI) or Hoechst with propidium iodide (PI), obtained from different flow cytometers were compared to the reference flow karyotype of DAPI or Hoechst with chromomycin A3, generated from a Mo‐Flo cell sorter using laser power settings of 300 mW each of UV and 457 nm. Good chromosome separation was observed in most of the flow cytometers used in the study. This study demonstrates that chromosome analysis and sorting can also be performed on benchtop flow cytometers equipped with the standard solid state 488 and 355 nm lasers, using a DNA dye combination of DAPI or Hoechst with PI. © 2018 The Authors. Cytometry Part A published by Wiley Periodicals, Inc. on behalf of International Society for Advancement of Cytometry.

Objective The number of adults with congenital heart disease (CHD) has increased substantially because of medical advances that are extending life expectancy beyond childhood. A historical investigation is timely not only because of this significant demographic shift, but also because stakeholder engagement is increasingly important in shaping research directions. The study questions were: From the perspective of stakeholders, what is known about the medical treatment for the adult CHD cohort in Canada and how has it changed over time? Design/methods We harnessed the use of historical research methods and conducted interviews with 21 key informants in order to articulate a contextualized understanding of the evolution of adult CHD treatment in Canada. The informants recruited were currently or previously located in and/or involved in treatment in seven provinces and two territories across Canada including patients, families, advocates, researchers, and practitioners located in disciplines that included cardiology, cardiovascular surgery, nursing, psychology, dietetics, and kinesiology. Results Alongside findings that highlighted the significant demographic shift, the findings highlight key themes related to temporal shifts in treatment, emergence of organizational structures and use of evidence, comprehensive approaches to care, and future directions. A critical finding that requires immediate attention is the significantly disproportionate resources to the number of adults living with CHD, and as a result, the real risk of premature death for this population. Conclusions The insights provided behoove the community of stakeholders to think creatively on how to draw attention to the inadequacy of resources and the unique and diverse needs of this population.

Background Most (>90%) children with congenital health defects are not active enough for optimal health. Proactively promoting physical activity during every clinic visit is recommended, but rarely implemented due to a lack of appropriate resources. Methods This cluster randomized controlled trial will implement an evidence-based, multi-faceted physical activity intervention. All eligible patients at small (London, ON), medium (Ottawa, ON) and large (Edmonton, AB) pediatric cardiac clinics will be approached, with randomization to intervention/control by clinic and week. Intervention patients will be counselled with 5 key physical activity messages, have questions about physical activity answered, and have access to a custom web site with personalized activity suggestions and support from a Registered Kinesiologist. The primary outcome is daily physical activity (number of steps, minutes of moderate-to-vigorous activity) assessed via pedometer one week per month for 6-months. Standardized questionnaires assess activity motivation and quality of life at baseline and end of study. Healthcare outcomes will be clinic visit time and contacts for physical activity concerns. Repeated measures ANCOVA will compare control/intervention pedometer outcomes, adjusting for covariates (alpha=0.05). Conclusions This trial aims to determine whether providing resources and protocols enables clinicians to counsel about physical activity as part of every pediatric cardiology appointment. Evaluations of healthcare system impact and intervention delivery in small, medium and large clinics will assess applicability for implementation in all pediatric cardiac clinics. The impact on physical activity motivation and participation will evaluate the effectiveness of this standardized approach for increasing physical activity in children with congenital heart defects.

Summary Multiple signatures of somatic mutations have been identified in cancer genomes. Exome sequences of 1,001 human cancer cell lines and 577 xenografts revealed most common mutational signatures, indicating past activity of the underlying processes, usually in appropriate cancer types. To investigate ongoing patterns of mutational-signature generation, cell lines were cultured for extended periods and subsequently DNA sequenced. Signatures of discontinued exposures, including tobacco smoke and ultraviolet light, were not generated in vitro. Signatures of normal and defective DNA repair and replication continued to be generated at roughly stable mutation rates. Signatures of APOBEC cytidine deaminase DNA-editing exhibited substantial fluctuations in mutation rate over time with episodic bursts of mutations. The initiating factors for the bursts are unclear, although retrotransposon mobilization may contribute. The examined cell lines constitute a resource of live experimental models of mutational processes, which potentially retain patterns of activity and regulation operative in primary human cancers., Graphical Abstract, Highlights • Annotation of mutational signatures across 1,001 cancer cell lines and 577 PDXs • Activities of mutational processes determined over time in cancer cell lines • APOBEC-associated mutagenesis is often ongoing and can be episodic • Detection of mutational signatures by single-cell sequencing, An analysis of 1,001 human cancer cell lines and 577 xenografts shows that mutagenesis associated with the cytodine deaminase APOBEC occurs in episodic bursts in contrast to mutation signatures associated with DNA replication and repair.

Shared resource laboratories (SRLs) offer instrumentation, training, and support to investigators and play an important role in the progress and development of science. To facilitate daily tasks and to provide an effective service, we have made use of computer scripts; a list of computer commands that are processed sequentially, to automate tasks in our flow cytometry facility. Using Python and an application programming interface (API), we automate user communication and produce a daily schedule display screen. We exploit the accessible nature of open standards to use R and Python to analyze and backup data from the BD Influx cell sorter. Finally, we show that through simple scripting, we can add value to an existing service by producing sort statistics from the Beckman Coulter XDP cell sorter. With these five examples, we demonstrate and wish to inspire other SRLs that the use of scripts helps to improve work efficiency, can solve problems, and can enhance the service provided by the SRL. © 2019 The Authors. Cytometry Part A published by Wiley Periodicals, Inc. on behalf of International Society for Advancement of Cytometry.