Genetic Regulation of SMC Gene Expression and Splicing Predict Causal CAD Genes.

BACKGROUND: Coronary artery disease (CAD) is the leading cause of death worldwide. Recent meta-analyses of genome-wide association studies have identified over 175 loci associated with CAD. The majority of these loci are in noncoding regions and are predicted to regulate gene expression. Given that vascular smooth muscle cells (SMCs) play critical roles in the development and progression of CAD, we aimed to identify the subset of the CAD loci associated with the regulation of transcription in distinct SMC phenotypes. METHODS: We measured gene expression in SMCs isolated from the ascending aortas of 151 heart transplant donors of various genetic ancestries in quiescent or proliferative conditions and calculated the association of their expression and splicing with ~6.3 million imputed single-nucleotide polymorphism markers across the genome. RESULTS: We identified 4910 expression and 4412 splicing quantitative trait loci (sQTLs) representing regions of the genome associated with transcript abundance and splicing. A total of 3660 expression quantitative trait loci (eQTLs) had not been observed in the publicly available Genotype-Tissue Expression dataset. Further, 29 and 880 eQTLs were SMC-specific and sex-biased, respectively. We made these results available for public query on a user-friendly website. To identify the effector transcript(s) regulated by CAD loci, we used 4 distinct colocalization approaches. We identified 84 eQTL and 164 sQTL that colocalized with CAD loci, highlighting the importance of genetic regulation of mRNA splicing as a molecular mechanism for CAD genetic risk. Notably, 20% and 35% of the eQTLs were unique to quiescent or proliferative SMCs, respectively. One CAD locus colocalized with a sex-specific eQTL (TERF2IP), and another locus colocalized with SMC-specific eQTL (ALKBH8). The most significantly associated CAD locus, 9p21, was an sQTL for the long noncoding RNA CDKN2B-AS1, also known as ANRIL, in proliferative SMCs. CONCLUSIONS: Collectively, our results provide evidence for the molecular mechanisms of genetic susceptibility to CAD in distinct SMC phenotypes.

FHL5 Controls Vascular Disease-Associated Gene Programs in Smooth Muscle Cells.

BACKGROUND: Genome-wide association studies have identified hundreds of loci associated with common vascular diseases, such as coronary artery disease, myocardial infarction, and hypertension. However, the lack of mechanistic insights for many GWAS loci limits their translation into the clinic. Among these loci with unknown functions is UFL1-four-and-a-half LIM (LIN-11, Isl-1, MEC-3) domain 5 (FHL5; chr6q16.1), which reached genome-wide significance in a recent coronary artery disease/ myocardial infarction GWAS meta-analysis. UFL1-FHL5 is also associated with several vascular diseases, consistent with the widespread pleiotropy observed for GWAS loci. METHODS: We apply a multimodal approach leveraging statistical fine-mapping, epigenomic profiling, and ex vivo analysis of human coronary artery tissues to implicate FHL5 as the top candidate causal gene. We unravel the molecular mechanisms of the cross-phenotype genetic associations through in vitro functional analyses and epigenomic profiling experiments in coronary artery smooth muscle cells. RESULTS: We prioritized FHL5 as the top candidate causal gene at the UFL1-FHL5 locus through expression quantitative trait locus colocalization methods. FHL5 gene expression was enriched in the smooth muscle cells and pericyte population in human artery tissues with coexpression network analyses supporting a functional role in regulating smooth muscle cell contraction. Unexpectedly, under procalcifying conditions, FHL5 overexpression promoted vascular calcification and dysregulated processes related to extracellular matrix organization and calcium handling. Lastly, by mapping FHL5 binding sites and inferring FHL5 target gene function using artery tissue gene regulatory network analyses, we highlight regulatory interactions between FHL5 and downstream coronary artery disease/myocardial infarction loci, such as FOXL1 and FN1 that have roles in vascular remodeling. CONCLUSIONS: Taken together, these studies provide mechanistic insights into the pleiotropic genetic associations of UFL1-FHL5. We show that FHL5 mediates vascular disease risk through transcriptional regulation of downstream vascular remodeling gene programs. These transacting mechanisms may explain a portion of the heritable risk for complex vascular diseases.

Author Correction: A massive core for a cluster of galaxies at a redshift of 4.3.

Change history: In this Letter, the Acknowledgements section should have included the following sentence: "The National Radio Astronomy Observatory is a facility of the National Science Foundation operated under cooperative agreement by Associated Universities, Inc.". This omission has been corrected online.

A massive core for a cluster of galaxies at a redshift of 4.3.

Massive galaxy clusters have been found that date to times as early as three billion years after the Big Bang, containing stars that formed at even earlier epochs1-3. The high-redshift progenitors of these galaxy clusters-termed 'protoclusters'-can be identified in cosmological simulations that have the highest overdensities (greater-than-average densities) of dark matter4-6. Protoclusters are expected to contain extremely massive galaxies that can be observed as luminous starbursts 7 . However, recent detections of possible protoclusters hosting such starbursts8-11 do not support the kind of rapid cluster-core formation expected from simulations 12 : the structures observed contain only a handful of starbursting galaxies spread throughout a broad region, with poor evidence for eventual collapse into a protocluster. Here we report observations of carbon monoxide and ionized carbon emission from the source SPT2349-56. We find that this source consists of at least 14 gas-rich galaxies, all lying at redshifts of 4.31. We demonstrate that each of these galaxies is forming stars between 50 and 1,000 times more quickly than our own Milky Way, and that all are located within a projected region that is only around 130 kiloparsecs in diameter. This galaxy surface density is more than ten times the average blank-field value (integrated over all redshifts), and more than 1,000 times the average field volume density. The velocity dispersion (approximately 410 kilometres per second) of these galaxies and the enormous gas and star-formation densities suggest that this system represents the core of a cluster of galaxies that was already at an advanced stage of formation when the Universe was only 1.4 billion years old. A comparison with other known protoclusters at high redshifts shows that SPT2349-56 could be building one of the most massive structures in the Universe today.

A new test method for biochemical analysis of plasmalogens in dried blood spots and erythrocytes from patients with peroxisomal disorders.

Measurement of plasmalogens is useful for the biochemical diagnosis of rhizomelic chondrodysplasia punctata (RCDP) and is also informative for Zellweger spectrum disorders (ZSD). We have developed a test method for the simultaneous quantitation of C16:0, C18:0, and C018:1 plasmalogen (PG) species and their corresponding fatty acids (FAs) in dried blood spots (DBS) and erythrocytes (RBC) by using capillary gas chromatography-mass spectrometry. Normal reference ranges for measured markers and 10 calculated ratios were established by the analysis of 720 and 473 unaffected DBS and RBC samples, respectively. Determination of preliminary disease ranges was made by using 45 samples from 43 unique patients: RCDP type 1 (DBS: 1 mild, 17 severe; RBC: 1 mild, 6 severe), RCDP type 2 (DBS: 2 mild, 1 severe; RBC: 2 severe), RCDP type 3 (DBS: 1 severe), RCDP type 4 (RBC: 2 severe), and ZSD (DBS: 3 severe; RBC: 2 mild, 7 severe). Postanalytical interpretive tools in Collaborative Laboratory Integrated Reports (CLIR) were used to generate an integrated score and a likelihood of disease. In conjunction with a review of clinical phenotype, phytanic acid, and very long-chain FA test results, the CLIR analysis allowed for differentiation between RCDP and ZSD. Data will continue to be gathered to improve CLIR analysis as more samples from affected patients with variable disease severity are analyzed. The addition of DBS analysis of PGs may allow for at-home specimen collection and second-tier testing for newborn screening programs.

Role of Dynamic Stabilizers of the Elbow in Radiocapitellar Joint Alignment: A Prospective In Vivo Study.

PURPOSE: To investigate the effect of dynamic stabilizers of the elbow on radiocapitellar joint alignment, before and after the administration of regional anesthesia. METHODS: At a single institution, 14 patients were prospectively enrolled in a study using a within-subjects control design. Before performing a supraclavicular regional block, 10 fluoroscopic images (1 anteroposterior and 9 lateral views) of the elbow were obtained for each patient. The lateral images were obtained with the forearm in maximal supination, neutral rotation, and maximal pronation, and these forearm positions were repeated for 3 elbow positions: (1) full extension; (2) flexion to 90°, with 0° of shoulder internal rotation; and (3) flexion to 90°, with 90° of shoulder internal rotation. After obtaining the 10 initial images, a block was performed to achieve less than 3/5 motor strength of the imaged extremity, followed by obtaining the same 10 images in each patient. Radiocapitellar ratio, defined as the minimal distance between the right bisector of the radial head and the center of the capitellum divided by the diameter of the capitellum, was measured in each image. RESULTS: The 14 patients had a mean age of 47.8 ± 15.7 years, and 10 (71.4%) patients were women. A difference between radiocapitellar ratios measured before and after the regional block administration was observed for all lateral images (-1.0% ± 7.2% to -2.2% ± 8.0%), although this difference was less than the minimum clinically important difference. CONCLUSIONS: Paralysis of the dynamic stabilizers of the elbow produces a difference in the radiocapitellar joint alignment, but this did not reach the minimum clinically important difference. CLINICAL RELEVANCE: Paralysis of the dynamic stabilizers of the elbow via a supraclavicular nerve block produces no clinically relevant effect on the radiocapitellar alignment of uninjured elbows.

Effective practices during emergency school lockdowns: shared experiences of four Australian schools.

This study investigates common features of a set of diverse schools' responses to the initial school lockdown period during the pandemic in 2020, with a focus on practices supporting learning, inclusion and wellbeing. It comprises a collective case study of four Australian schools that were selected based on their reputation for impactful support of students and teachers during the emergency remote teaching period. Methods included interviews and focus groups with school leaders, teachers and students. The schools had widely differing contexts, technology access and student needs. Despite these varied contexts, the findings provided important insights into common practices supporting effective remote teaching. Emerging principles of effective practice illuminate ways forward to mitigate the significant risks accompanying emergency remote teaching, and guide practices in a variety of school contexts.

Society for Vascular Surgery clinical practice guidelines of thoracic endovascular aortic repair for descending thoracic aortic aneurysms.

Thoracic aortic diseases, including disease of the descending thoracic aorta (DTA), are significant causes of death in the United States. Open repair of the DTA is a physiologically impactful operation with relatively high rates of mortality, paraplegia, and renal failure. Thoracic endovascular aortic repair (TEVAR) has revolutionized treatment of the DTA and has largely supplanted open repair because of lower morbidity and mortality. These Society for Vascular Surgery Practice Guidelines are applicable to the use of TEVAR for descending thoracic aortic aneurysm (TAA) as well as for other rarer pathologic processes of the DTA. Management of aortic dissections and traumatic injuries will be discussed in separate Society for Vascular Surgery documents. In general, there is a lack of high-quality evidence across all TAA diseases, highlighting the need for better comparative effectiveness research. Yet, large single-center experiences, administrative databases, and meta-analyses have consistently reported beneficial effects of TEVAR over open repair, especially in the setting of rupture. Many of the strongest recommendations from this guideline focus on imaging before, during, or after TEVAR and include the following: In patients considered at high risk for symptomatic TAA or acute aortic syndrome, we recommend urgent imaging, usually computed tomography angiography (CTA) because of its speed and ease of use for preoperative planning. Level of recommendation: Grade 1 (Strong), Quality of Evidence: B (Moderate). If TEVAR is being considered, we recommend fine-cut (≤0.25 mm) CTA of the entire aorta as well as of the iliac and femoral arteries. CTA of the head and neck is also needed to determine the anatomy of the vertebral arteries. Level of recommendation: Grade 1 (Strong), Quality of Evidence: A (High). We recommend routine use of three-dimensional centerline reconstruction software for accurate case planning and execution in TEVAR. Level of recommendation: Grade 1 (Strong), Quality of Evidence: B (Moderate). We recommend contrast-enhanced computed tomography scanning at 1 month and 12 months after TEVAR and then yearly for life, with consideration of more frequent imaging if an endoleak or other abnormality of concern is detected at 1 month. Level of recommendation: Grade 1 (Strong), Quality of Evidence: B (Moderate). Finally, based on our review, in patients who could undergo either technique (within the criteria of the device's instructions for use), we recommend TEVAR as the preferred approach to treat elective DTA aneurysms, given its reduced morbidity and length of stay as well as short-term mortality. Level of recommendation: Grade 1 (Strong), Quality of Evidence: A (High). Given the benefits of TEVAR, treatment using a minimally invasive approach is largely based on anatomic eligibility rather than on patient-specific factors, as is the case in open TAA repair. Thus, for isolated lesions of the DTA, TEVAR should be the primary method of repair in both the elective and emergent setting based on improved short-term and midterm mortality as well as decreased morbidity.

Responses of ichthyoplankton assemblages to the recent marine heatwave and previous climate fluctuations in several Northeast Pacific marine ecosystems.

The effects of climate warming on ecosystem dynamics are widespread throughout the world's oceans. In the Northeast Pacific, large-scale climate patterns such as the El Niño/Southern Oscillation and Pacific Decadal Oscillation, and recently unprecedented warm ocean conditions from 2014 to 2016, referred to as a marine heatwave (MHW), resulted in large-scale ecosystem changes. Larval fishes quickly respond to environmental variability and are sensitive indicators of ecosystem change. Categorizing ichthyoplankton dynamics across marine ecosystem in the Northeast Pacific can help elucidate the magnitude of assemblage shifts, and whether responses are synchronous or alternatively governed by local responses to regional oceanographic conditions. We analyzed time-series data of ichthyoplankton abundances from four ecoregions in the Northeast Pacific ranging from subarctic to subtropical: the Gulf of Alaska (1981-2017), British Columbia (2001-2017), Oregon (1998-2017), and the southern California Current (1981-2017). We assessed the impact of the recent (2014-2016) MHW and how ichthyoplankton assemblages responded to past major climate perturbations since 1981 in these ecosystems. Our results indicate that the MHW caused widespread changes in the ichthyoplankton fauna along the coast of the Northeast Pacific Ocean, but impacts differed between marine ecosystems. For example, abundances for most dominant taxa were at all-time lows since the beginning of sampling in the Gulf of Alaska and British Columbia, while in Oregon and the southern California Current species richness increased as did abundances of species associated with warmer waters. Lastly, species associated with cold waters also increased in abundances close to shore in southern California during the MHW, a pattern that was distinctly different from previous El Niño events. We also found several large-scale, synchronized ichthyoplankton assemblage composition shifts during past major climate events. Current climate projections suggest that MHWs will become more intense and thus our findings can help project future changes in larval dynamics, allowing for improved ecosystem management decisions.

Synthesis, Quantification, and Characterization of Fatty Acid Amides from In Vitro and In Vivo Sources.

Fatty acid amides are a diverse family of underappreciated, biologically occurring lipids. Herein, the methods for the chemical synthesis and subsequent characterization of specific members of the fatty acid amide family are described. The synthetically prepared fatty acid amides and those obtained commercially are used as standards for the characterization and quantification of the fatty acid amides produced by biological systems, a fatty acid amidome. The fatty acid amidomes from mouse N18TG2 cells, sheep choroid plexus cells, Drosophila melanogaster, Bombyx mori, Apis mellifera, and Tribolium castaneum are presented.

Developing a men's health program.

INTRODUCTION: Many healthcare disparities exist between men and women due to differences in lifestyles and health seeking behaviors. Such differences lead to higher mortality and lower life expectancy in men. The field of urology has the unique opportunity of acting as a gateway to men's overall health, where a urologist can diagnose medical diseases in patients and refer them to the appropriate specialist. In this review article we discuss the need for men's health programs and our experience with creating such program in Philadelphia. METHODS AND MATERIALS: In this review article we outline our experience with creating a men's health program to serve the diverse Philadelphia population. We discuss the healthcare needs and demographics of our geographical area. RESULTS: We identify factors essential for the success of our men's health program such as: developing a business model, drawing support from our institution, identifying key medical specialties to include in the program, assigning patient navigators and integration of electronic medical records. CONCLUSION: Men's health program provide tailored care for male patients that best suits their needs and healthcare seeking behaviors. The success of such programs requires commitment from physicians from many medical specialties to provide holistic care.

Zone 2 Flexor Tendon Repair Location and Risk of Catching on the A2 Pulley.

PURPOSE: To determine the region of the flexor digitorum profundus (FDP) and flexor digitorum superficialis (FDS) tendons in zone 2 that, when involved by a laceration repair, will reliably catch on the A2 pulley after surgery. METHODS: Using fresh-frozen cadavers (5 hands, 20 digits), excursions of the FDP and FDS tendons were measured in relation to the A2 pulley. The C1, A3, and C2 pulleys were resected. The digit was maximally flexed by applying traction to the flexor tendon in the forearm. An 8-0 suture tag was placed in the flexor tendons immediately distal to the A2 pulley. The digit was then passively fully extended to measure tendon excursion. Measurements were repeated with 50% venting and 100% release of the A4 pulley. Reference points such as tendon insertions and flexion creases were obtained. This protocol was repeated sequentially for the index, middle, ring, and little fingers. RESULTS: For all 20 fingers, the suture placed into the FDP just distal to the A2 pulley with the finger fully flexed traveled 1.6 ± 1.9 mm distal to the proximal edge of the A4 pulley with passive extension of the finger. The mean excursion for the FDP was 24.6 ± 3.2 mm, and 16.9 ± 3.1 mm for the FDS. The mean A2 pulley length was 16.2 ± 3.5 mm, and the mean distance between the distal edge of the A2 pulley and the proximal edge of the A4 pulley was 23.0 ± 3.3 mm. Venting the A4 pulley 50% and 100% increased FDP excursion a maximum of 0.9 and 1.9 mm, respectively. CONCLUSIONS: An FDP repair proximal to the A4 pulley will slide under the A2 pulley with full active digital flexion after surgery. If the distal FDP stump lies underneath the A4 pulley with the digit fully extended, the FDP repair will not likely engage the A2 pulley with full flexion after surgery. The FDP excursion can be reliably predicted as a percentage of the A2 (distal) to the A4 (distal) pulley distance. Most importantly, the distance between the repair site and the A4 pulley approximately equals the length of the A2 pulley that requires release to avoid postoperative triggering. CLINICAL RELEVANCE: Knowledge of this high-risk region of flexor tendon repair will guide surgeons regarding the potential need for partial release of the A2 pulley.

Resilience and return-to-work pain interventions: systematic review.

BACKGROUND: Resilience is a developing concept in relation to pain, but has not yet been reviewed in return-to-work (RTW) contexts. AIMS: To explore the role of resilience enhancement in promoting work participation for chronic pain sufferers, by reviewing the effectiveness of existing interventions. METHODS: Resilience was operationalized as: self-efficacy, active coping, positive affect, positive growth, positive reinforcement, optimism, purpose in life and acceptance. Five databases were searched for randomized controlled trials (RCTs) whose interventions included an element of resilience designed to help RTW/staying at work for chronic pain sufferers. Study appraisal comprised the Cochrane risk of bias (RoB) tool and additional quality assessment. Findings were synthesized narratively and between-group differences of outcomes were reported. Heterogeneous PICO (population, intervention, comparator, outcome) elements precluded meta-analysis. RESULTS: Thirty-four papers from 24 RCTs were included. Interventions varied; most were multidisciplinary, combining behavioural, physical and psychological pain management and vocational rehabilitation. Four found RTW/staying at work improved with intensive multidisciplinary interventions compared with less intensive, or no, treatment. Of these, one had low RoB; three scored poorly on allocation concealment and selective outcome reporting. Four trials had mixed results, e.g. interventions enabling reduced sick leave for people on short-term not long-term leave; 16 showed no improvement. Five trials reported resilience outcomes were improved by interventions but these were not always trials in which RTW improved. CONCLUSIONS: Effectiveness of resilience interventions for chronic pain sufferers on RTW is uncertain and not as helpful as anticipated. Further agreement on its conceptualization and terminology and that of RTW is needed.

APOL1, CDKN2A/CDKN2B, and HDAC9 polymorphisms and small vessel ischemic stroke.

OBJECTIVE: Worldwide, the highest frequencies of APOL1-associated kidney variants are found in indigenous West Africans among whom small vessel disease (SVD) ischemic stroke is the most common stroke phenotype. The objective of this study was to investigate the association and effect sizes of 23 selected SNPs in 14 genes of relevance, including the APOL1 G1 variants, with the occurrence of SVD ischemic stroke among indigenous West African participants in the Stroke Investigative Research and Education Network (SIREN) Study. MATERIALS AND METHODS: Cases were consecutively recruited consenting adults (aged 18 years or older) with neuroimaging-confirmed first clinical stroke. Stroke-free controls were ascertained using a locally validated version of the Questionnaire for Verifying Stroke-Free Status (QVSFS). Logistic regression models adjusting for known vascular risk factors were fitted to assess the associations of the 23 SNPs in rigorously phenotyped cases (N = 154) of SVD ischemic stroke and stroke-free (N = 483) controls. RESULTS: Apolipoprotein L1 (APOL1) rs73885319 (OR = 1.52; CI: 1.09-2.13, P-value = .013), rs2383207 in CDKN2A/CDKN2B (OR = 3.08; CI: 1.15-8.26, P -value = .026) and rs2107595 (OR = 1.70; CI: 1.12-2.60, P-value = .014) and rs28688791 (OR = 1.52; CI: 1.03-2.26, P-value = .036) in HDAC9 gene were associated with SVD stroke at 0.05 significance level. Polymorphisms in other genes did not show significant associations. CONCLUSION: This is the first report of a specific association of APOL1 with a stroke subtype. Further research is needed to confirm these initial findings and deepen understanding of the genetics of stroke in people of African ancestry with possible implications for other ancestries as all humans originated from Africa.

Salivary exRNA biomarkers to detect gingivitis and monitor disease regression.

AIM: This study tests the hypothesis that salivary extracellular RNA (exRNA) biomarkers can be developed for gingivitis detection and monitoring disease regression. MATERIALS AND METHODS: Salivary exRNA biomarker candidates were developed from a total of 100 gingivitis and non-gingivitis individuals using Affymetrix's expression microarrays. The top 10 differentially expressed exRNAs were tested in a clinical cohort to determine whether the discovered salivary exRNA markers for gingivitis were associated with clinical gingivitis and disease regression. For this purpose, unstimulated saliva was collected from 30 randomly selected gingivitis subjects, the gingival and plaque indexes scores were taken at baseline, 3 and 6 weeks and salivary exRNAs were assayed by means of reverse transcription quantitative polymerase chain reaction. RESULTS: Eight salivary exRNA biomarkers developed for gingivitis were statistically significantly changed over time, consistent with disease regression. A panel of four salivary exRNAs [SPRR1A, lnc-TET3-2:1, FAM25A, CRCT1] can detect gingivitis with a clinical performance of 0.91 area under the curve, with 71% sensitivity and 100% specificity. CONCLUSIONS: The clinical values of the developed salivary exRNA biomarkers are associated with gingivitis regression. They offer strong potential to be advanced for definitive validation and clinical laboratory development test.

The effect of implant macro-thread design on implant stability in the early post-operative period: a randomized, controlled pilot study.

INTRODUCTION: Available literature suggests there is a transient drop in implant stability from approximately week 0 to week 3-4 as a result of peri-implant bone remodeling as it transitions from a primary, mechanical stability to a secondary, biological stability. Research investigating the influence of macro-thread design on this process is scant. AIM: The specific aim of this study was to evaluate the role of macro-thread design on implant stability in the early post-operative healing period using resonance frequency analysis (RFA). MATERIAL AND METHODS: Seven patients, each missing at least two posterior teeth in the same arch, were included in the study. Three patients qualified for four implants resulting in a total of 10 matched pairs. All sites were healed (>6 months), non-grafted sites with sufficient bone to place implants. Each site in a matched pair was randomly assigned to receive either a control (Megagen EZ Plus Internal; EZ) or test (Megagen AnyRidge; AR) implant. The test implant incorporates a novel thread design with a wide thread depth and increased thread pitch. RFA was used to determine implant stability quotient (ISQ) values for each implant at the time of placement and weekly for the first 8 weeks. RESULTS: Implants consistently achieved a relatively high insertion torque (30-45 N/cm) and high initial ISQ value (79.8 ± 1.49). Baseline ISQ values for test (AR; 79.55 ± 1.61) and control (EZ; 80.05 ± 1.37) implants were similar. A general pattern of stability from baseline through all eight follow-up evaluations was observed for the test implants. A pattern of decreasing ISQ values was observed for the control implants across the early follow-up evaluations up to week four, where the value plateaued. There was a statistically significant main effect due to implant type (P < 0.01) and a statistically significant interaction between implant type and time (P < 0.01), indicating that the test and control implants performed differently at certain time points. CONCLUSIONS: Within the limitations of this study, macro-thread design appears to play a role in implant stability in the early post-operative healing period as assessed by RFA. These findings may have important implications related to immediate or early loading protocols.

The adaptation and translation of the PEACH™ RCT intervention: the process and outcomes of the PEACH™ in the community trial.

OBJECTIVE: To describe the process and report selected outcomes of translating an effective child weight management initiative (PEACH™) from a randomised controlled trial intervention to a community health programme. STUDY DESIGN AND METHODS: Pre-post study design utilising the reach, effectiveness, adoption, implementation and maintenance (RE-AIM) evaluation framework. Adaptation of PEACH™ required significant promotional activity and consideration of legal, ethical and financial issues. PEACH™ components were revised and an evaluation design based on the RE-AIM framework was developed. Facilitator training workshops were made available to South Australian health or education professionals initially, then opened up to new graduates, interstate dietitians and others interested in professional development. Facilitators completed pretraining and post-training questionnaires and a third questionnaire following programme delivery. Data were collected from families by facilitators and returned to university staff for assessment of change (baseline to programme end) in body mass index (BMI) and waist circumference (WC) z-scores. RESULTS: Changes to organisational and political environments prevented maximum programme reach and adoption. Nonetheless, data indicated that PEACH™ was effective at improving facilitators' confidence (P < 0.05) and children's (n = 37) BMI z-score (-0.17, 95% confidence interval [CI]: 0.03:0.30, P = 0.016), WC z-score (-0.14, 95% CI: -0.02:0.30, P = 0.09) and lifestyle behaviours. Collection of maintenance data was prevented due to time and financial constraints. CONCLUSIONS: Translational research needs to develop ways to effectively and efficiently bridge the gap between behavioural research and practice to improve the adoption of evidence-based approaches to child weight management. Nutrition educators and researchers can drive these nutrition-focussed translational research efforts forward. Funding bodies and health service organisations are encouraged to provide financial and structural support for such activity.

Does low-energy sweetener consumption affect energy intake and body weight? A systematic review, including meta-analyses, of the evidence from human and animal studies.

By reducing energy density, low-energy sweeteners (LES) might be expected to reduce energy intake (EI) and body weight (BW). To assess the totality of the evidence testing the null hypothesis that LES exposure (versus sugars or unsweetened alternatives) has no effect on EI or BW, we conducted a systematic review of relevant studies in animals and humans consuming LES with ad libitum access to food energy. In 62 of 90 animal studies exposure to LES did not affect or decreased BW. Of 28 reporting increased BW, 19 compared LES with glucose exposure using a specific 'learning' paradigm. Twelve prospective cohort studies in humans reported inconsistent associations between LES use and body mass index (-0.002 kg m(-)(2) per year, 95% confidence interval (CI) -0.009 to 0.005). Meta-analysis of short-term randomized controlled trials (129 comparisons) showed reduced total EI for LES versus sugar-sweetened food or beverage consumption before an ad libitum meal (-94 kcal, 95% CI -122 to -66), with no difference versus water (-2 kcal, 95% CI -30 to 26). This was consistent with EI results from sustained intervention randomized controlled trials (10 comparisons). Meta-analysis of sustained intervention randomized controlled trials (4 weeks to 40 months) showed that consumption of LES versus sugar led to relatively reduced BW (nine comparisons; -1.35 kg, 95% CI -2.28 to -0.42), and a similar relative reduction in BW versus water (three comparisons; -1.24 kg, 95% CI -2.22 to -0.26). Most animal studies did not mimic LES consumption by humans, and reverse causation may influence the results of prospective cohort studies. The preponderance of evidence from all human randomized controlled trials indicates that LES do not increase EI or BW, whether compared with caloric or non-caloric (for example, water) control conditions. Overall, the balance of evidence indicates that use of LES in place of sugar, in children and adults, leads to reduced EI and BW, and possibly also when compared with water.

Field-tunable spin-density-wave phases in Sr3Ru2O7.

The conduction electrons in a metal experience competing interactions with each other and the atomic nuclei. This competition can lead to many types of magnetic order in metals. For example, in chromium the electrons order to form a spin-density-wave (SDW) antiferromagnetic state. A magnetic field may be used to perturb or tune materials with delicately balanced electronic interactions. Here, we show that the application of a magnetic field can induce SDW magnetic order in a quasi-2D metamagnetic metal, where none exists in the absence of the field. We use magnetic neutron scattering to show that the application of a large (B ≈ 8 T) magnetic field to the perovskite metal Sr3Ru2O7 (refs 3-7) can be used to tune the material through two magnetically ordered SDW states. The ordered states exist over relatively small ranges in field (≲0.4 T), suggesting that their origin is due to a new mechanism related to the electronic fine structure near the Fermi energy, possibly combined with the stabilizing effect of magnetic fluctuations. The magnetic field direction is shown to control the SDW domain populations, which naturally explains the strong resistivity anisotropy or 'electronic nematic' behaviour observed in this material.

Multiple Metamagnetic Quantum Criticality in Sr_{3}Ru_{2}O_{7}.

Bilayer strontium ruthenate Sr_{3}Ru_{2}O_{7} displays pronounced non-Fermi liquid behavior at magnetic fields around 8 T, applied perpendicular to the ruthenate planes, which previously has been associated with an itinerant metamagnetic quantum critical end point (QCEP). We focus on the magnetic Grüneisen parameter Γ_{H}, which is the most direct probe to characterize field-induced quantum criticality. We confirm quantum critical scaling due to a putative two-dimensional QCEP near 7.845(5) T, which is masked by two ordered phases A and B, identified previously by neutron scattering. In addition, we find evidence for a QCEP at 7.53(2) T and determine the quantum critical regimes of both instabilities and the effect of their superposition.