Determination of Reaction Kinetics by Time-Resolved Small-Angle X-ray Scattering during Polymerization-Induced Self-Assembly: Direct Evidence for Monomer-Swollen Nanoparticles.

The kinetics of heterogeneous polymerization is determined directly using small-angle X-ray scattering (SAXS). This important advancement is exemplified for the synthesis of sterically-stabilized diblock copolymer nanoparticles by reversible addition-fragmentation chain transfer (RAFT) dispersion polymerization of benzyl methacrylate (BzMA) in mineral oil at 90 °C. The principle of mass balance is invoked to derive a series of equations for the analysis of the resulting time-resolved SAXS patterns. Importantly, there is a continuous change in the X-ray scattering length density for the various components within the reaction mixture. This enables the volume fraction of unreacted BzMA monomer to be calculated at any given time point, which enables the polymerization kinetics to be monitored in situ directly without relying on supplementary characterization techniques. Moreover, SAXS enables the local concentration of both monomer and solvent within the growing swollen nanoparticles to be determined during the polymerization. Data analysis reveals that the instantaneous rate of BzMA polymerization is proportional to the local monomer concentration within the nanoparticles. In principle, this powerful new time-resolved SAXS approach can be applicable to other heterogeneous polymerization formulations.

Cryptic community structure and metabolic interactions among the heritable facultative symbionts of the pea aphid.

Most insects harbour influential, yet non-essential heritable microbes in their hemocoel. Communities of these symbionts exhibit low diversity. But their frequent multi-species nature raises intriguing questions on roles for symbiont-symbiont synergies in host adaptation, and on the stability of the symbiont communities, themselves. In this study, we build on knowledge of species-defined symbiont community structure across US populations of the pea aphid, Acyrthosiphon pisum. Through extensive symbiont genotyping, we show that pea aphids' microbiomes can be more precisely defined at the symbiont strain level, with strain variability shaping five out of nine previously reported co-infection trends. Field data provide a mixture of evidence for synergistic fitness effects and symbiont hitchhiking, revealing causes and consequences of these co-infection trends. To test whether within-host metabolic interactions predict common versus rare strain-defined communities, we leveraged the high relatedness of our dominant, community-defined symbiont strains vs. 12 pea aphid-derived Gammaproteobacteria with sequenced genomes. Genomic inference, using metabolic complementarity indices, revealed high potential for cooperation among one pair of symbionts-Serratia symbiotica and Rickettsiella viridis. Applying the expansion network algorithm, through additional use of pea aphid and obligate Buchnera symbiont genomes, Serratia and Rickettsiella emerged as the only symbiont community requiring both parties to expand holobiont metabolism. Through their joint expansion of the biotin biosynthesis pathway, these symbionts may span missing gaps, creating a multi-party mutualism within their nutrient-limited, phloem-feeding hosts. Recent, complementary gene inactivation, within the biotin pathways of Serratia and Rickettsiella, raises further questions on the origins of mutualisms and host-symbiont interdependencies.

Reframing physically active learning as movement-centred pedagogy: a European priority action framework.

BACKGROUND: Physically active learning (PAL) has emerged as a promising way of eliciting health and education-based outcomes for pupils. Concurrently, research suggests large variability in how PAL is perceived, operationalized, and prioritized in practice across Europe. Therefore, this study aimed to co-develop a framework for action to support the adoption and implementation of PAL. METHODS: Adopting a design thinking approach, 40 international stakeholders representing 13 countries engaged in an idea generation workshop during a two-day PAL international conference. Participants included professionals from research (n = 20), practice (n = 4) and policy (n = 1) or a combination (n = 15). Their experience with PAL ranged from none to 19 years (with an average of 3.9 years). Participants were allocated into one of six heterogeneous and multidisciplinary groups and led through interactive tasks to identify: the landscape for PAL across Europe, barriers to the adoption and implementation of PAL, and key objectives for research, policy and practice to improve the adoption and implementation of PAL. All discussions were audio recorded and prioritized objectives were transcribed verbatim and analysed using inductive qualitative content analysis. RESULTS: Five interlinked and mutually reinforcing themes were identified: (1) Integration of the health and education paradigms (2) Coherent national policy and decision making (3) Building confident and competent teachers (4) Adopting a whole school approach for PAL (5) Strengthening the evidence base for PAL. CONCLUSIONS: The priority action framework identifies five key areas for action to facilitate PAL adoption and implementation across Europe. Central to the success of border uptake of PAL is the integration of the health and education paradigms. To achieve this aim, reframing PAL as movement-centered pedagogy would provide a more holistic and inclusive perspective.

Long-term ecological responses of a lowland dipterocarp forest to climate changes and nutrient availability.

Understanding the long-term impact of projected climate change on tropical rainforests is critical given their central role in the Earth's system. Palaeoecological records can provide a valuable perspective on this problem. Here, we examine the effects of past climatic changes on the dominant forest type of Southeast Asia - lowland dipterocarp forest. We use a range of proxies extracted from a 1400-yr-old lacustrine sedimentary sequence from north-eastern Philippines to determine long-term vegetation responses of lowland dipterocarp forest, including its dominant tree group dipterocarps, to changes in precipitation, fire and nutrient availability over time. Our results show a positive relationship between dipterocarp pollen accumulation rates (PARs) and leaf wax hydrogen isotope values, which suggests a negative effect of drier conditions on dipterocarp abundance. Furthermore, we find a positive relationship between dipterocarp PARs and the proxy for phosphorus availability, which suggests phosphorus controls the productivity of these keystone trees on longer time scales. Other pollen taxa show widely varying relationships with the abiotic factors, demonstrating a high diversity of plant functional responses. Our findings provide novel insights into lowland dipterocarp forest responses to changing climatic conditions in the past and highlight potential impacts of future climate change on this globally important ecosystem.

The treatment of mild upper respiratory tract infections - a position paper with recommendations for best practice.

Following the waning severity of COVID-19 due to vaccination and the development of immunity, the current variants of SARS-CoV-2 often lead to mild upper respiratory tract infections (MURTIs), suggesting it is an appropriate time to review the pathogenesis and treatment of such illnesses. The present article reviews the diverse causes of MURTIs and the mechanisms leading to symptomatic illness. Different symptoms of MURTIs develop in a staggered manner and require targeted symptomatic treatment. A wide variety of remedies for home treatment is available, including over-the-counter drugs and plant-derived substances. Recent pharmacological research has increased the understanding of molecular effects, and clinical studies have shown the efficacy of certain herbal remedies. However, the use of subjective endpoints in these clinical studies may suggest limited validity of the results. In this position paper, the importance of patient-centric outcomes, including a subjective perception of improved well-being, is emphasized. A best practice approach for the management of MURTIs, in which pharmacists and physicians create an improved multi-professional healthcare setting and provide healthcare education to patients, is proposed. Pharmacists act as first-line consultants and provide patients with remedies, considering the individual patient's preferences towards chemical or plant-derived drugs and providing advice for self-monitoring. Physicians act as second-line consultants if symptoms worsen and subsequently initiate appropriate therapies. In conclusion, general awareness of MURTIs should be increased amongst medical professionals and patients, thus improving their management.

Assessing the Impacts of Creating Active Schools on Organisational Culture for Physical Activity.

BACKGROUND: National and international guidance recommends whole-school approaches to physical activity, but there are few studies assessing their effectiveness, especially at an organisational level. This study assesses the impact of the Creating Active School's (CAS) programme on organisational changes to physical activity provision. METHODS: In-school CAS leads completed a 77-item questionnaire assessing school-level organisational change. The questionnaire comprised 19 domains aligned with the CAS framework and COM-B model of behaviour change. Wilcoxon Signed Rank Tests assessed the pre-to-nine-month change. RESULTS: >70% of schools (n = 53) pre-CAS had inadequate whole-school physical activity provision. After nine months (n = 32), CAS had a significant positive effect on organisational physical activity. The positive change was observed for: whole-school culture and ethos, teachers and wider school staff, academic lessons, physical education (PE) lessons, commute to/from school and stakeholder behaviour. CONCLUSIONS: This study provides preliminary evidence that CAS is a viable model to facilitate system-level change for physical activity in schools located within deprived areas of a multi-ethnic city. To confirm the results, future studies are required which adopt controlled designs combined with a holistic understanding of implementation determinants and underlying mechanisms.

A crossover pilot trial of the feasibility, acceptability, and effectiveness of LoveYourBrain Yoga for community-dwelling adults with multiple sclerosis.

BACKGROUND AND PURPOSE: Among people with multiple sclerosis (MS), yoga has potential to improve fatigue and other symptoms that undermine quality of life. The aim of this study was to assess the feasibility, acceptability, and effectiveness of LoveYourBrain Yoga, a six-week yoga with psychoeducation program, on fatigue and other health-related outcomes among people with MS in a rural, community-based setting in the United States. METHODS: This non-randomized 2x2 crossover pilot trial compared LoveYourBrain Yoga to a control among 15 people with MS. People were eligible if they were adults with MS (EDSS score ≤6), English-speaking, and ambulatory. Paired t-tests and Wilcoxon signed rank sum analyses assessed mean differences in PROMIS-FatigueMS, Multiple Sclerosis Impact Scale, Symbol Digit Modalities Test, NIH Neuro-QoL measures, and Liverpool Self-Efficacy scale. We assessed feasibility using recruitment and retention rates, mean attendance, fidelity, and acceptability using satisfaction measures. RESULTS: Significant improvements in fatigue (MD -4.34, SD 5.26, p = 0.012), positive affect and wellbeing (MD 2.76, SD 3.99, p = 0.028), and anxiety (MD -4.42, SD 5.36, p = 0.012) were found after LoveYourBrain Yoga compared to the control. Participants reported high satisfaction (M 9.5, SD 1.4) and a majority (92.3%) reported 'Definitely, yes' to recommending it to a friend or family. CONCLUSION: LoveYourBrain Yoga is feasible and acceptable when implemented in a rural, community-based setting for people with MS. It may improve a range of MS symptoms and offer a means for acquiring new skills for stress reduction, anxiety management, and overall wellbeing.

Impact of administration route on nanocarrier biodistribution in a murine colitis model.

The incidence of inflammatory bowel disease (IBD) is increasing worldwide. Although current diagnostic and disease monitoring tests for IBD sensitively detect gut inflammation, they lack the molecular and cellular specificity of positron emission tomography (PET). In this proof-of-concept study, we use a radiolabeled macrophage-targeted nanocarrier probe (64Cu-NOTA-D500) administered by oral, enema, and intraperitoneal routes to evaluate the delivery route dependence of biodistribution across healthy and diseased tissues in a murine model of dextran sodium sulfate (DSS)-induced colitis. High inter-subject variability of probe uptake in intestinal tissue was reduced by normalization to uptake in liver or total intestines. Differences in normalized uptake between healthy and DSS colitis animal intestines were highest for oral and IP routes. Differences in absolute liver uptake reflected a possible secondary diagnostic metric of IBD pathology. These results should inform the preclinical development of inflammation-targeted contrast agents for IBD and related gut disorders to improve diagnostic accuracy.

Liver Disease: Evaluation of Patients With Abnormal Liver Test Results.

The prevalence of abnormal liver test results in the general population is estimated to be between 10% and 20%. The terms liver tests or liver chemistries are recommended to describe more accurately the tests used to assess liver health, instead of the term liver function tests. Defining normal ranges for liver transaminase levels can be challenging. Levels are affected by factors such as body mass index and sex. Elevated transaminase levels are associated with increased risks of liver-related and all-cause mortality. Patient with signs or symptoms of liver disease or abnormal liver test results should be evaluated to determine the etiology. For patients with abnormal liver test results, the initial evaluation should include a review of previous laboratory test results, medical and family histories, substance use, and drugs, including over-the-counter drugs and herbal supplements. Physical examination results often are normal but findings may be consistent with acute disease. Tests should include a complete blood cell count; alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin, and albumin levels; prothrombin time; hepatitis B surface antigen; hepatitis B core antibody; hepatitis C antibody; ferritin and iron levels and transferrin saturation; and right upper quadrant abdominal ultrasonography. Additional tests and imaging should be based on patient-specific risk factors and the pattern of abnormal liver test results.

Liver Disease: Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) describes a spectrum of fatty infiltration, inflammation, and fibrosis of the liver caused by metabolic factors. It is projected to become the leading cause of cirrhosis and need for liver transplantation in the United States. Guidelines from the American Association for the Study of Liver Diseases (AASLD) do not recommend routine screening of patients at high risk of NAFLD. European guidelines recommend testing for certain high-risk patients. Hepatic steatosis and nonalcoholic steatohepatitis (NASH) are difficult to diagnose and often go unrecognized until patients have advanced fibrosis or cirrhosis. Noninvasive methods are used to assess fibrosis, such as fibrosis scores and vibration-controlled transient elastography. Liver biopsy remains the reference standard for NASH diagnosis and fibrosis staging. The mainstays of treatment for NAFLD, NASH, and fibrosis are weight loss and a healthy diet. Currently, no drugs have been approved by the Food and Drug Administration (FDA) for management of these conditions. Drugs for diabetes management (eg, glucagon-like peptide 1 receptor agonists, pioglitazone) can be useful in patients with diabetes and NASH. Among patients with NAFLD, cardiovascular disease is a common cause of mortality. Thus, the AASLD guidelines recommend consideration of omega-3 fatty acids for hypertriglyceridemia management in patients with NAFLD, and statins for hyperlipidemia management in most patients with NAFLD and NASH.

A fine-scale multi-step approach to understand fish recruitment variability.

Recruitment is one of the dominant processes regulating fish population productivity. It is, however, notoriously difficult to predict, as it is the result of a complex multi-step process. Various fine-scale drivers might act on the pathway from adult population characteristics to spawning behaviour and egg production, and then to recruitment. Here, we provide a holistic analysis of the Northwest Atlantic mackerel recruitment process from 1982 to 2017 and exemplify why broad-scale recruitment-environment relationships could become unstable over time. Various demographic and environmental drivers had a synergetic effect on recruitment, but larval survival through a spatio-temporal match with prey was shown to be the key process. Recruitment was also mediated by maternal effects and a parent-offspring fitness trade-off due to the different feeding regimes of adults and larvae. A mismatch curtails the effects of high larval prey densities, so that despite the abundance of food in recent years, recruitment was relatively low and the pre-existing relationship with overall prey abundance broke down. Our results reaffirm major recruitment hypotheses and demonstrate the importance of fine-scale processes along the recruitment pathway, helping to improve recruitment predictions and potentially fisheries management.

Association of Miglustat With Swallowing Outcomes in Niemann-Pick Disease, Type C1.

Importance: Niemann-Pick disease, type C1 (NPC1) is a progressive neurovisceral disease with no US Food and Drug Administration-approved therapy. Miglustat, a drug used off-label in the United States for the treatment of NPC1, appears to stabilize neurologic disease progression. Several prospective trials suggest that miglustat stabilizes oropharyngeal swallowing function; however, its effect on dysphagia and aspiration risk has not been demonstrated instrumentally. Objective: To determine if miglustat therapy is associated with stabilized swallowing dysfunction in individuals with NPC1. Design, Setting, and Participants: Patients with confirmed NPC1 diagnoses were evaluated in a single-center cohort study of NPC1 from April 1997 to November 2019. Longitudinal data from individuals with neurologic disease onset prior to age 15 years were analyzed. The study population was divided into those with neurologic disease onset in early childhood (age <6 years) and late childhood (age ≥6 years and <15 years). Analysis began September 2019. Exposures: Oral miglustat at baseline and at follow-up. Main Outcomes and Measures: Oropharyngeal swallowing function was assessed with videofluoroscopic swallowing studies. Overall swallowing ability and aspiration risk were evaluated using the American Speech-Language-Hearing Association National Outcome Measurement System swallowing domain and an adapted Rosenbek aspiration-penetration scale, respectively. Results: Overall, 50 participants were evaluated at baseline (median [interquartile range] age, 9.4 [3.4-16.4] years; 26 [52%] female). The median (interquartile range) duration of follow-up was 3.0 (1.1-4.4) years. Miglustat use was associated with decreased odds of worse American Speech-Language-Hearing Association National Outcome Measurement System swallowing domain outcomes in all 3 subsets (overall: odds ratio [OR], 0.09 [95% CI, 0.02-0.36); P < .001; early childhood: OR, 0.17 [95% CI, 0.04-0.67]; P = .01; late childhood: OR, 0.05 [95% CI, 0.01-0.29]; P = .001). Miglustat use was associated with decreased odds of worse Rosenbek aspiration-penetration scale outcomes in the overall cohort (OR, 0.28 [95% CI, 0.08-0.95]; P = .04) but not in each subgroup (early childhood: OR, 0.27 [95% CI, 0.06-1.22]; P = .09; late childhood: OR, 0.38 [95% CI, 0.06-2.33]; P = .29). Conclusions and Relevance: These data suggest that miglustat use is associated with stabilized swallowing function and reduced aspiration risk in NPC1, thus supporting its use in this population. In addition, these data demonstrate that a quantification of swallowing dysfunction can be used as a clinically relevant, functional outcome measure in future therapeutic trials in NPC1.

Unraveling biogeochemical phosphorus dynamics in hyperarid Mars-analogue soils using stable oxygen isotopes in phosphate.

With annual precipitation less than 20 mm and extreme UV intensity, the Atacama Desert in northern Chile has long been utilized as an analogue for recent Mars. In these hyperarid environments, water and biomass are extremely limited, and thus, it becomes difficult to generate a full picture of biogeochemical phosphate-water dynamics. To address this problem, we sampled soils from five Atacama study sites and conducted three main analyses-stable oxygen isotopes in phosphate, enzyme pathway predictions, and cell culture experiments. We found that high sedimentation rates decrease the relative size of the organic phosphorus pool, which appears to hinder extremophiles. Phosphoenzyme and pathway prediction analyses imply that inorganic pyrophosphatase is the most likely catalytic agent to cycle P in these environments, and this process will rapidly overtake other P utilization strategies. In these soils, the biogenic δ18 O signatures of the soil phosphate (δ18 OPO4 ) can slowly overprint lithogenic δ18 OPO4 values over a timescale of tens to hundreds of millions of years when annual precipitation is more than 10 mm. The δ18 OPO4 of calcium-bound phosphate minerals seems to preserve the δ18 O signature of the water used for biogeochemical P cycling, pointing toward sporadic rainfall and gypsum hydration water as key moisture sources. Where precipitation is less than 2 mm, biological cycling is restricted and bedrock δ18 OPO4 values are preserved. This study demonstrates the utility of δ18 OPO4 values as indicative of biogeochemical cycling and hydrodynamics in an extremely dry Mars-analogue environment.

Organizational diagnostics: a systematic approach to identifying technology and workflow issues in clinical settings.

OBJECTIVES: Healthcare organizations need to rapidly adapt to new technology, policy changes, evolving payment strategies, and other environmental changes. We report on the development and application of a structured methodology to support technology and process improvement in healthcare organizations, Systematic Iterative Organizational Diagnostics (SIOD). SIOD was designed to evaluate clinical work practices, diagnose technology and workflow issues, and recommend potential solutions. MATERIALS AND METHODS: SIOD consists of five stages: (1) Background Scan, (2) Engagement Building, (3) Data Acquisition, (4) Data Analysis, and (5) Reporting and Debriefing. Our team applied the SIOD approach in two ambulatory clinics and an integrated ambulatory care center and used SIOD components during an evaluation of a large-scale health information technology transition. RESULTS: During the initial SIOD application in two ambulatory clinics, five major analysis themes were identified, grounded in the data: putting patients first, reducing the chaos, matching space to function, technology making work harder, and staffing is more than numbers. Additional themes were identified based on SIOD application to a multidisciplinary clinical center. The team also developed contextually grounded recommendations to address issues identified through applying SIOD. DISCUSSION: The SIOD methodology fills a problem identification gap in existing process improvement systems through an emphasis on issue discovery, holistic clinic functionality, and inclusion of diverse perspectives. SIOD can diagnose issues where approaches as Lean, Six Sigma, and other organizational interventions can be applied. CONCLUSION: The complex structure of work and technology in healthcare requires specialized diagnostic strategies to identify and resolve issues, and SIOD fills this need.

Focus group discussions on low-flow oxygen and bubble CPAP treatments among mothers of young children in Malawi: a CPAP IMPACT substudy.

OBJECTIVE: To determine the acceptability of bubble continuous positive airway pressure (bCPAP) and low-flow oxygen among mothers of children who had received either therapy. SETTING: A district hospital in Salima, Malawi. PARTICIPANTS: We conducted eight focus group discussions (FGDs) with a total of 54 participants. Eligible participants were mothers of children 1 to 59 months of age with severe pneumonia and a comorbidity (HIV-infection, HIV-exposure, malnutrition or hypoxaemia) who, with informed consent, had been enrolled in a randomised clinical trial, CPAP IMPACT (Improving Mortality for Pneumonia in African Children Trial), comparing low-flow oxygen and bCPAP treatments (ClinicalTrials.gov, NCT02484183). PRIMARY AND SECONDARY OUTCOME MEASURES: FGDs assessed mothers' attitudes and feelings towards oxygen and bCPAP before and after therapy along with general community perceptions of respiratory therapies. Data was analysed using inductive thematic analysis to assess themes and subthemes of the transcripts. RESULTS: Community perceptions of oxygen and bCPAP were widely negative. Mothers recounted that they are told that 'oxygen kills babies'. They are often fearful of allowing their child to receive oxygen therapy and will delay treatment or seek alternative therapies. Mothers report limiting oxygen and bCPAP by intermittently removing the nasal cannulas or mask. After oxygen or bCPAP treatment, regardless of patient outcome, mothers were supportive of the treatment their child received and would recommend it to other mothers. CONCLUSION: There are significant community misconceptions around oxygen and bCPAP causing mothers to be fearful of either treatment. In order for low-flow oxygen treatment and bCPAP implementation to be effective, widespread community education is necessary.

A rapid ammonium fluoride method to determine the oxygen isotope ratio of available phosphorus in tropical soils.

RATIONALE: The isotopic composition of oxygen bound to phosphorus (δ18 OP value) offers an opportunity to gain insight into P cycling mechanisms. However, there is little information for tropical forest soils, which presents a challenge for δ18 OP measurements due to low available P concentrations. Here we report the use of a rapid ammonium fluoride extraction method (Bray-1) as an alternative to the widely used anion-exchange membrane (AEM) method for quantification of δ18 OP values of available P in tropical forest soils. METHODS: We compared P concentrations and δ18 OP values of available and microbial P determined by AEM and Bray-1 extraction for a series of tropical forest soils from Panama spanning a steep P gradient. This involved an assessment of the influence of extraction conditions, including temperature, extraction time, fumigation time and solution-to-soil ratio, on P concentrations and isotope ratios. RESULTS: Depending on the extraction conditions, Bray-1 P concentrations ranged from 0.2 to 66.3 mg P kg-1 across the soils. Extraction time and temperature had only minor effects on Bray-1 P, but concentrations increased markedly as the solution-to-soil ratio increased. In contrast, extraction conditions did not affect Bray-1 δ18 OP values, indicating that Bray-1 provides a robust measure of the isotopic composition of available soil P. For a relatively high P soil, available and fumigation-released (microbial) δ18 OP values determined by Bray-1 extraction (20‰ and 16‰, respectively) were higher than those determined by the AEM method (18‰ and 12‰, respectively), which we attribute to slightly different P pools extracted by the two methods and/or differences resulting from the longer extraction time needed for the AEM method. CONCLUSIONS: The short extraction time, insensitivity to extraction conditions and smaller mass of soil required to extract sufficient P for isotopic analysis make Bray-1extraction a suitable alternative to the AEM method for the determination of δ18 OP values of available P in tropical soils.

Increased Incidence of Central Venous Catheter-Related Infection in Patients Undergoing Cytoreductive Surgery and Hyperthermic Intra-Peritoneal Chemotherapy.

Background: Cytoreductive surgery (CRS) and hyperthermic intra-peritoneal chemotherapy (HIPEC) is a complex surgical intervention with associated risks. Central venous catheter (CVC) line sepsis is one of a number of potential morbidities. The aim of this study was to calculate the incidence of catheter-related infection (CRI) in a CRS and HIPEC patient population and to assess its influence on length of hospital stay. Methods: Data were collected on consecutive patients who underwent CRS HIPEC between August 2013 and October 2017. Data included patient demographics, timing of CVC insertion/removal, time spent in critical care, and CVC tip/blood culture results. Charts were reviewed for patients with both positive CVC culture and positive blood cultures to assess for evidence of catheter related infection and systemic inflammatory response syndrome (SIRS). Results: Data on 100 consecutive CRS HIPEC operations performed between August 2013 and October 2017 was analyzed. There were 11 CRIs in 100 CVCs, resulting in a CRI rate of 16.2 per 1,000 CVC days. Patients within the CRI group had a longer high-dependency unit (HDU) stay compared with the non-septic group (6 days vs. 4.07 days, p < 0.05). The CVC duration for the CRI and non-CRI group was 8.4 and 7.6 days, respectively (p = 0.12). The CRI group also had an increased total hospital length of stay (LOS; 20.8 days vs. 15.4 days, p < 0.05). On average, CRIs occurred eight days post-operative and four days post-HDU discharge. There was no association identified with longer CVC duration (p = 0.34). There has been an annual decline in CRI rates in CRS and HIPEC patients over the duration of the study period from 19.1 per 1,000 CVC days in 2016 to 8.2 per 1,000 CVC days in 2017. Conclusion: This is the first study to report on CRI rates in patients undergoing CRS and HIPEC. The CRI rate of 16.2 per 1,000 CVC days is higher than the overall national figure of 5.2 per 1,000 for CVC lines inserted in the operating room. Patients who developed line sepsis had longer HDU and longer overall hospital stay. Catheter-related infection was noted post-HDU discharge in all cases. Implementation of a CVC care bundle in the later years of the study period coincided with a reduction in CRI rates.

Mechanistic insights from targeted molecular profiling of repolarization alternans in the intact human heart.

AIMS: Action potential duration (APD) alternans is an established precursor or arrhythmia and sudden cardiac death. Important differences in fundamental electrophysiological properties relevant to arrhythmia exist between experimental models and the diseased in vivo human heart. To investigate mechanisms of APD alternans using a novel approach combining intact heart and cellular cardiac electrophysiology in human in vivo. METHODS AND RESULTS: We developed a novel approach combining intact heart electrophysiological mapping during cardiac surgery with rapid on-site data analysis to guide myocardial biopsies for laboratory analysis, thereby linking repolarization dynamics observed at the organ level with underlying ion channel expression. Alternans-susceptible and alternans-resistant regions were identified by an incremental pacing protocol. Biopsies from these sites (n = 13) demonstrated greater RNA expression in Calsequestrin (CSQN) and Ryanodine (RyR) and ion channels underlying IK1 and Ito at alternans-susceptible sites. Electrical restitution properties (n = 7) showed no difference between alternans-susceptible and resistant sites, whereas spatial gradients of repolarization were greater in alternans-susceptible than in alternans-resistant sites (P = 0.001). The degree of histological fibrosis between alternans-susceptible and resistant sites was equivalent. Mathematical modelling of these changes indicated that both CSQN and RyR up-regulation are key determinants of APD alternans. CONCLUSION: Combined intact heart and cellular electrophysiology show that regions of myocardium in the in vivo human heart exhibiting APD alternans are associated with greater expression of CSQN and RyR and show no difference in restitution properties compared to non-alternans regions. In silico modelling identifies up-regulation and interaction of CSQN with RyR as a major mechanism underlying APD alternans.

The effect of manual therapy on gastrocnemius muscle stiffness in healthy individuals.

STUDY DESIGN: Randomized clinical trial. BACKGROUND: Muscle stiffness is a potential complication after injury and has been shown to be a risk factor for injury in healthy individuals. OBJECTIVES: The primary purpose of this study was to assess the short-term effects of manual therapy (MT) on muscle stiffness of the gastrocnemius in both a relaxed and contracted state. The secondary purpose was to assess the reliability of a novel clinical tool (MyotonPRO) to measure muscle stiffness in the gastrocnemius in both a passive and contracted state. METHODS: Eighty-four consecutive healthy individuals were randomized to receive Manual Therapy (MT group) directed at the right-side ankle and foot or no treatment (CONTROL group). Muscle stiffness of the gastrocnemius was assessed bilaterally in all participants at baseline and then immediately after intervention in a relaxed and contracted state. Group (MT vs. CONTROL) by side (ipsilateral vs. contralateral) by time (pre vs. post) effects were compared through a 3-way interaction utilizing mixed model ANOVA. Reliability of the MyotonPRO was assessed with two-way mixed model intraclass correlation coefficients. RESULTS: There was a significant 3-way interaction for muscle stiffness of the gastrocnemius in a relaxed state (p<0.01), but not contracted state (p=0.54). All conditions had increased resting muscle stiffness from pre to post measures except for the ipsilateral limb of the MT group. There was not a significant interaction for muscle stiffness in a contracted state. Reliability estimates (ICC) for muscle stiffness measures ranged between 0.898 and 0.986. CONCLUSION: The change in muscle stiffness of the gastrocnemius in a relaxed state depended upon whether individuals received MT. Muscle stiffness measures were highly reliable based on single measurements. LEVEL OF EVIDENCE: Therapy, level 2.

Maternal dietary patterns during pregnancy and intelligence quotients in the offspring at 8 years of age: Findings from the ALSPAC cohort.

Dietary intake during pregnancy may influence child neurodevelopment and cognitive function. This study aims to investigate the associations between dietary patterns obtained in pregnancy and intelligence quotients (IQ) among offspring at 8 years of age. Pregnant women enrolled in the Avon Longitudinal Study of Parents and Children completed a food frequency questionnaire at 32 weeks' gestation (n = 12,195). Dietary patterns were obtained by cluster analysis. Three clusters best described women's diets during pregnancy: "fruit and vegetables," "meat and potatoes," and "white bread and coffee." The offspring's IQ at 8 years of age was assessed using the Wechsler Intelligence Scale for Children. Models, using variables correlated to IQ data, were performed to impute missing values. Linear regression models were employed to investigate associations between the maternal clusters and IQ in childhood. Children of women who were classified in the meat and potatoes cluster and white bread and coffee cluster during pregnancy had lower average verbal (ß = -1.74; p < .001 and ß = -3.05; p < .001), performance (ß = -1.26; p = .011 and ß = -1.75; p < .001), and full-scale IQ (ß = -1.74; p < .001 and ß = -2.79; p < .001) at 8 years of age when compared to children of mothers in the fruit and vegetables cluster in imputed models of IQ and all confounders, after adjustment for a wide range of known confounders including maternal education. The pregnant women who were classified in the fruit and vegetables cluster had offspring with higher average IQ compared with offspring of mothers in the meat and potatoes cluster and white bread and coffee cluster.