Household chaos and childhood obesity-related health outcomes.

OBJECTIVE: Household chaos, defined as a lack of organization, structure, and predictability, has been linked to deleterious childhood health outcomes and may hinder attempts to initiate and maintain healthy lifestyle changes. This study examined the associations of household chaos and obesity-related health conditions in a sample of youth being treated for obesity. METHODS: Participants were 715 patients (61.8% girls; Mage = 12.3 years; 68.7% non-Hispanic Black; M% of 95th BMI %-ile = 146.9%) enrolled in a pediatric weight management clinic. Caregiver report of household chaos was measured using the Confusion, Hubbub and Order Scale (CHAOS). Physiological obesity-related comorbidities (e.g., insulin resistance, hypertension, dyslipidemia) were assessed by a medical clinician and abstracted from electronic medical records; health conditions were dichotomized as present or not present. Psychological functioning was measured with the Pediatric Symptom Checklist, a caregiver-completed mental health screen that assesses internalizing, externalizing, and attention concerns. RESULTS: The Wilcoxon rank-sum test was used to test differences in household chaos scores for each obesity-related health condition. Caregivers of youth diagnosed with hypertension and obstructive sleep apnea reported significantly lower levels of household chaos, while caregivers who reported clinical levels of psychological dysfunction reported higher levels of chaos. CONCLUSIONS: Traditional management of childhood obesity requires changes across multiple health domains (e.g., dietary, exercise, sleep), and such change may be facilitated by structure and consistency. Present findings suggest that psychological resources within pediatric weight management settings should address individual patient-level factors associated with physiological and mental health as well as household functioning.

Constructing validity evidence from a pilot key-features assessment of clinical decision-making in cerebral palsy diagnosis: application of Kane's validity framework to implementation evaluations.

BACKGROUND: Physician decision-making skills training is a priority to improve adoption of the cerebral palsy (CP) clinical guideline and, through this, lower the age of CP diagnosis. Clinical guideline implementation aims to improve physician practice, but evaluating meaningful change is complex. Limitations in the validity evidence of evaluation instruments impact the evidence base. Validity frameworks, such as Kane's, enable a targeted process to gather evidence for instrument scores, congruent to context and purpose. Yet, application of argument-based methodology to implementation validation is rare. Key-features examination methodology has established validity evidence supporting its use to measure decision-making skills, with potential to predict performance. We aimed to apply Kane's framework to evaluate a pilot key-features examination on physician decision-making in early CP diagnosis. METHODS: Following Kane's framework, we evaluated evidence across inferences of scoring, generalisation, extrapolation and implications in a study design describing the development and pilot of a CP diagnosis key-features examination for practising physicians. If found to be valid, we proposed to use the key-feature scores as an outcome measure of decision-making post education intervention to expedite CP diagnosis and to correlate with real-world performance data to predict physician practice. RESULTS: Supporting evidence for acceptance of scoring inferences was achieved through examination development with an expert group (n = 10) and pilot results (n = 10): (1) high internal consistency (0.82); (2) acceptable mean item-discrimination (0.34); and (3) acceptable reliability of examination scorers (95.2% congruence). Decreased physician acceptance of examination time (70%) was identified as a threat and prioritised in case reduction processes. Partial acceptance of generalisation, extrapolation and implications inferences were defensible with: (1) accumulated development evidence following established key-features methodology; (2) high pilot acceptance for authenticity (90%); and (3) plausibility of assumptions of score correlation with population register data. CONCLUSIONS: Kane's approach is beneficial for prioritising sources of validity evidence alongside the iterative development of a key-features examination in the CP field. The validity argument supports scoring assumptions and use of scores as an outcome measure of physician decision-making for CP guideline education implementation interventions. Scoring evidence provides the foundation to direct future studies exploring association of key-feature scores with real-world performance.

Value of treatment by comprehensive stroke services for the reduction of critical gaps in acute stroke care in Europe.

Stroke is the second leading cause of death and dependency in Europe and costs the European Union more than €30bn, yet significant gaps in the patient pathway remain and the cost-effectiveness of comprehensive stroke care to meet these needs is unknown. The European Brain Council Value of Treatment Initiative combined patient representatives, stroke experts, neurological societies and literature review to identify unmet needs in the patient pathway according to Rotterdam methodology. The cost-effectiveness of comprehensive stroke services was determined by a Markov model, using UK cost data as an exemplar and efficacy data for prevention of death and dependency from published systematic reviews and trials, expressing effectiveness as quality-adjusted life-years (QALYs). Model outcomes included total costs, total QALYs, incremental costs, incremental QALYs and the incremental cost-effectiveness ratio (ICER). Key unmet needs in the stroke patient pathway included inadequate treatment of atrial fibrillation (AF), access to neurorehabilitation and implementation of comprehensive stroke services. In the Markov model, full implementation of comprehensive stroke services was associated with a 9.8% absolute reduction in risk of death of dependency, at an intervention cost of £9566 versus £6640 for standard care, and long-term care costs of £35 169 per 5.1251 QALYS vs. £32 347.40 per 4.5853 QALYs, resulting in an ICER of £5227.89. Results were robust in one-way and probabilistic sensitivity analyses. Implementation of comprehensive stroke services is a cost-effective approach to meet unmet needs in the stroke patient pathway, to improve acute stroke care and support better treatment of AF and access to neurorehabilitation.

Waitlist management in a pediatric weight management clinic: implementing an orientation session.

BACKGROUND: This study evaluates implementation of an orientation session to address a waitlist of more than 2000 referrals to a pediatric weight management clinic in the Mid-South United States. METHODS: An hour-long group-based orientation to the pediatric weight management clinic was implemented to provide information about the structure and expectations of the clinic as well as education on healthy lifestyle recommendations. Families were contacted from the waitlist by telephone and invited to attend an orientation session prior to scheduling a clinic appointment. RESULTS: Of 2251 patients contacted from the waitlist, 768 scheduled an orientation session, of which 264 (34 %) attended. Of the 264 orientation participants, 246 (93 %) scheduled a clinic appointment. Of those, 193 (79 %) completed a clinic visit. Waitlist times decreased from 297.8 ± 219.4 days prior to implementation of orientation sessions to 104.1 ± 219.4 days after. CONCLUSIONS: Orientation has been an effective and efficient way to triage patient referrals while maximizing attendance in limited clinic slots for patients and families demonstrating interest and motivation. Elements of this approach are likely generalizable to other pediatric clinical settings that must strategically manage a large volume of patient referrals.

Steroid hormones, energetic state, and immunocompetence vary across reproductive contexts in a parthenogenetic lizard.

Reproduction is energetically expensive and investing in this life history trait is likely accompanied by significant changes in physiological activity. Investment strategy necessary for achieving reproductive success in reptiles can vary with reproductive form and pattern, potentiating different consequences for competing fitness-related traits such as those key to survival. The goal of this study was to assess if and how energetic state (i.e., energy metabolites) and self-maintenance (i.e., immunocompetence) are hormonally modulated across reproductive contexts in an oviparous, parthenogenetic lizard, the Colorado Checkered Whiptail Aspidoscelis neotesselata. Here blood plasma samples were collected from lizards within the US Army Fort Carson Military Installation near Colorado Springs, CO, USA, during seasons of reproductive activity (i.e., June) and inactivity (i.e., August). Measures of reproductive (i.e., estradiol) and energy-mobilizing (i.e., corticosterone) hormones, energy metabolites (i.e., glucose, triglycerides, and free glycerol), and innate immunity (i.e., bactericidal ability) were compared by season and reproductive stage. Levels of energy metabolites and bactericidal ability were compared to levels of E2 and CORT. Bactericidal ability was also compared to levels of energy metabolites. Corticosterone and glucose levels were lower during the reproductive season while triglyceride levels and bactericidal ability were higher, but both estradiol and free glycerol levels did not differ between seasons. Throughout vitellogenesis, corticosterone and glucose levels as well as bactericidal ability did not differ, but estradiol levels were higher during early and mid-stage and both triglyceride and free glycerol levels were lower during gravidity. Corticosterone levels were negatively associated with circulating triglycerides and bactericidal ability, but were not related to glucose nor free glycerol levels. Estradiol levels were positively associated with free glycerol levels and bactericidal ability, but were not related to glucose nor triglyceride levels. Finally, bactericidal ability was negatively associated with glucose, but positively associated with triglycerides. Differences in energetic state and immunocompetence are thus reflected by shifts in hormone secretion across reproductive investment. These findings provide partial support for the hypothesis that energetic state is differentially regulated by steroid hormones to afford reproduction, potentially at the cost of future survival.

Low-flow apnoeic oxygenation for laryngeal surgery: a prospective observational study.

Laryngeal surgery requires a shared airway and close collaboration between surgeon and anaesthetist in order to optimise operating conditions. Apnoeic oxygenation uses the principle of aventilatory mass flow to maintain oxygenation of pulmonary capillary blood under apnoeic conditions while minimising laryngeal movement. Concerns regarding accumulation of carbon dioxide and resultant acidaemia have limited the use of the technique. We performed a prospective study of low-flow apnoeic oxygenation for patients undergoing microlaryngoscopy under general anaesthesia in order to evaluate the ability of the technique to maintain oxygenation and determine the resultant rate of carbon dioxide accumulation. Sixty-four patients undergoing microlaryngoscopy under general anaesthesia were studied between November 2016 and December 2018. Intra-operative oxygenation was provided via a 10-French oxygen catheter placed into the trachea delivering oxygen at 0.5-1.0 l.min-1 . Data regarding apnoea time, peripheral oxygen saturation and venous blood gas concentrations were recorded. The mean (SD) duration of apnoea was 18.7 (7.2) min. Apnoeic oxygenation allowed successful completion of the surgical procedure in 62/64 patients. Mean (SD) rate of rise of the venous partial pressure of carbon dioxide was 0.15 (0.10) kPa.min-1 . Operating conditions were recorded qualitatively as being adequate in all cases. No adverse effects were reported. Low-flow intra-tracheal apnoeic oxygenation is a simple, effective and inexpensive technique to maintain oxygenation for laryngeal surgery.

Smoking cessation in elective surgical patients offered free nicotine patches at listing: a pilot study.

Free nicotine patches may promote pre-operative smoking cessation. Smokers (≥ 10 cigarettes.day-1 ) awaiting non-urgent surgery were randomly assigned (3:1) to an offer of free nicotine patches or a control group who were not offered free nicotine patches. The suggested regimen lasted 5 weeks, with patch strength decreasing incrementally after 3 and 4 weeks. The primary outcome was smoking abstinence for ≥ 4 weeks, as self-reported by participants on the day of surgery, including, where possible, corroboration using exhaled carbon monoxide testing. Out of 600 included smokers, 447 (74.5%) were randomly assigned to an offer of pre-operative nicotine patches, with 175 (39.1%) of these accepting the offer and 56 (12.5%) using patches for ≥ 3 weeks. Out of 396 participants offered nicotine patches who were included for analysis, 36 (9.1%) quit smoking for ≥ 4 weeks before surgery as compared with 8 (5.9%) controls, OR 1.5 [95%CI 0.7-3.2], p = 0.300. Sixty-three (15.9%) quit smoking for 24 h before surgery as compared with 15 (11.1%) controls, OR 1.4 [95%CI 0.8-2.4], p = 0.200. Participants offered nicotine patches were more likely to engage in a cessation attempt lasting more than 24 h, 46 (11.6%) vs. 5 (3.7%), OR 3.4 [95%CI 1.8-8.8], p = 0.010. Out of 78 participants who quit smoking by the day of surgery and were followed up at 6 months, 46 (59%) had relapsed. Offering free nicotine patches stimulated interest in quitting compared with controls, but our protocol had limited effectiveness.

Psychosocial Functioning After One Year of Interdisciplinary Pediatric Weight Management.

Youth with obesity are more likely than normal-weight peers to experience psychosocial problems. Empirically-based recommendations for addressing pediatric obesity include intensive interdisciplinary weight management comprising medical, behavioral health, nutrition, and exercise components. The present study examined changes in psychosocial functioning associated with frequency of participation in an interdisciplinary pediatric weight management program. Participants were 86 patients (55.8% females; median age = 11.5 years; 67.4% Non-Hispanic Black; median BMI percentile = 99.5) enrolled in an interdisciplinary pediatric weight management program for at least one year. Psychosocial functioning was measured with the Pediatric Symptom Checklist (PSC-17), a caregiver-completed mental health screen that assesses internalizing, externalizing, and attention difficulties as well as global functioning. The PSC-17 was completed at the initial clinic visit (baseline) and repeated one-year later (annual). The Wilcoxon Signed Rank test indicated that annual PSC-17 scores were significantly lower than baseline scores across all domains. Spearman correlation coefficients revealed no significant association between total number of clinic visits and PSC-17 global or subscale scores. However, the number of visits for exercise-only sessions was significantly correlated with caregiver-reported improvement in internalizing behaviors. Findings suggest that participation in interdisciplinary pediatric weight management may improve psychosocial functioning in youth with obesity and that attending supervised exercise sessions may be especially beneficial for improving internalizing behavior symptoms.

Impact of ethnicity on adverse perinatal outcome in women with chronic hypertension: a cohort study.

OBJECTIVE: To assess the impact of maternal ethnicity on the risk of adverse perinatal outcome in pregnant women with chronic hypertension. METHODS: Demographic and delivery data were collated of women with chronic hypertension and singleton pregnancy who delivered at one of three UK obstetric units between 2000 and 2014. Multivariable logistic regression models were used to calculate risk ratios (RR), according to ethnic group, for adverse perinatal outcome, adjusted for other maternal characteristics including age, parity, body mass index, smoking status, deprivation index and year of delivery. The impact of maternal ethnicity on birth-weight centile calculation was investigated by comparing the birth-weight centile chart customized for ethnicity (Gestation Related Optimal Weight; GROW) with a birth-weight centile calculator that does not adjust for that factor (INTERGROWTH-21st ). RESULTS: The study cohort included 4481 pregnancies (4045 women) with chronic hypertension. Women of white ethnicity accounted for 47% (n = 2122) of the cohort and 36% (n = 1601) were of black, 8.5% (n = 379) of Asian and 8.5% (n = 379) of other ethnicity. The overall incidence of stillbirth was 1.6%, that of preterm birth < 37 weeks was 16% and that of fetal growth restriction (birth weight < 3rd centile) was 11%. Black women, compared with white women, had the highest risk for all adverse perinatal outcomes, with stillbirth occurring in 3.1% vs 0.6% of pregnancies (adjusted RR (aRR), 5.56 (95% CI, 2.79-11.09)), preterm birth < 37 weeks in 21% vs 11% (aRR, 1.70 (95% CI, 1.43-2.01)) and birth weight < 3rd centile in 15% vs 7.4% (aRR, 2.07 (95% CI, 1.71-2.51)). Asian women, compared with white women, were also at increased risk of adverse perinatal outcome, with stillbirth occurring in 1.6% vs 0.6% (aRR, 3.03 (95% CI, 1.11-8.28)), preterm birth < 37 weeks in 20% vs 11% (aRR, 1.82 (95% CI, 1.41-2.35)) and birth weight < 3rd centile in 12% vs 7.4% (aRR, 1.69 (95% CI, 1.24-2.30)). The sensitivity and specificity for prediction of infants requiring neonatal unit admission were 40% and 93%, respectively, for those with birth weight < 3rd centile according to GROW charts, compared with 16% and 96%, respectively, for those with birth weight < 3rd centile according to INTERGROWTH-21st charts. CONCLUSIONS: Black ethnicity, compared with white, is associated with the greatest risk of adverse perinatal outcome in women with chronic hypertension, even after adjusting for other maternal characteristics. Women of Asian ethnicity are also at increased risk, but to a lesser extent. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Heat-pipe Earth.

The heat transport and lithospheric dynamics of early Earth are currently explained by plate tectonic and vertical tectonic models, but these do not offer a global synthesis consistent with the geologic record. Here we use numerical simulations and comparison with the geologic record to explore a heat-pipe model in which volcanism dominates surface heat transport. These simulations indicate that a cold and thick lithosphere developed as a result of frequent volcanic eruptions that advected surface materials downwards. Declining heat sources over time led to an abrupt transition to plate tectonics. Consistent with model predictions, the geologic record shows rapid volcanic resurfacing, contractional deformation, a low geothermal gradient across the bulk of the lithosphere and a rapid decrease in heat-pipe volcanism after initiation of plate tectonics. The heat-pipe Earth model therefore offers a coherent geodynamic framework in which to explore the evolution of our planet before the onset of plate tectonics.

Resilient Entangling Gates for Trapped Ions.

Constructing a large-scale ion trap quantum processor will require entangling gate operations that are robust in the presence of noise and experimental imperfection. We experimentally demonstrate how a new type of Mølmer-Sørensen gate protects against infidelity caused by heating of the motional mode used during the gate. Furthermore, we show how the same technique simultaneously provides significant protection against slow fluctuations and mis-sets in the secular frequency. Since this parameter sensitivity is worsened in cases where the ions are not ground-state cooled, our method provides a path towards relaxing ion cooling requirements in practical realizations of quantum computing and simulation.

Potential Utility of a Loaded Treadmill Protocol for Tactical Athletes.

Swearingen, JT, Weiss, LW, Smith, WA, Stephenson, MD, and Schilling, BK. Potential utility of a loaded treadmill protocol for tactical athletes. J Strength Cond Res 32(3): 610-616, 2018-Aerobic capacity is an important variable for tactical athletes, with V[Combining Dot Above]O2max being the most direct way of estimating it in a laboratory setting. A mode-specific protocol involving fixed-weight, torso-borne loads was assessed in the current study. On 4 separate days, 15 men (age 22.1 ± 2.7 years, mass 85.1 ± 10.6 kg, height 179.0 ± 7.7 cm) performed a weighted treadmill walking protocol (2 trials) and a nonweighted treadmill running protocol (2 trials). Both the weighted and nonweighted protocols were reliable, with intraclass correlation coefficient values of 0.79 and 0.87, respectively. V[Combining Dot Above]O2peak values from both protocols were highly correlated (r = 0.90, p < 0.01). However, V[Combining Dot Above]O2peak was higher during the nonweighted protocol (t = 7.547, d = 2.47, p < 0.01). Work rate was calculated for both the last completed stage and stage during which participants reached fatigue. Work rates for both protocols on the last completed stage were similar (t = 1.44, d = 0.83, p = 0.17), although the work rate for the final attempted stage was greater for the weighted-walking protocol (t = 5.85, d = 3.60, p < 0.01). These data suggest a weighted-walking V[Combining Dot Above]O2peak that is highly associated with a running V[Combining Dot Above]O2peak. This test may be applied to those who routinely perform torso-borne load carriage, such as tactical athletes. Future weighted-walking protocols should seek achieve higher resolution, especially near the end stage of the test where subjects reach volitional fatigue. Large increases in work rate may not be feasible at the end stages of the test.

Transcriptomic variation of pharmacogenes in multiple human tissues and lymphoblastoid cell lines.

Variation in the expression level and activity of genes involved in drug disposition and action ('pharmacogenes') can affect drug response and toxicity, especially when in tissues of pharmacological importance. Previous studies have relied primarily on microarrays to understand gene expression differences, or have focused on a single tissue or small number of samples. The goal of this study was to use RNA-sequencing (RNA-seq) to determine the expression levels and alternative splicing of 389 Pharmacogenomics Research Network pharmacogenes across four tissues (liver, kidney, heart and adipose) and lymphoblastoid cell lines, which are used widely in pharmacogenomics studies. Analysis of RNA-seq data from 139 different individuals across the 5 tissues (20-45 individuals per tissue type) revealed substantial variation in both expression levels and splicing across samples and tissue types. Comparison with GTEx data yielded a consistent picture. This in-depth exploration also revealed 183 splicing events in pharmacogenes that were previously not annotated. Overall, this study serves as a rich resource for the research community to inform biomarker and drug discovery and use.

Elevated phosphodiester and T2 levels can be measured in the absence of fat infiltration in Duchenne muscular dystrophy patients.

Quantitative MRI and MRS are increasingly important as non-invasive outcome measures in therapy development for Duchenne muscular dystrophy (DMD). Many studies have focussed on individual measures such as fat fraction and metabolite levels in relation to age and functionality, but much less attention has been given to how these indices relate to each other. Here, we assessed spatially resolved metabolic changes in leg muscles of DMD patients, and classified muscles according to the degree of fat replacement compared with healthy controls. Quantitative MRI (three-point Dixon and multi-spin echo without fat suppression and a tri-exponential fit) and 2D-CSI 31 P MRS scans were obtained from 18 DMD patients and 12 healthy controls using a 3 T and a 7 T MR scanner. Metabolite levels, T2 values and fat fraction were individually assessed for five lower leg muscles. In muscles with extensive fat replacement, phosphodiester over adenosine triphosphate (PDE/ATP), inorganic phosphate over phosphocreatine, intracellular tissue pH and T2 were significantly increased compared with healthy controls. In contrast, in muscles without extensive fat replacement, only PDE/ATP and T2 values were significantly elevated. Overall, our results show that PDE levels and T2 values increase prior to the occurrence of fat replacement and remain elevated in later stages of the disease. This suggests that these individual measures could not only function as early markers for muscle damage but also reflect potentially reversible pathology in the more advanced stages.

A randomized, double-blind phase II study evaluating cediranib versus cediranib and saracatinib in patients with relapsed metastatic clear-cell renal cancer (COSAK).

BACKGROUND: Preclinical work suggests SRC proteins have a role in the development of resistance to vascular endothelial growth factor (VEGF) targeted therapy in metastatic clear-cell renal cancer (mRCC). This hypothesis was tested in this trial using the SRC inhibitor saracatinib and the VEGF inhibitor cediranib. PATIENTS AND METHODS: Patients with disease progression after ≥1 VEGF-targeted therapy were eligible to participate in this double-blind, randomized (1:1) phase II study. The study compared the combination cediranib 30 mg once daily (o.d.) and saracatinib 175 mg o.d. (CS) (n = 69) or cediranib 45 mg o.d. and placebo o.d. (C) (n = 69). Archived tissue was used for biomarker analysis [SRC, focal adhesion kinase (FAK), von Hippel-Lindau, protein tyrosine phosphatase 1b and hypoxia-inducible factor 2α : n = 86]. The primary end point was progression-free survival (PFS) by RECIST v1.1. RESULTS: Between 2010 and 2012, 138 patients were randomized across 16 UK sites. The characteristics of the two groups were well balanced. Partial responses were seen in 13.0% for C and 14.5% for CS (P > 0.05). There was no significant difference in PFS [5.4 months (3.6-7.3 months) for C and 3.9 (2.4-5.3 months) for CS; hazard ratio (HR) 1.18 (0.94-1.48)] or overall survival (OS) [14.2 months (11.2-16.8 months) for C and 10.0 (6.7-13.2 months) for CS; HR 1.28 (1.00-1.63)]. There was no significant difference in the frequency of key adverse events, dose reductions or drug discontinuations. None of the biomarkers were prognostic for PFS or OS. FAK overexpression correlated with an OS benefit [HR 2.29 (1.09-4.82), P > 0.05], but not PFS, for CS. CONCLUSIONS: Saracatinib did not increase the efficacy of a VEGF-targeted therapy (cediranib) in this setting. Biomarker analysis did not identify consistent predictive biomarkers. CLINICALTRIALSGOV: NCT00942877.

Therapeutic effects of inorganic nitrate and nitrite in cardiovascular and metabolic diseases.

Nitric oxide (NO) is generated endogenously by NO synthases to regulate a number of physiological processes including cardiovascular and metabolic functions. A decrease in the production and bioavailability of NO is a hallmark of many major chronic diseases including hypertension, ischaemia-reperfusion injury, atherosclerosis and diabetes. This NO deficiency is mainly caused by dysfunctional NO synthases and increased scavenging of NO by the formation of reactive oxygen species. Inorganic nitrate and nitrite are emerging as substrates for in vivo NO synthase-independent formation of NO bioactivity. These anions are oxidation products of endogenous NO generation and are also present in the diet, with green leafy vegetables having a high nitrate content. The effects of nitrate and nitrite are diverse and include vasodilatation, improved endothelial function, enhanced mitochondrial efficiency and reduced generation of reactive oxygen species. Administration of nitrate or nitrite in animal models of cardiovascular disease shows promising results, and clinical trials are currently ongoing to investigate the therapeutic potential of nitrate and nitrite in hypertension, pulmonary hypertension, peripheral artery disease and myocardial infarction. In addition, the nutritional aspects of the nitrate-nitrite-NO pathway are interesting as diets suggested to protect against cardiovascular disease, such as the Mediterranean diet, are especially high in nitrate. Here, we discuss the potential therapeutic opportunities for nitrate and nitrite in prevention and treatment of cardiovascular and metabolic diseases.

The technological future of 7 T MRI hardware.

In this article we present our projections of future hardware developments on 7 T human MRI systems. These include compact cryogen-light magnets, improved gradient performance, integrated RF-receive and direct current shimming coil arrays, new RF technology with adaptive impedance matching, patient-specific specific absorption rate estimation and monitoring, and increased integration of physiological monitoring systems. Copyright © 2015 John Wiley & Sons, Ltd.

Trapped-Ion Quantum Logic with Global Radiation Fields.

Trapped ions are a promising tool for building a large-scale quantum computer. However, the number of required radiation fields for the realization of quantum gates in any proposed ion-based architecture scales with the number of ions within the quantum computer, posing a major obstacle when imagining a device with millions of ions. Here, we present a fundamentally different approach for trapped-ion quantum computing where this detrimental scaling vanishes. The method is based on individually controlled voltages applied to each logic gate location to facilitate the actual gate operation analogous to a traditional transistor architecture within a classical computer processor. To demonstrate the key principle of this approach we implement a versatile quantum gate method based on long-wavelength radiation and use this method to generate a maximally entangled state of two quantum engineered clock qubits with fidelity 0.985(12). This quantum gate also constitutes a simple-to-implement tool for quantum metrology, sensing, and simulation.

Concurrent beneficial (vitamin D production) and hazardous (cutaneous DNA damage) impact of repeated low-level summer sunlight exposures.

BACKGROUND: The concurrent impact of repeated low-level summer sunlight exposures on vitamin D production and cutaneous DNA damage, potentially leading to mutagenesis and skin cancer, is unknown. OBJECTIVES: This is an experimental study (i) to determine the dual impact of repeated low-level sunlight exposures on vitamin D status and DNA damage/repair (via both skin and urinary biomarkers) in light-skinned adults; and (ii) to compare outcomes following the same exposures in brown-skinned adults. METHODS: Ten white (phototype II) and six South Asian volunteers (phototype V), aged 23-59 years, received 6 weeks' simulated summer sunlight exposures (95% ultraviolet A/5% ultraviolet B, 1·3 standard erythemal doses three times weekly) wearing summer clothing exposing ~35% body surface area. Assessments made were circulating 25-hydroxyvitamin D [25(OH)D], immunohistochemistry for cyclobutane pyrimidine dimer (CPD)-positive nuclei and urinary biomarkers of direct and oxidative (8-oxo-deoxyguanosine) DNA damage. RESULTS: Serum 25(OH)D rose from mean 36·5 ± 13·0 to 54·3 ± 10·5 nmol L-1 (14·6 ± 5·2 to 21·7 ± 4·2 ng mL-1 ) in phototype II vs. 17·2 ± 6·3 to 25·5 ± 9·5 nmol L-1 (6·9 ± 2·5 to 10·2 ± 3·8 ng mL-1 ) in phototype V (P < 0·05). Phototype II skin showed CPD-positive nuclei immediately postcourse, mean 44% (range 27-84) cleared after 24 h, contrasting with minimal DNA damage and full clearance in phototype V (P < 0·001). The findings did not differ from those following single ultraviolet radiation (UVR) exposure. Urinary CPDs remained below the detection threshold in both groups; 8-oxo-deoxyguanosine was higher in phototype II than V (P = 0·002), but was unaffected by UVR. CONCLUSIONS: Low-dose summer sunlight exposures confer vitamin D sufficiency in light-skinned people concurrently with low-level, nonaccumulating DNA damage. The same exposures produce minimal DNA damage but less vitamin D in brown-skinned people. This informs tailoring of sun-exposure policies.

Transcranial Doppler Ultrasound Detection of Microemboli as a Predictor of Cerebral Events in Patients with Symptomatic and Asymptomatic Carotid Disease: A Systematic Review and Meta-Analysis.

OBJECTIVE: Identification of patients who will benefit from carotid endarterectomy is not entirely effective, primarily utilising degree of carotid stenosis. This study aimed at determining if microembolic signals (MES) detected by transcranial Doppler ultrasound (TCD) can provide clinically useful information regarding stroke risk in patients with carotid atherosclerosis. METHODS: A meta-analysis of prospective studies was performed. Three analyses were proposed investigating MES detection as a predictor of: stroke or TIA, stroke alone, and stroke or TIA but with an increased positivity threshold. Subgroup analysis was used to compare pre-operative (symptomatic or asymptomatic) patients and peri- or post-operative patients. RESULTS: Twenty-eight studies reported data regarding both MES status and neurological outcome. Of these, 22 papers reported data on stroke and TIA as an outcome, 19 on stroke alone, and eight on stroke and TIA with increased positivity threshold. At the median pre-test probability of 3.0%, the post-test probabilities of a stroke after a positive and negative TCD were 7.1% (95% CI 5-10.1) and 1.2% (95% CI 0.6-2.5), respectively. In addition, the sensitivities and specificities of each outcome showed that increasing the threshold for positivity to 10 MES per hour would make TCD a more clinically useful tool in peri- and post-operative patients. CONCLUSION: TCD provides clinically useful information about stroke risk for patients with carotid disease and is technically feasible in most patients. However, the generally weak level of evidence constituting this review means definitive recommendations cannot be made.