Results of an American College of Radiology-Society of Interventional Radiology Membership Survey on Exclusive Contracts and the Attitudes of Interventional Radiologists.

PURPOSE: To assess the attitudes of interventional radiologists (IRs) and diagnostic radiologists (DRs) toward exclusive contracts and independently practicing IRs who may request privileges at a hospital where an exclusive contract exists with a different group of radiologists. MATERIALS AND METHODS: A total of 22,400 survey instruments were distributed to 4,490 IRs and 17,910 DRs in the United States. Statistical evaluation included multivariate ordinal logistic regression analysis with calculation of the odds ratios and forest plots. RESULTS: Completed surveys were received from 525 (11.69%) IRs and 401 (2.23%) DRs. Given the low response rate of DRs, data analysis was focused on IRs. Early-career IRs and those in outpatient practices had a more positive attitude toward independent IRs who requested admitting and/or procedural privileges. A supermajority of both IRs and DRs who responded to the survey agreed that the importance of IR to hospital and health system contracts will increase. CONCLUSIONS: This survey identified many interrelated and complex variables that significantly affected the attitudes of IRs in various practice settings toward independent IRs requesting hospital admitting and/or procedural privileges. It will benefit independent IRs seeking admitting privileges to better understand some of the factors that impact the potential willingness of the radiology groups and other IRs with exclusive hospital contracts to work toward mutually beneficial practice paradigms, especially as more clinically oriented IRs complete their training in the new, integrated residency programs.

Is glycaemic control associated with dietary patterns independent of weight change in people newly diagnosed with type 2 diabetes? Prospective analysis of the Early-ACTivity-In-Diabetes trial.

BACKGROUND: It is unclear whether diet affects glycaemic control in type 2 diabetes (T2D), over and above its effects on bodyweight. We aimed to assess whether changes in dietary patterns altered glycaemic control independently of effects on bodyweight in newly diagnosed T2D. METHODS: We used data from 4-day food diaries, HbA1c and potential confounders in participants of the Early-ACTivity-In-Diabetes trial measured at 0, 6 and 12 months. At baseline, a 'carb/fat balance' dietary pattern and an 'obesogenic' dietary pattern were derived using reduced-rank regression, based on hypothesised nutrient-mediated mechanisms linking dietary intake to glycaemia directly or via obesity. Relationships between 0 and 6 month change in dietary pattern scores and baseline-adjusted HbA1c at 6 months (n = 242; primary outcome) were assessed using multivariable linear regression. Models were repeated for periods 6-12 months and 0-12 months (n = 194 and n = 214 respectively; secondary outcomes). RESULTS: Reductions over 0-6 months were observed in mean bodyweight (- 2.3 (95% CI: - 2.7, - 1.8) kg), body mass index (- 0.8 (- 0.9, - 0.6) kg/m2), energy intake (- 788 (- 953, - 624) kJ/day), and HbA1c (- 1.6 (- 2.6, -0.6) mmol/mol). Weight loss strongly associated with lower HbA1c at 0-6 months (ß = - 0.70 [95% CI - 0.95, - 0.45] mmol/mol/kg lost). Average fat and carbohydrate intakes changed to be more in-line with UK healthy eating guidelines between 0 and 6 months. Dietary patterns shifting carbohydrate intakes higher and fat intakes lower were characterised by greater consumption of fresh fruit, low-fat milk and boiled/baked potatoes and eating less of higher-fat processed meats, butter/animal fats and red meat. Increases in standardised 'carb/fat balance' dietary pattern score associated with improvements in HbA1c at 6 months independent of weight loss (ß = - 1.54 [- 2.96, - 0.13] mmol/mol/SD). No evidence of association with HbA1c was found for this dietary pattern at other time-periods. Decreases in 'obesogenic' dietary pattern score were associated with weight loss (ß = - 0.77 [- 1.31, - 0.23] kg/SD) but not independently with HbA1c during any period. CONCLUSIONS: Promoting weight loss should remain the primary nutritional strategy for improving glycaemic control in early T2D. However, improving dietary patterns to bring carbohydrate and fat intakes closer to UK guidelines may provide small, additional improvements in glycaemic control. TRIAL REGISTRATION: ISRCTN92162869 . Retrospectively registered on 25 July 2005.

A Survey of Interventional Radiologists Regarding the Use of Morbidity and Mortality Conferencing in Departmental Quality Improvement Programs.

PURPOSE: To investigate the degree to which morbidity and mortality (M&M) conferencing is utilized in interventional radiology (IR), identify impediments to its adoption, and assess the experience of those using this tool. MATERIALS AND METHODS: Members of the Society of Interventional Radiology (SIR) were offered a 9-question survey of practices and experiences regarding M&M conferencing within their quality assessment (QA) programs. RESULTS: Among 604 respondents, 37.8% were university-based practitioners and 60% were from outside of university practices. Of all respondents, 43% reported practicing 100% IR, with 28.5% practicing IR 75%-99% and 11% practicing IR <50% of the time. The use of M&M conferencing was significantly greater in university practices (90.7%) than in nonuniversity practices (37.1%) and among practitioners performing at least 75% IR (71.2%) than among those practicing <75% (28.8%). The conferences were held monthly (66.6%) or more often, and the majority (56%) of the events identified were scored using the SIR severity score. Approximately 20% of M&M conferences were multidisciplinary, shared most commonly with vascular surgery. The reasons cited for not using M&M included the lack of time and the logistical challenges of the process. However, among those who participate in M&M conferences, the QA goals of the conference were met at very high rates. CONCLUSIONS: M&M conferencing is well established in university IR programs and among full-time practitioners but much less so elsewhere. For those sites that do not utilize M&M conferencing, there may be a considerable benefit to addressing the obstacles that are limiting their implementation of this tool.

Molecular identification of trematode parasites infecting the freshwater snail Bithynia siamensis goniomphalos in Thailand.

Digenetic trematodes are important parasites of humans and animals. They have complex life cycles and typically infect a gastropod as the first intermediate host. Bithynia siamensis goniomphalos, the first intermediate host of the liver fluke, Opisthorchis viverrini, harbours a wide variety of other trematode species. Morphological details of cercariae of 20 trematode taxa from B. s. goniomphalos, collected mainly in Thailand from 2009 to 2014, were provided in an earlier paper. Correct identification to the species or genus level based on morphology of these cercariae is generally not possible. Therefore, we used molecular data to improve identification and to investigate the diversity of the species of trematodes infecting B. s. goniomphalos. We were successful in extracting, amplifying and sequencing portions of the 28S ribosomal RNA (rRNA) gene for 19 of these 20 types of cercaria, and the internal transcribed spacer 2 region for 18 types. BLAST searches in GenBank and phylogenetic trees inferred from the 28S rRNA sequences identified members of at least nine superfamilies and 12 families. Only a few cercariae could be assigned confidently to genus or species on the basis of the sequence data. Matching sequence data from named adult trematodes will be required for definitive identification. There is clearly a great diversity of trematode species utilizing B. s. goniomphalos in Thailand.

Matrix metalloproteinases regulate ECM accumulation but not larval heart growth in Drosophila melanogaster.

The Drosophila heart provides a simple model to examine the remodelling of muscle insertions with growth, extracellular matrix (ECM) turnover, and fibrosis. Between hatching and pupation, the Drosophila heart increases in length five-fold. If major cardiac ECM components are secreted remotely, how is ECM "self assembly" regulated? We explored whether ECM proteases were required to maintain the morphology of a growing heart while the cardiac ECM expanded. An increase in expression of Drosophila's single tissue inhibitor of metalloproteinase (TIMP), or reduced function of metalloproteinase MMP2, resulted in fibrosis and ectopic deposition of two ECM Collagens; type-IV and fibrillar Pericardin. Significant accumulations of Collagen-IV (Viking) developed on the pericardium and in the lumen of the heart. Congenital defects in Pericardin deposition misdirected further assembly in the larva. Reduced metalloproteinase activity during growth also increased Pericardin fibre accumulation in ECM suspending the heart. Although MMP2 expression was required to remodel and position cardiomyocyte cell junctions, reduced MMP function did not impair expansion of the heart. A previous study revealed that MMP2 negatively regulates the size of the luminal cell surface in the embryonic heart. Cardiomyocytes align at the midline, but do not adhere to enclose a heart lumen in MMP2 mutant embryos. Nevertheless, these embryos hatch and produce viable larvae with bifurcated hearts, indicating a secondary pathway to lumen formation between ipsilateral cardiomyocytes. MMP-mediated remodelling of the ECM is required for organogenesis, and to prevent assembly of excess or ectopic ECM protein during growth. MMPs are not essential for normal growth of the Drosophila heart.

Loss of offspring Peg3 reduces neonatal ultrasonic vocalizations and increases maternal anxiety in wild-type mothers.

Depression and anxiety are the most common mental health conditions during pregnancy and can impair the normal development of mother-infant interactions. These adversities are associated with low birth weight and increased risk of behavioural disorders in children. We recently reported reduced expression of the imprinted gene PATERNALLY EXPRESSED GENE 3 (PEG3) in placenta of human infants born to depressed mothers. Expression of Peg3 in the brain has previously been linked maternal behaviour in rodents, at least in some studies, with mutant dams neglecting their pups. However, in our human study decreased expression was in the placenta derived from the fetus. Here, we examined maternal behaviour in response to reduced expression of Peg3 in the feto-placental unit. Prenatally we found novelty reactivity was altered in wild-type females carrying litters with a null mutation in Peg3. This behavioural alteration was short-lived and there were no significant differences the transcriptomes of either the maternal hypothalamus or hippocampus at E16.5. In contrast, while maternal gross maternal care was intact postnatally, the exposed dams were significantly slower to retrieve their pups and displayed a marked increase in anxiety. We also observed a significant reduction in the isolation-induced ultrasonic vocalizations (USVs) emitted by mutant pups separated from their mothers. USVs are a form of communication known to elicit maternal care suggesting Peg3 mutant pups drive the deficit in maternal behaviour. These data support the hypothesis that reduced placental PEG3 in human pregnancies occurs as a consequence of prenatal depression but leaves scope for feto-placental Peg3 dosage, during gestation, influencing aspects of maternal behaviour.

James Lind Alliance research priorities: should diet and exercise be used as an alternative to drugs for the management of type 2 diabetes or alongside them?

AIM: To review evidence on whether diet and exercise should be used as an alternative to drug therapy for the management of type 2 diabetes or alongside. METHOD: We present a narrative review that draws on evidence from other systematic reviews and meta-analyses, narrative reviews, trials and cohort studies. We focused mainly on glycaemic control rather than control of blood pressure or cholesterol. RESULTS: Good-quality dietary advice that results in weight loss of >5% and physical activity interventions of >150 min/week of moderate to vigorous physical activity, combined with resistance exercise, can produce improvements in HbA1c similar to those produced by the addition of glucose-lowering drugs. These improvements can be seen at all stages of the disease. There are recognized interactions between glucose-lowering drugs and physical activity which may not be synergistic, but these are not well understood, and it is not clear if they are considered in clinical practice. Studies that explicitly compare drugs with diet or physical activity or control for drug use found that lifestyle could delay or reduce medication use, but most people eventually needed to progress to drug treatment. There are few studies, however, that provide strategies for the long-term maintenance of weight loss or physical activity. CONCLUSION: Diet and physical activity are of key importance in type 2 diabetes management, and attention to them improves glycaemic control and cardiovascular disease risk, but it is not yet known whether maintained lifestyle changes provide an alternative to drug therapy in the long term.

Improving understanding of type 2 diabetes remission: research recommendations from Diabetes UK's 2019 remission workshop.

AIM: To describe the process and outputs of a workshop convened to identify key priorities for future research in the area of remission of type 2 diabetes, and provide recommendations to researchers and research funders on how best to address them. With the ultimate aim of enabling the remission of type 2 diabetes to become a possibility for more people. METHODS: A 1-day research workshop was conducted, bringing together 31 researchers, people living with diabetes, healthcare professionals and members of staff from Diabetes UK to identify and prioritize recommendations for future research into remission of type 2 diabetes. RESULTS: Workshop attendees identified 10 key themes for further research. Four of these themes were prioritized for further focus: (i) understanding how to personalize lifestyle approaches based on biology, patient choice and subtypes; (ii) understanding the biology of remission; (iii) understanding the most effective approaches to implementation of lifestyle interventions; and (iv) understanding the best approaches to combining therapies (gut hormones, other drugs, lifestyle approaches and bariatric surgery). CONCLUSIONS: This paper outlines recommendations to address the current gaps in knowledge related to remission of type 2 diabetes.

Development of a group structured education programme to support safe exercise in people with Type 1 diabetes: the EXTOD education programme.

AIM: To develop a structured education programme for individuals with Type 1 diabetes who are engaging in regular exercise. METHOD: A multidisciplinary team of experts in supporting exercise and physical activity for people with Type 1 diabetes, alongside researchers with experience of developing self-management education, developed an exercise programme using the Medical Research Council framework. The programme was informed by a review of the evidence relating to Type 1 diabetes and exercise, the behaviour change literature (including the behaviour change taxonomy), and qualitative interviews with stakeholders. The programme and supporting resources were refined using an iterative process of testing, delivery and collecting feedback from participants and the wider development team. RESULTS: The outcome of the intervention development was the design of a feasible and acceptable intervention for people with Type 1 diabetes to support safe exercise. The pilot allowed refinement of the intervention prior to testing in a two-site feasibility randomized controlled trial. Key findings from the pilot informed minor restructuring of the timetable (timings and order) and adaptation of supporting educational materials (participant handbook and teaching materials). CONCLUSION: The 'EXercise in people with Type One Diabetes' (EXTOD) education programme has been developed using robust methodology for the generation of educational interventions. It now needs testing in a randomized controlled trial.

Exercise-induced hypoglycaemia in type 1 diabetes.

NEW FINDINGS: What is the topic of this review? Hypoglycaemia is a commonly cited barrier to exercise in type 1 diabetes mellitus (T1D). Knowledge of approaches to prevent or manage exercise-induced hypoglycaemia can support patients to exercise and help clinicians to give advice. This review presents evidence-based strategies to prevent exercise-induced hypoglycaemia in T1D. What advances does it highlight? This review highlights approaches that can be used before, during and after exercise to mitigate the risk of hypoglycaemia. The approaches include the timing of exercise, the type of exercise, adjustments to insulin and carbohydrate, use of novel technology and education. ABSTRACT: Exercise is a key component for the management of type 1 diabetes mellitus (T1D) and is associated with reduced risk of cardiovascular disease, decreased daily insulin requirements and improved quality of life. Owing to these benefits, people with T1D are recommended to undertake regular physical activity, 150 min per week for adults and 60 min per day for children and adolescents. Despite the recommendations, many people do not meet these targets. One of the commonly cited barriers to exercise is fear of hypoglycaemia along with limited knowledge of effective preventative strategies. Hypoglycaemia can be difficult to predict, and symptoms are often masked during exercise or stress of competition. For athletes with T1D, hypoglycaemia can also limit sporting success. Hypoglycaemia before an event increases the risks of hypoglycaemia during competition and can reduce performance. To avoid hypoglycaemia, people with T1D may avoid exercise altogether or consume excessive amounts of carbohydrates, which mitigates many of the health benefits of exercise. Increased understanding of approaches to prevent or manage hypoglycaemia is therefore important to help increase levels of physical activity in people with T1D and to support athletes with T1D to compete at the highest level. This review outlines the prevalence of exercise-related hypoglycaemia, its underlying physiology and the strategies that can be used to prevent and manage exercise-induced hypoglycaemia in T1D. Our hope is that this knowledge will be used by people with T1D and their clinicians to find individual approaches to manage exercise-related hypoglycaemia.

Measurement of Motion beyond the Quantum Limit by Transient Amplification.

Through simultaneous but unequal electromechanical amplification and cooling processes, we create a method for a nearly noiseless pulsed measurement of mechanical motion. We use transient electromechanical amplification (TEA) to monitor a single motional quadrature with a total added noise -8.5±2.0 dB relative to the zero-point motion of the oscillator, or equivalently the quantum limit for simultaneous measurement of both mechanical quadratures. We demonstrate that TEA can be used to resolve fine structure in the phase space of a mechanical oscillator by tomographically reconstructing the density matrix of a squeezed state of motion. Without any inference or subtraction of noise, we directly observe a squeezed variance 2.8±0.3 dB below the oscillator's zero-point motion.

Baseline incidence of adverse birth outcomes and infant influenza and pertussis hospitalisations prior to the introduction of influenza and pertussis vaccination in pregnancy: a data linkage study of 78 382 mother-infant pairs, Northern Territory, Australia, 1994-2015.

We conducted probabilistic data linkage of three population datasets for the Northern Territory (NT), Australia, to describe the incidence of preterm births, stillbirths, low birthweight and small for gestational age (SGA) per 1000 NT births; and influenza and pertussis hospitalisations per 1 00 000 NT births in infants <7 months of age, in a pre-maternal vaccination era. The Perinatal Trends dataset (1994-2014) formed the cohort of 78 382 births. Aboriginal mother-infant pairs (37%) had disproportionately higher average annual rates (AR) for all adverse birth outcomes compared to their non-Aboriginal counterparts; rate ratios: preterm births 2.2 (AR 142.4 vs. 64.7); stillbirths 2.3 (AR 10.8 vs. 4.6); low birthweight 2.9 (AR 54 vs. 19); and SGA 1.7 (AR 187 vs. 111). Hospitalisation (2000-2015) and Immunisation Register datasets (1994-2015), showed that influenza hospitalisations (n = 53) and rates were 42.3 times higher in Aboriginal infants (AR 254 vs. 6); and that pertussis hospitalisations (n = 37) were 7.1 times higher in Aboriginal infants (AR 142.5 vs. 20.2) compared to non-Aboriginal infants. These baseline data are essential to assess the safety and effectiveness of influenza and pertussis vaccinations in pregnant women from the NT. Remote living Aboriginal women and infants stand to benefit the most from these vaccines.

Pertussis epidemiology prior to the introduction of a maternal vaccination program, Queensland Australia.

Pertussis morbidity is highest in infants too young to be fully protected by routine vaccination schedules. Alternate vaccine strategies are required to maximise protection in this age-group. To understand baseline pertussis epidemiology prior to the introduction of the maternal pertussis vaccination program in 2014, we conducted a retrospective case series analyses of 53 901 notifications and temporal trends from 1997 to 2014. Notifications were highest in infants younger than 4 months of age and highest annual notification rates in infants younger than 1 month of age (308/100 000 per year). Amongst Aboriginal and Torres Strait Islander infants aged younger than 1 month, this rate was 576/100 000 per year. Notification rates were 40% higher amongst women 15-44 years, 62·4/100 000 population compared with men (44·5/100 000) and 90% higher in Aboriginal and Torres Strait Islander women of the same age (38·2/100 000) compared with men (19·7/100 000). Six infant deaths were identified, all younger than 2 months of age. Monitoring epidemiology in at-risk groups - infants too young to be vaccinated, women of childbearing age and Aboriginal and Torres Strait Islander peoples - following implementation of the maternal pertussis vaccination program will be important to assess its impact and safety.

Calculation of the age of the first infection for skin sores and scabies in five remote communities in northern Australia.

Prevalence of skin sores and scabies in remote Australian Aboriginal communities remains unacceptably high, with Group A Streptococcus (GAS) the dominant pathogen. We aim to better understand the drivers of GAS transmission using mathematical models. To estimate the force of infection, we quantified the age of first skin sores and scabies infection by pooling historical data from three studies conducted across five remote Aboriginal communities for children born between 2001 and 2005. We estimated the age of the first infection using the Kaplan-Meier estimator; parametric exponential mixture model; and Cox proportional hazards. For skin sores, the mean age of the first infection was approximately 10 months and the median was 7 months, with some heterogeneity in median observed by the community. For scabies, the mean age of the first infection was approximately 9 months and the median was 8 months, with significant heterogeneity by the community and an enhanced risk for children born between October and December. The young age of the first infection with skin sores and scabies reflects the high disease burden in these communities.

Enabling recruitment success in bariatric surgical trials: pilot phase of the By-Band-Sleeve study.

BACKGROUND: Randomized controlled trials (RCTs) involving surgical procedures are challenging for recruitment and infrequent in the specialty of bariatrics. The pilot phase of the By-Band-Sleeve study (gastric bypass versus gastric band versus sleeve gastrectomy) provided the opportunity for an investigation of recruitment using a qualitative research integrated in trials (QuinteT) recruitment intervention (QRI). PATIENTS/METHODS: The QRI investigated recruitment in two centers in the pilot phase comparing bypass and banding, through the analysis of 12 in-depth staff interviews, 84 audio recordings of patient consultations, 19 non-participant observations of consultations and patient screening data. QRI findings were developed into a plan of action and fed back to centers to improve information provision and recruitment organization. RESULTS: Recruitment proved to be extremely difficult with only two patients recruited during the first 2 months. The pivotal issue in Center A was that an effective and established clinical service could not easily adapt to the needs of the RCT. There was little scope to present RCT details or ensure efficient eligibility assessment, and recruiters struggled to convey equipoise. Following presentation of QRI findings, recruitment in Center A increased from 9% in the first 2 months (2/22) to 40% (26/65) in the 4 months thereafter. Center B, commencing recruitment 3 months after Center A, learnt from the emerging issues in Center A and set up a special clinic for trial recruitment. The trial successfully completed pilot recruitment and progressed to the main phase across 11 centers. CONCLUSIONS: The QRI identified key issues that enabled the integration of the trial into the clinical setting. This contributed to successful recruitment in the By-Band-Sleeve trial-currently the largest in bariatric practice-and offers opportunities to optimize recruitment in other trials in bariatrics.

Adaptation of the By-Band randomized clinical trial to By-Band-Sleeve to include a new intervention and maintain relevance of the study to practice.

BACKGROUND: Recruitment into surgical RCTs can be threatened if new interventions available outside the trial compete with those being evaluated. Adapting the trial to include the new intervention may overcome this issue, yet this is not often done in surgery. This paper describes the challenges, rationale and methods for adapting an RCT to include a new intervention. METHODS: The By-Band study was designed in the UK in 2009-2010 to compare the effectiveness of laparoscopic adjustable gastric band and Roux-en-Y gastric bypass for severe obesity. It contained a pilot phase to establish whether recruitment was possible, and the grant proposal specified that an adaptation to include sleeve gastrectomy would be considered if practice changed and recruitment was successful. Information on changing obesity surgery practice, updated evidence and expert opinion about trial design were used to inform the adaptation. RESULTS: The pilot phase recruited over 13 months in 2013-2014 and randomized 80 patients (79 anticipated). During this time, major changes in obesity practice in the UK were observed, with gastric band reducing from 32·6 to 15·8 per cent and sleeve gastrectomy increasing from 9·0 to 28·1 per cent. The evidence base had not changed markedly. The British Obesity and Metabolic Surgery Society and study oversight committees supported an adaptation to include sleeve gastrectomy, and a proposal to do so was approved by the funder. CONCLUSION: Adaptation of a two-group surgical RCT can allow evaluation of a third procedure and maintain relevance of the RCT to practice. It also optimizes the use of existing trial infrastructure to answer an additional important research question. Registration number: ISRCTN00786323 (http://www.isrctn.com/).

Exercise to preserve ß-cell function in recent-onset Type 1 diabetes mellitus (EXTOD) - a randomized controlled pilot trial.

AIM: Residual ß-cell function is present at the time of diagnosis with Type 1 diabetes. Preserving this ß-cell function reduces complications. We hypothesized that exercise preserves ß-cell function in Type 1 diabetes and undertook a pilot trial to address the key uncertainties in designing a definitive trial to test this hypothesis. METHODS: A randomized controlled pilot trial in adults aged 16-60 years diagnosed with Type 1 diabetes within the previous 3 months was undertaken. Participants were assigned to control (usual care) or intervention (exercise consultation every month), in a 1 : 1 ratio for 12 months. The primary outcomes were recruitment rate, drop out, exercise adherence [weeks with ≥ 150 min of self-reported moderate to vigorous physical activity (MVPA)], and exercise uptake in the control group. The secondary outcomes were differences in insulin sensitivity and rate of loss of ß-cell function between intervention and control at 6 and 12 months. RESULTS: Of 507 individuals who were approached, 58 (28 control, 30 intervention) entered the study and 41 completed it. Participants were largely white European males, BMI 24.8 ± 3.8 kg/m2 , HbA1c 75 ± 25 mmol/mol (9 ± 2%). Mean level of objectively measured MVPA increased in the intervention group (mean 243 to 273 min/week) and 61% of intervention participants reached the target of ≥ 150 min/week of self-reported MVPA on at least 42 weeks of the year. Physical activity levels fell slightly in the control group (mean 277 to 235 min of MVPA/week). There was exploratory evidence that intervention group became more insulin sensitive and required less insulin. However, the rate of loss of ß-cell function appeared similar between the groups, although the change in insulin sensitivity may have affected this. CONCLUSION: We show that it is possible to recruit and randomize people with newly diagnosed Type 1 diabetes to a trial of an exercise intervention, and increase and maintain their exercise levels for 12 months. Future trials need to incorporate measures of greater adherence to exercise training targets, and include more appropriate measures of ß-cell function. (Clinical Trials Registry No; ISRCTN91388505).

Decreased levels of platelet-derived soluble glycoprotein VI detected prior to the first diagnosis of coronary artery disease in HIV-positive individuals.

HIV-positive patients are at increased risk for coronary artery disease (CAD); changes in platelet activation may play a role. This study was performed to determine if levels of soluble glycoprotein VI (sGPVI), a platelet-specific marker of activation, were different in HIV-positive patients compared with HIV-negative controls and further if levels were predictive of CAD in HIV. Twenty-four HIV-positive individuals (HIV cases) with CAD were compared with 46 age- and sex-matched HIV-positive controls without CAD and 41 HIV-negative controls (healthy controls). Platelet activation (represented by sGPVI level) was compared 12 months and 1 month prior to CAD diagnosis. sGPVI was quantified by ELISA. sGPVI levels were higher in HIV-positive subjects (combined) than healthy controls (122.5 ng/mL [interquartile ranges (IQR) 90.3-160.5] versus 84.7 ng/mL [IQR 48.6-119.5], p <0.001). Twelve months before the event, there was no difference in sGPVI between HIV cases and HIV controls (113.4 ng/mL [IQR 85.6-141.65] versus 128.0 ng/mL [IQR 96.6-179.4], p = 0.369). One month prior to the event, sGPVI was significantly lower in HIV cases compared with HIV controls (109.0 ng/mL [IQR 79.4-123.4] versus 133.9 ng/mL [IQR 112.7-171.9], p = 0.010). These results remained significant following adjustment for possible confounders. This work demonstrates that HIV infection is associated with higher sGPVI levels. A fall in sGPVI immediately prior to first coronary artery event may reflect a loss of negative-feedback mechanism and be an important pathological step in the development of symptomatic CAD, but further work is needed to confirm these findings and determine their clinical impact.

Laser Cooling of a Micromechanical Membrane to the Quantum Backaction Limit.

The radiation pressure of light can act to damp and cool the vibrational motion of a mechanical resonator, but even if the light field has no thermal component, shot noise still sets a limit on the minimum phonon occupation. In optomechanical sideband cooling in a cavity, the finite off-resonant Stokes scattering defined by the cavity linewidth combined with shot noise fluctuations dictates a quantum backaction limit, analogous to the Doppler limit of atomic laser cooling. In our work, we sideband cool a micromechanical membrane resonator to the quantum backaction limit. Monitoring the optical sidebands allows us to directly observe the mechanical object come to thermal equilibrium with the optical bath. This level of optomechanical coupling that overwhelms the intrinsic thermal decoherence was not reached in previous ground-state cooling demonstrations.

Reduced Sensitivity to Charge Noise in Semiconductor Spin Qubits via Symmetric Operation.

We demonstrate improved operation of exchange-coupled semiconductor quantum dots by substantially reducing the sensitivity of exchange operations to charge noise. The method involves biasing a double dot symmetrically between the charge-state anticrossings, where the derivative of the exchange energy with respect to gate voltages is minimized. Exchange remains highly tunable by adjusting the tunnel coupling. We find that this method reduces the dephasing effect of charge noise by more than a factor of 5 in comparison to operation near a charge-state anticrossing, increasing the number of observable exchange oscillations in our qubit by a similar factor. Performance also improves with exchange rate, favoring fast quantum operations.