Optical clocks at sea.

Deployed optical clocks will improve positioning for navigational autonomy1, provide remote time standards for geophysical monitoring2 and distributed coherent sensing3, allow time synchronization of remote quantum networks4,5 and provide operational redundancy for national time standards. Although laboratory optical clocks now reach fractional inaccuracies below 10-18 (refs. 6,7), transportable versions of these high-performing clocks8,9 have limited utility because of their size, environmental sensitivity and cost10. Here we report the development of optical clocks with the requisite combination of size, performance and environmental insensitivity for operation on mobile platforms. The 35 l clock combines a molecular iodine spectrometer, fibre frequency comb and control electronics. Three of these clocks operated continuously aboard a naval ship in the Pacific Ocean for 20 days while accruing timing errors below 300 ps per day. The clocks have comparable performance to active hydrogen masers in one-tenth the volume. Operating high-performance clocks at sea has been historically challenging and continues to be critical for navigation. This demonstration marks a significant technological advancement that heralds the arrival of future optical timekeeping networks.

Understanding primary care transformation and implications for ageing populations and health inequalities: a systematic scoping review of new models of primary health care in OECD countries and China.

BACKGROUND: Many countries have introduced reforms with the aim of primary care transformation (PCT). Common objectives include meeting service delivery challenges associated with ageing populations and health inequalities. To date, there has been little research comparing PCT internationally. Our aim was to examine PCT and new models of primary care by conducting a systematic scoping review of international literature in order to describe major policy changes including key 'components', impacts of new models of care, and barriers and facilitators to PCT implementation. METHODS: We undertook a systematic scoping review of international literature on PCT in OECD countries and China (published protocol: https://osf.io/2afym ). Ovid [MEDLINE/Embase/Global Health], CINAHL Plus, and Global Index Medicus were searched (01/01/10 to 28/08/21). Two reviewers independently screened the titles and abstracts with data extraction by a single reviewer. A narrative synthesis of findings followed. RESULTS: A total of 107 studies from 15 countries were included. The most frequently employed component of PCT was the expansion of multidisciplinary teams (MDT) (46% of studies). The most frequently measured outcome was GP views (27%), with < 20% measuring patient views or satisfaction. Only three studies evaluated the effects of PCT on ageing populations and 34 (32%) on health inequalities with ambiguous results. For the latter, PCT involving increased primary care access showed positive impacts whilst no benefits were reported for other components. Analysis of 41 studies citing barriers or facilitators to PCT implementation identified leadership, change, resources, and targets as key themes. CONCLUSIONS: Countries identified in this review have used a range of approaches to PCT with marked heterogeneity in methods of evaluation and mixed findings on impacts. Only a minority of studies described the impacts of PCT on ageing populations, health inequalities, or from the patient perspective. The facilitators and barriers identified may be useful in planning and evaluating future developments in PCT.

Alcohol use among people who inject drugs living with HIV in Kenya is associated with needle sharing, more new sex partners, and lower engagement in HIV care.

We assessed the prevalence and correlates of alcohol use among 870 people who inject drugs living with HIV in Kenya, with attention toward (1) sexual and injecting risk behaviors for HIV transmission and (2) HIV care engagement. We defined heavy alcohol use as > 14 drinks/week for men and > 7 drinks/week for women, moderate alcohol use as any lesser but non-zero amount, and any alcohol use as either moderate or heavy use. Approximately 39% of participants reported any alcohol use and 15% heavy use. In multivariate analysis, any alcohol use compared to no use was associated with needle sharing, > 3 new sex partners in the past 3 months, being unaware of HIV status, never enrolling in HIV care, and not being on ART (all p < 0.05). Heavy alcohol use as compared to no use was associated with needle sharing (aOR = 2.72; 95% CI 1.43, 5.13), injection equipment sharing (aOR = 1.80; 95% CI 1.00, 3.16), > 3 new sex partners in the past 3 months (aOR = 1.99; 95% CI 1.12, 3.49), and being unaware of HIV status (aOR = 2.77; 95% CI 1.46, 5.19). There was no association between any measure of alcohol use and unsuppressed viral load. Alcohol use among people who inject drugs living with HIV may carry elevated risk of HIV transmission mediated by sexual and injecting practices and is associated with lower engagement in multiple stages of the HIV care cascade.

Connectomic Basis for Tremor Control in Stereotactic Radiosurgical Thalamotomy.

BACKGROUND AND PURPOSE: Given the increased use of stereotactic radiosurgical thalamotomy and other ablative therapies for tremor, new biomarkers are needed to improve outcomes. Using resting-state fMRI and MR tractography, we hypothesized that a "connectome fingerprint" can predict tremor outcomes and potentially serve as a targeting biomarker for stereotactic radiosurgical thalamotomy. MATERIALS AND METHODS: We evaluated 27 patients who underwent unilateral stereotactic radiosurgical thalamotomy for essential tremor or tremor-predominant Parkinson disease. Percentage postoperative improvement in the contralateral limb Fahn-Tolosa-Marin Clinical Tremor Rating Scale (TRS) was the primary end point. Connectome-style resting-state fMRI and MR tractography were performed before stereotactic radiosurgery. Using the final lesion volume as a seed, "connectivity fingerprints" representing ideal connectivity maps were generated as whole-brain R-maps using a voxelwise nonparametric Spearman correlation. A leave-one-out cross-validation was performed using the generated R-maps. RESULTS: The mean improvement in the contralateral tremor score was 55.1% (SD, 38.9%) at a mean follow-up of 10.0 (SD, 5.0) months. Structural connectivity correlated with contralateral TRS improvement (r = 0.52; P = .006) and explained 27.0% of the variance in outcome. Functional connectivity correlated with contralateral TRS improvement (r = 0.50; P = .008) and explained 25.0% of the variance in outcome. Nodes most correlated with tremor improvement corresponded to areas of known network dysfunction in tremor, including the cerebello-thalamo-cortical pathway and the primary and extrastriate visual cortices. CONCLUSIONS: Stereotactic radiosurgical targets with a distinct connectivity profile predict improvement in tremor after treatment. Such connectomic fingerprints show promise for developing patient-specific biomarkers to guide therapy with stereotactic radiosurgical thalamotomy.

Contributions of side effects to contraceptive discontinuation and method switch among Kenyan women: a prospective cohort study.

OBJECTIVE: To determine the contribution of specific contraceptive side effects to method switch and modern-method discontinuation among Kenyan women. DESIGN: A prospective cohort study. SETTING: Five counties in Western Kenya. PARTICIPANTS: Women aged ≥18 years old and emancipated female minors ≥14 years old using modern, reversible contraception were recruited while attending 10 public health facilities. METHODS: Patient-reported adverse effect symptoms, method switch and discontinuation were reported through weekly text message-based surveys for 24 weeks. MAIN OUTCOME MEASUREMENTS: Prevalence, hazards ratio (HR). RESULTS: Among 825 women, 44% were using implants, 43% injectables, 7% an intrauterine device and 6% oral contraceptive pills at enrolment. Most (61%) women were continuing a method used in the previous month. During the 24-week follow up, incidence of contraceptive switch was 61.3 per 100 person-years (95% confidence interval [CI] 52.4-71.8) and incidence of discontinuation was 38.5 per 100 person-years (95% CI 31.6-47.0). On average, one-quarter (prevalence [Pr] 0.24, 95% CI 0.22-0.26) of participants reported side effects or method problems weekly, with sexual side effects the most prevalent symptom (Pr 0.15, 95% CI 0.13-0.16). Lack of expected bleeding was associated with higher risk of method switch (adjusted hazard ratio [aHR] 2.36, 95% CI 1.22-4.57). Risk of all-modern method discontinuation was higher among women experiencing irregular bleeding (aHR 2.39, 95% CI 1.20-4.77), weight changes (aHR 2.72, 95% CI 1.47-4.68) and sexual side effects (aHR 2.42, 95% CI 1.40-4.20). CONCLUSIONS: Addressing irregular bleeding, weight changes and sexual side effects through development of new products that minimise these specific side effects and anticipatory counseling may reduce method-related discontinuation. TWEETABLE ABSTRACT: Bleeding, weight changes, sexual problems associated with discontinuation of #contraception, but many continue despite side effects.

Closing the UK care home data gap - methodological challenges and solutions.

UK care home residents are invisible in national datasets. The COVID-19 pandemic has exposed data failings that have hindered service development and research for years. Fundamental gaps, in terms of population and service demographics coupled with difficulties identifying the population in routine data are a significant limitation. These challenges are a key factor underpinning the failure to provide timely and responsive policy decisions to support care homes. In this commentary we propose changes that could address this data gap, priorities include: (1) Reliable identification of care home residents and their tenure; (2) Common identifiers to facilitate linkage between data sources from different sectors; (3) Individual-level, anonymised data inclusive of mortality irrespective of where death occurs; (4) Investment in capacity for large-scale, anonymised linked data analysis within social care working in partnership with academics; (5) Recognition of the need for collaborative working to use novel data sources, working to understand their meaning and ensure correct interpretation; (6) Better integration of information governance, enabling safe access for legitimate analyses from all relevant sectors; (7) A core national dataset for care homes developed in collaboration with key stakeholders to support integrated care delivery, service planning, commissioning, policy and research. Our suggestions are immediately actionable with political will and investment. We should seize this opportunity to capitalise on the spotlight the pandemic has thrown on the vulnerable populations living in care homes to invest in data-informed approaches to support care, evidence-based policy making and research.

Repeat gamma knife stereotactic radiosurgery in the treatment of trigeminal neuralgia: A single-center experience and focused review of the literature.

OBJECTIVES: Repeat Gamma Knife stereotactic radiosurgery (GKSR) for refractory trigeminal neuralgia (TGN) is an increasingly common practice. Prior studies have reported varying success rates and incidence of trigeminal nerve dysfunction following repeated GKSR. We report treatment outcomes and toxicity in patients following repeat GKSR for TGN at the University of Alabama at Birmingham (UAB) with a focused review of the literature. METHODS: We retrospectively reviewed medical records of 55 TGN patients re-treated with radiosurgery using the Leksell Gamma Knife® at the University of Alabama at Birmingham between 1996 and 2012. Outcomes were defined using the Modified Marseille Scale. Demographics, prior treatments and symptom duration were correlated with outcomes. RESULTS: Eighteen patients (33%) achieved Marseille Class I or II, 14 (25%) Class III or IV, and 23 (42%) Class V at a mean follow-up of 14.4 months. Twenty-five patients (45%) developed new trigeminal nerve dysfunction after re-treatment. Of these, four (16%) did not develop dysfunction until subsequent microvascular decompression (MVD) for inadequate symptom relief. CONCLUSIONS: Although more than half of the patients undergoing repeat GKSR for refractory TGN maintained excellent or good outcomes (Marseille classes I-IV) at an average follow-up of 14.4 months, neither age, gender, nor pre-treatment duration of symptoms or interval between treatments had a statistically significant effect on outcomes. Following repeat GKSR, patients have increased risk for new-onset trigeminal nerve dysfunction and those undergoing MVD after repeat GKSR may have an increased risk for new-onset trigeminal nerve dysfunction.

Comorbidities in adults with asthma: Population-based cross-sectional analysis of 1.4 million adults in Scotland.

BACKGROUND: Comorbidity in people with asthma can significantly increase asthma morbidity and lower adherence to asthma guidelines. OBJECTIVE: The objective of this study was to comprehensively measure the prevalence of physical and mental health comorbidities in adults with asthma using a large nationally representative population. METHODS: Cross-sectional analysis of routine primary care electronic medical records for 1 424 378 adults in the UK, examining the prevalence of 39 comorbidities in people with and without asthma, before and after adjustment for age, sex, social deprivation and smoking status using logistic regression. RESULTS: Of 39 comorbidities measured, 36 (92%) were significantly more common in adults with asthma; 62.6% of adults with asthma had ≥1 comorbidity vs 46.2% of those without, and 16.3% had ≥4 comorbidities vs 8.7% of those without. Comorbidities with the largest absolute increase in prevalence in adults with asthma were as follows: chronic obstructive pulmonary disease (COPD) (13.4% vs 3.1%), depression (17.3% vs 9.1%), painful conditions (15.4% vs 8.4%) and dyspepsia (10.9% vs 5.2%). Comorbidities with the largest relative difference in adults with asthma compared to those without were as follows: COPD (adjusted odds ratio [aOR] 5.65, 95% CI 5.52-5.79), bronchiectasis (aOR 4.65, 95% CI 4.26-5.08), eczema/psoriasis (aOR 3.30, 95% CI 3.14-3.48), dyspepsia (aOR 2.20, 95% CI 2.15-2.25) and chronic sinusitis (aOR 2.12, 95% CI 1.99-2.26). Depression and anxiety were more common in adults with asthma (aOR 1.60, 95% CI 1.57-1.63, and aOR 1.53, 95% CI 1.48-1.57, respectively). CONCLUSIONS AND CLINICAL RELEVANCE: Physical and mental health comorbidities are the norm in adults with asthma. Appropriate recognition and management should form part of routine asthma care.

Low HDL-cholesterol among HIV-1 infected and HIV-1 uninfected individuals in Nairobi, Kenya.

BACKGROUND: Antiretroviral treatment (ART) is associated with dyslipidemia yet little is known about the burden of dyslipidemia in the absence of ART in sub-Saharan Africa. We compared the prevalence and risk factors for dyslipidemia among HIV-infected ART-naïve adults and their uninfected partners in Nairobi, Kenya. METHODS: Non-fasting total cholesterol (TC) and high density lipoprotein cholesterol (HDL) levels were measured by standard lipid spectrophotometry on thawed plasma samples obtained from HIV-infected participants and their uninfected partners. Dyslipidemia, defined by high TC (>200 mg/dl) or low HDL (<40 mg/dl) was compared between HIV-infected and uninfected men and women. RESULTS: Among 196 participants, median age was 32 years [IQR: 23-41]. Median CD4 count among the HIV-infected was 393 cells/ µl (IQR: 57-729) and 90% had a viral load >1000 copies/ml. Mean TC and HDL were comparable for HIV-infected and uninfected participants. Prevalence of dyslipidemia was 83.8% vs 78.4% (p = 0.27). Among the HIV-infected, those with a viral load >1000 copies/ml were 1.5-fold more likely to have dyslipidemia compared to those with ≤1000 copies/ml (adjusted prevalence ratio [aPR] 1.5, 95% CI: 1.22-30.99, p = 0.02). BMI, age, gender, blood pressure and smoking were not significantly associated with dyslipidemia. CONCLUSIONS: Among ART-naïve HIV-infected adults, high viral load and low CD4 cell count were independent predictors of dyslipidemia, underscoring the importance of early initiation of ART for viral suppression.

Widening access to medicine may improve general practitioner recruitment in deprived and rural communities: survey of GP origins and current place of work.

BACKGROUND: Widening access to medicine in the UK is a recalcitrant problem of increasing political importance, with associated strong social justice arguments but without clear evidence of impact on service delivery. Evidence from the United States suggests that widening access may enhance care to underserved communities. Additionally, rural origin has been demonstrated to be the factor most strongly associated with rural practice. However the evidence regarding socio-economic and rural background and subsequent practice locations in the UK has not been explored. The aim of this study was to investigate the association between general practitioners' (GPs) socio-economic and rural background at application to medical school and demographic characteristics of their current practice. METHOD: The study design was a cross-sectional email survey of general practitioners practising in Scotland. Socio-economic status of GPs at application to medical school was assessed using the self-coded National Statistics Socio-Economic Classification. UK postcode at application was used to define urban-rural location. Current practice deprivation and remoteness was measured using NHS Scotland defined measures based on registered patients' postcodes. RESULTS: A survey was sent to 2050 Scottish GPs with a valid accessible email address, with 801 (41.5 %) responding. GPs whose parents had semi-routine or routine occupations had 4.3 times the odds of working in a deprived practice compared to those with parents from managerial and professional occupations (95 % CI 1.8-10.2, p = 0.001). GPs from remote and rural Scottish backgrounds were more likely to work in remote Scottish practices, as were GPs originating from other UK countries. CONCLUSION: This study showed that childhood background is associated with the population GPs subsequently serve, implying that widening access may positively affect service delivery in addition to any social justice rationale. Longitudinal research is needed to explore this association and the impact of widening access on service delivery more broadly.

NSAID-exacerbated respiratory disease: a meta-analysis evaluating prevalence, mean provocative dose of aspirin and increased asthma morbidity.

BACKGROUND: The prevalence and mean provocative dose of oral aspirin (MPDA) triggering respiratory reactions in people with asthma have been inconsistently reported, and the relationship between NSAID-exacerbated respiratory disease (NERD) and asthma morbidity was less well quantified. METHODS: A systematic review was performed by identifying studies diagnosing NERD using blinded, placebo-controlled oral provocation challenge tests (OPCTs) or by self-reported history in people with asthma. Data were extracted, and effect estimates for changes in respiratory function, MPDA and asthma morbidity were pooled using random-effects meta-analysis. RESULTS: The prevalence of NERD in adults with asthma was 9.0% (95% CI 6-12%) using OPCTs and 9.9% (95% CI 9.4-10.5%) using self-reported history from questionnaires. The MPDA in adults with NERD was 85.8 mg (95% CI 73.9-97.6). In people with NERD, the risk of: uncontrolled asthma was increased twofold (RR 1.96 (95% CI 1.25-3.07)); severe asthma and asthma attacks was increased by 60% (RR 1.58 (95% CI 1.15-2.16) and RR 1.59 (95% CI 1.21-2.09), respectively); emergency room visits was increased by 80% (RR 1.79 (95% CI 1.29-2.49)); and asthma hospitalization was increased by 40% (RR 1.37 (95% CI 1.12-1.67)) compared to people with NSAID-tolerant asthma. CONCLUSIONS: Respiratory reactions triggered by oral aspirin in people with asthma are relatively common. At the population level, the prevalence of NERD was similar when measured using appropriately conducted OPCTs or by self-reported history. On average, respiratory reactions were triggered by clinically relevant doses of oral aspirin. Asthma morbidity was significantly increased in people with NERD who potentially require more intensive monitoring and follow-up.

Vascular comorbidities in younger people with dementia: a cross-sectional population-based study of 616†245 middle-aged people in Scotland.

INTRODUCTION: There is growing evidence of an aetiological relationship between vascular risk factors and the development of dementia in later life. Dementia in the under-65s has historically been considered to be more driven by genetic factors, but previous epidemiological studies in the young have been relatively small. This study aims to determine the prevalence of vascular comorbidity in people aged <65 with dementia in comparison to the general population. METHODS: Analysis of routine clinical data from 314 (30%) general medical practices in Scotland. RESULTS: From an overall population of 616 245 individuals, 1061 cases of 'all-cause' dementia were identified (prevalence 172/100 000 population, 95% CI 161 to 182). The prevalence of dementia was higher in people with vascular morbidities, and prevalence progressively increased from 129/100 000 in people with no vascular comorbidity to 999/100 000 in people with four or more (p=0.01). The strength of association was greatest with a previous transient ischaemic attack (TIA) or stroke and chronic kidney disease (adjusted OR=3.1 and 2.9, respectively). Statistically significant, but smaller associations were seen with the presence of hypertension, diabetes, ischaemic heart disease and peripheral vascular disease (adjusted OR=1.4, 2.0, 1.9 and 2.2, respectively). DISCUSSIONS: Vascular comorbid diseases were more commonly recorded in people aged 40-64 with dementia than those without. This finding indicates that vascular disease may be more important in the aetiology of young-onset dementia than previously believed, and is of concern given the continuing rise in obesity and diabetes internationally.

Changes in opioid and other analgesic use 1995-2010: repeated cross-sectional analysis of dispensed prescribing for a large geographical population in Scotland.

BACKGROUND: Despite recent concerns about increasing rates of analgesic prescribing, detailed epidemiological studies are lacking. We identified and described changes in the pattern of community-dispensed prescriptions to the Tayside population, Scotland, between 31st March 1995 (n = 301,020) and 31st March 2010 (n = 311,881). METHODS: Repeated cross-sectional analysis of patient-level population data on dispensed analgesics, stratified by sociodemographic variables; logistic regression to identify factors associated with strong opioid dispensing in 2010. RESULTS: The proportion of people currently dispensed any analgesic increased in 2010 (17.9%) compared with 1995 (15.7%). This increase was not equal across drug classes, with paracetamol, opioids and gabapentin/pregabalin showing an increase, but others showing a decrease. Weak opioids were less commonly dispensed in 2010 (8.2% vs. 8.4%) but dispensing of strong opioids increased 18-fold (3.6% vs. 0.2%), including a five-fold increase of morphine, fentanyl or oxycodone (0.75% vs. 0.15%). People receiving more non-analgesic drugs (odds ratio 20.7 if dispensed >14 non-analgesic medications vs. those dispensed <4) and those living in more deprived areas (OR 1.63 most deprived vs. most affluent) were more likely to receive a strong opioid in 2010. CONCLUSIONS: Analgesic use rose modestly between 1995 and 2010, but with larger changes within individual classes, only partly reflecting evidence-based guidance. Dispensing of strong opioids increased dramatically, largely driven by tramadol, although other strong opioids tripled. Polypharmacy and socio-economic deprivation were strongly associated with strong opioid use. Research is needed to establish the causes, benefits and harms of the increase in analgesic, and especially strong opioid use.

Factors associated with statin treatment for the primary prevention of cardiovascular disease in people within 2 years following diagnosis of diabetes in Scotland, 2006-2008.

AIM: To describe characteristics associated with statin prescribing for the primary prevention of cardiovascular disease in people with newly diagnosed diabetes. METHODS: Data from the Scottish Care Information-Diabetes Collaboration data set for 2006-2008 were used. This data set contains socio-demographic and prescribing data for over 99% of people with diagnosed diabetes in Scotland. Analyses were conducted on people aged over 40 years diagnosed with Type 1 or Type 2 diabetes between 2006 and 2008 with complete data and no previous history of cardiovascular or statin prescription. Logistic regression was used to calculate odds ratios for statin prescription in the 2 years following diagnosis of diabetes. RESULTS: There were 7157 men and 5601 women who met the inclusion criteria, 68% of whom had a statin prescription recorded in the 2 years following diagnosis of diabetes. The proportions receiving statins were lower above 65 years of age in men and 75 years of age in women. People with Type 1 diabetes had lower odds of receiving statins than people with Type 2 diabetes [odds ratio (95% CI) 0.42 (0.29-0.61) for men and 0.48 (0.28-0.81) for women, after adjustment for age, BMI, smoking status, cholesterol level and deprivation]. Higher total cholesterol, BMI and being a current smoker were associated with greater odds of statin prescription. CONCLUSION: Approximately one third of the study population had no record of statin prescription during the 2 years after diagnosis of diabetes. Cardiovascular disease risk reduction opportunities may be missed in some of these people.

Monitoring and adverse events in relation to ACE inhibitor/angiotensin receptor blocker initiation in people with diabetes in general practice: a population database study.

BACKGROUND AND AIM: To determine whether angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEI/ARB) initiation in people with diabetes is monitored as recommended by recent guidelines and the incidence of associated adverse renal events. DESIGN: Retrospective population database analysis of 4056 people in Tayside, Scotland with type 2 diabetes prescribed an ACEI/ARB between 1 January 2005 and 31 December 2009. METHOD: Measurement of urea and electrolytes (U&Es) before and after ACEI/ARB initiation and renal adverse events; defined as a ≥30% rise in serum creatinine and post-initiation potassium of ≥5.6 mmol/L. Associations of adverse events with patient demographics or co-prescription of drugs with known renal effects were examined. RESULTS: Overall, 89% of initiations were with an ACE inhibitor. A total of 18.84% (CI 95% 18.82-18.86) of patients initiating ACE inhibitor or ARB had U&Es measured in the 90 days before initiation and within 5-14 days after initiation. Only 1.7% of patients had an adverse renal event. Patients prescribed with an ARB were less likely to be monitored than those prescribed with an ACE inhibitor, but no less likely to suffer harm. CONCLUSIONS: Current clinical practice of biochemical monitoring of ACE inhibitor/ARB is poor, but adverse events are rare. Further studies with serial U&Es are needed to establish the critical time window for adverse renal events and evaluate whether intensive biochemical monitoring recommended is required in low-risk groups.

Preference mapping of lemon lime carbonated beverages with regular and diet beverage consumers.

UNLABELLED: The drivers of liking of lemon-lime carbonated beverages were investigated with regular and diet beverage consumers. Ten beverages were selected from a category survey of commercial beverages using a D-optimal procedure. Beverages were subjected to consumer testing (n = 101 regular beverage consumers, n = 100 diet beverage consumers). Segmentation of consumers was performed on overall liking scores followed by external preference mapping of selected samples. Diet beverage consumers liked 2 diet beverages more than regular beverage consumers. There were no differences in the overall liking scores between diet and regular beverage consumers for other products except for a sparkling beverage sweetened with juice which was more liked by regular beverage consumers. Three subtle but distinct consumer preference clusters were identified. Two segments had evenly distributed diet and regular beverage consumers but one segment had a greater percentage of regular beverage consumers (P < 0.05). The 3 preference segments were named: cluster 1 (C1) sweet taste and carbonation mouthfeel lovers, cluster 2 (C2) carbonation mouthfeel lovers, sweet and bitter taste acceptors, and cluster 3 (C3) bitter taste avoiders, mouthfeel and sweet taste lovers. User status (diet or regular beverage consumers) did not have a large impact on carbonated beverage liking. Instead, mouthfeel attributes were major drivers of liking when these beverages were tested in a blind tasting. PRACTICAL APPLICATION: Preference mapping of lemon-lime carbonated beverage with diet and regular beverage consumers allowed the determination of drivers of liking of both populations. The understanding of how mouthfeel attributes, aromatics, and basic tastes impact liking or disliking of products was achieved. Preference drivers established in this study provide product developers of carbonated lemon-lime beverages with additional information to develop beverages that may be suitable for different groups of consumers.

External validity of randomized controlled trials of glycaemic control and vascular disease: how representative are participants?

AIMS: To describe the proportion of people with Type 2 diabetes living in Scotland who meet eligibility criteria for inclusion in several large randomized controlled trials of glycaemic control to inform physicians and guideline developers about the generalizibility of trial results. METHODS: A literature review was performed to identify large trials assessing the impact of glycaemic control on risk of macrovascular disease. Inclusion and exclusion criteria from each trial were applied to data on the population of people with a diagnosis of Type 2 diabetes living in Scotland in 2008 (n = 180,590) in a population-based cross-sectional study and the number and proportion of people eligible for each trial was determined. RESULTS: Seven trials were identified. The proportion of people with Type 2 diabetes who met the eligibility criteria for the trials ranged from 3.5 to 50.7%. Trial participants were younger at age of diagnosis of diabetes and at time of trial recruitment than in the Scottish study population. The application of upper age criteria excluded the largest proportion of patients, with up to 39% of people with Type 2 diabetes ineligible for a trial with the most stringent criteria based on age alone. CONCLUSIONS: We found that many of the large trials of glycaemic control among people with Type 2 diabetes have limited external validity when applied to a population-based cohort of people with Type 2 diabetes. In particular, the age distribution of trial participants often does not reflect that of people with Type 2 diabetes in a contemporary British population.

Hospitalised hip fracture risk with rosiglitazone and pioglitazone use compared with other glucose-lowering drugs.

AIMS/HYPOTHESIS: Current drug labels for thiazolidinediones (TZDs) warn of increased fractures, predominantly for distal fractures in women. We examined whether exposure to TZDs affects hip fracture in women and men and compared the risk to that found with other drugs used in diabetes. METHODS: Using a nationwide database of prescriptions, hospital admissions and deaths in those with type 2 diabetes in Scotland we calculated TZD exposure among 206,672 individuals. Discrete-time failure analysis was used to model the effect of cumulative drug exposure on hip fracture during 1999-2008. RESULTS: There were 176 hip fractures among 37,479 exposed individuals. Hip fracture risk increased with cumulative exposure to TZD: OR per year of exposure 1.18 (95% CI 1.09, 1.28; p = 3 × 10(-5)), adjusted for age, sex and calendar month. Hip fracture increased with cumulative exposure in both men (OR 1.20; 95% CI 1.03, 1.41) and women (OR 1.18; 95% CI 1.07, 1.29) and risks were similar for pioglitazone (OR 1.18) and rosiglitazone (OR 1.16). The association was similar when adjusted for exposure to other drugs for diabetes and for other potential confounders. There was no association of hip fracture with cumulative exposure to sulfonylureas, metformin or insulin in this analysis. The 90-day mortality associated with hip fractures was similar in ever-users of TZD (15%) and in never-users (13%). CONCLUSIONS/INTERPRETATION: Hip fracture is a severe adverse effect with TZDs, affecting both sexes; labels should be changed to warn of this. The excess mortality is at least as much as expected from the reported association of pioglitazone with bladder cancer.

Spin-imbalance in a one-dimensional Fermi gas.

Superconductivity and magnetism generally do not coexist. Changing the relative number of up and down spin electrons disrupts the basic mechanism of superconductivity, where atoms of opposite momentum and spin form Cooper pairs. Nearly forty years ago Fulde and Ferrell and Larkin and Ovchinnikov (FFLO) proposed an exotic pairing mechanism in which magnetism is accommodated by the formation of pairs with finite momentum. Despite intense theoretical and experimental efforts, however, polarized superconductivity remains largely elusive. Unlike the three-dimensional (3D) case, theories predict that in one dimension (1D) a state with FFLO correlations occupies a major part of the phase diagram. Here we report experimental measurements of density profiles of a two-spin mixture of ultracold (6)Li atoms trapped in an array of 1D tubes (a system analogous to electrons in 1D wires). At finite spin imbalance, the system phase separates with an inverted phase profile, as compared to the 3D case. In 1D, we find a partially polarized core surrounded by wings which, depending on the degree of polarization, are composed of either a completely paired or a fully polarized Fermi gas. Our work paves the way to direct observation and characterization of FFLO pairing.