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Rationale & Objective: It is unclear whether the effect of canagliflozin on adverse kidney and cardiovascular events in those with diabetic kidney disease varies by age and sex. We assessed the effects of canagliflozin among age group categories and between sexes in the Canagliflozin and Renal Endpoints in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) study.Study Design: Secondary analysis of a randomized controlled trial.Setting & Participants: Participants in the CREDENCE trial.Intervention: Participants were randomly assigned to receive canagliflozin 100 mg/d or placebo.Outcomes: Primary composite outcome of kidney failure, doubling of serum creatinine concentration, or death due to kidney or cardiovascular disease. Prespecified secondary and safety outcomes were also analyzed. Outcomes were evaluated by age at baseline (Results: The mean age of the cohort was 63.0 ± 9.2 years, and 34% were female. Older age and female sex were independently associated with a lower risk of the composite of adverse kidney outcomes. There was no evidence that the effect of canagliflozin on the primary outcome (a composite of kidney failure, a doubling of serum creatinine concentration, or death from kidney or cardiovascular causes) differed between age groups (HRs, 0.67 [95% CI, 0.52-0.87], 0.63 [0.48-0.82], and 0.89 [0.61-1.29] for ages Limitations: This was a post hoc analysis with multiple comparisons.Conclusions: Canagliflozin consistently reduced the relative risk of kidney events in people with diabetic kidney disease in both sexes and across age subgroups. As a result of greater background risk, the absolute reduction in adverse kidney outcomes was greater in younger participants.Funding: This post hoc analysis of the CREDENCE trial was not funded. The CREDENCE study was sponsored by Janssen Research and Development and was conducted collaboratively by the sponsor, an academic-led steering committee, and an academic research organization, George Clinical.Trial Registration: The original CREDENCE trial was registered at ClinicalTrials.gov with study number NCT02065791.

For incumbents to be accountable for their issue stances, voters must sanction incumbents whose positions are “out of step” with their own. We test the electoral accountability of British legislators for their stance on Brexit. We find that there is very limited issue accountability. Individuals who disagreed with their representative’s stance on Brexit were 3 percentage points less likely to vote for them. The aggregate consequences of these individual effects are limited. A one-standard-deviation increase in the proportion of constituents agreeing with their incumbent’s Brexit stance is associated with an increase of 0.53 percentage points in incumbent vote share. These effects are one and a half times larger when the main challenger has a different Brexit stance to the incumbent. A follow-up survey of Members of Parliament (MPs) shows that MPs’ estimates of the effects of congruence are similar in magnitude. Our findings suggest that issue accountability is conditional in nature and limited in magnitude even for an issue such as Brexit, which should be maximally amenable to such effects.

Evidence suggests that as public opinion towards immigration becomes more negative, so the descriptive representation of ethnic minority groups is increasingly restricted. Recently, some initial research into the causal mechanism hinted that this effect is driven by patterns of candidacy. This suggests that political parties are creating an ‘ethnic penalty’ of their own in the selection stage. This paper investigates the relationship between patterns of candidacy, party strategy, and public opinion in Great Britain from 1997 to 2019, and proposes that ‘punitive parties’ are strongly responsible for shaping the representational outcomes of minority groups. I find support for earlier suggestions that parties are increasingly likely to place ethnic minority candidates away from ‘winnable’ contests as anti-immigrant hostility rises. These findings are important for our conceptions of ethnic penalties, of party behaviour in selection processes, and for the study and cause of improving political representation.

The choices voters made in response to the principal question put before them in the 2019 election—should Brexit be done—had a significant impact on the geography of party performance. Leave constituencies swung strongly to the Conservatives, while the party lost support in Remain seats. Labour struggled above all in the most pro-Leave parts of the country, while the Liberal Democrats’ limited advance was most evident in Remain seats. However, for the most part, this pattern did not arise because voters behaved differently in different kinds of constituency; it occurred because the prevalence of those voters who were more likely to swing from one party to another varied geographically. The geographical variation in party performance still had implications for the outcome in seats, enabling the Conservatives to secure a substantially larger majority than would otherwise have been the case. Geography mattered too because the single-member plurality system places a premium on unity. The geography of Remain support was potentially unfavourable to those on the pro-second referendum side of the Brexit debate even before a vote had been cast. But this was compounded by a fragmentation of Remain support across different parties. Resolving Brexit via a general election meant that the outcome was not simply determined by which was the most popular view, but also by the geographical distribution of the vote. On the one hand, the number of Leave MPs elected was reduced by the decision of the Brexit Party to stand. On the other hand, the greater fragmentation of Remain support and a less favourable electoral geography cost the pro-second referendum parties dear—and may well have played a decisive role in determining the choice the country eventually made.

Throughout recent decades, social science studies have systematically reported that citizens respond to their macro-social environments. While this is typically true in highly visible and salient policy domains, scholarship remains ambiguous about which macro-environmental factors are at the origins of citizens’ opinions on immigration. We contribute to this debate by theorising three factors that have the potential to move immigration opinions and subsequently testing their empirical relevance. We most notably emphasise the role of immigration itself and ask whether and how increasing immigration levels affect immigration opinions. We then examine to what extent the regional power structure and economic hardship interplay with this relationship. Through the dyadic ratios algorithm, we estimate a unique set of immigration opinion measures across regions in Belgium, France and the UK between 1990 and 2015. When modelling these measures, our findings are threefold. First, citizens are responsive to their environments, and specifically to immigration. Second, citizens become more favourable towards immigrants when immigration levels increase. Third, we find evidence that decentralisation (regional power) conditions this empirical relationship, while there is little to no indication that economic conditions affect immigration opinions, either directly or indirectly.

This research brings together literatures on public opinion and political representation into a political opportunity framework to investigate the impact that changing public opinion toward...

The authors regret that Alexandra Bargiota's name was spelt incorrectly in the author list. The details given in this correction are correct.

Modelling data over time requires a set of unique and bespoke processes in order to deal with problems induced by temporal dependency and autocorrelation. Methods are well developed and widely applied for working with such data when sample sizes are high, but the issue of how to fit models which are methodologically robust but not under-powered or over-fitted on short time series data remains vexing. This research proposes an interrupted time series analysis model solution to this problem, and uses a Type II Sum Squares ANCOVA Lagged Dependent Variable, variance-centric approach as part of a newly introduced R package - its.analysis. Using this model switches the null hypothesis situation to a much more reliable test and allows for a much more flexible approach to adding covariates in small sample conditions. The model performs very well under test conditions, appears more conservative than existing alternative techniques, and as such is recommended to researchers for future analysis of temporal data where observations are limited (between 15 and 45 observations).

Since the 1980s, Britain's two largest political parties have been converging ever closer on the political spectrum, in line with a Downsian model of two party majoritarian sys-tems. While both Labour and the Conservatives have been moving toward consensus, we investigate the extent to which the recent financial crisis, understood as a critical juncture, interrupted this movement. Using a “fuzzy set” ideal type analysis with claims making data, we asses whether or not we can detect the signs of this consensus breaking down as a result of the crisis and events which followed. Our results show that despite this most critical event, consensus was maintained as we found both parties adopting very similar framing and narrating strategies on the economic crisis in their public discourse. The study concludes that the shared discursive framing and narrating between both parties on the crisis demonstrates a continued Thatcherite, neoliberal consensus in British politics.

Using political claims analysis on 1,000 articles from five national newspapers (Daily Mail, The Sun, The Times, The Guardian, and Daily Mirror), this article demonstrates that press coverage of the financial crisis, recession, and austerity in the United Kingdom between 2007‐14 drew heavily on a neoliberal discourse. Political, market, and civil society actors discussed the impact of hard times on people using a reductionist neoliberal narrative, framing people as “economic actors” and consistently underplaying any social or political traits. By examining communicative, rather than coordinative, discourse this research expands the focus of previous studies which have examined the embeddedness of ideology in society, and highlights potential links to studies of citizen participation and mobilization.

The cardiovascular effect of liraglutide, a glucagon-like peptide 1 analogue, when added to standard care in patients with type 2 diabetes, remains unknown. METHODS In this double-blind trial, we randomly assigned patients with type 2 diabetes and high cardiovascular risk to receive liraglutide or placebo. The primary composite outcome in the time-to-event analysis was the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. The primary hypothesis was that liraglutide would be noninferior to placebo with regard to the primary outcome, with a margin of 1.30 for the upper boundary of the 95% confidence interval of the hazard ratio. No adjustments for multiplicity were performed for the prespecified exploratory outcomes. RESULTS A total of 9340 patients underwent randomization. The median follow-up was 3.8 years. The primary outcome occurred in significantly fewer patients in the liraglutide group (608 of 4668 patients [13.0%]) than in the placebo group (694 of 4672 [14.9%]) (hazard ratio, 0.87; 95% confidence interval [CI], 0.78 to 0.97; P, Novo Nordisk; National Institutes of Health; LEADER ClinicalTrials.gov

ObjectiveShort-term fasting is associated with increased GH pulsatility and mobilisation of fats, but underlying mechanisms are unclear. We studied ghrelin's role during fasting and the effects of exogenous ghrelin on lipid mobilisation.DesignRandomised placebo-controlled study.MethodsIn this study, ten controls (body mass index (BMI) 23.3±3.2), ten morbidly obese subjects (BMI 50.1±10.6) and six post-gastrectomy subjects (BMI 25.2±1.0) were fasted for 36 h undergoing regular blood sampling. On a separate occasion, subjects were infused with either i.v. ghrelin (5 pmol/kg per min) or saline over 270 min.ResultsObese and post-gastrectomy subjects had lower ghrelin compared with controls (ANOVA, P=0.02) during the fast. Controls and gastrectomy subjects showed a similar increase in GH pulsatility, circulating non-esterified fatty acids (NEFA) and 3β-hydroxybutyrate (3 HB). Obese subjects had an impaired GH response (PP=0.01) but no change in NEFA excursions (P=0.09) compared with controls. Ghrelin infusion increased GH, NEFA and ketone bodies (ANOVA, PP=0.001). Ghrelin also induced a significant (ANOVA, P=0.004) biphasic NEFA response to meals in all the subjects.ConclusionsDespite low circulating ghrelin, gastrectomy subjects maintain a normal metabolic response to fasting, implying that ghrelin plays a minimal role. In contrast, infused ghrelin has significant effects on lipid mobilisation and induces a marked biphasic NEFA response to meals. Hence, ghrelin may play a significant role in meal-related substrate utilisation and metabolic flexibility.

Diabet. Med. 27, 1289–1294 (2010) Abstract Aims At any given time, people with diabetes occupy approximately 10–20% of acute hospital beds. In addition, diabetes is associated with a greater length of stay. Patients undergoing elective procedures occupy approximately 50% of hospital beds. The aim of this 12-month project was to improve the quality of diabetes care for elective inpatients. The primary outcome measure was length of stay. Methods A team was established to improve the quality of care and reduce the length of stay of all patients admitted electively with diabetes. Specific areas of focus were surgical pre-assessment, planning the admission, post-operative care and planning a safe discharge. A retrospective audit of all elective patients with a coded diagnosis of diabetes admitted between June 2008 and June 2009 was performed. Results Comparing the year of the project with the preceding year day-case rates for patients with diabetes increased by 34.8% for diabetes vs. 13.7% for the total hospital population (P for difference = 0.048). There was a significant fall in diabetes length of stay of 0.34 days comparing 2008 and 2009 (P = 0.040). Over the same period, we have shown a smaller reduction in length of stay for all other admissions of 0.08 days (p = 0.039). Conclusion A team specifically employed to focus on elective inpatient diabetes care have a significant impact on length of stay of this patient group with potential cost savings.

The aim of this study was to test the hypothesis that specific referral guidelines are unhelpful because of wide variations in individual clinical practice. A series of representative diabetes case studies were given to a group of primary care, general practice (GP) clinicians for comment. The same cases were given to a group of secondary care clinicians. The suggested management strategies were compared. Overall the results show very little agreement among either primary care or secondary care clinicians for a series of commonly presenting clinical cases. Approximately a third of GP responses for each group of cases suggested primary care management with a third each split between secondary or shared care. Long term follow up of the cases was also disputed but a greater proportion felt that continuing specialist input would not be required. Patient choice was not considered an important factor in deciding the most appropriate place for care. Although specific management strategies would be helpful for service planners, in reality clinicians differ greatly in what they feel should be managed in primary or secondary care. This variability needs to be considered in future planning for long term conditions such as diabetes. Copyright © 2009 John Wiley & Sons, Ltd.

Summary Background: Delivery of diabetes services in resource-poor areas of Africa is difficult. Control is often poor and complications are common. However, adequate robust surveys are uncommon, particularly in remote rural areas. This makes needs assessment difficult and health-care planning impossible. Aim: To accurately assess the glycaemic control and burden of complications in a group of diabetic patients from a remote area of a resource-limited north African country. Design: Prospective cohort study. Methods: Over a 6-week period, all patients attending the diabetic clinic at Mekelle Hospital in northern Ethiopia were intensively assessed, using imported western technology as necessary. Glycated haemoglobin (HbA1c), lipid profile, serum creatinine and urinary albumin–creatinine ratio were measured. Complications were assessed as accurately as possible, including examination of fundi by an ophthalmic specialist, and biosthesiometry for neuropathy. Results: There were 105 patients, mean ( SD) age 41 16 years and diabetes duration 7 6 years. There were 74 (70%) males, and 69 (66%) on insulin. Median body mass index was low at 20.6 kg/m 2 , but mean HbA1c high at 11.3 2.8% (68% had an HbA1c over 10.0%). Cataract (12%), retinopathy (21%), neuropathy (41%) and microalbuminuria (51%) were common; but nephropathy (2%) was rare, as was large vessel disease (6% had peripheral vascular disease, and none had coronary artery disease or cerebrovascular disease). Risk factors such as hypertension (5%) and smoking (2%) were uncommon, and lipid profiles were generally good. Discussion: We conclude that in this severely resource-limited area of North Africa, glycaemic control amongst diabetic patients is very poor. Neuropathy, retinopathy and microalbuminuria are common; but large vessel disease risk factors are beneficial, and macroangiopathy prevalence is low. Scattered populations, shortage of drugs and insulin and lack of diabetes team care are major factors behind these serious issues of diabetic control and complications.

Background Weight loss is difficult to achieve in type 2 diabetes and many therapies are associated with weight gain, an effect attenuated by metformin. We studied the effects of metformin on energy expenditure, appetite and the regulation of PYY and ghrelin in type 2 diabetes. Methods Plasma peptide YY (PYY), ghrelin, resting metabolic rate (RMR), postprandial thermogenesis (PPTG), and appetite ratings were measured at baseline and following a mixed meal in 11 type 2 diabetic subjects treated with diet alone (T2D) and 10 treated with metformin monotherapy (T2MF). The groups were similar in age, gender and adiposity. Results There were no differences in baseline anthropometric, or metabolic variables between the groups. Postprandially, plasma ghrelin fell equally in both groups (23% versus 24.5%, p < 0.05 versus baseline, p = NS between groups) but were reduced for longer in T2MF (below baseline 60–240 min T2MF versus 60–180 min T2D) coincidentally with a prolonged sensation of fullness and suppression of hunger in the metformin-treated group. There were no differences in PYY concentrations, RMR or PPTG. Conclusions Metformin prolongs the postprandial fall in ghrelin concentrations. These effects may prolong the inter-meal interval, thereby decreasing snack intake and daily energy intake, promoting weight loss. Copyright © 2006 John Wiley & Sons, Ltd.

Obesity is a common sequel to hypothalamic tumors and their treatment, but the underlying mechanisms are not fully established.Our objective was to evaluate the role of ghrelin and peptide-YY (PYY) in human hypothalamic obesity.The study took place at a University Medical Center.Subjects included 14 adult patients (six male, eight female) with tumors of the hypothalamic region and 15 healthy controls (six male and nine female) matched for age, body mass index, and percentage of body fat.Plasma ghrelin and total PYY were measured using RIAs after an overnight fast and 15, 30, 60, 120, and 180 min after a mixed meal.We assessed ghrelin, PYY, and appetite ratings.The fall in ghrelin levels after the test meal was similar in the two groups. There was no statistically significant change postprandially in circulating PYY in the patients with hypothalamic damage. Fasting leptin levels and postprandial insulin responses were also similar in the two groups. Patients with hypothalamic damage reported higher hunger ratings at 3 h after the meal (P = 0.01) and a stronger desire to eat at 2 h (P = 0.01) and 3 h (P = 0.02) compared with the control group.Adult patients with structural hypothalamic damage show impaired satiety, but the changes observed in circulating ghrelin and PYY concentrations in response to a test meal do not indicate a central role for these gut hormones in the control of appetite and the pathogenesis of obesity in these patients.

Objective: We investigated the acute responses of plasma adiponectin levels to a test meal in lean and obese subjects. Research Methods and Procedures: We studied 13 lean and 11 obese subjects after a 10-hour overnight fast. Glucose, insulin, and adiponectin concentrations were measured at baseline and 15, 30, 60, 120, and 180 minutes after a fixed breakfast. Results: At baseline, fasting adiponectin concentrations were lower in the obese group vs. the lean group [mean (95% confidence interval): 2.9 (2.1 to 4.1) μg/mL vs. 8.6 (6.5 to 11.3) μg/mL], but rose 4-fold postprandially in the obese group, reaching a peak at 60 minutes [baseline: 2.9 (2.1 to 4.1) μg/mL vs. 60 minutes: 12.1 (8.5 to 17.4) μg/mL; p< 0.0001] and remaining elevated for the remainder of the study. There were no postprandial changes in plasma adiponectin concentrations in lean subjects. Discussion: This increase of adiponectin concentrations in obese individuals might have important beneficial effects on postprandial glucose and lipid metabolism and might be viewed as a mechanism for maintaining normal glucose tolerance in those who are obese and insulin resistant.

Summary Our understanding of the mechanisms involved in bodyweight regulation has increased enormously over the last 15 years. Unfortunately, the same time period has seen a trebling in the prevalence of childhood and adult obesity, the health consequences of which are enormous. While the cause for this increase undoubtedly lies in changes to our social environment, genetic factors strongly influence the response to these environmental changes. This article reviews current understanding of the systems controlling energy homeostasis, including the role of leptin and insulin as adiposity signals; neuropeptide Y and α -melanocyte-stimulating hormone as central mediators of the effects of these signals; and gut hormones such as ghrelin, which stimulates appetite, cholecystokinin, peptide YY 3–36, obestatin and oxyntomodulin in regulating meal size. It is hoped that our improving knowledge of the pathways regulating homeostasis and the dysregulation that occurs in obesity will lead to new, more effective treatments. The principal challenge, however, lies in changing the way we live so that obesity is not inevitable in a large proportion of the population.

In modern semiconductor manufacturing facilities maintenance strategies are increasingly shifting from traditional preventive maintenance (PM) based approaches to more efficient and sustainable predictive maintenance (PdM) approaches. This paper describes the development of such an online PdM module for the endpoint detection system of an ion beam etch tool in semiconductor manufacturing. The developed system uses optical emission spectroscopy (OES) data from the endpoint detection system to estimate the RUL of lenses, a key detector component that degrades over time. Simulation studies for historical data for the use case demonstrate the effectiveness of the proposed PdM solution and the potential for improved sustainability that it affords.

To the Editor: Weight loss appears to be particularly difficult to achieve in patients with type 2 diabetes compared to their non-diabetic counterparts [1]. The hormones peptide YY3–36 (PYY) and ghrelin are implicated in the regulation of appetite, energy balance and the pathophysiology of obesity. PYY is released from L-cells in the gut in response to food [2]. Fasting concentrations are lower and postprandial responses attenuated in obese subjects [3], and infusions of PYY to mimic the postprandial concentrations found in lean subjects reduce appetite and food intake in obese subjects [3, 4], suggesting a potential role in the pathogenesis of obesity. Peripheral administration of ghrelin increases food ingestion [5, 6], and prolonged administration leads to obesity [5, 7]. Circulating ghrelin shows preprandial peaks and postprandial troughs suggesting a role in meal initiation. Against this background, we sought to determine whether type 2 diabetes, independent of obesity status, affected the prandial regulation of PYY and ghrelin in a manner that would explain both the predisposition to increased energy intake and weight gain, and the difficulties in achieving weight loss seen in type 2 diabetes. The study was approved by the local ethics committee and subjects, who were volunteers, gave written informed consent. We studied 11 subjects with diet-controlled type 2 diabetes and 16 control subjects of similar age, sex and BMI. All subjects with diabetes were free from complications and had an HbA1c

A case is presented of a 39-year-old male with Down's Syndrome, who also had type 1 diabetes of 22 years duration. He presented with diabetic ketoacidosis (DKA)-arterial blood pH 7.17, plasma bicarbonate 13.6mmol/l, plasma glucose 26.4mmol/l and urine heavily positive for ketones. He recovered with standard intravenous fluid and insulin treatment, but on the third day of admission developed a swollen left arm (which had not been used for intravenous cannulation). Doppler ultrasound confirmed a left axillary vein thrombosis. This slowly resolved with anticoagulation. Review of the available literature revealed that though arterial thrombosis is a common complication of DKA, venous thromboembolism is surprisingly rare, and there appear to be no previous specific reports of axillary vein thrombosis complicating DKA.

The cost burden of managing type 2 diabetes and its complications could overwhelm the NHS in the next 20 years. The available therapies should be used wisely to conserve resource and maintain health. This article outlines a strategy for use of the available treatments.

Background: There is evidence that reducing blood glucose concentrations, inducing weight loss, and improving the lipid profile reduces cardiovascular risk in people with type 2 diabetes. Objective: We assessed the effect of various diets on glycemic control, lipids, and weight loss. Design: We conducted searches of PubMed, Embase, and Google Scholar to August 2011. We included randomized controlled trials (RCTs) with interventions that lasted $6 mo that compared lowcarbohydrate, vegetarian, vegan, low‐glycemic index (GI), highfiber, Mediterranean, and high-protein diets with control diets including low-fat, high-GI, American Diabetes Association, European Association for the Study of Diabetes, and low-protein diets. Results: A total of 20 RCTs were included (n = 3073 included in final analyses across 3460 randomly assigned individuals). The lowcarbohydrate, low-GI, Mediterranean, and high-protein diets all led to a greater improvement in glycemic control [glycated hemoglobin reductions of 20.12% (P = 0.04), 20.14% (P = 0.008), 20.47% (P , 0.00001), and 20.28% (P , 0.00001), respectively] compared with their respective control diets, with the largest effect size seen in the Mediterranean diet. Low-carbohydrate and Mediterranean diets led to greater weight loss [20.69 kg (P = 0.21) and 21.84 kg (P , 0.00001), respectively], with an increase in HDL seen in all diets except the high-protein diet. Conclusion: Low-carbohydrate, low-GI, Mediterranean, and highprotein diets are effective in improving various markers of cardiovascular risk in people with diabetes and should be considered in the overall strategy of diabetes management. Am J Clin Nutr 2013;97:505‐16.

6. Yang WS, Lee WJ, Funahashi T, et al. Weight reductionincreases plasma levels of an adipose-derived anti-inflamma-tory protein, adiponectin. J Clin Endocrinol Metab. 2001;86:3815–9.7. Holdstock C, Ede´n Engstro¨m B, O¨ hrvall M, Lind L, Sund-bom M, Karlsson FA. Ghrelin and adipose tissue regulatorypeptides: effect of gastric bypass surgery in obese humans.J Clin Endocrinol Metab. 2003;88:3177– 83.8. English PJ, Coughlin SR, Hayden K, Malik IA, Wild-ing JP. Plasma adiponectin increases postprandially inobese, but not in lean, subjects. Obes Res. 2003;11:839–44.9. Peake PW, Kriketos AD, Denyer GS, Campbell LV, Char-lesworth JA. The postprandial response of adiponectin to ahigh-fat meal in normal and insulin-resistant subjects.Int JObes Relat Metab Disord. 2003;27:657– 62.10. Hotta K, Funahashi T, Arita Y, et al. Plasma concentrationsof a novel, adipose-specific protein, adiponectin, in type 2diabetic patients. Ateriosclero Thromb Vasc Biol. 2000;20:1595–9.

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Background: a 76-year-old man presented with transient loss of consciousness associated with swelling of the neck, bruising in the suprasternal notch and an absent left carotid pulse. Blood pressure was equal in both arms and chest x-ray was normal, but computed tomography of the neck and thorax showed dissection and rupture of the thoracic aorta with extensive intra-mediastinal bleeding. Outcome: surgical intervention was inappropriate in this situation and the patient died within 4 hours of presentation. Conclusion: syncope is a common presentation to hospital in older people and its cause may be difficult to elucidate, particularly if the patient is unable to provide a reliable history. Syncope without pain is a rare presentation of aortic dissection and the occurrence of anterior chest wall bruising has not been described previously. Pulse deficits and abnormal chest x-ray findings are often cited as indicative of aortic dissection but are rare manifestations and their absence should not be used to exclude this diagnosis.

Surveys in northern Ethiopia have demonstrated that apparent type 1 diabetes occurs more frequently than elsewhere in Africa and, indeed, in other parts of the world. We therefore investigated in detail a cohort of diabetic patients from this region to clarify the nature of this type of diabetes. All patients attending the diabetic clinic at Mekelle Hospital in the Tigray region of northern Ethiopia were investigated over a 6 week period. Clinical, demographic and anthropometric data were collected, as well as measurements of HbA1c, fasting lipid profile, fasting serum C-peptide and serum markers of beta cell autoimmunity, i.e. islet antigen-2 and GAD antibodies (GADA). Of 105 patients seen, 69 (66%) were on insulin treatment and had been from or close to diagnosis. Their median age and diabetes duration were 30 and 5 years, respectively, with a male excess of 2:1. Median BMI was 20.6 kg/m2. Despite these clinical characteristics suggestive of type 1 diabetes, only 42 of 69 (61%) patients were C-peptide-negative and 35% GADA-positive. Overall, 38 (36%) of the total group (n = 105) had immunological or C-peptide characteristics inconsistent with typical type 1 or type 2 diabetes. The clinical characteristics, local prevalence of undernutrition, and GADA and C-peptide heterogeneity suggest a malnutrition-related form of diabetes. Not all patients in northern Ethiopia with apparent type 1 diabetes appear to have the form of disease seen in Europids; their disease may, in fact, be related to malnutrition.

Aims Diabetes is recognized as a complex, long term, largely asymptomatic condition requiring self management skills, a range of health care professionals and articulated health services. Diabetes Networks have been introduced to provide guidance from people with diabetes and local health professionals with different skills to ensure that diabetes care is well organized, sustainable and delivers quality care. We have considered the role of Diabetes Networks in the English setting. Methods Drawing on studies of health service organization and health policy, we describe the context in which diabetes commissioning is currently occurring in England, the role of Diabetes Networks and key components for an effective Diabetes Network. Results We have identified that Diabetes Networks are not currently mandatory and discovered policy approaches that are likely to work against safe, timely, integrated approaches to diabetes services with potentially harmful impacts on people with diabetes in the future. Practice Based Commissioning, where it sidelines Diabetes Networks, is a particular concern. We have identified key components of Diabetes Networks including explicit frameworks for leadership, membership, funding, decision making, communication and action. Conclusions Diabetes is a condition requiring collaboration between all involved. Diabetes Networks include patients and all relevant health professionals and should dictate what and how diabetes care should be commissioned within the local health economy.

In the resource-poor areas of the tropics, diabetic patients requiring insulin are often treated with once-daily injections of intermediate-acting insulin. Glycaemic control on this regime is usually poor. We trialled a simple change to twice-daily insulin (same total daily dose, two-thirds given in morning, and one-third in evening) in a group of 20 Ethiopian diabetic patients treated in this way. Nurse support and contact, and self-glucose monitoring were not available. After three months, the haemoglobin Alc (HbAlc) had improved from 10.5 ± 1.8 to 8.0 ± 1.5% (P < 0.001). No improvement occurred in the 20 control patients who remained on once-daily insulin. Among the twice-daily insulin group there was a small increase in weight and mild hypoglycaemic episodes. However, all patients were very satisfied and wished to continue the new system. We conclude that a simple change from once- to twice-daily insulin, without monitoring or support, can lead to a significant improvement in the overall glycaemic control, and is suitable for resource-limited tropical countries.

To examine the effects of ghrelin on appetite and energy expenditure in lean, obese and postgastrectomy subjects.A randomized, double-blind, placebo-controlled study.Nine lean subjects (mean body mass index (BMI) 23.5+/-3 kg/m(2)) and nine morbidly obese subjects (mean BMI 51.4+/-10 kg/m(2)) and eight postgastrectomy subjects (mean BMI 22.4+/-1.0 kg/m(2)).Subjects were infused with either intravenous ghrelin (5 pmol kg(-1) min(-1)) or saline over 270 min. They were given a fixed energy breakfast followed by a free buffet lunch towards the end of the infusion.Visual analogue scales were used to record hunger and energy expenditure was measured by indirect calorimetry.Ghrelin increased energy intake at the buffet lunch in lean subjects (a 41% increase, P0.01) and obese subjects (35% increase, P=0.04) but not in postgastrectomy subjects. Lean subjects showed a characteristic preprandial rise and postprandial fall in hunger scores, which was exaggerated by ghrelin infusion. Obese subjects showed little variation in hunger scores, but a 'lean-type' pattern was restored when given exogenous ghrelin. Ghrelin had no effect on resting metabolic rate but did increase respiratory quotient (RQ) in obese subjects. Ghrelin also increased RQ variability over time in all three groups (ANOVA, P0.001).Hunger scores are abnormal in the obese, perhaps because of impaired ghrelin secretion. The effect of ghrelin in restoring normal hunger profiles in the obese suggests causality, confirming an important role in eating behaviour. Ghrelin also increases RQ in obese humans and increased RQ variability in all groups. This suggests that ghrelin regulates substrate utilization and may promote metabolic flexibility.

Adiponectin, a hormone produced and secreted by adipocytes, is present in circulation in high circulating concentrations, suggesting an important physiological role. An indirect regulator of glucose metabolism, adiponectin increases insulin sensitivity, improves glucose tolerance and inhibits inflammation. Plasma adiponectin relates inversely to adiposity and, importantly, reflects the sequelae of accumulation of excess adiposity. The role of adiponectin in adults has been explored in detail. Studies in children are now available and, given the increasing rates of childhood obesity, it is important to establish the role of adiponectin in mediating insulin resistance and cardiovascular disease in this age group. This paper reviews the regulation of adiponectin, its effect on body mass, glucose metabolism and cardiovascular risk in infants, children and adolescents. It demonstrates clear links between adiponectin and features of the metabolic syndrome in obese children and adolescents. However, adiponectin's role as a predictor of metabolic dysfunction in healthy, normal-weight youngsters is less clear.

Familial partial lipodystrophy (FPLD) and obesity are both associated with increased risks of type 2 diabetes and cardiovascular disease. Although adipokines have been implicated, few data exist in subjects with FPLD; therefore we investigated a family with FPLD due to a lamin A/C mutation in order to determine how abnormalities of the plasma adipokine profile relate to insulin resistance and the metabolic syndrome.Plasma levels of adiponectin, leptin, resistin, IL-1beta, IL-6 and TNF-alpha in 30 subjects (ten patients, 20 controls) were correlated with indices of metabolic syndrome.Compared with controls, FPLD patients had significantly lower plasma levels of adiponectin (3.7+/-1.0 in FDLP cases vs 7.1+/-0.72 mug/ml in controls, p=0.02), leptin (1.23+/-0.4 vs 9.0+/-1.3 ng/ml, p=0.002) and IL-6 (0.59+/-0.12 vs 1.04+/-0.17 pg/ml, p=0.047) and elevated TNF-alpha (34.8+/-8.1 vs 13.7+/-2.7 pg/ml, p=0.028), whereas IL-1beta and resistin were unchanged. In both groups, adiponectin levels were inversely correlated with body fat mass (controls, r=-0.44, p=0.036; FDLP, r=-0.67, p=0.025), insulin resistance (controls, r=-0.62, p=0.003; FDLP, r=-0.70, p=0.025) and other features of the metabolic syndrome. TNF-alpha concentrations were positively related to fat mass (controls, r=0.68, p=0.001; FDLP, r=0.64, p=0.048) and insulin resistance (controls, r=0.86, p=0.001; FDLP, r=0.75, p=0.013). IL-6, IL-1beta and resistin did not demonstrate any correlations with the metabolic syndrome in either group.Low adiponectin and leptin and high TNF-alpha were identified as the major plasma adipokine abnormalities in FPLD, consistent with the hypothesis that low adiponectin and high TNF-alpha production may be mechanistically related, and perhaps responsible for the development of insulin resistance and cardiovascular disease in FPLD.

Objective: To determine whether impaired cell membrane permeability exists in critically ill patients with “sick cell” type hyponatraemia. Design and methods: A 36 year old male patient was identified in an intensive care unit (ICU) with liver disease and multi-organ failure. His initial serum sodium (Na) was 101 mmol/L and osmolar gap + 35 mmol/L. A flow cytometric system was used to assess lymphocyte membrane integrity using fluorescein diacetate (FDA) and propidium iodide (PI). Following this, similar studies were carried out in 17 hyponatraemic (Na 136 mmol/L) ICU patients. Results: Flow cytometry in the index patient showed two clear populations of cells—one was normal (with identical characteristics to a healthy control) and the other had dysfunctional cell membrane integrity. The extended patient series, however, revealed only 2 other patients with similar flow cytometric patterns—one hyponatraemic and one normonatraemic. Conclusions: Cell membrane studies in the index patient demonstrated supportive evidence for the “sick cell syndrome” in critically ill patients. The extended series revealed that 3/37 (8%) had this abnormality, which was however not consistently associated with hyponatraemia.

A 64-year-old lady with type 2 diabetes and a non-resolving right foot ulcer, had an indium-111 labelled white cell scan (indium-111 WCS) to investigate the possibility of underlying osteitis. The scan suggested the possibility of infective thrombophlebitis. Unknown to the clinical team who requested the scan and the radiologist who performed it, the lady was admitted to hospital 2 days following the procedure with cellulitis and septic thrombophlebitis in the right leg. There is only one previous report in the literature of septic thrombophlebitis being diagnosed in this way. Perhaps indium-111 WCS has something to offer in the diagnosis of this condition and in determining those who require antibiotic treatment.

Diabetic ketoacidosis, hyperglycaemic hyperosmolar state, and lactic acidosis represent three of the most serious acute complications of diabetes. There have been some advances in our understanding of the pathogenesis of these conditions over the last three decades, together with more uniform agreement on their treatment and innovations in technology. Accordingly their incidence, morbidity, and mortality are decreasing, but at rates that fall short of our aspirations. Hyperglycaemic crises in particular remain an important cause of morbidity and mortality in diabetic populations around the world. In this article, understanding of these conditions and advances in their management, and the available guidelines for their treatment, are reviewed. As far as is possible, the recommendations are based on clear published evidence; failing that, what is considered to be a common sense synthesis of consensus guidelines and recommendations is provided.

Introduction Ghrelin is the natural ligand of the growth hormone secretagogue receptor (GHS-R) and potently stimulates GH release in humans. Ghrelin is found in the hypothalamus, but most circulating ghrelin is derived from the stomach. Ghrelin stimulates food intake but circulating levels are low in obesity. We hypothesized that GH deficiency (GHD) might be associated with increased circulating ghrelin concentrations as a result of low GH levels. We therefore measured circulating ghrelin concentrations, leptin and body composition in subjects with GHD and healthy controls. Methods Subjects with GHD (n = 18) were compared to healthy control subjects (n = 18), matched for body mass index (BMI). They underwent assessment of body composition [waist circumference, BMI and percentage body fat (using bioimpedance)]. Plasma ghrelin, leptin, insulin, GH and IGF-1 were measured in the fasting state. Plasma ghrelin was measured using a specific radioimmunassay, and the other hormones using commercially available assays. Results The groups were well-matched for BMI (GHD vs. control; 32.9 +/- 10.8 vs. 31.3 +/- 11.7, P = ns) and waist circumference (GHD vs. control; 102.9 +/- 20.0 vs. 99.8 +/- 25.2, P = ns), but percentage body fat (GHD vs. control; 37.0 +/- 9.1 vs. 29.4 +/- 13.0, P = 0.06) tended to be higher in the GHD group. As expected, IGF-1 was lower in GHD (GHD vs. control; 12.5 +/- 6.8 vs. 19.2 +/- 5.8 nmol/l, P = 0.003). Ghrelin [GHD vs. controls; geometric mean (95% CI); 828.8 (95% CI 639.9-1074.2) vs. 487.9 (95% CI 297.2-800.2) pmol/l] and leptin [GHD vs. controls; 13.2 (95% CI 6.6-26.5) vs. 7.9 (95% CI 3.7-16.9) ng/ml] were similar in the two groups. Plasma ghrelin correlated inversely with waist circumference and waist hip ratio in GHD subjects (r = -0.6, P = 0.02) but not with IGF-1 or GH concentrations. There was no significant correlation in the control subjects. Conclusion Circulating ghrelin concentrations are influenced by body fat distribution, but not by levels of either GH or IGF-1. However, given that obesity is associated with reduced ghrelin concentrations and that GHD is commonly associated with increased body fat, it is possible that these two opposing influences on circulating ghrelin levels result in normal concentrations in subjects with GHD.

We describe a 71-year-old female diabetic patient with sensory distal lower limb neuropathy, who presented with painless swelling and erythema of the left ankle and lower shin. Diagnoses of cellulitis, deep venous thrombosis and Charcot neuroarthropathy were considered, but eventually a magnetic resonance scan showed complete rupture of the Achilles tendon. There was no history of trauma, and the absence of pain was presumed to be due to her dense sensory neuropathy. Copyright © 2007 John Wiley & Sons.

Ethnic minority groups have been and remain underrepresented in the British political system. However, we know little about how white immigrant origin groups—who share outgroup status based on non-native history, but differ to ethnic minority groups in terms of not having minority status—compare. Further, contemporary representational study also must concern itself with the quality, not just presence, of representation provided. This research therefore longitudinally compares the access to parliamentary roles for ethnic minority, white immigrant, and white British MPs. It finds that visibility of non-native status holds back descriptive representation—based on both appearance and non-British sounding names.