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This study applies Tribal Critical Race Theory in the Native business domain to analyze six distinct Native Nations’ approaches to for-profit enterprises by and through Native stories and voices. Specifically, Native management and legal scholars conducted a qualitative study asking Native American business leaders 24 open-ended questions pertaining to their experience in Native Nations Social Enterprise in order to critically analyze legal, organizational, business, social and cultural practices in this unique setting. Based on our findings, we build a model for Native Nations’ Social Enterprise as embedded in and affected by dominant culture’s legal, organizational and business norms, and through Native cultural values toward social and environmental sustainability. Framed using the tenets of Tribal Critical Race Theory, the model challenges Nation building as filtered through a non-Native legal, organizational and business economic lens, as assimilative forces that constrain Nation building. It conveys the root concerns toward interconnectedness of the People, Native culture, the environment, past and future generations, but these are not evidenced by creative Native adaptations. By exposing contradictory structures, norms and values, our analysis may enable greater transformation to enhance honoring past generations and encourage adaptive alternative Native enterprises.

This article considers the phenomenon of illustrators digitally mimicking traces of the handmade as ornament. It will explore whether these decorative tendencies are Adolf Loos' backward or degenerative tendency, or a generous contribution to our visual environment. It will ask why illustrators falsify the smudges, spills, textures and shadows of paper-based work within the digital workspace, what is gained and lost by doing so, and for whom? These questions will be explored in relation to interviews with two contemporary editorial illustrators and their work, to unpick the professional benefits of the phenomenon, coupled with a foray into theoretical perspectives on ornament. In this regard, the article will consider the benefit of treating ornament as labour, and also whether illustration is suffering from Herbert Read's horror vacui, in order to understand what happens when these terrifying empty spaces within images are filled with introduced artefacts. The discussion will also take skeuomorphism into account to explore the phenomenon, which then raises questions concerning illustration's 'usability'. The article draws upon wildly different perspectives and practices from other fields as it seeks to consider the pleasures and pitfalls of a richly-ornamented composition, and ultimately argues that making 'noise' can be seen as a generous, temporal and critical act.

Introduction: Medical associations and medicolegal bodies are urging for increased chaperone use by physicians during intimate physical examinations in clinical practice (such as breast or pelvic examinations). However, widespread chaperone use is limited by factors such as staff availability and financial considerations. Presently, there is a scarcity of information available regarding the cost of hiring a dedicated chaperone. This study investigates the cost of hiring a chaperone and its financial implications for a physician's clinical practice. Materials and Methods: Using data from the Government of Canada website, the range of salary rates for clinic staff who can act as a chaperone in Canada was analyzed. The cost of hiring a chaperone was estimated to be in the range between the cost of hiring a minimum-wage worker and a nurse (the highest-paid hired medical office staff). Obstetrics and Gynecology as well as Plastic Surgery urban community practices were consulted regarding the costs of operating a clinic. Results: The approximate annual income for a minimum-wage worker in Canada is $29,250 CAD. Registered nurses earn on average $72,783.75 CAD per year. The cost of operating a private clinic practice with one staff member in Canada is on average $102,500 CAD per year. Thus, hiring an additional full-time chaperone could increase clinic expenses by approximately 49% per year, bringing the clinic cost to approximately $153,517 CAD per year. For part-time employment, the annual cost of hiring a chaperone is approximately $10,203 CAD for each day/week of employment. Conclusion: In terms of financial considerations, hiring a chaperone can increase clinic expenses by approximately one-and-a-half times. The findings of this study provide an important reference for physicians and may assist with the decision to employ chaperones in clinical practice.

This article uses images from the visual essays produced for Plume of Feathers, an audio-visual project, to examine the notion of ‘reflective nostalgia’ as an attitude towards meaning-making within image creation, in particular illustration that can counter certain political uses of images that present a restorative–nostalgic world view. The project at the core of the article is concerned with the decline of public houses and their social function in the UK. However, the image of the pub is embroiled within the visual rhetoric related to the UK’s (2016) Brexit referendum. This article explores the ways in which the illustrated image can provide a different view of the pub that reveals the conceptual construction of the notion of ‘pub’ and offers a critical alternative. The constructed nature of the illustrated image is then explored for its potential to visualize the past differently, following Svetlana Boym’s proposal of reflective nostalgia in The Future of Nostalgia (2001) in order to address problems in the present. The article proposes that reflective nostalgia’s utility as a critical tool lies in its consideration of the key role played by the surface of the image, through the material signifiers of age. As illustrators, embracing these nostalgic triggers when making images allows the viewer to reconnect to the past with critical distance, thereby returning politics to the surface of the image, something that Fredric Jameson saw in Postmodernism, Or the Cultural Logic of Late Capitalism (1991) as recuperated and rendered politically neutral. Illustration is therefore cast as a meaning-making practice that shapes the world it operates within, with the article suggesting that by making nostalgic images, illustrators can exercise their agency as agitators.

The glial cell line-derived neurotrophic factor (GDNF) and its canonical receptor Ret can signal both in tandem and separately to exert many vital functions in the midbrain dopamine system. It is known that Ret has effects on maintenance, physiology, protection and regeneration in the midbrain dopamine system, with the physiological functions of GDNF still somewhat unclear. Notwithstanding, Ret ligands, such as GDNF, are considered as promising candidates for neuroprotection and/or regeneration in Parkinson's disease, although data from clinical trials are so far inconclusive. In this review, we discuss the current knowledge of GDNF/Ret signaling in the dopamine system in vivo as well as crosstalk with pathology-associated proteins and their signaling in mammals.

Diacylglycerol kinase ε (DGKε) catalyzes the phosphorylation of diacylglycerol, producing phosphatidic acid. DGKε demonstrates exquisite specificity for the acyl chains of diacylglycerol. This contributes to the enrichment of particular acyl chains within the lipids of the phosphatidylinositol cycle. Phosphatidylinositol is highly enriched with 1-stearoyl-2-arachidonoyl, which is important for maintaining cellular health. Dysregulation of DGKε perturbs lipid signaling and biosynthesis, which has been linked to epilepsy, Huntington's disease, and heart disease. Recessive loss-of-function mutations in the DGKε gene cause atypical hemolytic uremic syndrome. Because DGKε has never been purified, little is known about its molecular properties. We expressed human DGKε and a truncated version lacking the first 40 residues (DGKεΔ40) and purified both proteins to near homogeneity using nickel affinity chromatography. Kinase activity measurements showed that both purified constructs retained their acyl chain specificity for diacylglycerol with an activity level comparable to that of N-terminally FLAG epitope-tagged forms of these proteins expressed in COS7 cells. Both constructs lost activity upon being stored, particularly upon freezing and thawing, which was minimized by the addition of glycerol. Circular dichroism revealed that DGKε and DGKεΔ40 both contain significant amounts of α-helical and β structure and exhibit biphasic thermal denaturations. The loss of secondary structure upon heating was irreversible for both constructs, with relatively little effect of added dioleoylphosphatidylcholine. The addition of 50% glycerol stabilized both constructs and facilitated refolding of their secondary structures after heating. This is the first successful purification and characterization of DGKε's enzymatic and conformational properties. The purification of DGKε permits detailed analyses of this unique enzyme and will improve our understanding of DGKε-related diseases.

Signaling events at membranes are often mediated by membrane lipid composition or membrane physical properties. These membrane properties could act either by favoring the membrane binding of downstream effectors or by modulating their activity. Several proteins can sense/generate membrane physical curvature (i.e. shape). However, the modulation of the activity of enzymes by a membrane's shape has not yet been reported. Here, using a cell-free assay with purified diacylglycerol kinase ɛ (DGKɛ) and liposomes, we studied the activity and acyl-chain specificity of an enzyme of the phosphatidylinositol (PI) cycle, DGKɛ. By systematically varying the model membrane lipid composition and physical properties, we found that DGKɛ has low activity and lacks acyl-chain specificity in locally flat membranes, regardless of the lipid composition. On the other hand, these enzyme properties were greatly enhanced in membrane structures with a negative Gaussian curvature. We also found that this is not a consequence of preferential binding of the enzyme to those structures, but rather is due to a curvature-mediated allosteric regulation of DGKɛ activity and acyl-chain specificity. Moreover, in a fine-tuned interplay between the enzyme and the membrane, DGKɛ favored the formation of structures with greater Gaussian curvature. DGKɛ does not bear a regulatory domain, and these findings reveal the importance of membrane curvature in regulating DGKɛ activity and acyl-chain specificity. Hence, this study highlights that a hierarchic coupling of membrane physical property and lipid composition synergistically regulates membrane signaling events. We propose that this regulatory mechanism of membrane-associated enzyme activity is likely more common than is currently appreciated.

In Essouk-Tadmekka Sam Nixon and a team of scholars present the first archaeological exploration of the southern Saharan town of Essouk-Tadmekka, in early Islamic times an important market centre on the trans-Saharan camel-caravan routes linking the Mediterranean and West Africa.

Purpose: We aimed to examine the association between intake of different subgroups of dairy products and blood pressure and incident hypertension 10 years later, adjusting for confounding factors. Methods: We studied 1,750 British men and women from the 1946 British birth cohort from 1989 to 1999 (age 43 and 53 years, respectively). Diet was assessed by 5-day food diaries using photographs in the estimation of portion size. Systolic (sbp) and diastolic (dbp) blood pressure and prevalent hypertension were assessed at age 43 and 53 years. Linear regression and logistic regression were used to examine 10-year blood pressure levels and incident hypertension by baseline dairy intake. Results: There was a weak non-significant trend of a protective effect of total dairy intake on blood pressure and incident hypertension, but no evidence for a dose-response relationship (OR for incident hypertension: 0.88 (95% CI 0.68;1.14) 2nd vs. 1st tertile and 0.93 (95% CI 0.72;1.18) 3rd vs. 1st tertile). Higher intake of low-fat and fermented dairy was linked to a higher sbp but in a nonlinear manner. Adjustment for other dietary factors, health behaviours and BMI attenuated these associations. Conclusions: Total dairy intake and specific dairy subgroups were not associated with blood pressure and incident hypertension among a representative sample of British adults after adjustment for confounding factors

IQ in early adulthood has been inversely associated with risk of the metabolic syndrome in midlife. We tested this association in the British 1946 birth cohort, which assessed IQ at age eight years and ascertained the metabolic syndrome at age 53 years based on modified (non-fasting blood) ATPIII criteria. Childhood IQ was inversely associated with risk of the metabolic syndrome, but this association was almost entirely mediated by educational attainment and achieved occupational social class. This may be consistent with a pattern where childhood IQ is strongly associated with outcomes that reflect neurological disorder, such as the degenerative dementias, but less so with common chronic physical diseases of ageing.

Background: Genetic variants of the two adjacent genes, IL13 and IL4 have frequently been reported as being associated with susceptibility to atopy and asthma, both in adults and children, and some studies also suggest association with lung function and chronic obstructive pulmonary disease. Methods: In this study, we examined for the first time the effect of these variants in 2918 adults in a longitudinal birth cohort, the British National Survey of Health and Development, where there are extensive life style, developmental and environmental data. We examine two IL13 single nucleotide polymorphisms (SNPs) IL13 rs20541 (R110Q) and rs1800925 (−1024C>T) and one IL4 SNP, rs2070874 (−33C>T) with likely function. Results: We show that IL13 rs20541 and rs1800925 are each significantly associated with self-reported asthma and allergy, and that this association is not confounded by any of the known developmental and environmental risk factors for asthma and atopy, including in particular place of birth. IL13 rs20541 does however act as a confounder for the IL13 rs1800925 associations, meaning that there is no statistical support for rs1800925 having an independent effect. There is nevertheless evidence for interaction between smoking and rs1800925, with allergy as outcome. None of the SNPs showed association with measures of lung function, nor any interaction with the effect of smoking on lung function. Conclusion: In a longitudinal population cohort we have established a role for polymorphism of IL13 in determining susceptibility to both atopy and asthma.

Objective: To assess the associations between parental age at birth of first child and coronary heart disease (CHD) risk factors in men and women. To investigate whether the associations are explained by childhood predictors of age at parenthood or adult lifestyle factors related to child rearing. Methods: Data from 2540 men and women, with CHD risk factors measured at age 53 years, from a birth cohort study of individuals born in Britain in 1946 (Medical Research Council National Survey of Health and Development) and followed up regularly throughout life, were analysed. Results: Younger age at birth of first child in both men and women was associated with poorer mean body mass index (BMI), waist–hip ratio, blood pressure (BP), high-density lipoprotein cholesterol, triglyceride and glycated haemoglobin levels. Mean BMI decreased from 28.0 kg/m 2 (95% CI 27.2 to 28.8) in the teenage motherhood group to 26.8 kg/m 2 (25.9 to 27.7) in the oldest motherhood group (⩾30 years). For men, the equivalent mean values were 28.5 kg/m 2 (27.3 to 29.8) and 27.1 kg/m 2 (26.7 to 27.6). Associations with adiposity, lipid measures and glycated haemoglobin were largely explained by childhood antecedents and adult social and lifestyle variables. Associations with BP remained robust to adjustment: systolic blood pressure remained highest in teenage parents (7.5 mmHg (1.0 to 13.9) difference in women and 8.6 mmHg (0.4 to 16.8) difference in men between the youngest and the oldest parenthood groups) Conclusions: Lifestyle factors, rather than the biological impact of pregnancy, explain the relationship between age at motherhood and CHD risk factors. Family-based lifestyle interventions targeted at young parents may improve their future CHD risk.

Objective:To review antiviral management of influenza and discuss recent developments in antiviral resistance.Data Sources:Literature retrieval was accessed through MEDLINE/PubMed (1977–February 2007) using the terms influenza, resistance, adamantanes, and neuraminidase inhibitors, treatment, and prevention. In addition, reference citations from identified publications were reviewed.Study Selection and Data Extraction:All articles in English identified from the data sources were evaluated.Data Synthesis:Infection with influenza is associated with 36,000 deaths and more than 200,000 hospitalizations in the US each year and results in a large economic burden on society. We reviewed 7 trials describing management of influenza; the results showed that 92% of influenza cases demonstrated adamantane resistance in 2005. Selection of treatment for influenza with a neuraminidase inhibitor should be based on patient preference, past medical history, and managed care restrictions since one agent has not demonstrated superiority. Early initiation of treatment, within 12 hours of symptom onset (compared with 48 h), has resulted in illness being shortened by more than 3 days. Conclusions shown in the trials reviewed here regarding the consequences of increasing incidence of influenza A resistance include: viral surveillance cultures are important, influenza has a significant global impact, and inappropriate use of antiinfective agents results in local and global resistance.Conclusions:Therapeutic options for the management of influenza include the neuraminidase inhibitors, zanamavir and oseltamivir. Unfortunately, new classes of antiviral drugs for influenza will not be forthcoming in the near future. Adamantane resistance is now commonly demonstrated in influenza. At this time, efforts should be made to minimize patient risk for infection.

Before the current Ebola epidemic in West Africa, there were few documented cases of symptomatic Ebola patients traveling by commercial airline, and no evidence of transmission to passengers or crew members during airline travel. In July 2014 two persons with confirmed Ebola virus infection who were infected early in the Nigeria outbreak traveled by commercial airline while symptomatic, involving a total of four flights (two international flights and two Nigeria domestic flights). It is not clear what symptoms either of these two passengers experienced during flight; however, one collapsed in the airport shortly after landing, and the other was documented to have fever, vomiting, and diarrhea on the day the flight arrived. Neither infected passenger transmitted Ebola to other passengers or crew on these flights. In October 2014, another airline passenger, a U.S. health care worker who had traveled domestically on two commercial flights, was confirmed to have Ebola virus infection. Given that the time of onset of symptoms was uncertain, an Ebola airline contact investigation in the United States was conducted. In total, follow-up was conducted for 268 contacts in nine states, including all 247 passengers from both flights, 12 flight crew members, eight cleaning crew members, and one federal airport worker (81 of these contacts were documented in a report published previously). All contacts were accounted for by state and local jurisdictions and followed until completion of their 21-day incubation periods. No secondary cases of Ebola were identified in this investigation, confirming that transmission of Ebola during commercial air travel did not occur.

The Beck Depression Inventory (BDI) is widely used to assess depression in chronic pain despite doubts about its structure and therefore its interpretation. This study used a large sample of 1947 patients entering chronic pain management to establish the structure of the BDI. The sample was randomly divided to conduct separate exploratory (EFA) and confirmatory factor analyses (CFA). EFA produced many satisfactory two-factor solutions. The series of CFA generated showed reasonable fit for ten of those solutions. All included a first factor identified as negative view of the self (items: failure, guilt, self-blame, self-dislike, punishment and body image change), and a second factor identified as somatic and physical function (items: work difficulty, loss of appetite, loss of libido, fatigability, insomnia and somatic preoccupation). The remaining items (suicidal ideation, social withdrawal, dissatisfaction, sadness, pessimism, crying, indecisiveness, weight loss, irritability) loaded infrequently or not at all in the CFA solutions. They did not form a coherent factor but comprised items associated with negative affect. When compared with published data from samples of depressed patients drawn from mental health settings the mean item scores for items reflecting the negative view of the self were consistently statistically lower that that observed in samples; there was no consistent difference between the samples on the items reflecting somatic and physical function; but the mean scores for the remaining affect items were significantly greater in the mental health samples. This version of depression is strikingly different from the psychiatric model of depression (e.g. DSM-IV or ICD-10), which is primarily defined by affective disturbance, and secondarily supported by cognitive and somatic symptoms. The finding is consistent with a reconsideration of what constitutes depression in the presence of chronic pain. It also has important clinical implications: it may provide a way to distinguish depressed patients with typical cognitive biases, who require specific treatment for depression alongside pain management.

BackgroundMental wellbeing, conceptualised as positive affect, life satisfaction and realisation of needs that contribute to psychological growth, captures more than the absence of mental ill health. Several nations now aim to monitor and improve mental wellbeing. Whilst many studies document associations between adverse childhood experiences and mental disorders in adulthood, possible links between childhood experiences and adult mental wellbeing have so far received less attention.MethodsUsing data from 1976 men and women in the MRC National Survey for Health and Development, we investigated prospective associations between childhood socioeconomic and psychosocial environments and the Warwick Edinburgh Mental Wellbeing Scale, designed to capture both hedonic and eudaimonic facets of wellbeing, at age 60-64.ResultsWhilst there was no evidence that childhood socioeconomic circumstances were related to later wellbeing independently of other childhood experiences, elements of childrearing and parenting, parental health and adjustment, and childhood illness were related. More advantaged socioeconomic position was associated with greater wellbeing but this did not explain the links between these childhood exposures and adult wellbeing, suggesting alternative explanatory pathways should be considered.ConclusionsChildhood illness and family psychosocial environment are associated with mental wellbeing in early older age, with effects sizes that are larger or comparable to socioeconomic circumstances in adulthood. Initiatives to improve the nation’s mental wellbeing that include programmes targeted to supporting families and children may additionally have benefits that continue into older age.

To assess the relationship between patterns of overweight during adulthood and systolic (SBP) and diastolic (DBP) blood pressure (BP) at age 53.Data are from 3035 male and female participants of the 1946 British birth cohort study. Body mass index (BMI) was obtained at ages 20, 26, 36, 43 and 53 years. Censored regression models accounting for medication were used to investigate associations of BP at 53 years with overweight (BMI25 kg/m) at each age, age at first overweight and conditional weight gain. Sex interactions were also examined.Overweight at all ages except for 20 years in men was positively associated with BP at 53 years. After adjusting for current BMI, only overweight at age 43 contained additional information on BP in men. Men who were overweight at age 26 had a SBP 8.7 mmHg higher [95% confidence interval (CI) 4.4-13.0] than those first overweight at 53 years. Similar patterns but smaller associations were seen in women [P(interaction)0.001). All periods of adult weight gain (26-36, 36-43, 43-53 years) were associated with a higher BP. BMI tracked strongly through adulthood, the BMI at 53 years in men first overweight at 26 was 30.9 kg/m (95% CI 30.5-31.4) compared to 26.4 (95% CI 26.3-26.6) in those first overweight at age 53.Early adult overweight and all periods of adult weight gain irrespective of earlier BMI were associated with higher BPs. This highlights the importance for later health of preventing overweight in early adulthood.

We attempted to clarify the strength and nature of the association between personality and smoking status in early and middle adulthood, using a longitudinal study design. Data from the Medical Research Council National Survey of Health and Development, based on a stratified sample of all single, legitimate births occurring in England, Wales, and Scotland in one week of March 1946 (N = 5,362), were analyzed using generalized estimating equations methods to account for the correlation between the smoking status variables for the same individual over time. The unadjusted estimates indicated that the odds of being a current smoker increased with higher personality score for both extraversion (p

OBJECTIVE. To assess the Pediatric Risk of Mortality (PRISM, PRISM III-12, and PRISM III-24) systems and the Pediatric Index of Mortality (PIM and PIM2) systems for use in comparing the risk-adjusted mortality of children after admission for pediatric intensive care in the United Kingdom. METHODS. All PICUs in the United Kingdom were invited to participate. Predicted probability of PICU mortality was calculated using the published algorithms for PIM, PIM2, and PRISM and compared with observed mortality. These scores, along with PRISM III-12 and PRISM III-24, whose algorithms are not published, were optimized for the United Kingdom. RESULTS. Of 26 PICUs in the United Kingdom, 22 (85%) were recruited, and sufficient prospective data were collected from 18 (69%) units on 10197 (98%) of 10385 admissions between March 2001 and February 2002. All published tools were found to have poor calibration but provided good discriminatory power. After estimation of UK-specific coefficients, only PIM2, PRISM III-12, and PRISM III-24 had satisfactory calibration. All models provided good discriminatory power. Funnel plots for all of the recalibrated models indicated that the risk-adjusted mortality for all units was consistent with random variation. CONCLUSIONS. PIM2, PRISM III-12, and PRISM III-24 all were found to be suitable for use in a UK PICU setting. All tools provided similar conclusions in assessing the distribution of risk-adjusted mortality in UK PICUs. It now is important that these tools be used to monitor outcome and improve the quality of pediatric intensive care within the United Kingdom.

Background Maintaining wellbeing in later life is a key component of healthy ageing. Identifying modifiable factors associated with positive mental wellbeing in later life is thus an important priority, especially in the context of global population ageing. We aimed to investigate associations of monitored free-living and self-reported leisure time physical activity (LTPA) with positive mental wellbeing in early old age. Methods 1976 men and women from the MRC National Survey of Health and Development whose positive mental wellbeing and physical activity had been assessed at age 60–64 years were included in analyses. Wellbeing was assessed using the Warwick-Edinburgh Mental Wellbeing Scale (WEMWBS). Continuous free-living activity was assessed by combined heart rate and movement sensors worn for 2–5 days and LTPA was self-reported. Using linear regression models we tested the associations of five parameters of physical activity (physical activity energy expenditure (PAEE, kJ/kg/day), time spent in activities of light-moderate (1.5–3 metabolic equivalents (METs)) and moderate-vigorous (>3 METs) intensity, participation in LTPA (i.e. exercise and sports) in the previous month and number of hours/week spent walking for leisure) with WEMWBS scores. Adjustments were made for sex, long-term limiting illness, socio-economic circumstances, smoking status and personality traits. Results Participation in LTPA and more time spent walking for leisure were both associated with higher WEMWBS scores and these associations remained after adjustment for potential confounders. In fully-adjusted models: those people who walked for leisure for one hour or more per week had mean WEMWBS scores 1.58 (95% CI 0.57–2.59) higher than those that reported no walking for leisure; and those people who reported participating in LTPA at least 5 times per month had mean WEMWBS scores 1.60 (95% CI 0.61–2.59) higher than those that reported no LTPA. When these analyses were rerun using multiply imputed datasets to allow for missing data on covariates conclusions remained the same. There was no evidence of associations between any of the free-living physical activity measures (i.e. PAEE and time spent in different intensities of activity) and WEMWBS scores in sex-adjusted models. Conclusion Our results suggest that specific types of volitional activity (namely, leisure time physical activity and walking for leisure) are more beneficial for mental wellbeing in early old age than incidental free-living physical activity. Our finding of an association between walking and positive mental wellbeing provides further justification, alongside evidence of its positive impact on physical health and function, for its promotion among older adults.

IntroductionThe authors examined how body mass index (BMI) across life is linked to the risk of midlife knee osteoarthritis (OA), testing whether prolonged exposure to high BMI or high BMI at a particular period has the greatest influence on the risk of knee OA.MethodsA population-based British birth cohort of 3035 men and women underwent clinical examination for knee OA at age 53 years.Heights and weights were measured 10 times from 2 to 53 years. Analyses were stratified by gender and adjusted for occupation and activity levels.ResultsThe prevalence of knee OA was higher in women than in men (12.9% (n=194) vs 7.4% (n=108)). In men, the association between BMI and later knee OA was evident at 20 years (p=0.038) and remained until 53 years (OR per z-score 1.38 (95% CI 1.11 to 1.71)). In women, there was evidence for an association at 15 years (p=0.003); at 53 years, the OR was 1.89 (95% CI 1.59 to 2.24) per z-score increase in BMI. Changes in BMI from childhood in women and from adolescence in men were also positively associated with knee OA. A structured modelling approach to disentange the way in which BMI is linked to knee OA suggested that prolonged exposure to high BMI throughout adulthood carried the highest risk and that there was no additional risk conferred from adolescence once adult BMI had been accounted for.ConclusionThis study suggests that the risk of knee OA accumulates from exposure to a high BMI through adulthood.

BACKGROUND: Earlier studies have suggested that infant feeding may program long-term changes in cholesterol metabolism. OBJECTIVE: We aimed to examine whether breastfeeding is associated with lower blood cholesterol concentrations in adulthood. DESIGN: The study consisted of a systematic review of published observational studies relating initial infant feeding status to blood cholesterol concentrations in adulthood (ie, aged >16 y). Data were available from 17 studies (17 498 subjects; 12 890 breastfed, 4608 formula-fed). Mean differences in total cholesterol concentrations (breastfed minus formula-fed) were pooled by using fixed-effect models. Effects of adjustment (for age at outcome, socioeconomic position, body mass index, and smoking status) and exclusion (of nonexclusive breast feeders) were examined. RESULTS: Mean total blood cholesterol was lower (P = 0.037) among those ever breastfed than among those fed formula milk (mean difference: -0.04 mmol/L; 95% CI: -0.08, 0.00 mmol/L). The difference in cholesterol between infant feeding groups was larger (P = 0.005) and more consistent in 7 studies that analyzed "exclusive" feeding patterns (-0.15 mmol/L; -0.23, -0.06 mmol/L) than in 10 studies that analyzed nonexclusive feeding patterns (-0.01 mmol/L; -0.06, 0.03 mmol/L). Adjustment for potential confounders including socioeconomic position, body mass index, and smoking status in adult life had minimal effect on these estimates. CONCLUSIONS: Initial breastfeeding (particularly when exclusive) may be associated with lower blood cholesterol concentrations in later life. Moves to reduce the cholesterol content of formula feeds below those of breast milk should be treated with caution.