London South Bank University

BACKGROUND: The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. METHODS: We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors-the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). FINDINGS: Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57·8% (95% CI 56·6-58·8) of global deaths and 41·2% (39·8-42·8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. INTERPRETATION: Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. FUNDING: Bill & Melinda Gates Foundation.

IMPORTANCE: The Global Burden of Diseases, Injuries, and Risk Factors Study 2019 (GBD 2019) provided systematic estimates of incidence, morbidity, and mortality to inform local and international efforts toward reducing cancer burden. OBJECTIVE: To estimate cancer burden and trends globally for 204 countries and territories and by Sociodemographic Index (SDI) quintiles from 2010 to 2019. EVIDENCE REVIEW: The GBD 2019 estimation methods were used to describe cancer incidence, mortality, years lived with disability, years of life lost, and disability-adjusted life years (DALYs) in 2019 and over the past decade. Estimates are also provided by quintiles of the SDI, a composite measure of educational attainment, income per capita, and total fertility rate for those younger than 25 years. Estimates include 95% uncertainty intervals (UIs). FINDINGS: In 2019, there were an estimated 23.6 million (95% UI, 22.2-24.9 million) new cancer cases (17.2 million when excluding nonmelanoma skin cancer) and 10.0 million (95% UI, 9.36-10.6 million) cancer deaths globally, with an estimated 250 million (235-264 million) DALYs due to cancer. Since 2010, these represented a 26.3% (95% UI, 20.3%-32.3%) increase in new cases, a 20.9% (95% UI, 14.2%-27.6%) increase in deaths, and a 16.0% (95% UI, 9.3%-22.8%) increase in DALYs. Among 22 groups of diseases and injuries in the GBD 2019 study, cancer was second only to cardiovascular diseases for the number of deaths, years of life lost, and DALYs globally in 2019. Cancer burden differed across SDI quintiles. The proportion of years lived with disability that contributed to DALYs increased with SDI, ranging from 1.4% (1.1%-1.8%) in the low SDI quintile to 5.7% (4.2%-7.1%) in the high SDI quintile. While the high SDI quintile had the highest number of new cases in 2019, the middle SDI quintile had the highest number of cancer deaths and DALYs. From 2010 to 2019, the largest percentage increase in the numbers of cases and deaths occurred in the low and low-middle SDI quintiles. CONCLUSIONS AND RELEVANCE: The results of this systematic analysis suggest that the global burden of cancer is substantial and growing, with burden differing by SDI. These results provide comprehensive and comparable estimates that can potentially inform efforts toward equitable cancer control around the world.

Evidence-based practice includes, in part, implementation of the findings of well-conducted quality research studies. So being able to critique quantitative research is an important skill for nurses. Consideration must be given not only to the results of the study but also the rigour of the research. Rigour refers to the extent to which the researchers worked to enhance the quality of the studies. In quantitative research, this is achieved through measurement of the validity and reliability.1 Validity is defined as the extent to which a concept is accurately measured in a quantitative study. For example, a survey designed to explore depression but which actually measures anxiety would not be considered valid. The second measure of quality in a quantitative study is reliability , or the accuracy of an instrument. In other words, the extent to which a research instrument consistently has the same results if it is used in the same situation on repeated occasions. A simple example of validity and reliability is an alarm clock that rings at 7:00 each morning, but is set for 6:30. It is very reliable (it consistently rings the same time each day), but is not valid (it is not ringing at the desired time). It's important to consider validity and reliability of the data collection tools (instruments) when either conducting or critiquing research. There are three major types of validity. These are described in table 1. View this table: Table 1 Types of validity The first category is content validity . This category looks at whether the instrument adequately covers …

BACKGROUND: E-cigarettes are commonly used in attempts to stop smoking, but evidence is limited regarding their effectiveness as compared with that of nicotine products approved as smoking-cessation treatments. METHODS: We randomly assigned adults attending U.K. National Health Service stop-smoking services to either nicotine-replacement products of their choice, including product combinations, provided for up to 3 months, or an e-cigarette starter pack (a second-generation refillable e-cigarette with one bottle of nicotine e-liquid [18 mg per milliliter]), with a recommendation to purchase further e-liquids of the flavor and strength of their choice. Treatment included weekly behavioral support for at least 4 weeks. The primary outcome was sustained abstinence for 1 year, which was validated biochemically at the final visit. Participants who were lost to follow-up or did not provide biochemical validation were considered to not be abstinent. Secondary outcomes included participant-reported treatment usage and respiratory symptoms. RESULTS: A total of 886 participants underwent randomization. The 1-year abstinence rate was 18.0% in the e-cigarette group, as compared with 9.9% in the nicotine-replacement group (relative risk, 1.83; 95% confidence interval [CI], 1.30 to 2.58; P<0.001). Among participants with 1-year abstinence, those in the e-cigarette group were more likely than those in the nicotine-replacement group to use their assigned product at 52 weeks (80% [63 of 79 participants] vs. 9% [4 of 44 participants]). Overall, throat or mouth irritation was reported more frequently in the e-cigarette group (65.3%, vs. 51.2% in the nicotine-replacement group) and nausea more frequently in the nicotine-replacement group (37.9%, vs. 31.3% in the e-cigarette group). The e-cigarette group reported greater declines in the incidence of cough and phlegm production from baseline to 52 weeks than did the nicotine-replacement group (relative risk for cough, 0.8; 95% CI, 0.6 to 0.9; relative risk for phlegm, 0.7; 95% CI, 0.6 to 0.9). There were no significant between-group differences in the incidence of wheezing or shortness of breath. CONCLUSIONS: E-cigarettes were more effective for smoking cessation than nicotine-replacement therapy, when both products were accompanied by behavioral support. (Funded by the National Institute for Health Research and Cancer Research UK; Current Controlled Trials number, ISRCTN60477608 .).

STUDY OBJECTIVE: The concept of social capital has influenced mental health policies of nations and international organisations despite its limited evidence base. This papers aims to systematically review quantitative studies examining the association between social capital and mental illness. DESIGN AND SETTING: Twenty electronic databases and the reference sections of papers were searched to identify published studies. Authors of papers were contacted for unpublished work. Anonymised papers were reviewed by the authors of this paper. Papers with a validated mental illness outcome and an exposure variable agreed as measuring social capital were included. No limitations were put on date or language of publication. MAIN RESULTS: Twenty one studies met the inclusion criteria for the review. Fourteen measured social capital at the individual level and seven at an ecological level. The former offered evidence for an inverse relation between cognitive social capital and common mental disorders. There was moderate evidence for an inverse relation between cognitive social capital and child mental illness, and combined measures of social capital and common mental disorders. The seven ecological studies were diverse in methodology, populations investigated, and mental illness outcomes, making them difficult to summarise. CONCLUSIONS: Individual and ecological social capital may measure different aspects of the social environment. Current evidence is inadequate to inform the development of specific social capital interventions to combat mental illness.

The real part of the permittivity (ε) and the tan δ of sintered alumina (Al 2 O 3 ) at about 9 GHz have been measured. The dielectric properties have been examined as a function of purity, pore volume, and sintered grain size. The tan δ is found to depend very strongly on the pore volume, purity, and grain size. ε is far less sensitive to impurities and grain size. The dependence of ε on porosity can be described by simple mixture models as expected. A model of losses in single crystals cannot be extended easily to these materials where extrinsic factors such as porosity, random crystal orientation, grain boundaries, microcracks, and impurities dominate. These factors have been studied in an attempt to describe the tan δ and ε of sintered polycrystalline alumina. In this work, the tan δ for alumina has been studied in near‐theoretical density ranges between 9.1 times 10 ‐5 and 2.4 times 10 ‐5 depending on grain size.

With growing recognition of the social determinants of health, social capital is an increasingly important concept in international health research. Although there is relatively little experience of measuring social capital, particularly in developing countries, there are now a number of studies that allow the identification of some key issues that need to be considered when measuring social capital. After summarizing definitions and the rise of interest in the link between social capital and health, measures used in key studies of social capital and health are presented. Some important issues are then considered: obtaining a sufficiently comprehensive measure which empirically captures the latest theoretical developments in the field (particularly the concepts of cognitive, structural, bonding and bridging social capital); moving from the individual to the ecological level; consideration of confounding factors, and validity and reliability.

The clinical diagnosis of progressive supranuclear palsy (PSP) relies on the identification of characteristic signs and symptoms. A proportion of pathologically diagnosed cases do not develop these classic features, prove difficult to diagnose during life and are considered as atypical PSP. The aim of this study was to examine the apparent clinical dichotomy between typical and atypical PSP, and to compare the biochemical and genetic characteristics of these groups. In 103 consecutive cases of pathologically confirmed PSP, we have identified two clinical phenotypes by factor analysis which we have named Richardson's syndrome (RS) and PSP-parkinsonism (PSP-P). Cases of RS syndrome made up 54% of all cases, and were characterized by the early onset of postural instability and falls, supranuclear vertical gaze palsy and cognitive dysfunction. A second group of 33 (32%) were characterized by asymmetric onset, tremor, a moderate initial therapeutic response to levodopa and were frequently confused with Parkinson's disease (PSP-P). Fourteen cases (14%) could not be separated according to these criteria. In RS, two-thirds of cases were men, whereas the sex distribution in PSP-P was even. Disease duration in RS was significantly shorter (5.9 versus 9.1 years, P < 0.001) and age at death earlier (72.1 versus 75.5 years, P = 0.01) than in PSP-P. The isoform composition of insoluble tangle-tau isolated from the basal pons also differed significantly. In RS, the mean four-repeat:three-repeat tau ratio was 2.84 and in PSP-P it was 1.63 (P < 0.003). The effect of the H1,H1 PSP susceptibility genotype appeared stronger in RS than in PSP-P (odds ratio 13.2 versus 4.5). The difference in genotype frequencies between the clinical subgroups was not significant. There were no differences in apolipoprotein E genotypes. The classic clinical description of PSP, which includes supranuclear gaze palsy, early falls and dementia, does not adequately describe one-third of cases in this series of pathologically confirmed cases. We propose that PSP-P represents a second discrete clinical phenotype that needs to be clinically distinguished from classical PSP (RS). The different tau isoform deposition in the basal pons suggests that this may ultimately prove to be a discrete nosological entity.

When the London/New York Dialogues conference took place in London in November 2008, it was already clear that the crisis in the financial markets was going to take a heavy toll on the economies of...

Two decades ago, with the publication, we witnessed the rebirth of particle filtering (PF) as a methodology for sequential signal processing. Since then, PF has become very popular because of its ability to process observations represented by nonlinear state-space models where the noises of the model can be non-Gaussian. This methodology has been adopted in various fields, including finance, geophysical systems, wireless communications, control, navigation and tracking, and robotics. The popularity of PF has also spurred the publication of several review articles. In this article, the state of the art of resampling methods was reviewed. The methods were classified and their properties were compared in the framework of the proposed classifications. The emphasis in the article was on the classification and qualitative descriptions of the algorithms. The intention was to provide guidelines to practitioners and researchers.

Taking economic co‐ordination in EMU as a starting point, this article explores the development of the open method of co‐ordination, addressing whether it is a new form of governance from two related perspectives. First, to what extent can the method be effectively applied outside the scope of economic policy? Second, will it lead to policy transfer to the EU and hence act only as a transitional mode of governance? Identified at the Lisbon European Council, the method codified practices such as benchmarking, target‐setting and peer review developed in the Luxembourg, Cardiff and Cologne processes. The method offers a new approach to governance of the EU as a heterarchical, decentred and dynamic process. It supports and radicalizes the principle of subsidiarity; offers an alternative to the treaty rules on enhanced co‐operation; and addresses some of the legitimacy issues inherent in the EU. In EMU, the method arose out of a specific policy framework with a common monetary policy complemented by the coordination of national economic policies. The recent recommendation issued against Ireland is the first example of the operation of the method in EMU and shows how debate can be stimulated and how different and arguably equally valid perspectives defended. The particular experience of EMU with a sound money, sound finance paradigm, a long history of project‐building by key elites and the central role of the European Council suggest similar conditions are required for the effective application of the method in other policy spheres. The context within which the method has operated to date is contingent and could change either over time or between policy fields. If so, the very openness of the method may serve to reconfigure the boundaries of competence between the Member States and the Union, after all.

In this article, the authors examine the implications of extending calls for reflexivity in qualitative research generally to cross-language research with interpreters. Drawing on the concept of ‘borders’, they present two research projects to demonstrate the need to locate the interpreter as active in producing research accounts. They extend the concept of ‘border crossing’, relating this to identity politics and the benefits of making the interpreter visible in research.

BACKGROUND: There is evidence that the process of transition from paediatric (child) to adult health services is often associated with deterioration in the health of adolescents with chronic conditions.Transitional care is the term used to describe services that seek to bridge this care gap. It has been defined as 'the purposeful, planned movement of adolescents and young adults with chronic physical and medical conditions from child-centred to adult-oriented health care systems'. In order to develop appropriate services for adolescents, evidence of what works and what factors act as barriers and facilitators of effective interventions is needed. OBJECTIVES: To evaluate the effectiveness of interventions designed to improve the transition of care for adolescents from paediatric to adult health services. SEARCH METHODS: We searched The Cochrane Central Register of Controlled Trials 2015, Issue 1, (including the Cochrane Effective Practice and Organisation of Care Group Specialised Register), MEDLINE, EMBASE, PsycINFO, and Web of Knowledge to 19 June 2015. We also searched reference lists of included studies and relevant reviews, and contacted experts and study authors for additional studies. SELECTION CRITERIA: We considered randomised controlled trials (RCTs), controlled before- and after-studies (CBAs), and interrupted time-series studies (ITSs) that evaluated the effectiveness of any intervention (care model or clinical pathway), that aimed to improve the transition of care for adolescents from paediatric to adult health services. We considered adolescents with any chronic condition that required ongoing clinical care, who were leaving paediatric services and going on to receive services in adult healthcare units, and their families. Participating providers included all health professionals responsible for the care of young people. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data from included papers, assessed the risk of bias of each study, and assessed the certainty of the evidence for the main comparisons using GRADE. Discrepancies were resolved by discussion. Authors were contacted for missing data. We reported the findings of the studies as pre- and post-intervention means and calculated the unadjusted absolute change from baseline with 95% confidence intervals (CI). MAIN RESULTS: We included four RCTs (N = 238 participants) that explored: a two-day workshop-based transition preparation training for adolescents with spina bifida; a nurse-led, one-on-one, teaching session with the additional support of a 'health passport' for adolescents with heart disease; a web- and SMS-based educational intervention for adolescents with a range of different conditions; and a structured comprehensive transition programme with a transition co-ordinator for adolescents with type 1 diabetes.One study evaluating a one-on-one nurse-led intervention, and one evaluating a technology-based intervention suggested that these interventions may lead to slight improvements in transitional readiness and chronic disease self-management measured at six- to eight-month follow-ups (low certainty evidence). Results with the TRAQ self-management tool were: MD 0.20; 95% CI -0.16 to 0.56 and MD 0.43; 95% CI; -0.09 to 0.95; with the TRAQ self-advocacy tool: MD 0.37; 95% CI -0.06 to 0.80; and with the PAM tool were: MD 10; 95% CI 2.96 to 17.04. In contrast, transition-preparation training delivered via a two-day workshop for patients with spina bifida may lead to little or no difference in measures of self-care practice and general health behaviours when measured using the DSCPI-90©.Two studies evaluated the use of health services. One study evaluated a technology-based intervention and another a comprehensive transition programme; these interventions may lead to slightly more young people taking positive steps to initiate contact with health professionals themselves (Relative risk (RR): 4.87; 95% CI 0.24 to 98.12 and RR 1.50; 95% CI 0.32 to 6.94, respectively; low certainty evidence.Young people's knowledge of their disease may slightly improve with a nurse-led, one-on-one intervention to prepare young people for transition to an adult congenital heart programme (MD 14; 95% CI 2.67 to 25.33; one study; low certainty evidence).Disease-specific outcome measures were reported in two studies, both of which led to little or no difference in outcomes (low certainty evidence). One study found little or no difference between intervention and control groups. A second study found that follow-up HbA1c in young people with type 1 diabetes mellitus increased by 1.2% for each percentage increase in baseline HbA1c, independent of treatment group (1.2%; 95% CI 0.4 to 1.9; P = 0.01).Transition interventions may lead to little or no difference in well-being or quality of life as measured with the PARS III or PedsQ (two studies; low certainty evidence). Both the technology-based intervention and the two-day workshop for young people with spina bifida found little or no difference between intervention and control groups (MD 1.29; 95% CI -4.49 to 7.07). One study did not report the data.Four telephone support calls from a transition co-ordinator may lead to little or no difference in rates of transfer from paediatric to adult diabetes services (one study; low certainty evidence). At 12-month follow-up, there was little or no difference between groups of young people receiving usual care or a telephone support (RR 0.80; 95% CI 0.59 to 1.08)). They may slightly reduce the risk of disease-related hospital admissions at 12-month follow-up (RR 0.29; 95% CI 0.03 to 2.40). AUTHORS' CONCLUSIONS: The available evidence (four small studies; N = 238), covers a limited range of interventions developed to facilitate transition in a limited number of clinical conditions, with only four to 12 months follow-up. These follow-up periods may not be long enough for any changes to become apparent as transition is a lengthy process. There was evidence of improvement in patients' knowledge of their condition in one study, and improvements in self-efficacy and confidence in another, but since few studies were eligible for this review, and the overall certainty of the body of this evidence is low, no firm conclusions can be drawn about the effectiveness of the evaluated interventions. Further research is very likely to have an important impact on our confidence in the intervention effect and likely could change our conclusions. There is considerable scope for the rigorous evaluation of other models of transitional care, reporting on clinical outcomes with longer term follow-up.

Ninety-three different commercial essential oils were screened for activity against 20 Listeria monocytogenes strains in vitro and the results correlated against the actual chemical composition of each oil. There was a substantial difference in the activity between different essential oils as expected, but there was also a difference in activity between different samples of the same essential oil. Strong anti-Listeria activity was often correlated with essential oils containing a high percentage of monoterpenes, eugenol, cinnamaldehyde, thymol, and sometimes with citronellol, limonene and geraniol. However, as there was often no correlation between the anti-Listeria activity and the main chemical components, it is possible that either there is a more complex relationship with the chemical composition (which includes the minor components) or that substantial adulteration had occurred in some essential oil samples.

This paper is the first of two that highlights key elements needed for consideration in the planning and implementation of interprofessional educational (IPE) interventions at both the pre and post-licensure qualification education levels. There is still much to be learned about the pedagogical constructs related to IPE. Part 1 of this series discusses the learning context for IPE and considers questions related to the "who, what, where, when and how" related to IPE. Through a systematic literature review that was conducted for Health Canada in its move to advance Interprofessional Education for Patient Centred Practice (IECPCP), this paper provides background information that can be helpful for those involved in an interprofessional initiative. A historical review of IPE sets the international context for this area and reflects the work that has been done and is currently being initiated and implemented to advance IPE for health professional students. Much can be learned from the literature related to the pedagogical approaches that have been tried and the issues that need to be addressed related to the learner, the educator and the learning context which this paper examines.

Improved competitiveness, as we all know, is the path to economic nirvana. Plainly, it is a sought after property of any economy: the term trips frequently off the lips of politicians and commentators on economic and business matters. As cities increasingly engage in competition with one another at different levels, the determinants of competitive advantage are coming under intense scrutiny. Many

In recent years, there has been an intense public and policy debate about ethnic diversity, community cohesion, and immigration in Britain and other societies worldwide. In addition, there has been a growing preoccupation with the possible dangers to social cohesion represented by growing immigration flows and ethnic diversity. This paper proposes a critical framework for assessing the links between immigration, social cohesion, and social capital. It argues that the concept of social capital is episodic, socially constructed and value-based, depending on the prevailing ideological climate. Considerations of social capital as a public policy tool to achieve social cohesion need to incorporate an appreciation of alternative conceptions of social capital rooted in a textured under-standing of immigrant processes and migration contexts.

The `Inventing Adulthoods' study seeks to document transitions to adulthood reported by over 100 young people living in five contrasting communities in the UK over a five-year period. A principal aim of the study is to identify `critical moments' in young people's biographies and to explore how these moments are implicated in processes of social inclusion and exclusion. This article reports on an analysis of the first of three rounds of one-to-one interviews. We begin by mapping young people's critical moments, exploring the relationship between the social and geographical location in which they live and the kinds of events that they report as having particular biographical significance. We suggest that the character of these `critical moments' is socially structured, as are young people's responses to them. The argument is illustrated by case studies that show the interaction of choice, chance and opportunity in three young people's lives.

Although the cause of dopaminergic cell death in Parkinson's disease (PD) remains unknown, oxidative stress has been strongly implicated. Because of their ability to combat oxidative stress, diet derived phenolic compounds continue to be considered as potential agents for long-term use in PD. This study was aimed at investigating whether the natural phenolic compounds curcumin, naringenin, quercetin, fisetin can be neuroprotective in the 6-OHDA model of PD. Unilateral infusion of 6-OHDA into the medial forebrain bundle produced a significant loss of tyrosine hydroxylase (TH)-positive cells in the substantia nigra (SN) as well as a decreased of dopamine (DA) content in the striata in the vehicle-treated animals. Rats pretreated with curcumin or naringenin showed a clear protection of the number of TH-positive cells in the SN and DA levels in the striata. However, neither pretreatment with quercetin nor fisetin had any effects on TH-positive cells or DA levels. The ability of curcumin and naringenin to exhibit neuroprotection in the 6-OHDA model of PD may be related to their antioxidant capabilities and their capability to penetrate into the brain.

Abstract Replication is little discussed in the statistical literature nor practiced widely by statistically minded researchers. It is needed not merely to validate one's findings, but more importantly, to establish the increasing range of radically different conditions under which the findings hold, and the predictable exceptions. This article describes how to design highly differentiated replications. The irrelevance and/or impossibility of identical replications are also discussed. Practical illustrations of the success and failure of replicated studies are given.