Ethnic density and first episode psychosis in the British Pakistani population: findings from the East Lancashire Early Intervention Service.

BACKGROUND: Elevated risk of psychosis for ethnic minority groups has generally been shown to be mitigated by high ethnic density. However, past survey studies examining UK Pakistani populations have shown an absence of protective ethnic density effects, which is not observed in other South Asian groups. AIMS: To assess the ethnic density effect at a local neighbourhood level, in the UK Pakistani population in East Lancashire. METHOD: Data was collected by the East Lancashire Early Intervention Service, identifying all cases of first episode psychosis (FEP) within their catchment area between 2012 and 2020. Multilevel Poisson regression analyses were used to compare incidence rates between Pakistani and White majority groups, while controlling for age, gender and area-level deprivation. The ethnic density effect was also examined by comparing incidence rates across high and low density areas. RESULTS: A total of 455 cases of FEP (364 White, 91 Pakistani) were identified. The Pakistani group had a higher incidence of FEP compared to the White majority population. A clear effect of ethnic density on rates of FEP was shown, with those in low density areas having higher incidence rates compared to the White majority, whereas incidence rates in high density areas did not significantly differ. Within the Pakistani group, a dose-response effect was also observed, with risk of FEP increasing incrementally as ethnic density decreased. CONCLUSIONS: Higher ethnic density related to lower risk of FEP within the Pakistani population in East Lancashire, highlighting the impact of local social context on psychosis incidence.

The relationship between ethnicity and multiple sclerosis characteristics in the United Kingdom: A UK MS Register study.

BACKGROUND: Previous studies have suggested differences in multiple sclerosis (MS) severity according to ethnicity. METHODS: Data were obtained from the UK MS Register, a prospective longitudinal cohort study of persons with MS. We examined the association between self-reported ethnic background and age at onset, symptom of onset and a variety of participant-reported severity measures. We used adjusted multivariable linear regression models to explore the association between ethnicity and impact of MS, and Cox proportional hazards models to assess disability progression. RESULTS: We analysed data from 17,314 people with MS, including participants from self-reported Black (n = 157) or South Asian (n = 230) ethnic backgrounds. Age at MS onset and diagnosis was lower in those of South Asian (median 30.0) and Black (median 33.0) ethnicity compared with White ethnicity (median 35.0). In participants with online MS severity measures available, we found no statistically significant evidence for an association between ethnic background and physical disability in MS in both cross-sectional and longitudinal analyses. CONCLUSION: We found no association between ethnic background and MS severity in a large, diverse UK cohort. These findings suggest that other factors, such as socioeconomic status and structural inequalities, may explain previous findings.

Interpersonal symptoms in adolescence depression across Asian and European regions: a network approach.

BACKGROUND: Major Depressive Disorder (MDD) poses a significant global health challenge, with symptom presentation potentially varying between adolescents and adults. Adolescence is a critical period marked by heightened vulnerability to interpersonal stresses, yet the impact of these stresses on the structure of depressive symptoms is not well understood. Recognizing the cultural nuances in how depression manifests among adolescents is crucial. To this end, this paper employs a network analysis approach, utilizing a comprehensive symptom checklist from the Multidimensional Depression Assessment Scale (MDAS). Our study investigates the role of interpersonal symptoms within the broader cluster of emotional, cognitive, and somatic symptoms and explores variations in adolescent groups in four Asian and European regions. METHODS: We recruited a diverse sample of 6,348 adolescents aged 12 to 18 from Hong Kong, Taiwan, the UK, China, and the Netherlands using the Qualtrics platform. Employing the Gaussian Graphical Model, we established a network model of depressive symptoms as measured by the MDAS, segregating the sample into Asian and European regions to examine the interconnections between them. The study focused on identifying central symptom nodes and comparing the network structures between the two groups. RESULTS: The analysis identified feeling worthless, low energy, being a burden to others, and low mood as central symptoms of depression. Notably, there were significant differences in the connections between depressive symptoms among Asian (Hong Kong, China and Taiwan) and European (UK and the Netherlands) adolescents, highlighting cultural variations in how interpersonal symptoms interact with emotional, cognitive, and somatic symptoms. CONCLUSION: This study is pioneering in applying network analysis to include interpersonal symptoms in examining depression among a diverse adolescent population. It demonstrates that interpersonal symptoms are integral to the central features of depressive symptoms. Furthermore, our findings suggest that, compared to their UK and Dutch peers, interpersonal symptoms in Asian adolescents are uniquely connected to other symptom clusters, reflecting distinct cultural patterns. LIMITATIONS: The study engaged a broad community sample; however, future research could benefit from including a larger sample size to allow for a more detailed analysis of a greater number of symptom nodes.

Scalable probabilistic PCA for large-scale genetic variation data.

Principal component analysis (PCA) is a key tool for understanding population structure and controlling for population stratification in genome-wide association studies (GWAS). With the advent of large-scale datasets of genetic variation, there is a need for methods that can compute principal components (PCs) with scalable computational and memory requirements. We present ProPCA, a highly scalable method based on a probabilistic generative model, which computes the top PCs on genetic variation data efficiently. We applied ProPCA to compute the top five PCs on genotype data from the UK Biobank, consisting of 488,363 individuals and 146,671 SNPs, in about thirty minutes. To illustrate the utility of computing PCs in large samples, we leveraged the population structure inferred by ProPCA within White British individuals in the UK Biobank to identify several novel genome-wide signals of recent putative selection including missense mutations in RPGRIP1L and TLR4.

Quantifying and Understanding the Higher Risk of Atherosclerotic Cardiovascular Disease Among South Asian Individuals: Results From the UK Biobank Prospective Cohort Study.

BACKGROUND: Individuals of South Asian ancestry represent 23% of the global population, corresponding to 1.8 billion people, and have substantially higher risk of atherosclerotic cardiovascular disease compared with most other ethnicities. US practice guidelines now recognize South Asian ancestry as an important risk-enhancing factor. The magnitude of enhanced risk within the context of contemporary clinical care, the extent to which it is captured by existing risk estimators, and its potential mechanisms warrant additional study. METHODS: Within the UK Biobank prospective cohort study, 8124 middle-aged participants of South Asian ancestry and 449 349 participants of European ancestry who were free of atherosclerotic cardiovascular disease at the time of enrollment were examined. The relationship of ancestry to risk of incident atherosclerotic cardiovascular disease-defined as myocardial infarction, coronary revascularization, or ischemic stroke-was assessed with Cox proportional hazards regression, along with examination of a broad range of clinical, anthropometric, and lifestyle mediators. RESULTS: The mean age at study enrollment was 57 years, and 202 405 (44%) were male. Over a median follow-up of 11 years, 554 of 8124 (6.8%) individuals of South Asian ancestry experienced an atherosclerotic cardiovascular disease event compared with 19 756 of 449 349 (4.4%) individuals of European ancestry, corresponding to an adjusted hazard ratio of 2.03 (95% CI, 1.86-2.22; P<0.001). This higher relative risk was largely consistent across a range of age, sex, and clinical subgroups. Despite the >2-fold higher observed risk, the predicted 10-year risk of cardiovascular disease according to the American Heart Association/American College of Cardiology Pooled Cohort equations and QRISK3 equations was nearly identical for individuals of South Asian and European ancestry. Adjustment for a broad range of clinical, anthropometric, and lifestyle risk factors led to only modest attenuation of the observed hazard ratio to 1.45 (95% CI, 1.28-1.65, P<0.001). Assessment of variance explained by 18 candidate risk factors suggested greater importance of hypertension, diabetes, and central adiposity in South Asian individuals. CONCLUSIONS: Within a large prospective study, South Asian individuals had substantially higher risk of atherosclerotic cardiovascular disease compared with individuals of European ancestry, and this risk was not captured by the Pooled Cohort Equations.

Genome-wide association analysis of 350 000 Caucasians from the UK Biobank identifies novel loci for asthma, hay fever and eczema.

Even though heritability estimates suggest that the risk of asthma, hay fever and eczema is largely due to genetic factors, previous studies have not explained a large part of the genetics behind these diseases. In this genome-wide association study, we include 346 545 Caucasians from the UK Biobank to identify novel loci for asthma, hay fever and eczema and replicate novel loci in three independent cohorts. We further investigate if associated lead single nucleotide polymorphisms (SNPs) have a significantly larger effect for one disease compared to the other diseases, to highlight possible disease-specific effects. We identified 141 loci, of which 41 are novel, to be associated (P ≤ 3 × 10-8) with asthma, hay fever or eczema, analyzed separately or as disease phenotypes that includes the presence of different combinations of these diseases. The largest number of loci was associated with the combined phenotype (asthma/hay fever/eczema). However, as many as 20 loci had a significantly larger effect on hay fever/eczema only compared to their effects on asthma, while 26 loci exhibited larger effects on asthma compared with their effects on hay fever/eczema. At four of the novel loci, TNFRSF8, MYRF, TSPAN8, and BHMG1, the lead SNPs were in Linkage Disequilibrium (LD) (>0.8) with potentially casual missense variants. Our study shows that a large amount of the genetic contribution is shared between the diseases. Nonetheless, a number of SNPs have a significantly larger effect on one of the phenotypes, suggesting that part of the genetic contribution is more phenotype specific.

Clinical and laboratory phenotypes in juvenile-onset Systemic Lupus Erythematosus across ethnicities in the UK.

Systemic lupus erythematosus (SLE) is a systemic autoimmune/inflammatory disease. Patients diagnosed with juvenile-onset SLE (jSLE), when compared to individuals with adult-onset SLE, develop more severe organ involvement, increased disease activity and greater tissue and organ damage. In adult-onset SLE, clinical characteristics, pathomechanisms, disease progression and outcomes do not only vary between individuals and age groups, but also ethnicities. However, in children and young people, the influence of ethnicity on disease onset, phenotype and outcome has not been investigated in detail. In this study, we investigated clinical and laboratory characteristics in pediatric SLE patients from different ethnic backgrounds (White Caucasian, Asian, Black African/Caribbean) accessing data from a national cohort of jSLE patients (the UK JSLE Cohort Study). Among jSLE patients in the UK, ethnicity affects both the disease's clinical course and outcomes. At diagnosis, Black African/Caribbean jSLE patients show more "classical" laboratory and clinical features when compared to White Caucasian or Asian patients. Black African/Caribbean jSLE patients exhibit more renal involvement and more frequently receive cyclophosphamide and rituximab. Studies targeting ethnicity-specific contributors to disease expression and phenotypes are necessary to improve our pathophysiological understanding, diagnosis and treatment of jSLE.

The fine-scale genetic structure of the British population.

Fine-scale genetic variation between human populations is interesting as a signature of historical demographic events and because of its potential for confounding disease studies. We use haplotype-based statistical methods to analyse genome-wide single nucleotide polymorphism (SNP) data from a carefully chosen geographically diverse sample of 2,039 individuals from the United Kingdom. This reveals a rich and detailed pattern of genetic differentiation with remarkable concordance between genetic clusters and geography. The regional genetic differentiation and differing patterns of shared ancestry with 6,209 individuals from across Europe carry clear signals of historical demographic events. We estimate the genetic contribution to southeastern England from Anglo-Saxon migrations to be under half, and identify the regions not carrying genetic material from these migrations. We suggest significant pre-Roman but post-Mesolithic movement into southeastern England from continental Europe, and show that in non-Saxon parts of the United Kingdom, there exist genetically differentiated subgroups rather than a general 'Celtic' population.

A Cross-Cultural Analysis of Early Prelinguistic Gesture Development and Its Relationship to Language Development.

Many Western industrialized nations have high levels of ethnic diversity but to date there are very few studies which investigate prelinguistic and early language development in infants from ethnic minority backgrounds. This study tracked the development of infant communicative gestures from 10 to 12 months (n = 59) in three culturally distinct groups in the United Kingdom and measured their relationship, along with maternal utterance frequency and responsiveness, to vocabulary development at 12 and 18 months. No significant differences were found in infant gesture development and maternal responsiveness across the groups, but relationships were identified between gesture, maternal responsiveness, and vocabulary development.

Association between inflammatory bowel disease and prostate cancer: A large-scale, prospective, population-based study.

Inflammatory bowel disease (IBD) is an established risk factor for colorectal cancer. Recent reports suggesting IBD is also a risk factor for prostate cancer (PC) require further investigation. We studied 218 084 men in the population-based UK Biobank cohort, aged 40 to 69 at study entry between 2006 and 2010, with follow-up through mid-2015. We assessed the association between IBD and subsequent PC using multivariable Cox regression analyses, adjusting for age at assessment, ethnic group, UK region, smoking status, alcohol drinking frequency, body mass index, Townsend Deprivation Index, family history of PC and previous prostate-specific antigen testing. Mean age at study entry was 56 years, 94% of the men were white, and 1.1% (n = 2311) had a diagnosis of IBD. After a median follow-up of 78 months, men with IBD had an increased risk of PC (adjusted hazard ratio [aHR] = 1.31, 95% confidence interval [CI] = 1.03-1.67, P = .029). The association with PC was only among men with the ulcerative colitis (UC; aHR = 1.47, 95% CI = 1.11-1.95, P = .0070), and not Crohn's disease (aHR 1.06, 95% CI = 0.63-1.80, P = .82). Results are limited by lack of data on frequency of health care interactions. In a large-scale, prospective cohort study, we detected an association between IBD, and UC specifically, with incident PC diagnosis.

Evaluating polygenic risk scores in assessing risk of nine solid and hematologic cancers in European descendants.

Genome-wide association studies (GWAS) have identified many genetic risk variants for cancers. The utility of these variants in assessing risk of esophageal, gastric and endometrial cancers, as well as melanoma, glioma, diffuse large B-cell lymphoma, follicular lymphoma, chronic lymphoid leukemia and multiple myeloma, has not been adequately investigated. We constructed a site-specific polygenic risk score (PRS) for each of these nine cancers using their GWAS-identified risk variants. Using data from 400 807 participants of European descent in the UK Biobank, a population-based cohort study, we estimated the hazard ratios of each cancer associated with its PRS using Cox proportional hazard models. During a median follow-up of 5.8 years, 3905 incident cases of these nine cancers were identified in the cohort. The area under the receiver operating characteristic curve ranged from 0.53 to 0.69 for these cancers. Except for esophageal cancer, significant dose-response associations were observed between PRS and cancer risk. Compared to individuals in the middle quintile (40%-60%) at an average risk, those among the highest 5% of the PRS had a twofold elevated risk of melanoma, glioma, follicular lymphoma or multiple myeloma, and a fourfold elevated risk of chronic lymphoid leukemia. Using PRS, 63.0% of the participants could be classified as having an over twofold elevated risk for at least one cancer. The PRS derived using risk variants identified to date by GWAS showed the potential in identifying individuals at a significantly elevated risk of cancer for prevention.

Compromised CD4:CD8 ratio recovery in people living with HIV aged over 50 years: an observational study.

OBJECTIVES: Persistent CD4:CD8 ratio inversion (< 1) is associated with mortality in older people. We investigated the interaction of the effects of baseline CD8 count and age at HIV diagnosis on CD4:CD8 ratio recovery with antiretroviral therapy (ART). METHODS: An observational study (1 January 2007 to 31 December 2016) was carried out using routinely collected data from the HIV outpatient services at Imperial College Healthcare NHS Trust, London, UK. CD4 and CD8 counts, prior to and during ART, treatment during primary HIV infection (PHI) and HIV-1 viral load were included in univariate and multivariate analyses using Cox proportional hazard regression. RESULTS: Data were included for 876 patients starting ART, where HIV suppression was achieved. Of these patients, 741 of 876 (84.6%) were male and 507 of 876 (57.9%) were Caucasian. The median time on ART was 38 [interquartile range (IQR) 17-66] months. CD8 count change on ART was bidirectional; low CD8 counts (≤ 600 cells/µL) increased and high CD8 counts (> 900 cells/µL) decreased. The median pre-ART CD4:CD8 ratio was 0.41 (IQR 0.24-0.63), and recovery (≥ 1) occurred in 274 of 876 patients (31.3%). Pre- and post-ART CD4:CD8 ratios were lower in those aged > 50 years compared with young adults aged 18-30 years (P < 0.001 and P = 0.002, respectively). After adjustment, younger age at HIV diagnosis (P < 0.001) and treatment during PHI (P < 0.001) were favourable for CD4:CD8 ratio normalization. CONCLUSIONS: Older age (> 50 years) at HIV diagnosis was associated with persistent CD4:CD8 ratio inversion, whereas treatment of PHI was protective. These findings confirm the need for testing and early treatment of people aged > 50 years, and could be used in a risk management algorithm for enhanced surveillance.

Factors associated with obesity in the Pharmacokinetic and Clinical Observations in People over Fifty (POPPY) cohort: an observational cross-sectional analysis.

OBJECTIVES: The aims of the study were to describe the prevalence of obesity in the Pharmacokinetic and Clinical Observations in People over Fifty (POPPY) cohort, to identify demographic, clinical and HIV-specific factors associated with obesity, and to characterize the association between obesity and sociodemographic, clinical and HIV-specific factors and quality of life (QoL). METHODS: A cross-sectional analysis was carried out of baseline data from the three groups ["older" people with HIV infection (PWH) aged ≥ 50 years, "younger" PWH aged < 50 years and HIV-negative controls aged ≥ 50 years] within the POPPY cohort. Obesity was defined as a body mass index (BMI) > 30 kg/m2 . RESULTS: A total of 1361 subjects were included in the study, of whom 335 (24.6%) were obese. The prevalence of obesity was higher in controls (22.3%) than in older (16.8%) and younger (14.2%) PWH, with no differences between the two groups of PWH. Factors associated with obesity were older age, female gender, black African ethnicity and alcohol consumption. Recreational drug use and a higher current CD4 T-cell count (in PWH) were associated with lower and higher odds of being obese, respectively. The presence of obesity was associated with worse physical health QoL scores, higher odds of having cardiovascular disease, type 2 diabetes and hypertension, but lower odds of having osteopenia/osteoporosis, irrespective of HIV status. CONCLUSIONS: Despite a lower prevalence of obesity in PWH, specific subgroups (women, people of black African origin and older people) were more likely to be obese, and negative health consequences of obesity were evident, regardless of HIV status. Whether targeted preventive strategies can reduce the burden of obesity and its complications in PWH remains to be determined.

Estimated glomerular filtration rate slopes on tenofovir alafenamide.

OBJECTIVES: The aim of the study was to analyse and compare estimated glomerular filtration rate (eGFR) slopes during exposure to tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF) in individuals who initiated TAF, regardless of prior regimen, before October 2016. METHODS: An observational cohort study was conducted at 11 clinics in the UK and Ireland. Mixed effects models with random intercept and time terms fitted were used to generate and compare eGFR slopes while participants were exposed to TDF and TAF, with adjustment for age, eGFR at TDF/TAF initiation, gender, ethnicity, and time-updated CD4 cell count and HIV RNA measurements. RESULTS: Data were available for 357 subjects (median age 50 years; 80% male; 82% white/other ethnicity; 51% men who have sex with men; median nadir CD4 count 216 cells/µL). The median duration of exposure to TAF was 2.0 (interquartile range 1.6, 2.3) years. At TAF initiation, the median CD4 count was 557 cells/µL, the median eGFR was 80 mL/min/1.73 m2, and 86% had suppressed HIV infection. The mean adjusted eGFR slope during TDF and TAF exposure was -2.08 [95% confidence interval (CI) -2.24, -1.92] and 1.18 (95% CI 0.20, 1.52) mL/min/1.73 m2/year, respectively (P < 0.001). Individuals who experienced rapid eGFR decline (> 3 or 5 mL/min/1.73 m2/year) while receiving TDF experienced significant eGFR recovery while on TAF (P < 0.001). CONCLUSIONS: Significant improvement in eGFR slope was observed in patients who switched from TDF- to TAF-containing antiretroviral regimens. These data provide further support for the renal safety of TAF, and for switching those who experience progressive worsening of renal function from TDF to TAF.

Mental health and COVID-19: is the virus racist?

COVID-19 has changed our lives and it appears to be especially harmful for some groups more than others. Black and Asian ethnic minorities are at particular risk and have reported greater mortality and intensive care needs. Mental illnesses are more common among Black and ethnic minorities, as are crisis care pathways including compulsory admission. This editorial sets out what might underlie these two phenomena, explaining how societal structures and disadvantage generate and can escalate inequalities in crises.

Identifying interventions with Gypsies, Roma and Travellers to promote immunisation uptake: methodological approach and findings.

BACKGROUND: In the UK, Gypsy, Roma and Traveller (GRT) communities are generally considered to be at risk of low or variable immunisation uptake. Many strategies to increase uptake for the general population are relevant for GRT communities, however additional approaches may also be required, and importantly one cannot assume that "one size fits all". Robust methods are needed to identify content and methods of delivery that are likely to be acceptable, feasible, effective and cost effective. In this paper, we describe the approach taken to identify potential interventions to increase uptake of immunisations in six GRT communities in four UK cities; and present the list of prioritised interventions that emerged. METHODS: This work was conducted in three stages: (1) a modified intervention mapping process to identify ideas for potential interventions; (2) a two-step prioritisation activity at workshops with 51 GRTs and 25 Service Providers to agree a prioritised list of potentially feasible and acceptable interventions for each community; (3) cross-community synthesis to produce a final list of interventions. The theoretical framework underpinning the study was the Social Ecological Model. RESULTS: Five priority interventions were agreed across communities and Service Providers to improve the uptake of immunisation amongst GRTs who are housed or settled on an authorised site. These interventions are all at the Institutional (e.g. cultural competence training) and Policy (e.g. protected funding) levels of the Social Ecological Model. CONCLUSIONS: The "upstream" nature of the five interventions reinforces the key role of GP practices, frontline workers and wider NHS systems on improving immunisation uptake. All five interventions have potentially broader applicability than GRTs. We believe that their impact would be enhanced if delivered as a combined package. The robust intervention development and co-production methods described could usefully be applied to other communities where poor uptake of immunisation is a concern. STUDY REGISTRATION: Current Controlled Trials ISRCTN20019630, Date of registration 01-08-2013, Prospectively registered.

Psychological distress among migrant groups in Australia: results from the 2015 National Health Survey.

PURPOSE: To understand the relationship between migration and psychological distress, we (a) calculated the prevalence of psychological distress in specific migrant groups, and (b) examined the association between specific birth groups and psychological distress, while controlling for confounding variables to understand vulnerabilities across migrant groups. METHODS: The prevalence of psychological distress, disaggregated by birthplace, was calculated using data from the Australian 2015 National Health Survey, which measures psychological distress via the Kessler Screening Scale for Psychological Distress (K10). Multivariable logistic regression models, with adjustments for complex survey design, were fitted to examine the association between country of birth and psychological distress once extensive controls for demographic, and socioeconomics factors were included. RESULTS: 14,466 individuals ≥ 18 years completed the K10. Migrants from Italy (20.7%), Greece (20.4%), Southern and Eastern European (18.2%), and North African and Middle Eastern (21.9%) countries had higher prevalence estimates of distress compared to Australian born (12.4%) or those born in the United Kingdom (UK) (9.5%)-the largest migrant group in Australia. After adjusting for demographics, SES factors, duration in Australia, a birthplace in Italy (OR = 2.79 95% CI 1.4, 5.7), Greece (OR = 2.46 95% CI 1.1, 5.5), India (OR = 2.28 95% CI 1.3, 3.9), Southern and Eastern Europe (excluding Greece and Italy) (OR = 2.43 95% CI 1.5, 3.9), North Africa and the Middle East (OR = 3.39 95% CI 1.9, 6.2) was associated with increased odds of distress relative to those born in the UK. CONCLUSIONS: Illuminating variability in prevalence of psychological distress across migrant communities, highlights vulnerabilities in particular migrant groups, which have not previously been described. Identifying such communities can aid mental health policy-makers and service providers provide targeted culturally appropriate care.

A cross-cultural investigation into the influence of eye gaze on working memory for happy and angry faces.

Previous long-term memory (LTM) research found that angry faces were more poorly recognised when encoded with averted vs. direct gaze, while memory for happy faces was unaffected by gaze. Contrastingly, working memory (WM) accuracy for angry faces was unaffected by gaze, but WM was enhanced for happy faces with averted vs. direct gaze. Because the LTM study was conducted in an Eastern culture (Japan) with Japanese faces, while the WM study was conducted in a Western culture (UK) with Caucasian faces, here we investigated WM further to examine whether gaze effects diverge due to cultural variation between the faces and participants. When Western participants viewed Japanese faces (Experiment 1), the happy-averted gaze advantage in WM was replicated. In contrast, Japanese participants viewing Caucasian faces (Experiment 2a) showed poorer WM for angry faces with averted vs. direct gaze, and no influence of gaze on WM for happy faces. When Japanese participants viewed Japanese faces (Experiment 2b), gaze did not modulate WM. Therefore, the way in which expression and gaze interact to influence face WM does not appear to rely on the specific memory system engaged, but instead may be attributed to cultural differences in display rules between Eastern and Western cultures.

A Wide Spectrum Study of α-Globin Chain Variants: Cases from the UK.

Over many years, cases of suspected α-globin chain variants were collected from different parts of the UK. The suspicion was based on the clinical picture, high performance liquid chromatography (HPLC) variant percentage, retention time (RT) and isoelectric focusing (IEF). DNA sequencing and the restriction enzyme EaeI were used for definitive diagnosis. One hundred and forty-eight variants were confirmed on one or both of the two α-globin genes (HBA2, HBA1). These cases were identified as 46 different α-globin chain variants. The most common variants were Hb J-Meerut [HBA2: c.362C>A (or HBA1)] (10.1%) and Hb Q-India (HBA1: c.193G>C) (8.1%), followed by Hb J-Paris-I [HBA2: c.38C>A (or HBA1)] and Hb Manitoba II (HBA1: c.309C>A) (7.4% for each). Other α variants were detected at lower frequencies. Two novel alleles were also detected: Hb Walsgrave [α116(GH4)Glu→Val (HBA2: c.350A>T)] and Hb Coombe Park [α127(H10)Lys→Glu (HBA2: c.382A>G)]. The majority of the ethnic origin was Indian. The positive predictive value for α variant identification by HPLC-RT analysis was 65.9%, 41.9% by IEF, and using both RT and IEF, the value was 72.1%. The number of variants was higher in HBA1 than in HBA2 genes and in exons 1 and 2 than in exon 3. There was no clustering of mutations in consecutive codons. This study, the characterization of a wide spectrum of α-globin chain variants, can facilitate the presumptive diagnosis of these variants prior to screening by a panel of amplification refractory mutation system-polymerase chain reaction (ARMS-PCR), and a definitive diagnosis by DNA sequencing.