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Epidemiology of multiple sclerosis in U.S. veterans: V. Ancestry and the risk of multiple sclerosis.

Self-reported ancestry data for the U.S. population from the 1980 decennial census and multiple sclerosis (MS) risk data derived from a large series of World War II white male veterans with MS and matched controls were aggregated on a state level and analyzed to determine the relationship between ancestry and MS risk. A significant portion of the state-by-state variation in MS risk is explainable statistically by differences in ancestry among state populations, even when geographic latitude is included in analyses. In the main, Swedish and other Scandinavian ancestry is most consistently associated with places with increased MS risk. In some analyses, Italian, French, and (to a lesser extent) Scottish ancestries are also associated with increased risk, whereas English and Dutch ancestries are each associated with decreased risk, but most of these non-Scandinavian correlations may reflect predominantly geography per se. These findings provide evidence that ancestry of the resident population, a confounded measure of genetic susceptibility and cultural environment, is part of the complicated picture of MS as a disease of place.

Analysis of Variance↗

[Not Available].

In studying the genesis of 'Generalplan Ost' one can elucidate the alliance of academic research and military expansion in Nazi Germany in a unique way. By 'Generalplan Ost' we understand the total German planning effort in transforming the territories of Poland, the Baltic republics and Soviet Union, which were occupied since the beginning of World War II. In this scientists were not only provided with ample opportunities for research by the National Socialist government, but the Nazi policy of occupation created the preconditions necessary for putting theoretical models into practice. this was done in complete disregard of pre-existing structures in population, settlement, society, economy, and patterns of traffic. The principal aim consisted in the total transformation of the envisaged Eastern European sphere and the implantation of a new National Socialist social order style in Eastern Europe. Scientific planning not only implied a declaration of war against the very people living in the geographic sphere covered by the plan, but presupposed the existence of war in order to put the plan into practice. In a rare mixture of social science, geography and biology, instruments of science made possible and provoked the social selection and deportation of human beings as well as attempts at 'Germanization' and 'Umvolkung'. It is a well known fact, that deportation and extermination became a brutal reality as an intrinsic ingredient of these planning efforts.

Europe↗

Mechanistic Insights Into the Association Between Gut Microbiota Diversity and Atherosclerosis, Acute Coronary Syndrome, and Peripheral Arterial Disease Progression.

BACKGROUND: The gut microbiome has emerged as a potential contributor to cardiovascular diseases (CVDs), including atherosclerosis, acute coronary syndrome (ACS), and peripheral arterial disease (PAD). While observational studies link dysbiosis to CVD, causal relationships remain uncertain. METHODS: This narrative review synthesizes evidence from human observational studies, clinical interventions, and experimental models to distinguish association from mechanistic plausibility and clinical causality. Literature was searched through July 2026 in PubMed/MEDLINE, Web of Science, and Scopus. RESULTS: Microbial metabolites-including trimethylamine N-oxide (TMAO), short-chain fatty acids (SCFAs), bile acids, and lipopolysaccharide (LPS)-modulate endothelial function, immune cell programming, platelet activity, and plaque stability through receptor-mediated signaling and epigenetic regulation. SCFAs demonstrate potentially protective effects via GPCR and HDAC pathways, while TMAO is associated with atherothrombotic risk. However, much mechanistic evidence derives from preclinical studies. Heterogeneity from diet, geography, host characteristics, renal function, and medications substantially influences microbiota-CVD associations. CONCLUSION: The gut-vascular connection is biologically plausible, but definitive clinical causality remains unproven. Microbiome-directed therapies (dietary modulation, pre/pro/synbiotics, targeted metabolite inhibition) are investigational. Prospective, standardized, adequately powered human studies with clinically meaningful outcomes are essential before routine cardiovascular application.

Gastrointestinal Microbiome↗

Racial treatment trends in localized/regional prostate carcinoma: 1992-1999.

BACKGROUND: African-American men have a greater incidence of and mortality from prostate carcinoma compared with white men, and they are less likely to receive definitive therapy (radical prostatectomy or external beam radiation therapy). During the 1990s, the use of brachytherapy increased; however, its influence on racial and ethnic prostate carcinoma treatment trends remains unclear. The objective of this study was to describe treatment trends over the period 1992-1999 for localized/regional prostate carcinoma among white, Hispanic, and African-American men. METHODS: Using the Surveillance, Epidemiology, and End Results (SEER) registry data from 1992 through 1999, logistic regression models were used to determine whether the odds of receiving a specific treatment modality differed by racial and ethnic group and whether the differences changed over time when the models were adjusted for age, marital status, tumor grade, and SEER site (geography). RESULTS: The authors identified 142,340 men, including white men (81.6%), Hispanic men (6.4%), and African-American men (12.0%). Racial and ethnic differences in the rates of use of androgen-deprivation therapy/expectant management were noted; however, these differences appeared to lessen over time (P < 0.001). The rate of utilization of radical prostatectomy increased for Hispanic men, remained flat for African-American men, and decreased for white men. The utilization of brachytherapy and combination therapy increased for all three groups; however, the greatest increase in utilization was among white men. CONCLUSIONS: Further research will be required to determine the patient-level and provider-level variables that influence racial and ethnic treatment differences in localized/regional prostate cancer.

Black or African American↗

Incidence of noncutaneous melanomas in the U.S.

BACKGROUND: Description of the epidemiology of noncutaneous melanoma has been hampered by its rarity. The current report was the largest in-depth descriptive analysis of incidence of noncutaneous melanoma in the United States, using data from the North American Association of Central Cancer Registries. METHODS: Pooled data from 27 states and one metropolitan area were used to examine the incidence of noncutaneous melanoma by anatomic subsite, gender, age, race, and geography (northern/southern and coastal/noncoastal) for cases diagnosed between 1996 and 2000. Percent distribution by stage of disease at diagnosis and histology were also examined. RESULTS: Between 1996 and 2000, 6691 cases of noncutaneous melanoma (4885 ocular and 1806 mucosal) were diagnosed among 851 million person-years at risk. Ocular melanoma was more common among men compared with women (6.8 cases per million men compared with 5.3 cases per million women, age-adjusted to the 2000 U.S. population standard), whereas mucosal melanoma was more common among women (2.8 cases per million women compared with 1.5 cases per million men). Rates of ocular melanoma among whites were greater than eight times higher than among blacks. Rates of mucosal melanoma were approximately two times higher among whites compared with blacks. CONCLUSIONS: In contrast to cutaneous melanoma, there was no apparent pattern of increased noncutaneous melanoma among residents of southern or coastal states, with the exception of melanoma of the ciliary body and iris. Despite their shared cellular origins, both ocular and mucosal melanomas differ from cutaneous melanoma in terms of incidence by gender, race, and geographic area.

Adolescent↗

How study of geographic epidemiology of disease can help in detection of adverse drug reactions.

The geographic epidemiology of adverse drug reactions can often help in their recognition and in pinpointing the responsible drug. Since different countries often introduce new drugs at varying periods of time and they achieve varying degrees of popularity and use, this information may sometimes aid the epidemiologist in the search for the etiology of unwanted drug effects. Some examples where geography helped unravel the story behind certain adverse drug reactions are presented.

Adolescent↗

DNA profiling resolves the limited importance of flower colour in defining varieties of Lantana camara.

Randomly amplified polymorphic DNA (RAPD), successfully used to establish flower colour, is of limited importance in characterising weedy varieties of Lantana camara. Initially the internal transcribed spacer 1 (ITS1) region was sequenced for common pink and common pink-edged red varieties of L. camara from Australia and L. urticofolia from the neotropics. This proved unhelpful in differentiating varieties due to a lack of variation and the hybrid origin of L. camara, necessitating the utilisation of DNA profiling techniques. Unweighted pair group method arithmetic average (UPGMA) analysis of RAPD data demonstrated that geographical proximity contributes more significantly to genetic relatedness than flower colour. Analysis of molecular variance (AMOVA) likewise demonstrated that geography accounts for a relatively large variance component. These data indicate that the use of flower colour as a primary identification tool needs to be reevaluated. The use of RAPD may prove useful in characterising the weedy varieties of lantana present in Australia and the South Pacific. Since biological control efforts are being hindered by the inadequacy of current morphological taxonomy, it is expected that DNA profiling will underpin continuing studies on the management and control of L. camara.

Australia↗

Polymorphism in the promoter region of the apolipoprotein AI gene associated with differences in apolipoprotein AI levels: the European Atherosclerosis Research Study.

The effect associated with the substitution of adenine (A) for guanidine (G) in the promoter region of the apolipoprotein AI gene (-75 bp) with plasma apo AI and high-density lipoprotein (HDL) levels was investigated in the European Atherosclerosis Research Study (EARS). This is a study of healthy offspring (cases) of fathers who had suffered premature myocardial infarction (MI) before age 55 years (n = 565) and age- and sex-matched controls (n = 1,078) from 12 European countries, divided into 5 regions based on geography and language. The frequency of the polymorphism was not significantly different among the regions and the relative frequency of the rare A allele was similar in cases and controls (0.159 vs. 0.142) combining data from all regions. Individuals with one or more A allele had significantly higher plasma apo AI levels (P < 0.05) than individuals homozygous for the G allele. This effect was consistent in all regions. The data were analyzed separately in males and females. In females, those with one or more A allele had significantly higher apo AI levels (P = 0.05) than individuals homozygous for the G allele, and this raising effect of the A allele was greater in cases than controls for both apo AI (5.23% vs. 1.56%) and HDL (4.48% vs. 1.89%). In males, the A allele was associated with higher levels of apo AI and HDL, but the effect was much smaller and the differences did not reach statistical significance. In the females, where the effect of the A allele was strongest, the effect on apo AI associated with genotype was evident in non-smokers, and individuals with one or two A alleles had 3.6% higher apo AI and 3.14% higher HDL levels than individuals homozygous for the G allele. However, in the female smokers the raising effect of the A allele was greatly reduced (0.56%). Thus genetic variation in the promoter region of the apo AI gene is associated with differences in apo AI and HDL levels in healthy individuals throughout Europe, but the effect is modulated by gender, environmental factors such as smoking, and a family history of MI.

Adenine↗

Public health expenditure and spatial interactions in a decentralized national health system.

One of the limitations of cross-country health expenditure analysis refers to the fact that the financing, the internal organization and political restraints of health care decision-making are country-specific and heterogeneous. Yet, a way through is to examine the influence of such effects in those countries that have undertaken decentralization processes. In such a setting, it is possible to examine potential expenditure spillovers across the geography of a country as well as the influence of the political ideology of regional incumbents and institutional factors on public health expenditure. This paper examines the determinants of public health expenditure within Spanish region-states (Autonomous Communities, ACs), most of them subject to similar financing structures although exhibiting significant heterogeneity as a result of the increasing decentralization, region-specific political factors along with different use of health care inputs, economic dimension and spatial interactions.

Health Expenditures↗

The predominance of hepatitis delta virus genotype I among chronically infected Italian patients.

The sera of 46 Italian patients with chronic hepatitis delta virus (HDV) infection were analyzed for HDV RNA by polymerase chain reaction (PCR) amplification. Genetic analysis of sequences amplified from two regions of the HDV genome indicated that all HDV RNA-positive patients (98%) were infected with HDV genotype I. In Italy, infection with this genotype appeared to be associated with a broad spectrum of chronic disease. No subtypes of HDV genotype I were identified, nor were genetic variations clearly associated with different disease patterns; however, clustering of some sequences suggested correlations with geography and transmission route. Italian HDV genotype I sequences were more diverse than those from east Asia and North America, suggesting that HDV genotype I was likely introduced to Italy earlier and/or from multiple sources as compared to those areas. All sequences analyzed were predicted to fold into the unbranched rod structure typical of HDV RNA. Within this structure, three conserved features were identified, including sequences around the RNA editing site and the polyadenylation signal site. We conclude that in Italy, where HDV infection has been endemic, the overwhelmingly predominant genotype of HDV is genotype I.

Adult↗

Population-based case-control study of measles, mumps, and rubella and inflammatory bowel disease.

BACKGROUND: Previous controversy was generated over the hypothesis that a paramyxovirus such as measles or vaccination against such viruses might be causally associated with inflammatory bowel disease (IBD). We aimed to determine if Crohn's disease (CD) or ulcerative colitis (UC) subjects are more likely to be seropositive for measles, mumps, or rubella than controls. METHODS: Using our population-based University of Manitoba IBD Research Registry we recruited CD (n = 235) and UC (n = 137) subjects ages 18-50 years for a study involving detailed questionnaires and venipuncture. We accessed the population-based databases of Manitoba Health (single provincial health insurer) to get age-, gender-, and geography-matched non-IBD controls (n = 310). We used a standard enzyme-linked immunosorbent assay (ELISA) to measure serum antibodies. RESULTS: Seropositivity for measles and mumps was similar in controls (98.1%, 78.4%, respectively) as in CD (96.2%, 72.3% respectively) and in UC (95.5%, 74.6%, respectively). However, controls were significantly more likely to be seropositive for rubella (98.1%) than were CD cases (91.0%, P < 0.0002) or UC cases (93.3%, P = 0.01). Males accounted for the significantly lower rates of seropositivity to rubella with CD. While we determined that significantly more controls than CD were vaccinated, we cannot be sure if the increased rate of rubella seropositivity in controls is secondary to wildtype or vaccine-associated infection. CONCLUSIONS: These data suggest there is no association of having acquired measles, mumps, or rubella (by natural infection or through vaccination) and CD or UC. If anything, these data may suggest some protective effect of having acquired rubella infection or vaccine against acquiring CD.

Adolescent↗

Geographic pathology revisited: development of an atlas of cancer in India.

Information on 217,174 microscopically diagnosed cancers diagnosed in 2001-2002 was collected from pathology laboratories in 68 districts across India. Data collection took place primarily via the Internet. Average annual age-adjusted incidence rates for microscopically diagnosed cases (MAAR) by gender and site were calculated for each of the 593 districts in the country. The rates were compared to those from established population based cancer registries (PBCR). In 82 districts, the MAAR for 'all cancer sites' was above a "completeness" threshold of 36.2/100,000 (based on results of a rural PBCR). The results confirmed some known features of the geography of cancer in India, and brought to light new ones. Cancers of the mouth and tongue are particularly frequent in both genders in the southern states. Very high rates of nasopharynx cancer were found in the northeastern states (Nagaland, Manipur). There was clear geographic correlation between the rates of cervical and penile cancer, and a high rate of stomach and lung cancer (in both genders) in many districts of Mizoram State. The area of high risk for gallbladder cancer seems larger than suspected previously, involving a wide band of northern India. There is a belt of high incidence of thyroid cancer in females in southwest coastal districts. Other than identifying possible existence of high-risk areas of specific cancers, our study has recognized places where PBCR could be established. The study was remarkably cost-effective and the electronic data-capture methodology provides a model for health informatics in the setting of a developing country.

Female↗

Reduced incidence of cervical cancer in mothers of sons with allergic rhinoconjunctivitis, asthma or eczema.

Because infection with human papillomavirus is a necessary cause of cervical cancer, it is likely that host immunological factors involved in defense against such infections are important for susceptibility to this cancer. By examining associations between allergy in sons and cervical cancer in their mothers, we aimed to test for genetic components involved in both allergy and cervical cancer development. Women born in Sweden between 1932 and 1960 with at least 1 son with medical records from military conscription examination were included in the study (N = 717,963). Among these women there were 41,910 in situ and 3,618 invasive cases of cervical cancer. Hazard ratios of in situ and invasive cervical cancer were estimated as functions of allergic rhinoconjunctivitis, asthma and eczema diagnoses in sons. Adjustment was made for the possible confounders: age, year of birth, education, socio-economic index, geography, number of conscripted sons and total number of offspring. The risk of in situ and invasive cervical cancer was lower for women having sons diagnosed with hypersensitivity (allergic rhinoconjunctivitis, asthma or eczema). Fully adjusted hazard ratios for women with 1 hypersensitive son were for in situ 0.86 (95% CI 0.84-0.88) and for invasive cervical cancer 0.82 (95% CI 0.74-0.91). The protective effects were similar between the 3 allergic diagnoses and increased with number of sons with a diagnosis. There was no significant association between non-cervical cancer in mothers and allergy in sons. These results strengthen the hypothesis that inherited immunological factors are important in determining risk of cervical cancer, probably by affecting mechanisms for viral persistence.

Adolescent↗

Building families-Implementing balanced sexual and reproductive health: A Joint IFFS and ISA Scientific Statement.

One of the main initiatives of the World Health Organization (WHO) is the promotion of Sexual and Reproductive Health (SRH). Sexuality, infertility, and contraception are three interconnected pillars of SRH, each essential for achieving global equity in family planning and family building. This scientific Statement, jointly developed by the International Federation of Fertility Societies (IFFS) and the International Society of Andrology (ISA), advocates for inclusive, evidence-based care for all individuals and couples, regardless of geography or socioeconomic status. The Statement underscores the need to enhance practitioner and policymaker education to support access to infertility evaluations and treatments for both men and women and to promote the availability of comprehensive contraceptive services for all in need. The Statement addresses three core domains: sexuality, infertility, and contraception. It emphasizes a biopsychosocial approach to SRH, highlighting the complex interplay between sexual function and fertility. Infertility is a multifactorial condition requiring early, holistic, and multidisciplinary management, including integrated male and female evaluations, medically assisted reproduction, and fertility preservation strategies. Contraception is explored through the lens of global unmet needs, expanding options for male contraceptives, and the importance of socio-culturally sensitive education and counseling. The joint efforts of the IFFS and ISA call for couple-centered SRH, acknowledging the sociocultural and policy challenges that affect access to care in a region-specific manner. This Statement aims to serve as a clinical and advocacy guide for practitioners and stakeholders, reinforcing that reproductive autonomy and access to care are vital components and duties for policymakers when developing public health strategies.

contraception↗

Monolayer studies of insulin-lipid interactions.

The interactions between insulin and various lipids were studied by monolayer penetration experiments at constant surface area. The increase in surface pressure, delta II, of a lipid film depended upon the particular lipid used and the concentration of insulin in the subphase. For all lipids studied, delta II was dependent on the initial surface pressure of the lipid film. Evidence of the interaction between insulin and the lipids was found in the ability of insulin to penetrate lipid films with initial pressures greater than 16 dynes/cm, the maximum surface pressure obtained by insulin alone. For phospholipids, both the nonpolar and polar regions influenced the degree of interaction with insulin. Saturated chain lecithins exhibited less penetration than phospholipids with unsaturated hydrocarbon chains. The net charge of the lipid was not found to be an important determinant of penetration; however, the structure of the polar group can have a dramatic effect. Insulin penetration of mixed lipid films cannot be predicted by the penetration characteristics of the pure components. The possible role of these interactions in determining the geography of the insulin molecule within the liposome and its resultant effects on the stability is discussed.

Animals↗

Parkinson's disease and LRRK2: frequency of a common mutation in U.S. movement disorder clinics.

The G2019S mutation in the LRRK2 gene is reportedly a common cause of familial Parkinson's disease (PD) and may also have a significant role in nonfamilial PD. The objective of this study was to assess mutation carrier frequency in PD patients from movement disorder clinics in the United States, stratified by family history, age at onset, and geography; to determine carrier frequency in a large and well-characterized control population; to examine segregation of mutation in families of patients; and to correlate genotype with clinical phenotype. One thousand four hundred twenty-five unrelated PD patients from movement disorder clinics in Oregon, Washington, and New York and 1,647 unrelated controls were studied. The G2019S mutation was detected using a TaqMan assay and verified by sequencing. Eighteen of 1,425 patients and one of 1,647 controls had the mutation. Carrier frequency (+/- 2SE) in patients was 0.013 +/- 0.006 overall, 0.030 +/- 0.019 in familial PD, 0.007 +/- 0.005 in nonfamilial PD, 0.016 +/- 0.013 in early-onset PD, and 0.012 +/- 0.007 in late-onset PD. Geographic differences were insignificant. Age at onset of mutation carriers ranged from 28 to 71 years. Mutation carriers were clinically indistinguishable from idiopathic PD. LRRK2 G2019S is the single most common pathogenic mutation linked to neurodegenerative disease to date.

Adolescent↗

Adjustments for non-telephone bias in random-digit-dialling surveys.

Telephone surveys are widely used in the U.S.A. for the study of health-related topics. They are subject to 'coverage bias' because they cannot sample households that do not have telephones. Although only around 5 per cent of households do not have a telephone, rates of telephone coverage show substantial variation by geography, demographic factors and socio-economic factors. In particular, lack of telephone service is more common among households that contain ethnic and racial minorities or that have lower socio-economic status with fewer opportunities for access to medical care and poorer health outcomes. Thus, failure to adequately account for households without telephones in health surveys may yield estimates of health outcomes that are misleading, particularly in states with at least moderate telephone non-coverage. The dynamic nature of the population of households without telephones offers a way of accounting for such households in telephone surveys. At any given time the population of telephone households includes households that have had a break or interruption in telephone service. Empirical results strongly suggest that these households are very similar to households that have never had telephone service. Thus, sampled households that report having had an interruption in telephone service may be used also to represent the portion of the population that has never had telephone service. This strategy can lead to a reduction in non-coverage bias in random-digit-dialling surveys. This paper presents two methods of adjusting for non-coverage of non-telephone households. The effectiveness of these methods is examined using data from the National Health Interview Survey. The interruption-in-telephone-service methods reduce non-coverage bias and can also result in a lower mean squared error. The application of the interruption-in-telephone-service methods to the National Immunization Survey is also discussed. This survey produces estimates for the 50 states and 28 urban areas. The interruption-in-telephone-service estimates tend be slightly lower than estimates resulting from poststratification and from another non-coverage adjustment method. The results suggest that the reduction in bias is greatest for variables that are highly correlated with the presence or absence of telephone service.

Bias↗

Using hierarchical models to attribute sources of variation in consumer assessments of health care.

The Consumer Assessments of Healthcare Providers and Systems (CAHPS) Medicare Advantage (MA-CAHPS) survey has provided extensive and uniform data for 8 years on the quality of Medicare health plans in the United States. The complex structure of the data makes hierarchical modelling an appropriate analytic tool. After describing the CAHPS survey and the analytic methods used in standard reports, we review research using two multilevel modelling strategies, each addressing a different aspect of the structure of the CAHPS data. The first fits a 2-level Fay-Herriott-type model to data aggregated by plan to estimate plan-level correlations among summary scores on different items. By forming separate measures for healthier and sicker members of each plan, we were able to determine which items measured distinct dimensions of quality depending on health status. The second analysis evaluated the relative contributions of geography and organizational units to the various quality measures, and the amount of variation over time in each. Geographical variation predominated for aspects of member experiences that are not typically under the direct control of plans, and the geographical effects were very stable over time. Each of the two analyses can be regarded as a simplification for particular objectives of a larger underlying model. Further methodological development is needed to better characterize variation in quality.

Data Interpretation, Statistical↗