Equity of access to renal transplant waiting list and renal transplantation in Scotland: cohort study

Objective To examine the access to the renal transplant waiting list and renal transplantation in Scotland.Design Cohort study.Setting Renal and transplant units in Scotland.Participants 4523 adults starting renal replacement therapy in Scotland between 1 January 1989 and 31 December 1999.Main outcome measures Impact of age, sex, social deprivation, primary renal disease, renal or transplant unit, and geography on access to the waiting list and renal transplantation.Results 1736 of 4523 (38.4%) patients were placed on the waiting list for renal transplantation and 1095 (24.2%) underwent transplantation up to 31 December 2000, the end of the study period. Patients were less likely to be placed on the list if they were female, older, had diabetes, were in a high deprivation category, and were treated in a renal unit in a hospital with no transplant unit. Patients living furthest away from the transplant centre were listed more quickly. The only factors governing access to transplantation once on the list were age, primary renal disease, and year of listing. A significant centre effect was found in access to the waiting list and renal transplantation.Conclusions A major disparity exists in access to the renal transplant waiting list and renal transplantation in Scotland. Comorbidity may be an important factor.     

Las Alpujarras region (South East Spain) HLA genes study: evidence of a probable success of 17th century repopulation from North Spain

Conquest of Granada Muslim Kingdom (1492 AD) finished with Muslim occupation; they were mostly North African Berbers who had reached Iberia by 711 AD. A politics of Iberian Christianization followed after this date: Jewish were expelled in 1492 and Moriscos (Spaniards practicing Muslim religion or speaking Arab) were expelled from all Spanish territory on 1609 AD. Las Alpujarras is a southern Spain mountainous secluded region, which underwent a repopulation from North Spain and a specific Muslim (Moriscos)–Christian war took place according to historical records. Both Las Alpujarras repopulation by northern Iberians and Moriscos expulsion success have been debated and are regarded as non-clarified episodes. In this study, we have addressed the question whether the repopulation succeeded by determining HLA genes of present day Las Alpujarras inhabitants and compared with those of other Mediterranean populations HLA frequencies and genealogies. HLA frequencies show ambiguous results because of extant HLA similar gene frequencies there exist in North Africa and Spain. This is reflected by the finding of North and South western Mediterraneans close relatedness of HLA dendrograms and correspondence analyses. However, the genealogical study of extended HLA haplotypes particularly Alpujarran high frequency of HLA-A29-B44-DRB1*0701-DQA1*02-DQB1*02 (not found in Algerians but frequent in North and Central Spain) and Alpujarran low frequency extended haplotype HLA-A3-B7-DRB1*1501-DQA1*0102-DQB1*0602 (frequent in North Europe) reveals that a significant HLA gene flow from North Spain is observed in present day Alpujarrans: both haplotypes are characteristic of North Spain and North Europe, respectively. This may indicate that enforced Alpujarran repopulation from North Spain may have been a success, which was started by Spanish King Philip II in 1571 AD.     

HLA gene and haplotype frequencies in galicia (NW Spain)

The genetic structure of six populations of Iran (Turks, Kurds, Lurs, Zabolis, Baluchis and Zoroastrians) was examined using data on blood groups, serum proteins and cell enzymes. Our results show conclusively that there are genetic differences among the six populations and the analysis of superimposed R and S matrices defined by Harpending & Jenkins (1973) show that the dispersion of some of the alleles correspond to the dispersion of the populations. The F_ST estimates are not large enough to favour selection on any of the loci studied. The F_IT and F_IS estimates are positive and moderately high suggesting that the genetic differentiation to some extent is influenced by inbreeding.     

Anisakis simplex: the high prevalence in Madrid (Spain) and its relation with fish consumption

Anisakiosis is a nematodosis with high prevalence in Spain. In this work we (a) investigated whether a recently introduced ELISA of Anisakis simplex-specific IgE in serum suffers from cross-reactivity with other common allergens; (b) used this assay to obtain an estimate of the prevalence of A. simplex-specific IgE in the population of Madrid; and (c) related positivity to fish consumption habits. No evidence of cross-reactivity between the ELISA and other allergens was found. The prevalence of positivity was 12.4% (11.7% among healthy subjects and 16% among patients with non-digestive non-allergic pathologies). All interviewed subjects reported consumption of uncooked fish (known to be the most likely source of infection); in addition, positivity was more prevalent among subjects who habitually consumed fresh and possibly undercooked fish than among those who generally consumed frozen fish or boiled or baked fish. These results are discussed in relation to the much lower prevalence observed in Galicia (N.W. Spain).     

Poaceae pollen in the atmosphere of Aranjuez,Madrid and Toledo (central Spain)

The main aim of this work is to study the aerobiological behaviour of Poaceae pollen in three areas of central Spain (Aranjuez, Madrid and Toledo), all of which are similar from a geographical, climatic and biogeographical point of view, and they are located nearby one another. The samplings were carried out over a period of 4 years (2005–2008) using Hirst-type spore traps. Grass pollen is responsible for most spring allergic reactions in the pollen-sensitive population in central Spain, and they are very abundant in the atmosphere of this part of Iberian Peninsula. The average amount of this pollen type, as a percentage of the annual total pollen amount, is 7.4% in Aranjuez, 9.2% in Madrid and 11.3% in Toledo. Poaceae pollen is present in the atmosphere over a long period of time (February–October), and its maximum concentrations are detected during May and June (weeks 16–25). The city of Toledo has the highest annual concentrations of grass pollen (average 5,797 grains) with a great number of days exceeding the allergy thresholds proposed by the Spanish Aerobiology Network (REA). Madrid and Aranjuez present similar annual concentrations of grass pollen with values of 2,961 grains and 2,751 grains, respectively. The correlation analysis between the daily levels of grass pollen and meteorological variables of temperature and rainfall show a significant correlation, positive with temperature (maximum, mean and minimum) and negative with rainfall.     

Molecular surveillance of HIV-1 in Madrid, Spain: a phylogeographic analysis

The molecular epidemiology of HIV-1 is constantly changing, mainly as a result of human migratory flows and the high adaptive ability of the virus. In recent years, Spain has become one of Europe''s main destinations for immigrants and one of the western European countries with the highest rates of HIV-positive patients. Using a phylogeographic approach, we have analyzed the relationship between HIV-1 variants detected in immigrant and native populations of the urban area of Madrid. Our project was based on two coincidental facts. First, resistance tests were extended to naïve and newly diagnosed patients, and second, the Spanish government legislated the provision of legal status to many immigrants. This allowed us to obtain a large data set (n = 2,792) from 11 Madrid hospitals of viral pol sequences from the two populations, and with this unique material, we explored the impact of immigration in the epidemiological trends of HIV-1 variants circulating in the largest Spanish city. The prevalence of infections by non-B HIV-1 variants in the studied cohort was 9%, rising to 25% among native Spanish patients. Multiple transmission events involving different lineages and subsubtypes were observed in all the subtypes and recombinant forms studied. Our results also revealed strong social clustering among the most recent immigrant groups, such as Russians and Romanians, but not in those groups who have lived in Madrid for many years. Additionally, we document for the first time the presence of CRF47_BF and CRF38_BF in Europe, and a new BG recombinant form found in Spaniards and Africans is tentatively proposed. These results suggest that the HIV-1 epidemic will evolve toward a more complex epidemiological landscape.     

HLA in Jaidukama: an Amerindian secluded Colombian population with new haplotypes and Asian and Pacific-shared alleles

America first inhabitants and peopling are still debated. In order to increase knowledge about these questions, we have aimed to detect HLA genes of an Amerindian secluded community: Jaidukama, who lives in North Colombia Equatorial forest. HLA genotyping and extended haplotype calculations were carried out in 39 healthy individuals belonging to 13 families. HLA frequencies were compared to other Amerindians and worldwide populations by calculating genetic distances, relatedness dendrograms and correspondence analyses. Only four DRB1 alleles were found (*0404, *0407, *1402 and *1602); however a total of 17 Amerindian different extended class I–class II HLA haplotypes were directly counted from the family studies, nine of them were specific of Jaidukamas. Some of the alleles or group of alleles within an extended haplotype (i.e. DQB1–DRB1) were also found in Asians and Pacific Islanders, further supporting existence of Asian and Pacific gene flow with Amerindians or a common founder effect. It is further supported that HLA extended haplotypes vary faster than alleles in populations. It is concluded that this unique model of Amerindian secluded families study suggests that rapid HLA haplotype variation may be more important than allele variation for survival (starting immune responses). This work may also be useful for future transplant programs in the area.     

Temporal Distribution and Weather Correlates of Norway Rat (Rattus norvegicus) Infestations in the City of Madrid, Spain

Urban Norway rats are challenging pests, posing significant health and economic threats. Implementing ecologically based integrated rodent management (EBIRM) programmes relies primarily on the understanding of ecological relationships between rodents and their environments, with emphasis on the processes influencing rodent populations in the target ecosystem. We investigated the temporal distribution of urban Norway rat infestations in Madrid, Spain, and tested for the association of such infestations with temperature, relative humidity and precipitation by fitting a multivariate Poisson generalized linear model to a 3-year (2006–2008) daily time series of 4,689 Norway rat sightings. Norway rat infestations showed a marked seasonality, peaking in the summer. Most Norway rat sightings were reported on Mondays. Minimum temperature and relative humidity were positively associated with Norway rat infestation, whereas the association with precipitation was negative. The time series was adequately explained by the model. We identified previously unrecognized time periods that are more prone to Norway rat infestation than others and generated hypotheses about the association between weather, human outdoor activity, resource availability, rodent activity and population size. This provided local authorities engaged in preserving urban ecosystem health with basic research information to predict future rodent outbreaks and support the implementation of EBIRM programmes in urban areas.     

Population genetic analysis of the genes APOE, APOB(3'VNTR) and ACE in some black and Amerindian communities from Colombia

A population genetic study was carried out with the APOE, APOB and ACE loci in 17 Colombian human populations. Ten of them were Amerindian communities coming from the northeastern part of Colombia, Pacific region, Eastern Plains and Amazonia. Six were black populations from Providence Island, Caribbean and Pacific coasts. Finally, the Mestizo population of Bogota was studied as well. The APOE and ACE loci were in Hardy-Weinberg equilibrium, whereas the APOB locus was not studied in all populations. The genetic heterogeneity was substantially greater among the Amerindian populations (G(ST) = 0.059) than in the Afrocolombian populations (G(ST) = 0.009). Also the gene flow population pair estimates were so much higher among the Afrocolombian populations (Nm = 49.08 +/- 43.07) than among Amerindian populations (Nm = 9.66 +/- 18.04). Different phylogenetic and multivariant analyses showed that the Amerindian populations analyzed were clustered in three different arrays: one constituted by the Colombian northeastern and Pacific populations, the second one by the two Amazon populations (Coreguaje and Nukak) and the last one by the Yuco (the unique Caribbe-speaking population among those studied). The latter population was highly divergent from a genetic point of view from the remainder Amerindian populations studied. By using the Mantel test, the existence of a positive and significant correlation between the genetic and geographical distances found among Amerindian populations was demonstrated. This fact was not observed among the Afrocolombian populations. Nevertheless, an isolation-by-distance Slatkin analysis test did not show a significant clear structure of this special pattern among the Indian tribes studied.     

Integrated archaeobotanical research into vegetation management and land use in El Llano de la Horca (Santorcaz, Madrid, central Spain)

This paper presents an integrated archaeobotanical analysis carried out at the site known as “El Llano de la Horca”, a Bronze and Late Iron Age (3rd–1st century b.c.) Carpetanian settlement in central Spain (3600?±?80 b.p.). Pollen and spore analysis indicates an open landscape dominated by the herb taxa Asteraceae, Chenopodiaceae and Poaceae with an important representation of Glomus. The combination of pollen and charcoal studies also reveals the presence of Pinus sylvestris-nigra, P. pinaster-pinea, Juniperus thurifera, Quercus faginea, Q. ilex and Q. suber as the main trees used. Occurrences of Alnus, Corylus, Fraxinus and Juglans suggest the existence of water courses nearby. The archaeobotanical data is correlated with the geographical setting and archaeological context. The evolution of settlement patterns in central Spain, as well as the economy of other Carpetanian sites, is also considered to evaluate how this territory was managed for its vegetational resources since the Bronze Age (BA). Changes are expected as a consequence of different socio-economic factors at this site, especially when the settlement became an important Carpetanian oppidum. The combined results demonstrate a subsistence system based on cereal agriculture, in which naked wheat was dominant, together with some hulled barley and some erratic occurrences of hulled wheat. Furthermore, livestock breeding and metalwork activities seem to have resulted in a significant loss of woodland in order to clear land for crop fields and cattle grazing to cope with the needs of the growing Carpetanian community.     

Two critical genes (HLA-DRB1 and ABCF1)in the HLA region are associated with the susceptibility to autoimmune pancreatitis

We have previously reported that autoimmune pancreatitis (AIP) is a bioclinical entity characterized by high serum immunoglobulin G4 concentrations and association with the HLA-DRB1*0405-DQB1*0401 haplotype. However, the precise identity of gene(s) within this haplotype directly responsible for AIP pathogenesis is yet to be established. To dissect the genetic contribution of the incriminated haplotype, we have now performed an association analysis within the human leukocyte antigen (HLA) region using various types of polymorphic markers. Genomic DNAs from 43 AIP patients and 213 unrelated Japanese controls were used in this analysis. In each DNA sample, we established the genotype of 25 microsatellite markers distributed throughout the HLA region, that of single nucleotide polymorphism within the 5'-flanking regions of the TNFA and IkBLI (also known as NFKBIL1) as well as HLA class I and II genes. The HLA-linked susceptibility regions for AIP were localized to two segments: HLA-DRB1 (*0405; OR = 3.20, P = 0.00063, Pc = 0.0016) -DQB1 (*0401; OR = 3.29, P = 0.00046, Pc = 0.0069) in the HLA class II and C3-2-11 microsatellite (allele 219; OR = 2.96, P = 0.0076, Pc = 0.099) in the HLA class I regions. Upon stratification analysis in search for a synergistic effect given the extensive linkage disequilibrium within the major histocompatibility complex, it was established that each segment contributed to disease pathogenesis. The two critical HLA regions for susceptibility to AIP are limited to the HLA-DRB1*0405-DQB1*0401 in the class II and the ABCF1 proximal to C3-2-11, telomeric of HLA-E, in the class I regions.     

Clustered environments and randomized genes: a fundamental distinction between conventional and genetic epidemiology

Background

In conventional epidemiology confounding of the exposure of interest with lifestyle or socioeconomic factors, and reverse causation whereby disease status influences exposure rather than vice versa, may invalidate causal interpretations of observed associations. Conversely, genetic variants should not be related to the confounding factors that distort associations in conventional observational epidemiological studies. Furthermore, disease onset will not influence genotype. Therefore, it has been suggested that genetic variants that are known to be associated with a modifiable (nongenetic) risk factor can be used to help determine the causal effect of this modifiable risk factor on disease outcomes. This approach, mendelian randomization, is increasingly being applied within epidemiological studies. However, there is debate about the underlying premise that associations between genotypes and disease outcomes are not confounded by other risk factors. We examined the extent to which genetic variants, on the one hand, and nongenetic environmental exposures or phenotypic characteristics on the other, tend to be associated with each other, to assess the degree of confounding that would exist in conventional epidemiological studies compared with mendelian randomization studies.

Methods and Findings

We estimated pairwise correlations between nongenetic baseline variables and genetic variables in a cross-sectional study comparing the number of correlations that were statistically significant at the 5%, 1%, and 0.01% level (α = 0.05, 0.01, and 0.0001, respectively) with the number expected by chance if all variables were in fact uncorrelated, using a two-sided binomial exact test. We demonstrate that behavioural, socioeconomic, and physiological factors are strongly interrelated, with 45% of all possible pairwise associations between 96 nongenetic characteristics (n = 4,560 correlations) being significant at the p < 0.01 level (the ratio of observed to expected significant associations was 45; p-value for difference between observed and expected < 0.000001). Similar findings were observed for other levels of significance. In contrast, genetic variants showed no greater association with each other, or with the 96 behavioural, socioeconomic, and physiological factors, than would be expected by chance.

Conclusions

These data illustrate why observational studies have produced misleading claims regarding potentially causal factors for disease. The findings demonstrate the potential power of a methodology that utilizes genetic variants as indicators of exposure level when studying environmentally modifiable risk factors.     

Risk of pollen allergy in Nerja (southern Spain): a pollen calendar

An aeropalynological study was carried out in the atmosphere of the city of Nerja (southern Spain) during a period of 4 years (2000–2003), using a Hirst type volumetric pollen trap. An annual pollen index of 59,750 grains, on average, was obtained with 80–85% of the total pollen recorded from February to May, with Pinus, Olea, Urticaceae, Cupressaceae, Quercus and Poaceae being the principal pollen producers in abundance order. A total of 29 pollen types that reached a 10-day mean equal to or greater than 1 grain of pollen per m³ of air is reflected in a pollen calendar. The results were compared with those obtained for nearby localities and a correlation analysis was made between the daily fluctuations of the main pollen types and total pollen, and meteorological parameters (temperature, rainfall and hours of sun). The daily, monthly and annual values reached by the most important pollen types from an allergenic point of view (Olea, Urticaceae and Poaceae) confirms Nerja as a high-risk locality for the residents and the numerous tourists who visit the area.