The epidemiology of travel-associated campylobacteriosis is still largely unclear, and various known risk factors could only explain limited proportions of the recorded cases.Using data from 28,704 notifications of travel-associated campylobacteriosis in Sweden 1997 to 2003 and travel patterns of 16,255 Swedish residents with overnight travel abroad in the same years, we analysed risks for travel-associated campylobacteriosis in 19 regions of the world, and looked into the seasonality of the disease in each of these regions.The highest risk was seen in returning travellers from the Indian subcontinent , and the lowest in travellers from the other Nordic countries . In Africa, large differences in risk between regions were noted, with 502 /100,000 in travellers from East Africa, compared to 76/100,00 from West Africa and 50/100,000 from Central Africa. A distinct seasonal pattern was seen in all temperate regions with peaks in the summer, while no or less distinct seasonality was seen in tropical regions. In travellers to the tropics, the highest risk was seen in children below the age of six.Data on infections in returning travellers together with good denominator data could provide comparable data on travel risks in various regions of the world. Campylobacter infection is a zoonotic disease, observed in most parts of the world. The disease is caused by Campylobacter jejuni, or less commonly Campylobacter coli. It is estimated to cause 5–14% of diarrhoea, worldwide [Campylobacter infection has emerged to be most important bacterial cause of gastrointestinal infection. Animals  are the major reservoir for the bacteria. Campylobacter does not easily grow in food, but the critical infective dose is low [orldwide . Also ine is low .Unlike salmonellosis with well-known routes of transmission, the epidemiology of campylobacteriosis is still largely unclear, and various known risk factors could only explain limited proportions of the recorded cases . Known rCampylobacter infection is a leading cause together with infections due to enterotoxigenic Escherichia coli (ETEC), salmonellosis, and shigellosis [Approximately 80 million persons from industrialized countries travel every year to places in Africa, Asia, Pacific Islands, Latin America and remote areas of Eastern Europe, and between, 25 and 50 % of travellers to these areas experience travellers' diarrhoea -12. Abougellosis ,13.In this study we have used returning travellers to Sweden as sentinels to estimate the comparative risks for travel-associated campylobacteriosis in 19 regions of the world, and looked into the seasonality of the disease in each of these regions.Campylobacteriosis is a notifiable disease according to the Swedish communicable disease act. Cases are notified in parallel to the Swedish Institute for Infectious Disease Control (SMI) by the clinician having seen the patient  and the laboratory having diagnosed the pathogen (laboratory notification). At the SMI the notifications from the two sources are merged into case records, using a unique personal identification number issued to all Swedes, and used in all health care contacts. The clinical notifications contain epidemiological information of relevance, including country of infection. For this study we retrieved notification information  from the national surveillance database  on all cData on travel patterns were obtained from a commercial database, the Swedish Travel and Tourist Database (TDB) . This daCampylobacter infection (cases) as numerator and extrapolated total numbers of travellers from the TDB as denominator. The actual numbers of interviewed persons (controls) were used for the calculations of 95% confidence intervals (95% CI) for the estimates, using the formula:The age, sex and geographical distribution of the interviewees in the TDB, were standardised against the total population of Sweden to give an extrapolation of the actual number of travellers to each country during the seven years. We then estimated risks per 100,000 travellers  using notifications on In risk ± 1.96*√ (1/cases+1/controls)eTo adjust for possible confounding and test for interaction, we also calculated odds ratios (OR) with corresponding 95% CI for the same exposures with a logistic regression model.In an initial crude analysis, odds ratios (ORs) for all exposures  on the outcome campylobacteriosis were analysed, with the lowest incidence in each category used as reference. Confounding was then assessed using Mantel-Haenszel stratification. ORs for exposures with significant association with the outcome were included in a logistic regression analysis if they were shown to contribute significantly to the model in a Wald test. The presence of significant interaction was tested with tests for homogeneity. For each region we analysed seasonality separately . All analyses were done using the Stata 6.0 software .Notification data is regulated by the Swedish Communicable disease act, and contain full personal identification. The TDB contains aggregated data only. The Medical Ethics Committee of the Karolinska Institute, Stockholm, Sweden, approved the study.Of 53,223 persons notified with campylobacteriosis in the period 1997 to 2003, 28,704 (54%) were travel-associated, corresponding to 42.3 cases per 100,000 travellers , East Africa , East Asia , North Africa  and Arab countries/Iran . Adjusting for age, sex, and month in the logistic regression model did not change the rank between the regions  versus 40.8 cases per 100,000 95 % CI 39.7–41.9). After adjusting for destination, age, and month in the multivariate logistic regression model, the risks were reversed with a significantly higher OR in males . However, travel destination was an effect modifier on the association between sex and campylobacteriosis, and this higher risk for males were only significant for travellers returning from a European country   and in small children 0–6 years old . Also the association between age and campylobacteriosis was modified by travel destination, and in travellers from tropical destinations, especially from Africa and Asia/Oceania the highest risk was seen in the youngest children , Western Europe , Eastern Europe , North America , Southern Europe , Northern Africa , Arab countries and Iran , and Australia/New Zealand . In the Eastern Mediterranean the peak risk was seen in the spring , and in Russia and former USSR in late fall . In the tropical regions the seasonality was considerably less distinct. In East Asia the risk peak was in December with nadir in May  and in the Caribbean in February with nadir in September . In the Indian Subcontinent, Sub-Saharan Africa, and Central/South America no distinct, significant seasonal peaks could be identified.In this study we report the risks for travel-associated campylobacteriosis and seasonality of the risks in various parts of the world, based on more than 28,000 notified cases. The large number of cases gives more precise risk estimates for this disease than in previous studies, although the estimates are given for quite large regions in parts of the world with few Swedish travellers. The denominator data from the TDB has previously been used in studies on dengue fever  and rickCampylobacter infections. One should therefore be cautious in drawing conclusions from the magnitude of the figures, and rather focus on the relative risks between the various regions, as estimated by the odds ratios. Since the data are all from the same source, the risk figures from the various regions are directly comparable. However, there may be a tendency of investigating travellers from the tropics more vigorous than travellers from e.g. the other Nordic countries, thus underestimating the risks in nearby countries. However, such selection bias could likely not explain the huge differences between say West Africa and East Africa.Notification data only reflects a small (but unknown) proportion of all travel-related Since we have no comparable data on the length of stay among the cases in our study, we were not able to include length of stay in our logistic regression model. However, the TDB clearly shows a longer median stay among travellers in far-away destinations. For instance the median stay in Spain was 6 nights, while in Thailand it was 14 nights. On the other hand, only cases detected after the return to Sweden are included in the analysis. The disease data therefore mainly reflect infections contracted during the last week of stay at the travel destination. Differences in length of travel are therefore to some extent evened out.It has previously been suggested that the risk of travellers' diarrhoea is higher during the first two weeks in highly endemic areas ,18. The Campylobacter jejuni infection was 10 per 100,000 travellers returning from Spain and Portugal, and 50, 60, and 80 per 100,000 returning travellers from China, Thailand and India, respectively [The differences in risk between various regions were considerable, not only between industrialized and developing countries, but also between different developing countries. The Indian Subcontinent, East Africa, East Asia, and North Africa stood out as special high-risk areas. In a recent Finnish study, the risk of travel associated ectively . The lowectively ,21, but Age, sex and season (month of travel/infection) were identified as possible confounders for the association between travel destination and risk for campylobacteriosis and were thus included in the logistic regression model. All three variables contributed significantly to the model, but the overall effect of these confounders did not alter the rank order between the regions in the logistic regression model compared to the crude analysis.The highest risks were seen in young adults and small children, and especially in the tropics the highest risks were seen in the youngest. This is consistent with previous findings that in developed countries the disease most of hits children below the age of 5 years and young adults, while in developing countries it is most often seen in children below the age of 2 years, with an annual incidence of 40–60 % . The datCampylobacter infection. This pattern is also seen in domestically acquired Swedish campylobacteriosis cases, where 56% of the notified cases in 2003 were males, and in the US where campylobacteriosis is more common in males of all age groups [In travellers returning from Europe, male gender was an independent risk factor for e groups ,9. The he groups .In each of the 19 regions in the study, we looked closely at the seasonality of the disease. As has previously been shown ,6-9, theCampylobacter infection was seen between November and April [In the tropical regions, seasonal peaks of campylobacteriosis have not previously been recognized . Also innd April . With onData on infections in returning travellers together with good denominator data could provide comparable data on travel risks in various regions of the world. This study has revealed large and unexplained regional incidence differences, e.g. between East and Central Africa. The very distinct seasonal pattern seen in all temperate regions could not be discerned in the tropics.The author(s) declare that they have no competing interests.KE raised the original idea of the study, did the statistical analyses, and prepared the first draft of the manuscript. YA contributed with in depth knowledge of campylobacteriosis and revised the draft manuscript. Both authors have read and approved the final manuscript.The pre-publication history for this paper can be accessed here:


No two countries have adopted identical regulatory measures on cloning. Understanding the complexity of these regulatory variations is essential. It highlights the challenges associated with the regulation of a controversial and rapidly evolving area of science and sheds light on a regulatory framework that can accommodate this reality.Using the most reliable information available, we have performed a survey of the regulatory position of thirty countries around the world regarding the creation and use of cloned embryos (see Table While most of the countries studied have enacted national legislation, the absence of legislation in seven of these countries should not be equated with the absence of regulation. Senator Morin was not correct in stating that the majority of recent legislation bans both RC and NRC. Recent regulatory moves are united only with regard to the banning of RC. While NRC is not permitted in seventeen of the countries examined, it could be permitted in up to thirteen countries.There is little consensus on the various approaches to cloning laws and policies, and the regulatory position in many countries remains uncertain. We understand that conservative opinion is of the view that this interpretation is in conflict with Article 18(2) of the Convention itself. However, neither the Convention nor the Protocol on Cloning provide any sanctions for violation.The United Nations' struggle to agree on a cloning treaty exemplifies both the variation of approaches and the challenges associated with seeking consensus in a morally contested area . In DeceThere has, however, been little consensus on how to proceed. Though all countries agree that RC should be banned, there is deep division regarding NRC. Neither the Ad Hoc cloning committee nor the UN's Legal Committee could reach a consensus on which proposal to support and bring before the General Assembly. In November 2003 the Legal Committee voted (80-79) to recommend a two-year deferral on a General Assembly decision – a compromise that was put forward and supported by most of the members of the Organization of the Islamic Conference. This decision was largely seen as a victory for those countries supporting a more permissive approach to cloning policy . Indeed,The fact that the deep division at the UN is primarily about NRC reflects the lack of any consistent approach to cloning policy. For example, one would expect an emerging trend toward the banning of NRC, as suggested in the quote by Senator Morin, to be reflected in the building of consensus or, at least, a degree of flexibility at the UN General Assembly.Few areas of regulation are as evidentially driven by ethical views as the regulation of cloning and cloning research. This is not the place for in-depth analysis of the underlying debate. Elsewhere we have both argued that existing regulatory attempts to prohibit RC have rarely been underpinned by thoughtful exposition of underlying ethical principles ,10,34. PLawyers rarely look to regulatory outcome to understand ethical debates. Unfortunately, in the area of cloning many commentators do that very thing. As our starting quotation demonstrates, politicians and commentators are all too ready to find support for their ethical views in regulatory positions adopted elsewhere. There are, however, varying levels of ethical agreement. Agreement on the appropriate regulatory position does not imply agreement on the underlying ethical principles.full status position would grant the embryo the same level of moral duties as you or I. The no status position would grant the embryo no more status or dignity than your hair or nails. The limited status position would grant the embryo a fixed or gradualist level of intrinsic moral value between these two extremes. The full status position will require the prohibition of NRC (destructive use of embryos is considered murder) and the no status position will usually require NRC to be permitted . The limited status position is, however, potentially compatible with either regulatory position, depending on the particular status given to the early embryo and the weight given to potential benefits of NRC. It follows that the fact that the regulatory position permits or prohibits NRC does not do even tell us what status the embryo is considered to have. This is further complicated by the fact that supporters of the no or limited status position might be prepared to accept more restrictions than are strictly required by their position to protect a more important moral goal. Only supporters of the full status position cannot coherently make such pragmatic compromises [Consider the relationship between ethical positions on the moral status (or dignity) of the cloned embryo and NRC. The cloned embryo could be considered to have full, no, or limited moral status ,35. The promises .Similarly, the existing positions on RC could be supported by radically different ethical views. Prohibitions could be supported by those who hold that RC is absolutely wrong  and by those who hold that cloning at present would be wrong. Even time-limited prohibition does not enable us to discern whether it is underpinned by, for example, the view that RC is wrong because of current safety issues or the view that RC is not wrong but the most effective way to get there is by initially prohibiting it.In sum, the majority of regulatory outcomes could be coherently explained by reference to one or more underlying ethical positions. Thus, similar or even identical regulatory outcomes imply less by way of ethical agreement than some may be inclined to believe.Cloning laws and policies are far from uniform across the globe and the legal position in some countries remains uncertain. This will give little comfort to scientists and policy makers hoping to gain clear direction from the international position. For the time being at least, policymakers must accept the reality of international "dissensus" and scientists wishing to undertaken research on NRC are best advised to consider conducting their research in only a handful of countries. Even where there is agreement as to the regulatory outcome, policy-makers should not confuse this with agreement on underlying ethical principles. Like many topics concerning the developing genetic and reproductive technologies, cloning remains controversial.The author(s) declare that they have no competing interests.Both authors contributed to the original concept for the paper, the writing and revision of the manuscript and the analysis of the law.The pre-publication history for this paper can be accessed here:


These women had low urinary percentages of monomethylated As (MMA) and high percentages of dimethylated As (DMA). MMA has been associated with adverse health effects, and DMA has the lowest body retention of the metabolites. The genes studied were arsenic(+III)methyltransferase (AS3MT), glutathione S-transferase omega 1 (GSTO1), 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR), methylenetetrahydrofolate reductase (MTHFR), and glutathione S-transferases mu 1 (GSTM1) and theta 1 (GSTT1). We found three intronic polymorphisms in AS3MT  associated with a lower percentage of MMA (%MMA) and a higher percentage of DMA (%DMA) in urine. The variant homozygotes showed approximately half the %MMA compared with wild-type homozygotes. These polymorphisms were in strong linkage, with high allelic frequencies (72–76%) compared with other populations. We also saw minor effects of other polymorphisms in the multivariate regression analysis with effect modification for the deletion genotypes for GSTM1 (affecting %MMA) and GSTT1 (affecting %MMA and %DMA). For pregnant women, effect modification was seen for the folate-metabolizing genes MTR and MTHFR. In conclusion, these findings indicate that polymorphisms in AS3MT—and possibly GSTM1, GSTT1, MTR, and MTHFR—are responsible for a large part of the interindividual variation in As metabolism and susceptibility.The susceptibility to arsenic-induced diseases differs greatly between individuals, possibly due to interindividual variations in As metabolism that affect retention and distribution of toxic metabolites. To elucidate the role of genetic factors in As metabolism, we studied how polymorphisms in six genes affected the urinary metabolite pattern in a group of indigenous women ( Millions of people around the world drink water with elevated concentrations of arsenic, a potent human carcinogen. It is well established that chronic exposure to As is associated with skin, lung, and bladder cancers  as well In vitro studies have shown that the trivalent forms, particularly monomethylarsonous acid (MMAIII), are generally more toxic than the pentavalent forms (Inorganic As (iAs) is metabolized by reduction of pentavalent iAs to trivalent, followed by oxidative methylation to monomethylated As (MMA), further reduction from pentavalent MMA to trivalent, and at last methylation to dimethylated As (DMA) . Not allnt forms . Thus, tnt forms . This, int forms  and an int forms .S-transferase (GST) omega 1 (GSTO1), which encodes an enzyme that can reduce pentavalent As species, might be related to enzyme activity and patterns of methylated As metabolites , which is known to methylate trivalent As, was found to have three intronic single nucleotide polymorphisms (SNPs) that were significantly related to DMA/MMA ratios. However, this association was only valid for children (S-Adenosyl-methionine (SAM) is the methyl donor for methylation of As (MTHFR) and 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR), may affect As metabolism.Part of the interindividual variation in As metabolism may be due to environmental factors, but earlier studies have shown that hereditary differences are very likely to contribute . So far,abolites . A few sabolites . In anotchildren . S-Adenoon of As , and pola) searching for new and previously reported polymorphisms in GSTO1 and AS3MT by sequencing; and b) screening for previously reported polymorphisms in GSTM1, GSTT1, GSTO1, MTR, and MTHFR.Our aim was to elucidate how variations in the various As metabolism-related genes affect the distribution of As metabolites. Therefore, we genotyped and phenotyped inhabitants from a city in the northern Argentinean Andes, where the inhabitants are exposed to high levels of As and have an unusual metabolism . The genn = 111). Metabolite data was missing for one individual. Because the metabolite pattern changes during pregnancy (n = 37).Participants in this study were women living in San Antonio de los Cobres (SAC), a village in the northern Argentinean Andes. Men were excluded from the study because they often worked in other geographic locations for extended periods of time. All individuals in SAC used drinking water from the same source; the As concentration of this water was around 200 μg/L (with little variation over time) because of the As content of the bedrock . Urine aregnancy , all pre2), and coca usage (49% were users). For pregnant women, data were available on age  and gestational week . The subjects were recruited via the local radio announcements and hospital registers and were interviewed about history of residence, residences of parents and grandparents, parity, and water consumption. The interviews revealed that individuals from SAC were mainly of indigenous (Atacameño) origin, but there was a variation in Hispanic and indigenous origin. All individuals were genetically unrelated.For women sampled in 2004–2005, data were available on age , weight , body mass index  informed the women of all details of the research project, and all study participants gave written informed consent.We determined values of As in water and total concentration of As metabolites in urine (U-As) using hydride generation-atomic absorption spectrophotometry (HG-AAS) . DetailsDNA was isolated from either whole blood by a modified salting-out method , or fromGSTO1 ; an independent variable was included that provided a p-value < 0.2. The final models were performed with an interaction term between the main independent variable and genotype. Data from individuals with no variant alleles (0) were used as references values and data from individuals with one or two variant alleles were compared with these values. For GSTM1 and GSTT1, we used individuals with GSTM1*1/GSTT1*1 as referents. All statistical analyses were performed using SPSS .We tested deviation from Hardy-Weinberg equilibrium using chi-square analysis. Associations between genotypes (independent variables) and urinary As metabolites (dependent variables) were analyzed with one-way analysis of variance (ANOVA). For subsequent post hoc tests, adjustments for multiple testing between subgroups (i.e. genotypes) were made with Bonferroni correction. The values for metabolites used in the statistical analyses were %iAs, %MMA, %DMA, MMA/iAs ratio (first methylation step), DMA/MMA ratio (second methylation step), and U-As [all natural log (ln) transformed]. AS3MT, all exons except exon 2 were successfully sequenced. We found nine previously reported polymorphisms . Of the remaining six polymorphisms, one was an exonic polymorphism (Met287Thr), and five were intronic .For rphisms b in the irphisms b: G12390CGSTO1, we found no polymorphisms with an allele frequency > 20%. However, we did identify a novel genetic variant, T2562C (one heterozygous carrier), and we verified five previously reported polymorphisms—three exonic , and two intronic (A2207G and a GGC deletion at 2609). These GSTO1 polymorphisms were present in one to three individuals, mostly in heterozygous form, with allele frequencies between 1.2–6.0%. The frequencies of polymorphisms in other genes studied are shown in For III in any of the urine samples, and we did not look for dimethylarsinous acid (DMAIII), because any small amounts present would have been oxidized before freezing.The urinary metabolite patterns for the group of 2004–2005 women and for pregnant women are shown in AS3MT G12390C, C14215T, and A35991G and the As metabolite pattern for the 2004–2005 group . We found a difference between all genotypes: the variant homozygotes displayed the lowest %MMA and the highest %DMA. The effect was strongest for %MMA, where the difference was statistically significant between all genotypes for SNP12390, SNP14215, and SNP35991, except for the comparison between heterozygotes and variant homozygotes for SNP35991 (p = 0.10). The %MMA for SNP35991 is shown in When performing ANOVA, we found a statistically significant association between the genotypes AS3MT SNPs for pregnant women, where the difference in %DMA between SNP35991 wild types and variant homozygotes was statistically significant (n = 76). In this group, the allelic frequency for the variant allele of 35991 was 77.7%. The differences in %MMA between the genotypes were even higher . For the other genes studied, no such differences were seen. Among the individuals with less documented indigenous origin (n = 34) the variant allelic frequency was 72% and the %MMA was 11.5% for GG and 8.7% for AA.The pattern was also valid for all nificant , whereasMTR had lower %DMA and higher %MMA, and thus lower DMA/MMA ratios (MTR had lower %DMA (p = 0.051) for GSTT1*0.Among the 2004–2005 women, variant homozygotes of A ratios . Howeverwer %DMA  and highp-values < 0.1 for the interaction term are shown. No significant interaction was found between AS3MT and U-As, but there was still a strong effect of genotype only, with a magnitude similar to the ANOVA tests (data not shown). For the pregnant women, the effects of U-As or GW on As metabolite distribution differed depending on certain genotypes. Carriage of the variant allele of MTHFR affected the percentage of all metabolites, as well as the DMA/MMA ratio  and GW and U-As for pregnant women (interaction term between GW and genotype). The results from the multivariate regression analysis are presented in 05 women  and GW afor %MMA  and DMA/MA, %DMA , and DMAWe observed no effect on the MMA/iAs ratio for any genotype studied (data not shown).AS3MT that significantly affected the As metabolite pattern. Carriers of the variant alleles, especially homozygotes, had lower %MMA and higher %DMA, and consequently, a higher DMA/MMA ratio. For example, variant homozygotes of the SNP35991 had about half the %MMA compared with wild-type homozygotes. Among individuals with more documented indigenous origin, the variant homozygotes had only about one-third of the %MMA compared with wild-type homozygotes. The %iAs was also lower in carriers of variant alleles, although not significantly. This indicates that the effects of the SNPs are strongly associated with the second methylation step in particular. The first methylation step, which is less sensitive than the second methylation step to factors such as sex, excess exposure to As, alcohol, and smoking, may be catalyzed by several different methyltransferases. It may even occur without an enzyme , and was similar to the distribution found in those with European ancestry. Our findings from indigenous Andean women strongly indicate that these variants represent a haplotype for indigenous ancestry associated with a specific As-metabolism profile, irrespective of age.The three er study  involviner study . That ster study . In the AS3MT in the SAC population. Only two individuals from SAC, both pregnant women, were heterozygous carriers of the high-activity variant Met287Thr reported by AS3MT genotype and metabolite distribution in this group, but the results were not as strong as for the 2004–2005 group. This may be due to the smaller number of pregnant subjects. However, increased gene expression of AS3MT, possibly also other methyltransferases, during pregnancy are likely to blur the association between the genetic variants of the gene and metabolite pattern.Pregnancy affects the metabolite pattern by increasing the %DMA in urine with increasing gestational age, probably in concert with the induction of other methylation reactions required for tissue growth and development . TherefoAS3MT. In this “explorative” study, multiple testing was performed. Multiple polymorphisms and metabolites were considered, and several multivariate regression models were tested. We are aware of the problems with false-positive findings, which are influenced by the significance level, statistical power, and prior credibility of the association tested , as well as increased tissue concentrations . Our mule levels . As expe in %DMA  and a de in %DMA  when ther cancer . We obse and MTR  polymorpGSTM1 (%MMA and DMA/MMA) and GSTT1  modified the metabolite pattern. GSTM1*0 individuals excreted more MMA, but we did not see this effect in the present study using ANOVA; however, GSTM1*0 carriers had higher fractions of MMA with increasing U-As. GSTM1*0. We found no clear effects on %iAs for this genotype in 2004–2005 women (p = 0.7) or in pregnant women (p = 0.4). Unlike GSTT1*0.Also GSTO1, the frequencies of polymorphisms were far too low to affect the distribution of urinary As metabolites among the population. The effect of the novel GSTO1 2562 T/C substitution is still to be elucidated. For AS3MT, associated with increased formation and excretion of DMA in urine, were very high compared with other populations (The population from SAC has been exposed to As for thousands of years , and we ulations . Little ulations  we obserulations . Also, Aulations , who areulations . ObviousIdentifying polymorphisms, gene–environment interactions, and related effects on As metabolism will provide important information about the mechanisms behind the biotransformation of As and also facilitate understanding individual differences in As metabolism. This will help us to identify susceptible groups and may provide better risk estimates for As. Furthermore, this research has clinical implications in that it may be used for evaluation of the risks associated with the current use of arsenicals as a contemporary pharmaceutical agent.


Continuous exposure to various environmental carcinogens and genetic polymorphisms of xenobiotic-metabolizing enzymes (XME) are associated with many types of human cancers, including esophageal squamous cell carcinoma (ESCC). Huaian, China, is one of the endemic regions of ESCC, but fewer studies have been done in characterizing the risk factors of ESCC in this area. The aims of this study is to evaluate the etiological roles of demographic parameters, environmental and food-borne carcinogens exposure, and XME polymorphisms in formation of ESCC, and to investigate possible gene-gene and gene-environment interactions associated with ESCC in Huaian, China.A population based case-control study was conducted in 107 ESCC newly diagnosed cases and 107 residency- age-, and sex-matched controls in 5 townships of Huaian. In addition to regular epidemiological and food frequency questionnaire analyses, genetic polymorphisms of phase I enzymes CYP1A1, CYP1B1, CYP2A6, and CYP2E1, and phase II enzymes GSTM1, GSTT1, GSTP1, and microsomal epoxide hydrolase (EPHX) were assessed from genomic DNA using PCR based techniques.GSTT1 null genotype was higher in cases (59.4%) compared to controls (47.2%) with an odds ratio (OR) of 1.68 and 95% confidence interval (CI) from 0.96 to 2.97 (P = 0.07), especially in males . No associations were found between polymorphisms of CYP1A1, CYP1B1, CYP2A6, CYP2E1, GSTM1, GSTP1, and EPHX and ESCC (P > 0.05).Consuming acrid food, fatty meat, moldy food, salted and pickled vegetables, eating fast, introverted personality, passive smoking, a family history of cancer, esophageal lesion, and infection with Helicobacter pylori were significant risk factors for ESCC (P < 0.05). Regular clean up of food storage utensils, green tea consumption, and alcohol abstinence were protective factors for ESCC (P < 0.01). The frequency of the GSTT1 may play important roles in the development of ESCC in Huaian area, China.Our results demonstrated that dietary and environmental exposures, some demographic parameters and genetic polymorphism of  Esophageal cancer is the eighth most commonly occurring cancer and the sixth leading cause of cancer deaths in the world, with the majority of cases occurring in developing countries . China, CYP2E1 c1/c1 allele, GSTM1 and GSTT1 non-null genotype and EPHX slow allele, were associated with increased risk of ESCC, while CYP1A1 3' polymorphism  may be one of the protective factors for ESCC [Previous epidemiological studies have demonstrated that exposure to environmental carcinogens plays a significant role in the etiology of ESCC -7. The rfor ESCC ,23. It ifor ESCC .Although extensive studies have been carried out during the last two to three decades in the southern Taihang Mountain area ,11,22,23This population based matched case-control study consisted of 107 patients with ESCC and 107 healthy controls. All subjects were unrelated ethnic Han Chinese and residents in 5 townships of Chuzhou District, which were located at the north side of the General Irrigation Canal, Huaian City, Jiangsu Province, China. Based on a database at the malignant tumor registry of Huaian Center for Disease Control and Prevention (CDC), all cases were newly diagnosed with primary ESCC between 2002 and 2003. Cases were diagnosed at local hospitals and confirmed by endoscopy, X-ray or clinical histopathology. Control subjects were randomly selected healthy individuals confirmed by physical examination, clinical and biochemical analyses during the same period of case recruitment. Eligible controls included individuals without a history of cancer and were matched to cases on the basis of age (± 5 years), gender, and residency. Informed consent was obtained from each subject. The study protocol was approved by the Institutional Review Boards of the Texas Tech University, the Southeast University, and Huaian CDC for human subject protection. Sample collection, storage and shipment were complied with guidelines of both Chinese and US governments.A unified questionnaire, administered by trained personnel, was used to obtain study information. The questionnaire included demographic and residential characteristics, consisting of age, gender, height, weight, personal medical history, family cancer history, cigarette smoking, alcohol drinking, personality, dietary behaviors, green tea consumption, and exposure to pesticides and water-borne toxicants. Data on cigarette smoking included age started and ceased, number of cigarettes per day and duration. Participants were defined as current smokers if they smoked at least one cigarette per day for at least six months consecutively before the diagnosis for cases or to the date the controls were interviewed. Alcohol history included general information such as age started and ceased, as well as specific questions about the types of alcohol consumed, such as beer, yellow rice wine, red wine and liquor. Drinking status was defined as drinking at least once per day for at least six months continuously. The personality was classified into 3 categories including optimistic (or extrovert), relative optimistic (intermediate extrovert), and introvert. Extrovert was defined as sociable, active, assertive, energetic, animated, enthusiastic outgoing, impulsive, emotionally expressive, talkative, act before thinking, and broad experience. Introvert was defined as shy, unsociable, often appear reserved, quiet and thoughtful, usually do not have many friends, and have difficulties in making new contacts, like concentration and quiet. Esophageal lesion in our study was defined as including one or more of the following clinically diagnosed esophagus diseases or changes: 1) chronic esophagitis; 2) reflux esophagitis; 3) esophageal epithelium regeneration; 4) esophageal epithelium metaplasia; 5) esophageal polyps; and 6) esophageal erosion. All subjects were asked to fill out a quantitative food frequency questionnaire on 8 categories including 1) staple diet; 2) fried food; 3) pickled and salty food; 4) animal meat, egg and milk; 5) bean and bean product; 6) vegetables; 7) fresh fruits; and 8) nuts and dried fruits. A total of 120 food items were included in these 8 categories. These were considered representative of the usual diets of local residents.In addition to epidemiological and food frequency questionnaires, 7 mL blood samples were collected from each subject, and separated into white blood cell (WBC) and plasma. Serological markers of Hepatitis B virus and Helicobacter pylori (HP) infection were detected. All samples were stored at -80°C and then shipped to the Institute of Environmental and Human Health, Texas Tech University for further analysis.CYP1A1 3'-UTR, CYP1A1 exon7, CYP1B1, CYP2E1, GSTP1, EPHX113 and EPHX1 genotypes were analyzed using PCR-RFLP methods as described previously [CYP2A6 deletion allele [GSTM1, GSTT1 [2, 0.3 mM of each deoxynucleotide triphosphate (dNTPs) , 0.8 μM (20 pmol) of each primer, 2.5 μL 10X PCR buffer and 1.25 Units Platinum Taq polymerase . A programmable thermocycler  was used. In each reaction, amplification of the beta-globin gene was used as an internal standard. The amplification protocol was set up for an initial denaturation of 2 min at 95°C, followed by a total of 30 cycles of 15 sec at 94°C, 30 sec at 61°C and 45 sec at 72°C. A final extension step was performed at 72°C for 5 min. The amplified products were visualized by electrophoresis on ethidium bromide-stained 2.0 % MetaPhor Agarose gel  in 1X TAE buffer.Genomic DNA was extracted from WBC using the Qiagen QIAamp DNA Blood Mini Kit  according to the procedure provided by the manufacture. Ten polymorphic alleles in 8 genes were investigated using PCR based techniques Table . The CYPeviously ,25-29. An allele . A modif1, GSTT1 . BrieflyFor quality control, 10% of the samples were randomly selected and regenotyped for all of the selected genes, and the results were 100% concordant.2 test. The association between individual variables including demographic characteristics, dietary and environmental factors, or genetic polymorphisms, and risk of ESCC was estimated by conditional logistic regression. Odds ratios (ORs) and their 95% confidence interval (CIs) were determined. The simultaneous effects of statistically significant variables on cancer risk were then examined using multivariable conditional logistic regression model. Interactions between genotypes and genotypes or between genotypes and environmental factors were also estimated by using conditional logistic regression. A p-value of ≤0.05 was considered statistically significant. The statistical analyses were performed with STATA 6.0.Database on epidemiological and food intake frequency questionnaire data was established before analyses. Genotype frequencies among cases and controls were compared with values predicted by the Hardy-Weinberg equilibrium using χDemographic information of study subjects was summarized in Table Among the 32 dietary behavioral factors in the epidemiological questionnaire, 12 variables showed statistically significant associations with ESCC . This association was more significant in male patients  . Allele frequencies of phase I metabolic enzymes , and CYP2E1) and phase II metabolic enzymes  were not significantly different between cases and controls (P > 0.05) Figure . In addi) Figure .When examined simultaneously, a family history of cancer, esophageal lesions, eating fast, and HP infection increased the risk of developing ESCC Table , while rGene-gene and gene-environment interactions were examined by conditional logistic regression and no statistical significances were found (P > 0.05).1 (FB1), are associated with ESCC [In the present study, introverted personality, passive smoking, a family history of cancer, esophageal lesion, HP infection, eating fast, fatty meat consumption, pickled vegetables intake, moldy food intake, favor to salty and acrid food were all associated with increased risk of ESCC. However, regular clean up of food storage utensils, alcohol abstinence lasted for more than half a year, and tea drinking were protective for ESCC. Among the factors associated with ESCC in this study, an introverted personality type, clean up of food storage utensils, and alcohol abstinence are first reported. Other major findings are consistent with previous studies conducted in China and elsewhere -33 incluith ESCC . This maith ESCC .We found that passive smoking is significantly associated with increased risk of ESCC. Passive smoking is a major risk factor for lung cancer, and emerging studies have shown that it may also be related to increased risk of breast cancer in women . It has We also found that alcohol abstinence is a protective factor for ESCC. It is possible that genetic damage such as chromosome aberrations and micronuclei caused by alcohol are reversible by abstinence . AlthougData from the present study revealed that HP infection was a risk factor for ESCC in the high risk population. However, results on HP infection and risk of ESCC have been inconsistent to date, an inverse relationship between HP infection and esophageal adenocarcinoma risk has been reported ,48. FurtOur study indicated that green tea is an important protective factor for ESCC, which is consistent with previous studies conducted in the same area  and in SGSTT1 null genotypes between cases and controls; however, the difference only approached statistical significance. This difference was more striking in the male subjects, resulting in a 2.8-fold increase in risk of ESCC compared to male subjects who carried the GSTT1 non-null genotype. This suggests that the GSTT1 null genotype may contribute to the development of ESCC in this high risk population. Although this was different from previous studies on ESCC [GSTT1 null genotype leads to lower GST enzyme activity levels and, consequently, impaired detoxification of environmental or dietary carcinogens. In addition, GSTT1 null has been shown to play a role in esophageal carcinogenesis through a pathway of abnormalities in the p53 tumor suppressor gene, which is highly reported in ESCC [CYP1A1 Val/Val and CYP2E1 c1/c1 genotypes were related with increased risk of ESCC [EPHX was also reported to be associated with high susceptibility of ESCC [CYP1A1, CYP2E1, CYP2A6, and EPHX and ESCC. The exact reasons for these inconsistent findings remain to be elucidated, but it is demonstrated that the variation in enzyme activity with ethnicity and gender may contribute to the differences in effects on the risk of cancers [Numerous studies have investigated the association between different XME polymorphisms and ESCC, but with conflicting results . In the  on ESCC ,23,55, i in ESCC . Previou of ESCC ,56. EPHX cancers .In order to find an overall risk for ESCC, variables with statistical significance in univariate conditional logistic regression were analyzed in a multivariable model. Esophageal lesion, eating fast, a family history of cancer, and HP infection were risk factors for ESCC (P < 0.05), while clean up of storage utensils and green tea consumption were protective factors for ESCC (P < 0.05). Personal character, fatty meat intake, pickled vegetables intake, and alcohol abstinence were not statistically significant in the multivariable model which might be due to their colinearity with other variables in the multivariable analysis. For instance, eating fast and pickled vegetables intake was highly correlated . Although, gene-gene and gene-environment interactions have been reported for ESCC ,58, we dGSTT1 null genotype and risk of ESCC in male subjects. One potential limitation of the current study is the relatively smaller sample size, which may reduce statistical power for detecting gene-gene and gene-environmental differences. Hence, further studies with larger sample size and prospective cohort are mandated to confirm the present findings.The present study indicated that fatty meat consumption, eating fast, consuming pickled vegetables, moldy food intake, preference for salty and acrid food along with esophageal lesion, HP infection, passive smoking, and a family history of cancer are risk factors for ESCC in Huaian area, China. Regular cleaning of food storage utensils, green tea consumption, and alcohol abstinence are important protective factors for ESCC in this high risk population. In addition, there was a significant association between the XME = xenobiotic-metabolizing enzymes; ESCC = esophageal squamous cell carcinoma; CYP = cytochrome P450; GST = glutathione S-transferase; EPHX = microsomal epoxide hydrolase; PCR = polymerase chain reaction; RFLP = restriction fragment length polymorphism; OR = odds ratio; CI = confidence interval; HP = helicobacter pylori.The author(s) declare that they have no competing interests.ZW carried out the genotyping studies, participated in the statistical analysis of the data and drafted the manuscript. LT participated in the design of the study, helped to coordinate sample usage and in drafting the manuscript. GS participated in the design of the study and in the acquisition of the epidemiological data and the samples. YT participated in genomic DNA extraction. YX participated in the acquisition of the samples. SW participated in the acquisition of the samples. XH organized the epidemiological field study and participated in the acquisition of the samples. WG participated in the statistical analysis of the data and helped to draft the manuscript. SBC participated in the statistical analysis of the data and helped to draft the manuscript. J-SW conceived of the study, participated in its design, and helped to draft the manuscript. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:


It is well known that simultaneous presentation of incongruent audio and visual stimuli can lead to illusory percepts. Recent data suggest that distinct processes underlie non-specific intersensory speech as opposed to non-speech perception. However, the development of both speech and non-speech intersensory perception across childhood and adolescence remains poorly defined. Thirty-eight observers aged 5 to 19 were tested on the McGurk effect , the Illusory Flash effect and the Fusion effect  to investigate the development of audio-visual interactions and contrast speech vs. non-speech developmental patterns. Whereas the strength of audio-visual speech illusions varied as a direct function of maturational level, performance on non-speech illusory tasks appeared to be homogeneous across all ages. These data support the existence of independent maturational processes underlying speech and non-speech audio-visual illusory effects. It has repeatedly been shown that intersensory redundancy, the congruent bimodal presentation of stimuli over two sensory modalities, can enhance perception in both modalities e.g. . It is aBased on these findings, theoretical accounts relating how the senses interact to create a unified percept have emerged equivalence  determining the presence of non-specific, non-speech intersensory effects at different developmental stages; and ii) describing and contrasting the developmental course of non-specific speech/non-speech illusory effects.In the present study, speech (McGurk effect) and non-speech (Illusory Flash effect and Fusion) illusions were presented to the same observers across three age categories . Hence, we aimed at a priori: 5–9 (11 subjects), 10–14 (16 subjects), and 15–19 (11 subjects) years of age. The study was approved by the institutional Research Ethics Board of Hôpital Sainte-Justine and written informed consent was obtained from all participants and their parents. Individuals with a diagnosed or suspected neurodevelopmental disorder, attention deficit and hyperactivity disorder or learning disorder were excluded from the study. All participant had normal or corrected-to-normal vision as well as normal hearing.Thirty-eight French-speaking subjects  aged 5 to 19 years participated in the study. Each age (e.g. 9 years old) was represented by at least two participants. Three age groups were defined Participants were seated in a semi-dark room with the head on a chin rest located 57 cm from the computer screen (and speakers) where the stimuli were presented. The McGurk effect, the Illusory Flash effect and the Fusion effect tasks were performed in a single session, in counterbalanced order. In all tasks, visual stimuli were presented either at fixation or 5 degrees below fixation. This procedure was implemented because the strength of at least one of the illusions used in the present study has been shown to be greater for parafoveal presentations  or bimodal manner. In bimodal trials, the auditory stimulus and the video of the articulatring face  were presented simultaneously. In congruent trials, the auditory (voice) and visual (face) signals carried the same information whereas in incongruent trials, they did not. Five different experimental conditions were used: 1) unimodal auditory/va/; 2) unimodal auditory/ba/; 3) bimodal congruent/va/; 4) bimodal congruent/ba/; and 5) bimodal incongruent auditory/ba/and visual/va/. The bimodal and unimodal trials were repeated ten times each in random order.Participants were instructed to look at a fixation cross that was presented at the center of the screen for 1000 ms before each trial. Immediately following the disappearance of the cross, a stimulus was presented. Observers were told to simply repeat the syllable they had heard as clearly and precisely as possible. A break was systematically offered at 3 different times during the experiment, but participants could also take a break at any moment if needed. All incorrect responses in the incongruent bimodal condition (anything other than/ba/) were considered manifestations of the McGurk effect.After the McGurk effect task, a mute control task was performed in order to assess the participants' lip-reading abilities. In this task, the stimuli were unimodal visual/ba/and/va/lip movements. Again, the stimuli were presented at fixation and 5 degrees below fixation. Each condition was repeated 10 times for a total of 40 trials .The characteristics of the stimuli used in the Illusory Flash effect task and Fusion effect were similar to those used in Shams et al. Pilot trials revealed that the inter-flash delay of 67 ms used by Shams et al. age  as a between-subjects factor and position  as a within-subjects factor indicated that performance in control trials was homogeneous across age groups , a 3×2 repeated measures ANOVA with age as a between-subjects factor and position as a within-subjects factor was performed on bimodal incongruent trials. There were main effects of age  and position  . The interaction between factors was not significant . Post hoc t-tests revealed that the 5–9 year-old group perceived significantly fewer McGurk illusions than the 10–14 (p = 0.02) and the 15–19 year-old groups (p = 0.04)  . In addiTo further test the effect of age on the McGurk effect, individual subjects' ages were correlated with the number of trials in which a McGurk illusion was perceived. A two-tailed Pearson correlation revealed significant effects in both central  and peripheral  locations, as well as when both these conditions were collapsed  as a between-subjects factor and position  as a within-subjects factor revealed a main effect for position , but no main effect for age . The interaction was also non-significant . This is in line with previous work, where the Illusory Flash effect has been shown to be more robust at a perifoveal location . The strength of the illusion was not correlated with participant age . As for the Fusion effect  or position  and the interaction was non-significant .The original illusion  was replicated as the number of correct responses in the 1 flash/2 beeps condition was drastically reduced . A 3×2 rn effect , there wThere was no correlation between the Illusory Flash effect and the McGurk effect  or the Fusion effect and the McGurk effect .The purpose of this study was to investigate the developmental course of non-specific audio-visual effects on a maturational continuum. Our main finding is a discrepancy in the maturational patterns of speech and non-speech audio-visual effects.th year” Illusory percepts of audio-visual speech elements have been shown to occur in infants To our knowledge, a single study has shown that non-speech illusions can occur in infants. In the “Streaming-Bouncing” effect per se that varies with attention It is important to note that both illusion categories not only differ with respect to the speech/non speech content but also in the way participants respond. In the McGurk effect, children must report what they hear whereas in the two non-speech illusions they report what they see. Some have suggested that the strength of a single modality on perceptual judgment depends on the attention it is given both audio-visual speech Finally, the suggestion that speech and non-speech integration follow different developmental time courses does not exclude the possibility that they share common mechanisms. Indeed, it may be hypothesized that both illusory phenomena are subtended similarly at low hierarchical levels whereas audio-visual integration of speech elements requires supplementary processing. For example, it has been shown that brainstem structures are involved in


For remote identification of mosquito habitats the first step is often to construct a discrete tessellation of the region. In applications where complex geometries do not need to be represented such as urban habitats, regular orthogonal grids are constructed in GIS and overlaid on satellite images. However, rice land vector mosquito aquatic habitats are rarely uniform in space or character. An orthogonal grid overlaid on satellite data of rice-land areas may fail to capture physical or man-made structures, i.e paddies, canals, berms at these habitats. Unlike an orthogonal grid, digitizing each habitat converts a polygon into a grid cell, which may conform to rice-land habitat boundaries. This research illustrates the application of a random sampling methodology, comparing an orthogonal and a digitized grid for assessment of rice land habitats.Imagine V8.7® using QuickBird data acquired July 2005, for three villages within the Mwea Rice Scheme, Kenya. An orthogonal grid was overlaid on the images. In the digitized dataset, each habitat was traced in Arc Info 9.1®. All habitats in each study site were stratified based on levels of rice stageA land cover map was generated in Erdas An. arabiensis at the three study sites to be significantly higher during the post-transplanting stage of the rice cycle.The orthogonal grid did not identify any habitat while the digitized grid identified every habitat by strata and study site. An analysis of variance test indicated the relative abundance of Anopheles abundance, based on digitized grid cell information probably reflect underlying differences in abundance of mosquito habitats in a rice land environment, which is where limited control resources could be concentrated to reduce vector abundance.Regions of higher  Anopheles arabiensis have adapted to take advantage of relatively ephemeral and irregular shaped aquatic habitats [Rice land habitats -5, wherehabitats -11. A grhabitats . GIS griAn. arabiensis aquatic habitat data intolerable. Efficient handling of boundary conditions is a difficult problem in GIS grid-cell-based modeling [® can generate polygons (grid cells) which may conform better to paddy and canal boundaries and help characterize mosquito larval habitats in relation to ecological attributes about a mosquito aquatic habitat. Digitized grid cell data using fine resolution satellite data may determine a reliable source of data sensitive to a number of rice land habitat features thought to be important for developing and implementing an integrated vector management (IVM) programme based on An. arabiensis larval productivity. QuickBird data can distinguish unambiguously between types of spatial objects and land uses solely in terms of detected spectral reflectance [However, due to asymmetrically shaped aquatic habitats in rice lands, an orthogonal grid may straddle habitat boundaries making statistical inferences of seasonal rice land modeling . Applyinlectance . TherefoThe studies were conducted in Kangichiri, Kiuria and Rurumi villages within the Mwea rice scheme. The scheme is located 100 km north east of Nairobi. The scheme is situated on the foot hills of Mount Kenya at 112 km NE of Nairobi at 37°20'E and 0°, 41'S. Mwea is located at 1,159 m above sea level. It has a mean minimum and maximum temperature of 17°C and 26°C, respectively. The annual rainfall varies from a minimum of 356 mm to a maximum of 1,626 mm averaging 950 mm/year. Maximum precipitation takes place in April/May (long rains) and October/November (short rains). The average maximum temperatures are in the range of 16–26.5°C with relative humidity varying from 52–67%. Rurumi is located at the central-west region of the scheme and has 225 homesteads and 900 residents. Kangichiri and Kiuria are located in the north east of the scheme and have approximately 158 and 222 homesteads respectively with over 750 residents in each village.An. gambiae complex were identified to sibling species using Polymerase Chain Reaction (PCR) technique [Paddies and canals located within a 1 km buffer in the Kangichiri, Kiuria and Rurumi study sites were identified and mapped using a CSI-Wireless differentially corrected global positioning systems (DGPS) Max receiver using an OmniStar L-Band satellite signal with a positional accuracy of less than 1 m (Advanced Computer Resources Corp (ACR), 100 Perimeter Road Nashua, NH, USA) . Water bechnique .An. arabiensis aquatic habitats in the Kangichiri, Kiuria and Rurumi study sites involved assessing the level of rice development. The general hydrological duration of the rice cycle in the three study sites varies between 120–150 days. The cycle includes a field preparation phase comprising of flooding and ploughing stages prior to transplanting of rice seedlings, a post-transplanting stage with limited water, tillering, flowering/maturation and a post-harvest  season. Tillering extends from the appearance of the first tiller until the maximum tiller (5–9) number is reached. Stem elongation occurs and the tillers continue to increase in number and height, with increasing ground cover and canopy formation. The end of this stage marks the onset of flowering and maturation stage when plants stop growing and orient towards the development of the panicles and grains (water is drained), and in which plants senesce and their water content drops. The flowering/maturation phase lasts 20–30 days and includes the panicle initiation, booting, heading and flowering stages. Harvesting occurs 120–150 days post-transplanting when the grains fill, turn yellow and the plants senesce. After harvesting, the land is left fallow awaiting the next crop cycle.Stratifying the rice land ® , 100 Perimeter Road Nashua, NH, USA) database. VCMS supported the mobile field data acquisition in each village through a Microsoft PocketPC™. All two-way, remote synchronizing of data, geocoding, and spatial display were processed using the embedded GIS Interface Kit™ that was built using ESRI's MapObjects™ 2 technology. The VCMS database plotted and updated DGPS ground coordinates of aquatic larval habitats seasonal information and supported exporting data to a spatial format whereby any combination of rice land An. arabiensis larval habitats and supporting data in the Kangichiri, Kiuria and Rurumi study sites were exported in a GIS as a shape file format. This information was displayed onto a user-defined field base map.Base maps for this study including major roads and hydrography were created using the DGPS data in ArcInfo 9.1The QuickBird 0.61 m spatial resolution image encompassing the visible and NIR bands was acquired of the three study sites July16, 2005. Flooding in the Mwea rice scheme begins in late June in most rice cycles . Mosquit® was used to integrate field data, such as DGPS coordinates and GIS data, with the Erdas Imagine from QuickBird data. The QuickBird 0.61 m visible and NIR data was classified using the Iterative Self-Organizing Data Analysis Technique (ISODATA) supervised routine in ERDAS Imagine V8.7®. A supervised classification can assign spectral signatures automatically generated by the ISODATA algorithm (24) for remote identification of mosquito aquatic habitats [ArcInfo 9.1®. The area of the orthogonal grids that were overlaid on the QuickBird visible and NIR data were 64.3 m × 64.3 m in Kangichiri, 68.4 m × 68.4 m in Kiuria and 49.7 m × 49.7 m in Rurumi. Unique identifiers were placed in each grid cell unit. The grids extended out to a 1 km distance from the external boundary of each study site providing a 1 km radial area.The grid cell size in the orthogonal grid was calculated by the mean size of the paddy in ArcInfo 9.1An. arabiensis aquatic habitat was generated in Arc Info 9.1® for the 3 study sites. Unique identifiers were placed in each grid cell . The grid extended out to a 1 km distance from the external boundary of each study site.A digitized grid tracing each rice land An. arabiensis aquatic habitats. Due to the variation in the number of dips collected per habitat based on the size, we based our results on the number of larvae collected per dip. The entomological variable was total rice land anopheline larvae. An ANOVA test was performed to compare the differences in larval abundance between different paddy categories in each study site. An independent sample t-test was used to compare differences in larval abundance between paddies and canals as well as between vegetated and non-vegetated canals. Robust standard errors were used because data were collected at both the orthogonal grid cell and digitized grid cell level. An alpha level of 0.05 was used to indicate significance. All data management and calculations were performed using SAS 9.1.3® .The orthogonal grid and the digitized gridded image were 'screened' to determine fit and to provide an indication of the location of rice land An. arabiensis aquatic habitat in the study sites . Similarly, the abundance of 2nd instar larvae differed significantly among villages with that of 0.66 in the Rurumi study site being significantly lower than 1.09 or 2.11 in Kangichiri and Kiuria study sites, respectively . The abundance of 3rd and 4th instar larvae as well as that of pupae did not differ significantly among villages . Table An. arabiensis larvae/20 dips collected in the paddy and canal habitats at the 3 study sites. In the Kangichiri study site, the difference in the abundance of pupae and 1st, 2nd and 3rd instar larvae collected in paddy and canal habitats was not significant (p > 0.05) while that of 4th instar larvae was significantly higher in the paddy habitats than in the canals . In the Kiuria study site, significantly higher abundance of 3rd instar larvae were collected in the canals  while the other immature stages did not differ significantly between canal and paddy habitats. In the Rurumi study site, paddy habitats had significantly higher abundance of 1st and 2nd instar larvae compared with the canals  but the other immature stages did not vary significantly between paddy and canal habitats.The digitized grid cell data was used determine abundance of rice land An. arabiensis at the three study sites to be significantly higher during the post-transplanting and the tillering stages of the rice growth (P < 0.05). In the other rice stages, the immature stages of An. arabiensis were either absent or occurring in low numbers.The distribution of larvae in rice fields at different stages of the rice cycle is shown in Table An. arabiensis larvae in vegetated and non-vegetated canal habitats identified by the digitized grid and the statistical comparisons of larval abundance between the two categories are represented in Tables st and 2nd instar larvae was significantly higher in non-vegetated than vegetated canals while the differences in the other aquatic stages was not significant. In the Kiuria study site, the abundance of all the 4 larval instars of An. arabiensis was significantly higher in non-vegetated canals whereas in the Rurumi study site, the same trend was observed for the 2nd and 3rd instar larvae.The relative abundance of rice land Anopheles aquatic habitats in the three study sites. Building a digitized grid geodatabase can identify relationships between rice land mosquito aquatic habitats, rice plant stage of development and agro-village-complex within the framework of relational database technology. By digitally tracing rice land An. arabiensis aquatic habitats using QuickBird visible and NIR data in GIS; we can generate polygons that approximate the curvature of the paddy and canal habitat boundaries. Field attribute tables can be associated to the polygons. Multiple data layers can be created using different coded values for various field attributes to the same digitized grid cell which can allow for multiple interactions between compatible ecological data bases enabling retrieval and transformation of seasonal larval habitat data efficiently regardless of spatial dimensionality of a rice land aquatic habitat.Results of this study demonstrated digitized grid cell data to be superior to orthogonal grid cell data for identification of rice land Bacillus thuringiensis ssp. israelensis (Bti), Bacillus sphaericus (Neide) (Bsph) and Bti: Bsph ratios to determine lethal concentration parameters on all highly productive rice land An. arabiensis aquatic habitats in the three study sites. Confirmation of LC50 and LC95 values should be tested in each study site with two levels  of productivity. Overall product design goals may include: high efficacy (based on feeding behavior and susceptibility to bacteria toxins), minimal impact of ultraviolet radiation on efficacy, ease of use through conventional application equipment, and cost profile similar to other larvicides. Final candidate formulations should be evaluated in village-scale tests. Controlling a small proportion of productive rice land An. arabiensis aquatic habitats may yield significant reductions in a rice environment. For larval control, we assume that treatments applied to individual habitats are 100% effective in eliminating all immatures, i.e. treated habitats produce zero contribution to the total productivity.Determining spatial heterogeneity in larval habitat distribution using a digitized grid cell database can have important operational significance because vector control operations can be designed to target zones where high larval densities occur. Treatments or habitat perturbations should be based on surveillance of larvae in the most productive areas of the agro-ecosystem and adjacent village . The impAn. arabiensis aquatic habitat in the study sites. The display of the rice land data in a digitized grid format clearly identifies highly productive rice land An. arabiensis aquatic habitats. Inventory of digitized grid cells regarding their larval productivity can provide critical information for characterizing rice land mosquito vector oviposition habitat selection and planning of IVM. Rice land mosquito surveillance systems based on an orthogonal grid may lack sensitivity for early warning as well as crucial larval abundance data for targeting effective prevention efforts.In conclusion, the digitized grids identified and classified all rice land aquatic habitats examined in the three study sites by strata while the orthogonal grids did not identify any rice land ® overlay operations and generated the gridded maps; JS supervised the field data collection and helped analyze the data; JG, and IK jointly conceived and designed the study; RJN is the principal investigator of the study. All authors interpreted the results and wrote the paper.BGJ, helped conceive of the study and led the drafting of this manuscript; EJM, helped analyze the data; JF did the ArcInfo 9.1


Furthermore, estrogen confers atheroprotection via COX-2–dependent PGI2 in mice, raising the possibility that COX inhibitors may undermine the cardioprotection, suggested by observational studies, of endogenous or exogenous estrogens.Suppression of prostacyclin (PGIp < 0.002) interaction. The OR when taking aspirin at doses of 150 mg/d or more was 1.41 (95% CI 0.47–4.22). However, a similar interaction was not observed with other commonly used drugs, including lower doses of aspirin, which target preferentially COX-1.To identify an interaction between hormone therapy (HT) and COX inhibition, we measured a priori the association between concomitant nonsteroidal anti-inflammatory drugs (NSAIDs), excluding aspirin, in peri- and postmenopausal women on HT and the incidence of myocardial infarction (MI) in a population-based epidemiological study. The odds ratio (OR) of MI in 1,673 individuals and 7,005 controls was increased from 0.66  when taking HT in the absence of traditional (t)NSAIDs to 1.50 (95% CI 0.85–2.64) when taking the combination of HT and tNSAIDs, resulting in a significant  consisting of replacement estrogen, and sometimes progesterone as well, is often taken by women experiencing symptoms of menopause. Evidence from observational studies and the Womens' Health Initiative (WHI) trial has suggested that HT protects against heart disease in perimenopausal women. However, researchers have suggested that any beneficial effect of hormone replacement therapy on the heart might be counteracted by the effects of certain types of painkillers also being taken by women involved in the studies. These painkillers, nonsteroidal anti inflammatory drugs ( NSAIDs), prevent production of a molecule called prostacyclin. Prostacyclin plays a role in preventing blood clotting and is therefore thought to be important in protecting the heart. Estrogen, however, acts to increase production of prostacyclin, and it is therefore theoretically possible that hormone replacement therapy does have a beneficial effect on heart health, but which is counteracted by the negative effects of NSAIDs.In this study, the researchers wanted to find out whether there was any evidence for an interaction between NSAID use, hormone replacement therapy, and heart disease. Such understanding in turn might help to identify more clearly whether hormone replacement therapy protects against heart disease in specific subgroups of postmenopausal women.This study was carried out using information from the UK's General Practice Research Database, which is the largest computer database of anonymous medical records from primary care anywhere in the world. It contains information entered by UK general practitioners on their patients' drug prescriptions, diagnoses, referrals to hospital, and other data. The researchers here searched for all individuals from the database who were aged between 50 and 84 years on 1 January 1997, and then followed them up through the database for four years, or until the individual died, reached 85 years of age, or was diagnosed with a heart attack or cancer. From this search, the researchers found 1,673 women who had heart attacks or who died from coronary heart disease; these were considered “cases.” Then, these 1,673 women were matched against 20,000 “control” women of similar age. Information was pulled out for each case or control on their use of hormone replacement therapy, NSAIDs , and various risk factors for heart disease. The researchers then compared use of hormone replacement therapy and NSAIDs between the cases and controls, while making statistical adjustments for other risk factors .   The researchers found that current use of hormone replacement therapy was associated with a lower risk of heart attack than non-use. The odds ratio (chance of a heart attack among HT users compared to the chance among non-users of HT) was 0.78. However, when looking at women who used NSAIDs at the same time as hormone replacement therapy, the researchers found no suggestion of a reduction in risk of heart attack: the odds ratio for the chance of heart attack among this group of women, as compared to nonusers of both NSAIDs and hormone replacement therapy, was 1.50.These findings suggest that hormone replacement therapy and NSAIDs might interact, with NSAIDs acting against a role for hormone replacement therapy in preventing heart attacks. At face value, these results are in conflict with the findings of one large trial, the WHI trial, which failed to find a benefit of HT in preventing heart attacks. However, a recent analysis of WHI suggests cardioprotective effects of HT in women close to the time of the menopause and this coincides with the younger age of women in the observational studies such as the present one rather than in the WHI overall. Observational research studies, such as the present one, are often difficult to interpret because the groups being compared are not necessarily equivalent. It's possible that women who take hormone replacement therapy, or NSAIDs, are in some way different from women who do not, which will bias the findings. Determination of the clinical implications of these findings would most appropriately be resolved in future trials, designed to address the question of interest.http://dx.doi.org/10.1371/journal.pmed.0040157.Please access these Web sites via the online version of this summary at menopausal hormone therapy, including links to information about the Women's Health Initiative trials, information about managing menopausal symptoms, and moreResources from the US National Institutes of Health on heart disease in womenResources from the US National Institutes of Health (MedlinePlus) about hormone replacement therapyInformation from NHS Direct, the UK National Health Service, about UK General Practice Research Database is the database utilized in this articleThe nonsteroidal anti-inflammatory drugs (NSAIDs) (note: Wikipedia is an internet encyclopedia anyone can edit)Wikipedia entry on  Indeed, deletion of the I prostanoid receptor undermined substantially the vascular benefit of estrogen therapy in ovariectomized mice rendered prone to atherogenesis by deletion of the low-density lipoprotein receptor [Premenopausal women are less susceptible to myocardial infarction (MI) and stroke than are males of the same age group, an advantage that is lost after menopause . Howeverreceptor .2 in vivo. Sufficient information is currently unavailable to address this question for selective inhibitors of COX-2. However, traditional (t) nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen, variably inhibit both COX-1 and COX-2, unlike low-dose aspirin, which targets preferentially, albeit not exclusively, COX-1 [These observations prompted us to address the possibility that the failure to detect a benefit from estrogen might be partly attributable to a pharmacodynamic interaction with inhibitors of COX-2, the major source of PGIy, COX-1 ,5. The oThe General Practice Research Database contains computerized medical information entered systematically by general practitioners (GPs) in the UK and sent anonymously to the Medicines and Healthcare Products Regulatory Agency . The infn = 1,673) in the present study. We considered as fatal those individuals who died within the first 30 d after the occurrence of AMI and patients who died from CHD before reaching the hospital. Therefore in this study, designed a priori, AMI includes, if not otherwise stated, both fatal and nonfatal outcomes in the participants. A random date within the study period was generated for each of the study cohort members. All individuals with a random date included in their period of observation (from study entry to end of follow-up) were eligible as controls. A group of 20,000 control participants, frequency-matched by age, sex, and calendar year, was randomly sampled among with the study cohort. We applied to the controls the same computer-based exclusion criteria as we applied to AMI indviduals, using each participant's random date as his or her index date. For the present study, we included all women as control participants .We recently evaluated the association between tNSAIDs and acute MI , where m2, was calculated from the registered height and weight. Alcohol intake was used as directly registered by the GP. We also elicited the participants' use of the health services  in the two years before the index date.Information on coronary risk factors, comorbidities, and drug utilization was obtained from the database. Hypertension, diabetes, hyperlipidemia, smoking, cardiovascular disease, arthritis, and recent anemia were considered present when these specific diagnoses were registered in the database before the index date. History of CHD was defined by the presence of MI and/or angina. Cerebrovascular disease was defined by the presence of ischemic or hemorrhagic stroke. Body mass index, expressed in kg/mA list of all medications containing estrogens and/or progestogens recommended for HT and available in the UK during the study period was extracted from the British National Formulary. These drugs were grouped into the following regimens: (a) oral oestrogens; (b) transdermal oestradiol; (c) oestradiol implant; and (d) tibolone. In addition, oral oestrogens and transdermal oestradiol were classified as opposed  or unopposed  depending on whether a progestin was supplied along with oestrogens. Exposure to HT was classified into three groups: “current users” when the supply of the most recent prescription lasted until index date or ended in the year before the index date; “past users” when it ended more than one year before the index date; and “nonusers” when there was no recorded use before the index date. When current use was restricted to those exposed only in the month before the index date, the estimate for the interaction was slightly higher. There was considerable—73%—overlap in the women considered current users by the two definitions. The definition of current use for all other studied drugs, including tNSAIDs, was use of the drug in the month before the index date.A nested case-control analysis was performed to estimate the effect of HT as well as the interaction between HT and tNSAIDs on the risk of MI. We calculated the odds ratio (OR) and 95% confidence intervals (CIs) of MI using unconditional logistic regression. All estimates of risk were adjusted for age, smoking, hypertension, diabetes, obesity, hypercholesterolemia, ischemic heart disease, use of low-dose aspirin, and antihypertensive drugs.p = 0.0012. The figure also shows that these estimates of risk did not vary by duration of HT. The interaction was apparent in women taking both opposed and unopposed estrogens, with ORs of 1.39 (95% CI 0.65–2.95) and 1.86 (95% CI 0.79–4.42), respectively. Also, the interaction between HT and tNSAIDs was already evident within months of starting the tNSAID and was sustained, irrespective of the duration of tNSAID therapy or HT  . The corpy or HT . MenopauPrompted by these results, we sought the interaction in a secondary analysis of current and past HT users and in HT nonusers for patients on low- and high-dose aspirin, antihypertensives, antidepressants, and gastric acid–suppressing drugs—a further 15 comparisons. Clearly, it is possible that a significant result might be attained amongst such multiple comparisons by chance. Concomitant use of aspirin at 75mg/d, which preferentially targets COX-1 for inhibition, was associated with an OR of 0.71 (95% CI 0.26–1.94) approximating that in aspirin nonusers . However, the OR of a MI rose to 1.41 (95% CI 0.47–4.22) amongst users of HT with concomitant doses of aspirin 150 mg/d and above, where coincident inhibition of COX-2 should be more pronounced. We replicated these analyses adjusting for health services utilization, and the results were materially unchanged (unpublished data). We investigated whether this interaction was specific to tNSAIDs, and found that commonly used drugs, such as antihypertensive drugs, acid-suppressing drugs (proton pump inhibitors and/or histamine II antagonists), and tricyclic antidepressants failed to reveal an interaction with HT (unpublished data). Thus, the interaction between COX inhibitors and HT appeared to be specific. Also, when we performed a sensitivity analysis using a one-month time window instead of one year to define current use of HT, the OR of HT in women who were taking tNSAIDS concomitantly further rose to 1.85 (95% CI 1.01–3.41). Although we adjusted for matching factors  in our analysis and for a series of known cardiovascular risk factors, an unrecognized and therefore unmeasured factor that strongly related both to concomitant use of HT and NSAIDs on one hand, and to the risk of MI on the other might theoretically contribute to our results.The results of this study raise the possibility that concomitant medication with NSAIDs might undermine a cardioprotective effect of HT in perimenopausal women. Mechanistically, this might relate particularly to inhibition of COX-2. However, the present study pertained to tNSAIDs, which inhibit COX-2, but vary in their comcomitant inhibtion of COX-1 and did not include NSAIDs designed to attain specific inhibition of COX-2.Both the pattern of incidence and the manifestation of vascular disease differ between women and men. Premenopausal women exhibit a diminished burden of vascular disease compared with males of similar age; this difference is eclipsed after menopause . FurtherThe present study raises the possibility of a drug–drug interaction with cardiovascular implications involving COX inhibitors. Much controversy has surrounded the putative cardioprotective effects of HT reported in observational studies . Indeed,2 impacted particularly on initiation and early development of atherosclerosis [2 [Generally, when the results of observational studies are in conflict with an RCT, the balance of evidence favors the latter. While observational studies can control for recognized variables, they are vulnerable to an imbalanced distribution of unrecognized variables of relevance to the outcome of the study. On the other hand, WHI was also affected by some methodological constraints. The first was a differential detection bias . Close tclerosis . Thus, aclerosis —the apparosis [2 . Thus, w2. Scant information is presently available concerning the combined use of specific COX–2 inhibitors and HT. However, we examined a priori a database for an interaction between tNSAIDs and HT. Generally, the coincident, time-dependent inhibition of platelet COX-1–derived thromboxane A2 might be expected, if anything, to mitigate the impact of COX-2 inhibition by the tNSAIDs examined in this study [We have reported that estrogen dependent atheroprotection in mice depends in substantial part on COX-2 derived PGIis study . We do nis study ,23. Futuis study  is unsurIn summary, these observations, based on small numbers, are provocative rather than conclusive and are not intended to guide clinical practice, but rather to prompt additional research. However, they raise the possibility that coincident inhibition of COX-2 by tNSAIDs may undermine cardioprotective effects of HT in peri- and postmenopausal women. If evidence consistent with this interaction were obtained in other larger epidemiological datasets, the possibility could fruitfully be addressed directly in randomized controlled clinical trials.