Technical design and performance of the NEMO3 detector

The development of the NEMO3 detector, which is now running in the Frejus Underground Laboratory (L.S.M. Laboratoire Souterrain de Modane), was begun more than ten years ago. The NEMO3 detector uses a tracking-calorimeter technique in order to investigate double beta decay processes for several isotopes. The technical description of the detector is followed by the presentation of its performance.Comment: Preprint submitted to Nucl. Instrum. Methods A Corresponding author: Corinne Augier ([email protected]

The epidemiology of suicide and attempted suicide in Dutch general practice 1983–2003

BACKGROUND: Many patients attempting or committing suicide consult their general practitioner (GP) in the preceding period, indicating that GPs might play an important role in prevention. The aim of the present study was to analyse the epidemiology of suicidal behaviour in Dutch General Practice in order to find possible clues for prevention. METHOD: Description of trends in suicide and suicide attempts occurring from 1983–2003 in the Dutch General Practice Sentinel Network, representing 1% of the Dutch population. The data were analysed with regard to: 1) suicidal behaviour trends and their association with household situation; 2) presence of depression, treatment of depression and referral rate by GPs; 3) contact with GP before suicide or suicide attempt and discussion of suicidal ideation. RESULTS: Between 1983 and 2003 the annual number of suicide and suicide attempts decreased by 50%. Sixty percent of the patients who committed or attempted suicide were diagnosed as depressed, of whom 91% were treated by their GP with an antidepressant. Living alone was a risk factor for suicide (odds ratio 1.99; 95% CI 1.50 to 2.64), whereas living in a household of 3 or more persons was a relative risk for a suicide attempt (odds ratio 1.81; 95% CI 1.34 to 2.46). Referral to a psychiatrist or other mental health professionals occurred in 65% of the cases. GPs recalled having discussed suicidal ideation in only 7% of the cases, and in retrospect estimated that they had foreseen suicide or suicide attempts in 31% and 22% of the cases, respectively, if there had been contact in the preceding month. CONCLUSION: With regard to the prescription of antidepressants and referral of suicidal patients to a psychiatrist, Dutch GPs fulfil their role as gatekeeper satisfactorily. However, since few patients discuss their suicidal ideation with their GP, there is room for improvement. GPs should take the lead to make this subject debatable. It may improve early recognition of depressed patients at risk and accelerate their referral to mental health professionals

Internet-based monitoring of influenza-like illness (ILI) in the general population of the Netherlands during the 2003–2004 influenza season

BACKGROUND: An internet-based survey of influenza-like illness (ILI) – the Great Influenza Survey or GIS – was launched in the Netherlands in the 2003–2004 influenza season. The aim of the present study was to validate the representativeness of the GIS population and to compare the GIS data with the official ILI data obtained by Dutch GPs participating in the Dutch Sentinel Practice Network. METHOD: Direct mailings to schools and universities, and repeated interviews on television and radio, and in newspapers were used to kindle the enthusiasm of a broad section of the public for GIS. Strict symptomatic criteria for ILI were formulated with the assistance of expert institutes and only participants who responded at least five times to weekly e-mails asking them about possible ILI symptoms were included in the survey. Validation of GIS was done at different levels: 1) some key demographic (age distribution) and public health statistics (prevalence of asthma and diabetes, and influenza vaccination rates) for the Dutch population were compared with corresponding figures calculated from GIS; 2) the ILI rates in GIS were compared with the ILI consultation rates reported by GPs participating in the Dutch Sentinel Practice Network. RESULTS: 13,300 persons (53% of total responders), replied at least five times to weekly e-mails and were included in the survey. As expected, there was a marked under-representation of the age groups 0–10 years and 81->90 years in the GIS population, although the similarities were remarkable for most other age groups, albeit that the age groups between 21 and 70 years were slightly overrepresented. There were striking similarities between GIS and the Dutch population with regard to the prevalence of asthma (6.4% vs. 6.9%) and the influenza vaccination rates, and to a lesser degree for diabetes (2.4% vs. 3.5%). The vaccination rates in patients with asthma or diabetes, and persons older than 65 years were 68%, 85%, and 85% respectively in GIS, while the corresponding percentages in the Dutch population were 73%, 85% and 87%. There was also a marked similarity between the seasonal course of ILI measured by GIS and the GPs. Although the ILI rate in GIS was about 10 times higher, the curves followed an almost similar pattern, with peak incidences occurring in the same week. CONCLUSION: The current study demonstrates that recruitment of a high number of persons willing to participate in on-line health surveillance is feasible. The information gathered proved to be reliable, as it paralleled the information obtained via an undisputed route. We believe that the interactive nature of GIS and the appealing subject were keys to its success

Interleukin 12B (IL12B) Genetic Variation and Pulmonary Tuberculosis: A Study of Cohorts from The Gambia, Guinea-Bissau, United States and Argentina

We examined whether polymorphisms in interleukin-12B (IL12B) associate with susceptibility to pulmonary tuberculosis (PTB) in two West African populations (from The Gambia and Guinea-Bissau) and in two independent populations from North and South America. Nine polymorphisms (seven SNPs, one insertion/deletion, one microsatellite) were analyzed in 321 PTB cases and 346 controls from Guinea-Bissau and 280 PTB cases and 286 controls from The Gambia. For replication we studied 281 case and 179 control African-American samples and 221 cases and 144 controls of European ancestry from the US and Argentina. First-stage single locus analyses revealed signals of association at IL12B 3′ UTR SNP rs3212227 (unadjusted allelic p = 0.04; additive genotypic p = 0.05, OR = 0.78, 95% CI [0.61–0.99]) in Guinea-Bissau and rs11574790 (unadjusted allelic p = 0.05; additive genotypic p = 0.05, OR = 0.76, 95% CI [0.58–1.00]) in The Gambia. Association of rs3212227 was then replicated in African-Americans (rs3212227 allelic p = 0.002; additive genotypic p = 0.05, OR = 0.78, 95% CI [0.61–1.00]); most importantly, in the African-American cohort, multiple significant signals of association (seven of the nine polymorphisms tested) were detected throughout the gene. These data suggest that genetic variation in IL12B, a highly relevant candidate gene, is a risk factor for PTB in populations of African ancestry, although further studies will be required to confirm this association and identify the precise mechanism underlying it

Genetic Determination and Linkage Mapping of Plasmodium falciparum Malaria Related Traits in Senegal

Plasmodium falciparum malaria episodes may vary considerably in their severity and clinical manifestations. There is good evidence that host genetic factors contribute to this variability. To date, most genetic studies aiming at the identification of these genes have used a case/control study design for severe malaria, exploring specific candidate genes. Here, we performed a family-based genetic study of falciparum malaria related phenotypes in two independent longitudinal survey cohorts, as a first step towards the identification of genes and mechanisms involved in the outcome of infection. We studied two Senegalese villages, Dielmo and Ndiop that differ in ethnicity, malaria transmission and endemicity. We performed genome-scan linkage analysis of several malaria-related phenotypes both during clinical attacks and asymptomatic infection. We show evidence for a strong genetic contribution to both the number of clinical falciparum malaria attacks and the asymptomatic parasite density. The asymptomatic parasite density showed linkage to chromosome 5q31 (LOD = 2.26, empirical p = 0.0014, Dielmo), confirming previous findings in other studies. Suggestive linkage values were also obtained at three additional chromosome regions: the number of clinical malaria attacks on chromosome 5p15 (LOD = 2.57, empirical p = 0.001, Dielmo) and 13q13 (LOD = 2.37, empirical p = 0.0014 Dielmo), and the maximum parasite density during asymptomatic infection on chromosome 12q21 (LOD = 3.1, empirical p<10−4, Ndiop). While regions of linkage show little overlap with genes known to be involved in severe malaria, the four regions appear to overlap with regions linked to asthma or atopy related traits, suggesting that common immune related pathways may be involved

Gluons and the quark sea at high energies: distributions, polarization, tomography

This report is based on a ten-week program on "Gluons and the quark sea at high-energies", which took place at the Institute for Nuclear Theory in Seattle in Fall 2010. The principal aim of the program was to develop and sharpen the science case for an Electron-Ion Collider (EIC), a facility that will be able to collide electrons and positrons with polarized protons and with light to heavy nuclei at high energies, offering unprecedented possibilities for in-depth studies of quantum chromodynamics. This report is organized around four major themes: i) the spin and flavor structure of the proton, ii) three-dimensional structure of nucleons and nuclei in momentum and configuration space, iii) QCD matter in nuclei, and iv) Electroweak physics and the search for physics beyond the Standard Model. Beginning with an executive summary, the report contains tables of key measurements, chapter overviews for each of the major scientific themes, and detailed individual contributions on various aspects of the scientific opportunities presented by an EIC.Comment: 547 pages, A report on the joint BNL/INT/Jlab program on the science case for an Electron-Ion Collider, September 13 to November 19, 2010, Institute for Nuclear Theory, Seattle; v2 with minor changes, matches printed versio

1,25-Dihydroxyvitamin D3 modulates the phenotype and function of Monocyte derived dendritic cells in cattle

Abstract Background The active form of the vitamin D3, 1,25-Dihydroxyvitamin D3 (1,25-(OH)2D3) has been shown to have major effects not only on physiological processes but also on the regulation of the immune system of vertebrates. Dendritic cells are specialised antigen presenting cells which are in charge of the initiation of T-cell dependant immune responses and as such are key regulators of responses towards pathogens. In this study we set out to evaluate the effects of 1,25-(OH)2D3 on the phenotype of cattle monocyte-derived dendritic cells (MoDCs) and how the conditioning with this vitamin affects the function of these myeloid cells. Results MoDCs were generated from CD14+ monocytes with bovine IL-4 and GM-CSF with or without 1,25-(OH)2D3 supplementation for 10 days. Vitamin D conditioned MoDCs showed a reduced expression of co-stimulatory and antigen presenting molecules, as well as a reduced capability of endocytose ovalbumin. Furthermore, the capacity of MoDCs to induce proliferation in an allogeneic mixed leukocyte reaction was abolished when MoDCs were generated in presence of 1,25-(OH)2D3. LPS induced maturation of 1,25-(OH)2D3conditioned MoDCs resulted in lower secretion of IL-12 and higher IL-10 than that observed in MoDCs. Conclusions The typical immunotolerant phenotype observed in cattle DCs after exposure to 1,25-(OH)2D3 has a significant effect on the functionality of these immune cells, inhibiting the T-cell stimulatory capacity of MoDCs. This could have profound implications on how the bovine immune system deals with pathogens, particularly in diseases such as tuberculosis or paratuberculosis

The antitumour activity of the interferon inducer bropirimine is partially mediated by endogenous tumour necrosis factor α

Pyrimidinones, like 2-amino-5-bromo-6-phenyl-4-pyrimidinone (bropirimine), are potent immunomodulators. Natural killer cell activity and macrophage cytotoxicity are increased after bropirimine treatment, an effect exerted through induction of cytokines. Up to now, the interferons have been supposed to be the main mediators but we have found that tumour necrosis factor α (TNFα) can also be an important mediator of the bropirimine antitumour effects. Increased serum levels of TNFα were seen in rats after intraperitoneal administration of 200 mg/kg bropirimine on 2 consecutive days. We also found that the tumour-growth-inhibiting effect of the drug on a colon carcinoma in rats could be reduced about 40% by giving the rats rabbit anti-TNFα serum just prior to drug treatment. These results indicate that bropirimine can induce the release of TNFα in vivo and that this endogenous TNFα may be important as far as the antitumour effect of the drug is concerned.</p