One spatial filter limits speed of detecting low and middle frequency gratings

AbstractReaction times for detecting sinusoidal gratings depend jointly on grating contrast and spatial frequency. We examine whether the effect of spatial frequency results from low-pass filtering in a single channel or reflects processing of different frequencies by two or more different processing streams. Observers performed a speeded two-alternative spatial forced-choice detection. Errors and reaction times were measured. Contrasts varied from 0.05 to 0.67, and spatial frequencies from 0.72 to 6.51 cpd. No effect of uncertainty about spatial frequency was found, arguing against multiple channels. The data are well fit by a single channel model driven by a low pass filter

Real-time PCR/MCA assay using fluorescence resonance energy transfer for the genotyping of resistance related DHPS-540 mutations in Plasmodium falciparum

BACKGROUND: Sulphadoxine-pyrimethamine has been abandoned as first- or second-line treatment by most African malaria endemic countries in favour of artemisinin-based combination treatments, but the drug is still used as intermittent preventive treatment during pregnancy. However, resistance to sulphadoxine-pyrimethamine has been increasing in the past few years and, although the link between molecular markers and treatment failure has not been firmly established, at least for pregnant women, it is important to monitor such markers. METHODS: This paper reports a novel sensitive, semi-quantitative and specific real-time PCR and melting curve analysis (MCA) assay using fluorescence resonance energy transfer (FRET) for the detection of DHPS-540, an important predictor for SP resistance. FRET/MCA was evaluated using 78 clinical samples from malaria patients and compared to PCR-RFLP. RESULTS: Sixty-two samples were in perfect agreement between both assays. One sample showed a small wild type signal with FRET/MCA that indicates a polyclonal infection. Four samples were not able to generate enough material in both assays to distinguish mutant from wild-type infection, six samples gave no signal in PCR-RFLP and five samples gave no amplification in FRET/MCA. CONCLUSION: FRET/MCA is an effective tool for the identification of SNPs in drug studies and epidemiological surveys on resistance markers in general and DHPS-540 mutation in particular

Gametocytes: insights gained during a decade of molecular monitoring

In vertebrate hosts, malaria parasites produce specialized male and female sexual stages (gametocytes). Soon after being taken up by a mosquito, gametocytes rapidly produce gametes and, once mated, they infect their vector and can be transmitted to new hosts. Despite being the parasite stages that were first identified (over a century ago), gametocytes have remained elusive, and basic questions remain concerning their biology. However, the postgenomic era has substantiated information on the specialized molecular machinery of gametocytogenesis and expedited the development of molecular tools to detect and quantify gametocytes. The application of such highly sensitive and specific tools has opened up novel approaches and provided new insights into gametocyte biology. Here, we review the discoveries made during the past decade, highlight unanswered questions and suggest new directions

CENPHER five year report 2009-2014: From a research project to a research center

Other than the influence of ionizing radiation and benign thyroid disease, little is known about the risk factors for differentiated thyroid cancer (TC) which is an increasing common cancer worldwide. Consistent evidence shows that body mass is positively associated with TC risk. As excess weight is a state of chronic inflammation, we investigated the relationship between concentrations of leptin, adiponectin, C-reactive protein, interleukin (IL)-6, IL-10 and tumor necrosis factor (TNF)-α and the risk of TC. A case-control study was nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) study and included 475 first primary incident TC cases (399 women and 76 men) and 1,016 matched cancer-free cohort participants. Biomarkers were measured in serum samples using validated and highly sensitive commercially available immunoassays. Odds ratios (ORs) of TC by levels of each biomarker were estimated using conditional logistic regression models, adjusting for BMI and alcohol consumption. Adiponectin was inversely associated with TC risk among women (ORT3vs.T1 = 0.69, 95% CI: 0.49-0.98, Ptrend = 0.04) but not among men (ORT3vs.T1 = 1.36, 95% CI: 0.67-2.76, Ptrend = 0.37). Increasing levels of IL-10 were positively associated with TC risk in both genders and significantly so in women (ORT3vs.T1 = 1.59, 95% CI: 1.13-2.25, Ptrend = 0.01) but not in men (ORT3vs.T1 = 1.78, 95% CI: 0.80-3.98, Ptrend = 0.17). Leptin, CRP, IL-6 and TNF-α were not associated with TC risk in either gender. These results indicate a positive association of TC risk with IL-10 and a negative association with adiponectin that is probably restricted to women. Inflammation may play a role in TC in combination with or independently of excess weight

Prediagnostic circulating concentrations of plasma insulin-like growth factor-I and risk of lymphoma in the European Prospective Investigation into Cancer and Nutrition

Insulin-like growth factor (IGF)-I has cancer promoting activities. However, the hypothesis that circulating IGF-I concentration is related to risk of lymphoma overall or its subtypes has not been examined prospectively. IGF-I concentration was measured in pre-diagnostic plasma samples from a nested case-control study of 1,072 cases of lymphoid malignancies and 1,072 individually matched controls from the European Prospective Investigation into Cancer and Nutrition. Odds ratios (ORs) and confidence intervals (CIs) for lymphoma were calculated using conditional logistic regression. IGF-I concentration was not associated with overall lymphoma risk (multivariable-adjusted OR for highest versus lowest third = 0.77 [95% CI = 0.57-1.03], ptrend  = 0.06). There was no statistical evidence of heterogeneity in this association with IGF-I by sex, age at blood collection, time between blood collection and diagnosis, age at diagnosis, or body mass index (pheterogeneity for all  ≥ 0.05). There were no associations between IGF-I concentration and risk for specific BCL subtypes, T-cell lymphoma or Hodgkin lymphoma, although number of cases were small. In this European population, IGF-I concentration was not associated with risk of overall lymphoma. This study provides the first prospective evidence on circulating IGF-I concentrations and risk of lymphoma. Further prospective data are required to examine associations of IGF-I concentrations with lymphoma subtypes.The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ), Federal Ministry of Education and Research (BMBF), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum and Federal Ministry of Education and Research (Germany); the Hellenic Health Foundation (Greece); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands); ERC-2009-AdG 232997 and Nordforsk, Nordic Centre of Excellence programme on Food, Nutrition and Health (Norway); Health Research Fund (FIS), PI13/00061 to Granada, PI13/01162 to EPIC-Murcia, Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, ISCIII RETIC (RD06/0020) (Spain); Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden); Cancer Research UK (14136 to EPIC-Norfolk; C570/A11692, C570/A16491 and C8221/A19170 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) (United Kingdom)

Adipokines and inflammation markers and risk of differentiated thyroid carcinoma: The EPIC study

Other than the influence of ionizing radiation and benign thyroid disease, little is known about the risk factors for differentiated thyroid cancer (TC) which is an increasing common cancer worldwide. Consistent evidence shows that body mass is positively associated with TC risk. As excess weight is a state of chronic inflammation, we investigated the relationship between concentrations of leptin, adiponectin, C-reactive protein, interleukin (IL)-6, IL-10 and tumor necrosis factor (TNF)-α and the risk of TC. A case-control study was nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) study and included 475 first primary incident TC cases (399 women and 76 men) and 1,016 matched cancer-free cohort participants. Biomarkers were measured in serum samples using validated and highly sensitive commercially available immunoassays. Odds ratios (ORs) of TC by levels of each biomarker were estimated using conditional logistic regression models, adjusting for BMI and alcohol consumption. Adiponectin was inversely associated with TC risk among women (ORT3vs.T1 = 0.69, 95% CI: 0.49-0.98, Ptrend = 0.04) but not among men (ORT3vs.T1 = 1.36, 95% CI: 0.67-2.76, Ptrend = 0.37). Increasing levels of IL-10 were positively associated with TC risk in both genders and significantly so in women (ORT3vs.T1 = 1.59, 95% CI: 1.13-2.25, Ptrend = 0.01) but not in men (ORT3vs.T1 = 1.78, 95% CI: 0.80-3.98, Ptrend = 0.17). Leptin, CRP, IL-6 and TNF-α were not associated with TC risk in either gender. These results indicate a positive association of TC risk with IL-10 and a negative association with adiponectin that is probably restricted to women. Inflammation may play a role in TC in combination with or independently of excess weight

Circulating insulin-like growth factor I in relation to melanoma risk in the European Prospective Investigation into Cancer and Nutrition

Insulin-like growth factor-I (IGF-I) regulates cell proliferation and apoptosis, and is thought to play a role in tumour development. Previous prospective studies have shown that higher circulating concentrations of IGF-I are associated with a higher risk of cancers at specific sites, including breast and prostate. No prospective study has examined the association between circulating IGF-I concentrations and melanoma risk. A nested case-control study of 1,221 melanoma cases and 1,221 controls was performed in the European Prospective Investigation into Cancer and Nutrition cohort, a prospective cohort of 520,000 participants recruited from 10 European countries. Conditional logistic regression was used to estimate odds ratios (ORs) for incident melanoma in relation to circulating IGF-I concentrations, measured by immunoassay. Analyses were conditioned on the matching factors and further adjusted for age at blood collection, education, height, BMI, smoking status, alcohol intake, marital status, physical activity and in women only, use of menopausal hormone therapy. There was no significant association between circulating IGF-I concentration and melanoma risk (OR for highest vs lowest fifth = 0.93 [95% confidence interval [CI]: 0.71 to 1.22]). There was no significant heterogeneity in the association between IGF-I concentrations and melanoma risk when subdivided by gender, age at blood collection, BMI, height, age at diagnosis, time between blood collection and diagnosis, or by anatomical site or histological subtype of the tumour (Pheterogeneity≥0.078). We found no evidence for an association between circulating concentrations of IGF-I measured in adulthood and the risk of melanoma

Coffee and tea drinking in relation to the risk of differentiated thyroid carcinoma: results from the European Prospective Investigation into Cancer and Nutrition (EPIC) study.

PURPOSE: Coffee and tea constituents have shown several anti-carcinogenic activities in cellular and animal studies, including against thyroid cancer (TC). However, epidemiological evidence is still limited and inconsistent. Therefore, we aimed to investigate this association in a large prospective study. METHODS: The study was conducted in the EPIC (European Prospective Investigation into Cancer and Nutrition) cohort, which included 476,108 adult men and women. Coffee and tea intakes were assessed through validated country-specific dietary questionnaires. RESULTS: During a mean follow-up of 14 years, 748 first incident differentiated TC cases (including 601 papillary and 109 follicular TC) were identified. Coffee consumption (per 100 mL/day) was not associated either with total differentiated TC risk (HRcalibrated 1.00, 95% CI 0.97-1.04) or with the risk of TC subtypes. Tea consumption (per 100 mL/day) was not associated with the risk of total differentiated TC (HRcalibrated 0.98, 95% CI 0.95-1.02) and papillary tumor (HRcalibrated 0.99, 95% CI 0.95-1.03), whereas an inverse association was found with follicular tumor risk (HRcalibrated 0.90, 95% CI 0.81-0.99), but this association was based on a sub-analysis with a small number of cancer cases. CONCLUSIONS: In this large prospective study, coffee and tea consumptions were not associated with TC risk.Cancer Research UK (14136 to EPIC-Norfolk; C570/A16491 and C8221/A19170 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) (United Kingdom)

Consumption of fruits, vegetables and fruit juices and differentiated thyroid carcinoma risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study.

Fruit and vegetable (F&V) intake is considered as probably protective against overall cancer risk, but results in previous studies are not consistent for thyroid cancer (TC). The purpose of this study is to examine the association between the consumption of fruits, vegetables, fruit juices and differentiated thyroid cancer risk within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. The EPIC study is a cohort including over half a million participants, recruited between 1991 and 2000. During a mean follow-up of 14 years, 748 incident first primary differentiated TC cases were identified. F&V and fruit juice intakes were assessed through validated country-specific dietary questionnaires. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox regression models adjusted for potential confounding factors. Comparing the highest versus lowest quartile of intake, differentiated TC risk was not associated with intakes of total F&V (HR: 0.89; 95% CI: 0.68-1.15; p-trend = 0.44), vegetables (HR: 0.89; 95% CI: 0.69-1.14; p-trend = 0.56), or fruit (HR: 1.00; 95% CI: 0.79-1.26; p-trend = 0.64). No significant association was observed with any individual type of vegetable or fruit. However, there was a positive borderline trend with fruit juice intake (HR: 1.23; 95% CI: 0.98-1.53; p-trend = 0.06). This study did not find any significant association between F&V intakes and differentiated TC risk; however a positive trend with fruit juice intake was observed, possibly related to its high sugar content

Incident Tuberculosis during Antiretroviral Therapy Contributes to Suboptimal Immune Reconstitution in a Large Urban HIV Clinic in Sub-Saharan Africa

Antiretroviral therapy (ART) effectively decreases tuberculosis (TB) incidence long-term, but is associated with high TB incidence rates in the first 6 months. We sought to determine the incidence and the long-term effects of TB during ART on HIV treatment outcome, and the risk factors for incident TB during ART in a large urban HIV clinic in Uganda.Routinely collected longitudinal clinical data from all patients initiated on first-line ART was retrospectively analysed. 5,982 patients were included with a median baseline CD4+ T cell count (CD4 count) of 117 cells/mm(3) (interquartile range [IQR]; 42, 182). In the first 2 years, there were 336 (5.6%) incident TB events in 10,710 person-years (py) of follow-up (3.14 cases/100 pyar [95% CI 2.82-3.49]); incidence rates at 0-3, 3-6, 6-12 and 12-24 months were 11.25 (9.58-13.21), 6.27 (4.99-7.87), 2.47 (1.87-3.36) and 1.02 (0.80-1.31), respectively. Incident TB during ART was independently associated with baseline CD4 count of <50 cells/mm(3) (hazard ratio [HR] 1.84 [1.25-2.70], P = 0.002) and male gender (HR 1.68 [1.34-2.11], P<0.001). After two years on ART, the patients who had developed TB in the first 12 months had a significantly lower median CD4 count increase (184 cells/mm(3) [IQR; 107, 258, n = 118] vs 209 cells/mm(3) [124, 309, n = 2166], P = 0.01), a larger proportion of suboptimal immune reconstitution according to two definitions (increase in CD4 count <200 cells/mm(3): 57.4% vs 46.9%, P = 0.03, and absolute CD4 count <200 cells/mm(3): 30.4 vs 19.9%, P = 0.006), and a higher percentage of immunological failure according to the WHO criteria (13.6% vs 6.5%, P = 0.003). Incident TB during ART was independently associated with poor CD4 count recovery and fulfilling WHO immunological failure definitions.Incident TB during ART occurs most often within 3 months and in patients with CD4 counts less than 50 cells/mm(3). Incident TB during ART is associated with long-term impairment in immune recovery