Treatment of Chlordecone (Kepone) Toxicity with Cholestyramine — Results of a Controlled Clinical Trial

Abstract Industrial workers exposed to the organochlorine pesticide, chlordecone (Kepone), had signs of toxicity in several organs. The extent of toxicity was proportional to the levels of this chemical in the tissues. In 22 patients, chlordecone was eliminated slowly from blood (half time of 165±27 days — mean ± S.E.M.) and fat (half time of 125 days, with a range of 97 to 177), chiefly in the stool. Output of chlordecone in bile was 10 to 20 times greater than in stool, suggesting that chlordecone is reabsorbed in the intestine. Cholestyramine, an anion-exchange resin that binds chlordecone, increased its fecal excretion by seven times. In a five-month trial, cholestyramine significantly accelerated elimination of chlordecone from blood, with a half life of 80±4 days (S.E.M.) (

GJ 367b: A dense, ultrashort-period sub-Earth planet transiting a nearby red dwarf star

Ultrashort-period (USP) exoplanets have orbital periods shorter than 1 day. Precise masses and radii of USP exoplanets could provide constraints on their unknown formation and evolution processes. We present the work from Lam et al. 2021 (Science, 374, 1271) and report the detection and characterization of the USP planet GJ 367b using high-precision photometry and radial velocity observations. GJ 367b orbits a bright (V-band magnitude of 10.2), nearby, and red (M-type) dwarf star every 7.7 hours. GJ 367b has a radius of 0.718 ± 0.054 Earth-radii and a mass of 0.546 ± 0.078 Earth-masses, making it a sub-Earth planet. The corresponding bulk density is 8.106 ± 2.165 grams per cubic centimeter - close to that of iron. An interior structure model predicts that the planet has an iron core radius fraction of 86 ± 5%, similar to that of Mercury's interior

Associations of obesity and circulating insulin and glucose with breast cancer risk: a Mendelian randomization analysis.

BACKGROUND: In addition to the established association between general obesity and breast cancer risk, central obesity and circulating fasting insulin and glucose have been linked to the development of this common malignancy. Findings from previous studies, however, have been inconsistent, and the nature of the associations is unclear. METHODS: We conducted Mendelian randomization analyses to evaluate the association of breast cancer risk, using genetic instruments, with fasting insulin, fasting glucose, 2-h glucose, body mass index (BMI) and BMI-adjusted waist-hip-ratio (WHRadj BMI). We first confirmed the association of these instruments with type 2 diabetes risk in a large diabetes genome-wide association study consortium. We then investigated their associations with breast cancer risk using individual-level data obtained from 98 842 cases and 83 464 controls of European descent in the Breast Cancer Association Consortium. RESULTS: All sets of instruments were associated with risk of type 2 diabetes. Associations with breast cancer risk were found for genetically predicted fasting insulin [odds ratio (OR) = 1.71 per standard deviation (SD) increase, 95% confidence interval (CI) = 1.26-2.31, p  =  5.09  ×  10-4], 2-h glucose (OR = 1.80 per SD increase, 95% CI = 1.3 0-2.49, p  =  4.02  ×  10-4), BMI (OR = 0.70 per 5-unit increase, 95% CI = 0.65-0.76, p  =  5.05  ×  10-19) and WHRadj BMI (OR = 0.85, 95% CI = 0.79-0.91, p  =  9.22  ×  10-6). Stratified analyses showed that genetically predicted fasting insulin was more closely related to risk of estrogen-receptor [ER]-positive cancer, whereas the associations with instruments of 2-h glucose, BMI and WHRadj BMI were consistent regardless of age, menopausal status, estrogen receptor status and family history of breast cancer. CONCLUSIONS: We confirmed the previously reported inverse association of genetically predicted BMI with breast cancer risk, and showed a positive association of genetically predicted fasting insulin and 2-h glucose and an inverse association of WHRadj BMI with breast cancer risk. Our study suggests that genetically determined obesity and glucose/insulin-related traits have an important role in the aetiology of breast cancer

Physical activity, sedentary time and breast cancer risk: a Mendelian randomisation study

Objectives: Physical inactivity and sedentary behaviour are associated with higher breast cancer risk in observational studies, but ascribing causality is difficult. Mendelian randomisation (MR) assesses causality by simulating randomised trial groups using genotype. We assessed whether lifelong physical activity or sedentary time, assessed using genotype, may be causally associated with breast cancer risk overall, pre/post-menopause, and by case-groups defined by tumour characteristics. Methods: We performed two-sample inverse-variance-weighted MR using individual-level Breast Cancer Association Consortium case-control data from 130 957 European-ancestry women (69 838 invasive cases), and published UK Biobank data (n=91 105–377 234). Genetic instruments were single nucleotide polymorphisms (SNPs) associated in UK Biobank with wrist-worn accelerometer-measured overall physical activity (nsnps=5) or sedentary time (nsnps=6), or accelerometer-measured (nsnps=1) or self-reported (nsnps=5) vigorous physical activity. Results: Greater genetically-predicted overall activity was associated with lower breast cancer overall risk (OR=0.59; 95% confidence interval (CI) 0.42 to 0.83 per-standard deviation (SD;~8 milligravities acceleration)) and for most case-groups. Genetically-predicted vigorous activity was associated with lower risk of pre/perimenopausal breast cancer (OR=0.62; 95% CI 0.45 to 0.87,≥3 vs. 0 self-reported days/week), with consistent estimates for most case-groups. Greater genetically-predicted sedentary time was associated with higher hormone-receptor-negative tumour risk (OR=1.77; 95% CI 1.07 to 2.92 per-SD (~7% time spent sedentary)), with elevated estimates for most case-groups. Results were robust to sensitivity analyses examining pleiotropy (including weighted-median-MR, MR-Egger). Conclusion: Our study provides strong evidence that greater overall physical activity, greater vigorous activity, and lower sedentary time are likely to reduce breast cancer risk. More widespread adoption of active lifestyles may reduce the burden from the most common cancer in women

Two truncating variants in FANCC and breast cancer risk

Fanconi anemia (FA) is a genetically heterogeneous disorder with 22 disease-causing genes reported to date. In some FA genes, monoallelic mutations have been found to be associated with breast cancer risk, while the risk associations of others remain unknown. The gene for FA type C, FANCC, has been proposed as a breast cancer susceptibility gene based on epidemiological and sequencing studies. We used the Oncoarray project to genotype two truncating FANCC variants (p.R185X and p.R548X) in 64,760 breast cancer cases and 49,793 controls of European descent. FANCC mutations were observed in 25 cases (14 with p.R185X, 11 with p.R548X) and 26 controls (18 with p.R185X, 8 with p.R548X). There was no evidence of an association with the risk of breast cancer, neither overall (odds ratio 0.77, 95% CI 0.44-1.33, p = 0.4) nor by histology, hormone receptor status, age or family history. We conclude that the breast cancer risk association of these two FANCC variants, if any, is much smaller than for BRCA1, BRCA2 or PALB2 mutations. If this applies to all truncating variants in FANCC it would suggest there are differences between FA genes in their roles on breast cancer risk and demonstrates the merit of large consortia for clarifying risk associations of rare variants.Peer reviewe

The use of political risk assessment techniques in Jordanian multinational corporations

This paper describes and explains the use of political risk assessment techniques in Jordanian multinational corporations (MNCs). A multi-method approach to collect data was followed. A self-report questionnaire was delivered by hand to the general managers of all Jordanian MNCs which were identified as operating internationally. Semi-structured interviews were used as a means of elaborating on the findings from the questionnaire. The study identified the extensive use of heuristic political risk assessment techniques (due to their flexibility, simplicity and low cost). Scientific techniques, on the other hand, were used by only a minority of MNCs. As has been the case in earlier studies, flexibility, simplicity and cost considerations were all found to be influential in this regard. However, the study also found that key decision-makers in Jordanian MNCs believe that official data are subject to censorship and are therefore not reliable. This undermines the efficiency of using highly sophisticated scientific techniques. Since there are a number of other countries in the Middle East - and elsewhere - in which these considerations also apply, this finding has important implications for international businesses which operate in these countries, whatever their home country

GJ 367b: A dense, ultrashort-period sub-Earth planet transiting a nearby red dwarf star

Ultrashort-period (USP) exoplanets have orbital periods shorter than 1 day. Precise masses and radii of USP exoplanets could provide constraints on their unknown formation and evolution processes. We report the detection and characterization of the USP planet GJ 367b using high-precision photometry and radial velocity observations. GJ 367b orbits a bright (V-band magnitude of 10.2), nearby, and red (M-type) dwarf star every 7.7 hours. GJ 367b has a radius of 0.718 ± 0.054 Earth-radii and a mass of 0.546 ± 0.078 Earth-masses, making it a sub-Earth planet. The corresponding bulk density is 8.106 ± 2.165 grams per cubic centimeter—close to that of iron. An interior structure model predicts that the planet has an iron core radius fraction of 86 ± 5%, similar to that of Mercury’s interior.Fil: Lam, Kristine W.F.. German Aerospace Center; Alemania. Technishe Universitat Berlin; AlemaniaFil: Csizmadia, Szilárd. German Aerospace Center; AlemaniaFil: Astudillo Defru, Nicola. Universidad Católica de la Santísima Concepción; ChileFil: Bonfils, Xavier. Universite Grenoble Alpes; FranciaFil: Gandolfi, Davide. Università di Torino; ItaliaFil: Padovan, Sebastiano. European Organisation for the Exploitation of Meteorological Satellites; Alemania. German Aerospace Center; AlemaniaFil: Esposito, Massimiliano. Thüringer Landessternwarte Tautenburg; AlemaniaFil: Hellier, Coel. Keele University; Reino UnidoFil: Hirano, Teruyuki. Tokyo Institute Of Technology; JapónFil: Livingston, John. The University Of Tokyo; JapónFil: Murgas, Felipe. Instituto Astrofisico de Canarias; España. Universidad de La Laguna; EspañaFil: Smith, Alexis M.S.. German Aerospace Center; AlemaniaFil: Collins, Karen A.. Harvard-Smithsonian Center for Astrophysics; Estados UnidosFil: Mathur, Savita. Instituto Astrofisico de Canarias; España. Universidad de La Laguna; EspañaFil: Garcia, Rafael A.. Universite Paris-Saclay;Fil: Howell, Steve B.. NASA Ames Research Center; Estados UnidosFil: Santos, Nuno C.. Universidad de Porto; PortugalFil: Dai, Fei. California Institute of Technology; Estados UnidosFil: Ricker, George R.. Massachusetts Institute of Technology; Estados UnidosFil: Vanderspek, Roland. Massachusetts Institute of Technology; Estados UnidosFil: Latham, David W.. Harvard-Smithsonian Center for Astrophysics; Estados UnidosFil: Seager, Sara. Massachusetts Institute of Technology; Estados UnidosFil: Winn, Joshua N.. University of Princeton; Estados UnidosFil: Jenkins, Jon M.. Nasa Ames Research Center; Estados UnidosFil: Albrecht, Simon. University Aarhus; DinamarcaFil: Almenara, Jose M.. Universite Grenoble Alpes; FranciaFil: Artigau, Etienne. Universite Grenoble Alpes; FranciaFil: Barragán, Oscar. University of Oxford; Reino UnidoFil: Bouchy, François. Universidad de Ginebra; SuizaFil: Cabrera, Juan. Universite Grenoble Alpes; FranciaFil: Diaz, Rodrigo Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Ciencias Físicas. - Universidad Nacional de San Martín. Instituto de Ciencias Físicas; Argentin