Genetic variants determining survival and fertility in an adverse African environment:a population-based large-scale candidate gene association study

Molecular Technology and Informatics for Personalised Medicine and Healt

Dielectronic Recombination of Ground-State and Metastable Li+ Ions

Dielectronic recombination has been investigated for Delta-n = 1 resonances of ground-state Li+(1s^2) and for Delta-n = 0 resonances of metastable Li+(1s2s ^3S). The ground-state spectrum shows three prominent transitions between 53 and 64 eV, while the metastable spectrum exhibits many transitions with energies < 3.2 eV. Reasonably good agreement of R-matrix, LS coupling calculations with the measured recombination rate coefficient is obtained. The time dependence of the recombination rate yields a radiative lifetime of 52.2 +- 5.0 s for the 2 ^3S level of Li+.Comment: Submitted to Phys. Rev. A; REVTeX, 4 pages, 3 figure

Heating of nuclei with energetic anti-protons

International audienceHigh-energy γ rays associated with the decay of the giant dipole resonance have been measured for two fusion reactions leading to the 140Sm compound nucleus at an excitation energy of 71 MeV. The observed yield increases with the asymmetry in the ratios of the number of neutrons to protons in the entrance channel. This is interpreted as resulting from giant dipole phonons excited at the moment of collision in an N/Z asymmetric reaction

Economic predictors of differences in interview faking between countries : economic inequality matters, not the state of economy

Many companies recruit employees from different parts of the globe, and faking behavior by potential employees is a ubiquitous phenomenon. It seems that applicants from some countries are more prone to faking compared to others, but the reasons for these differences are largely unexplored. This study relates country-level economic variables to faking behavior in hiring processes. In a cross-national study across 20 countries, participants (N = 3839) reported their faking behavior in their last job interview. This study used the random response technique (RRT) to ensure participants anonymity and to foster honest answers regarding faking behavior. Results indicate that general economic indicators (gross domestic product per capita [GDP] and unemployment rate) show negligible correlations with faking across the countries, whereas economic inequality is positively related to the extent of applicant faking to a substantial extent. These findings imply that people are sensitive to inequality within countries and that inequality relates to faking, because inequality might actuate other psychological processes (e.g., envy) which in turn increase the probability for unethical behavior in many forms

Polysulfates block SARS‐CoV‐2 uptake through electrostatic interactions

Here we report that negatively charged polysulfates can bind to the spike protein of SARS-CoV-2 via electrostatic interactions. Using a plaque reduction assay, we compare inhibition of SARS-CoV-2 by heparin, pentosan sulfate, linear polyglycerol sulfate (LPGS) and hyperbranched polyglycerol sulfate (HPGS). Highly sulfated LPGS is the optimal inhibitor, with a half-maximal inhibitory concentration (IC50) of 67 μg/mL (approx. 1.6 μM). This synthetic polysulfates exhibit more than 60-fold higher virus inhibitory activity than heparin (IC50: 4084 μg/mL), along with much lower anticoagulant activity. Furthermore, in molecular dynamics simulations, we verified that LPGS can bind stronger to the spike protein than heparin, and that LPGS can interact even more with the spike protein of the new N501Y and E484K variants. Our study demonstrates that the entry of SARS-CoV-2 into host cells can be blocked via electrostatic interaction, therefore LPGS can serve as a blueprint for the design of novel viral inhibitors of SARS-CoV-2

Selection for Genetic Variation Inducing Pro-Inflammatory Responses under Adverse Environmental Conditions in a Ghanaian Population

BACKGROUND:Chronic inflammation is involved in the pathogenesis of chronic age-associated, degenerative diseases. Pro-inflammatory host responses that are deleterious later in life may originate from evolutionary selection for genetic variation mediating resistance to infectious diseases under adverse environmental conditions. METHODOLOGY/PRINCIPAL FINDINGS:In the Upper-East region of Ghana where infection has remained the leading cause of death, we studied the effect on survival of genetic variations at the IL10 gene locus that have been associated with chronic diseases. Here we show that an IL10 haplotype that associated with a pro-inflammatory innate immune response, characterised by low IL-10 (p = 0.028) and high TNF-alpha levels (p = 1.39 x 10(-3)), was enriched among Ghanaian elders (p = 2.46 x 10(-6)). Furthermore, in an environment where the source of drinking water (wells/rivers vs. boreholes) influences mortality risks (HR 1.28, 95% CI [1.09-1.50]), we observed that carriers of the pro-inflammatory haplotype have a survival advantage when drinking from wells/rivers but a disadvantage when drinking from boreholes (p(interaction) = 0.013). Resequencing the IL10 gene region did not uncover any additional common variants in the pro-inflammatory haplotype to those SNPs that were initially genotyped. CONCLUSIONS/SIGNIFICANCE:Altogether, these data lend strong arguments for the selection of pro-inflammatory host responses to overcome fatal infection and promote survival in adverse environments

Prospective Observational Study of Pazopanib in Patients with Advanced Renal Cell Carcinoma (PRINCIPAL Study)

Background: Real-world data are essential to accurately assessing efficacy and toxicity of approved agents in everyday practice. PRINCIPAL, a prospective, observational study, was designed to confirm the real-world safety and efficacy of pazopanib in patients with advanced renal cell carcinoma (RCC). Subjects, Materials, and Methods: Patients with clear cell advanced/metastatic RCC and a clinical decision to initiate pazopanib treatment within 30 days of enrollment were eligible. Primary objectives included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), relative dose intensity (RDI) and its effect on treatment outcomes, change in health-related quality of life (HRQoL), and safety. We also compared characteristics and outcomes of clinical-trial-eligible (CTE) patients, defined using COMPARZ trial eligibility criteria, with those of non-clinical-trial-eligible (NCTE) patients. Secondary study objectives were to evaluate clinical efficacy, safety, and RDI in patient subgroups. Results: Six hundred fifty-seven patients were enrolled and received ≥1 dose of pazopanib. Median PFS and OS were 10.3 months (95% confidence interval [CI], 9.2–12.0) and 29.9 months (95% CI, 24.7 to not reached), respectively, and the ORR was 30.3%. HRQoL showed no or little deterioration over time. Treatment-related serious adverse events (AEs) and AEs of special interest occurred in 64 (9.7%), and 399 (60.7%) patients, respectively. More patients were classified NCTE than CTE (85.2% vs. 14.8%). Efficacy of pazopanib was similar between the two groups. Conclusion: PRINCIPAL confirms the efficacy and safety of pazopanib in patients with advanced/metastatic RCC in a real-world clinical setting. Implications for Practice: PRINCIPAL is the largest (n = 657) prospective, observational study of pazopanib in patients with advanced/metastatic renal cell carcinoma, to the authors’ knowledge. Consistent with clinical trial results that often contain specific patient types, the PRINCIPAL study demonstrated that the effectiveness and safety of pazopanib is similarly safe and effective in patients with advanced kidney cancer in a real-world clinical setting. The PRINCIPAL study showed that patients with advanced kidney cancer who are treated with first-line pazopanib generally do not show disease progression for approximately 10 months and generally survive for nearly 30 months

Neglected Tropical Diseases in Sub-Saharan Africa: Review of Their Prevalence, Distribution, and Disease Burden

The neglected tropical diseases (NTDs) are the most common conditions affecting the poorest 500 million people living in sub-Saharan Africa (SSA), and together produce a burden of disease that may be equivalent to up to one-half of SSA's malaria disease burden and more than double that caused by tuberculosis. Approximately 85% of the NTD disease burden results from helminth infections. Hookworm infection occurs in almost half of SSA's poorest people, including 40–50 million school-aged children and 7 million pregnant women in whom it is a leading cause of anemia. Schistosomiasis is the second most prevalent NTD after hookworm (192 million cases), accounting for 93% of the world's number of cases and possibly associated with increased horizontal transmission of HIV/AIDS. Lymphatic filariasis (46–51 million cases) and onchocerciasis (37 million cases) are also widespread in SSA, each disease representing a significant cause of disability and reduction in the region's agricultural productivity. There is a dearth of information on Africa's non-helminth NTDs. The protozoan infections, human African trypanosomiasis and visceral leishmaniasis, affect almost 100,000 people, primarily in areas of conflict in SSA where they cause high mortality, and where trachoma is the most prevalent bacterial NTD (30 million cases). However, there are little or no data on some very important protozoan infections, e.g., amebiasis and toxoplasmosis; bacterial infections, e.g., typhoid fever and non-typhoidal salmonellosis, the tick-borne bacterial zoonoses, and non-tuberculosis mycobaterial infections; and arboviral infections. Thus, the overall burden of Africa's NTDs may be severely underestimated. A full assessment is an important step for disease control priorities, particularly in Nigeria and the Democratic Republic of Congo, where the greatest number of NTDs may occur

An Emerging Epidemic of Noncommunicable Diseases in Developing Populations Due to a Triple Evolutionary Mismatch

With their transition from adverse to affluent environments, developing populations experience a rapid increase in the number of individuals with noncommunicable diseases. Here, we emphasize that developing populations are more susceptible than western populations to acquire these chronic diseases, because their genetic, cultural, and epigenetic characteristics do not match with the eagerly awaited affluent environments. In regard to this, there is an urgent need for public health organizations to reorganize current environments in developing populations so as to fit their inherited characteristics. Unfortunately, this need is neglected as an essential part of the Sustainable Development Goals that form the core of the United Nations' Post-2015 Development Agenda. Only through global collaborative efforts can the environments in developing populations be reorganized and, thereby, the emerging epidemic of noncommunicable diseases be stalled