Does One Size Fit All? Drug Resistance and Standard Treatments: Results of Six Tuberculosis Programmes in Former Soviet Countries.

SETTING: After the collapse of the Soviet Union, countries in the region faced a dramatic increase in tuberculosis cases and the emergence of drug resistance. OBJECTIVE: To discuss the relevance of the DOTS strategy in settings with a high prevalence of drug resistance. DESIGN: Retrospective analysis of one-year treatment outcomes of short-course chemotherapy (SCC) and results of drug susceptibility testing (DST) surveys of six programmes located in the former Soviet Union: Kemerovo prison, Russia; Abkhasia, Georgia; Nagorno-Karabagh, Azerbaijan; Karakalpakstan, Uzbekistan; Dashoguz Velayat, Turkmenistan; and South Kazakhstan Oblast, Kazakhstan. Results are reported for new and previously treated smear-positive patients. RESULTS: Treatment outcomes of 3090 patients and DST results of 1383 patients were collected. Treatment success rates ranged between 87% and 61%, in Nagorno-Karabagh and Kemerovo, respectively, and failure rates between 7% and 23%. Any drug resistance ranged between 66% and 31% in the same programmes. MDR rates ranged between 28% in Karakalpakstan and Kemerovo prison and 4% in Nagorno-Karabagh. CONCLUSION: These results show the limits of SCC in settings with a high prevalence of drug resistance. They demonstrate that adapting treatment according to resistance patterns, access to reliable culture, DST and good quality second-line drugs are necessary

Characteristics of drug-resistant tuberculosis in Abkhazia (Georgia), a high-prevalence area in Eastern Europe

Although multidrug-resistant (MDR) tuberculosis (TB) is a major public health problem in Eastern Europe, the factors contributing to emergence, spread and containment of MDR-TB are not well defined. Here, we analysed the characteristics of drug-resistant TB in a cross-sectional study in Abkhazia (Georgia) between 2003 and 2005, where standard short-course chemotherapy is supplemented with individualized drug-resistance therapy. Drug susceptibility testing (DST) and molecular typing were carried out for Mycobacterium tuberculosis complex strains from consecutive smear-positive TB patients. Out of 366 patients, 60.4% were resistant to any first-line drugs and 21% had MDR-TB. Overall, 25% of all strains belong to the Beijing genotype, which was found to be strongly associated with the risk of MDR-TB (OR 25.9, 95% CI 10.2-66.0) and transmission (OR 2.8, 95% CI 1.6-5.0). One dominant MDR Beijing clone represents 23% of all MDR-TB cases. The level of MDR-TB did not decline during the study period, coinciding with increasing levels of MDR Beijing strains among previously treated cases. Standard chemotherapy plus individualized drug-resistance therapy, guided by conventional DST, might be not sufficient to control MDR-TB in Eastern Europe in light of the spread of "highly transmissible" MDR Beijing strains circulating in the community

It's the Motivation Stupid!

This paper attempts to explain the success of secondary currencies. Success is defined as the degree to which the initiators of these currencies manage to reach their original goals. In order to do so, we draw on two explanatory factors: the motivation of a currency’s founder and the degree of organization. We employed a combination of qualitative interviews, secondary literature review and standardized questionnaires with seven secondary currency projects in Croatia (CROM), Germany (KannWas, Engelgeld), Greece (Ovolos, TEM) and the United Kingdom (Bristol Pound, Brixton Pound). The main findings are that projects which pursue several different motivations are more successful than those with fewer goals. As for the degree of organization, projects which score high on all dimensions of organization are correlated with higher project success. Building on this we propose a typology of two groups: Type 1 cases have low diversity of motivation and organization (CROM and Engelgeld) and Type 2 cases have high diversity of motivation and organization (Bristol Pound, Brixton Pound, and TEM). The two remaining cases, the Ovolos and the KannWas cannot be clearly assigned to any of the types. The "motivation-organization typology" can guide future research on the motivation of founding and using secondary currencies

Industrial Hemp as a Resource for Birds in Agroecosystems: Human–Wildlife Conflict or Conservation Opportunity?

Industrial hemp (Cannabis sativa L.; hemp) is an emerging crop in the United States with little known about bird use or the potential for birds to become an agricultural pest. We identified birds associated with hemp fields, using repeated visits to oilseed plots in North Dakota, USA (n = 6) and cannabinoid (CBD) plots in Florida, USA (n = 4) from August to November 2020. We did not control for plot area or density; our observations were descriptive only. We observed 10 species in hemp, 12 species flying over hemp, and 11 species both foraging in and flying over hemp fields in North Dakota. In Florida, we observed 4 species in hemp, 5 species flying over hemp, and 4 species exhibiting both behaviors. When we observed birds in hemp, we found them perched in the canopy or foraging on the ground. Counts were highest in oilseed and lowest in CBD varieties. The Florida sites were mainly CBD varieties, which explains lower species diversity and raw counts of birds given the lack of seeds produced. Maximum raw counts of the most common birds (mourning doves [Zenaida macroura] = 116; house finches [Haemorhous mexicanus] = 53; and American goldfinches [Spinus tristis] = 40) using very small fields (116–324 m2) in North Dakota suggest oilseed hemp could suffer yield losses but potentially benefit farmland bird conservation and act as a decoy crop to protect other commodities (e.g., sunflower [Helianthus annuus L.])

SpitzerSpitzer Parallax of OGLE-2018-BLG-0596: A Low-mass-ratio Planet around an M-dwarf

We report the discovery of a $Spitzer$ microlensing planet OGLE-2018-BLG-0596Lb, with preferred planet-host mass ratio $q \sim 2\times10^{-4}$. The planetary signal, which is characterized by a short $(\sim 1~{\rm day})$ "bump" on the rising side of the lensing light curve, was densely covered by ground-based surveys. We find that the signal can be explained by a bright source that fully envelops the planetary caustic, i.e., a "Hollywood" geometry. Combined with the source proper motion measured from $Gaia$, the $Spitzer$ satellite parallax measurement makes it possible to precisely constrain the lens physical parameters. The preferred solution, in which the planet perturbs the minor image due to lensing by the host, yields a Uranus-mass planet with a mass of $M_{\rm p} = 13.9\pm1.6~M_{\oplus}$ orbiting a mid M-dwarf with a mass of $M_{\rm h} = 0.23\pm0.03~M_{\odot}$. There is also a second possible solution that is substantially disfavored but cannot be ruled out, for which the planet perturbs the major image. The latter solution yields $M_{\rm p} = 1.2\pm0.2~M_{\oplus}$ and $M_{\rm h} = 0.15\pm0.02~M_{\odot}$. By combining the microlensing and $Gaia$ data together with a Galactic model, we find in either case that the lens lies on the near side of the Galactic bulge at a distance $D_{\rm L} \sim 6\pm1~{\rm kpc}$. Future adaptive optics observations may decisively resolve the major image/minor image degeneracy.Comment: 34 pages, 8 figures, Submitted to AAS journa

Bapineuzumab for mild to moderate Alzheimer’s disease in two global, randomized, phase 3 trials

Background Our objective was to evaluate the efficacy (clinical and biomarker) and safety of intravenous bapineuzumab in patients with mild to moderate Alzheimer’s disease (AD). Methods Two of four phase 3, multicenter, randomized, double-blind, placebo-controlled, 18-month trials were conducted globally: one in apolipoprotein E ε4 carriers and another in noncarriers. Patients received bapineuzumab 0.5 mg/kg (both trials) or 1.0 mg/kg (noncarrier trial) or placebo every 13 weeks. Coprimary endpoints were change from baseline to week 78 on the 11-item Alzheimer’s Disease Assessment Scale–Cognitive subscale and the Disability Assessment for Dementia. Results A total of 683 and 329 patients completed the current carrier and noncarrier trials, respectively, which were terminated prematurely owing to lack of efficacy in the two other phase 3 trials of bapineuzumab in AD. The current trials showed no significant difference between bapineuzumab and placebo for the coprimary endpoints and no effect of bapineuzumab on amyloid load or cerebrospinal fluid phosphorylated tau. (Both measures were stable over time in the placebo group.) Amyloid-related imaging abnormalities with edema or effusion were confirmed as the most notable adverse event. Conclusions These phase 3 global trials confirmed lack of efficacy of bapineuzumab at tested doses on clinical endpoints in patients with mild to moderate AD. Some differences in the biomarker results were seen compared with the other phase 3 bapineuzumab trials. No unexpected adverse events were observed. Trial registration Noncarriers (3000) ClinicalTrials.gov identifier NCT00667810; registered 24 Apr 2008. Carriers (3001) ClinicalTrials.gov identifier NCT00676143; registered 2 May 2008

Hypoaminoacidemia underpins glucagon-mediated energy expenditure and weight loss

Glucagon analogs show promise as components of next-generation, multi-target, anti-obesity therapeutics. The biology of chronic glucagon treatment, in particular, its ability to induce energy expenditure and weight loss, remains poorly understood. Using a long-acting glucagon analog, G108, we demonstrate that glucagon-mediated body weight loss is intrinsically linked to the hypoaminoacidemia associated with its known amino acid catabolic action. Mechanistic studies reveal an energy-consuming response to low plasma amino acids in G108-treated mice, prevented by dietary amino acid supplementation and mimicked by a rationally designed low amino acid diet. Therefore, low plasma amino acids are a pre-requisite for G108-mediated energy expenditure and weight loss. However, preventing hypoaminoacidemia with additional dietary protein does not affect the ability of G108 to improve glycemia or hepatic steatosis in obese mice. These studies provide a mechanism for glucagon-mediated weight loss and confirm the hepatic glucagon receptor as an attractive molecular target for metabolic disease therapeutics

The European Marine Observation and Data Network (EMODnet): Visions and roles of the gateway to marine data in Europe

Marine data are needed for many purposes: for acquiring a better scientific understanding of the marine environment, but also, increasingly, as marine knowledge for decision making as well as developing products and services supporting economic growth. Data must be of sufficient quality to meet the specific users' needs. It must also be accessible in a timely manner. And yet, despite being critical, this timely access to known-quality data proves challenging. Europe's marine data have traditionally been collected by a myriad of entities with the result that much of our data are scattered throughout unconnected databases and repositories. Even when data are available, they are often not compatible, making the sharing of the information and data aggregation particularly challenging. In this paper, we present how the European Marine Observation and Data network (EMODnet) has developed over the last decade to tackle these issues. Today, EMODnet is comprised of more than 150 organizations which gather marine data, metadata, and data products and make them more easily accessible for a wider range of users. EMODnet currently consists of seven sub-portals: bathymetry, geology, physics, chemistry, biology, seabed habitats, and human activities. In addition, Sea-basin Checkpoints have been established to assess the observation capacity in the North Sea, Mediterranean, Atlantic, Baltic, Artic, and Black Sea. The Checkpoints identify whether the observation infrastructure in Europe meets the needs of users by undertaking a number of challenges. To complement this, a Data Ingestion Service has been set up to tackle the problem of the wealth of marine data that remain unavailable, by reaching out to data holders, explaining the benefits of sharing their data and offering a support service to assist them in releasing their data and making them available through EMODnet. The EMODnet Central Portal (www.emodnet.eu) provides a single point of access to these services, which are free to access and use. The strategic vision of EMODnet in the next decade is also presented, together with key focal areas toward a more user-oriented service, including EMODnet for business, internationalization for global users, and stakeholder engagement to connect the diverse communities across the marine knowledge value chain

Tissue-specific genetic variation suggests distinct molecular pathways between body shape phenotypes and colorectal cancer

It remains unknown whether adiposity subtypes are differentially associated with colorectal cancer (CRC). To move beyond single-trait anthropometric indicators, we derived four multi-trait body shape phenotypes reflecting adiposity subtypes from principal components analysis on body mass index, height, weight, waist-to-hip ratio, and waist and hip circumference. A generally obese (PC1) and a tall, centrally obese (PC3) body shape were both positively associated with CRC risk in observational analyses in 329,828 UK Biobank participants (3728 cases). In genome-wide association studies in 460,198 UK Biobank participants, we identified 3414 genetic variants across four body shapes and Mendelian randomization analyses confirmed positive associations of PC1 and PC3 with CRC risk (52,775 cases/45,940 controls from GECCO/CORECT/CCFR). Brain tissue-specific genetic instruments, mapped to PC1 through enrichment analysis, were responsible for the relationship between PC1 and CRC, while the relationship between PC3 and CRC was predominantly driven by adipose tissue-specific genetic instruments. This study suggests distinct putative causal pathways between adiposity subtypes and CRC