Genetic structure and drug resistance of <i>Mycobacterium tuberculosis</i> strains in the Kemerovo Region — Kuzbass

Background. Kemerovo Region has a high burden of tuberculosis (TB) with incidence rates twice the national average. The circulating variants of Mycobacterium tuberculosis significantly influence the TB epidemic process. Screening of epidemically significant variants of the pathogen in areas with a high burden of TB underlies epidemiological diagnosis and is necessary for the development of effective prevention measures. However, the population structure of M. tuberculosis in the Kemerovo Region — Kuzbass is poorly understood. Aims: to study genetic heterogeneity and phenotypic resistance to anti-tuberculosis drugs of M. tuberculosis strains in the Kemerovo Region. Materials and methods. The MIRU-VNTR genotyping of 163 M. tuberculosis strains isolated from TB patients in the Kemerovo Region in March–October 2022 was carried out. Cultivation of M. tuberculosis, drug susceptibility testing, and isolation of genomic DNA were carried out by standard methods. Genotypic identification was performed using MIRU-VNTR (24 loci) typing. In parallel, express genotyping was carried out: identification of isolates of the Beijing genotype (by RD105/207) and non-Beijing; subtyping Beijing using real-time PCR tests for detection of Central Asian Russian and B0/W148; identification of the non-Beijing group by real-tine PCR RT tests for LAM, S, Ural. Results. The isolates of the Beijing genotype (67.5%) were found to dominate both among newly diagnosed (64.4%) and previously treated patients (88.5%). MIRU-VNTR typing revealed 75 profiles, of which 94-32 (35.3%) and 100-32 (15.7%) were the most abundant and belonged to the Beijing genotype. Overall, 39.9% and 20.9% of isolates, respectively, were assigned to the Beijing Central Asian Russian and B0/W148 epidemic clusters, which differed significantly in MDR levels (50.8% and 85.3%, respectively; p = 0.005). The second most common were strains of the genetic family of the Euro-American lineage (L4) (31.9%): LAM (6.7%) Ural (7.4%) Haarlem (4.9%) and L4-unclassified (12.9%), MDR among of these minor genotypes was significantly lower than among Beijing genotype strains, and amounted to 11.5% (p 0.001). Strains from HIV-TB patients (56.4% of the total sample) carried an MDR profile more often (54.8%) compared to TB cases without HIV infection (35.2%) (p = 0.005), which may be due to higher proportion of Beijing genotype strains in the HIV-TB group (75.0% vs. 57.7%; p = 0.026). Complete comparability of the SNP analysis (in-house tests) to identify the main genotypes and epidemically significant Beijing subtypes was shown, which made it possible to characterize 75.5% of the sample by the express method. Conclusions. The molecular genetic screening carried out in the Kemerovo Region revealed the heterogeneity of the M. tuberculosis population, which was dominated by strains of the Beijing genotype, with the frequency of subtypes comparable with other territories of the Siberian Federal District

Wolf Creek Cold Regions Model Set-up, Parameterisation and Modelling Summary

Non-Peer ReviewedWolf Creek Research Basin is in the Upper Yukon River Basin near Whitehorse, Yukon and is representative of headwaters in the northern Coast Mountains. It was established in 1993 to better develop northern hydrological models, and related hydrological process, ecosystem and climate science. Yukon Environment maintains Wolf Creek hydrometeorological and hydrometric stations and conducts regular snow surveys in the basin. A number of hydrological models have been tested on Wolf Creek and all have had great difficulty in simulating the cold regions hydrological processes that dominate its streamflow response to snowmelt and rainfall events. Developments in understanding hydrological processes and their interaction with terrestrial ecosystems and climate at Wolf Creek have lead to the development of the Cold Regions Hydrological Model (CRHM) by a consortium of scientists led by the University of Saskatchewan and Environment Canada. CRHM comprehensively incorporates the blowing snow, intercepted snow, sublimation, melt energetics, infiltration to frozen soils, organic terrain runoff and other cold regions hydrological phenomenon and discretizes the catchment on a hydrological response unit basis for applying water and energy balance calculations. The model is intended for prediction of ungauged basins with parameter selection from physically measurable properties of the river basin or regional transference of calibrated values. In Russia, a long tradition of cold regions hydrological research has led to the development of the Hydrograph model by the State Hydrological Institute, St. Petersburg. The Hydrograph model contains several promising innovations regarding the formation and routing of runoff, discretizes the basin using hydrological response units and addresses some (but not all) cold regions hydrological processes. Hydrograph parameter selection is made from both physically measured properties and those that are calibrated, but the calibrations can be easily regionalized. Test simulations of runoff processes using CRHM and Hydrograph for Wolf Creek Research Basin was undertaken using data archives that had been assembled and cleaned up in a related project by the University of Saskatchewan. The test simulations are a demonstration of model capabilities and a way to gain familiarity with the basin, its characteristics and data and to better compare model features. Data available included a GIS database of basin characteristics (topography and vegetation distribution) and the hydrometeorological and hydrometric observational dataset from Yukon Environment. The sub-surface hydrology presented a formidable unknown in parameterising the model. Hydrograph performed well in initial simulations of the basin hydrograph for multi-year runs. Several issues with observational data quality created substantial uncertainty in evaluating the model runs

Structured headache services as the solution to the ill-health burden of headache: 1. Rationale and description

In countries where headache services exist at all, their focus is usually on specialist (tertiary) care. This is clinically and economically inappropriate: most headache disorders can effectively and more efficiently (and at lower cost) be treated in educationally supported primary care. At the same time, compartmentalizing divisions between primary, secondary and tertiary care in many health-care systems create multiple inefficiencies, confronting patients attempting to navigate these levels (the “patient journey”) with perplexing obstacles. High demand for headache care, estimated here in a needs-assessment exercise, is the biggest of the challenges to reform. It is also the principal reason why reform is necessary. The structured headache services model presented here by experts from all world regions on behalf of the Global Campaign against Headache is the suggested health-care solution to headache. It develops and refines previous proposals, responding to the challenge of high demand by basing headache services in primary care, with two supporting arguments. First, only primary care can deliver headache services equitably to the large numbers of people needing it. Second, with educational supports, they can do so effectively to most of these people. The model calls for vertical integration between care levels (primary, secondary and tertiary), and protection of the more advanced levels for the minority of patients who need them. At the same time, it is amenable to horizontal integration with other care services. It is adaptable according to the broader national or regional health services in which headache services should be embedded. It is, according to evidence and argument presented, an efficient and cost-effective model, but these are claims to be tested in formal economic analyses

Atrial fibrillation genetic risk differentiates cardioembolic stroke from other stroke subtypes

AbstractObjectiveWe sought to assess whether genetic risk factors for atrial fibrillation can explain cardioembolic stroke risk.MethodsWe evaluated genetic correlations between a prior genetic study of AF and AF in the presence of cardioembolic stroke using genome-wide genotypes from the Stroke Genetics Network (N = 3,190 AF cases, 3,000 cardioembolic stroke cases, and 28,026 referents). We tested whether a previously-validated AF polygenic risk score (PRS) associated with cardioembolic and other stroke subtypes after accounting for AF clinical risk factors.ResultsWe observed strong correlation between previously reported genetic risk for AF, AF in the presence of stroke, and cardioembolic stroke (Pearson’s r=0.77 and 0.76, respectively, across SNPs with p &lt; 4.4 × 10−4 in the prior AF meta-analysis). An AF PRS, adjusted for clinical AF risk factors, was associated with cardioembolic stroke (odds ratio (OR) per standard deviation (sd) = 1.40, p = 1.45×10−48), explaining ∼20% of the heritable component of cardioembolic stroke risk. The AF PRS was also associated with stroke of undetermined cause (OR per sd = 1.07, p = 0.004), but no other primary stroke subtypes (all p &gt; 0.1).ConclusionsGenetic risk for AF is associated with cardioembolic stroke, independent of clinical risk factors. Studies are warranted to determine whether AF genetic risk can serve as a biomarker for strokes caused by AF.</jats:sec