Estimation of efficiency of the use of financial resources on enterprises

Стаття присвячена дослідженню теоретичних та практичних питань аналітичного забезпечення управління використанням фінансових ресурсів підприємств. Запропоновані комплексні показники оцінки даного процесуThe article is devoted to research of theoretical and practical questions of the analytical providing of management the use of financial resources of enterprises. The complex indexes of estimation of this process are offere

Benefits of combination of insulin degludec and liraglutide are independent of baseline glycated haemoglobin level and duration of type 2 diabetes

AIM: To evaluate, using post hoc analyses, whether the novel combination of a basal insulin, insulin degludec, and a glucagon‐like peptide‐1 receptor agonist, liraglutide (IDegLira), was consistently effective in patients with type 2 diabetes (T2D), regardless of the stage of T2D progression. METHODS: Using data from the DUAL I extension [insulin‐naïve patients uncontrolled on oral antidiabetic drugs (OADs), n = 1660, 52 weeks] and DUAL II (patients uncontrolled on basal insulin plus OADs, n = 398, 26 weeks) randomized trials, the efficacy of IDegLira was investigated with regard to measures of disease progression stage including baseline glycated haemoglobin (HbA1c), disease duration and previous insulin dose. RESULTS: Across four categories of baseline HbA1c (≤7.5–9.0%), HbA1c reductions were significantly greater with IDegLira (1.1–2.5%) compared with IDeg or liraglutide alone in DUAL I. In DUAL II, HbA1c reductions were significantly greater with IDegLira (0.9–2.5%) than with IDeg in all but the lowest HbA1c category. In DUAL I, insulin dose and hypoglycaemia rate were lower across all baseline HbA1c categories for IDegLira versus IDeg, while hypoglycaemia was higher with IDegLira than liraglutide, irrespective of baseline HbA1c. In DUAL II, insulin dose and hypoglycaemia rate were similar with IDegLira and IDeg (maximum dose limited to 50 U) independent of baseline HbA1c. The reduction in HbA1c with IDegLira was independent of disease duration and previous insulin dose but varied depending on pre‐trial OAD treatment. CONCLUSIONS: IDegLira effectively lowered HbA1c across a range of measures, implying suitability for patients with either early or advanced T2D

Mouse vendor influence on the bacterial and viral gut composition exceeds the effect of diet

Often physiological studies using mice from one vendor show different outcome when being reproduced using mice from another vendor. These divergent phenotypes between similar mouse strains from different vendors have been assigned to differences in the gut microbiome. During recent years, evidence has mounted that the gut viral community plays a key role in shaping the gut microbiome and may thus also influence mouse phenotype. However, to date inter-vendor variation in the murine gut virome has not been studied. Using a metavirome approach, combined with 16S rRNA gene sequencing, we here compare the composition of the viral and bacterial gut community of C57BL/6N mice from three different vendors exposed to either a chow-based low-fat diet or high-fat diet. Interestingly, both the bacterial and the viral component of the gut community differed significantly between vendors. The different diets also strongly influenced both the viral and bacterial gut community, but surprisingly the effect of vendor exceeded the effect of diet. In conclusion, the vendor effect is substantial not only on the gut bacterial community but also strongly influences viral community composition. Given the effect of GM on mice phenotype, this is essential to consider for increasing reproducibility of mouse studies

Home care providers to the rescue:a novel first-responder programme

To describe the implementation of a novel first-responder programme in which home care providers equipped with automated external defibrillators (AEDs) were dispatched in parallel with existing emergency medical services in the event of a suspected out-of-hospital cardiac arrest (OHCA).We evaluated a one-year prospective study that trained home care providers in performing cardiopulmonary resuscitation (CPR) and using an AED in cases of suspected OHCA. Data were collected from cardiac arrest case files, case files from each provider dispatch and a survey among dispatched providers. The study was conducted in a rural district in Denmark.Home care providers were dispatched to 28 of the 60 OHCAs that occurred in the study period. In ten cases the providers arrived before the ambulance service and subsequently performed CPR. AED analysis was executed in three cases and shock was delivered in one case. For 26 of the 28 cases, the cardiac arrest occurred in a private home. Ninety-five per cent of the providers who had been dispatched to a cardiac arrest reported feeling prepared for managing the initial resuscitation, including use of AED.Home care providers are suited to act as first-responders in predominantly rural and residential districts. Future follow-up will allow further evaluation of home care provider arrivals and patient survival

Extensive sampling sheds light on species-level diversity in Palearctic Placobdella (Annelida: Clitellata: Glossiphoniiformes)

The bloodfeeding leech genus Placobdella is dominated by North American diversity, with only a single nominal species known from Central America and one from the Palearctic region. This is likely due to considerable underestimation of Palearctic biodiversity, but investigations into potential hidden diversity are lacking. To shed light on this, the present study introduces new data for specimens initially identified as Placobdella costata from Ukraine (close to the type locality), Italy, Germany, Latvia, Montenegro, Bulgaria, Slovenia, Turkey, Azerbaijan, Tunisia, and Algeria, and uses both nuclear (Internal Transcribed Spacer [ITS] region) and mitochondrial (cytochrome c oxidase subunit I [COI]) sequence data in phylogenetic and DNA barcoding frameworks, in order to better understand species-level diversity. Seven independent lineages are present in the trees, five of which show adequate separation at the COI locus to suggest their unique species-level status (COI distances between these clades range from 4.86 to 8.10%). However, the ITS data suggest that speciation is recent or incipient in these clades, and that not enough time has passed for clear separation at this locus. We discuss the evolutionary and taxonomic implications of our findings and speculate on dispersal events that may have contributed to shaping this pattern of geographic distribution

Potential for increased connectivity between differentiated wolverine populations

Information on genetic population structure provides important knowledge for species conservation. Yet, few studies combine extensive genetic data to evaluate the structure and population dynamics of transboundary populations. Here we used single nucleotide polymorphisms (SNPs), microsatellites and mitochondrial haplotypes to analyze the genetic population structure of wolverines (Gulo gulo) across Fennoscandia using a long-term monitoring dataset of 1708 individuals. Clear population subdivision was detected between the Scandinavian and the eastern Finnish population with a steep cline in the contact zone. While the Scandinavian population showed isolation by distance, large swaths of this population were characterized by high connectivity. Areas with high resistance to gene flow are likely explained by a combination of factors, such as historical isolation and founder effects. From a conservation perspective, promoting gene flow from the population in eastern Finland to the northwest of Scandinavia could augment the less variable Scandinavian population, and increase the demographic resilience of all subpopulations. Overall, the large areas of low resistance to gene flow suggest that transboundary cooperation with aligned actions of harvest and conflict mitigation could improve genetic connectivity across Finland, Sweden, and Norway

DEVOTE 3: Temporal relationships between severe hypoglycaemia, cardiovascular outcomes and mortality

Aims/hypothesis The double-blind Trial Comparing Cardiovascular Safety of Insulin Degludec vs Insulin Glargine in Patients with Type 2 Diabetes at High Risk of Cardiovascular Events (DEVOTE) assessed the cardiovascular safety of insulin degludec. The incidence and rates of adjudicated severe hypoglycaemia, and all-cause mortality were also determined. This paper reports a secondary analysis investigating associations of severe hypoglycaemia with cardiovascular outcomes and mortality. Methods In DEVOTE, patients with type 2 diabetes were randomised to receive either insulin degludec or insulin glargine U100 (100 units/ml) once daily (between dinner and bedtime) in an event-driven, double-blind, treat-to-target cardiovascular outcomes trial. The primary outcome was the first occurrence of an adjudicated major adverse cardiovascular event (MACE; cardiovascular death, non-fatal myocardial infarction or non-fatal stroke). Adjudicated severe hypoglycaemia was the pre-specified secondary outcome. In the present analysis, the associations of severe hypoglycaemia with both MACE and all-cause mortality was evaluated in the pooled trial population using time-to-event analyses, with severe hypoglycaemia as a time-dependent variable and randomised treatment as a fixed factor. An investigation with interaction terms indicated that the effect of severe hypoglycaemia on the risk of MACE and all-cause mortality were the same for both treatment arms, and so the temporal association for severe hypoglycaemia with subsequent MACE and all-cause mortality is reported for the pooled population. Results There was a non-significant difference in the risk of MACE for individuals who had vs those who had not experienced severe hypoglycaemia during the trial (HR 1.38, 95% CI 0.96, 1.96; p = 0.080) and therefore there was no temporal relationship between severe hypoglycaemia and MACE. There was a significantly higher risk of all-cause mortality for patients who had vs those who had not experienced severe hypoglycaemia during the trial (HR 2.51, 95% CI 1.79, 3.50; p < 0.001). There was a higher risk of all-cause mortality 15, 30, 60, 90, 180 and 365 days after experiencing severe hypoglycaemia compared with not experiencing severe hypoglycaemia in the same time interval. The association between severe hypoglycaemia and all-cause mortality was maintained after adjustment for the following baseline characteristics: age, sex, HbA1c, BMI, diabetes duration, insulin regimen, hepatic impairment, renal status and cardiovascular risk group. Conclusions/interpretation The results from these analyses demonstrate an association between severe hypoglycaemia and all-cause mortality. Furthermore, they indicate that patients who experienced severe hypoglycaemia were particularly at greater risk of death in the short term after the hypoglycaemic episode. These findings indicate that severe hypoglycaemia is associated with higher subsequent mortality; however, they cannot answer the question as to whether severe hypoglycaemia serves as a risk marker for adverse outcomes or whether there is a direct causal effect

The type 1 diabetes gene TYK2 regulates beta-cell development and its responses to interferon-alpha

The TYK2 gene is associated with development of type 1 diabetes. Here the authors show that TYK2 regulates beta-cell development, but at the same time TYK2 inhibition in the islets prevents IFN alpha responses and enhances their survival against CD8(+) T-cell cytotoxicity; representing a potent therapeutic target to halt T1D progression. Type 1 diabetes (T1D) is an autoimmune disease that results in the destruction of insulin producing pancreatic beta-cells. One of the genes associated with T1D is TYK2, which encodes a Janus kinase with critical roles in type-Iota interferon (IFN-Iota) mediated intracellular signalling. To study the role of TYK2 in beta-cell development and response to IFN alpha, we generated TYK2 knockout human iPSCs and directed them into the pancreatic endocrine lineage. Here we show that loss of TYK2 compromises the emergence of endocrine precursors by regulating KRAS expression, while mature stem cell-islets (SC-islets) function is not affected. In the SC-islets, the loss or inhibition of TYK2 prevents IFN alpha-induced antigen processing and presentation, including MHC Class Iota and Class Iota Iota expression, enhancing their survival against CD8(+) T-cell cytotoxicity. These results identify an unsuspected role for TYK2 in beta-cell development and support TYK2 inhibition in adult beta-cells as a potent therapeutic target to halt T1D progression.Peer reviewe

Exposure to persistent organic pollutants and sperm sex chromosome ratio in men from the Faroe Islands

People in the Arctic as well as fishermen on the polluted Swedish east coast are highly exposed to persistent organic pollutants (POPs). These compounds have been shown to affect the sperm Y:X chromosome ratio. In present study, the aim was to investigate whether polychlorinated biphenyl (PCB) congeners and 1,1,-dichloro-2,2,-bis(p-chlorophenyl)ethane (p,p′-DDE) influence sperm sex chromosome ratio in Faroese men, and whether these men differ regarding Y:X ratio compared to Greenland Inuit and Swedish fishermen. The study population (n = 449) consisted of young men from the general population (n = 276) as well as proven fertile men (n = 173). The Y:X ratio was assessed by fluorescent in situ hybridization. Serum concentrations of POPs were measured using gas chromatography. Associations between POP concentrations and Y:X ratio were calculated using linear and non-linear regression models as well as trend analysis and pairwise comparison of exposure data categorized into quartiles. The selected POPs were associated with Y:X ratio in fertile Faroese men, but not in the total population; p,p′-DDE (95% CI for B = − 0.005 to − 0.001, p = 0.005) and ΣPCB (95% CI for B = − 0.005 to − 0.001, p = 0.012). Since p,p′-DDE and ΣPCB correlated significantly (r = 0.927, p < 0.001), the results involving the exposure variables can be regarded as a single finding. The Y:X ratio for the total Faroese population was 0.500 ± 0.018, which was statistically significantly lower than in both Inuit and Swedish fishermen (0.512 for both). In conclusion, Faroese men presented with lower Y:X ratio than Greenland Inuit and Swedish fishermen. Although no direct health effects are expected due to the lower Faroese Y:X ratio, it could be indicative of adverse effects on the reproductive system