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

Characterization of an IncFII Plasmid Encoding NDM-1 from Escherichia coli ST131

Background: The current spread of the gene encoding the metallo-ß-lactamase NDM-1 in Enterobacteriaceae is linked to a variety of surrounding genetic structures and plasmid scaffolds. Methodology: The whole sequence of plasmid pGUE-NDM carrying the bla NDM-1 gene was determined by high-density pyrosequencing and a genomic comparative analysis with other blaNDM-1-negative IncFII was performed. Principal Findings: Plasmid pGUE-NDM replicating in Escherichia coli confers resistance to many antibiotic molecules including b-lactams, aminoglycosides, trimethoprim, and sulfonamides. It is 87,022 bp in-size and carries the two b-lactamase genes bla NDM-1 and bla OXA-1, together with three aminoglycoside resistance genes aacA4, aadA2, and aacC2. Comparative analysis of the multidrug resistance locus contained a module encompassing the blaNDM-1 gene that is actually conserved among different structures identified in other enterobacterial isolates. This module was constituted by the blaNDM-1 gene, a fragment of insertion sequence ISAba125 and a bleomycin resistance encoding gene. Significance: This is the first characterized bla NDM-1-carrying IncFII-type plasmid. Such association between the bla NDM-1 gene and an IncFII-type plasmid backbone is extremely worrisome considering that this plasmid type is known to sprea

Costs and difficulties of recruiting patients to provide e-health support: pilot study in one primary care trust

<p>Abstract</p> <p>Background</p> <p>Better use of e-health services by patients could improve outcomes and reduce costs but there are concerns about inequalities of access. Previous research in outpatients suggested that anonymous personal email support may help patients with long term conditions to use e-health, but recruiting earlier in their 'journey' may benefit patients more. This pilot study explored the feasibility and cost of recruiting patients for an e-health intervention in one primary care trust.</p> <p>Methods</p> <p>The sample comprised 46 practices with total patient population of 250,000. We approached all practices using various methods, seeking collaboration to recruit patients via methods agreed with each practice. A detailed research diary was kept of time spent recruiting practices and patients. Researcher time was used to estimate costs. Patients who consented to participate were offered email support for their use of the Internet for health.</p> <p>Results</p> <p>Eighteen practices agreed to take part; we recruited 27 patients, most (23/27) from five practices. Practices agreed to recruit patients for an e-health intervention via waiting room leaflets (16), posters (16), practice nurses (15), doctors giving patients leaflets (5), a study website link (7), inclusion in planned mailshots (2), and a special mailshot to patients selected from practice computers (1). After low recruitment response we also recruited directly in five practices through research assistants giving leaflets to patients in waiting rooms. Ten practices recruited no patients. Those practices that were more difficult to recruit were less likely to recruit patients. Leaving leaflets for practice staff to distribute and placing posters in the practice were not effective in recruiting patients. Leaflets handed out by practice nurses and website links were more successful. The practice with lowest costs per patient recruited (£70) used a special mailshot to selected patients.</p> <p>Conclusion</p> <p>Recruitment via general practice was not successful and was therefore expensive. Direct to consumer methods and recruitment of patients in outpatients to offer email support may be more cost effective. If recruitment in general practice is required, contacting practices by letter and email, not following up non-responding practices, and recruiting patients with selected conditions by special mailshot may be the most cost-effective approach.</p

NLRP12 Suppresses Colon Inflammation and Tumorigenesis through the Negative Regulation of Noncanonical NF-κB Signaling

In vitro data suggest that a subgroup of NLR proteins, including NLRP12, inhibits the transcription factor NF-κB, although physiologic and disease-relevant evidence is largely missing. Dysregulated NF-κB activity is associated with colonic inflammation and cancer, and we found Nlrp12(-/-) mice were highly susceptible to colitis and colitis-associated colon cancer. Polyps isolated from Nlrp12(-/-) mice showed elevated noncanonical NF-κB activation and increased expression of target genes that were associated with cancer, including Cxcl13 and Cxcl12. NLRP12 negatively regulated ERK and AKT signaling pathways in affected tumor tissues. Both hematopoietic- and nonhematopoietic-derived NLRP12 contributed to inflammation, but the latter dominantly contributed to tumorigenesis. The noncanonical NF-κB pathway was regulated upon degradation of TRAF3 and activation of NIK. NLRP12 interacted with both NIK and TRAF3, and Nlrp12(-/-) cells have constitutively elevated NIK, p100 processing to p52 and reduced TRAF3. Thus, NLRP12 is a checkpoint of noncanonical NF-κB, inflammation, and tumorigenesis

The NLRP3 inflammasome functions as a negative regulator of tumorigenesis during colitis-associated cancer

Colitis-associated cancer (CAC) is a major complication of inflammatory bowel diseases. We show that components of the inflammasome are protective during acute and recurring colitis and CAC in the dextran sulfate sodium (DSS) and azoxymethane + DSS models. Mice lacking the inflammasome adaptor protein PYCARD (ASC) and caspase-1 demonstrate increased disease outcome, morbidity, histopathology, and polyp formation. The increased tumor burden is correlated with attenuated levels of IL-1β and IL-18 at the tumor site. To decipher the nucleotide-binding domain, leucine-rich-repeat-containing (NLR) component that is involved in colitis and CAC, we assessed Nlrp3 and Nlrc4 deficient mice. Nlrp3−/− mice showed an increase in acute and recurring colitis and CAC, although the disease outcome was less severe in Nlrp3−/− mice than in Pycard−/− or Casp1−/− animals. No significant differences were observed in disease progression or outcome in Nlrc4−/− mice compared with similarly treated wild-type animals. Bone marrow reconstitution experiments show that Nlrp3 gene expression and function in hematopoietic cells, rather than intestinal epithelial cells or stromal cells, is responsible for protection against increased tumorigenesis. These data suggest that the inflammasome functions as an attenuator of colitis and CAC

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease