Projecting seismicity induced by complex alterations of underground stresses with applications to geothermal systems.

Seismicity associated with subsurface operations is a major societal concern. It is therefore critical to improve predictions of the induced seismic hazard. Current statistical approaches account for the physics of pore pressure increase only. Here, we present a novel mathematical model that generalises adopted statistics for use in arbitrary injection/production protocols and applies to arbitrary physical processes. In our model, seismicity is driven by a normalised integral over the spatial reservoir volume of induced variations in frictional Coulomb stress, which-combined with the seismogenic index-provides a dimensionless proxy of the induced seismic hazard. Our model incorporates the classical pressure diffusion based and poroelastic seismogenic index models as special cases. Applying our approach to modeling geothermal systems, we find that seismicity rates are sensitive to imposed fluid-pressure rates, temperature variations, and tectonic conditions. We further demonstrate that a controlled injection protocol can decrease the induced seismic risk and that thermo-poroelastic stress transfer results in a larger spatial seismic footprint and in higher-magnitude events than does direct pore pressure impact for the same amount of injected volume and hydraulic energy. Our results, validated against field observations, showcase the relevance of the novel approach to forecast seismic hazards induced by subsurface activities.

[The emotional burnout effect on labor efficiency of stomatologists].

The article presents the results of the study of factors effecting on professional deformation of stomatologists and its relationship with their personal characteristics, labor experience and medical specialization. the information is compiled with purpose of elaborating comprehensive recommendations on diagnostics of phases of development of syndrome of emotional burnout in this category of medical specialists at the initial stages of its occurrence and proposing measures of its adjustment including social and personal prevention.

[Influence of monotony of work on psychophysiological health of drivers of electric rolling stock of railway transport].

The article presents the results of the author's research that determines the degree of influence of monotonous (monotonous) labor processes on the drivers (and their assistants) of traction rolling stock of railway transport. Information is collected in order to develop a set of measures to overcome the monotony of work, improve the quality of working life and psychophysiological health of employees, and as a result, ensure traffic safety, improving the safety system for drivers and improving the quality of passenger transport.

Access-Site Complications in Mechanical Thrombectomy for Acute Ischemic Stroke: A Review of Prospective Trials.

BACKGROUND: A shift has occurred in interventional cardiology from transfemoral to transradial access due to a 70%-80% decrease in complications. This shift has not yet taken place in other interventional specialties, perhaps owing to the lack of generalizability of findings in the cardiology data. PURPOSE: Our aim was to assess data from the recent mechanical thrombectomy prospective trials to better understand the access-site complication rate. DATA SOURCES: Articles were systematically sourced from the National Center for Biotechnology Information PubMed archive. STUDY SELECTION: According to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, prospective, randomized controlled trials published after 2008 with mention of major and/or minor femoral access-site complications in neuroendovascular mechanical thrombectomies were included. DATA ANALYSIS: Major and minor femoral access-site complications were extracted. A total complication rate was calculated with major access-site complications alone and combined with minor access-site complications. DATA SYNTHESIS: Seven prospective studies of 339 total screened met the inclusion criteria. Eleven major access-site complications were identified in of 660 total interventions, revealing a major access-site complication rate of 1.67% for patients undergoing mechanical thrombectomy with transfemoral access. If minor access-site complications were included, 35 total incidents were detected in 763 interventions, resulting in a total complication rate of 4.59%. LIMITATIONS: Multiple unspecified vessel and procedure-related complications were mentioned in the studies. CONCLUSIONS: The overall rate of major access-site complications was 1.67% in this review, which is not low and poses a risk to patients. We suggest further investigation into the feasibility and complication rates of alternative access sites for neurointerventional procedures.

Reversal of direct oral anticoagulants.

An understanding of how to counteract the anticoagulant effect of direct oral anticoagulants is essential in the event of haemorrhage, emergency surgery and overdose. This review summarizes strategies for the reversal of direct oral anticoagulants, including the use of novel agents.

Detection of Copy Number Imbalance in Canine Urothelial Carcinoma With Droplet Digital Polymerase Chain Reaction.

Urothelial carcinoma (UC) is the most common neoplasm of the canine urinary tract. Clinical presentation of UC is shared with several other, more common urinary tract disorders, and this often delays diagnosis of the UC. Definitive diagnosis of UC requires histopathologic examination of a biopsy specimen, but the cost and invasiveness for these diagnostic tests often result in most diagnoses being made on the basis of clinical findings, diagnostic imaging, and cytologic examination of urine sediment. Regardless of the diagnostic process used, most UCs currently are not diagnosed until they are at an advanced clinical stage and so are associated with poor prognosis. Improved methods for earlier and less invasive detection are needed. In a previous study, the authors demonstrated the presence of highly recurrent DNA copy number aberrations (CNAs) in canine UC and hypothesized that detection of these CNAs in tumor cells can be used as a molecular diagnostic for UC. In this study, a multiplexed droplet digital polymerase chain reaction (ddPCR) assay was detected to detect and quantify CNAs of specific regions of canine chromosomes 8, 13, 19, and 36. The assay was effective at differentiating 31 neoplastic and 25 nonneoplastic bladder tissues based on copy number, with 100% sensitivity and specificity in tissue samples. CNAs were also detected by ddPCR in 67% (12 of 18) of urine DNA specimens derived from UC patients. The findings show that ddPCR is a useful molecular technique to detect CNAs and may be used as a noninvasive molecular diagnostic test for canine UC.

Co-expression of fibulin-5 and VEGF165 increases long-term patency of synthetic vascular grafts seeded with autologous endothelial cells.

Small caliber synthetic vascular grafts are commonly used for bypass surgery and dialysis access sites but have high failure rates because of neointima formation and thrombosis. Seeding synthetic grafts with endothelial cells (ECs) provides a biocompatible surface that may prevent graft failure. However, EC detachment following exposure to blood flow still remains a major obstacle in the development of biosynthetic grafts. We tested the hypothesis that induced expression by the seeded EC, of vascular endothelial growth factor165 (VEGF165) and of fibulin-5, an extracellular matrix glycoprotein that has a crucial role in elastin fiber organization and increase EC adherence to surfaces, may improve long-term graft patency. Autologous ECs were isolated from venous segments, and were transduced with retroviral vectors expressing fibulin-5 and VEGF165. The modified cells were seeded on expanded polytetrafluoroethylene (ePTFE) grafts and implanted in a large animal model. Three months after transplantation, all grafts seeded with modified EC were patent on a selective angiography, whereas only a third of the control grafts were patent. Similar results were shown at 6 months. Thus, seeding ePTFE vascular grafts with genetically modified EC improved long-term small caliber graft patency. The biosynthetic grafts may provide a novel therapeutic modality for patients with peripheral vascular disease and patients requiring vascular access for hemodialysis.

A cultured approach to canine urothelial carcinoma: molecular characterization of five cell lines.

BACKGROUND: Urothelial carcinoma (UC), also known as transitional cell carcinoma (TCC), of the bladder is the most common neoplasm affecting the canine urogenital system. To facilitate study of the disease in vitro, cell line models have been established from primary tumor biopsies. Their resemblance to the primary disease, however, has not been well defined. In the present study, we evaluated five canine UC cell lines via oligonucleotide array comparative genomic hybridization (oaCGH), fluorescence in situ hybridization (FISH), and gene expression analysis. RESULTS: Comparison of genome wide DNA copy number profiles of the cell lines with primary biopsy specimens revealed redundancies in genomic aberrations, indicating that the cell lines retain the gross genomic architecture of primary tumors. As in the primary tumors, gain of canine chromosomes 13 and 36 and loss of chromosome 19 were among the most frequent aberrations evident in the cell lines. FISH analysis revealed chromosome structural aberrations, including tandem duplications, bi-armed chromosomes, and chromosome fusions, suggesting genome instability during neoplastic transformation. Gene expression profiling highlighted numerous differentially expressed genes, including many previously shown as dysregulated in primary canine UC and human bladder cancer. Pathway enrichment analysis emphasized pathways suspected to be at the crux of UC pathogenesis, including xenobiotic and lipid compound metabolism. CONCLUSIONS: These data support valid use of the canine UC cell lines evaluated by confirming they provide an accurate and practical means to interrogate the UC at a molecular level. Moreover, the cell lines may provide a valuable model for furthering our understanding of aberrant metabolic pathways in UC development.

Veno-venous anastomoses in twin-twin transfusion syndrome: A multicenter study.

INTRODUCTION: The aim of this study is to evaluate the prevalence of veno-venous (VV) anastomoses in a large cohort of monochorionic (MC) twin placentas with twin-twin transfusion syndrome (TTTS) compared to a control group of MC placentas without TTTS. METHODS: All TTTS placentas not treated with fetoscopic laser surgery (TTTS group) and examined at five international fetal therapy centers were included in this study and compared with a control group of MC placentas without TTTS (non-TTTS group). MC placentas were routinely injected with colored dye. We recorded the presence of VV and arterio-arterial (AA) anastomoses. RESULTS: A total of 414 MC placentas were included in this study (TTTS group, n = 106; non-TTTS group, n = 308). The prevalence of VV anastomoses was significantly higher in the TTTS group than in the non-TTTS group, 36% (38/106) and 25% (78/308), respectively (p = .04; odds ratio (OR) 1.65; 95% confidence interval (CI): 1.03-2.64). In the subgroup of MC placentas without AA anastomoses, the prevalence of VV anastomoses in the TTTS group and non-TTTS group was 32% (18/57) and 8% (2/25), respectively (p = .03; OR: 5.31; 95% CI: 1.13-24.98). DISCUSSION: VV anastomoses are detected more frequently in TTTS placentas than in MC placentas without TTTS and may thus play a role in the development of TTTS.

Long-term menopausal hormone therapy and health consequences ­ how to choose sides?

There is no debate any more on the good safety profile of postmenopausal hormone therapy (HT) in healthy perimenopausal and early postmenopausal women, but there are still many open issues related to the consequences of long-term HT, especially in older women. A recent Cochrane meta-analysis showed that women who started HT less than 10 years after the menopause had lower mortality and coronary heart disease (CHD), but more venous thromboembolism (DVT). However, in those who started treatment more than 10 years after the menopause, there was high-quality evidence that it had little effect on death or CHD between HT and placebo groups but there was an increased risk of stroke and DVT. In contrast, many large, observational studies such as a recent one from Finland (3.3 million years of HT exposure) have shown that the risk of CHD or stroke death and all-cause mortality was significantly reduced, both in those who initiated HT below or above age 60 years. Because of conflicting data concerning long-term HT use, it seems that every health-care provider chooses as reference those studies that can support his/her individual views and therapeutic approach.

Canine urothelial carcinoma: genomically aberrant and comparatively relevant.

Urothelial carcinoma (UC), also referred to as transitional cell carcinoma (TCC), is the most common bladder malignancy in both human and canine populations. In human UC, numerous studies have demonstrated the prevalence of chromosomal imbalances. Although the histopathology of the disease is similar in both species, studies evaluating the genomic profile of canine UC are lacking, limiting the discovery of key comparative molecular markers associated with driving UC pathogenesis. In the present study, we evaluated 31 primary canine UC biopsies by oligonucleotide array comparative genomic hybridization (oaCGH). Results highlighted the presence of three highly recurrent numerical aberrations: gain of dog chromosome (CFA) 13 and 36 and loss of CFA 19. Regional gains of CFA 13 and 36 were present in 97 % and 84 % of cases, respectively, and losses on CFA 19 were present in 77 % of cases. Fluorescence in situ hybridization (FISH), using targeted bacterial artificial chromosome (BAC) clones and custom Agilent SureFISH probes, was performed to detect and quantify these regions in paraffin-embedded biopsy sections and urine-derived urothelial cells. The data indicate that these three aberrations are potentially diagnostic of UC. Comparison of our canine oaCGH data with that of 285 human cases identified a series of shared copy number aberrations. Using an informatics approach to interrogate the frequency of copy number aberrations across both species, we identified those that had the highest joint probability of association with UC. The most significant joint region contained the gene PABPC1, which should be considered further for its role in UC progression. In addition, cross-species filtering of genome-wide copy number data highlighted several genes as high-profile candidates for further analysis, including CDKN2A, S100A8/9, and LRP1B. We propose that these common aberrations are indicative of an evolutionarily conserved mechanism of pathogenesis and harbor genes key to urothelial neoplasia, warranting investigation for diagnostic, prognostic, and therapeutic applications.

Thrombospondin-1 restrains neutrophil granule serine protease function and regulates the innate immune response during Klebsiella pneumoniae infection.

Neutrophil elastase (NE) and cathepsin G (CG) contribute to intracellular microbial killing but, if left unchecked and released extracellularly, promote tissue damage. Conversely, mechanisms that constrain neutrophil serine protease activity protect against tissue damage but may have the untoward effect of disabling the microbial killing arsenal. The host elaborates thrombospondin-1 (TSP-1), a matricellular protein released during inflammation, but its role during neutrophil activation following microbial pathogen challenge remains uncertain. Mice deficient in TSP-1 (thbs1(-/-)) showed enhanced lung bacterial clearance, reduced splenic dissemination, and increased survival compared with wild-type (WT) controls during intrapulmonary Klebsiella pneumoniae infection. More effective pathogen containment was associated with reduced burden of inflammation in thbs1(-/-) mouse lungs compared with WT controls. Lung NE activity was increased in thbs1(-/-) mice following K. pneumoniae challenge, and thbs1(-/-) neutrophils showed enhanced intracellular microbial killing that was abrogated with recombinant TSP-1 administration or WT serum. Thbs1(-/-) neutrophils exhibited enhanced NE and CG enzymatic activity, and a peptide corresponding to amino-acid residues 793-801 within the type-III repeat domain of TSP-1 bridled neutrophil proteolytic function and microbial killing in vitro. Thus, TSP-1 restrains proteolytic action during neutrophilic inflammation elicited by K. pneumoniae, providing a mechanism that may regulate the microbial killing arsenal.

Placental weight, birth weight and fetal:placental weight ratio in dichorionic and monochorionic twin gestations in function of gestational age, cord insertion type and placental partition.

INTRODUCTION: We established reference values for placental weight, birth weight, and fetal:placental weight ratio (FPR) (a possible index of placental functional efficiency) in monochorionic and dichorionic twin gestations. METHODS: Placental weight, birth weight, and FPR in function of gestational age, cord insertion type and placental sharing were determined in 151 dye-injected diamniotic-monochorionic and 198 double-disc diamniotic-dichorionic twin placentas (25-39 weeks' gestation). RESULTS: As expected, FPR values increased with gestational age in both groups. Birth weights and placental weights of monochorionic twins >28 weeks' gestation were significantly lower than those of age-matched dichorionic twins. When stratified per placental weight, the birth weights and FPR values of monochorionic twins were overall lower than those of dichorionic twins within the same placental weight category. However, in the subset of monochorionic twins with small share in unevenly partitioned placentas, birth weights and FPR values per placental weight were similar to those of dichorionic twins, and significantly higher than those of monochorionic twins with larger share or even placental sharing. Cord insertion type did not correlate with birth weight or FPR values per placental weight in either twin type. DISCUSSION: Reference values were generated for placental weight, birth weight and FPR in monochorionic and double-disc dichorionic twins. The generally lower FPR per placental weight in monochorionic twins compared with dichorionic twins is suggestive of inherently lower placental functional efficiency in monochorionic gestations. The mechanisms and clinical implications of the apparent differential modulation of FPR/efficiency in monochorionic twins according to placental partitioning remain to be determined.

Graduated compression stockings to treat acute leg pain associated with proximal DVT. A randomised controlled trial.

Acute deep venous thrombosis (DVT) causes leg pain. Elastic compression stockings (ECS) have potential to relieve DVT-related leg pain by diminishing the diameter of distended veins and increasing venous blood flow. It was our objective to determine whether ECS reduce leg pain in patients with acute DVT. We performed a secondary analysis of the SOX Trial, a multicentre randomised placebo controlled trial of active ECS versus placebo ECS to prevent the post-thrombotic syndrome.The study was performed in 24 hospital centres in Canada and the U.S. and included 803 patients with a first episode of acute proximal DVT. Patients were randomised to receive active ECS (knee length, 30-40 mm Hg graduated pressure) or placebo ECS (manufactured to look identical to active ECS, but lacking therapeutic compression). Study outcome was leg pain severity assessed on an 11-point numerical pain rating scale (0, no pain; 10, worst possible pain) at baseline, 14, 30 and 60 days after randomisation. Mean age was 55 years and 60% were male. In active ECS patients (n=409), mean (SD) pain severity at baseline and at 60 days were 5.18 (3.29) and 1.39 (2.19), respectively, and in placebo ECS patients (n=394) were 5.38 (3.29) and 1.13 (1.86), respectively. There were no significant differences in pain scores between groups at any assessment point, and no evidence for subgroup interaction by age, sex or anatomical extent of DVT. Results were similar in an analysis restricted to patients who reported wearing stockings every day. In conclusion, ECS do not reduce leg pain in patients with acute proximal DVT.

Prevention of diseases after menopause.

Women may expect to spend more than a third of their lives after menopause. Beginning in the sixth decade, many chronic diseases will begin to emerge, which will affect both the quality and quantity of a woman's life. Thus, the onset of menopause heralds an opportunity for prevention strategies to improve the quality of life and enhance longevity. Obesity, metabolic syndrome and diabetes, cardiovascular disease, osteoporosis and osteoarthritis, cognitive decline, dementia and depression, and cancer are the major diseases of concern. Prevention strategies at menopause have to begin with screening and careful assessment for risk factors, which should also include molecular and genetic diagnostics, as these become available. Identification of certain risks will then allow directed therapy. Evidence-based prevention for the diseases noted above include lifestyle management, cessation of smoking, curtailing excessive alcohol consumption, a healthy diet and moderate exercise, as well as mentally stimulating activities. Although the most recent publications from the follow-up studies of the Women's Health Initiative do not recommend menopause hormonal therapy as a prevention strategy, these conclusions may not be fully valid for midlife women, on the basis of the existing data. For healthy women aged 50-59 years, estrogen therapy decreases coronary heart disease and all-cause mortality; this interpretation is entirely consistent with results from other randomized, controlled trials and observational studies. Thus. as part of a comprehensive strategy to prevent chronic disease after menopause, menopausal hormone therapy, particularly estrogen therapy may be considered as part of the armamentarium.

Risks and benefits of hormone therapy: has medical dogma now been overturned?

BACKGROUND: In an integrated overview of the benefits and risks of menopausal hormone therapy (HT), the Women's Health Initiative (WHI) investigators have claimed that their 'findings … do not support use of this therapy for chronic disease prevention'. In an accompanying editorial, it was claimed that 'the WHI overturned medical dogma regarding menopausal [HT]'. OBJECTIVES: To evaluate those claims. METHODS: Epidemiological criteria of causation were applied to the evidence. RESULTS: A 'global index' purporting to summarize the overall benefit versus the risk of HT was not valid, and it was biased. For coronary heart disease, an increased risk in users of estrogen plus progestogen (E + P), previously reported by the WHI, was not confirmed. The WHI study did not establish that E+ P increases the risk of breast cancer; the findings suggest that unopposed estrogen therapy (ET) does not increase the risk, and may even reduce it. The findings for stroke and pulmonary embolism were compatible with an increased risk, and among E+ P users there were credible reductions in the risk of colorectal and endometrial cancer. For E+ P and ET users, there were credible reductions in the risk of hip fracture. Under 'worst case' and 'best case' assumptions, the changes in the incidence of the outcomes attributable to HT were minor. CONCLUSIONS: Over-interpretation and misrepresentation of the WHI findings have damaged the health and well-being of menopausal women by convincing them and their health professionals that the risks of HT outweigh the benefits.

Is that a rodent in your luggage? A mixed method approach to describe bushmeat importation into the United States.

Bushmeat, defined as meat derived from wild animals, is a potential source of zoonotic pathogens. Bushmeat from restricted animals is illegal to import into the United States under US federal regulations. We reviewed US Centers for Disease Control and Prevention (CDC) port of entry surveillance records from September 2005 through December 2010 and conducted focus group studies to describe trends in and reasons for bushmeat importation into the United States. In total, 543 confiscated bushmeat items were recorded. Half of the confiscated bushmeat items identified were rodents. Africa was the most frequent continent of origin. Seasonality was evident, with bushmeat confiscations peaking in late spring to early summer. Four times more bushmeat was confiscated during an enhanced surveillance period in June 2010 compared with the same period in previous years, suggesting that routine surveillance underestimated the amount of bushmeat detected at US Ports of Entry. Focus groups held in three major US cities revealed that bushmeat importation is a multifaceted issue. Longstanding cultural practices of hunting and eating bushmeat make it difficult for consumers to acknowledge potential health and ecologic risks. Also, US merchants selling African goods, including bushmeat, in their stores have caused confusion among importers as to whether importation is truly illegal. Enhancing routine surveillance for bushmeat and consistent enforcement of penalties at all ports of entry, along with health education aimed at bushmeat importers, might be useful to deter illegal importation.