Miracle-dz/UniFAR-FTUs huggingface dataset:
Questions and answers on the use of dabigatran and perpectives on the use of other new oral anticoagulants in patients with atrial fibrillation.

Summary Dabigatran and other new oral anticoagulants (OAC) represent a step forward in stroke prevention in patients with atrial fibrillation (AF). They indeed have been shown to be an alternative to vitamin K antagonists (VKAs) without the burden of laboratory control. However, these new drugs compete with an effective and well-established therapy, thus bringing about a series of questions and doubts. In this report members of the board of the Italian Federation of Thrombosis Centers (FCSA) answer some questions every clinician might be confronted with.
Growth and Debt: An Endogenous Smooth Coefficient Approach

The new growth theories with an emphasis on fundamental determinants such as institutions suggest a non-linear cross-country growth process. In this paper, we investigate the public debt and economic growth relationship using the semi-parametric smooth coefficient approach that allows democracy to influence this relationship and parameter heterogeneity in the unknown functional form and addresses the endogeneity of variables. We find results consistent with the previous literature that identified a significant adverse effect of public debt on growth for the countries below a particular democracy level. However, we also find conclusive evidence that countries with high institutional quality have an adverse effect of public debt on growth for the period 1980–2009, as well as for the extended period including the years 2010–2014. A 10-percentage point increase in the debt-to-GDP ratio is associated with a 0.12% and 0.07% decrease in the subsequent 10-year period real GDP growth rate for the zero democracy countries and for the countries with a democracy score of 10, respectively.
Progress, Innovation and Regulatory Science in Drug Development

This paper examines international standard-setting in the toxicology of pharmaceuticals during the 1990s, which has involved both the pharmaceutical industry and regulatory agencies in an organization known as the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). The analysis shows that the relationships between innovation, regulatory science and `progress' may be more complex and controversial than is often assumed. An assessment of the ICH's claims about the implications of `technical' harmonization of drug-testing standards for the maintenance of drug safety, via toxicological testing, and the delivery of therapeutic progress, via innovation, is presented. By demonstrating that there is not a technoscientific validity for these claims, it is argued that, within the ICH, a discourse of technological innovation and scientific progress has been used by regulatory agencies and prominent parts of the transnational pharmaceutical industry to legitimize the lowering and loosening of toxicological standards for drug testing. The mobilization and acceptance of this discourse are shown to be pivotal to the ICH's transformation of reductions in safety standards, which are apparently against the interests of patients and public health, into supposed therapeutic benefits derived from promises of greater access to more innovative drug products. The evidence suggests that it is highly implausible that these reductions in the standards of regulatory toxicology are consistent with therapeutic progress for patients, and highlights a worrying aspect embedded in the `technical trajectories' of regulatory science.
Dietary fish oil preserves cardiac function in the hypertrophied rat heart

Regular fish or fish oil intake is associated with a low incidence of heart failure clinically, and fish oil-induced reduction in cardiac remodelling seen in hypertrophy models may contribute. We investigated whether improved cardiac energy efficiency in non-hypertrophied hearts translates into attenuation of cardiac dysfunction in hypertrophied hearts. Male Wistar rats (n 33) at 8 weeks of age were sham-operated or subjected to abdominal aortic stenosis to produce pressure-overload cardiac hypertrophy. Starting 3 weeks post-operatively to follow initiation of hypertrophy, rats were fed a diet containing 10 % olive oil (control) or 5 % fish oil (ROPUFA® 30 (17 % EPA, 10 % DHA))+5 % olive oil (FO diet). At 15 weeks post-operatively, ventricular haemodynamics and oxygen consumption were evaluated in the blood-perfused, isolated working heart. Resting and maximally stimulated cardiac output and external work were >60 % depressed in hypertrophied control hearts but this was prevented by FO feeding, without attenuating hypertrophy. Cardiac energy efficiency was lower in hypertrophy, but greater in FO hearts for any given cardiac mass. Coronary blood flow, restricted in hypertrophied control hearts, increased with increasing work in hypertrophied FO hearts, revealing a significant coronary vasodilator reserve. Pronounced cardiac dysfunction in hypertrophied hearts across low and high workloads, indicative of heart failure, was attenuated by FO feeding in association with membrane incorporation of n-3 PUFA, principally DHA. Dietary fish oil may offer a new approach to balancing the high oxygen demand and haemodynamic requirements of the failing hypertrophied heart independently of attenuating hypertrophy.
Non-recurrent SEPT9 duplications cause hereditary neuralgic amyotrophy

Background Genomic copy number variants have been shown to be responsible for multiple genetic diseases. Recently, a duplication in septin 9 (SEPT9) was shown to be causal for hereditary neuralgic amyotrophy (HNA), an episodic peripheral neuropathy with autosomal dominant inheritance. This duplication was identified in 12 pedigrees that all shared a common founder haplotype. Methods and results Based on array comparative genomic hybridisation, we identified six additional heterogeneous tandem SEPT9 duplications in patients with HNA that did not possess the founder haplotype. Five of these novel duplications are intragenic and result in larger transcript and protein products, as demonstrated through reverse transcription-PCR and western blotting. One duplication spans the entire SEPT9 gene and does not generate aberrant transcripts and proteins. The breakpoints of all the duplications are unique and contain regions of microhomology ranging from 2 to 9 bp in size. The duplicated regions contain a conserved 645 bp exon within SEPT9 in which HNA-linked missense mutations have been previously identified, suggesting that the region encoded by this exon is important to the pathogenesis of HNA. Conclusions Together with the previously identified founder duplication, a total of seven heterogeneous SEPT9 duplications have been identified in this study as a causative factor of HNA. These duplications account for one third of the patients in our cohort, suggesting that duplications of various sizes within the SEPT9 gene are a common cause of HNA.
[Effect of preoperative transcatheter arterial chemoembolization on the perioperative outcome of patients with hepatocellular carcinoma].

OBJECTIVE To explore the surgical risk, perioperative outcome and the response of patients with hepatocellular carcinoma (HCC) after preoperative transcatheter arterial chemoembolization (TACE). METHODS A retrospective case-matched study was conducted to compare the characteristics and corresponding measures of patients in the preoperative TACE group and the control group without TACE. A total of 105 patients (82 patients with selective and dynamic region-specific vascular occlusion to perform hepatectomy for patients with complex hepatocellular carcinoma) was included in this study, in which 35 patients underwent TACE therapy, and a 1:2 matched control group of 70 subjects. RESULTS The patients of preoperative TACE therapy group had a higher level of γ-glutamyl transpeptidase before operation (119.52±98.83) U/L vs. (67.39±61.25) U/L (P=0.040). The operation time was longer in the TACE group than that in the control group but with a non-significant difference (232.60±95.43) min vs. (218.70±75.13) min (P=0.052). The postoperative recovery of liver function and severe complications in the preoperative TACE group were similar to that in the control group (P>0.05). There were no massive hemorrhage, biliary fistula and 30-d death neither in the treatment group and matched control group. CONCLUSIONS Preoperative TACE therapy has certain negative effect on liver function. It is preferable to use selective and dynamic region-specific vascular occlusion technique during hepatectomy and combine with reasonable perioperative treatment for this group of patients, that can ensure safety of patients and promote their rapid recovery.
Passive smoking and lung function in cystic fibrosis.

The relationship between passive exposure to cigarette smoking and objective measures of health was examined in 340 patients with cystic fibrosis attending a large hospital-based clinic. Patients who came from households with smokers did not differ from those living in smoke-free households in terms of nutritional status, clinical scores, spirometry, or colonization with Pseudomonas. The number of cigarettes smoked in the household was not significantly related to nutritional status, clinical score, spirometry, or hospitalization. Similar results were found when children 6 to 11 yr of age were analyzed separately, except that height percentile was negatively related to the number of cigarettes smoked in the household. The effects of household exposure to cigarette smoke were further evaluated by analyzing changes in nutritional status, clinical score, and spirometry over a 15-yr period among patients whose families never, always, stopped, or started smoking during this time. Height percentile increased slightly during this interval among those whose households never smoked, whereas no change occurred among patients whose households always smoked, and a decline was seen among patients whose households quit. These differences were statistically significant. Patients whose households never smoked had consistently higher pulmonary function measurements than did patients whose families always smoked, although the differences were not statistically significant. The rates of decline were similar in these two groups. Patients whose households stopped smoking had significantly lower pulmonary functions at the end of the study than did subjects whose households never smoked. (ABSTRACT TRUNCATED AT 250 WORDS)
Location of Sentinel Lymph Node in Cervical Carcinoma and Factors Associated With Unilateral Detection

Objective The aims of this study were to assess locality of the sentinel lymph node (SLN) in cervical carcinoma and examine factors affecting bilateral SLN detection. Methods This was a retrospective review of SLN data (anatomical location, count and laterality) in patients with early-stage cervical cancer (International Federation of Gynecology and Obstetrics stage IA1 with lymphovascular space invasion to stage IIA) using intraoperative gamma probe and blue dye. The preoperative single-photon emission computed tomography with computed tomography was used to detect laterality, number of the SLNs, and rare locations. Patients were treated between January 2005 to January 2015 at the West Kent Gynaecological Oncology Centre, Maidstone Hospital, Maidstone, United Kingdom. Results A total of 132 women were investigated. The most common SLN location was the external iliac (38.6%) followed by obturator (25.3%) and internal iliac (23.6%) regions. A small percentage was identified in presacral (1.4%) and para-aortic regions (0.7%). Older age (P = 0.01) and an elevated body mass index (P = 0.03) were associated with decreased SLN count by preoperative single-photon emission computed tomography with computed tomography, and only age affected SLN count by gamma probe (P = 0.01). Initial surgery, large loop excision of the transformation zone, or cone biopsy of the cervix had no effect on SLN count. There was no difference observed in bilateral detection with respect to surgical approach (open: n = 48/laparoscopic: n = 84). However, older age was independently associated with a decrease in bilateral SLN detection (P = 0.003). In these patients who underwent unilateral full pelvic lymphadenectomy, all the nonsentinel nodes were negative. Conclusions The majority of SLNs were located in the external iliac, obturator, and internal iliac regions. Both older age and an elevated body mass index were associated with a reduced SLN count. Unilateral detection of SLN was independently associated with older age, which may be due to sclerosis in the lymphatic vessels or reduced perfusion in the pelvis in these women. If no SLN is detected on one side, the consensus is to perform a full pelvic lymphadenectomy on that side of the pelvis.
Inflation and Wage Rigidity/Flexibility in the Short Run

A recent literature uses accurate wage data from payroll records and provides compelling evidence against the conventional belief that nominal wages are downward sticky. This paper provides a unique contribution to this literature by conducting a formal analysis of the role of inflation in cyclical wage rigidity/flexibility. Analysis of payroll-based wage data from the Korean labor market for the period 1971 to 2014 finds that the degree of downward nominal wage flexibility is countercyclical, and the countercyclicality becomes stronger during a deflationary, relative to inflationary, recession. This serves as a counter-example to the conventional theory of cyclical wage rigidity.
Differences in basal levels of CREB and NPY in nucleus accumbens regions between C57BL/6 and DBA/2 mice differing in inborn alcohol drinking behavior

An increasing body of evidence suggests that genetic factors play a role in alcohol drinking behaviors. C57BL/6J (C57) mice innately consume larger amounts of alcohol compared to that consumed by DBA/2J (DBA) mice. Furthermore, alterations in cAMP‐responsive element binding (CREB) protein function in the brain have been implicated in alcohol drinking behaviors. The present investigation examined innate expression and phosphorylation of CREB in various brain structures of C57 and DBA mice. It was found that CREB expression and phosphorylation was lower, specifically in the shell structure of the nucleus accumbens, in C57 mice compared to that in DBA mice. CREB expression and phosphorylation were similar in other brain regions such as the nucleus accumbens core and the cortical, amygdaloid, hippocampal, and striatal structures of C57 and DBA mice. The expression of a cAMP‐inducible gene, neuropeptide Y (NPY), was also investigated in the nucleus accumbens region of C57 and DBA mice. It was found that in C57 mice, NPY protein levels were lower in the shell but not in the core structure of the nucleus accumbens compared to that in DBA mice. It was also found that C57 mice are not innately anxious, but they consume larger amounts of alcohol than do DBA mice. Because the shell structure of the nucleus accumbens has been implicated in reward mechanisms of alcohol, it is possible that lower CREB function in this brain structure may be in part associated with the excessive alcohol drinking behavior of C57 mice. © 2003 Wiley‐Liss, Inc.
Granulocyte colony stimulating factor in HCV genotype‐1 patients who develop Peg‐IFN‐α2b related severe neutropenia: A preliminary report on treatment, safety and efficacy

Dose reductions of Peg‐IFNa because of severe neutropenia may affect the virologic response in patients with hepatitis C infection (HCV). Granulocyte colony‐stimulating factor (G‐CSF) has been used occasionally but studies addressing its safety and efficacy in the current treatment of HCV infection are missing. The database of 232 naïve patients with HCV genotype‐1 who received PEG‐IFNα2b 1.5 mcg/kg/week plus Ribavirin 800–1,400 mg/day and completed the treatment was examined. Nineteen patients who exhibited significant neutropenia and received 150–300 µg G‐CSF (Group A) with 19 matched control patients who had dose reductions of Peg‐IFNα according to the standard recommendations (Group B) were examined. None of the patients had treatment modifications due to thrombocytopenia or anemia. The mean decline of the neutrophils was similar in groups A and B (1,760 ± 1,030/mm3 at 11 ± 8.6 weeks and 1,630 ± 890 at 12.3 ± 6.1, respectively). Nadir neutrophil values were also not statistically different. Patients who received G‐CSF two before IFNα, maintained neutrophils between 1,400/mm3 and 2,700/mm3 and remained on G‐CSF for 29 weeks (2–40). Virologic response at the end of treatment was observed in 12/19 (63%) patients and at 6 months follow‐up in 6/19 (32%) in group A as compared to 9/19 (47%) and 4/19 (21%) in group B, respectively. No side effects related to G‐CSF were encountered. Administration of G‐CSF 2 days before Peg‐IFNα is safe, maintains sustained neutrophil count, improves adherence to treatment and seems to increase the virologic response in patients infected with HCV genotype 1 who develop Peg‐IFN‐α2b related severe neutropenia. J. Med. Virol. 81:848–852, 2009. © 2009 Wiley‐Liss, Inc.
Conscience and Parliament

Abortion, Susan Mills and Sally Sheldon homosexuality, Melvyn D. Read and David Marsh war crimes, Gabriele Ganz divorce, Philip Cowley Sunday trading, Melvyn D. Read disability rights, Matthew Bailey and Kevin Shinkwin animal welfare, Robert Garner censorship, Martin Durham voting without a party? , Charles Pattie, Ron Johnston and Mark Stuart.
Transvaginal duplex ultrasonography appears to be the gold standard investigation for the haemodynamic evaluation of pelvic venous reflux in the ovarian and internal iliac veins in women

Objectives To assess the suitability of transvaginal duplex ultrasonography to identify pathological reflux in the ovarian and internal iliac veins in women. Methods A retrospective study of patients treated in 2011 and 2012 was performed in a specialised vein clinic. Diagnostic transvaginal duplex ultrasonography in women presenting with symptoms or signs of pelvic vein reflux were compared with the outcomes of treatment from pelvic vein embolisation. A repeat transvaginal duplex ultrasonography was performed 6 weeks later by a blinded observer and any residual reflux was identified. Results Results from 100 sequential patients were analysed. Mean age 44.2 years (32–69) with mode average parity of 3 (0–5 deliveries). Pre-treatment, 289/400 veins were refluxing (ovarian – 29 right, 81 left; internal iliac – 93 right, 86 left). Coil embolisation was successful in 86/100 patients and failed partially in 14/100 – 5 due to failure to cannulate the target vein. One false-positive diagnosis was made. Conclusion Currently there is no accepted gold standard for pelvic vein incompetence. Comparing transvaginal duplex ultrasonography with the outcome from selectively treating the veins identified as having pathological reflux with coil embolisation, there were no false-negative diagnoses and only one false-positive. This study suggests that transvaginal duplex ultrasonography could be the gold standard in assessing pelvic vein reflux.
Do Couples Pool Their Income?: Evidence from Demand System Estimation for Germany

Whether couples pool their resources and behave like a unit or spend their income individually is crucial for social and tax policy. In this paper, I provide a test of the income pooling hypothesis using administrative cross-sectional survey data on expenditures and individual incomes of couple households in Germany. The test is performed within the Quadratic Almost Ideal Demand System (QUAIDS) framework, which allows for an endogenous expenditure budget and endogenous individual income contribution shares in an instrumental variables approach. Although the hypothesis is broadly rejected, there are significant differences regarding the marital status, the presence of at least one child in the household and whether the household is located in a former West or East German federal state. Married couples and couples with children are closer to the acceptance of the hypothesis than unmarried couples without children.
Epidermal growth factor inhibits Fas-mediated apoptosis in salivary epithelial cells of patients with primary Sjögren's syndrome.

OBJECTIVES Cell death is detected in the ducts of labial salivary glands (LSG) of patients with primary Sjögren's syndrome (pSS). However, the counter-mechanism to inhibit the apoptotic process remains unclear. In this study, we studied the ability of epidermal growth factor (EGF) to activate the PI3K-Akt pathway and NF-kB in primary cultured salivary gland epithelial cells (SGEC) of pSS patients. METHODS SGEC, obtained from 2 female pSS patients, were cultured and used for Hoechst staining and deoxynucleotidyltransferase-mediated dUTP nick end-labeling (TUNEL) assay. The frequency of apoptosis, detected by Hoechst staining, was quantified, and statistical significance was determined through unpaired student's t-test. RESULTS Following twelve hours of stimulation, both PI3K inhibitors and anti-Fas antibody failed to induce apoptosis in primary cultured SGEC. However, the combination of anti-Fas antibody, along with LY294002 or Bay 11-7082, induced apoptosis which was statistically more significant than apoptosis found in the control cells (p < 0.01). Interestingly, the apoptosis induced by anti-Fas antibody along with LY294002 was clearly inhibited by the addition of 10 ng/ml EGF. Furthermore, the results of the TUNEL assay clearly indicated apoptosis through stimulation with anti-Fas antibody and LY294002 or Bay 11-7082. Furthermore, the apoptosis was completely blocked by the addition of EGF. CONCLUSION Our results suggest that salivary epithelial cells are protected from Fas mediated apoptosis, through cell survival factors including either the PI3K-Akt pathway or NF-kB.
Why Do They Keep Coming Back? The Effect of Push Motives vs. Pull Motives, and Attribute Satisfaction on Repeat Visitation of Tourist Destinations

ABSTRACT We conjecture that attribute satisfaction, push motives and pull motives will be positively related to return visitation of tourist destinations. We also hypothesize that push factors will be stronger related to return visitation of tourist destinations than pull factors, both directly and indirectly as mediators of the relationship between attribute satisfaction and return visitation. In addition, we predict that age and gender will moderate the effect of push and pull factors on repeat visitation. Finally, we argue that push factors and pull factors will be mutually reinforcing. To test these hypotheses, we conducted an online survey of repeat tourists’ motives, and received 986 complete responses. Survey participants were randomly chosen from a group that met a series or qualifying questions. PLS-SEM analysis of the data showed that, as we hypothesized, attribute satisfaction and push motives were positively related to repeat visitation. In contrast, pull motives were not related to repeat visitation, either directly or indirectly, but did reinforce the effect of push motives; gender did not moderate either push or pull motives and age moderated only pull motives. We discuss the theoretical and practical implications of these findings.