Miracle-dz/UniFAR-FTUs huggingface dataset:
Progressive nature of paroxysmal atrial fibrillation. Observations from a 14-year follow-up study.

BACKGROUND Atrial fibrillation (AF) is believed to occur first as paroxysmal, then be gradually perpetuated, and finally become chronic as the end result. However, this presumed clinical course has not been well confirmed. METHODS AND RESULTS The clinical course of recurrent paroxysmal AF (PAF) from its onset was examined in 171 patients (mean follow-up period: 14.1+/-8.1 years). This study population consisted of patients with no structural heart disease (n=88), ischemic heart disease (n=28), dilated or hypertrophic cardiomyopathy (n=17), valvular heart disease (n=35) or other cardiac diseases. The mean age at the onset of AF was 58.3 +/-11.8 years old. During the mean follow-up period of 14.1 years, PAF eventually developed into its chronic form in 132 patients under conventional antiarrhythmic therapy (77.2%, 5.5% of patients per year). The independent factors for early development into chronic AF were aging (hazard ratio (HR) 1.27 per 10 years, 95% confidence interval (CI) 1.06-1.47)), dilated left atrium (HR 1.39 per 10 mm, 95% CI 1.11-1.69), myocardial infarction (HR 2.33, 95% CI 1.13-4.81), and valvular diseases (HR 2.29, 95% CI 1.22-4.30). CONCLUSIONS The present long-term observations definitely and quantitatively revealed the progressive nature of PAF.
The management of pre-hypertension in primary care: Is it adequate?

Abstract Background. Pre-hypertension (pHT) is frequently diagnosed in the primary care setting, but its management by primary care physicians (PCPs) is not well characterized. Methods. All individuals aged 30–45 years who were insured by Clalit Health services in the Tel Aviv district and had their blood pressure (BP) measured from January 2006 to December 2010 were evaluated. Individuals were divided into three groups based on their initial BP value: optimal (< 120/80 mmHg), normal (systolic BP 120–129 or diastolic 80–84 mmHg) and borderline (130–139/85–89 mmHg). Groups were compared regarding clinical and laboratory follow-up performed by their PCP. Results. Of the 20,214 individuals included in the study, 6576 (32.5%) had values in the pHT range. Of these, 2126 (32.3% of those with pHT) had BP values defined as “borderline” and 4450 (67.6% of those with pHT) had BP values defined as “normal”. The number of follow-up visits by the PCP and repeat BP measurement were similar in those with “optimal” BP and pHT. A third and fourth BP measurement were recorded more frequently in those with pHT. In those with pHT, there were more recorded BP measurements than in those with borderline BP (3.35 ± 3 vs 3.23 ± 2.6), but the time from the initial to the second measurement and a record of a third and fourth measurement were the same in the two groups. Conclusion. Identification of pHT does not lead to a significant change in follow-up by PCPs, irrespective of BP values in the pHT range.
What drives corporate governance quality in emerging African economies? Evidence from Ghana

This paper investigates the determinants of good corporate governance across Ghanaian listed firms for the study period 2000 to 2009. The Ghanaian Code of corporate governance introduced in 2003 was the first attempt to make official corporate governance guidelines on best practices not backed by the force of law of which the Ghanaian firms were encouraged to comply with its provisions. As such, firms listed on the Ghana Stock Exchange are expected to comply with the recommended governance provisions in order to promote good corporate governance. Some of the key provisions in the code are separating the posts of the Chief Executive Officer and the Chairman of the board of directors, limiting the board size to between eight and sixteen directors, having at least one-third of the total membership of the board to be independent directors, and the establishment of separate board committees to be responsible for audit and executive remuneration. Other provisions call for improvement of the relationship between shareholders and managers, and provisions on financial affairs, auditing and disclosure practices. We develop a corporate governance index and its six subindices to measure firm-level governance quality. Annual reports of the Ghanaian listed firms are scored according to their governance disclosure during the whole period, 2000–2009 and pre 2003 and post 2003 introduction of the Ghanaian Code. A panel data analytical framework was used to find the determinants of strong corporate governance in Ghanaian listed firms. The empirical results over the whole period, 2000–2009 show statistically significant and positive relationship between external financing needs, firm size, institutional shareholdings and governance quality measured by the Ghanaian corporate governance index. While we find no relationship between external financing needs, director shareholding and governance quality pre 2003, the result is positive and statistically significant for post 2003. The most consistent relationship we find concerns firm size and institutional shareholdings. However, growth opportunities and firm performance measures appear to have no association with strong governance in Ghanaian firms. The results have important implications for the Ghanaian firms and regulators. In particular, the Ghanaian firms with high external financing needs would have to improve their governance structures in order to attract such facility. For regulators, it is important to have clear code of corporate governance guidelines in place where firms’ governance practices can be benchmarked. In addition, the study contributes to our understanding of the firm attributes affecting strong corporate governance in emerging African economies.
The Harrod trade multiplier and the importance of export-led growth

The paper attempts to revive the idea that the level and growth of output of countries in a balance of payments constrained framework are determined by the workings of the foreign trade multiplier; an idea first put forward by Harrod in 1933. Evidence is presented for a range of developed and developing countries, which suggests that the Harrod trade multiplier works in developed countries, but much more loosely in developing countries where capital flows and terms of trade changes are more important in determining growth performance. The relevance of the model for explaining regional growth, and the growth of industry in the early stages of development, is also discussed.
Concordance among three self-reported measures of medication adherence and pharmacy refill records.

OBJECTIVE To evaluate the level of agreement among three previously validated self-reported medication adherence measures and pharmacy refill records (RRs). DESIGN Cross-sectional study. SETTING Five primary care physician office sites in rural northeast Georgia. PARTICIPANTS 139 adult patients with one or more of these chronic diseases: hypertension, diabetes mellitus, hypercholesterolemia, hypothyroidism, or a condition requiring hormone replacement therapy. INTERVENTIONS Study participants completed the Brief Medication Questionnaire (BMQ), the Medication Adherence Survey (MAS), and the Medical Outcomes Study (MOS) instruments; pharmacy RRs for the medication or medications being used to treat the target disease were obtained from pharmacies used by the study participants. MAIN OUTCOME MEASURES Adherence to medication therapy for target disease. RESULTS Participants were nearly all white (98.6%), consistent with the Appalachian area in which the study was conducted, and mostly women (71.9%). While 91.4% of study participants reported taking their study medication most or all of the time, RRs showed mean adherence rates of 82.6%, 82.1%, 79.1%, 74.6%, and 69.8% for diabetes mellitus, hypertension, hypothyroidism, hypercholesterolemia, and hormone replacement therapy, respectively. Moderate correlations of . 234, . 261, and . 213 were found between RRs and the MAS, MOS, and BMQ belief screen, respectively. Spearman correlations ranged from . 091 between RRs and the BMQ regimen subscale to . 313 between MOS and MAS. Pearson chi-square tests showed that only the BMQ belief subscale was significant in this study. CONCLUSION Because of the weak to moderate concordance found among validated measures of adherence, the selection of a useful adherence measure in pharmacy practice is difficult. These findings underscore the difficulty in both assessing patients' medication-taking behavior and assessing and comparing the results of adherence research. The development of valid and reliable measures for easily assessing medication adherence behavior in community pharmacies is needed.
A closed-loop control scheme for intraaortic balloon pumping

The beneficial hemodynamic efforts of intraaortic balloon pumping (IABP) are critically dependent on balloon timing relative to the diastolic phase of the cardiac cycle. A microprocessor-based controller has been developed to implement real-time automation of IABP using P-R intervals to regulate balloon deflation and systolic time intervals to trigger balloon inflation in a semiautomatic fashion. Experiments were performed on anesthetized open-chest dogs. Simultaneous measurements of aortic pressure and flow, coronary flow, and left ventricular pressure were recorded. Muscle segment lengths in normal and ischemic border zones were also measured from implanted pairs of endocardial ultrasonic dimension gages. P-waves were obtained from atrial cardiograms, and heart sounds were detected using a special filtering circuit. Both signals were input together with ECG to automate IABP timing. Systolic time intervals were calculated in real time. IABP efficacy was assessed from changes in aortic flow, coronary flow, tension time index, end diastolic pressure, and the endocardial viability ratio. <<ETX>>
Insulin Release and Insulin mRNA Levels in Rat Islets of Langerhans Cultured on Extracellular Matrix

Primary culture of rat islets of Langerhans lose glucose responsiveness and eventually die when cultured for a long period of time. In this study we evaluated the effect of matrigel, a basement membrane extract, on (i) islet cell survival, (ii) cell responsiveness following a glucose challenge, and (iii) mRNA levels for insulin, glu-cagon, and somatostatin. Pancreatic islets were isolated by collagenase digestion and plated in culture dishes either coated or not with a matrigel layer. Using the reverse hemolytic plaque assay, we determined the total number of insulin-secreting cells and the amount of insulin secreted by individual beta cells. After 1 h of exposure to 5 mM glucose, β cells from 6-month-old rat islets cultured for 6 weeks on matrigel showed an equal number of insulin-secreting cells compared to freshly isolated islets cultured for only 3 days in the absence of matrigel (39.5 ± 2.5 vs. 37.1 ± 9.6%). Furthermore, the release of insulin by cells cultured on matrigel for 6 weeks increased in a glucose-dependent manner (p < 0.001) and showed an ED50 of 7 mM. However, the amount of insulin released per single β cell was reduced by 40–60% (p < 0.02) compared to that released from isolated β cells derived from a 3-day culture of islets. Finally, there was a 35–55% increase (p < 0.05) in the levels of insulin, glucagon, and somatostatin mRNAs in cells cultured for 6 weeks on matrigel. These data suggest a trophic effect of matrigel on the maintenance of normal β-cell activity and function and may lead the way to the development of a new model for the study of pancreatic islets in long-term culture.
Genomic Imbalance in Products of Conception: Single-Nucleotide Polymorphism Chromosomal Microarray Analysis

OBJECTIVE: To report the full cohort of identifiable anomalies, regardless of known clinical significance, in a large-scale cohort of postmiscarriage products-of-conception samples analyzed using a high-resolution single-nucleotide polymorphism (SNP)–based microarray platform. High-resolution chromosomal microarray analysis allows for the identification of visible and submicroscopic cytogenomic imbalances; the specific use of SNPs permits detection of maternal cell contamination, triploidy, and uniparental disomy. METHODS: Miscarriage specimens were sent to a single laboratory for cytogenomic analysis. Chromosomal microarray analysis was performed using a SNP-based genotyping microarray platform. Results were evaluated at the cytogenetic and microscopic (greater than 10 Mb) and submicroscopic (less than 10 Mb) levels. Maternal cell contamination was assessed using information derived from fetal and maternal SNPs. RESULTS: Results were obtained on 2,389 of 2,392 specimens (99.9%) that were less than 20 weeks of gestation. Maternal cell contamination was identified in 528 (22.0%) specimens. The remaining 1,861 specimens were considered to be of true fetal origin. Of these, 1,106 (59.4%) showed classical cytogenetic abnormalities: aneuploidy accounted for 945 (85.4%), triploidy for 114 (10.3%), and structural anomalies or tetraploidy for the remaining 47 (4.2%). Of the 755 (40.6%) cases considered normal at the cytogenetic level, SNP chromosomal microarray analysis revealed a clinically significant copy number change or whole-genome uniparental disomy in 12 (1.6%) and three (0.4%) cases, respectively. CONCLUSION: Chromosomal microarray analysis of products-of-conception specimens yields a high diagnostic return. Using SNPs extends the scope of detectable genomic abnormalities and facilitates reporting “true” fetal results. This supports the use of SNP chromosomal microarray analysis for cytogenomic evaluation of miscarriage specimens when clinically indicated. LEVEL OF EVIDENCE: III
Differing effect of modifiable cardiovascular risk factors on intima-media thickening and plaque formation at different sites of the arterial vasculature

Objective The effects of cardiovascular risk factors on the vascular anatomy at differing sites of the arterial vasculature have not been well described. The aim of this study was to compare the effect of cardiovascular risk factors on the intima media thickness (IMT) of the wall of the right and left common carotid artery (CCA) at their bifurcation and proximal from their bifurcation, and the effects on the presence of plaque at carotid and femoral arteries. Design Cross-sectional population-based study. Setting/participants Random samples of men (n=425) and women (n=367) aged 56–77 years were recruited from two general practices participating in the British Regional Heart Study. Main outcome measures Ultrasound examination ascertained IMT and the presence of atheromatous plaque. A model for correlated outcomes was used to simultaneously model all risk factor on all measured vascular sites. Results All cardiovascular risk factors (HbA1c, waist-to-hip ratio, hypertension, LDL and smoking) showed a larger association with IMT thickening at the wall of the CCA at its bifurcation than proximal to its bifurcation. The IMT was greater on the left wall of the CCA than on the right. The association between hypertension with the wall of the CCA depended on age. Smoking was the only risk factor that demonstrated an increased odds (45%, 95% CI 14% to 65%) of the presence of plaque at the femoral arteries when compared with the CCA. Conclusions The associations of cardiovascular risk factors with the vascular anatomy are not uniform for IMT thickening or the presence of plaque. These differences in local arterial anatomy may result in differences between trial outcomes that investigate surrogate endpoints such as IMT.
Inhibitory Cross-talk by cAMP Kinase on the Calmodulin-dependent Protein Kinase Cascade*

The calmodulin-dependent kinase (CaM-K) cascade, a Ca2+-triggered system involving phosphorylation and activation of CaM-KI and CaM-KIV by CaM kinase kinase (CaM-KK), regulates transcription through direct phosphorylation of transcription factors such as cAMP response element-binding protein. We have shown previously that activated CaM-KIV can activate the mitogen-activated protein kinases (Enslen, H., Tokumitsu, H., Stork, P. J. S., Davis, R. J., and Soderling, T. R. (1996) Proc. Natl. Acad. Sci. U. S. A. 93, 10803–10808), and the present paper describes a novel regulatory cross-talk between cAMP kinase (PKA) and CaM-KK. PKA gave rapid phosphorylation in vitro and in cells of recombinant CaM-KK, resulting in 50–75% inhibition of CaM-KK activity, part of which was due to suppression of CaM-binding by phosphorylation of Ser458 in the CaM-binding domain. However, the Ser458 → Ala mutant, or a truncation mutant in which the CaM-binding and autoinhibitory domains were deleted, was still partially suppressed by PKA-mediated phosphorylation. The second inhibitory site was identified as Thr108 by site-specific mutagenesis. Treatments of COS-7, PC12, hippocampal, or Jurkat cells with the PKA activators forskolin or isoproterenol gave 30–90% inhibition of either endogenous or transfected CaM-KK and/or CaM-KIV activities. These results demonstrate that the CaM kinase cascade is negatively regulated in cells by the cAMP/PKA pathway.
Distribution of cyclosporin A metabolites among plasma and cells in whole blood: effect of temperature, hematocrit, and metabolite concentration.

Drug-free whole-blood samples supplemented with the cyclosporines and samples from 10 transplant patients receiving cyclosporin A (CsA) were equilibrated at 4, 22, and 37 degrees C for 2.5 h; the plasma and cells were separated; and the fractions were assayed by high-performance liquid chromatography (HPLC). Partitioning of CsA and metabolites among plasma and cells was diverse and not always predictable for patients' samples. Overall, although widely variable, greater than 50% of the total concentration of metabolites M1, M8, M9, M10, M16, M17, U1, U8, and U9 in whole blood was associated with the cells, whereas greater than 50% of M13, M18, M21, M25, M26, M203-218, U2, U3, U4, U5, U6, and U7 was associated with plasma. A decrease in hematocrit from 47.8% to 24%, an increase of the sample's temperature (from 4 to 37 degrees C), or an increase in analyte concentration (usually greater than 500 micrograms/L for selected metabolites) increased the relative portion associated with plasma in a nonlinear fashion. Parent CsA was most influenced by these changes; its relative concentrations in plasma varied from 18% to 50%. These data support the preferential use of whole blood for therapeutic monitoring of "cyclosporines. " Through additional studies, we suggest possible mechanisms affecting the distribution phenomenon and ascribe chemical structure-distribution relationships.
Increased IFN-α–Producing Plasmacytoid Dendritic Cells (pDCs) in Human Th1-Mediated Type 1 Diabetes: pDCs Augment Th1 Responses through IFN-α Production

Increasing evidence suggests that type 1 IFN (IFN-αβ) is associated with pathogenesis of Th1-mediated type 1 diabetes (T1D). A major source of IFN-αβ is plasmacytoid dendritic cells (pDCs). In this study, we analyzed peripheral blood pDC numbers and functions in at-risk, new-onset, and established T1D patients and controls. We found that subjects at risk for T1D and new-onset and established T1D subjects possessed significantly increased pDCs but similar number of myeloid DCs when compared with controls. pDC numbers were not affected by age in T1D subjects but declined with increasing age in control subjects. It was demonstrated that IFN-α production by PBMCs stimulated with influenza viruses was significantly higher in T1D subjects than in controls, and IFN-α production was correlated with pDC numbers in PBMCs. Of interest, only T1D-associated Coxsackievirus serotype B4 but not B3 induced majority of T1D PBMCs to produce IFN-α, which was confirmed to be secreted by pDCs. Finally, in vitro studies demonstrated IFN-α produced by pDCs augmented Th1 responses, with significantly greater IFN-γ–producing CD4+ T cells from T1D subjects. These findings indicate that increased pDCs and their IFN-αβ production may be associated with this Th1-mediated autoimmune disease, especially under certain viral infections linked to T1D pathogenesis.
Enhanced preventive programme at a beryllium oxide ceramics facility reduces beryllium sensitisation among new workers

Background: A 1998 survey at a beryllium oxide ceramics manufacturing facility found that 10% of workers hired in the previous 6 years had beryllium sensitisation as determined by the beryllium lymphocyte proliferation test (BeLPT). In response, the facility implemented an enhanced preventive programme to reduce sensitisation, including increased respiratory and dermal protection and particle migration control. Aim: To assess the programme’s effectiveness in preventing sensitisation. Methods: In 2000, the facility began testing newly hired workers for beryllium sensitisation with the BeLPT at time of hire and during employment. The sensitisation rate and prevalence for workers hired from 2000 to 2004 were compared with that for workers hired from 1993 to 1998, who were tested in the 1998 survey. Facility environmental conditions for both time periods were evaluated. Results: Newly hired workers in both cohorts worked for a mean of 16 months. Of the 97 workers hired from 2000 to 2004 with at least one employment BeLPT result, four had abnormal results at time of hire and one became sensitised during employment. Of the 69 workers hired from 1993 to 1998 and tested in 1998, six were found to be sensitised. The sensitisation rate for the 2000–4 workers was 0.7–2.7/1000 person-months of employment, and that for the 1993–8 workers was 5.6/1000 person-months, at least 2.1 (95% confidence interval (CI) 0.6 to 8.4) and up to 8.2 (95% CI 1.2 to 188.8) times higher than that for the 2000–4 workers. The sensitisation prevalence for the 2000–4 workers was 1% and that for the 1993–8 workers was 8.7%, 8.4 (95% CI 1.04 to 68.49) times higher than that for the 2000–4 workers. Airborne beryllium levels for production workers for the two time periods were similar. Conclusions: A comprehensive preventive programme reduced beryllium sensitisation in new workers during the first years of employment, despite airborne beryllium levels for production workers that were similar to pre-programme levels.
Troponin-based risk stratification of patients with acute nonmassive pulmonary embolism: systematic review and metaanalysis.

BACKGROUND Controversy exists regarding the usefulness of troponin testing for the risk stratification of patients with acute pulmonary embolism (PE). We conducted an updated systematic review and a metaanalysis of troponin-based risk stratification of normotensive patients with acute symptomatic PE. The sources of our data were publications listed in Medline and Embase from 1980 through April 2008 and a review of cited references in those publications. METHODS We included all studies that estimated the relation between troponin levels and the incidence of all-cause mortality in normotensive patients with acute symptomatic PE. Two reviewers independently abstracted data and assessed study quality. From the literature search, 596 publications were screened. Nine studies that consisted of 1,366 normotensive patients with acute symptomatic PE were deemed eligible. Pooled results showed that elevated troponin levels were associated with a 4.26-fold increased odds of overall mortality (95% CI, 2.13 to 8.50; heterogeneity chi(2) = 12.64; degrees of freedom = 8; p = 0.125). Summary receiver operating characteristic curve analysis showed a relationship between the sensitivity and specificity of troponin levels to predict overall mortality (Spearman rank correlation coefficient = 0.68; p = 0.046). Pooled likelihood ratios (LRs) were not extreme (negative LR, 0.59 [95% CI, 0.39 to 0.88]; positive LR, 2.26 [95% CI, 1.66 to 3.07]). The Begg rank correlation method did not detect evidence of publication bias. CONCLUSIONS The results of this metaanalysis indicate that elevated troponin levels do not adequately discern normotensive patients with acute symptomatic PE who are at high risk for death from those who are at low risk for death.