Miracle-dz/UniFAR-FTUs huggingface dataset:
Do dictatorships affect people's long term beliefs and preferences? An empirical assessment of the Latin American case

Does the political regime experienced during youth have long lasting effects on political beliefs and preferences? I exploit time and country variation in political regimes in Latin America using data from the 1995 to 2010 Latinobarometer and find that exposure to non-democratic regimes during youth reduces subsequent preference for democracy, satisfaction with democracy and confidence in institutions. These results suggest exposure to dictatorships during formative years permanently eroded democratic values. Exposure to non-democratic regimes also aspects self-location in an ideology scale, reducing identification with the Right and increasing identification with the Left; which suggests dictatorships also shaped the political orientation of voters.
Budgeting in Kazakhstan

The Republic of Kazakhstan is the largest economy in central Asia, and one of the fastest growing in the region. Having benefited from oil wealth as well as a diversifying and liberalised economy, Kazakhstan envisages a progressive modernisation of the political, administrative and juridical culture within the country. While strong progress has already been made on several fronts, other aspects of these envisaged reforms are at early stages. This OECD review takes stock of these reform efforts, and is designed to assist the national authorities in charting a course for future reforms and innovations.
Single-nucleotide polymorphisms in the Toll-like receptor pathway increase susceptibility to infections in severely injured trauma patients

BACKGROUND Sepsis and subsequent multiple-organ failure are the predominant causes of late mortality in trauma patients. Susceptibility and response to infection is, in part, heritable. Single-nucleotide polymorphisms (SNPs) in Toll-like receptor (TLR) and cluster of differentiation 14 (CD14) genes of innate immunity may play a key role. The aim of this study was to assess if SNPs in TLR/CD14 predisposed trauma patients to infection. METHODS A prospective cohort of trauma patients (age 18–80 years; injury severity score [ISS] ≥ 16) admitted to a Level I trauma center between January 2008 and April 2011 was genotyped for SNPs in TLR2 (T-16934A and R753Q), TLR4 (D299G and T399I), TLR9 (T-1486C and T-1237C), and CD14 (C-159T) using high-resolution melting analysis. Association of genotype with prevalence of positive culture findings (gram positive, gram negative, fungi), systemic inflammatory response syndrome (SIRS), sepsis, septic shock, and mortality was tested with &khgr;2 and logistic regression analysis. RESULTS Genotyping was performed for 219 patients, of whom 51% developed positive culture findings in sputum, wounds, blood, or urine. SIRS developed in 64%, sepsis in 36%, and septic shock in 17%. The TLR2 T-16934A TA genotype increased the risk of a gram-positive infection (odds ratio, 2.816; 95% confidence interval, 1.249–6.348; p = 0.013) and SIRS (odds ratio, 2.386; 95% confidence interval, 1.011–5.632; p = 0.047). Trends were noted for TLR9 and CD14 SNPs but did not reach statistical significance. Sepsis and septic shock were unrelated to any of the SNPs studied. CONCLUSION Aberrant functioning of the TLR/CD14 pathway of innate immunity changes the risk of infectious complications in severely injured trauma patients. Of the seven SNPs studied, the TLR2 T-16934A increased the risk, the TLR9 T-1486C SNPs may decrease the risk, and TLR4 variation seemed unrelated to outcome. Early genotyping may prove to be helpful in the future in identifying polytraumatized patients at risk for infectious outcome. LEVEL OF EVIDENCE Prognostic and epidemiologic study, level II.
Statin use after renal transplantation: a systematic quality review of trial-based evidence.

BACKGROUND AND OBJECTIVES HMG-CoA reductase inhibitor (statin) therapy reduces cardiovascular risk in the general population and may modulate rejection in solid organ transplant recipients. We assessed whether current clinical evidence supports the use of statins to improve cardiac and/or renal outcomes after kidney transplantation. METHODS We performed a systematic review of randomized, controlled intervention trials of statins among renal allograft recipients. Clinical trials published between January 1, 1993 and January 1, 2004 were identified by systematic search of electronic databases. Eligible studies measured the impact of therapy on acute allograft rejection, surrogates of cardiovascular risk and/or cardiovascular morbidity and mortality. We abstracted descriptive summaries of trial design elements and primary effect estimates, and assessed trial quality with a standardized quality evaluation tool. RESULTS Thirteen eligible trials were identified. Statin therapy was associated with less acute allograft rejection in two early studies but was ineffective in three subsequent, larger trials. Therapeutic benefit was also seen in six of seven small studies that evaluated cardiovascular risk surrogates. Statin use did not significantly alter the primary composite outcome in a single large cardiac events trial, but was associated with reductions in secondary end-points of cardiac death analysed alone or with myocardial infarction. Important design distinctions included statin preparation and dose, concomitant interventions, study power and randomization methods. Median total quality scores were 52 for the rejection trials, 41 for the studies of cardiovascular risk surrogates and 69 for the cardiac events trial, and showed a trend towards variation by outcome measure (P = 0.05). CONCLUSIONS Heterogeneous study designs and methodological quality contribute to discrepant conclusions on the benefit of statin therapy to renal allograft recipients. Trial-based clinical evidence does not support the use of statins to lower acute rejection risk after kidney transplantation, but does indicate effectiveness for improvement in cardiovascular risk markers and possibly for reduction of clinical cardiac events.
DOES EDUCATION MEDIATE THE RELATIONSHIP BETWEEN IQ AND AGE OF FIRST BIRTH? A BEHAVIOURAL GENETIC ANALYSIS

This study presents a multivariate behavioural genetic analysis of the relationship between education, intelligence and age of first birth. Analyses investigated the mediational role of education in explaining the relationship between intelligence and age of first birth at both the phenotypic and behavioural genetic level. The data come from the National Longitudinal Survey of Youth (NLSY), a nationally representative survey that included genetically informative full- and half-sibling pairs (n=1423 pairs). Respondents were aged 14 to 22 when contacted in 1979. Heritability estimates were 0·32, 0·50 and 0·06 for IQ, education and age of first birth, respectively. Shared environment estimates were 0·35, 0·23 and 0·20 respectively. Common genetic and shared environmental factors were substantial in explaining the relationship between intelligence and education, and also education and age of first birth. Education partially mediated the relationship between intelligence and age of first birth only in the phenotypic analyses. After considering the genetic and shared environmental factors that influence all three variables, evidence for mediation was less convincing. This pattern of results suggests that the apparent mediational role of education at the phenotypic level is in fact the result of underlying genetic and shared environmental influences that affect education, IQ and age of first birth in common.
Working Paper 298 - Governance and Development in Africa: A Review Essay

Given the increasing importance of governance in economic development and the yearning for Africa to catch up, the present paper provides a concise review of the literature relevant to the region. First, it presents stylized facts showing that Africa as a region, since about the late 1990s, substantially improved its growth and economic outcomes in the form of per capita income, human development, and poverty. Second, it shows that both economic governance and political governance have improved considerably since about the late 1980s to early 1990s. Economic governance is measured by economic freedom and political governance by the index of electoral competitiveness, executive constraint and polity 2, and by indicators of political stability. Finally, the paper flags the challenge of the likely disequilibrium between the economic and political equilibria under multiparty democracy, with adverse implications for fiscal allocation.JEL classification: O11, O15, O43, O55. Keywords: Governance, economic development, human development, poverty
Rat as Model for Studying Behavior Effects of hCG

The demonstration of receptors for luteinizing hormone (LH)/human chorionic gonadotropin (hCG) in several parts of rat brain suggested their novel functional role. Subsequent studies tested the effect of hCG (intraperitoneally or intracerebroventricularly) on brain arousal and different types of stress situations in an intact female rat model on the day of proestrus. Treatment resulted in changes of activity and several other behavioral patterns associated with sites of brain hCG/LH receptors. hCG given peripherally caused a longer sleeping time and a decreased activity level. Whereas administration of indomethacin alone had no effect, coadministration inhibited the effects of hCG. hCG increased immunoreactive prostaglandin D2 (PGD2) and decreased PGE2 in brain areas controlling activity and sleep. hCG effects were probably mediated via prostaglandin pathways. After central hCG treatment, animals were less active and showed less exploratory behavior in an open-field box than the control animals. Taste and odor neophobias were dramatically decreased following central injection of hCG. hCG-treated rats were less anxious and exhibited a higher level of maternal interest than the controls. hCG treatment also had a beneficial effect against stress ulcer, which was prevented by pretreatment with antisense receptor oligonucleotide, suggesting a direct hCG receptor-mediated effect. In summary, because hCG can cross the blood-brain barrier, both peripheral administration and central administration affect several behavioral patterns. This effect is similar to treatment with anxiolytics and suggests the functional relevance of brain LH/hCG receptors. Some observed behavioral changes have parallels in pregnant women.
Optimization and Application of a Multiplex Bead-Based Assay To Quantify Serotype-Specific IgG against Streptococcus pneumoniae Polysaccharides: Response to the Booster Vaccine after Immunization with the Pneumococcal 7-Valent Conjugate Vaccine

ABSTRACT We describe the optimization and application of a multiplex bead-based assay (Luminex) to quantify antibodies against polysaccharides of 13 pneumococcal serotypes. In the optimized multiplex immunoassay (MIA), intravenous immune globulin was introduced as an in-house reference serum, and nonspecific reacting antibodies were adsorbed with the commercial product pneumococcal C polysaccharides Multi. The antibody concentrations were assessed in 188 serum samples obtained pre- and post-booster vaccination at 11 months after administration of a primary series of the pneumococcal seven-valent conjugate vaccine (PCV-7) at 2, 3, and 4 months of age. The results of the MIA were compared with those of the ELISA for the serotypes included in the seven-valent conjugated polysaccharide vaccine and for a non-vaccine serotype, serotype 6A. The geometric mean concentrations of the antibodies determined by MIA were slightly higher than those determined by ELISA. The correlations between the assays were good, with R2 values ranging from 0.84 to 0.91 for all serotypes except serotype 19F, for which R2 was 0.70. The concentrations of antibody against serotype 6A increased after the administration of PCV-7 due to cross-reactivity with serotype 6B. The differences between the results obtained by ELISA and MIA suggest that the internationally established protective threshold of 0.35 μg/ml should be reevaluated for use in the MIA and may need to be amended separately for each serotype.
Nitric Oxide Treatment for the Control of Reverse Osmosis Membrane Biofouling

ABSTRACT Biofouling remains a key challenge for membrane-based water treatment systems. This study investigated the dispersal potential of the nitric oxide (NO) donor compound, PROLI NONOate, on single- and mixed-species biofilms formed by bacteria isolated from industrial membrane bioreactor and reverse osmosis (RO) membranes. The potential of PROLI NONOate to control RO membrane biofouling was also examined. Confocal microscopy revealed that PROLI NONOate exposure induced biofilm dispersal in all but two of the bacteria tested and successfully dispersed mixed-species biofilms. The addition of 40 μM PROLI NONOate at 24-h intervals to a laboratory-scale RO system led to a 92% reduction in the rate of biofouling (pressure rise over a given period) by a bacterial community cultured from an industrial RO membrane. Confocal microscopy and extracellular polymeric substances (EPS) extraction revealed that PROLI NONOate treatment led to a 48% reduction in polysaccharides, a 66% reduction in proteins, and a 29% reduction in microbial cells compared to the untreated control. A reduction in biofilm surface coverage (59% compared to 98%, treated compared to control) and average thickness (20 μm compared to 26 μm, treated compared to control) was also observed. The addition of PROLI NONOate led to a 22% increase in the time required for the RO module to reach its maximum transmembrane pressure (TMP), further indicating that NO treatment delayed fouling. Pyrosequencing analysis revealed that the NO treatment did not significantly alter the microbial community composition of the membrane biofilm. These results present strong evidence for the application of PROLI NONOate for prevention of RO biofouling.
Augmentation of smad‐dependent BMP signaling in neural crest cells causes craniosynostosis in mice

Craniosynostosis describes conditions in which one or more sutures of the infant skull are prematurely fused, resulting in facial deformity and delayed brain development. Approximately 20% of human craniosynostoses are thought to result from gene mutations altering growth factor signaling; however, the molecular mechanisms by which these mutations cause craniosynostosis are incompletely characterized, and the causative genes for diverse types of syndromic craniosynostosis have yet to be identified. Here, we show that enhanced bone morphogenetic protein (BMP) signaling through the BMP type IA receptor (BMPR1A) in cranial neural crest cells, but not in osteoblasts, causes premature suture fusion in mice. In support of a requirement for precisely regulated BMP signaling, this defect was rescued on a Bmpr1a haploinsufficient background, with corresponding normalization of Smad phosphorylation. Moreover, in vivo treatment with LDN‐193189, a selective chemical inhibitor of BMP type I receptor kinases, resulted in partial rescue of craniosynostosis. Enhanced signaling of the fibroblast growth factor (FGF) pathway, which has been implicated in craniosynostosis, was observed in both mutant and rescued mice, suggesting that augmentation of FGF signaling is not the sole cause of premature fusion found in this model. The finding that relatively modest augmentation of Smad‐dependent BMP signaling leads to premature cranial suture fusion suggests an important contribution of dysregulated BMP signaling to syndromic craniosynostoses and potential strategies for early intervention.
Is Chronic Migraine One End of a Spectrum of Migraine or a Separate Entity?

Chronic migraine is associated with abnormalities in the periaqueductal grey that may be progressive. The condition is also associated with a greater degree of impairment in cortical processing of sensory stimuli than episodic migraine, perhaps due to more pervasive or persistent cortical hyperexcitability These findings fit with the model of migraine as a spectrum disorder, in which the clinical and pathophysiological features may progress over time. This progression may result from changes in nociceptive thresholds and ensuing central sensitization caused by recurrent migraine in susceptible individuals. This may lead to changes in baseline neurological function between headaches, evident not only in electrophysiological and functional imaging studies, but also as psychological and somatic complaints that occur after years of episodic migraine. From current research and migraine models, a conceptualization of chronic migraine is emerging in which relatively permanent and pervasive central changes have occurred that warrant novel and tolerable treatments.
Application of the who fracture risk assessment tool (FRAX) to predict need for dexa scanning and treatment in patients with inflammatory bowel disease at risk of osteoporosis

Introduction Although patients with inflammatory bowel disease (IBD) are at increased risk of osteoporosis, low bone mineral density (BMD) confers only a modest increase in the risk of fracture. The FRAX score is a web-based clinical scale designed by the WHO to measure in individual patients the 10-year risk of fracture: it divides the level of risk into high, intermediate and low and can be calculated with or without BMD score. Using guidelines from the National Osteoporosis Guidelines Group (NOGG), the tool then recommends the need for treatment, DEXA scanning or lifestyle advice/reassurance. In order to prevent unnecessary DEXA scanning and anti-osteoporotic therapy, we aimed to assess the accuracy of pre-BMD FRAX scores in identifying at risk patients with IBD who need BMD measurement (intermediate risk) and/or preventive therapy (high risk with or without DEXA scan). Methods We retrospectively calculated FRAX scores in 81 patients with Crohn's disease and 35 with ulcerative colitis in whom DEXA scans had been requested during the years 2005–2009 because they were considered by their clinicians to be at risk of osteoporosis. Scores were assessed before and after inclusion of BMD results obtained from the DEXA scans. Results On DEXA scans, 47% (38/81) and 12% (10/81) patients with Crohn's disease were osteopaenic and osteoporotic, respectively; equivalent figures for patients with UC were 34% (12/35) and 14% (5/35). The clinical FRAX score alone, when compared to the FRAX score including the BMD result, had a sensitivity of 100% (95% CI: 70%>100%), specificity of 40% (95% CI: 31%>50%), positive predictive value of 16% (95% CI: 9%>27%) and negative predictive value of 100% (95% CI: 90%>100%) in identifying those patients needing BMD measurement (intermediate risk) or preventive therapy (high risk). On the basis of their BMD alone and as part of our routine practice, eleven patients were started on treatment for osteoporosis with a bisphosphonate following their DEXA scan. In this small group of patients, there was no significant difference between our existing practice and that suggested by NOGG (post BMD inclusion) in the 97 patients at low or intermediate risk for fracture. However, according to the NOGG guidance, 10% (9/97) patients were being treated unnecessarily. Moreover, in the high risk group, while treatment was recommended by NOGG in 11/19 (58%) patients, only 1 patient was being treated with a bisphosphonate (p<0.01). Conclusion In patients with IBD who are perceived by their clinicians as being at increased risk of osteoporosis and/or osteopaenia, the clinical criteria of the FRAX score can be used to predict more accurately than DEXA scan alone the risk of osteoporotic fracture.
Expression and Functional Analysis of Dkk1 during Early Gonadal Development

WNT signalling plays a central role in mammalian sex determination by promoting ovarian development and repressing aspects of testis development in the early gonad. Dickkopf homolog 1 (DKK1) is a WNT signalling antagonist that plays critical roles in multiple developmental systems by modulating WNT activity. Here, we examined the role of DKK1 in mouse sex determination and early gonadal development. Dkk1 mRNA was upregulated sex-specifically during testis differentiation, suggesting that DKK1 could repress WNT signalling in the developing testis. However, we observed overtly normal testis development in Dkk1-null XY gonads, and found no significant upregulation of Axin2 or Sp5 that would indicate increased canonical WNT signalling. Nor did we find significant differences in expression of key markers of testis and ovarian development. We propose that DKK1 may play a protective role that is not unmasked by loss-of-function in the absence of other stressors.
Receptor Activator of NF-κB and Osteoprotegerin Expression by Human Microvascular Endothelial Cells, Regulation by Inflammatory Cytokines, and Role in Human Osteoclastogenesis*

The receptor activator of NF-κB (RANKL) is the essential signal required for full osteoclast (OC) development, activation, and survival. RANKL is highly expressed in areas of trabecular bone remodeling and inflammatory bone loss, is increased on marrow stromal cells or osteoblasts by osteotropic hormones or cytokines, and is neutralized by osteoprotegerin (OPG), a soluble decoy receptor also crucial for preventing arterial calcification. Vascular endothelial cells (VEC) are critically involved in bone development and remodeling and influence OC recruitment, formation, and activity. Although OCs develop and function in close association with bone VEC and sinusoids, signals mediating their interactions are not well known. Here, we show for the first time that human microvascular endothelial cells (HMVEC) express transcripts for both RANKL and OPG; inflammatory cytokines tumor necrosis factor-α and interleukin-1α elevate RANKL and OPG expression 5–40-fold in HMVEC (with an early OPG peak that declines as RANKL rises), and RANKL protein increases on the surface of tumor necrosis factor-α-activated HMVEC. Cytokine-activated HMVEC promoted the formation, fusion, and bone resorption of OCs formed in co-cultures with circulating human monocytic precursors via a RANKL-mediated mechanism fully antagonized by exogenous OPG. Furthermore, paraffin sections of human osteoporotic fractured bone exhibited increased RANKL immunostaining in vivo on VEC located near resorbing OCs in regions undergoing active bone turnover. Therefore, cytokine-activated VEC may contribute to inflammatory-mediated bone loss via regulated production of RANKL and OPG. VEC-derived OPG may also serve as an autocrine signal to inhibit blood vessel calcification.
Surface T-antigen expression in simian virus 40-transformed mouse cells: correlation with cell growth rate

Cell growth control appears to be drastically altered as a consequence of transformation. Because the cell surface appears to have a role in modulating cell growth and simian virus 40 (SV40)-transformed cells express large T antigen (T-Ag) in the plasma membrane, we investigated whether surface T-Ag expression varies according to cell growth rate. Different growth states were obtained by various combinations of seeding density, serum concentration, and temperature, and cell cycle distributions were determined by flow microcytofluorometry. Actively dividing SV40-transformed mouse cell cultures were consistently found to express higher levels of surface T-Ag and T-Ag/p53 complex than cultures in which cells were mostly resting. In addition, the T-Ag/p53 complex disappeared from the surface of tsA7-transformed cells cultured under restrictive conditions known to induce complete growth arrest (39.5 degrees C), although the surface complex did not disappear from other tsA transformants able to keep cycling at 39.5 degrees C. These results suggest that surface SV40 T-Ag or surface T-Ag/p53 complex, or both, are involved in determining the growth characteristics of SV40-transformed cells.