Miracle-dz/UniFAR-FTUs huggingface dataset:
Effective sterilized foreign exchange intervention? Evidence from a rule-based policy

We investigate the effectiveness of sterilized foreign exchange interventions by exploiting a discontinuous policy rule used by the Central Bank of Colombia (CBoC). We use a unique data set from CBoC comprised of tick by tick intervention and order book data, daily capital in- and outflow data, and balance sheet information of financial institutions. We apply regression discontinuity methods to identify the surprise component of rule based exchange rate interventions of the CBoC and use this variation to measure how interventions affect exchange rates and capital flows. At horizons of a few days, our empirical findings support sterilized exchange rate intervention effectiveness via a portfolio channel. The exchange rate effects we see are short-lived. At horizons of a month or longer, capital flows originating from foreign investors restore the exchange rate back to its original level. Our findings also show that the effects of sterilized interventions are amplified by capital controls. A methodological contribution of the paper is to extend regression discontinuity designs to a time series environment and to show how these techniques can be used to identify and estimate non-linear impulse response functions.
Outcomes-Based Reimbursement Policies for Chronic Care Pathways

We consider contracting issues in the care of patients with chronic conditions within the principal-agent framework. The government, acting as a principal, contracts with several health care providers in an effort to maximise population health minus the cost. We consider the decision of whether to contract with individual health care providers or groups of such providers, as well as which contract type to use. We show that the first best outcome can be achieved by both individual and group contracts through the use of either outcomes-adjusted capitation or outcomes-adjusted per-patient contracts. We also examine possible issues which can arise as the entities that are contracted with are not necessarily the ones making decisions about patient care. Individual contracts can fail to provide the desired incentives if providers under such contracts jointly make decisions about the care for their patients (collusion); however, so can group contracts if the group members fail to coordinate their actions (free-riding). We show that both of those result in potential deviations from optimal decisions, with direction and magnitude of deviation depending on the contract type held. We conduct numerical experiments calibrated using data from United Kingdom's NHS and demonstrate that individual outcomes-adjusted capitation contracts are the most robust to these adverse effects.
Recycling and resource recovery under the Basel Convention: historical analysis and outlook

The history of the Basel Convention still needs to be written. This chapter attempts to provide a narrative based on experience and the events of the last decades. The past 25 years have seen the rise of the Basel Convention as a key international environmental instrument which aims at reducing the export of hazardous waste and ensuring that any such waste be managed in a way to protect human health and the environment. There are two interconnected factors that explain why the Convention only partially succeeded in achieving its aims. First, trade issues came into collision with the control system of the Convention, and second, a large majority of countries parties to the Convention did not and still do not possess the capacity to manage the hazardous waste they generate in an environmentally sound way. Throughout its history, parties made constant efforts to keep a balance between environmental protection and trade while implementing the Convention. This resulted in reducing the potential of the Convention to become a universal landmark for the environmentally sound waste management based on principles applicable to hazardous waste. As a consequence, and despite its concrete achievements, the Convention disappeared from the radar screen of politicians and became a technical instrument. The issue of recycling and recovery was never resolved in a satisfactory manner within the scope of the Convention. From an historical perspective, one could witness a loss of influence of the Basel Convention. One reason is that the parties, being preoccupied by the way the Convention would relate to trade, did not invest in exploring its potential to contribute to the emerging green economy movement. However, it might not be too late to face up to this new challenge.
Multiple functions of the E3 ubiquitin ligase CHIP in immunity

ABSTRACT The carboxyl terminal of Hsp70-interacting protein (CHIP) is an E3 ubiquitin ligase that plays a pivotal role in the protein quality control system by shifting the balance of the folding-refolding machinery toward the degradative pathway. However, the precise mechanisms by which nonnative proteins are selected for degradation by CHIP either directly or indirectly via chaperone Hsp70 or Hsp90 are still not clear. In this review, we aim to provide a comprehensive model of the mechanism by which CHIP degrades its substrate in a chaperone-dependent or direct manner. In addition, through tight regulation of the protein level of its substrates, CHIP plays important roles in many physiological and pathological conditions, including cancers, neurological disorders, cardiac diseases, bone metabolism, immunity, and so on. Nonetheless, the precise mechanisms underlying the regulation of the immune system by CHIP are still poorly understood despite accumulating developments in our understanding of the regulatory roles of CHIP in both innate and adaptive immune responses. In this review, we also aim to provide a view of CHIP-mediated regulation of immune responses and the signaling pathways involved in the model described. Finally, we discuss the roles of CHIP in immune-related diseases.
Evolution of Factor V Leiden

Summary Factor V Leiden is a procoagulant mutation associated with venous and arterial thrombosis and pregnancy complications. Its high prevalence of 5% in Caucasians suggests that there are evolutionary benefits as well. Carriers are indeed reported to have various advantageous phenotypes related to haemostasis, inflammation and fertility: less acute blood loss; less menstrual blood loss; decreased risk of intracranial haemorrhage; milder phenotypes of haemophilia; higher survival in and lower susceptibility to severe sepsis; higher survival in acute respiratory distress syndrome; less severe diabetic nephropathy and higher fecundity in both men and women. Not all these associations come from high quality adequately powered studies and many have not been confirmed by further research. The evolutionary influence of the alleged associations varies and is difficult to establish, partly due to a shift over time in risk factors of the diseases concerned. For most of the phenotypes possible mechanistic explanations can be provided. The procoagulant phenotype and perhaps also certain pregnancy complications follow from activated protein C (APC) resistance. Elevated APC levels possibly mediate anti-inflammatory effects. Higher sperm counts and more successful embryo implantation seem to play a role in the increased fecundity.
Placental anionic and cationic amino acid transporter expression in growth hormone overexpressing and null IGF-II or null IGF-I receptor mice.

The role of growth hormone (GH), insulin-like growth factor (IGF)-II and the IGF-I receptor (IGF-Ir) in the regulation of the in vivo expression of Na(+)-coupled anionic [System X-AG; GLAST1 (EAAT1), GLT1 (EAAT2), EAAC1 (EAAT3), EAAT4; where the human homologues of amino acid transport proteins first cloned in the rat are given in parentheses] and Na(+)-independent cationic (System y(+);CAT1) amino acid transport proteins was evaluated by comparing transporter expression in day 17 placentae of mice that overexpressed bovine GH (GH+) or that carried null gene mutations for IGF-II or IGF-Ir. Northern analysis revealed no apparent difference in the mRNA content of GLAST1 (EAAT1), EAAC1 (EAAT3), or EAAT4, in homogenates of GH+ placentae, but levels of GLT1 (EAAT2) and CAT1 mRNA were increased. Immunoblot analysis revealed that whole-placental steady-state GLAST1 (EAAT1), EAAC1 (EAAT3), and EAAT4 protein levels were not affected by GH+, whereas GLT1 (EAAT2) levels were increased. Immunohistochemical analysis showed that the cell-specific expression of the anionic and CAT1 transporters was not affected by overexpression of GH. Similar analyses of null IGF-II placentae demonstrated increases in GLAST1 (EAAT1), EAAT4 and CAT1 mRNAs. Parallel immunoblot analysis demonstrated decreased expression of GLT1 (EAAT2), GLAST1 (EAAT1) and EAAC1 (EAAT3) protein, but an increased expression of EAAT4. In null IGF-II and IGF-Ir placentae, however, GLT1 (EAAT2) and EAAC1 (EAAT3) protein content was decreased in junctional zone cells, whereas CAT1 content was increased in junctional and labyrinth zone cells. These data indicate that an excess level of GH stimulates GLT1 (EAAT2) expression and that a normal level of IGF-II is required for typical expression of GLT1 (EAAT2), GLAST1 (EAAT1) and EAAC1 (EAAT3), but that IGF-II downregulates the expression of EAAT4 and CAT1.
Views on health information and perceptions of standardized electronic records among staff in Child and School Health Services.

AIM To investigate how nurses and physicians in the Child and School Health Services view the documentation and transfer of health information. Another aim concerns their perceptions of a nationally standardized electronic health record. BACKGROUND Problems of mental health among children and adolescents currently pose one of the greatest challenges facing all European countries. The continuity of health work demands that all health information follow the child's development, disregarding the organizational arrangement. METHODS The study was descriptive and comprised 484 questionnaires to nurses and physicians in the Child and School Health Services in Sweden. RESULTS More information about children's health was transferred than documented in the health record when children started school. This additional health information concerned psychosocial health and foremost family function. There was a consensus concerning the usefulness of a nationally standardized electronic health record, although there were group differences between nurses and physicians. CONCLUSIONS All information about children's health is not documented although the professional's positive perceptions to electronic health records may provide a basis to improve documentation. IMPLICATIONS FOR NURSING MANAGEMENT The results indicate challenges to develop a common language to document psychosocial issues necessary for providing a holistic view of children's health.
Depressive Symptom Frequency and Prevalence of Cardiovascular Diseases—Analysis of Patients in the National Health and Nutrition Examination Survey

Although depression has been reported to be associated with various cardiovascular risk factors, whether an association exists between depression and prevalence of cardiovascular events is not well known. In particular, the effect of symptom frequency and cardiovascular events has not been described. Data were collected for patients older than 45 years from the 2007–2008 National Health and Nutrition Examination Survey (NHANES) data to study whether an association exists between depression and prevalence of coronary artery disease (CAD), myocardial infarction (MI), congestive heart failure (CHF), and stroke. The NHANES database is a nationally representative probability sample of noninstitutionalized US civilians. We divided patients feeling down/depressed/hopeless into 1 of the 2 categories: symptoms less than half the days of the week and those with less frequent symptoms. Logistic regression analysis was used to adjust for other covariates. A P value of <0.05 was considered statistically significant. More than 2700 patients were studied to analyze the association between severity of depression and prevalence of CAD, MI, CHF, and stroke. Significant associations were noted between depressive symptoms and prevalence of CAD, MI, CHF, and stroke. Those who reported being depressed more than half of the days of the week had 1.95 times greater odds of CAD [95% confidence interval (CI), 1.2473–3.0523], 2.54 times greater odds of CHF (95% CI, 1.6114–4.0126), 2.65 times greater odds of MI (95% CI, 1.7789–3.9521), and 1.91 greater odds of stroke (95% CI, 1.2002–3.0356) when compared with those who reported being depressed less than half of the days of the week. The results of this study suggest that the prevalence of CAD, MI, CHF, and stroke are significantly increased in individuals who report feeling down/depressed/hopeless for more than half the days of the week.
Rosiglitazone modulates the behaviors of diabetic host‐derived fibroblasts in a carboxymethyllysine‐modified collagen model

Utilizing a three‐dimensional in vitro glycated collagen model, we evaluated the therapeutic effects of a peroxisome proliferator‐activated receptor‐γ ligand, rosiglitazone, and its potential as a topical treatment of diabetic chronic wounds. Rosiglitazone induced fibroblast migration, α‐smooth muscle actin production, and transformation into myofibroblasts in the presence of advanced glycation end products. Both transforming growth factor β and peroxisome proliferator‐activated receptor‐γ expression were induced, while the receptor for advanced glycation end products was suppressed. Lastly, the reduced activities of matrix metalloproteinase‐2 and matrix metalloproteinases‐9 in the carboxymethyllysine‐modified collagen matrices by rosiglitazone increases extracellular matrix deposition. Our findings identify rosiglitazone as a candidate for localized topical treatment of diabetic chronic wounds.
High-throughput identification and rational design of synergistic small-molecule pairs for combating and bypassing antibiotic resistance

Antibiotic-resistant infections kill approximately 23,000 people and cost $20,000,000,000 each year in the United States alone despite the widespread use of small-molecule antimicrobial combination therapy. Antibiotic combinations typically have an additive effect: the efficacy of the combination matches the sum of the efficacies of each antibiotic when used alone. Small molecules can also act synergistically when the efficacy of the combination is greater than the additive efficacy. However, synergistic combinations are rare and have been historically difficult to identify. High-throughput identification of synergistic pairs is limited by the scale of potential combinations: a modest collection of 1,000 small molecules involves 1 million pairwise combinations. Here, we describe a high-throughput method for rapid identification of synergistic small-molecule pairs, the overlap2 method (O2M). O2M extracts patterns from chemical-genetic datasets, which are created when a collection of mutants is grown in the presence of hundreds of different small molecules, producing a precise set of phenotypes induced by each small molecule across the mutant set. The identification of mutants that show the same phenotype when treated with known synergistic molecules allows us to pinpoint additional molecule combinations that also act synergistically. As a proof of concept, we focus on combinations with the antibiotics trimethoprim and sulfamethizole, which had been standard treatment against urinary tract infections until widespread resistance decreased efficacy. Using O2M, we screened a library of 2,000 small molecules and identified several that synergize with the antibiotic trimethoprim and/or sulfamethizole. The most potent of these synergistic interactions is with the antiviral drug azidothymidine (AZT). We then demonstrate that understanding the molecular mechanism underlying small-molecule synergistic interactions allows the rational design of additional combinations that bypass drug resistance. Trimethoprim and sulfamethizole are both folate biosynthesis inhibitors. We find that this activity disrupts nucleotide homeostasis, which blocks DNA replication in the presence of AZT. Building on these data, we show that other small molecules that disrupt nucleotide homeostasis through other mechanisms (hydroxyurea and floxuridine) also act synergistically with AZT. These novel combinations inhibit the growth and virulence of trimethoprim-resistant clinical Escherichia coli and Klebsiella pneumoniae isolates, suggesting that they may be able to be rapidly advanced into clinical use. In sum, we present a generalizable method to screen for novel synergistic combinations, to identify particular mechanisms resulting in synergy, and to use the mechanistic knowledge to rationally design new combinations that bypass drug resistance.
Risk factors for loss of virological suppression in patients receiving lopinavir/ritonavir monotherapy for maintenance of HIV suppression

Background Risk factors for loss of virological response in patients receiving lopinavir/ritonavir (LPV/r) monotherapy as maintenance treatment have not been determined. Methods In 121 patients enrolled in the OK and OK04 clinical trials assigned to receive monotherapy with LPV/r, we attempted to identify factors associated with loss of virological suppression at 48 weeks, defined as confirmed serum HIV type-1 RNA>50 copies/ml, with missing data or changes caused by toxicity censored. Univariate and multivariate Cox proportional hazard models were used to calculate hazard ratios for the risk of loss of virological suppression. Results At week 48, 15 patients experienced loss of virological suppression. Probability of loss of virological suppression was 12.7%. Less than 9 months of maintenance of virological suppression prior to monotherapy, a lower baseline haemoglobin and low adherence measured by self-reported total missed doses in the week prior to study visit were associated with loss of virological suppression in the univariate analyses. Independent factors associated with loss of virological suppression by multivariate analyses were ≥2 visits with self-reported missed doses in the week prior to the study visit, a lower baseline haemoglobin and a nadir CD4+ T-cell count <100 cells/μl Conclusions Suboptimal adherence, lower baseline haemoglobin and a nadir CD4+ T-cell count <100 cells/μl were the main risk factors for losing virological suppression in patients randomized to monotherapy with LPV/r.
Essays on development economics and industrial organization

This dissertation studies two disparate topics in development economics and industrial organization respectively: (a) the role of financial intermediation in promoting economic growth in developing countries and (b) the effects of learning on agents’ search behavior. The first essay investigates the effects of commercial banking on economic growth. The tendency of banks to locate in profitable areas experiencing higher growth typically complicates the identification of banking effects. I exploit a previously unstudied reform of bank branching policy in India between 2005-06 that led to a large expansion in private bank credit to financially underserved areas. Using iterations of a regression discontinuity design, I trace the exogenous expansion of banking services through time at the district level. I show this expansion produced positive effects in agriculture and manufacturing. I confirm greater gains in local GDP growth using remote sensing data to overcome the lack of official GDP statistics at the district level. These results offer evidence of a causal impact of financial system expansion on economic development. The second essay examines how the geographic reach of a bank’s network of branches can affect its ability to spread risks across spatially separated regions. I investigate the causal impact of the spatial expansion of Indian banks resulting from the bank branching policy reform on smoothing the consumption of households with respect to local weather and agricultural productivity shocks. The third essay (coauthored with Sergei Koulayev) extends a model of sequential search
The bone marrow histological pattern has independent prognostic value in early stage chronic lymphocytic leukaemia

Summary. The initial diagnostic bone marrow specimens from 90 consecutive, untreated patients with chronic lymphocytic leukaemia were examined for the pattern of lymphocytic infiltration in relation to clinical stage (International Workshop System) and survival. Three non‐diffuse (interstitial, nodular, mixed nodular–interstitial) and one diffuse pattern were recognized. Generally, the bone marrow patterns correlated well with clinical stage: a non‐diffuse pattern prevailed in early, and a diffuse pattern in later stages. However, with a Cox analysis of the covariate effect of clinical stage and bone marrow pattern on survival, the bone marrow pattern was shown to have independent prognostic significance in the early stage A in which a diffuse pattern carried a fourfold increase in death rate as compared to a non‐diffuse pattern. These high risk patients could not be identified by the Rai substages of the International Workshop System.
Perceived injustice moderates the relationship between pain and depressive symptoms among individuals with persistent musculoskeletal pain.

BACKGROUND Numerous investigations report that depressive symptoms frequently coexist with persistent pain. However, evidence suggests that symptoms of depression are not an inevitable consequence of pain. Diathesis-stress formulations suggest that psychological factors interact with the stress of pain to heighten the risk of depressive symptoms. Perceptions of injustice have recently emerged as a factor that may interact with the stress of pain to increase depressive symptoms. OBJECTIVES The purpose of the present study was to examine whether perceived injustice moderates the relationship between pain and depressive symptoms. METHODS A total of 107 individuals with persistent musculoskeletal pain completed self-report measures of pain severity, depressive symptoms, perceived injustice and catastrophizing. RESULTS A hierarchical regression analysis revealed that the interaction between pain severity and perceived injustice uniquely contributed an additional 6% of the variance to the prediction of depressive symptoms, beyond the main effects of these variables. Post hoc probing indicated that pain was significantly related to depressive symptoms at high, but not low levels of perceived injustice. This finding remained statistically significant even when controlling for pain catastrophizing. CONCLUSIONS The results suggest that perceived injustice augments the relationship between pain severity and depressive symptoms. The inclusion of techniques specifically targeting perceptions of injustice may enhance the effectiveness of interventions aimed at reducing symptoms of depression for individuals presenting with strong perceptions of injustice.