56 research outputs found

    The Information Content of Municipal Financial Statements: Large-sample Evidence

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    The usefulness of financial disclosures is a source of considerable debate in the municipal setting, given their lack of timeliness. This paper empirically examines the extent to which municipal financial disclosures have information content. Using the entire universe of annual financial disclosures from 2009 to 2020, we show that trading activity in the secondary market for municipal bonds increases after the disclosures are filed. Both institutional and retail trades increase around disclosure filings, but the effect is pronounced for retail traders, for whom the reports are more likely to provide new information. Moreover, the heightened trading is pronounced for timelier disclosures, consistent with regulators' views that untimely disclosures are less likely to provide new information. We also find a pronounced response when investors' risk is high and when the disclosures contain risk-related discussions. Our results contrast with earlier research and provide the first large-scale evidence that participants in the U.S. market for municipal bonds perceive financial disclosures to have informational value

    A New Class of Small Molecule Inhibitor of BMP Signaling

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    Growth factor signaling pathways are tightly regulated by phosphorylation and include many important kinase targets of interest for drug discovery. Small molecule inhibitors of the bone morphogenetic protein (BMP) receptor kinase ALK2 (ACVR1) are needed urgently to treat the progressively debilitating musculoskeletal disease fibrodysplasia ossificans progressiva (FOP). Dorsomorphin analogues, first identified in zebrafish, remain the only BMP inhibitor chemotype reported to date. By screening an assay panel of 250 recombinant human kinases we identified a highly selective 2-aminopyridine-based inhibitor K02288 with in vitro activity against ALK2 at low nanomolar concentrations similar to the current lead compound LDN-193189. K02288 specifically inhibited the BMP-induced Smad pathway without affecting TGF-β signaling and induced dorsalization of zebrafish embryos. Comparison of the crystal structures of ALK2 with K02288 and LDN-193189 revealed additional contacts in the K02288 complex affording improved shape complementarity and identified the exposed phenol group for further optimization of pharmacokinetics. The discovery of a new chemical series provides an independent pharmacological tool to investigate BMP signaling and offers multiple opportunities for pre-clinical development

    Impact of oil on bacterial community structure in bioturbated sediments

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    Oil spills threaten coastlines where biological processes supply essential ecosystem services. Therefore, it is crucial to understand how oil influences the microbial communities in sediments that play key roles in ecosystem functioning. Ecosystems such as sediments are characterized by intensive bioturbation due to burrowing macrofauna that may modify the microbial metabolisms. It is thus essential to consider the bioturbation when determining the impact of oil on microbial communities. In this study, an experimental laboratory device maintaining pristine collected mudflat sediments in microcosms closer to true environmental conditions - with tidal cycles and natural seawater - was used to simulate an oil spill under bioturbation conditions. Different conditions were applied to the microcosms including an addition of: standardized oil (Blend Arabian Light crude oil, 25.6 mg.g21 wet sediment), the common burrowing organism Hediste (Nereis) diversicolor and both the oil and H. diversicolor. The addition of H. diversicolor and its associated bioturbation did not affect the removal of petroleum hydrocarbons. After 270 days, 60% of hydrocarbons had been removed in all microcosms irrespective of the H. diversicolor addition. However, 16S-rRNA gene and 16S-cDNA T-RFLP and RT-PCR-amplicon libraries analysis showed an effect of the condition on the bacterial community structure, composition, and dynamics, supported by PerMANOVA analysis. The 16S-cDNA libraries from microcosms where H. diversicolor was added (oiled and un-oiled) showed a marked dominance of sequences related to Gammaproteobacteria. However, in the oiled-library sequences associated to Deltaproteobacteria and Bacteroidetes were also highly represented. The 16S-cDNA libraries from oiled-microcosms (with and without H. diversicolor addition) revealed two distinct microbial communities characterized by different phylotypes associated to known hydrocarbonoclastic bacteria and dominated by Gammaproteobacteria and Deltaproteobacteria. In the oiled-microcosms, the addition of H. diversicolor reduced the phylotype-richness, sequences associated to Actinobacteria, Firmicutes and Plantomycetes were not detected. These observations highlight the influence of the bioturbation on the bacterial community structure without affecting the biodegradation capacities

    Satisfaction with care after total hip or knee replacement predicts self-perceived health status after surgery

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    <p>Abstract</p> <p>Background</p> <p>Inpatient satisfaction with care is a standard indicator of the quality of care delivered during hospitalization. Total hip and knee replacement (THR/TKR) for osteoarthritis (OA) are among the most successful orthopaedic interventions having a positive impact on health-related quality of life (HRQoL). The aim was to evaluate the effect of satisfaction shortly after hospital discharge on 1-month, 6-month and 1-year Medical Outcomes Study 36-item Short Form (SF-36) scores for OA patients after THR and TKR, controlling for patient characteristics, clinical presentation and preoperative SF-36 scores.</p> <p>Methods</p> <p>A multicenter prospective cohort study recruited 231 patients with OA scheduled to receive THR or TKR. Satisfaction was assessed by the Patients Judgment of Hospital Quality (PJHQ) questionnaire and HRQoL by the SF-36 questionnaire. Linear models for repeated measures assessed the relation between satisfaction (scores were dichotomized) and postoperative SF-36 scores.</p> <p>Results</p> <p>Of 231 participants, 189 were followed up 12 months after discharge (mean age 69 SD = 8; 42.6% male). The mean length of hospital stay was 13.5 (SD = 4) days. After adjustment for preoperative SF-36 scores, sociodemographic and clinical patient characteristics, satisfied patients (PJHQ score > 70) had higher SF-36 scores 1 year after surgery than did less-satisfied patients. Admission, medical care, and nursing and daily care scores mainly predicted bodily pain, mental health, social functioning, vitality and general health scores of the SF-36.</p> <p>Conclusion</p> <p>Besides being a quality-of-care indicator, immediate postoperative patient satisfaction with care may bring a new insight into clinical practice, as a predictor of self-perceived health status after surgery.</p

    Towards the development of ecosystem-based indicators of mangroves functioning state in the context of the EU water framework directive

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    European Water Framework Directive is enforced in five tropical French Oversea Territories where mangroves are present. Developing bioindication tools to support the ecosystem-based management approach of the Directive is needed. A series of expert workshops was organized and led to the proposal of a strategy and of an applied research program to develop bioindication tools. The proceedings of the workshops are presented as a case study, as this is the first time such an integrative ecosystem-based approach is proposed in mangroves, combining structural and functional aspects, from forest structure to benthic community functioning

    Significant benefits of AIP testing and clinical screening in familial isolated and young-onset pituitary tumors

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    Context Germline mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene are responsible for a subset of familial isolated pituitary adenoma (FIPA) cases and sporadic pituitary neuroendocrine tumors (PitNETs). Objective To compare prospectively diagnosed AIP mutation-positive (AIPmut) PitNET patients with clinically presenting patients and to compare the clinical characteristics of AIPmut and AIPneg PitNET patients. Design 12-year prospective, observational study. Participants & Setting We studied probands and family members of FIPA kindreds and sporadic patients with disease onset ≤18 years or macroadenomas with onset ≤30 years (n = 1477). This was a collaborative study conducted at referral centers for pituitary diseases. Interventions & Outcome AIP testing and clinical screening for pituitary disease. Comparison of characteristics of prospectively diagnosed (n = 22) vs clinically presenting AIPmut PitNET patients (n = 145), and AIPmut (n = 167) vs AIPneg PitNET patients (n = 1310). Results Prospectively diagnosed AIPmut PitNET patients had smaller lesions with less suprasellar extension or cavernous sinus invasion and required fewer treatments with fewer operations and no radiotherapy compared with clinically presenting cases; there were fewer cases with active disease and hypopituitarism at last follow-up. When comparing AIPmut and AIPneg cases, AIPmut patients were more often males, younger, more often had GH excess, pituitary apoplexy, suprasellar extension, and more patients required multimodal therapy, including radiotherapy. AIPmut patients (n = 136) with GH excess were taller than AIPneg counterparts (n = 650). Conclusions Prospectively diagnosed AIPmut patients show better outcomes than clinically presenting cases, demonstrating the benefits of genetic and clinical screening. AIP-related pituitary disease has a wide spectrum ranging from aggressively growing lesions to stable or indolent disease course

    La place du thermalisme en dermatologie

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    CHATENAY M.-PARIS 11-BU Pharma. (920192101) / SudocSudocFranceF

    Disclosure and Competition for Capital

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    Politically connected governments

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    This paper examines the consequences of powerful political connections for local governments. We find that governments located within the constituencies of, and thus connected to, powerful congressional members reduce their stewardship over public resources. Using plausibly exogenous declines in the power of congressional representation, we show that the effect is causal. To better understand why connected local governments can reduce stewardship, we study electoral characteristics. Our findings suggest that the increased resources that come with powerful congressional representation allow local‐government officials to reduce stewardship without material adverse effects on their reelection prospects. In sum, we provide evidence of a cost of political connections: they weaken local governments’ incentives to act in a socially optimal manner.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/156454/2/joar12325_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/156454/1/joar12325.pd
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