The evolving maintenance of certification process: update on the financial status of the medical boards

Medical board organizations have accumulated large asset balances, in part due to the monetization of physician board recertification, as well as capital gains in positive investment conditions. Physicians across the country have raised concerns regarding the effectiveness and efficiency of existing recertification processes, to which the American Board of Medical Specialties and independent accreditation boards have responded with newly instituted changes. The present article analyzes the publicly available F990 tax forms of the medical boards in an effort to provide data to the ongoing debate. Although some boards have begun to mobilize assets in recent years, many continue to accumulate wealth. It remains to be seen whether the new recertification programs will bring about change or perpetuate organizational wealth

Different paths to the modern state in Europe: the interaction between domestic political economy and interstate competition

Theoretical work on state formation and capacity has focused mostly on early modern Europe and on the experience of western European states during this period. While a number of European states monopolized domestic tax collection and achieved gains in state capacity during the early modern era, for others revenues stagnated or even declined, and these variations motivated alternative hypotheses for determinants of fiscal and state capacity. In this study we test the basic hypotheses in the existing literature making use of the large date set we have compiled for all of the leading states across the continent. We find strong empirical support for two prevailing threads in the literature, arguing respectively that interstate wars and changes in economic structure towards an urbanized economy had positive fiscal impact. Regarding the main point of contention in the theoretical literature, whether it was representative or authoritarian political regimes that facilitated the gains in fiscal capacity, we do not find conclusive evidence that one performed better than the other. Instead, the empirical evidence we have gathered lends supports to the hypothesis that when under pressure of war, the fiscal performance of representative regimes was better in the more urbanized-commercial economies and the fiscal performance of authoritarian regimes was better in rural-agrarian economie

In Vitro Downregulation of Matrix Metalloproteinase-9 in Rat Glial Cells by CCR5 Antagonist Maraviroc: Therapeutic Implication for HIV Brain Infection

BACKGROUND: Matrix metalloproteinases (MMPs) released by glial cells are important mediators of neuroinflammation and neurologic damage in HIV infection. The use of antiretroviral drugs able to combat the detrimental effect of chronic inflammation and target the exaggerated MMP activity might represent an attractive therapeutic challenge. Recent studies suggest that CCR5 antagonist maraviroc (MVC) exerts immunomodulant and anti-inflammatory activity beyond its anti-HIV properties. We investigated the in vitro effect of MVC on the activity of MMPs in astrocyte and microglia cultures. METHODOLOGY/PRINCIPAL FINDINGS: Primary cultures of rat astrocytes and microglia were activated by exposure to phorbol myristate acetate (PMA) or lypopolysaccharide (LPS) and treated in vitro with MVC. Culture supernatants were subjected to gelatin zymography and quantitative determination of MMP-9 and MMP-2 was done by computerized scanning densitometry. MMP-9 levels were significantly elevated in culture supernatants from both LPS- and PMA-activated astrocytes and microglia in comparison to controls. The treatment with MVC significantly inhibited in a dose-dependent manner the levels and expression of MMP-9 in PMA-activated astrocytes (p<0,05) and, to a lesser extent, in PMA-activated microglia. By contrast, levels of MMP-2 did not significantly change, although a tendency to decrease was seen in PMA-activated astrocytes after treatment with MVC. The inhibition of levels and expression of MMP-9 in PMA-activated glial cells did not depend on cytotoxic effects of MVC. No inhibition of MMP-9 and MMP-2 were found in both LPS-activated astrocytes and microglia. CONCLUSIONS: The present in vitro study suggests that CCR5 antagonist compounds, through their ability to inhibit MMP-9 expression and levels, might have a great potential for the treatment of HIV-associated neurologic damage

Attempting to stop antipsychotic medication: success, supports, and efforts to cope

Purpose To explore supports and coping strategies used during attempts to discontinue antipsychotic medication and test for associations with success. Method 144 people who were taking or had taken antipsychotics completed The Experiences of Antipsychotic Medication Survey. Among them, 105 people had made at least one discontinuation attempt and answered a series of questions about their most recent attempt to stop. Content analysis and Chi-square tests of independence were used to categorise the data and explore associations. Success was defined as stopping all AM use irrespective of the duration of the medication-free period or whether relapse occurred, which were explored separately. Results Among the 105 people who had attempted discontinuation, 61.9% described unwanted withdrawal effects and 27.6% of the group described psychotic or manic relapse during the withdrawal period. Within this group 55% described successfully stopping all AM for varying lengths of time, half reported no current use, and half described having some form of professional, family, friend, and/or service user or peer support for their attempt. Having support was positively associated with success and negatively associated with both current use, and relapse during withdrawal. A range of coping efforts were described, but having coping strategies failed to show significant associations with any of the dependent variables explored. Among those who described successfully stopping, some described returning to AM for short periods when needed, while others reported managing well with alternative methods alone. Conclusions Findings cannot be readily generalised due to sampling constraints, but results suggest a wide range of supports and coping strategies may be used when attempting to discontinue antipsychotics. Many people may attempt to discontinue antipsychotics without any support. Those who have support for their attempts may be significantly less likely to relapse during withdrawal and more likely to succeed in their attempt. There is a pressing need for further research in this area

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Analysis of shared heritability in common disorders of the brain

ience, this issue p. eaap8757 Structured Abstract INTRODUCTION Brain disorders may exhibit shared symptoms and substantial epidemiological comorbidity, inciting debate about their etiologic overlap. However, detailed study of phenotypes with different ages of onset, severity, and presentation poses a considerable challenge. Recently developed heritability methods allow us to accurately measure correlation of genome-wide common variant risk between two phenotypes from pools of different individuals and assess how connected they, or at least their genetic risks, are on the genomic level. We used genome-wide association data for 265,218 patients and 784,643 control participants, as well as 17 phenotypes from a total of 1,191,588 individuals, to quantify the degree of overlap for genetic risk factors of 25 common brain disorders. RATIONALE Over the past century, the classification of brain disorders has evolved to reflect the medical and scientific communities' assessments of the presumed root causes of clinical phenomena such as behavioral change, loss of motor function, or alterations of consciousness. Directly observable phenomena (such as the presence of emboli, protein tangles, or unusual electrical activity patterns) generally define and separate neurological disorders from psychiatric disorders. Understanding the genetic underpinnings and categorical distinctions for brain disorders and related phenotypes may inform the search for their biological mechanisms. RESULTS Common variant risk for psychiatric disorders was shown to correlate significantly, especially among attention deficit hyperactivity disorder (ADHD), bipolar disorder, major depressive disorder (MDD), and schizophrenia. By contrast, neurological disorders appear more distinct from one another and from the psychiatric disorders, except for migraine, which was significantly correlated to ADHD, MDD, and Tourette syndrome. We demonstrate that, in the general population, the personality trait neuroticism is significantly correlated with almost every psychiatric disorder and migraine. We also identify significant genetic sharing between disorders and early life cognitive measures (e.g., years of education and college attainment) in the general population, demonstrating positive correlation with several psychiatric disorders (e.g., anorexia nervosa and bipolar disorder) and negative correlation with several neurological phenotypes (e.g., Alzheimer's disease and ischemic stroke), even though the latter are considered to result from specific processes that occur later in life. Extensive simulations were also performed to inform how statistical power, diagnostic misclassification, and phenotypic heterogeneity influence genetic correlations. CONCLUSION The high degree of genetic correlation among many of the psychiatric disorders adds further evidence that their current clinical boundaries do not reflect distinct underlying pathogenic processes, at least on the genetic level. This suggests a deeply interconnected nature for psychiatric disorders, in contrast to neurological disorders, and underscores the need to refine psychiatric diagnostics. Genetically informed analyses may provide important "scaffolding" to support such restructuring of psychiatric nosology, which likely requires incorporating many levels of information. By contrast, we find limited evidence for widespread common genetic risk sharing among neurological disorders or across neurological and psychiatric disorders. We show that both psychiatric and neurological disorders have robust correlations with cognitive and personality measures. Further study is needed to evaluate whether overlapping genetic contributions to psychiatric pathology may influence treatment choices. Ultimately, such developments may pave the way toward reduced heterogeneity and improved diagnosis and treatment of psychiatric disorders

Maintenance of certification and the financial status of the medical boards

Abstract Background: The Maintenance of Certification (MOC) program proposed by the American Board of Medical Specialties (ABMS) gained approval in 2006. The implementation of this program will impact all physicians who are board certified. Therefore, The Financial Status of the Medical Boards is an increasingly relevant topic of discussion amongst all physicians and those interested in medical education and certification. With this study we aim to bring greater attention to the already publicly available financial status of the Medical Boards (MB) so that it can become part of the ongoing discussion of MOC.Method: We analyzed the yearly revenue, expenses, net gain or loss and end of year balance for the ABMS and its 24 MB, additional member boards, as well as the Accreditation Council for Graduate Medical Education (ACGME), American Osteopathic Association (AOA) and Accreditation Council for Continuing Medical Education (ACCME) organizations.Results: We have commented on notable trends based on the available IRS Form 990s spanning from 1997 to 2012. When comparing the most recently available reported end of year balance to the first available reported end of year balance, 87% (27/31) of the member boards have reported an increase. All three of the additional organizations studied, ACGME, AOA and ACCME reported an increase as well.Conclusions: It is clear from the data and analysis that the majority of MB have financially benefited from the MOC program. It remains to be proven whether or not this economic benefit will translate into an improvement in physician education and patient care

Pemphigus foliaceus exacerbated by radiation, in association with myasthenia gravis

Pemphigus foliaceus (PF) is a sporadic autoimmune blistering disease of unknown etiology. The production of immunoglobulin G4 antibodies against desmoglein-1 is responsible for the clinical manifestation of PF. We present a case of a woman with a recent diagnosis of myasthenia gravis (MG), who was also recently treated with radiation therapy for breast cancer. The clinical exam, supported by biopsy and direct immunofluorescence, were consistent with PF. We present this case to increase the awareness of the potential exacerbation or induction of PF with radiation, and of the association of PF and myasthenia gravis. Only five prior cases of radiation-exacerbated or radiation-induced PF have been reported in the literature to date. Furthermore, the co-existence of the autoimmune entities of myasthenia gravis and PF has been reported in the literature in only 9 cases and was also noted in this patient