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Significant developments in schizophrenia psychopathology are ready to be incorporated into clinical practice. These advances allow a way forward through the well-described challenges experienced with current diagnostic and psychopathological frameworks. This article discusses approaches that will enable clinicians to access a wider and richer spectrum of patient experience; describes process-based models of schizophrenia in the domains of both the brain and the mind; and considers how different levels of analysis might be linked via the predictive processing framework. Multiple levels of analysis provide different targets for varying modalities of treatment – dopamine blockade at the molecular level, psychological therapy at the level of the mind, and social interventions at the personal level. Psychiatry needs to align itself closer to neuroscientific research. It should move from a symptom-based understanding to a model based on process. That is – after having asked about a patient's symptoms and experience clinicians need to introduce steps involving a consideration of what might be the brain and mind processes underlying the experience.
Choice of antibiotic should be dictated by spectrum of activity, tissue penetration, potency and cost, and local patterns of infection. While advising prescribers to check with their local microbiologist or use their smartphone formulary app, the author describes the most common infectious disease presentations, and the first- and second-line antibiotic therapy based on national guidelines.
OBJECTIVES/GOALS: African-Americans have a 3-fold higher risk of end-stage kidney disease (ESKD) compared to Whites due in part to APOL1 risk alleles. Whether resistant hypertension (RH) magnifies the risk of ESKD among African Americans beyond APOL1 is not known. We examined the interaction between RH and race on ESKD risk and the independent effect of RH beyond APOL1. METHODS/STUDY POPULATION: We designed a retrospective cohort of 240,038 veterans with HTN, enrolled in the Million Veteran Program with an estimated glomerular filtration rate (eGFR) >30 ml/min/1.73m2. The primary exposure was incident RH (time-varying). The primary outcome was incident ESKD during a 13.5 year follow up: 2004-2017. Secondary outcomes were myocardial infarction (MI), stroke, and death. Incident RH was defined as failure to achieve outpatient blood pressure (BP) <140/90 mmHg with 3 antihypertensive drugs, including a thiazide, or use of 4 or more drugs. Poisson models were used to estimate incidence rates and test additive interaction with race and APOL1 genotype. Multivariable Cox models (with Fine-Gray competing-risks models as sensitivity analyses) were used to examine independent effects. RESULTS/ANTICIPATED RESULTS: The cohort comprised 235,046 veterans; median age was 60 years; 21% were African-American and 6% were women, with 23,010 incident RH cases observed over a median follow-up time of 10.2 years [interquartile range, 5.6-12.6]. Patients with RH had higher incidence rates [per 1000 person-years] of ESKD (4.5 vs. 1.3), myocardial infarction (6.5 vs. 3.0), stroke (16.4 vs. 7.6) and death (12.0 vs. 6.9) than non-resistant hypertension (NRH). African-Americans with RH had a 2.6-fold higher risk of ESKD compared to African-Americans with NRH; 3-fold the risk of Whites with RH, and 9.6-fold the risk of Whites with NRH [p-interaction<.001]. Among African-Americans, RH was associated with a 2.2-fold (95%CI, 1.86-2.58) higher risk of incident ESKD in models adjusted for APOL1 genotype and in the subset of African-Americans with no APOL1 risk alleles, RH was associated with an adjusted 2.75-fold (95% CI: 2.00-3.50) higher risk of incident ESKD. DISCUSSION/SIGNIFICANCE OF IMPACT: RH was independently associated with a higher risk of ESKD and cardiovascular outcomes, especially among African-Americans. This elevated risk is independent of APOL1 genotype. Interventions that achieve BP targets among patients with RH could curtail the incidence of ESKD and cardiovascular outcomes in this high-risk population. CONFLICT OF INTEREST DESCRIPTION: None.
Early modern European warfare features prominently in several important discussions of early modern violence, notably the debate on the Military Revolution and its variants, as well as forming part of the standard narrative of state formation and the emergence of an international order based on sovereign states. While the dominant trend was towards establishing the state as a monopoly of legitimate violence, the patterns and practices of European warfare remained diverse, as were the ways in which they interacted with state and ‘international’ structures. The creation of permanent forces was slow and uneven, while their implications varied depending on whether they were navies or armies. This chapter contests conventional conceptual models, such as that of ‘limited war’ waged by allegedly disinterested ‘mercenaries’. It argues that efforts to impose tighter discipline arose from multiple political, cultural, social and religious impulses, and varied in effectiveness. War was certainly not limited in terms of its capacity for violence and destruction, but it nonetheless remained broadly within established Christian concepts of ‘just war’ directed by a ‘proper authority’ for legitimate ends. The risks inherent in military operations were an additional constraining factor, despite this period becoming known as an ‘age of battles’.
This is the second volume of A Social and Economic History of the Theatre to 300 BC and focuses exclusively on theatre culture in Attica (Rural Dionysia) and the rest of the Greek world. It presents and discusses in detail all the documentary and material evidence for theatre culture and dramatic production from the first two centuries of theatre history, namely the period c.500 to c.300 BC. The traditional assumption is laid to rest that theatre was an exclusively or primarily Athenian institution, with the inclusion of all sources of information for theatrical performances in twenty-two deme sites and over one hundred and twenty independent Greek (and some non-Greek) cities. All texts are translated and made accessible to non-specialists and specialists alike. The volume will be a fundamental work of reference for all classicists and theatre historians interested in ancient theatre and its wider historical contexts.