Independence Day?

Two recent and influential papers, van Rooij 2007 and Lassiter 2012, propose solutions to the proviso problem that make central use of related notions of independence—qualitative in the first case, probabilistic in the second. We argue here that, if these solutions are to work, they must incorporate an implicit assumption about presupposition accommodation, namely that accommodation does not interfere with existing qualitative or probabilistic independencies. We show, however, that this assumption is implausible, as updating beliefs with conditional information does not in general preserve independencies. We conclude that the approach taken by van Rooij and Lassiter does not succeed in resolving the proviso problem

Definiteness Projection

We argue that definite noun phrases give rise to uniqueness inferences characterized by a pattern we call definiteness projection. Definiteness projection says that the uniqueness inference of a definite projects out unless there is an indefinite antecedent in a position that filters presuppositions. We argue that definiteness projection poses a serious puzzle for e-type theories of (in)definites; on such theories, indefinites should filter existence presuppositions but not uniqueness presuppositions. We argue that definiteness projection also poses challenges for dynamic approaches, which have trouble generating uniqueness inferences and predicting some filtering behavior, though unlike the challenge for e-type theories, these challenges have mostly been noted in the literature, albeit in a piecemeal way. Our central aim, however, is not to argue for or against a particular view, but rather to formulate and motivate a generalization about definiteness which any adequate theory must account for

Roads to Necessitarianism

We show that each of three natural sets of assumptions about the conditional entails necessitarianism: that anything possible is necessary

Census 2020: The effect of a census undercount in Pierce County

CAUR is partnering with GTCF to provide data for a Census 2020 campaign in Pierce County. The purpose of this campaign is to provide materials and information about the importance of a complete and accurate census count. The research materials provided by CAUR will be used to provide information for a public education video and materials to be distributed to community leaders as they encourage constituents to actively participate in the upcoming 2020 Census. Census data has a wide variety of applications, both public/government and in private industry. CAUR worked closely with GTCF to identify four different use cases for census data that help convey the importance of having a complete and accurate count. These use cases represent aspects of day-to-day life for Pierce County residents that might be changed if the census count is inaccurate. For example, we present details on how bus routes might be altered if are using inaccurate census data, due to significant undercounts, potentially missing entire neighborhoods where bus service would be needed. We also evaluate the difference in federal funding to Pierce County if 10% of residents do not complete their census forms. The examples we use here provide insight into the issues that arise from both inaccurate and incomplete census data. In some of our use cases, we simulate an inaccurate census count in key areas. For example, we simulate the differences of siting a new health clinic if some houses incorrectly report the number of children in their homes. In other cases we examine the repercussions of failing to complete the census entirely. Federal grants are sometimes based on the number of residents in an area, and if the census count does not include all residents, then there is a proportional drop in grant funding. It is important to relay the message that the census is important, and that it should be completed honestly and accurately

The association between neurodegeneration and local complement activation in the thalamus to progressive multiple sclerosis outcome

The extent of grey matter demyelination and neurodegeneration in the progressive multiple sclerosis (PMS) brains at post‐mortem associates with more severe disease. Regional tissue atrophy, especially affecting the cortical and deep grey matter, including the thalamus, is prognostic for poor outcomes. Microglial and complement activation are important in the pathogenesis and contribute to damaging processes that underlie tissue atrophy in PMS. We investigated the extent of pathology and innate immune activation in the thalamus in comparison to cortical grey and white matter in blocks from 21 cases of PMS and 10 matched controls. Using a digital pathology workflow, we show that the thalamus is invariably affected by demyelination and had a far higher proportion of active inflammatory lesions than forebrain cortical tissue blocks from the same cases. Lesions were larger and more frequent in the medial nuclei near the ventricular margin, whilst neuronal loss was greatest in the lateral thalamic nuclei. The extent of thalamic neuron loss was not associated with thalamic demyelination but correlated with the burden of white matter pathology in other forebrain areas (Spearman r = 0.79, p < 0.0001). Only thalamic neuronal loss, and not that seen in other forebrain cortical areas, correlated with disease duration (Spearman r = −0.58, p = 0.009) and age of death (Spearman r = −0.47, p = 0.045). Immunoreactivity for the complement pattern recognition molecule C1q, and products of complement activation (C4d, Bb and C3b) were elevated in thalamic lesions with an active inflammatory pathology. Complement regulatory protein, C1 inhibitor, was unchanged in expression. We conclude that active inflammatory demyelination, neuronal loss and local complement synthesis and activation in the thalamus, are important to the pathological and clinical disease outcomes of PMS

“It’s just another added layer of difficulty”: Language access equity and inclusion in pediatric interpreted medical encounters — Provider and interpreter perspectives

Limited English proficient or language-diverse patients and families in pediatric interpreted medical encounters (IME) are susceptible to health disparities and inequities in the US compared to English proficient patients and families in language-concordant medical encounters. Policies to improve access to language services intend to bridge this gap, yet evidence suggests that significant inequities still exist. This study explores perspectives of interpreters and pediatric critical care medical providers to better understand the complexities of IME in pediatric settings. Qualitative data were analyzed from two interview studies with medical interpreters and providers using thematic coding and inductive analysis. Several factors were identified by both interpreters and medical providers that negatively affected communication, equity, and inclusion. These included systems-level factors (e.g., time constraints and language variety), interpersonal factors (e.g., difficulties with communication and mistrust), and intrapersonal factors (e.g., implicit biases and judgements). These results highlight multiple layers of potential inequities which adversely affect patients and families in pediatric IME.; En los encuentros médicos interpretados (EMI) en pediatría en los EE.UU., las personas y familiares que acuden a una consulta médica con un dominio limitado del inglés o con otras lenguas están expuestas a perjuicios y desigualdades en materia de salud, en comparación con aquellas que dominan el inglés y que asisten a las consultas en su idioma. Las políticas para mejorar el acceso a los servicios lingüísticos pretenden salvar esta brecha, pero los datos indican que siguen dándose desigualdades significativas. Este estudio explora las perspectivas de intérpretes y de proveedores de atención sanitaria crítica pediátrica para comprender mejor las complejidades de los EMI en contextos pediátricos. Se analizan los datos cualitativos procedentes de dos estudios con entrevistas a intérpretes y proveedores de atención sanitaria utilizando codificación temática y análisis inductivo. Los resultados muestran que ambos grupos detectan varios factores que afectan negativamente a la comunicación, la equidad y la inclusión. Estos factores se localizan a nivel sistémico (como son las limitaciones de tiempo y la variedad lingüística), interpersonal (por ejemplo, las dificultades de comunicación y la desconfianza) y a nivel intrapersonal (como son los sesgos implícitos y los prejuicios). Estos resultados ponen de manifiesto las múltiples capas de desigualdades potenciales que perjudican a pacientes y familiares en los EMI en pediatría.; En les trobades mèdiques interpretades (EMI) en pediatria als EUA, les persones i familiars que acudeixen a una consulta mèdica amb un domini limitat de l'anglés o amb llengües diferents a aquesta s’exposen a perjudicis i desigualtats en matèria de salut, en comparació amb les que dominen l'anglès i que assisteixen a les consultes en el seu idioma. Les polítiques per millorar l'accés als serveis lingüístics pretenen salvar aquesta escletxa, però les dades indiquen que continuen donant-se desigualtats significatives. Aquest estudi explora les perspectives d’intèrprets i de proveïdors d’atenció sanitària crítica en pediatria per comprendre millor les complexitats de les EMI en contextos pediàtrics. S’analitzen les dades qualitatives procedents de dos estudis amb entrevistes a intèrprets i proveïdors d’atenció sanitària utilitzant una codificació temàtica i una anàlisi inductiva. Els resultats mostren que tots dos grups detecten diversos factors que afecten negativament la comunicació, l'equitat i la inclusió. Aquests factors es localitzen a nivell sistèmic (com són les limitacions de temps i la varietat lingüística), interpersonal (per exemple, les dificultats de comunicació i la desconfiança) i a nivell intrapersonal (com ara els biaixos implícits i els prejudicis). Aquests resultats palesen les múltiples capes de desigualtats potencials que perjudiquen pacients i familiars als EMI en pediatria

Sustaining remission of psychotic depression: rationale, design and methodology of STOP-PD II

BACKGROUND: Psychotic depression (PD) is a severe disabling disorder with considerable morbidity and mortality. Electroconvulsive therapy and pharmacotherapy are each efficacious in the treatment of PD. Expert guidelines recommend the combination of antidepressant and antipsychotic medications in the acute pharmacologic treatment of PD. However, little is known about the continuation treatment of PD. Of particular concern, it is not known whether antipsychotic medication needs to be continued once an episode of PD responds to pharmacotherapy. This issue has profound clinical importance. On the one hand, the unnecessary continuation of antipsychotic medication exposes a patient to adverse effects, such as weight gain and metabolic disturbance. On the other hand, premature discontinuation of antipsychotic medication has the potential risk of early relapse of a severe disorder. METHODS/DESIGN: The primary goal of this multicenter randomized placebo-controlled trial is to assess the risks and benefits of continuing antipsychotic medication in persons with PD once the episode of depression has responded to treatment with an antidepressant and an antipsychotic. Secondary goals are to examine age and genetic polymorphisms as predictors or moderators of treatment variability, potentially leading to more personalized treatment of PD. Individuals aged 18-85 years with unipolar psychotic depression receive up to 12 weeks of open-label treatment with sertraline and olanzapine. Participants who achieve remission of psychosis and remission/near-remission of depressive symptoms continue with 8 weeks of open-label treatment to ensure stability of remission. Participants with stability of remission are then randomized to 36 weeks of double-blind treatment with either sertraline and olanzapine or sertraline and placebo. Relapse is the primary outcome. Metabolic changes are a secondary outcome. DISCUSSION: This trial will provide clinicians with much-needed evidence to guide the continuation and maintenance treatment of one of the most disabling and lethal of psychiatric disorders. TRIAL REGISTRATION AND URL: NCT: NCT01427608

Effect of Continuing Olanzapine vs Placebo on Relapse Among Patients With Psychotic Depression in Remission: The STOP-PD II Randomized Clinical Trial

Importance: Psychotic depression is a severely disabling and potentially lethal disorder. Little is known about the efficacy and tolerability of continuing antipsychotic medication for patients with psychotic depression in remission. Objective: To determine the clinical effects of continuing antipsychotic medication once an episode of psychotic depression has responded to combination treatment with an antidepressant and antipsychotic agent. Design, Setting, and Participants: Thirty-six week randomized clinical trial conducted at 4 academic medical centers. Patients aged 18 years or older had an episode of psychotic depression acutely treated with sertraline plus olanzapine for up to 12 weeks and met criteria for remission of psychosis and remission or near-remission of depressive symptoms for 8 weeks before entering the clinical trial. The study was conducted from November 2011 to June 2017, and the final date of follow-up was June 13, 2017. Interventions: Participants were randomized either to continue olanzapine (n = 64) or switch from olanzapine to placebo (n = 62). All participants continued sertraline. Main Outcomes and Measures: The primary outcome was risk of relapse. Main secondary outcomes were change in weight, waist circumference, lipids, serum glucose, and hemoglobin A1c (HbA1c). Results: Among 126 participants who were randomized (mean [SD] age, 55.3 years [14.9 years]; 78 women [61.9%]), 114 (90.5%) completed the trial. At the time of randomization, the median dosage of sertraline was 150 mg/d (interquartile range [IQR], 150-200 mg/d) and the median dosage of olanzapine was 15 mg/d (IQR, 10-20 mg/d). Thirteen participants (20.3%) randomized to olanzapine and 34 (54.8%) to placebo experienced a relapse (hazard ratio, 0.25; 95% CI, 0.13 to 0.48; P \u3c .001). The effect of olanzapine on the daily rate of anthropometric and metabolic measures significantly differed from placebo for weight (0.13 lb; 95% CI, 0.11 to 0.15), waist circumference (0.009 inches; 95% CI, 0.004 to 0.014), and total cholesterol (0.29 mg/dL; 95% CI, 0.13 to 0.45) but was not significantly different for low-density lipoprotein cholesterol (0.04 mg/dL; 95% CI, -0.01 to 0.10), high-density lipoprotein cholesterol (-0.01 mg/dL; 95% CI, -0.03 to 0.01), triglyceride (-0.153 mg/dL; 95% CI, -0.306 to 0.004), glucose (-0.02 mg/dL; 95% CI, -0.12 to 0.08), or HbA1c levels (-0.0002 mg/dL; 95% CI, -0.0021 to 0.0016). Conclusions and Relevance: Among patients with psychotic depression in remission, continuing sertraline plus olanzapine compared with sertraline plus placebo reduced the risk of relapse over 36 weeks. This benefit needs to be balanced against potential adverse effects of olanzapine, including weight gain. Trial Registration: ClinicalTrials.gov Identifier: NCT01427608

Resting state functional connectivity in patients with remitted psychotic depression: A multi-centre STOP-PD study

BACKGROUND: There is paucity of neurobiological knowledge about major depressive disorder with psychotic features ( psychotic depression ). This study addresses this knowledge gap by using resting state functional magnetic resonance imaging (R-fMRI) to compare functional connectivity in patients with psychotic depression and healthy controls. METHODS: We scanned patients who participated in a randomized controlled trial as well as healthy controls. All patients achieved remission from depressive and psychotic symptoms with sertraline and olanzapine. We employed Independent Component Analysis in independent samples to isolate the default mode network (DMN) and compared patients and controls. FINDINGS: The Toronto sample included 28 patients (mean [SD], age 56.2 [13.7]) and 39 controls (age 55.1 [13.5]). The Replication sample included 29 patients (age 56.1 [17.7]) and 36 controls (age 48.3 [17.9]). Patients in the Toronto sample demonstrated decreased between-network functional connectivity between the DMN and bilateral insular, somatosensory/motor, and auditory cortices with peak activity in the right planum polare (t=4.831; p=0.001, Family Wise Error (FWE) corrected). A similar pattern of between-network functional connectivity was present in our Replication sample with peak activity in the right precentral gyrus (t=4.144; p=0.003, FWE corrected). INTERPRETATION: Remission from psychotic depression is consistently associated with an absence of increased DMN-related functional connectivity and presence of decreased between-network functional connectivity. Future research will evaluate this abnormal DMN-related functional connectivity as a potential biomarker for treatment trajectories. FUNDING: National Institute of Mental Health