Publications by authors named "PM Grant"

Background And Hypothesis: In accordance with the Cognitive Model of Negative Symptoms, defeatist performance beliefs (DPBs) are an important psychosocial mechanism of negative symptoms in schizophrenia-spectrum groups. DPBs are also mediators of negative symptom improvement in clinical trials. Despite the clinical significance of DPBs and their inclusion as a mechanism of change measure in clinical trials, the psychometric properties of the DPB scale have not been examined in any schizophrenia-spectrum group.

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Article Synopsis
  • The study investigates the Cognitive Model of Negative Symptoms, focusing on how defeatist performance beliefs (DPB) influence negative symptoms in individuals with schizophrenia compared to healthy controls.
  • Researchers utilized ecological momentary assessment (EMA) over six days with 52 outpatients with schizophrenia and 55 healthy individuals to assess daily experiences.
  • Findings revealed that those with schizophrenia had higher DPB and that these beliefs were directly linked to escalations in negative symptoms like anhedonia and avolition, supporting the model's implications for treatments like Cognitive Behavioral Therapy.
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  • Dolutegravir (DTG) is a highly effective medication in HIV treatment, but there's limited data on the risk of drug-resistance mutations arising in patients taking it.
  • A review of 2131 studies showed that in various patient scenarios, the prevalence of drug-resistance mutations was generally low, particularly in trials involving experienced patients or those on monotherapy.
  • To better understand drug-resistance risks, more innovative methods need to be applied in real-world studies, as trial data may not fully represent broader patient experiences.
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The genus Thraulus is widespread throughout much of the Eastern Hemisphere. Since Eaton established Thraulus in 1881, 62 species have, at one time or another, been placed in this genus. Thirty-eight of those species were eventually moved to other genera.

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Background: Hepatitis C virus (HCV) genotype 4 is the predominant type of HCV found in sub-Saharan Africa. Various genotype 4 subtypes, such as 4r, frequently have resistance-associated substitutions that can increase rates of treatment failure with common direct-acting antiviral regimens. In-vitro studies suggest that the NS5A inhibitor velpatasvir is effective against viral isolates containing such resistance-associated substitutions, but its clinical efficacy against genotype 4 non-a/d subtypes in sub-Saharan Africa remains to be confirmed.

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Background: Hepatitis C virus (HCV) genotype 4 non-a/d subtypes, which frequently have NS5A resistance-associated substitutions, are highly prevalent in sub-Saharan Africa. These subtypes, particularly genotype 4r, have been associated with higher rates of failure of treatment regimens containing the NS5A inhibitors ledipasvir or daclatasvir, which are the most accessible direct-acting antivirals in low-income countries. Clinical evidence regarding the efficacy of re-treatment options for these subtypes is limited.

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  • Fostemsavir is an FDA-approved HIV-1 attachment inhibitor that prevents the virus from attaching to host cells by targeting the gp120 protein.
  • Fostemsavir is effective and well-tolerated, showing virologic suppression in many patients with multidrug-resistant HIV-1 when used alongside other therapies.
  • The drug's unique mechanism and lack of cross-resistance make it a significant option for patients who have exhausted other treatment avenues, indicating potential for broader use in the future.
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Chronic inflammation is thought to be a major cause of morbidity and mortality in aging, but whether similar mechanisms underlie dysfunction in infection-associated chronic inflammation is unclear. Here, we profiled the immune proteome, and cellular composition and signaling states in a cohort of aging individuals versus a set of HIV patients on long-term antiretroviral therapy therapy or hepatitis C virus (HCV) patients before and after sofosbuvir treatment. We found shared alterations in aging-associated and infection-associated chronic inflammation including T cell memory inflation, up-regulation of intracellular signaling pathways of inflammation, and diminished sensitivity to cytokines in lymphocytes and myeloid cells.

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In sub-Saharan Africa, there exist distinct HCV genotype (GT) subtypes harbouring resistance-associated substitutions to commonly used non-structural protein 5A (NS5A) inhibitor-based direct-acting antiviral (DAA) regimens. In particular, GT4r subtype has demonstrated high rates of treatment failure. In the absence of routine viral sequencing in sub-Saharan Africa, it is important to identify sociodemographic, epidemiologic, and clinical characteristics that may be associated with GT4r infection.

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BACKGROUNDElevated levels of inflammatory cytokines have been associated with poor outcomes among COVID-19 patients. It is unknown, however, how these levels compare with those observed in critically ill patients with acute respiratory distress syndrome (ARDS) or sepsis due to other causes.METHODSWe used a Luminex assay to determine expression of 76 cytokines from plasma of hospitalized COVID-19 patients and banked plasma samples from ARDS and sepsis patients.

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Natural killer (NK) cells are the predominant antiviral cells of the innate immune system, and may play an important role in acquisition and disease progression of HIV. While untreated HIV infection is associated with distinct alterations in the peripheral blood NK cell repertoire, less is known about how NK phenotype is altered in the setting of long-term viral suppression with antiretroviral therapy (ART), as well as how NK memory can impact functional responses. As such, we sought to identify changes in NK cell phenotype and function using high-dimensional mass cytometry to simultaneously analyze both surface and functional marker expression of peripheral blood NK cells in a cohort of ART-suppressed, HIV+ patients and HIV- healthy controls.

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Objective(s): The aim of this study was to develop and evaluate the activity of bispecific antibodies (bsAbs) to enhance natural killer (NK) cell antibody-dependent cellular cytotoxicity (ADCC) against HIV-infected cells.

Design: These bsAbs are based on patient-derived antibodies targeting the conserved gp41 stump of HIV Env, and also incorporate a high-affinity single chain variable fragment (scFv) targeting the activating receptor CD16 on NK cells. Overall, we expect the bsAbs to provide increased affinity and avidity over their corresponding mAbs, allowing for improved ADCC activity against Env-expressing target cells.

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Background: Characterizing the mutations selected by the integrase strand transfer inhibitor (INSTI) dolutegravir and their effects on susceptibility is essential for identifying viruses less likely to respond to dolutegravir therapy and for monitoring persons with virological failure (VF) on dolutegravir therapy.

Methods: We systematically reviewed dolutegravir resistance studies to identify mutations emerging under dolutegravir selection pressure, the effect of INSTI resistance mutations on in vitro dolutegravir susceptibility, and the virological efficacy of dolutegravir in antiretroviral-experienced persons.

Results And Conclusions: We analysed 14 studies describing 84 in vitro passage experiments, 26 studies describing 63 persons developing VF plus INSTI resistance mutations on a dolutegravir-containing regimen, 41 studies describing dolutegravir susceptibility results, and 22 clinical trials and 16 cohort studies of dolutegravir-containing regimens.

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Aim: Few interventions address social cognition or functioning in individuals at clinical risk (CR) for psychosis. Theatre Improvisation Training to Promote Social Cognition (TIPS) is a manualized intervention based on drama therapy. We aim to describe TIPS, evaluate feasibility and acceptability, and present a preliminary investigation of outcomes in a quasi-experimental design.

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Background: Limited treatment data are available for hepatitis C virus (HCV) in sub-Saharan Africa, especially for genotype 4. Our objective was to establish the safety and efficacy of ledipasvir-sofosbuvir for chronic HCV genotype 1 or 4 infection in adults in Rwanda.

Methods: We did a single-arm trial to evaluate the safety and efficacy of ledipasvir-sofosbuvir in Rwandan adults with chronic HCV infection at a single study site (Rwanda Military Hospital, Kigali, Rwanda).

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Background And Aim: Non-alcoholic fatty liver disease (NAFLD) is common among HIV-infected (HIV+) adults. The Liver Fat Score (LFS) is a non-invasive, rapid, inexpensive diagnostic tool that uses routine clinical data and is validated against biopsy in HIV-uninfected (HIV-) persons. CT liver-to-spleen (L/S) attenuation ratio is another validated method to diagnose NAFLD.

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Nuclear fusion experiments performed at the National Ignition Facility produce radioactive debris, arising in reactions of fast neutrons with the target assembly. We have found that postshot debris collections are fractionated, such that isotope ratios in an individual debris sample may not be representative of the radionuclide inventory produced by the experiment. We discuss the potential sources of this fractionation and apply isotope-correlation techniques to calculate unfractionated isotope ratios that are used in measurements of nuclear reaction cross sections.

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A large area solid radiochemistry collector was deployed at the National Ignition Facility (NIF) with a collection efficiency for post-shot, solid target debris of approximately 1% of the total 4π solid angle. The collector consisted of a 20-cm diameter vanadium foil surrounded by an aluminum side-enclosure and was fielded 50 cm from the NIF target. The collector was used on two NIF neutron yield shots, both of which had a monolayer of U embedded in the capsule ablator 10 m from the inner surface.

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HIV-infected men have increased rates of osteoporosis and fracture compared to HIV-uninfected men. Testosterone use among HIV-infected men is common. In HIV-uninfected men, testosterone increases bone mineral density (BMD), but its effects have not been evaluated in HIV-infected men.

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Cognitive impairments and negative symptoms in schizophrenia are associated with poorer outcomes and are typically resistant to pharmacological interventions. However, these features can vary dramatically in their level of expression, and they can improve as a function of external context (by providing performance-contingent incentives and a more stimulating environment) and internal context (by challenging defeatist performance beliefs and by reducing stress and improving physical health). This Open Forum briefly reviews some of this evidence for the situational variability of cognitive impairments and negative symptoms in schizophrenia and highlights psychosocial treatments that capitalize on this variability.

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A requisite step for testing cognitive theories regarding the role of self-concept in schizophrenia is the development of measures that follow a cognitive conceptualization and better capture the multifaceted nature of this construct. The purpose of this study was to examine the psychometric properties a new self-concept measure, the Beck Self-Esteem Scale-Short Form (BSES-SF), based on a sample of 204 individuals with schizophrenia or schizoaffective disorder. We evaluated the BSES-SF's dimensionality, internal consistency reliability, and construct and divergent validity using confirmatory factor analysis, Cronbach's alpha, Pearson correlations, independent samples t-tests, and one-way analysis of variance.

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Theorists, clinicians, and investigators have attempted to find a common source for the negative and positive symptoms of schizophrenia. We propose that a unified theory, based on a common cognitive structure not only has explanatory value, but can serve as a framework for a psychotherapeutic intervention. Specifically, we propose that the cognitive triad - the negative view of the self, others, and the future - is the source of the content for the negative and positive symptoms.

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Introduction: HIV-1 genotypic resistance test (GRT) interpretation systems (IS) require updates as new studies on HIV-1 drug resistance are published and as treatment guidelines evolve.

Methods: An expert panel was created to provide recommendations for the update of the Stanford HIV Drug Resistance Database (HIVDB) GRT-IS. The panel was polled on the ARVs to be included in a GRT report, and the drug-resistance interpretations associated with 160 drug-resistance mutation (DRM) pattern-ARV combinations.

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