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Objectives. To describe and control an outbreak of HIV infection among people who inject drugs (PWID).Methods. The investigation included people diagnosed with HIV infection during 2015 to 2018 linked to 2 cities in northeastern Massachusetts epidemiologically or through molecular analysis. Field activities included qualitative interviews regarding service availability and HIV risk behaviors.Results. We identified 129 people meeting the case definition; 116 (90%) reported injection drug use. Molecular surveillance added 36 cases to the outbreak not otherwise linked. The 2 largest molecular groups contained 56 and 23 cases. Most interviewed PWID were homeless. Control measures, including enhanced field epidemiology, syringe services programming, and community outreach, resulted in a significant decline in new HIV diagnoses.Conclusions. We illustrate difficulties with identification and characterization of an outbreak of HIV infection among a population of PWID and the value of an intensive response.Public Health Implications. Responding to and preventing outbreaks requires ongoing surveillance, with timely detection of increases in HIV diagnoses, community partnerships, and coordinated services, all critical to achieving the goal of the national Ending the HIV Epidemic initiative.
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Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Transtornos Relacionados ao Uso de Opioides/epidemiologia , Prática de Saúde Pública , Abuso de Substâncias por Via Intravenosa/epidemiologia , Adolescente , Adulto , Participação da Comunidade , Feminino , Genótipo , Infecções por HIV/diagnóstico , Infecções por HIV/etiologia , Acessibilidade aos Serviços de Saúde , Pessoas Mal Alojadas/estatística & dados numéricos , Humanos , Masculino , Massachusetts/epidemiologia , Pessoa de Meia-Idade , Programas de Troca de Agulhas/organização & administração , Reação em Cadeia da Polimerase , Grupos Raciais , População Urbana/estatística & dados numéricos , Adulto Jovem , Produtos do Gene pol do Vírus da Imunodeficiência Humana/genéticaRESUMO
Major depressive disorder and bipolar disorder share symptoms that may reflect core mood disorder features. This has led to the pursuit of intermediate phenotypes and a dimensional approach to understand neurobiological disruptions in mood disorders. Executive dysfunction, including cognitive control, may represent a promising intermediate phenotype across major depressive disorder and bipolar disorder. This study examined dimensions of cognitive control in women with major depressive disorder or bipolar disorder in comparison to healthy control subjects using two separate, consecutive experiments. For Experiment 1, participants completed a behavioural cognitive control task (healthy controls = 150, major depressive disorder = 260, bipolar disorder = 202; age range 17-84 years). A sample of those participants (healthy controls = 17, major depressive disorder = 19, and bipolar disorder = 16) completed a similar cognitive control task in an event-related design functional magnetic resonance imaging protocol for Experiment 2. Results for Experiment 1 showed greater impairments on the cognitive control task in patients with mood disorders relative to healthy controls (P < 0.001), with more of those in the mood disorder group falling into the 'impaired' range when using clinical cut-offs (<5th percentile). Experiment 2 revealed only a few areas of shared activation differences in mood disorder greater than healthy controls. Activation analyses using performance as a regressor, irrespective of diagnosis, revealed within and extra-network areas that were more active in poor performers. In summary, performance and activation during cognitive control tasks may represent an intermediate phenotype for mood disorders. However, cognitive control dysfunction is not uniform across women with mood disorders, and activation is linked to performance more so than disease. These findings support subtype and dimensional approaches to understanding risk and expression of mood disorders and are a promising area of inquiry, in line with the Research Domain Criteria initiative of NIMH.
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Transtorno Bipolar/fisiopatologia , Encéfalo/patologia , Transtornos Cognitivos/fisiopatologia , Cognição/fisiologia , Transtorno Depressivo Maior/fisiopatologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Transtorno Bipolar/diagnóstico , Encéfalo/fisiopatologia , Transtornos Cognitivos/diagnóstico , Transtorno Depressivo Maior/diagnóstico , Manual Diagnóstico e Estatístico de Transtornos Mentais , Feminino , Humanos , Pessoa de Meia-Idade , Testes Neuropsicológicos , Adulto JovemRESUMO
OBJECTIVES: Specific demographic and illness characteristics have been identified as predictors of overall morbidity and treatment course among individuals with bipolar disorder. However, the role of specific cognitive limitations on disease severity and treatment response is unclear. The present study evaluated whether impulsiveness during acute mania was a significant predictor of achieving euthymia within one year following psychiatric hospitalization. METHODS: Participants were 94 adult inpatients (60 manic) with bipolar I disorder. Baseline symptom severity was assessed using the Young Mania Rating Scale and the Montgomery-Åsberg Depression Rating Scale. Impulsivity was measured with the Stop Signal Task, Degraded Stimulus Continuous Performance Task, Delayed Response Task, and Barratt Impulsiveness Scale-11. RESULTS: Individual predictors of time to reach euthymia included fewer depressive symptoms and better impulse control at baseline, later age at illness onset, shorter illness duration, and the absence of comorbid attention-deficit hyperactivity disorder. Self-reported impulsivity was a significant independent predictor of time to euthymia, even after accounting for relevant clinical variables. CONCLUSIONS: Better trait impulse control may be associated with better treatment responsiveness among adults with bipolar disorder.
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Transtorno Bipolar/diagnóstico , Transtorno Bipolar/fisiopatologia , Comportamento Impulsivo/fisiologia , Adolescente , Adulto , Transtorno do Deficit de Atenção com Hiperatividade/etiologia , Transtorno Bipolar/mortalidade , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/etiologia , Feminino , Humanos , Modelos Logísticos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Valor Preditivo dos Testes , Escalas de Graduação Psiquiátrica , Análise de Sobrevida , Adulto JovemRESUMO
Objective: Parental and other caregiving leave is important to postdoctoral fellows, yet there is no field-wide recommendation for leave policies among clinical neuropsychology postdoctoral training programs, which is of particular relevance given the two-year requirement for eligibility for board certification. The aims of this manuscript are to (a) discuss general guidelines and recommendations for leave policies, both informed by prior empirical evidence as well as relevant existing policy guidelines from various academic and healthcare organizations, and (b) use vignettes to provide possible solutions for potential leave scenarios. Method: A critical review of literature on family leave from public policy and political science, industrial-organizational psychology, academic medicine, and psychology was conducted and findings were synthesized. Results and Conclusions: Fellowship training programs are encouraged to adopt a competency-based model that permits flexibility in leave during training without necessarily requiring an extended end date. Programs should adopt clear policies and make this information readily available to trainees and think flexibly about training options that best meet the training needs and goals of each individual. We also encourage neuropsychologists at all levels to engage in advocacy for broader systemic supports of trainees seeking equitable family leave.
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Comitês Consultivos , Neuropsicologia , Humanos , Feminino , Neuropsicologia/métodos , Pós-Doutorado , Inquéritos e Questionários , Testes Neuropsicológicos , Licença para Cuidar de Pessoa da FamíliaRESUMO
Purpose: Recent advances to preserve neurocognitive function in patients treated for brain metastases include stereotactic radiosurgery, hippocampal avoidance whole brain radiation therapy (WBRT), and memantine administration. The hippocampus, corpus callosum, fornix, and amygdala are key neurocognitive substructures with a low propensity for brain metastases. Herein, we report our preliminary experience using a "memory-avoidance" WBRT (MA-WBRT) approach that spares these substructures for patients with >15 brain metastases. Methods and Materials: Ten consecutive patients treated with MA-WBRT on a phase 2 clinical trial were reviewed. In each patient, the hippocampi, amygdalae, corpus callosum, and fornix were contoured. Patients were not eligible for MA-WBRT if they had metastases in these substructures. A memory-avoidance region was created using a 5-mm volumetric expansion around these substructures. Hotspots were avoided in the hypothalamus and pituitary gland. Coverage of brain metastases was prioritized over memory avoidance dose constraints. Dose constraints for these avoidance structures included a D100% ≤ 9 Gy and D0.03 cm3 ≤ 16 Gy (variation acceptable to 20 Gy). LINAC-based volumetric modulated arc therapy plans were generated for a prescription dose of 30 Gy in 10 fractions. Results: On average, the memory avoidance structure volume was 37.1 cm3 (range, 25.2-44.6 cm3), occupying 2.5% of the entire whole brain target volume. All treatment plans met the D100% dose constraint, and 8 of 10 plans met the D0.03 cm3 constraint, with priority given to tumor coverage for the remaining 2 cases. Target coverage (D98% > 25 Gy) and homogeneity (D2% ≤ 37.5 Gy) were achieved for all plans. Conclusions: Modern volumetric modulated arc therapy techniques allow for sparing of the hippocampus, amygdala, corpus callosum, and fornix with good target coverage and homogeneity. After enrollment is completed, quality of life and cognitive data will be evaluated to assess the efficacy of MA-WBRT to mitigate declines in quality of life and cognition after whole brain radiation.
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Objective: The Relative Value Unit (RVU) system was initially developed to account for costs associated with clinical services and has since been applied in some settings as a metric for monitoring productivity. That practice has come under fire in the medical literature due to perceived flaws in determination of "work RVU" for different billing codes and negative impacts on healthcare rendered. This issue also affects psychologists, who bill codes associated with highly variable hourly wRVUs. This paper highlights this discrepancy and suggests alternative options for measuring productivity to better equate psychologists' time spent completing various billable clinical activities. Method: A review was performed to identify potential limitations to measuring providers' productivity based on wRVU alone. Available publications focus almost exclusively on physician productivity models. Little information was available relating to wRVU for psychology services, including neuropsychological evaluations, specifically. Conclusions: Measurement of clinician productivity using only wRVU disregards patient outcomes and under-values psychological assessment. Neuropsychologists are particularly affected. Based on the existing literature, we propose alternative approaches that capture productivity equitably among subspecialists and support provision of non-billable services that are also of high value (e.g. education and research).
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Objective: The alpha-synuclein gene (SNCA) is implicated in both Parkinson's disease (PD) and dementia with Lewy bodies (DLB). The purpose of this case study was to describe the neuropsychological profile, clinical trajectory, and treatment course of an individual with a known SNCA gene duplication who was followed over the course of three years. Methods: The patient was a healthy man who developed olfactory changes in early adulthood followed by parkinsonism and cognitive concerns around age 40. He underwent serial neurologic and neuropsychological evaluations and neuroimaging, as well as genetic testing for PD gene mutations. He consented to share his medical information to increase awareness of his condition. Results: Initial neuropsychological evaluation (age 44) revealed mild cognitive impairment primarily affecting executive and frontal/subcortical functions. Follow-up evaluations showed rapid cognitive decline that far surpassed the patient's Parkinsonism, which responded well to carbidopa-levodopa. As symptoms progressed, he also developed features characteristic of DLB, including cognitive fluctuations, rapid eye movement sleep behavior disorder, and visual hallucinations. Conclusion: SNCA gene duplication has classically been associated with a slowly progressive syndrome closely resembling idiopathic PD, but less frequently it can cause rapidly progressive dementia. This case study is the first to describe this rare phenotype in terms of its full neuropsychological profile and trajectory. The case highlights the value of a transdisciplinary evaluation and treatment and brings up important ethical and practical issues that should be considered when working with patients who have suspected or known genetic disorders.
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Doença de Parkinson , Transtornos Parkinsonianos , Carbidopa , Humanos , Levodopa , Masculino , Testes Neuropsicológicos , Doença de Parkinson/complicações , Doença de Parkinson/genética , Doença de Parkinson/psicologia , Transtornos Parkinsonianos/complicações , Transtornos Parkinsonianos/diagnóstico , Transtornos Parkinsonianos/genética , alfa-Sinucleína/genéticaRESUMO
Objective: This retrospective analysis assessed regression-based reliable change (RC) of cognition in a sample of essential tremor (ET) patients who underwent unilateral deep brain stimulation of the ventral intermediate nucleus of the thalamus (VIM-DBS).Method: Thirty patients (mean age at pre-evaluation = 70.4 ± 6.3 years) underwent neuropsychological evaluation pre- and post-unilateral VIM-DBS placement (mean time between pre and post-evaluation = 13.1 ± 4.0 months). Paired samples t-tests and RC analyses were employed.Results: No significant within-group differences were observed when cognitive scores were compared between evaluations. The vast majority of patients demonstrated stability across pre-and post-surgical evaluations (i.e. 29 out of 30); however, those with high-risk co-morbid medical conditions may be vulnerable to post-surgical cognitive decline as indicated by RC measures.Conclusions: The use of regression-based RC indices to assess individual cognitive changes between pre and post-surgical evaluations control for systematic and measurement errors that can occur over repeated evaluations, and may be able to identify cognitive changes that evade detection in traditional within-group comparisons.
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The COVID-19 pandemic highlighted mRNA as a promising platform for vaccines and therapeutics. Many of the analytical tools used to characterize the critical quality attributes of mRNA are inherently singleplex and are not necessarily optimal from a labor and cost perspective. Here, we demonstrate the feasibility of a multiplexed platform (VaxArray) for efficient identity verification and concentration determination for both monovalent and multivalent mRNA formulations. A model system comprising mRNA constructs for influenza hemagglutinin and neuraminidase was used to characterize the analytical performance metrics for a VaxArray mRNA assay. The assay presented herein had a time to result of less than 2 h, required no PCR-based amplification nor extraction of mRNA from lipid nanoparticles, and exhibited high construct specificity that enabled application to the bivalent mixture. The sensitivity for influenza hemagglutinin and neuraminidase mRNA was sub-µg/mL, which is vaccine-relevant, and the average accuracy (%recovery of a check standard) and precision were 104 ± 2% and 9 ± 2%, respectively.
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PURPOSE: We previously described the magnitude of rural-urban differences in the prevalence of stroke risk factors and stroke mortality. In this report, we sought to extend the understanding of rural-urban differences in the prevalence of stroke risk factors by using an enhanced definition of rural-urban status and assessing the impact of neighborhood socioeconomic status (nSES) on risk factor differences. METHODS: This analysis included 28,242 participants without a history of stroke from the REasons for Geographic And Racial Differences in Stroke (REGARDS) cohort. Participants were categorized into the 6-level ordinal National Center for Health Statistics Urban-Rural Classification Scheme. The prevalence of stroke risk factors (hypertension, diabetes, smoking, atrial fibrillation, left ventricular hypertrophy, and heart disease) was assessed across the rural-urban scale with adjustment for demographic characteristics and further adjustment for nSES score. FINDINGS: Hypertension, diabetes, and heart disease were more prevalent in rural than urban regions. Higher odds were observed for these risk factors in the most rural compared to the most urban areas (odds ratios [95% CI]: 1.25 [1.11-1.42] for hypertension, 1.15 [0.99-1.33] for diabetes, and 1.19 [1.02-1.39] for heart disease). Adjustment for nSES score partially attenuated the odds of hypertension and heart disease with rurality, completely attenuated the odds of diabetes, and unmasked an association of current smoking. CONCLUSIONS: Some of the higher stroke mortality in rural areas may be due to the higher burden of stroke risk factors in rural areas. Lower nSES contributed most notably to rural-urban differences for diabetes and smoking.
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Diabetes Mellitus , Cardiopatias , Hipertensão , Acidente Vascular Cerebral , Estudos Transversais , Diabetes Mellitus/epidemiologia , Cardiopatias/complicações , Humanos , Hipertensão/epidemiologia , Prevalência , Fatores de Risco , População Rural , Acidente Vascular Cerebral/epidemiologia , População UrbanaRESUMO
Next generation poliovirus vaccines are critical to reaching global poliovirus eradication goals. Recent efforts have focused on creating inactivated vaccines using attenuated Sabin strains that maintain patient safety benefits and immunogenicity of conventional inactivated vaccines while increasing manufacturing safety and lowering production costs, and on developing novel oral vaccines using modified Sabin strains that provide critical mucosal immunity but are further attenuated to minimize risk of reversion to neurovirulence. In addition, there is a push to improve the analytical tools for poliovirus vaccine characterization. Conventional and Sabin inactivated poliovirus vaccines typically rely on standard plate-based ELISA as in vitro D-antigen potency assays in combination with WHO international standards as calibrants. While widely utilized, the current D-antigen ELISA assays have a long time to result (up to 72 h), can suffer from lab-to-lab inconsistency due to non-standardized protocols and reagents, and are inherently singleplex. For D-antigen quantitation, we have developed the VaxArray Polio Assay Kit, a multiplexed, microarray-based immunoassay that uses poliovirus-specific human monoclonal antibodies currently under consideration as standardized reagents for characterizing inactivated Sabin and Salk vaccines. The VaxArray assay can simultaneously quantify all 3 poliovirus serotypes with a time to result of less than 3 h. Here we demonstrate that the assay has limits of quantification suitable for both bioprocess samples and final vaccines, excellent reproducibility and precision, and improved accuracy over an analogous plate-based ELISA. The assay is suitable for adjuvanted combination vaccines, as common vaccine additives and crude matrices do not interfere with quantification, and is intended as a high throughput, standardized quantitation tool to aid inactivated poliovirus vaccine manufacturers in streamlining vaccine development and manufacturing, aiding the global polio eradication effort.
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Poliomielite , Poliovirus , Anticorpos Antivirais , Antígenos Virais , Ensaio de Imunoadsorção Enzimática , Humanos , Poliomielite/diagnóstico , Poliomielite/prevenção & controle , Vacina Antipólio de Vírus Inativado , Vacina Antipólio Oral , Reprodutibilidade dos Testes , Vacinas de Produtos InativadosRESUMO
Brain metastases (BMs) account for a disproportionately high percentage of cancer morbidity and mortality. Historically, studies have focused on improving survival outcomes, and recent radiation oncology clinical trials have incorporated HRQOL and cognitive assessments. We are now equipped with a battery of assessments in the radiation oncology clinic, but there is a lack of consensus regarding how to incorporate them in modern clinical practice. Herein, we present validated assessments for BM patients, current recommendations for future clinical studies, and treatment advances that have improved HRQOL and cognitive outcomes for BM patients.
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Pneumonia accounts for over 20% of deaths worldwide in children aged 1 to 5 years, disproportionately affecting lower- and middle-income countries. Effective, highly multivalent pneumococcal vaccines are available to decrease disease burden, with numerous new vaccines currently under development to serve a variety of worldwide markets. However, pneumococcal conjugate vaccines are among the hardest biologics to manufacture and characterize due to their complexity and heterogeneity. Current characterization methods are often inherently singleplex, requiring separate tests for each serotype present. In addition, identity and quantity are often determined with separate methods. We developed the VaxArray pneumococcal assay for applications in identity, quantity, and stability testing of pneumococcal polysaccharide and pneumococcal conjugate vaccines. The VaxArray pneumococcal assay has a time to result of less than 30 min and is an off-the-shelf multiplexed, microarray-based immunoassay kit that can identify and simultaneously quantify 23 pneumococcal polysaccharide serotypes common to many on-market and in-development vaccines. Here, we highlight the potential of the assay for identity testing by showing high reactivity and serotype specificity to a wide variety of native polysaccharides, CRM197-conjugated polysaccharides, and drug product. The assay also has vaccine-relevant lower limits of quantification in the low-to-mid ng/mL range and can be used for accurate quantification even in adjuvanted vaccines. Excellent correlation to the anthrone assay is demonstrated, with VaxArray resulting in significantly improved precision over this antiquated chemical method.
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Objectives: In response to the coronavirus disease 2019 (COVID-19) pandemic, neuropsychologists rapidly adopted teleneuropsychology (TeleNP) services to ensure continued clinical care. Prior to COVID-19, TeleNP was not widely used nor was it included in the majority of traditional practice or training models across graduate, internship, and postdoctoral programs. Out of necessity, the pandemic was a catalyst that promoted greater adoption of TeleNP services. In response, neuropsychological guidelines for modified assessments were developed and further empirical studies have been published. Numerous surveys in response to service delivery changes during COVID-19 now exist, but what follows is a commentary based on neuropsychologists' experiences with adapting clinical practice to TeleNP. Methods: Co-authors represent settings across academic medical centers, Veterans Affairs hospitals, and private practices that serve multiculturally diverse pediatric, adult, and geriatric populations in the United States. Results: The perspectives within this commentary aim to highlight the growth of TeleNP and highlight lessons learned from implementation across practice settings. Conclusions: Our goal is to help foster the development of further empirical studies through candid discussion of various TeleNP experiences and approaches. Through this reflective process, TeleNP presents both opportunities and challenges but it ultimately has potential to reduce healthcare disparities and enhance patient care.
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COVID-19 , Telemedicina , Adulto , Idoso , Criança , Humanos , Testes Neuropsicológicos , Neuropsicologia , Pandemias , Inquéritos e Questionários , Estados UnidosRESUMO
Shiga toxin-producing Escherichia coli O157 is a leading cause of foodborne illness worldwide. To evaluate better methods to rapidly detect and genotype E. coli O157 strains, the present study evaluated the use of ampliPHOX, a novel colorimetric detection method based on photopolymerization, for pathogen identification with DNA microarrays. A low-density DNA oligonucleotide microarray was designed to target stx1 and stx2 genes encoding Shiga toxin production, the eae gene coding for adherence membrane protein, and the per gene encoding the O157-antigen perosamine synthetase. Results from the validation experiments demonstrated that the use of ampliPHOX allowed the accurate genotyping of the tested E. coli strains, and positive hybridization signals were observed for only probes targeting virulence genes present in the reference strains. Quantification showed that the average signal-to-noise ratio values ranged from 47.73 ± 7.12 to 76.71 ± 8.33, whereas average signal-to-noise ratio values below 2.5 were determined for probes where no polymer was formed due to lack of specific hybridization. Sensitivity tests demonstrated that the sensitivity threshold for E. coli O157 detection was 100-1000 CFU/mL. Thus, the use of DNA microarrays in combination with photopolymerization allowed the rapid and accurate genotyping of E. coli O157 strains.
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Escherichia coli O157/classificação , Escherichia coli O157/genética , Tipagem Molecular/métodos , Adesinas Bacterianas/genética , Adesinas Bacterianas/metabolismo , Antígenos de Bactérias/genética , Antígenos de Bactérias/metabolismo , Biotina/química , Carboidratos Epimerases/genética , Carboidratos Epimerases/metabolismo , Colorimetria , Escherichia coli O157/isolamento & purificação , Escherichia coli O157/patogenicidade , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Doenças Transmitidas por Alimentos/prevenção & controle , Genes Bacterianos , Genótipo , Indicadores e Reagentes/química , Análise de Sequência com Séries de Oligonucleotídeos , Reação em Cadeia da Polimerase , Polimerização , Toxina Shiga I/genética , Toxina Shiga I/metabolismo , Toxina Shiga II/genética , Toxina Shiga II/metabolismo , Estreptavidina/química , Transaminases/genética , Transaminases/metabolismo , Virulência/genética , Fatores de Virulência/genética , Fatores de Virulência/metabolismoRESUMO
Rapid, sensitive, and precise multiplexed assays for serological analysis during candidate COVID-19 vaccine development would streamline clinical trials. The VaxArray Coronavirus (CoV) SeroAssay quantifies IgG antibody binding to 9 pandemic, potentially pandemic, and endemic human CoV spike antigens in 2â¯h with automated results analysis. IgG antibodies in serum bind to the CoV spike protein capture antigens printed in a microarray format and are labeled with a fluorescent anti-species IgG secondary label. The assay demonstrated excellent lower limits of quantification ranging from 0.3 to 2.0â¯ng/mL and linear dynamic ranges of 76 to 911-fold. Average precision of 11 % CV and accuracy (% recovery) of 92.5 % over all capture antigens were achieved over 216 replicates representing 3 days and 3 microarray lots. Clinical performance on 263 human serum samples (132 SARS-CoV-2 negatives and 131 positives based on donor-matched RT-PCR and/or date of collection) produced 98.5 % PPA and 100 % NPA.
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Anticorpos Antivirais/sangue , Infecções por Coronavirus/diagnóstico , Coronavirus/isolamento & purificação , Análise em Microsséries/métodos , Testes Sorológicos/métodos , Antígenos Virais/imunologia , COVID-19/diagnóstico , COVID-19/imunologia , Teste de Ácido Nucleico para COVID-19 , Teste para COVID-19/métodos , Coronavirus/imunologia , Infecções por Coronavirus/imunologia , Humanos , Imunoensaio/métodos , Imunoglobulina G/sangue , Reprodutibilidade dos Testes , SARS-CoV-2/isolamento & purificação , Sensibilidade e Especificidade , Glicoproteína da Espícula de Coronavírus/imunologiaRESUMO
Mitigation of the COVID-19 pandemic requires an understanding of the antibody response to SARS-CoV-2. However, throughout the development of SARS-CoV-2 IgG antibody assays during the past year, cross-reactivity to other coronaviruses remained a question. To address these issues, we evaluated IgG in COVID-19 convalescent plasma samples for reactivity against three SARS-CoV-2 antigens including full-length spike, receptor binding domain, and the proximal extracellular fusion domain, and spike antigens from other coronaviruses (SARS-CoV, MERS-CoV, hCoV-HKU1, hCoV-OC43, hCoV-229E and hCoV-NL63) using the VaxArray Coronavirus SeroAssay which is a multiplexed antigen assay developed by InDevR Inc. These results were compared to two commercial SARS-CoV-2 IgG ELISAs targeting either the SARS-CoV-2 nucleocapsid or spike antigens and a live virus focus reduction neutralizing antibody test (FRNT). The VaxArray platform showed high specificity for detection of SARS-CoV-2 IgG, evident from lack of reactivity to SARS-CoV-2 antigens despite significant reactivity to endemic coronavirus antigens in pre-pandemic samples. SARS-CoV-2 IgG positive samples reacted weakly to SARS-CoV spike but not to MERS-CoV. While the VaxArray platform had overall comparable results to the spike and nucleocapsid IgG ELISAs, results were more similar to the spike antigen ELISA and the platform displayed a higher sensitivity and specificity than both ELISAs. Samples with FRNT titers below 1/23 reported negative on VaxArray, while positive samples on VaxArray had significantly higher neutralizing antibody titers. These results suggest that the VaxArray Coronavirus SeroAssay performs with high sensitivity and specificity for the detection of SARS-CoV-2 IgG, and positive results on the platform indicate SARS-CoV-2 neutralizing activity.
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Anticorpos Antivirais/imunologia , Antígenos Virais/imunologia , COVID-19/diagnóstico , Imunoensaio/métodos , Imunoglobulina G/imunologia , SARS-CoV-2/imunologia , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/sangue , COVID-19/epidemiologia , COVID-19/virologia , Reações Cruzadas/imunologia , Ensaio de Imunoadsorção Enzimática/métodos , Humanos , Imunoglobulina G/sangue , Pandemias/prevenção & controle , Reprodutibilidade dos Testes , SARS-CoV-2/fisiologia , Sensibilidade e Especificidade , Glicoproteína da Espícula de Coronavírus/imunologiaRESUMO
BACKGROUND: To investigate the underlying causes of a sudden increase in HIV among people who inject drugs (PWID) and initiate an appropriate response to the outbreak, we engaged in in-depth qualitative interviews with members of the PWID community in Lawrence and Lowell, Massachusetts. METHODS: We interviewed 34 PWID who were currently or recently unstably housed, then transcribed interviews and coded transcripts, grouping codes into categories from which we identified key themes. RESULTS: Participants described a heightened threat of overdose prompting PWID to inject together, increasing opportunities for sharing injection equipment. There were misunderstandings about safe injection practices to prevent HIV transmission and a low threshold for injection-related risk taking. Stigma regarding HIV prevented conversations about HIV status. Less thought was given to sexual risks than injection-related risks for HIV transmission. CONCLUSIONS: We found multiple facilitators of HIV transmission. Additional HIV education and prevention interventions focusing on both injection and sexual risk practices would benefit this population, in addition to structural interventions such as increased access and availability of syringe service programs.
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Infecções por HIV , Preparações Farmacêuticas , Abuso de Substâncias por Via Intravenosa , Surtos de Doenças , Infecções por HIV/epidemiologia , Humanos , Assunção de Riscos , Comportamento Sexual , Abuso de Substâncias por Via Intravenosa/epidemiologiaRESUMO
Measles-containing vaccines (MCV), specifically vaccines against measles and rubella (MR), are extremely effective and critical for the eradication of measles and rubella diseases. In developed countries, vaccination rates are high and vaccines are readily available, but continued high prevalence of both diseases in developing countries and surges in measles deaths in recent years have highlighted the need to expand vaccination efforts. To meet demand for additional vaccines at a globally affordable price, it is highly desirable to streamline vaccine production thereby reducing cost and speeding up time to delivery. MR vaccine characterization currently relies on the 50% cell culture infectious dose (CCID50) assay, an endpoint assay with low reproducibility that requires 10-14 days to complete. For streamlining bioprocess analysis and improving measurement precision relative to CCID50, we developed the VaxArray Measles and Rubella assay kit, which is based on a multiplexed microarray immunoassay with a 5-hour time to result. Here we demonstrate vaccine-relevant sensitivity ranging from 345 to 800 IFU/mL up to 100,000 IFU/mL (infectious units per mL) and specificity that allows simultaneous analysis in bivalent vaccine samples. The assay is sensitive to antigen stability and has minimal interference from common vaccine additives. The assay exhibits high reproducibility and repeatability, with 15% CV, much lower than the typical 0.3 log10 error (â¼65%) observed for the CCID50 assay. The intact protein concentration measured by VaxArray is reasonably correlated to, but not equivalent to, CCID50 infectivity measurements for harvest samples. However, the measured protein concentration exhibits equivalency to CCID50 for more purified samples, including concentrated virus pools and monovalent bulks, making the assay a useful new tool for same-day analysis of vaccine samples for bioprocess development, optimization, and monitoring.