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There has been considerable emphasis recently on the zoonotic origins of emerging infectious diseases in humans, including the SARS-CoV-2 pandemic; however, reverse zoonoses (infections transmitted from humans to other animals) have received less attention despite their potential importance. The effects can be devastating for the infected species and can also result in transmission of the pathogen back to human populations or other animals either in the original form or as a variant. Humans have transmitted SARS-CoV-2 to other animals, and the virus is able to circulate and evolve in those species. As global travel resumes, the potential of SARS-CoV-2 as a reverse zoonosis threatens humans and endangered species. Nonhuman primates are of particular concern given their susceptibility to human respiratory infections. Enforcing safety measures for all people working in and visiting wildlife areas, especially those with nonhuman primates, and increasing access to safety measures for people living near protected areas that are home to nonhuman primates will help mitigate reverse zoonotic transmission.
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BACKGROUND: SARS-CoV-2 antigen-detection rapid diagnostic tests (Ag-RDTs) have become widely utilized but longitudinal characterization of their community-based performance remains incompletely understood. METHODS: This prospective longitudinal study at a large public university in Seattle, WA utilized remote enrollment, online surveys, and self-collected nasal swab specimens to evaluate Ag-RDT performance against real-time reverse transcription polymerase chain reaction (rRT-PCR) in the context of SARS-CoV-2 Omicron. Ag-RDT sensitivity and specificity within 1 day of rRT-PCR were evaluated by symptom status throughout the illness episode and Orf1b cycle threshold (Ct). RESULTS: From February to December 2022, 5757 participants reported 17 572 Ag-RDT results and completed 12 674 rRT-PCR tests, of which 995 (7.9%) were rRT-PCR positive. Overall sensitivity and specificity were 53.0% (95% confidence interval [CI], 49.6%-56.4%) and 98.8% (95% CI, 98.5%-99.0%), respectively. Sensitivity was comparatively higher for Ag-RDTs used 1 day after rRT-PCR (69.0%), 4-7 days after symptom onset (70.1%), and Orf1b Ct ≤20 (82.7%). Serial Ag-RDT sensitivity increased with repeat testing ≥2 (68.5%) and ≥4 (75.8%) days after an initial Ag-RDT-negative result. CONCLUSIONS: Ag-RDT performance varied by clinical characteristics and temporal testing patterns. Our findings support recommendations for serial testing following an initial Ag-RDT-negative result, especially among recently symptomatic persons or those at high risk for SARS-CoV-2 infection.
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Prueba Serológica para COVID-19 , COVID-19 , SARS-CoV-2 , Sensibilidad y Especificidad , Humanos , COVID-19/diagnóstico , SARS-CoV-2/inmunología , SARS-CoV-2/aislamiento & purificación , SARS-CoV-2/genética , Estudios Prospectivos , Estudios Longitudinales , Masculino , Femenino , Persona de Mediana Edad , Adulto , Prueba Serológica para COVID-19/métodos , Antígenos Virales/análisis , Prueba de Ácido Nucleico para COVID-19/métodos , Anciano , Washingtón , Adulto Joven , AdolescenteRESUMEN
The United States Department of Agriculture (USDA) Division of Agricultural Select Agents and Toxins (DASAT) established a list of biological agents (Select Agents List) that threaten crops of economic importance to the United States and regulates the procedures governing containment, incident response, and the security of entities working with them. Every 2 years the USDA DASAT reviews their select agent list, utilizing assessments by subject matter experts (SMEs) to rank the agents. We explored the applicability of multi-criteria decision analysis (MCDA) techniques and a decision support framework (DSF) to support the USDA DASAT biennial review process. The evaluation includes both current and non-select agents to provide a robust assessment. We initially conducted a literature review of 16 pathogens against 9 criteria for assessing plant health and bioterrorism risk and documented the findings to support this analysis. Technical review of published data and associated scoring recommendations by pathogen-specific SMEs was found to be critical for ensuring accuracy. Scoring criteria were adopted to ensure consistency. The MCDA supported the expectation that select agents would rank high on the relative risk scale when considering the agricultural consequences of a bioterrorism attack; however, application of analytical thresholds as a basis for designating select agents led to some exceptions to current designations. A second analytical approach used agent-specific data to designate key criteria in a DSF logic tree format to identify pathogens of low concern that can be ruled out for further consideration as select agents. Both the MCDA and DSF approaches arrived at similar conclusions, suggesting the value of employing the two analytical approaches to add robustness for decision making.
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The Gram stain classifies most bacteria into one of two groups, Gram-negative or Gram-positive, based on the composition of their cell walls [...].
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This chapter canvasses the current relevance of behavioral neuroscience to the law, especially to issues of criminal responsibility and competence. It begins with an explanation of the legal doctrines at stake. I then explore the source of the often-inflated claims for the legal relevance of neuroscience. The next section discusses the scientific status of behavioral neuroscience. Then, it addresses two radical challenges to current conceptions of criminal responsibility that neuroscience allegedly poses: determinism and the death of agency. The question of the specific relevance of neuroscience to criminal law doctrine, practice, and institutions is considered next. This is followed by a discussion of how neuroscience evidence is being used in criminal cases in five different countries, including the United States. The penultimate section points to some areas warranting modest optimism. A brief conclusion suggests that neuroscience is at present of limited legal relevance, and advances in the science might alter that judgment.
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Juicio , Neurociencias , HumanosRESUMEN
Objectives: The study aim was to investigate multidrug-resistant (MDR) plasmids from a collection of 10 carbapenemase-producing Klebsiella pneumoniae clinical isolates identified within the same healthcare institution in Pakistan. Full characterization of the MDR plasmids including structure, typing characteristics, and AMR content as well as determination of their plasmid-based antimicrobial susceptibility profiles were carried out. Methods: Plasmids were isolated from 10 clinical isolates of Klebsiella pneumoniae, and from a corresponding set of Escherichia coli transconjugants, then sequenced using Nanopore/Illumina technology to generate plasmid hybrid assemblies. Full characterization of MDR plasmids, including determination of next generation sequencing (NGS)-based AMR profiles, plasmid incompatibility groups, and types, was carried out. The structure of MDR plasmids was analyzed using the Galileo AMR platform. For E. coli transconjugants, the NGS-based AMR profiles were compared to NGS-predicted AMR phenotypes and conventional broth microdilution (BMD) antimicrobial susceptibility testing (AST) results. Results: All carbapenemase-producing K. pneumoniae isolates (carrying either blaNDM-1, or/and blaOXA-48) carried multiple AMR plasmids encoding 34 antimicrobial resistance genes (ARGs) conferring resistance to antimicrobials from 6 different classes. The plasmid incompatibility groups and types identified were: IncC (types 1 and 3), IncFIA (type 26) IncFIB, IncFII (types K1, K2, K7, and K9), IncHI1B, and IncL. None of the blaNDM-1 and blaESBL-plasmids identified in this study were previously described. Most blaNDM-1-plasmids shared identical AMR regions suggesting potential genetic material/plasmid exchange between K. pneumoniae isolates of this collection. The majority of NGS-based AMR profiles from the E. coli transconjugants correlated well with both NGS-based predicted and conventional AST results. Conclusion: This study highlights the complexity and diversity of the plasmid-based genetic background of carbapenemase-producing clinical isolates from Pakistan. This study emphasizes the need for characterization of MDR plasmids to determine their complete molecular background and monitor AMR through plasmid transmission between multi-resistant bacterial pathogens.
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The continued emergence and spread of antimicrobial resistance among pathogenic bacteria are ever-growing threats to health and economy. Here, we report the draft genomes for 45 Enterobacterales clinical isolates, including historical and contemporary drug-resistant organisms, obtained in Pakistan between 1998 and 2016: 5 Serratia, 3 Salmonella, 3 Enterobacter, and 34 Klebsiella.
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The United States Department of Agriculture (USDA), Division of Agricultural Select Agents and Toxins (DASAT) established a list of biological agents and toxins (Select Agent List) that potentially threaten agricultural health and safety, the procedures governing the transfer of those agents, and training requirements for entities working with them. Every 2 years the USDA DASAT reviews the Select Agent List, using subject matter experts (SMEs) to perform an assessment and rank the agents. To assist the USDA DASAT biennial review process, we explored the applicability of multi-criteria decision analysis (MCDA) techniques and a Decision Support Framework (DSF) in a logic tree format to identify pathogens for consideration as select agents, applying the approach broadly to include non-select agents to evaluate its robustness and generality. We conducted a literature review of 41 pathogens against 21 criteria for assessing agricultural threat, economic impact, and bioterrorism risk and documented the findings to support this assessment. The most prominent data gaps were those for aerosol stability and animal infectious dose by inhalation and ingestion routes. Technical review of published data and associated scoring recommendations by pathogen-specific SMEs was found to be critical for accuracy, particularly for pathogens with very few known cases, or where proxy data (e.g., from animal models or similar organisms) were used to address data gaps. The MCDA analysis supported the intuitive sense that select agents should rank high on the relative risk scale when considering agricultural health consequences of a bioterrorism attack. However, comparing select agents with non-select agents indicated that there was not a clean break in scores to suggest thresholds for designating select agents, requiring subject matter expertise collectively to establish which analytical results were in good agreement to support the intended purpose in designating select agents. The DSF utilized a logic tree approach to identify pathogens that are of sufficiently low concern that they can be ruled out from consideration as a select agent. In contrast to the MCDA approach, the DSF rules out a pathogen if it fails to meet even one criteria threshold. Both the MCDA and DSF approaches arrived at similar conclusions, suggesting the value of employing the two analytical approaches to add robustness for decision making.
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BACKGROUND: Although there is limited literature on medication adherence (including HIV care engagement) and COVID-19 vaccine hesitancy in general populations (i.e., non-sexual or gender minority populations), even less is known about whether HIV care engagement correlates with COVID-19 vaccine hesitancy among sexual and gender minorities, especially those from intersectional backgrounds. The objective of the current study was to examine if an association exists between HIV status neutral care (i.e., current pre-exposure prophylaxis [PrEP] or antiretroviral therapy [ART] use) and COVID-19 vaccination hesitancy among Black cisgender sexual minority men and transgender women at the initial peak of the pandemic. METHODS: We conducted the N2 COVID Study in Chicago from 20 April 2020 to 31 July 2020 (analytic n = 222), including Black cisgender sexual minority men and transgender women who were vulnerable to HIV as well as those who were living with HIV. The survey included questions regarding HIV care engagement, COVID-19 vaccination hesitancy and COVID-19 related socio-economic hardships. Multivariable associations estimated adjusted risk ratios (ARRs) using modified Poisson regressions for COVID vaccine hesitancy adjusting for baseline socio-demographic characteristics and survey assessment time period. RESULTS: Approximately 45% of participants reported COVID-19 vaccine hesitancy. PrEP and ART use were not associated with COVID-19 vaccine hesitancy when examined separately or combined (p > 0.05). There were no significant multiplicative effects of COVID-19 related socio-economic hardships and HIV care engagement on COVID-19 vaccine hesitancy. CONCLUSIONS: Findings suggest no association between HIV care engagement and COVID-19 vaccine hesitancy among Black cisgender sexual minority men and transgender women at the initial peak of the pandemic. It is therefore essential that COVID-19 vaccine promotion interventions focus on all Black sexual and gender minorities regardless of HIV care engagement and COVID-19 vaccine uptake is likely related to factors other than engagement in HIV status neutral care.
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Introduction During the COVID-19 pandemic, there was an unprecedented and forced closure of dental offices worldwide. As American state recommendations differed considerably during this period, this research strives to better define the effects of this pause on dental care.Materials and methods A 16-question Qualtrics survey was sent to the membership of the New York State Dental Association (NYSDA) and Georgia Dental Association (GDA). Licenced, actively practising dental members of the NYSDA and GDA (n = 680) answered questions about their practice demographics, appointment cancellations, reopening times and the volume of individual dental procedures performed from 1 March through to 1 August 2020, compared to the same five-month period in 2019.Results Demographic characteristics of respondent NYSDA and GDA members were statistically similar. Nonetheless, NYSDA members reported significantly larger decreases in provision of all types of dental procedures, except for antibiotic prescription, including prophylaxis, elective care, emergency dental care and speciality procedures.Discussion and conclusions All dental procedures declined significantly during the COVID-19 pandemic, with greater decrease in New York than in Georgia. This study raises concerns about the negative impact of the pandemic on oral public health and mandates both further research and clinical strategies to mitigate against this future risk.
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Many countries have worked diligently to establish and implement policies and processes to regulate high consequence pathogens and toxins that could have a significant public health impact if misused. In the United States, the Antiterrorism and Effective Death Penalty Act of 1996 (Public Law 104-132, 1996), as amended by the Bioterrorism Preparedness and Response Act of 2002 (Public Law 107-188, 2002) requires that the Department of Health and Human Services (HHS) [through the Centers for Disease Control and Prevention (CDC)] establish a list of bacteria, viruses, and toxins that have the potential to pose a severe threat to public health and safety. Currently, this list is reviewed and updated on a biennial basis using input from subject matter experts (SMEs). We have developed decision support framework (DSF) approaches to facilitate selection of select toxins and, where toxicity data are known, conducted modelling studies to inform selection of toxin amounts that should be excluded from select agent regulations. Exclusion limits allow laboratories to possess toxins under an established limit to support their research or teaching activities without the requirement to register with the Federal Select Agent Program. Fact sheets capturing data from a previously vetted SME workshop convened by CDC, literature review and SME input were developed to assist in evaluating toxins using the DSF approach. The output of the DSF analysis agrees with the current select toxin designations, and no other toxins evaluated in this study were recommended for inclusion on the select agent and toxin list. To inform the selection of exclusion limits, attack scenarios were developed to estimate the amount of toxin needed to impact public health. Scenarios consisted of simulated aerosol releases of a toxin in high-population-density public facilities and the introduction of a toxin into a daily consumable product supply chain. Using published inhalation and ingestion median toxic dose (TD50) and median lethal dose (LD50) values, where available, a range of toxin amounts was examined to estimate the number of people exposed to these amounts in these scenarios. Based on data generated by these models, we proposed toxin exclusion values corresponding to levels below those that would trigger a significant public health response (i.e., amounts estimated to expose up to ten people by inhalation or one hundred people by ingestion to LD50 or TD50 levels of toxin in the modeled scenarios).
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The Centers for Disease Control and Prevention (CDC) Select Agent Program establishes a list of biological agents and toxins that potentially threaten public health and safety, the procedures governing the possession, utilization, and transfer of those agents, and training requirements for entities working with them. Every 2 years the Program reviews the select agent list, utilizing subject matter expert (SME) assessments to rank the agents. In this study, we explore the applicability of multi-criteria decision analysis (MCDA) techniques and logic tree analysis to support the CDC Select Agent Program biennial review process, applying the approach broadly to include non-select agents to evaluate its generality. We conducted a literature search for over 70 pathogens against 15 criteria for assessing public health and bioterrorism risk and documented the findings for archiving. The most prominent data gaps were found for aerosol stability and human infectious dose by inhalation and ingestion routes. Technical review of published data and associated scoring recommendations by pathogen-specific SMEs was found to be critical for accuracy, particularly for pathogens with very few known cases, or where proxy data (e.g., from animal models or similar organisms) were used to address data gaps. Analysis of results obtained from a two-dimensional plot of weighted scores for difficulty of attack (i.e., exposure and production criteria) vs. consequences of an attack (i.e., consequence and mitigation criteria) provided greater fidelity for understanding agent placement compared to a 1-to-n ranking and was used to define a region in the upper right-hand quadrant for identifying pathogens for consideration as select agents. A sensitivity analysis varied the numerical weights attributed to various properties of the pathogens to identify potential quantitative (x and y) thresholds for classifying select agents. The results indicate while there is some clustering of agent scores to suggest thresholds, there are still pathogens that score close to any threshold, suggesting that thresholding "by eye" may not be sufficient. The sensitivity analysis indicates quantitative thresholds are plausible, and there is good agreement of the analytical results with select agent designations. A second analytical approach that applied the data using a logic tree format to rule out pathogens for consideration as select agents arrived at similar conclusions.
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We conducted a comprehensive, multiphase laboratory evaluation of InBios Active Melioidosis Detect (AMD) rapid test, a lateral flow immunoassay designed to detect capsular polysaccharides produced by Burkholderia mallei or Burkholderia pseudomallei, used in conjunction with the Omni Array Reader (OAR) for the rapid detection of B mallei or B pseudomallei in environmental (nonclinical) samples at 2 sites. The limit of detection, using reference strains B mallei strain ATCC 23344 and B pseudomallei strain ATCC 11668, was determined to be 103 to 104 CFU/mL. In different phases of the evaluation, inclusivity strains that included geographically diverse strains of B mallei (N = 13) and B pseudomallei (N = 22), geographically diverse phylogenetic near neighbor strains (N = 66), environmental background strains (N = 64), white powder samples (N = 26), and environmental filter extracts (N = 1 pooled sample from 10 filter extracts) were also tested. A total of 1,753 tests were performed, which included positive and negative controls. Visual and OAR results showed that the AMD test detected 92.3% of B mallei and 95.5% of B pseudomallei strains. Of the 66 near-neighbor strains tested, cross-reactivity was observed with only B stabilis 2008724195 and B thailandensis 2003015869. Overall, the specificity and sensitivity were 98.8% and 98.7%, respectively. The results of this evaluation support the use of the AMD test as a rapid, qualitative assay for the presumptive detection of B mallei and B pseudomallei in suspicious environmental samples such as white powders and aerosol samples by first responders and laboratory personnel.
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Burkholderia mallei , Burkholderia pseudomallei , Melioidosis , Humanos , Melioidosis/diagnóstico , Filogenia , Extractos VegetalesRESUMEN
We conducted a comprehensive, multiphase laboratory evaluation of the InBios Active Melioidosis Detect (AMD) rapid test, a lateral flow immunoassay designed to detect capsular polysaccharides produced by Burkholderia mallei or Burkholderia pseudomallei, used in conjunction with the Omni Array Reader for the rapid identification of culture isolates of B mallei or B pseudomallei to support clinical diagnosis for response and triage during a mass casualty event, such as a biological attack. The study was conducted at 2 sites to assess the performance of the AMD test. The sensitivity, specificity, and reproducibility of the assay was determined using 5 replicates of 35 inclusivity strains and 64 clinical background strains. A total of 520 tests were performed, which included both positive and negative controls. Results obtained visually and with the Omni Array Reader showed a sensitivity of 92.3% for B mallei and 95.6% for B pseudomallei; no cross-reactivity was observed with any of the 64 clinical background organisms. The results from this study indicate that the AMD test for the presumptive identification of B mallei and B pseudomallei isolates to support clinical diagnosis is highly robust, specific, and sensitive. This evaluation supports the use of this test as a rapid, qualitative assay for the presumptive identification of B mallei and B pseudomallei in a clinical setting.
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Burkholderia mallei , Burkholderia pseudomallei , Melioidosis , Humanos , Melioidosis/diagnóstico , Reproducibilidad de los ResultadosRESUMEN
Community-acquired bacterial meningitis (CABM) morbidity and mortality remains high in those infected. Rapid diagnosis and treatment is paramount to reducing mortality and improving outcome. This retrospective cohort study aims to assess the time from presentation to diagnosis and treatment of vaccine preventable CABM as well as identify possible factors associated with delays in diagnosis and antibiotic administration. A retrospective chart review was conducted of individuals who presented to Columbia University Irving Medical Center (CUIMC), Children's Hospital of New York (CHONY), Mount Sinai Medical Center, and Weill Cornell Medical Center with BM due to Haemophilus influenzae type B, Streptococcus pneumoniae, and Neisseria meningitidis between January 1, 2012 and December 31, 2017. Diagnosis was delayed by more than 8 hours in 13 patients (36.1%) and 5 individuals (13.9%) had a delay of 4 hours or more from presentation to the administration of antibiotics with appropriate CNS coverage. All of these patients were also initially misdiagnosed at an outpatient clinic, outside hospital, or emergency department. This retrospective study identified febrile and/or viral infections not otherwise specified and otitis media as the most common misdiagnoses underlying delays from presentation to diagnosis and to antibiotic treatment in those with BM.
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This paper clarifies the conceptual space of discussion of legal insanity by considering the virtues of the 'medical model' model that has been used in Norway for almost a century. The medical model identifies insanity exclusively with mental disorder, and especially with psychosis, without any requirement that the disorder causally influenced the commission of the crime. We explore the medical model from a transdisciplinary perspective and show how it can be utilised to systematise and reconsider the central philosophical, legal and medical premises involved in the insanity debate. A key concern is how recent transdiagnostic and dimensional approaches to psychosis can illuminate the law's understanding of insanity and its relation to mental disorder. The authors eventually raise the question whether the medical model can be reconstructed into a unified insanity model that is valid across the related disciplinary perspectives, and that moves beyond current insanity models.
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Trastornos Mentales , Trastornos Psicóticos , Crimen , Derecho Penal , Humanos , Defensa por Insania/historia , Trastornos Mentales/diagnóstico , Noruega , Trastornos Psicóticos/diagnósticoRESUMEN
The new coronavirus (COVID-19) has generated an unprecedented degree of social and economic impact on the planet, but few researchers have explored the repercussion of COVID-19 for sustainable development (SD) and corporate social responsibility (CSR), especially from the perspective of Chinese businesses. This paper is the first to outline the priority changes of both SD and CSR over the period of COVID-19 incidence in China. An online questionnaire survey of 1161 owners and managers of Chinese companies was conducted, and respondents were asked to score the priorities of their company over the pre, during and post COVID-19 periods. The research was carried out at the end of the first COVID-19 wave in China but during the period of lockdown in some parts of the country. It was found that there was a priority change regarding three dimensions of sustainable development and 13 aspects of CSR. While the social dimension of SD was prioritized during and post COVID-19, the environmental dimension was the only one deemed to be less important and less prioritized over the longer term after the pandemic. The top three short-term CSR priorities were having in place a workplace health and safety plan, engaging in philanthropic activities and protecting biodiversity, and the top three longer-term CSR priorities were job creation, protecting biodiversity and having in place a workplace health and safety plan. Environmental protection and using clean energy were not reported as a CSR priority. The paper concludes that China's recovery mode cannot be called 'green' and suggests ways this could be changed.