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Like other congregate living settings, military basic training has been subject to outbreaks of COVID-19. We sought to identify improved strategies for preventing outbreaks in this setting using an agent-based model of a hypothetical cohort of trainees on a U.S. Army post. Our analysis revealed unique aspects of basic training that require customized approaches to outbreak prevention, which draws attention to the possibility that customized approaches may be necessary in other settings, too. In particular, we showed that introductions by trainers and support staff may be a major vulnerability, given that those individuals remain at risk of community exposure throughout the training period. We also found that increased testing of trainees upon arrival could actually increase the risk of outbreaks, given the potential for false-positive test results to lead to susceptible individuals becoming infected in group isolation and seeding outbreaks in training units upon release. Until an effective transmission-blocking vaccine is adopted at high coverage by individuals involved with basic training, need will persist for non-pharmaceutical interventions to prevent outbreaks in military basic training. Ongoing uncertainties about virus variants and breakthrough infections necessitate continued vigilance in this setting, even as vaccination coverage increases. Significance StatementCOVID-19 has presented enormous disruptions to society. Militaries are not immune to these disruptions, with outbreaks in those settings posing threats to national security. We present a simulation model of COVID-19 outbreaks in a U.S. Army basic training setting to inform improved approaches to prevention there. Counterintuitively, we found that outbreak risk is driven more by virus introductions from trainers than the large number of trainees, and that outbreak risk is highly sensitive to false-positive results during entry testing. These findings suggest practical ways to improve prevention of COVID-19 outbreaks in basic training and, as a result, maintain the flow of new soldiers into the military. This work highlights the need for bespoke modeling to inform prevention in diverse institutional settings.
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Chest pain is one of the most common reasons for patients to present to healthcare professionals. One of the main challenges with the management of chest pain is the wide differential diagnosis, ranging from minor chest trauma to potentially life-threatening acute myocardial infarction. In a patient-centered health service pathway, the aim is to assess, investigate, diagnose, and treat patients in the safest and most accurate, time, and cost-efficient manner. This report describes the concept of clinical pathways and their importance. It iterates different perspectives of the investigation of chest pain and the barriers to understanding the clinical sequence of events. By considering the patient, clinician, and healthcare service perspective, it is possible to critically evaluate the current stable chest pain pathway. This exercise gives consideration into the way in which patient care could be improved.
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Dolor en el Pecho , Infarto del Miocardio , Dolor en el Pecho/diagnóstico , Dolor en el Pecho/etiología , Dolor en el Pecho/terapia , Atención a la Salud , Diagnóstico Diferencial , Servicio de Urgencia en Hospital , Humanos , Infarto del Miocardio/diagnósticoRESUMEN
A problem was identified where patient care was affected because of delays in receiving specialist cardiology input. This report describes the experience of developing a specialist cardiac assessment where senior cardiac nurses were trained to provide a 24-hour presence in the emergency department (ED). We describe the service and our evaluation of the service. These dedicated specialised nurses can optimise patient management including admission or safely discharge patients with relevant follow-up when necessary. The team also runs three clinics per week with consultant support. The team of 10 nurses provides a cardiology opinion to approximately 400 patients a month in the ED and 100 patients a month in the acute medical unit (AMU). Eighty-seven per cent of patients are seen in the ED within 30 minutes of referral. Approximately 40% of patients reviewed are accepted directly into cardiology beds thus avoiding admission to the AMU. It has been estimated that 6 bed-days are saved each day, which translated to an estimated £400,000 each year. The team also provides outpatient rapid access services which generates £121,792 income for the directorate. We demonstrate that a cardiac nurse assessment team can provide a cost-effective 24-hour presence in the ED.
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During development of the vertebrate CNS, the basic helix-loop-helix (bHLH) transcription factor Olig2 sustains replication competence of progenitor cells that give rise to neurons and oligodendrocytes. A pathological counterpart of this developmental function is seen in human glioma, wherein Olig2 is required for maintenance of stem-like cells that drive tumor growth. The mitogenic/gliomagenic functions of Olig2 are regulated by phosphorylation of a triple serine motif (S10, S13, and S14) in the amino terminus. Here, we identify a set of three serine/threonine protein kinases (glycogen synthase kinase 3α/ß [GSK3α/ß], casein kinase 2 [CK2], and cyclin-dependent kinases 1/2 [CDK1/2]) that are, collectively, both necessary and sufficient to phosphorylate the triple serine motif. We show that phosphorylation of the motif itself serves as a template to prime phosphorylation of additional serines and creates a highly charged "acid blob" in the amino terminus of Olig2. Finally, we show that small molecule inhibitors of this forward-feeding phosphorylation cascade have potential as glioma therapeutics.
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Carcinogénesis/metabolismo , Carcinogénesis/patología , Glioma/metabolismo , Factor de Transcripción 2 de los Oligodendrocitos/metabolismo , Animales , Quinasa de la Caseína II/metabolismo , Línea Celular Tumoral , Quinasas Ciclina-Dependientes/metabolismo , Modelos Animales de Enfermedad , Glioma/patología , Glucógeno Sintasa Quinasa 3/metabolismo , Humanos , Ratones , Fosforilación/efectos de los fármacos , Fosfoserina/metabolismo , Bibliotecas de Moléculas Pequeñas/farmacología , Proteína p53 Supresora de Tumor/metabolismoRESUMEN
The underlying principles involved in the interpretation of shoeprint comparisons have become a topical subject due to criticisms in the 2009 National Academy of Science (NAS) report on forensic sciences[1]. Difficulties in the application and understanding of these principles were also highlighted in a recent court ruling [2-5] and subsequent discussion of the ruling. We report here a survey that may inform some aspects of this interpretation and discuss the implications of findings from this survey in the light of that court ruling and more importantly the NAS report. 1,511 shoeprints were taken from student volunteers in Auckland, Wellington and Dunedin, New Zealand. 500 shoeprints were sampled from student volunteers at Australian universities. 100 from each of the University of Technology in Sydney, University of Queensland in Brisbane, University of Newcastle, Charles Sturt University in Bathurst and University of Canberra, Australia. These cities are distributed along the east coast of Australia. The shoeprints, taken from each country, were compared against each other for the presence of any pattern correspondences However shoeprints have not been compared between countries. In all locations the pattern of some common and many rare outsole patterns was repeated, with Converse Chuck Taylor All Stars and Vans Canvas Era common in all locations.
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GSK-3 is an essential mediator of several signaling pathways that regulate cortical development. We therefore created conditional mouse mutants lacking both GSK-3α and GSK-3ß in newly born cortical excitatory neurons. Gsk3-deleted neurons expressing upper layer markers exhibited striking migration failure in all areas of the cortex. Radial migration in hippocampus was similarly affected. In contrast, tangential migration was not grossly impaired after Gsk3 deletion in interneuron precursors. Gsk3-deleted neurons extended axons and developed dendritic arbors. However, the apical dendrite was frequently branched while basal dendrites exhibited abnormal orientation. GSK-3 regulation of migration in neurons was independent of Wnt/ß-catenin signaling. Importantly, phosphorylation of the migration mediator, DCX, at ser327, and phosphorylation of the semaphorin signaling mediator, CRMP-2, at Thr514 were markedly decreased. Our data demonstrate that GSK-3 signaling is essential for radial migration and dendritic orientation and suggest that GSK-3 mediates these effects by phosphorylating key microtubule regulatory proteins.DOI: http://dx.doi.org/10.7554/eLife.02663.001.
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Movimiento Celular , Corteza Cerebral/citología , Dendritas/metabolismo , Glucógeno Sintasa Quinasa 3/metabolismo , Transducción de Señal , Animales , Proteínas de Dominio Doblecortina , Proteína Doblecortina , Eliminación de Gen , Glucógeno Sintasa Quinasa 3 beta , Hipocampo/citología , Ratones Endogámicos C57BL , Proteínas Asociadas a Microtúbulos/metabolismo , Mutación/genética , Neuropéptidos/metabolismo , Fosfohidrolasa PTEN/metabolismo , Fosforilación , Especificidad por Sustrato , Vía de Señalización Wnt , beta Catenina/metabolismo , Proteína de Unión al GTP cdc42/metabolismoRESUMEN
The underlying principles involved in the interpretation of shoeprint comparisons have become a topical subject due to criticisms in the 2009 National Academy of Science (NAS) report on forensic sciences [1]. Difficulties in the application and understanding of these principles were also highlighted in a recent court ruling [2-5]. We report here a survey that may inform some aspects of this interpretation and discuss the implications of findings from this survey in the light of that court ruling and more importantly the NAS report. Five hundred shoeprints taken from student volunteers in Auckland, New Zealand were compared against each other for the presence of any pattern correspondences. Comparisons were undertaken of the full outsole and of smaller portions of the more common patterns. Of the 500 shoe impressions collected 488 (97.6%) were ultimately represented only once in the survey. The greatest number of corresponding patterns was for the most common brand of shoe (Converse Chuck Taylor All Star) and occurred in 3 of 500 observations. No instances of an imitation brand matching the authentic brand were found. Smaller sections of the common patterns showed a greater number of corresponding prints. However, the greatest number of matching partial patterns was again for the most common brand of shoe (Converse Chuck Taylor All Star) and occurred in 29 of 500 observations. We conclude that pattern match alone is of considerable evidential value even when the print is partial.
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Modelos Estadísticos , Zapatos , Diseño de Equipo , Ciencias Forenses , Humanos , ProbabilidadRESUMEN
We have defined functions of MEK in regulating gliogenesis in developing cerebral cortex using loss- and gain-of-function mouse genetics. Radial progenitors deficient in both Mek1 and Mek2 fail to transition to the gliogenic mode in late embryogenesis, and astrocyte and oligodendroglial precursors fail to appear. In exploring mechanisms, we found that the key cytokine-regulated gliogenic pathway is attenuated. Further, the Ets transcription family member Etv5/Erm is strongly regulated by MEK and Erm overexpression can rescue the gliogenic potential of Mek-deleted progenitors. Remarkably, Mek1/2-deleted mice surviving postnatally exhibit cortices almost devoid of astrocytes and oligodendroglia and exhibit neurodegeneration. Conversely, expression of constitutively active MEK1 leads to a major increase in numbers of astrocytes in the adult brain. We conclude that MEK is essential for acquisition of gliogenic competence by radial progenitors and that levels of MEK activity regulate gliogenesis in the developing cortex.
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Encéfalo , Regulación del Desarrollo de la Expresión Génica/genética , MAP Quinasa Quinasa 1/deficiencia , MAP Quinasa Quinasa 2/deficiencia , Neuroglía/fisiología , Factores de Edad , Animales , Animales Recién Nacidos , Encéfalo/citología , Encéfalo/embriología , Encéfalo/crecimiento & desarrollo , Recuento de Células , Diferenciación Celular/efectos de los fármacos , Diferenciación Celular/genética , Células Cultivadas , Factor Neurotrófico Ciliar/farmacología , Proteínas de Unión al ADN/metabolismo , Electroporación , Embrión de Mamíferos , Transportador 1 de Aminoácidos Excitadores/metabolismo , Proteínas del Ojo/metabolismo , Proteínas Fluorescentes Verdes/genética , Proteínas Fluorescentes Verdes/metabolismo , Proteínas de Homeodominio/metabolismo , Antígeno Ki-67/metabolismo , MAP Quinasa Quinasa 1/genética , MAP Quinasa Quinasa 2/genética , Ratones , Ratones Transgénicos , Proteína Quinasa 1 Activada por Mitógenos/genética , Proteína Quinasa 3 Activada por Mitógenos/genética , Proteínas del Tejido Nervioso/metabolismo , Neuronas/efectos de los fármacos , Factor de Transcripción PAX6 , Factores de Transcripción Paired Box/metabolismo , Proteínas Represoras/metabolismo , Transducción de Señal/genética , Células Madre/efectos de los fármacos , Células Madre/fisiología , Factores de Transcripción/metabolismoRESUMEN
Treponema denticola is found ubiquitously in the human oral cavity and is mainly associated with bacterial communities implicated in the establishment and development of periodontal disease. The ability to become integrated within biofilm communities is crucial to the growth and survival of oral bacteria, and involves inter-bacterial coaggregation, metabolic cooperation, and synergy against host defences. In this article we show that the chymotrypsin-like proteinase (CTLP), found within a high-molecular-mass complex on the cell surface, mediates adherence of T. denticola to other potential periodontal pathogens, Porphyromonas gingivalis, Fusobacterium nucleatum, Prevotella intermedia and Parvimonas micra. Proteolytic activity per se did not appear to be required for the interactions, and expression of the major outer-sheath protein (Msp) was not necessary, except for binding Parv. micra. Biofilms of densely packed cells and matrix, up to 40 µm in depth, were formed between T. denticola and P. gingivalis on salivary pellicle, with T. denticola cells enriched in the upper layers. Expression of CTLP, but not Msp, was critical for dual-species biofilm formation with P. gingivalis. T. denticola did not form dual-species biofilms with any of the other three periodontal bacterial species under various conditions. Synergy between T. denticola and P. gingivalis was also shown by increased inhibition of blood clotting, which was CTLP-dependent. The results demonstrate the critical role of CTLP in interactions of T. denticola with other oral micro-organisms, leading to synergy in microbial community development and host tissue pathogenesis.
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Adhesión Bacteriana , Quimasas/metabolismo , Interacciones Microbianas , Boca/microbiología , Treponema denticola/fisiología , Biopelículas/crecimiento & desarrollo , Biota , Humanos , Treponema denticola/enzimología , Treponema denticola/crecimiento & desarrollo , Treponema denticola/metabolismoRESUMEN
First, the clothing and shoes from 29 participants who had recently filled their vehicles with petrol were analysed for any traces of petrol. No traces of petrol were found on any of these items. Secondly, the clothing and shoes from 17 participants who had recently used a petrol-powered lawn mower were also analysed for petrol. Petrol was detected on two pairs of shoes from different participants. Components of petrol were detected on a set of clothing from a third participant, however, there were insufficient components present in this sample to confirm the presence of petrol. No traces of petrol were found on the items from the remaining 14 participants. Thirdly, the clothing from a forecourt attendant, a mechanic and a professional lawn mower were analysed at the end of a number of shifts. Petrol was detected on the upper and lower clothing from the forecourt attendant at the end of one shift. No petrol residues were found on the forecourt attendant after a second shift, or on the mechanic's clothing after two separate shifts or on the professional lawn mower's clothing after three separate shifts. These results can be used to assist the forensic analyst in assessing the chance of finding traces of petrol on clothing and shoes after the wearer has performed common activities that involve petrol.
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Negro o Afroamericano , Relaciones Comunidad-Institución , Industria de Alimentos , Frutas/provisión & distribución , Federación para Atención de Salud , Obesidad/prevención & control , Religión , Verduras/provisión & distribución , Conducta Cooperativa , Humanos , Missouri , Obesidad/etnologíaRESUMEN
In 1998/99 the New Zealand Fire Service implemented compressed air foam delivery systems for the suppression of fires in rural areas. This study investigated whether the introduction of the foam to the seat of the fire created any problems in subsequent analyses of fire debris samples. No significant interferences from the foam were found when the samples were analysed by direct headspace using activated carbon strips. The only foam component detected was limonene.
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Aire , Sistemas de Extinción de Incendios , Incendios , Piromanía/diagnóstico , Medicina Legal/métodos , Combustibles Fósiles/análisis , Hidrocarburos/análisis , Sesgo , Emulsiones , Humanos , Nueva Zelanda , Población RuralRESUMEN
This study was aimed at measuring the approximate amount of petrol transferred on to the clothing and shoes of a person during the action of pouring petrol around a room. Two different heights of pouring and two different types of floor surface (carpet and concrete) were investigated. Results show that for all the combinations examined petrol was always transferred to the shoes and often transferred to the upper and lower clothing. This information illustrates the necessity of analysing the clothing and particularly the shoes of any suspected arsonists for the presence of hydrocarbon fuels.