Anthropogenic change decouples a freshwater predator's density feedback.

Intraspecific interactions within predator populations can affect predator-prey dynamics and community structure, highlighting the need to better understand how these interactions respond to anthropogenic change. To this end, we used a half-century (1969-2018) of abundance and size-at-age data from Lake Erie's walleye (Sander vitreus) population to determine how anthropogenic alterations have influenced intraspecific interactions. Before the 1980s, the length-at-age of younger walleye (ages 1 and 2) negatively correlated with older (age 3 +) walleye abundance, signaling a 'density feedback' in which intraspecific competition limited growth. However, after the early 1980s this signal of intraspecific competition disappeared. This decoupling of the density feedback was related to multiple anthropogenic changes, including a larger walleye population resulting from better fisheries management, planned nutrient reductions to improve water quality and transparency, warmer water temperatures, and the proliferation of a non-native fish with novel traits (white perch, Morone americana). We argue that these changes may have reduced competitive interactions by reducing the spatial overlap between older and younger walleye and by introducing novel prey. Our findings illustrate the potential for anthropogenic change to diminish density dependent intraspecific interactions within top predator populations, which has important ramifications for predicting predator dynamics and managing natural resources.

A Pragmatic Randomized Trial Comparing Surgical Clipping and Endovascular Treatment of Unruptured Intracranial Aneurysms.

BACKGROUND AND PURPOSE: Surgical clipping and endovascular treatment are commonly used in patients with unruptured intracranial aneurysms. We compared the safety and efficacy of the 2 treatments in a randomized trial. MATERIALS AND METHODS: Clipping or endovascular treatments were randomly allocated to patients with one or more 3- to 25-mm unruptured intracranial aneurysms judged treatable both ways by participating physicians. The study hypothesized that clipping would decrease the incidence of treatment failure from 13% to 4%, a composite primary outcome defined as failure of aneurysm occlusion, intracranial hemorrhage during follow-up, or residual aneurysms at 1 year, as adjudicated by a core lab. Safety outcomes included new neurologic deficits following treatment, hospitalization of >5 days, and overall morbidity and mortality (mRS > 2) at 1 year. There was no blinding. RESULTS: Two hundred ninety-one patients were enrolled from 2010 to 2020 in 7 centers. The 1-year primary outcome, ascertainable in 290/291 (99%) patients, was reached in 13/142 (9%; 95% CI, 5%-15%) patients allocated to surgery and in 28/148 (19%; 95% CI, 13%-26%) patients allocated to endovascular treatments (relative risk: 2.07; 95% CI, 1.12-3.83; P = .021). Morbidity and mortality (mRS >2) at 1 year occurred in 3/143 and 3/148 (2%; 95% CI, 1%-6%) patients allocated to surgery and endovascular treatments, respectively. Neurologic deficits (32/143, 22%; 95% CI, 16%-30% versus 19/148, 12%; 95% CI, 8%-19%; relative risk: 1.74; 95% CI, 1.04-2.92; P = .04) and hospitalizations beyond 5 days (69/143, 48%; 95% CI, 40%-56% versus 12/148, 8%; 95% CI, 5%-14%; relative risk: 0.18; 95% CI, 0.11-0.31; P < .001) were more frequent after surgery. CONCLUSIONS: Surgical clipping is more effective than endovascular treatment of unruptured intracranial aneurysms in terms of the frequency of the primary outcome of treatment failure. Results were mainly driven by angiographic results at 1 year.

Physical activity and the prevention, reduction, and treatment of alcohol and other drug use across the lifespan (The PHASE review): A systematic review.

The aim of this review is to systematically describe and quantify the effects of PA interventions on alcohol and other drug use outcomes, and to identify any apparent effect of PA dose and type, possible mechanisms of effect, and any other aspect of intervention delivery (e.g. key behaviour change processes), within a framework to inform the design and evaluation of future interventions. Systematic searches were designed to identify published and grey literature on the role of PA for reducing the risk of progression to alcohol and other drug use (PREVENTION), supporting individuals to reduce alcohol and other drug use for harm reduction (REDUCTION), and promote abstinence and relapse prevention during and after treatment of alcohol and other drug use (TREATMENT). Searches identified 49,518 records, with 49,342 excluded on title and abstract. We screened 176 full text articles from which we included 32 studies in 32 papers with quantitative results of relevance to this review. Meta-analysis of two studies showed a significant effect of PA on prevention of alcohol initiation (risk ratio [RR]: 0.72, 95%CI: 0.61 to 0.85). Meta-analysis of four studies showed no clear evidence for an effect of PA on alcohol consumption (Standardised Mean Difference [SMD]: 0.19, 95%, Confidence Interval -0.57 to 0.18). We were unable to quantitatively examine the effects of PA interventions on other drug use alone, or in combination with alcohol use, for prevention, reduction or treatment. Among the 19 treatment studies with an alcohol and other drug use outcome, there was a trend for promising short-term effect but with limited information about intervention fidelity and exercise dose, there was a moderate to high risk of bias. We identified no studies reporting the cost-effectiveness of interventions. More rigorous and well-designed research is needed. Our novel approach to the review provides a clearer guide to achieve this in future research questions addressed to inform policy and practice for different populations and settings.

Publisher Correction: The observation of vibrating pear-shapes in radon nuclei.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Evolution of Octupole Deformation in Radium Nuclei from Coulomb Excitation of Radioactive

There is sparse direct experimental evidence that atomic nuclei can exhibit stable "pear" shapes arising from strong octupole correlations. In order to investigate the nature of octupole collectivity in radium isotopes, electric octupole (E3) matrix elements have been determined for transitions in ^{222,228}Ra nuclei using the method of sub-barrier, multistep Coulomb excitation. Beams of the radioactive radium isotopes were provided by the HIE-ISOLDE facility at CERN. The observed pattern of E3 matrix elements for different nuclear transitions is explained by describing ^{222}Ra as pear shaped with stable octupole deformation, while ^{228}Ra behaves like an octupole vibrator.

Advances in the treatment of cytomegalovirus.

BACKGROUND: Human cytomegalovirus (HCMV) is a threat to immunologically weak patients. HCMV cannot yet be eliminated with a vaccine, despite recent advances. SOURCES OF DATA: Sources of data are recently published research papers and reviews about HCMV treatments. AREAS OF AGREEMENT: Current antivirals target the UL54 DNA polymerase and are limited by nephrotoxicity and viral resistance. Promisingly, letermovir targets the HCMV terminase complex and has been recently approved by the FDA and EMA. AREAS OF CONTROVERSY: Should we screen newborns for HCMV, and use antivirals to treat sensorineural hearing loss after congenital HCMV infection? GROWING POINTS: Growing points are developing drugs against latently infected cells. In addition to small molecule inhibitors, a chemokine-based fusion toxin protein, F49A-FTP, has shown promise in killing both lytically and latently infected cells. AREAS TIMELY FOR DEVELOPING RESEARCH: We need to understand what immune responses are required to control HCMV, and how best to raise these immune responses with a vaccine.

Synergising tools for capacity assessment and One Health operationalisation.

Multisectoral, One Health collaboration is essential for addressing national and international health threats that arise at the human-animal-environment interface. Thanks to the efforts of multiple organisations, countries now have an array of One Health tools available to assess capacities within and between sectors, plan and prioritise activities, and strengthen multisectoral, One Health coordination, communication, and collaboration. By doing so, they are able to address health threats at the human-animal-environment interface, including emerging zoonotic and infectious diseases, more efficiently. However, to ensure optimal outcomes for the countries using these One Health tools, the partners responsible for implementation should regularly collaborate and share information such as implementation timelines, results and lessons learned, so that one process can inform the next. This paper presents a consensus framework on how commonly implemented One Health tools might align to best support countries in strengthening One Health systems. Twelve One Health tools were selected based on their high implementation rates, authors' experience with these tools and their focus on multisectoral, One Health coordination. Through a four-step process, the authors: a) jointly carried out a landscape analysis of One Health tools, using a Cloudbased spreadsheet to share the unique characteristics and applications of each tool; b) performed an implementation analysis to identify and share implementation dynamics and identify respective outcomes and synergies; c) jointly created a consensus conceptual model of how the authors suggest the tools might logically work together; and d) extrapolated from steps 1-3 an agreed-upon overarching conceptual framework for how current and future One Health tools could be categorised to best support One Health system strengthening at the national level. Highlighted One Health tools include the States Parties Annual Reporting Tool under the International Health Regulations (IHR), the World Organisation for Animal Health Performance of Veterinary Services (PVS) Pathway, the Joint External Evaluation process, IHR/PVS National Bridging Workshops, the Centers for Disease Control and Prevention One Health Zoonotic Disease Prioritization Tool, the Food and Agriculture Organization (FAO) Laboratory Mapping Tool, the FAO Assessment Tool for Laboratories and Antimicrobial Resistance Surveillance Systems, the FAO Surveillance Evaluation Tool, the One Health Systems Mapping and Analysis Resource Toolkit, the National Action Plan for Health Security, and IHR Monitoring and Evaluation Framework tools for After Action Reviews and Simulation Exercises. A new guidance document entitled, Taking a Multisectoral, One Health Approach: A Tripartite Guide to Addressing Zoonotic Diseases in Countries was also included as a framework that provides guidance to support the implementation of the outputs of the tools described.

La collaboration multisectorielle suivant l'approche Une seule santé est essentielle pour répondre aux menaces sanitaires survenant à l'interface homme­animal­ environnement à l'échelle nationale et internationale. Grâce aux efforts conjugués de nombreuses organisations, les pays disposent désormais d'une gamme d'outils Une seule santé permettant à la fois d'évaluer les capacités intra et intersectorielles, de planifier et prioriser les activités, et de renforcer la coordination, la communication et la collaboration multisectorielles suivant cette approche. Grâce à ces outils, les pays sont mieux armés pour faire face avec efficacité aux menaces sanitaires à l'interface homme­animal­environnement, en particulier celles liées aux maladies zoonotiques et infectieuses émergentes. Néanmoins, pour optimiser les retombées pour les pays du recours aux outils Une seule santé, les partenaires chargés de leur mise en oeuvre devraient régulièrement collaborer et partager leurs informations, notamment le calendrier de mise en oeuvre, les résultats obtenus et les enseignements tirés, afin que chaque processus contribue à l'amélioration des suivants. Les auteurs présentent un cadre consensuel sur la manière dont les outils Une seule santé les plus courants peuvent converger afin d'aider le mieux possible les pays à renforcer leurs systèmes basés sur cette approche. Douze outils ont été choisis en fonction de leur fréquence d'utilisation, de l'expérience acquise par les auteurs et de l'accent mis sur la coordination multisectorielle Une seule santé. Les auteurs ont ensuite procédé à un examen en quatre étapes, comme suit : a) analyse générale des outils sélectionnés, au moyen d'un tableur sur serveur dématérialisé permettant de saisir et de partager les caractéristiques et les applications spécifiques de chaque outil ; b) analyse de la mise en oeuvre des outils, visant à déterminer et à partager la dynamique et les caractéristiques de mise en oeuvre, ainsi que les résultats respectifs et les synergies qui en ressortent ; c) création d'un modèle conceptuel consensuel contenant les propositions des auteurs en vue d'une convergence raisonnée des fonctionnalités de ces outils ; d) à partir des trois étapes précédentes, conception d'un cadre conceptuel transversal destiné à catégoriser les outils Une seule santé actuels et futurs afin d'apporter un soutien optimal au renforcement des systèmes Une seule santé à l'échelle des pays. Parmi les outils examinés figurent l'Outil d'autoévaluation pour l'établissement de rapports annuels par les États Parties de l'Organisation mondiale de la santé (OMS), qui concerne l'application du Règlement sanitaire international (RSI) ; le Processus sur les Performances des Services vétérinaires (PVS) de l'Organisation mondiale de la santé animale (OIE) ; le processus d'Évaluation extérieure conjointe ; les ateliers nationaux de liaison RSI/PVS ; l'outil Une seule santé de priorisation des maladies zoonotiques des Centres pour le contrôle et la prévention des maladies (CDC) ; l'Outil de cartographie des laboratoires de l'Organisation des Nations Unies pour l'alimentation et l'agriculture (FAO) ; l'Outil d'évaluation de la FAO pour les laboratoires et les systèmes de surveillance de l'antibiorésistance ; l'Outil d'évaluation de la FAO sur la surveillance ; la Boîte à outils cartographiques et analytiques sur les systèmes Une seule santé ; les Plans d'action nationaux de sécurité sanitaire ; et enfin les outils d'examen après action et protocoles de simulation du Cadre de suivi et d'évaluation du RSI. Le document d'orientation récemment publié sous le titre Taking a multisectoral One Health approach: a Tripartite guide to addressing zoonotic diseases in countries [Adopter une approche multisectorielle Une seule santé : Guide tripartite pour lutter contre les maladies zoonotiques] est également présenté, en tant qu'il fournit un cadre directeur en appui de la mise en oeuvre des résultats des outils d'évaluation ci-dessus.

La colaboración multisectorial en clave de Una sola salud es esencial para responder a las amenazas sanitarias de dimensión nacional e internacional que surgen en la confluencia de personas, animales y medio ambiente. Gracias al trabajo de numerosas organizaciones, los países disponen ahora de un repertorio de herramientas concebidas desde la óptica de Una sola salud para evaluar las capacidades existentes dentro de los sectores y entre ellos, planificar y jerarquizar actividades y potenciar las labores de coordinación, comunicación y colaboración multisectoriales en clave de Una sola salud. Gracias a todo ello, los países están en condiciones de luchar más eficazmente contra las amenazas sanitarias en la interfaz de personas, animales y medio ambiente, en particular las enfermedades infecciosas y zoonóticas emergentes. No obstante, para que los países obtengan resultados óptimos del uso de estas herramientas de Una sola salud es preciso que los distintos colaboradores encargados de aplicarlas colaboren e intercambien información periódicamente, por ejemplo sobre plazos de ejecución, resultados obtenidos y enseñanzas extraídas, de tal manera que un proceso pueda alimentar el siguiente. Los autores presentan un conjunto de principios consensuados sobre el modo en que cabría armonizar entre sí las herramientas de Una sola salud utilizadas con frecuencia para que los países cuenten con un apoyo idóneo a la hora de fortalecer los sistemas de Una sola salud. Ante todo, los autores seleccionaron doce de esas herramientas atendiendo a su (elevado) nivel de utilización, la experiencia de los propios autores con ellas y la medida en que privilegian la coordinación multisectorial en clave de Una sola salud. Después, siguiendo un proceso en cuatro etapas: a) efectuaron colectivamente un análisis general de las herramientas existentes, empleando una hoja de cálculo situada en la «nube¼ para poner en común las características y aplicaciones únicas de cada herramienta; b) analizaron la utilización práctica de esas herramientas de Una sola salud para dilucidar y poner en común la dinámica de aplicación de cada una y determinar sus respectivos resultados y sinergias; c) elaboraron de forma concertada un modelo teórico del modo en que, a su juicio, sería lógico que las herramientas funcionaran conjuntamente; y d) a partir de los pasos 1 a 3, extrapolaron consensuadamente un marco teórico global con el que se podrían clasificar las herramientas de Una sola salud, actuales y futuras, para prestar un apoyo idóneo al fortalecimiento del sistema de Una sola salud en cada país. Las herramientas de Una sola salud seleccionadas son: el instrumento de evaluación para la presentación anual de informes de los Estados Partes que forma parte del Reglamento Sanitario Internacional (RSI); el proceso PVS (Prestaciones de los Servicios Veterinarios) de la Organización Mundial de Sanidad Animal (OIE); la herramienta de evaluación externa conjunta del RSI; los talleres nacionales de coordinación RSI-PVS; la herramienta de jerarquización de enfermedades zoonóticas en clave de Una sola salud de los Centros para el Control y la Prevención de Enfermedades (CDC); la herramienta de inventario de laboratorios de la Organización de las Naciones Unidas para la Alimentación y la Agricultura (FAO); la herramienta de evaluación de laboratorios y sistemas de vigilancia de las resistencias a los antimicrobianos de la FAO; la herramienta de evaluación de la vigilancia de la FAO; el juego de herramientas y material de análisis y cartografía de los sistemas de Una sola salud; los planes de acción nacional de seguridad sanitaria de la OMS; las herramientas del marco de seguimiento y evaluación del RSI para la realización de exámenes posteriores a la acción y ejercicios de simulación. También se incluyó una nueva guía de la Tripartita para combatir las enfermedades zoonóticas en los países desde la lógica multisectorial de Una sola salud (Taking a multisectoral One Health approach: a Tripartite guide to addressing zoonotic diseases in countries), en el cual se ofrecen pautas para secundar la aplicación en la práctica de los resultados obtenidos con las citadas herramientas.

Importance of a One Health approach in advancing global health security and the Sustainable Development Goals.

The One Health approach supports global health security by improving coordination, collaboration and communication at the human-animal-environment interface to address shared health threats such as zoonotic diseases, antimicrobial resistance, food safety and others. Over the past decade, country after country has implemented the One Health approach and demonstrated recognised benefits. However, in order to build sustainability of One Health in these efforts, One Health champions and implementers need to collect and provide government decision-makers with country-level data on One Health's impact to help justify policy decisions and resource allocations. Due to the broad, often seemingly all encompassing, nature of One Health in promoting synergies of multiple disciplines and sectors, the One Health community has faced difficulties in determining specific One Health impact indicators for formally evaluating One Health successes. In this paper, the author a) briefly reviews the ongoing commentary on the recognised benefits of the implementation of a One Health approach in the global health security context, b) discusses challenges in measuring the impact of One Health, and c) proposes possible solutions for evaluating the impact of One Health on global health security.

L'approche Une seule santé soutient la sécurité sanitaire mondiale en améliorant la coordination, la collaboration et la communication à l'interface entre les humains, les animaux et l'environnement afin de répondre aux menaces qui leur sont communes, qu'il s'agisse des maladies zoonotiques, de la résistance aux agents antimicrobiens, de la sécurité sanitaire des aliments ou d'autres encore. Au cours de la dernière décennie, les pays ont peu à peu adopté l'approche. Une seule santé et perçu les bénéfices qu'elle apporte. Toutefois, pour asseoir la durabilité des efforts déployés selon l'approche Une seule santé, les principaux pionniers et acteurs de sa mise en œuvre doivent recueillir des données sur l'impact de cette approche au niveau national et les communiquer aux décideurs politiques afin de les aider à justifier les politiques menées et les allocations de ressources. En raison de l'ampleur de l'approche Une seule santé et du caractère souvent globalisant qu'elle peut présenter dans la promotion des synergies pluridisciplinaires et intersectorielles, la communauté Une seule santé rencontre quelques difficultés à déterminer des indicateurs d'impact spécifiques permettant d'évaluer formellement les résultats positifs d'Une seule santé. Dans cet article, l'auteur a) fait le point sur la perception actuelle des bénéfices reconnus de la mise en œuvre de l'approche Une seule santé dans le contexte de la sécurité sanitaire mondiale ; b) examine les défis liés à l'estimation de l'impact d'Une seule santé ; c) propose quelques solutions envisageables pour évaluer cet impact sur la sécurité sanitaire mondiale.

La filosofía de Una sola salud favorece la seguridad sanitaria mundial porque mejora la labor de coordinación, colaboración y comunicación en la confluencia de personas, animales y medio ambiente para afrontar amenazas sanitarias comunes, como puedan ser enfermedades zoonóticas, resistencias a los antimicrobianos o peligros para la inocuidad de los alimentos. De un decenio a esta parte, en un país tras otro, la noción de Una sola salud ha sido aplicada en la práctica y deparado indudables beneficios. Sin embargo, para inscribirla duraderamente en este quehacer, quienes la promueven y pugnan por aplicarla deben reunir datos que demuestren su incidencia real en cada país y hacer llegar esos datos a las instancias decisorias de los gobiernos para que estos puedan fundamentar en ellos sus decisiones sobre políticas y sobre distribución de los recursos. Por la propia amplitud de la noción de Una sola salud, percibida a menudo como una filosofía global para promover sinergias entre múltiples disciplinas y sectores, quienes trabajan en el tema han tenido dificultades para dar con indicadores referidos específicamente al impacto de Una sola salud que ayuden a evaluar oficialmente los éxitos que haya podido deparar. El autor procede: a) repasar brevemente las observaciones actuales sobre las reconocidas ventajas de abordar las cuestiones de seguridad sanitaria mundial desde la óptica de Una sola salud; b) examinar los problemas que se plantean para cuantificar el impacto de esta filosofía; y c) proponer posibles soluciones para determinar el impacto de Una sola salud en la seguridad sanitaria mundia.

The observation of vibrating pear-shapes in radon nuclei.

There is a large body of evidence that atomic nuclei can undergo octupole distortion and assume the shape of a pear. This phenomenon is important for measurements of electric-dipole moments of atoms, which would indicate CP violation and hence probe physics beyond the Standard Model of particle physics. Isotopes of both radon and radium have been identified as candidates for such measurements. Here, we observed the low-lying quantum states in 224Rn and 226Rn by accelerating beams of these radioactive nuclei. We show that radon isotopes undergo octupole vibrations but do not possess static pear-shapes in their ground states. We conclude that radon atoms provide less favourable conditions for the enhancement of a measurable atomic electric-dipole moment.

Metameric spinal AVM: Long-term symptomatic relief achieved by embolization of the extradural component.

BACKGROUND: Metameric spinal cord arteriovenous malformations (AVMs) are rare lesions characterized by an intradural and extradural component. They are difficult to treat surgically by the endovascular route. We report a case in which symptomatic relief was achieved by embolization of the extradural component only. CASE PRESENTATION: A 35-year-old woman presented with acute worsening of back pain, weakness in the left leg and urinary retention. Spinal angiography showed a metameric spinal cord AVM with partial common venous drainage of the extradural and intradural components. CONCLUSIONS: Targeted embolization of the extradural component led to dramatic improvement of the patient's symptoms, probably by achieving venous decongestion. She remains neurologically stable at two years' follow-up.

The effect of cut-off frequency when high-pass filtering equine sEMG signals during locomotion.

High-pass filtering (HPF) is a fundamental signal processing method for the attenuation of low-frequency noise contamination, namely baseline noise and movement artefact noise, in human surface electromyography (sEMG) research. Despite this, HPF is largely overlooked in equine sEMG research, with many studies not applying, or failing to describe, the application of HPF. An optimal HPF cut-off frequency maximally attenuates noise while minimally affecting sEMG signal power, but this has not been investigated for equine sEMG signals. The aim of this study was to determine the optimal cut-off frequency for attenuation of low-frequency noise in sEMG signals from the Triceps Brachii and Biceps Femoris of 20 horses during trot and canter. sEMG signals were HPF with cut-off frequencies ranging from 0 to 80 Hz and were subjected to power spectral analysis and enveloped using RMS to calculate spectral peaks, indicative of motion artefact, and signal loss, respectively. Processed signals consistently revealed a low-frequency peak between 0 and 20 Hz, which was associated with motion artefact. Across all muscles and gaits, a 30-40 Hz cut-off fully attenuated the low-frequency peak with the least amount of signal loss and was therefore considered optimal for attenuating low-frequency noise from the sEMG signals explored in this study.

A hexagon in Saturn's northern stratosphere surrounding the emerging summertime polar vortex.

Saturn's polar stratosphere exhibits the seasonal growth and dissipation of broad, warm vortices poleward of ~75° latitude, which are strongest in the summer and absent in winter. The longevity of the exploration of the Saturn system by Cassini allows the use of infrared spectroscopy to trace the formation of the North Polar Stratospheric Vortex (NPSV), a region of enhanced temperatures and elevated hydrocarbon abundances at millibar pressures. We constrain the timescales of stratospheric vortex formation and dissipation in both hemispheres. Although the NPSV formed during late northern spring, by the end of Cassini's reconnaissance (shortly after northern summer solstice), it still did not display the contrasts in temperature and composition that were evident at the south pole during southern summer. The newly formed NPSV was bounded by a strengthening stratospheric thermal gradient near 78°N. The emergent boundary was hexagonal, suggesting that the Rossby wave responsible for Saturn's long-lived polar hexagon-which was previously expected to be trapped in the troposphere-can influence the stratospheric temperatures some 300 km above Saturn's clouds.

Pre-operative versus post-operative radiosurgery for brain metastasis: Effects on treatment volume and inter-observer variability.

PURPOSE/OBJECTIVES: Compared to post-operative whole brain radiotherapy, resection cavity radiosurgery reduces impact on neuro-cognitive function and improves quality-of-life. However, coverage of the operative tract, in addition to tumour bed, may lead to large treatment volumes and inter-observer variability. We hypothesized that pre-operative radiosurgery reduces target volume size and inter-observer variability compared to post-operative radiosurgery. MATERIALS/METHODS: We identified 10 consecutive patients, with solitary brain metastasis, treated with post-operative cavity radiosurgery.Pre- and post-operative axial T1 contrast MRI were co-registered with the planning CT scans. Three radiation oncologists independently contoured the target volumes on the pre- and post-operative imaging. A 2mm-PTV margin was utilized for both strategies and radiosurgery treatment plans were generated. The following parameters were evaluated in the 2 plans: Mean target volume (cc), 50% isodose volume (cc), Inter-observer variability (Jaccard Index JI) and Conformity Index (CI). RESULTS: There was no significant difference in the mean target volume, nor 50% isodose volume, between pre- and post-operative strategies. (17.6 (95% CI 9.98 - 25.22) versus 19.4 (95% CI 10.11 - 28.69) cc, P=0.80; 61.7 (95% CI 38.4 - 85.0) vs 77.7 (95% CI 34.94 - 120.46) cc, P=0.65). There was significantly less inter-observer variability and improved conformity in the pre-operative group (Mean JI 0.84(95% CI 0.82 - 0.86) versus 0.70 (95% CI 0.62 - 0.78), P = 0.005; Mean CI 1.32 (95% CI 1.26 - 1.38) vs 1.45 (95% CI 1.36 - 1.54), P= 0.01). Planned subgroup analysis did not reveal any significant difference (between pre- vs post-op) in the mean volume of cystic versus non-cystic metastasis. Deep lesions (>2.5cm from dura) had a larger post-operative target volume (25.8 (95% CI 15.1 - 36.5) vs 12.3 (95% CI 6.54 - 18.06) cc, P=0.06) compared to superficial lesions. CONCLUSION: Pre-operative radiosurgery has less inter-observer variability and improved plan conformity. However, there was no difference in mean target volume between the pre- versus post-operative radiation. Contouring guidelines, and peer review, may help to reduce inter-observer variability for cavity radiosurgery.

Diagnostic Accuracy of Centrally Restricted Diffusion in the Differentiation of Treatment-Related Necrosis from Tumor Recurrence in High-Grade Gliomas.

BACKGROUND AND PURPOSE: Centrally restricted diffusion has been demonstrated in recurrent high-grade gliomas treated with bevacizumab. Our purpose was to assess the accuracy of centrally restricted diffusion in the diagnosis of radiation necrosis in high-grade gliomas not treated with bevacizumab. MATERIALS AND METHODS: In this prospective study, we enrolled patients with high-grade gliomas who developed a new ring-enhancing necrotic lesion and who underwent re-resection. The presence of a centrally restricted diffusion within the ring-enhancing lesion was assessed visually on diffusion trace images and by ADC measurements on 3T preoperative diffusion tensor examination. The percentage of tumor recurrence and radiation necrosis in each surgical specimen was defined histopathologically. The association between centrally restricted diffusion and radiation necrosis was assessed using the Fisher exact test. Differences in ADC and the ADC ratio between the groups were assessed via the Mann-Whitney U test, and receiver operating characteristic curve analysis was performed. RESULTS: Seventeen patients had re-resected ring-enhancing lesions: 8 cases of radiation necrosis and 9 cases of tumor recurrence. There was significant association between centrally restricted diffusion by visual assessment and radiation necrosis (P = .015) with a sensitivity of 75% and a specificity of 88.9%, a positive predictive value 85.7%, and a negative predictive value of 80% for the diagnosis of radiation necrosis. There was a statistically significant difference in the ADC and ADC ratio between radiation necrosis and tumor recurrence (P = .027). CONCLUSIONS: The presence of centrally restricted diffusion in a new ring-enhancing lesion might indicate radiation necrosis rather than tumor recurrence in high-grade gliomas previously treated with standard chemoradiation without bevacizumab.

Evidence-based guides in tracheostomy use in critical patients

Objetivos: Proporcionar guías de traqueostomía para el paciente crítico, basadas en la evidencia científica disponible, y facilitar la identificación de áreas en las cuales se requieren mayores estudios. Métodos: Un grupo de trabajo formado con representantes de 10 países pertenecientes a la Federación Panamericana e Ibérica de Sociedades de Medicina Crítica y Terapia Intensiva y a la Latin American Critical Care Trial Investigators Network(LACCTIN) desarrollaron estas recomendaciones basadas en el sistema Grading of Recommendations Assessment, Development and Evaluation (GRADE). Resultados: El grupo identificó 23 preguntas relevantes entre las 87 preguntas planteadas inicialmente. En la búsqueda inicial de la literatura se identificaron 333 estudios, de los cuales se escogieron un total de 226. El equipo de trabajo generó un total de 19 recomendaciones: 10 positivas (1B = 3, 2C = 3, 2D = 4) y 9 negativas (1B = 8, 2C = 1). En 6 ocasiones no se pudieron establecer recomendaciones. Conclusión: La traqueostomía percutánea se asocia a menor riesgo de infecciones en comparación con la traqueostomía quirúrgica. La traqueostomía precoz solo parece reducir la duración de la ventilación mecánica pero no la incidencia de neumonía, la duración de la estancia hospitalaria o la mortalidad a largo plazo. La evidencia no apoya el uso de broncoscopia de forma rutinaria ni el uso de máscara laríngea durante el procedimiento. Finalmente, el entrenamiento adecuado previo es tanto o más importante que la técnica utilizada para disminuir las complicaciones.(AU)

OBJECTIVES: Provide evidence based guidelines for tracheostomy in critically ill adult patients and identify areas needing further research. METHODS: A task force composed of representatives of 10 member countries of the Pan-American and Iberic Federation of Societies of Critical and Intensive Therapy Medicine and of the Latin American Critical Care Trial Investigators Network developed recommendations based on the Grading of Recommendations Assessment, Development and Evaluation system. RESULTS: The group identified 23 relevant questions among 87 issues that were initially identified. In the initial search, 333 relevant publications were identified of which 226 publications were chosen. The task force generated a total of 19 recommendations: 10 positive (1B=3, 2C=3, 2D=4) and 9 negative (1B=8, 2C=1). A recommendation was not possible in six questions. CONCLUSION: Percutaneous techniques are associated with a lower risk of infections compared to surgical tracheostomy. Early tracheostomy only seems to reduce the duration of ventilator use but not the incidence of pneumonia, the length of stay, or the long-term mortality rate. The evidence does not support the use of routine bronchoscopy guidance or laryngeal masks during the procedure. Finally, proper prior training is as important or even a more significant factor in reducing complications than the technique used.(AU)

Evidence-based guides in tracheostomy use in critical patients. / Guías basadas en la evidencia para el uso de traqueostomía en el paciente crítico.

OBJECTIVES: Provide evidence based guidelines for tracheostomy in critically ill adult patients and identify areas needing further research. METHODS: A task force composed of representatives of 10 member countries of the Pan-American and Iberic Federation of Societies of Critical and Intensive Therapy Medicine and of the Latin American Critical Care Trial Investigators Network developed recommendations based on the Grading of Recommendations Assessment, Development and Evaluation system. RESULTS: The group identified 23 relevant questions among 87 issues that were initially identified. In the initial search, 333 relevant publications were identified of which 226 publications were chosen. The task force generated a total of 19 recommendations: 10 positive (1B=3, 2C=3, 2D=4) and 9 negative (1B=8, 2C=1). A recommendation was not possible in six questions. CONCLUSION: Percutaneous techniques are associated with a lower risk of infections compared to surgical tracheostomy. Early tracheostomy only seems to reduce the duration of ventilator use but not the incidence of pneumonia, the length of stay, or the long-term mortality rate. The evidence does not support the use of routine bronchoscopy guidance or laryngeal masks during the procedure. Finally, proper prior training is as important or even a more significant factor in reducing complications than the technique used.

Targeting the latent cytomegalovirus reservoir with an antiviral fusion toxin protein.

Reactivation of human cytomegalovirus (HCMV) in transplant recipients can cause life-threatening disease. Consequently, for transplant recipients, killing latently infected cells could have far-reaching clinical benefits. In vivo, myeloid cells and their progenitors are an important site of HCMV latency, and one viral gene expressed by latently infected myeloid cells is US28. This viral gene encodes a cell surface G protein-coupled receptor (GPCR) that binds chemokines, triggering its endocytosis. We show that the expression of US28 on the surface of latently infected cells allows monocytes and their progenitor CD34+ cells to be targeted and killed by F49A-FTP, a highly specific fusion toxin protein that binds this viral GPCR. As expected, this specific targeting of latently infected cells by F49A-FTP also robustly reduces virus reactivation in vitro. Consequently, such specific fusion toxin proteins could form the basis of a therapeutic strategy for eliminating latently infected cells before haematopoietic stem cell transplantation.

Public Health Implications of Changing Rodent Importation Patterns - United States, 1999-2013.

The United States imports a large volume of live wild and domestic animal species; these animals pose a demonstrated risk for introduction of zoonotic diseases. Rodents are imported for multiple purposes, including scientific research, zoo exhibits and the pet trade. Current U.S. public health regulatory restrictions specific to rodent importation pertain only to those of African origin. To understand the impacts of these regulations and the potential public health risks of international rodent trade to the United States, we evaluated live rodent import records during 1999-2013 by shipment volume and geographic origin, source (e.g. wild-caught versus captive- or commercially bred), intended purpose and rodent taxonomy. Live rodent imports increased from 2737 animals during 1999 to 173 761 animals during 2013. Increases in both the number and size of shipments contributed to this trend. The proportion of wild-captured imports declined from 75% during 1999 to <1% during 2013. Nearly all shipments during these years were imported for commercial purposes. Imports from Europe and other countries in North America experienced notable increases in volume. Gerbils and hamsters arriving from Europe and chinchillas, guinea pigs and hamsters arriving from other countries in North America were predominant taxa underlying this trend. After 2003, African-origin imports became sporadic events under the federal permit process. These patterns suggest development of large-scale captive rodent breeding markets abroad for commercial sale in the United States. While the shift from wild-captured imports alleviates many conservation concerns and risks for novel disease emergence, such consolidated sourcing might elevate exposure risks for zoonotic diseases associated with high-density rodent breeding (e.g. lymphocytic choriomeningitis or salmonellosis). A responsive border health system must periodically re-evaluate importation regulations in conjunction with key stakeholders to ensure a balance between the economic benefits of rodent trade against the potential public health risks.