Five years ago, the Melanoma Research Foundation (MRF) conducted an assessment of the challenges and opportunities facing the melanoma research community and patients with melanoma. Since then, ...remarkable progress has been made on both the basic and clinical research fronts. However, the incidence, recurrence, and death rates for melanoma remain unacceptably high and significant challenges remain. Hence, the MRF Scientific Advisory Council and Breakthrough Consortium, a group that includes clinicians and scientists, reconvened to facilitate intensive discussions on thematic areas essential to melanoma researchers and patients alike, prevention, detection, diagnosis, metastatic dormancy and progression, response and resistance to targeted and immune-based therapy, and the clinical consequences of COVID-19 for patients with melanoma and providers. These extensive discussions helped to crystalize our understanding of the challenges and opportunities facing the broader melanoma community today. In this report, we discuss the progress made since the last MRF assessment, comment on what remains to be overcome, and offer recommendations for the best path forward.
Herein we describe the design and synthesis of a series of pyridopyrazine-1,6-dione γ-secretase modulators (GSMs) for Alzheimer’s disease (AD) that achieve good alignment of potency, metabolic ...stability, and low MDR efflux ratios, while also maintaining favorable physicochemical properties. Specifically, incorporation of fluorine enabled design of metabolically less liable lipophilic alkyl substituents to increase potency without compromising the sp3-character. The lead compound 21 (PF-06442609) displayed a favorable rodent pharmacokinetic profile, and robust reductions of brain Aβ42 and Aβ40 were observed in a guinea pig time-course experiment.
Despite broad recognition of the value of social sciences and increasingly vocal calls for better engagement with the human element of conservation, the conservation social sciences remain ...misunderstood and underutilized in practice. The conservation social sciences can provide unique and important contributions to society's understanding of the relationships between humans and nature and to improving conservation practice and outcomes. There are 4 barriers—ideological, institutional, knowledge, and capacity—to meaningful integration of the social sciences into conservation. We provide practical guidance on overcoming these barriers to mainstream the social sciences in conservation science, practice, and policy. Broadly, we recommend fostering knowledge on the scope and contributions of the social sciences to conservation, including social scientists from the inception of interdisciplinary research projects, incorporating social science research and insights during all stages of conservation planning and implementation, building social science capacity at all scales in conservation organizations and agencies, and promoting engagement with the social sciences in and through global conservation policy-influencing organizations. Conservation social scientists, too, need to be willing to engage with natural science knowledge and to communicate insights and recommendations clearly. We urge the conservation community to move beyond superficial engagement with the conservation social sciences. A more inclusive and integrative conservation science—one that includes the natural and social sciences—will enable more ecologically effective and socially just conservation. Better collaboration among social scientists, natural scientists, practitioners, and policy makers will facilitate a renewed and more robust conservation. Mainstreaming the conservation social sciences willfacilitate the uptake of the full range of insights and contributions from these fields into conservation policy and practice. A pesar del reconocimiento general del valor de las ciencias sociales y los crecientes llamados por un mejor compromiso con el elemento humano de la conservación, las ciencias sociales de la conservación siguen siendo malentendidas y poco utilizadas en la práctica. Las ciencias sociales de la conservación pueden proporcionar contribuciones únicas e importantes para el entendimiento de la sociedad de las relaciones entre los humanos y la naturaleza y para la mejora de las prácticas de la conservación y sus resultados. Existen cuatro barreras - ideológicas, institucionales, de conocimiento y de capacidad - para la integración significativa de las ciencias sociales dentro de la conservación. Proporcionamos una guia práctica sobre cómo sobreponerse a estas barreras paraJncorporar la perspectiva de las ciencias sociales a la ciencia, las prácticas y las políticas de conservación. En general, recomendamos promover el conocimiento sobre el alcance y las contribuciones de las ciencias sociales para la conservación, incluir a los científicos sociales desde el origen de los proyectos de investigación interdisciplinaria, incorporar la investigación de las ciencias sociales y las percepciones durante todas las fases de la planificación y la implementación de la conservación, construir la capacidad de las ciencias sociales en todas las escalas de las organizaciones y agencias de conservación y promover el compromiso con las ciencias sociales en y a través de organizaciones de conservación con influencia política. Los científicos sociales de la conservación, también, necesitan estar dispuestos a involucrarse con el conocimiento de las ciencias naturales y a comunicar percepciones y recomendaciones de manera clara. Le urgimos a la comunidad de la conservación que vaya más allá del compromiso superficial con las ciencias sociales de la conservación. Una ciencia de la conservación más incluyente y integradora - una que incluya a las ciencias sociales y naturales - permitirá una conservación más justa socialmente y más efectiva ecológicamente. Una mejor colaboración entre los científicos sociales, los científicos naturales, los practicantes y quienes elaboran las políticas facilitará una conservación más renovada y más sólida. Incorporar la perspectiva de las ciencias sociales de la conservación facilitará la absorción de la extensión completa de conocimiento y contribuciones de estos campos a la práctica y las políticas de la conservación.
Cirrhosis and hepatic encephalopathy (HE) can adversely affect survival, but their effect on socioeconomic and emotional burden on the family is not clear. The aim was to study the emotional and ...socioeconomic burden of cirrhosis and HE on patients and informal caregivers.
A cross-sectional study in two transplant centers (Veterans and University) of cirrhotic patients and their informal caregivers was performed. Demographics for patient/caregivers, model-for-end-stage liver disease (MELD) score, and cirrhosis complications were recorded. Patients underwent a cognitive battery, sociodemographic, and financial questionnaires. Caregivers were given the perceived caregiver burden (PCB; maximum=155) and Zarit Burden Interview (ZBI)-Short Form (maximum=48) and questionnaires for depression, anxiety, and social support.
A total of 104 cirrhotics (70% men, 44% previous HE, median MELD 12, 49% veterans) and their caregivers (66% women, 77% married, relationship duration 32±14 years) were included. Cirrhosis severely impacted the family unit with respect to work (only 56% employed), finances, and adherence. Those with previous HE had worse unemployment (87.5 vs. 19%, P=0.0001) and financial status (85 vs. 61%, P=0.019) and posed a higher caregiver burden; PCB (75 vs. 65, P=0.019) and ZBI (16 vs. 11, P=0.015) compared with others. Cognitive performance and MELD score were significantly correlated with employment and caregiver burden. Veterans and non-veterans were equally affected. On regression, depression score, MELD, and cognitive tests predicted both PCB and ZBI score.
Previous HE and cognitive dysfunction are associated with worse employment, financial status, and caregiver burden. Cirrhosis-related expenses impact the family unit's daily functioning and medical adherence. A multidisciplinary approach to address this burden is required.
A Multi-Point Contact HPGe Detector Dion, Michael P.; Fast, James E.; Hull, Ethan L. ...
IEEE transactions on nuclear science,
12/2014, Letnik:
61, Številka:
6
Journal Article
Recenzirano
A novel, multi-point contact high-purity germanium detector has been developed for applications in high-rate gamma environments. The planar detector was fabricated with seven point contacts, a ...high-voltage steering grid and bias electrode using amorphous germanium technology. We have characterized this detector and report herein on the depletion profile, leakage current, energy resolution, and charge-sharing behavior.
Most melanoma patients present with thin (<or=1.0 mm) lesions. Indications for sentinel lymph node (SLN) biopsy are not well defined for this group. Previously, we reported an association between ...mitotic rate (MR) and SLN positivity in these patients. The study was limited by a relatively small sample size and low statistical power. In this study, we evaluated a large population of patients with thin melanoma from the pre-SLN era to identify predictors of regional nodal disease (RND) that may serve as a surrogate for SLN positivity.
Eight hundred eighty-two patients evaluated between 1972 and 1991 were included in the study. Univariate and multivariate regression analyses were performed by using clinical and histological data to identify factors associated with RND. A multivariate logistic regression model was developed and applied to the previously reported group of patients with thin melanomas who underwent SLN biopsy between 1996 and 2004 for validation.
Thirty-eight patients (4.3%) had evidence of RND. In the multivariate analysis, a MR>0, vertical growth phase (VGP), male sex, and ulceration were statistically significant predictors of RND. Patients at the highest risk according to a classification tree analysis (VGP and MR>0) had an RND rate of 11.9%. The regression model developed predicted well the SLN status in the validation sample.
Investigation of a large pre-SLN population identified MR>0, ulceration, VGP, and male sex as independently predictive of RND in patients with thin melanomas. These factors may help to identify subgroups of these patients that have clinically significant risks of SLN positivity.
Accurate representation of global stratospheric aerosols from volcanic and nonvolcanic sulfur emissions is key to understanding the cooling effects and ozone losses that may be linked to volcanic ...activity. Attribution of climate variability to volcanic activity is of particular interest in relation to the post‐2000 slowing in the rate of global average temperature increases. We have compiled a database of volcanic SO2 emissions and plume altitudes for eruptions from 1990 to 2014 and developed a new prognostic capability for simulating stratospheric sulfate aerosols in the Community Earth System Model. We used these combined with other nonvolcanic emissions of sulfur sources to reconstruct global aerosol properties from 1990 to 2014. Our calculations show remarkable agreement with ground‐based lidar observations of stratospheric aerosol optical depth (SAOD) and with in situ measurements of stratospheric aerosol surface area density (SAD). These properties are key parameters in calculating the radiative and chemical effects of stratospheric aerosols. Our SAOD calculations represent a clear improvement over available satellite‐based analyses, which generally ignore aerosol extinction below 15 km, a region that can contain the vast majority of stratospheric aerosol extinction at middle and high latitudes. Our SAD calculations greatly improve on that provided for the Chemistry‐Climate Model Initiative, which misses about 60% of the SAD measured in situ on average during both volcanically active and volcanically quiescent periods.
Key Points
We developed a global aerosol reconstruction for 1990‐2014 using CESM1(WACCM) and volcanic emissions
Satellite‐based forcing data neglect 50‐95% of extratropical stratospheric aerosol
Our output agrees much better with in situ and ground‐based observations than standard forcing data
The Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Initiative, established by the National Office of Public Health Genomics at the Centers for Disease Control and Prevention, ...supports the development and implementation of a rigorous, evidence-based process for evaluating genetic tests and other genomic applications for clinical and public health practice in the United States. An independent, non-federal EGAPP Working Group (EWG), a multidisciplinary expert panel selects topics, oversees the systematic review of evidence, and makes recommendations based on that evidence. This article describes the EGAPP processes and details the specific methods and approaches used by the EWG.
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