Multiple independent genomic profiling efforts have recently identified clinically and molecularly distinct subgroups of ependymoma arising from all three anatomic compartments of the central nervous ...system (supratentorial brain, posterior fossa, and spinal cord). These advances motivated a consensus meeting to discuss: (1) the utility of current histologic grading criteria, (2) the integration of molecular-based stratification schemes in future clinical trials for patients with ependymoma and (3) current therapy in the context of molecular subgroups. Discussion at the meeting generated a series of consensus statements and recommendations from the attendees, which comment on the prognostic evaluation and treatment decisions of patients with intracranial ependymoma (WHO Grade II/III) based on the knowledge of its molecular subgroups. The major consensus among attendees was reached that treatment decisions for ependymoma (outside of clinical trials) should not be based on grading (II vs III). Supratentorial and posterior fossa ependymomas are distinct diseases, although the impact on therapy is still evolving. Molecular subgrouping should be part of all clinical trials henceforth.
Terrorism is a major problem worldwide, causing thousands of fatalities and billions of dollars in damage every year. To address this threat, we propose a novel feature representation method and ...evaluate machine learning models that learn from localized news data in order to predict whether a terrorist attack will occur on a given calendar date and in a given state. The best model (a Random Forest aided by a novel variable-length moving average method) achieved area under the receiver operating characteristic (AUROC) of greater than or equal to 0.667 (statistically significant w.r.t. random guessing with p less than or equal to .0001) on four of the five states that were impacted most by terrorism between 2015 and 2018. These results demonstrate that treating terrorism as a set of independent events, rather than as a continuous process, is a fruitful approach-especially when historical events are sparse and dissimilar-and that large-scale news data contains information that is useful for terrorism prediction. Our analysis also suggests that predictive models should be localized (i.e., state models should be independently designed, trained, and evaluated) and that the characteristics of individual attacks (e.g., responsible group or weapon type) were not correlated with prediction success. These contributions provide a foundation for the use of machine learning in efforts against terrorism in the United States and beyond.
The sociology of religion today faces new and remarkable opportunities to contribute interesting and important knowledge and understanding about the role of religion in social, political, economic ...and cultural life for scholarly and public audiences. But in order to meet and capitalize successfully upon those opportunities, the field at present needs to shake off some besetting habits of mind, expand its horizons, re-orient its debates, construct a new agenda for priority investigations, and rethink some of its larger theoretical assumptions, frameworks and paradigms. The author's purpose in this article is to help the field move forward toward a greater clarity of vision and purpose, to help solidify a firmer sense of the substantive and theoretical agendas that matter most in the field's endeavor to make its contribution to the larger discipline of sociology and to public understanding. First, he outlines a series of specific substantive and methodological concerns that deserve greater scholarly attention by sociologists in the coming years and sets the stage for the eight separate articles in this special section. Second, he considers a recent theoretical innovation concerning the model of modernity and social change--the hypothesis of "multiple modernities"--that in his view deserves much greater attention and development, particularly when it comes to the study of religion in modernity and post-modernity. Third, he advocates an alternative meta-theoretical basis on which to better pursue the sociology of religion--in fact, actually, all of sociology--in a way that he believes will be more fruitful than the two background approaches that currently govern most scholarship, namely, positivist empiricism and hermeneutical interpretivism. That alternative is the philosophy of (social) science known as critical realism.
Walking speed has been associated with many clinical outcomes (e.g., frailty, mortality, joint replacement need, etc.). Accurately measuring walking speed (stride length x step count/time) typically ...requires significant clinician/staff time or a gait lab with specialized equipment (i.e., electronic timers or motion capture). In the present study, our goal was to measure "step count" via smartphones through novel software and to compare with step tracking software that come standard with iOS and Android smartphones as a first step in walking speed measurement.
A separate calibration and validation data collection was performed. Individuals in the calibration collection (n = 5) walked 20m at normal and slow speed (<1.0 m/s). Appropriate settings for the novel mobile application were chosen to measure step count. Individuals in the validation (n = 52) collection walked at 6m, 10m, and 20m at normal and slow walking speeds. We compared step difference (absolute difference) from observed step counts to native step tracking software and our novel software derived step counts. We used generalized estimated equation adjusted (participant level) negative binomial regression models of absolute step difference from observed step counts, to determine optimal settings (calibration) and subsequently to gauge performance of the shake algorithm settings and native step tracking software across different distances and speeds (validation).
For iOS/iPhone 6, when compared to observed step count, the shake service (software driven approach) significantly outperformed the embedded native step tracking software across all distances at slow speed, and for short distance (6m) at normal speed. On the Android phone, the shake service outperformed the native step tracking software at slow speed at 6 meters and 20 meters, while its performance eclipsed the native step tracking software only at 20 meters at normal speed.
Our software based approach outperformed native step tracking software across various speeds and distances and carries the advantage of having adjustable measurement parameters that can be further optimized for specific medical conditions. Such software applications will provide an effective way to capture standardized data across multiple commercial smartphone devices, facilitating the future capture of walking speed and other clinically important performance parameters that will influence clinical and home care in the era of value based care.
The Public Trust Doctrine (PTD) is considered the cornerstone of the North American Model of Wildlife Conservation. Effective application of the PTD requires a clear understanding of the doctrine and ...appropriate behavior by trustees, trust managers, and beneficiaries. Most PTD literature refers generically to the role of the government as the people's trustee, without addressing the differences between the legislative, executive, and judicial branches of government in the United States or recognizing the distinction between elected and appointed officials and career civil servants. Elected and appointed officials, especially in the legislative branch, have policy-level decision-making authority that makes them trustees of the people's wildlife under the PTD. In contrast, career professionals working for state wildlife agencies (SWA's) have ministerial duties as trust managers. The differences between the roles of trustees and trust managers are important. By focusing on their role as trust managers, while supporting and respecting the role of elected and appointed officials as trustees, SWA professionals can more effectively advance application of the PTD.
In the United States, the public has a constitutional right to access criminal trial proceedings. In practice, it can be difficult or impossible for the public to exercise this right. We present ...JUSTFAIR: Judicial System Transparency through Federal Archive Inferred Records, a database of criminal sentencing decisions made in federal district courts. We have compiled this data set from public sources including the United States Sentencing Commission, the Federal Judicial Center, the Public Access to Court Electronic Records system, and Wikipedia. With nearly 600,000 records from the years 2001-2018, JUSTFAIR is the first large scale, free, public database that links information about defendants and their demographic characteristics with information about their federal crimes, their sentences, and, crucially, the identity of the sentencing judge.
Diffuse intrinsic pontine glioma (DIPG) is an aggressive brain tumour that occurs in the pons of the brainstem and accounts for over 80% of all brainstem gliomas. The median age at diagnosis is ...6-7 years old, with less than 10% overall survival 2 years after diagnosis and less than 1% after 5 years. DIPGs are surgically inaccessible, and radiation therapy provides only transient benefit, with death ensuing from relentless local tumour infiltration. DIPGs are now the leading cause of brain tumour deaths in children, with a societal cancer burden in years of life lost (YLL) of more than 67 per individual,
approximately 14 and 16 YLL for lung and breast cancer respectively. More than 95 clinical drug trials have been conducted on children with DIPGs, and all have failed to improve survival. No single or combination chemotherapeutic strategy has been successful to date because of our inability to identify targeted drugs for this disease and to deliver these drugs across an intact blood-brain barrier (BBB). Accordingly, there has been an increased focus on immunotherapy research in DIPG, with explorations into treatments such as chimeric antigen receptor T (CAR-T) cells, immune checkpoint blockades, cancer vaccines, and autologous cell transfer therapy. Here, we review the most recent advances in identifying genetic factors influencing the development of immunotherapy for DIPG. Additionally, we explore emerging technologies such as Magnetic Resonance-guided Focused Ultrasound (MRgFUS) in potential combinatorial approaches to treat DIPG.
Mosquitoes in the genera
and
are vectors of Rift Valley fever virus (RVFV), which emerges in periodic epidemics in Africa and Saudi Arabia. Factors that influence the transmission dynamics of RVFV ...are not well characterized. To address this, we interrogated mosquito host-signaling responses through analysis of differentially expressed genes (DEGs) in two mosquito species with marked differences in RVFV vector competence:
(
, low competence) and
(
, high competence). Mosquito-host transcripts related to three different signaling pathways were investigated. Selected genes from the Wingless (Wg, WNT-beta-catenin) pathway, which is a conserved regulator of cell proliferation and differentiation, were assessed. One of these,
(
), differentially regulates progression/inhibition of the WNT and JNK (c-Jun N-terminal Kinase) pathways. A negative regulator of the JNK-signaling pathway, puckered, was also assessed. Lastly, Janus kinase/signal transducers and activators of transcription (JAK-STAT) are important for innate immunity; in this context, we tested domeless levels. Here, individual
and
were exposed to RVFV MP-12 via oral bloodmeals and held for 14 days. Robust decreases in DEGs in both
and
were observed. In particular,
expression, but not
, was correlated to the presence/absence of viral RNA at 14 days post-challenge (dpc). Moreover, there was an inverse relationship between the viral copy number and
expression.
silencing resulted in increased viral copy numbers compared to controls at 3 dpc, consistent with a role for
in antiviral immunity. Analysis of cis-regulatory regions for the genes of interest revealed clues to upstream regulation of these pathways.
Abstract The blood brain barrier (BBB) is a major impediment to the delivery of therapeutics into the central nervous system (CNS). Gold nanoparticles (AuNPs) have been successfully employed in ...multiple potential therapeutic and diagnostic applications outside the CNS. However, AuNPs have very limited biodistribution within the CNS following intravenous administration. Magnetic resonance imaging guided focused ultrasound (MRgFUS) is a novel technique that can transiently increase BBB permeability allowing delivery of therapeutics into the CNS. MRgFUS has not been previously employed for delivery of AuNPs into the CNS. This work represents the first demonstration of focal enhanced delivery of AuNPs into the CNS using MRgFUS in a rat model both safely and effectively. Histologic visualization and analytical quantification of AuNPs within the brain parenchyma suggest BBB transgression. These results suggest a role for MRgFUS in the delivery of AuNPs with therapeutic potential into the CNS for targeting neurological diseases. From the Clinical Editor Gold nanoparticles have been successfully utilized in experimental diagnostic and therapeutic applications; however, the blood-brain barrier (BBB) is not permeable to these particles. In this paper, the authors demonstrated that MRI guided focused ultrasound is capable to transiently open the BBB thereby enabling CNS access.
PDF
