Crowdsourcing the General Public for Large Scale Molecular Pathology Studies in Cancer

Background: Citizen science, scientific research conducted by non-specialists, has the potential to facilitate biomedical research using available large-scale data, however validating the results is challenging. The Cell Slider is a citizen science project that intends to share images from tumors with the general public, enabling them to score tumor markers independently through an internet-based interface. Methods: From October 2012 to June 2014, 98,293 Citizen Scientists accessed the Cell Slider web page and scored 180,172 sub-images derived from images of 12,326 tissue microarray cores labeled for estrogen receptor (ER). We evaluated the accuracy of Citizen Scientist's ER classification, and the association between ER status and prognosis by comparing their test performance against trained pathologists. Findings: The area under ROC curve was 0.95 (95% CI 0.94 to 0.96) for cancer cell identification and 0.97 (95% CI 0.96 to 0.97) for ER status. ER positive tumors scored by Citizen Scientists were associated with survival in a similar way to that scored by trained pathologists. Survival probability at 15 years were 0.78 (95% CI 0.76 to 0.80) for ER-positive and 0.72 (95% CI 0.68 to 0.77) for ER-negative tumors based on Citizen Scientists classification. Based on pathologist classification, survival probability was 0.79 (95% CI 0.77 to 0.81) for ER-positive and 0.71 (95% CI 0.67 to 0.74) for ER-negative tumors. The hazard ratio for death was 0.26 (95% CI 0.18 to 0.37) at diagnosis and became greater than one after 6.5 years of follow-up for ER scored by Citizen Scientists, and 0.24 (95% CI 0.18 to 0.33) at diagnosis increasing thereafter to one after 6.7 (95% CI 4.1 to 10.9) years of follow-up for ER scored by pathologists. Interpretation: Crowdsourcing of the general public to classify cancer pathology data for research is viable, engages the public and provides accurate ER data. Crowdsourced classification of research data may offer a valid solution to problems of throughput requiring human input

KLF4 is a key determinant in the development and progression of cerebral cavernous malformations

Cerebral cavernous malformations (CCMs) are vascular malformations located within the central nervous system often resulting in cerebral hemorrhage. Pharmacological treatment is needed, since current therapy is limited to neurosurgery. Familial CCM is caused by loss-of-function mutations in any of Ccm1, Ccm2, and Ccm3 genes. CCM cavernomas are lined by endothelial cells (ECs) undergoing endothelial-to-mesenchymal transition (EndMT). This switch in phenotype is due to the activation of the transforming growth factor beta/bone morphogenetic protein (TGF\u3b2/BMP) signaling. However, the mechanism linking Ccm gene inactivation and TGF\u3b2/BMP-dependent EndMT remains undefined. Here, we report that Ccm1 ablation leads to the activation of a MEKK3-MEK5-ERK5-MEF2 signaling axis that induces a strong increase in Kruppel-like factor 4 (KLF4) in ECs in\ua0vivo. KLF4 transcriptional activity is responsible for the EndMT occurring in CCM1-null ECs. KLF4 promotes TGF\u3b2/BMP signaling through the production of BMP6. Importantly, in endothelial-specific Ccm1 and Klf4 double knockout mice, we observe a strong reduction in the development of CCM and mouse mortality. Our data unveil KLF4 as a therapeutic target for CCM

Origins of the Ambient Solar Wind: Implications for Space Weather

The Sun's outer atmosphere is heated to temperatures of millions of degrees, and solar plasma flows out into interplanetary space at supersonic speeds. This paper reviews our current understanding of these interrelated problems: coronal heating and the acceleration of the ambient solar wind. We also discuss where the community stands in its ability to forecast how variations in the solar wind (i.e., fast and slow wind streams) impact the Earth. Although the last few decades have seen significant progress in observations and modeling, we still do not have a complete understanding of the relevant physical processes, nor do we have a quantitatively precise census of which coronal structures contribute to specific types of solar wind. Fast streams are known to be connected to the central regions of large coronal holes. Slow streams, however, appear to come from a wide range of sources, including streamers, pseudostreamers, coronal loops, active regions, and coronal hole boundaries. Complicating our understanding even more is the fact that processes such as turbulence, stream-stream interactions, and Coulomb collisions can make it difficult to unambiguously map a parcel measured at 1 AU back down to its coronal source. We also review recent progress -- in theoretical modeling, observational data analysis, and forecasting techniques that sit at the interface between data and theory -- that gives us hope that the above problems are indeed solvable.Comment: Accepted for publication in Space Science Reviews. Special issue connected with a 2016 ISSI workshop on "The Scientific Foundations of Space Weather." 44 pages, 9 figure

Formation of dense partonic matter in relativistic nucleus-nucleus collisions at RHIC: Experimental evaluation by the PHENIX collaboration

Extensive experimental data from high-energy nucleus-nucleus collisions were recorded using the PHENIX detector at the Relativistic Heavy Ion Collider (RHIC). The comprehensive set of measurements from the first three years of RHIC operation includes charged particle multiplicities, transverse energy, yield ratios and spectra of identified hadrons in a wide range of transverse momenta (p_T), elliptic flow, two-particle correlations, non-statistical fluctuations, and suppression of particle production at high p_T. The results are examined with an emphasis on implications for the formation of a new state of dense matter. We find that the state of matter created at RHIC cannot be described in terms of ordinary color neutral hadrons.Comment: 510 authors, 127 pages text, 56 figures, 1 tables, LaTeX. Submitted to Nuclear Physics A as a regular article; v3 has minor changes in response to referee comments. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm

A self-help version of the New Forest Parenting Programme for parents of children with attention deficit hyperactivity disorder:a qualitative study of parent views and acceptability

Background Although parent interventions are recommended as a frontline treatment approach for children with attention deficit hyperactivity disorder (ADHD), a number of practical and situational barriers can impact accessibility and availability. Self-help parent interventions offer a potential alternative to therapist-led interventions when barriers prevent access to face-to-face treatment. This qualitative study aims to explore participant views and acceptability of self-help parent interventions. Method Semi-structured interviews were conducted with parents/carers of 12 children (age 6–10 years) with ADHD who received the self-help version of the New Forest Parenting Programme (NFPP-SH) as part of a randomised controlled trial. Thematic analysis (as proposed by Braun and Clarke) was used to analyse the data. Results Overall, participants had favourable views of the self-help intervention but also experienced some barriers to treatment adherence. Six key themes were identified in parent interviews related to parental desire to learn more; acquisition of new skills; the flexibility of the intervention; self-help intervention vs. traditional therapist-led formats; barriers to engagement in the home environment; and need for earlier access to help. Conclusions NFPP-SH was an acceptable intervention for parents. However, some parents may need additional support to overcome barriers associated with completing an intervention at home. Implications for healthcare providers and researchers developing self-help parent interventions for ADHD and child behaviour are discussed

Burden of Neurological Disorders across the US from 1990-2017: A Global Burden of Disease Study

Importance: Accurate and up-to-date estimates on incidence, prevalence, mortality, and disability-adjusted life-years (burden) of neurological disorders are the backbone of evidence-based health care planning and resource allocation for these disorders. It appears that no such estimates have been reported at the state level for the US. Objective: To present burden estimates of major neurological disorders in the US states by age and sex from 1990 to 2017. Design, Setting, and Participants: This is a systematic analysis of the Global Burden of Disease (GBD) 2017 study. Data on incidence, prevalence, mortality, and disability-adjusted life-years (DALYs) of major neurological disorders were derived from the GBD 2017 study of the 48 contiguous US states, Alaska, and Hawaii. Fourteen major neurological disorders were analyzed: stroke, Alzheimer disease and other dementias, Parkinson disease, epilepsy, multiple sclerosis, motor neuron disease, migraine, tension-type headache, traumatic brain injury, spinal cord injuries, brain and other nervous system cancers, meningitis, encephalitis, and tetanus. Exposures: Any of the 14 listed neurological diseases. Main Outcome and Measure: Absolute numbers in detail by age and sex and age-standardized rates (with 95 uncertainty intervals) were calculated. Results: The 3 most burdensome neurological disorders in the US in terms of absolute number of DALYs were stroke (3.58 95% uncertainty interval UI], 3.25-3.92] million DALYs), Alzheimer disease and other dementias (2.55 95% UI, 2.43-2.68 million DALYs), and migraine (2.40 95% UI, 1.53-3.44 million DALYs). The burden of almost all neurological disorders (in terms of absolute number of incident, prevalent, and fatal cases, as well as DALYs) increased from 1990 to 2017, largely because of the aging of the population. Exceptions for this trend included traumatic brain injury incidence (-29.1% 95% UI, -32.4% to -25.8%); spinal cord injury prevalence (-38.5% 95% UI, -43.1% to -34.0%); meningitis prevalence (-44.8% 95% UI, -47.3% to -42.3%), deaths (-64.4% 95% UI, -67.7% to -50.3%), and DALYs (-66.9% 95% UI, -70.1% to -55.9%); and encephalitis DALYs (-25.8% 95% UI, -30.7% to -5.8%). The different metrics of age-standardized rates varied between the US states from a 1.2-fold difference for tension-type headache to 7.5-fold for tetanus; southeastern states and Arkansas had a relatively higher burden for stroke, while northern states had a relatively higher burden of multiple sclerosis and eastern states had higher rates of Parkinson disease, idiopathic epilepsy, migraine and tension-type headache, and meningitis, encephalitis, and tetanus. Conclusions and Relevance: There is a large and increasing burden of noncommunicable neurological disorders in the US, with up to a 5-fold variation in the burden of and trends in particular neurological disorders across the US states. The information reported in this article can be used by health care professionals and policy makers at the national and state levels to advance their health care planning and resource allocation to prevent and reduce the burden of neurological disorders.. © 2021 American Medical Association. All rights reserved

Mesquite Pod Removal by Cattle, Feral Hogs, and Native Herbivores

The dispersal of woody plant seeds by livestock has been implicated as one of the causes of woody plant encroachment in semiarid ecosystems worldwide. In the southern Great Plains, United States, cattle are suspected to have increased encroachment of the woody legume honey mesquite (Prosopis glandulosa Torr.) because they are effective consumers of mesquite pods and pass viable seed from those pods through their digestive systems. Since other animal species also consume or gather mesquite pods and seeds, our objective was to compare the removal of mesquite pods by cattle, other vertebrate herbivores, and insects. Mature pods were collected from trees in late summer and placed within each level of a hierarchical exclusion design using fences and cages that blocked cattle; other large vertebrates (deer, feral hogs); smaller vertebrates (rabbits, birds, rodents); and insects at replicate sites in north and south Texas locations. Pod removal was quantified during 60-d trials in the fall of each of 3 yr. The treatment that allowed cattle to have access to pods had the greatest or tied for the greatest pod removal at trial end in all trials. Final pod removal in the feral hog and white-tailed deer treatments was numerically lower but statistically similar (P ≤ 0.05) to cattle. However, the rate of pod removal during the first 20 d in several of the trials was greatest (P ≤ 0.05) in the cattle treatment at both locations. Pod removal by rodents was high in 1 yr at both locations, which we attributed to high growing season precipitation at both locations during that year. Results may have implications regarding seed-centric grazing management decisions and keeping cattle out of pastures when mesquite pods are abundantly present on the ground. © 2017 The Society for Range Management. Published by Elsevier Inc. All rights reserved.The Rangeland Ecology & Management archives are made available by the Society for Range Management and the University of Arizona Libraries. Contact [email protected] for further information