458 research outputs found
Meeting the Emerging Public Health Needs of Persons With Blood Disorders
In its decades-long history, the Division of Blood Disorders (DBD) at CDC has evolved from a patient-focused, services-supporting entity at inception, to one of the world leaders in the practice of public health to improve the lives of people at risk for or affected by nonmalignant blood disorders. The DBD’s earliest public health activities consisted of working with care providers in a network of hemophilia treatment centers to provide AIDS risk reduction services to people with hemophilia. Because this infectious disease threat has been reduced over time as a result of the development of safer treatment products, the DBD—under the auspices of congressional appropriations guidance—has expanded its core activities to encompass blood disorders other than hemophilia, including hemoglobinopathies such as thalassemia and sickle cell disease, and Diamond Blackfan anemia. Simultaneously, in transitioning to a greater public health role, the DBD has expanded its network of partners to new consumer and professional organizations, as well as state and other federal health agencies. The DBD has also developed and maintains many surveillance and registry activities beyond the Universal Data Collection system aimed at providing a better understanding of the health status, health needs, and health-related quality of life of people with nonmalignant blood disorders. The DBD has integrated applicable components of the Essential Services of Public Health successfully to promote and advance the agenda of blood disorders in public health
Rationale and design: telepsychology service delivery for depressed elderly veterans
BACKGROUND: Older adults who live in rural areas experience significant disparities in health status and access to mental health care. "Telepsychology," (also referred to as "telepsychiatry," or "telemental health") represents a potential strategy towards addressing this longstanding problem. Older adults may benefit from telepsychology due to its: (1) utility to address existing problematic access to care for rural residents; (2) capacity to reduce stigma associated with traditional mental health care; and (3) utility to overcome significant age-related problems in ambulation and transportation. Moreover, preliminary evidence indicates that telepsychiatry programs are often less expensive for patients, and reduce travel time, travel costs, and time off from work. Thus, telepsychology may provide a cost-efficient solution to access-to-care problems in rural areas. METHODS: We describe an ongoing four-year prospective, randomized clinical trial comparing the effectiveness of an empirically supported treatment for major depressive disorder, Behavioral Activation, delivered either via in-home videoconferencing technology ("Telepsychology") or traditional face-to-face services ("Same-Room"). Our hypothesis is that inhome Telepsychology service delivery will be equally effective as the traditional mode (Same-Room). Two-hundred twenty-four (224) male and female elderly participants will be administered protocol-driven individual Behavioral Activation therapy for depression over an 8-week period; and subjects will be followed for 12-months to ascertain longer-term effects of the treatment on three outcomes domains: (1) clinical outcomes (symptom severity, social functioning); (2) process variables (patient satisfaction, treatment credibility, attendance, adherence, dropout); and (3) economic outcomes (cost and resource use). DISCUSSION: Results from the proposed study will provide important insight into whether telepsychology service delivery is as effective as the traditional mode of service delivery, defined in terms of clinical, process, and economic outcomes, for elderly patients with depression residing in rural areas without adequate access to mental health services. TRIAL REGISTRATION: National Institutes of Health Clinical Trials Registry (ClinicalTrials.gov identifier# NCT00324701)
Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas
Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN
Highly Volcanic Exoplanets, Lava Worlds, and Magma Ocean Worlds:An Emerging Class of Dynamic Exoplanets of Significant Scientific Priority
Highly volcanic exoplanets, which can be variously characterized as 'lava
worlds', 'magma ocean worlds', or 'super-Ios' are high priority targets for
investigation. The term 'lava world' may refer to any planet with extensive
surface lava lakes, while the term 'magma ocean world' refers to planets with
global or hemispherical magma oceans at their surface. 'Highly volcanic
planets', including super-Ios, may simply have large, or large numbers of,
active explosive or extrusive volcanoes of any form. They are plausibly highly
diverse, with magmatic processes across a wide range of compositions,
temperatures, activity rates, volcanic eruption styles, and background
gravitational force magnitudes. Worlds in all these classes are likely to be
the most characterizable rocky exoplanets in the near future due to
observational advantages that stem from their preferential occurrence in short
orbital periods and their bright day-side flux in the infrared. Transit
techniques should enable a level of characterization of these worlds analogous
to hot Jupiters. Understanding processes on highly volcanic worlds is critical
to interpret imminent observations. The physical states of these worlds are
likely to inform not just geodynamic processes, but also planet formation, and
phenomena crucial to habitability. Volcanic and magmatic activity uniquely
allows chemical investigation of otherwise spectroscopically inaccessible
interior compositions. These worlds will be vital to assess the degree to which
planetary interior element abundances compare to their stellar hosts, and may
also offer pathways to study both the very young Earth, and the very early form
of many silicate planets where magma oceans and surface lava lakes are expected
to be more prevalent. We suggest that highly volcanic worlds may become second
only to habitable worlds in terms of both scientific and public long-term
interest.Comment: A white paper submitted in response to the National Academy of
Sciences 2018 Exoplanet Science Strategy solicitation, from the NASA Sellers
Exoplanet Environments Collaboration (SEEC) of the Goddard Space Flight
Center. 6 pages, 0 figure
The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe
The preponderance of matter over antimatter in the early Universe, the
dynamics of the supernova bursts that produced the heavy elements necessary for
life and whether protons eventually decay --- these mysteries at the forefront
of particle physics and astrophysics are key to understanding the early
evolution of our Universe, its current state and its eventual fate. The
Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed
plan for a world-class experiment dedicated to addressing these questions. LBNE
is conceived around three central components: (1) a new, high-intensity
neutrino source generated from a megawatt-class proton accelerator at Fermi
National Accelerator Laboratory, (2) a near neutrino detector just downstream
of the source, and (3) a massive liquid argon time-projection chamber deployed
as a far detector deep underground at the Sanford Underground Research
Facility. This facility, located at the site of the former Homestake Mine in
Lead, South Dakota, is approximately 1,300 km from the neutrino source at
Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino
charge-parity symmetry violation and mass ordering effects. This ambitious yet
cost-effective design incorporates scalability and flexibility and can
accommodate a variety of upgrades and contributions. With its exceptional
combination of experimental configuration, technical capabilities, and
potential for transformative discoveries, LBNE promises to be a vital facility
for the field of particle physics worldwide, providing physicists from around
the globe with opportunities to collaborate in a twenty to thirty year program
of exciting science. In this document we provide a comprehensive overview of
LBNE's scientific objectives, its place in the landscape of neutrino physics
worldwide, the technologies it will incorporate and the capabilities it will
possess.Comment: Major update of previous version. This is the reference document for
LBNE science program and current status. Chapters 1, 3, and 9 provide a
comprehensive overview of LBNE's scientific objectives, its place in the
landscape of neutrino physics worldwide, the technologies it will incorporate
and the capabilities it will possess. 288 pages, 116 figure
Targeting DNA Damage Response and Replication Stress in Pancreatic Cancer
Background and aims:
Continuing recalcitrance to therapy cements pancreatic cancer (PC) as the most lethal malignancy, which is set to become the second leading cause of cancer death in our society. The study aim was to investigate the association between DNA damage response (DDR), replication stress and novel therapeutic response in PC to develop a biomarker driven therapeutic strategy targeting DDR and replication stress in PC.
Methods:
We interrogated the transcriptome, genome, proteome and functional characteristics of 61 novel PC patient-derived cell lines to define novel therapeutic strategies targeting DDR and replication stress. Validation was done in patient derived xenografts and human PC organoids.
Results:
Patient-derived cell lines faithfully recapitulate the epithelial component of pancreatic tumors including previously described molecular subtypes. Biomarkers of DDR deficiency, including a novel signature of homologous recombination deficiency, co-segregates with response to platinum (P < 0.001) and PARP inhibitor therapy (P < 0.001) in vitro and in vivo. We generated a novel signature of replication stress with which predicts response to ATR (P < 0.018) and WEE1 inhibitor (P < 0.029) treatment in both cell lines and human PC organoids. Replication stress was enriched in the squamous subtype of PC (P < 0.001) but not associated with DDR deficiency.
Conclusions:
Replication stress and DDR deficiency are independent of each other, creating opportunities for therapy in DDR proficient PC, and post-platinum therapy
Rationale and design: telepsychology service delivery for depressed elderly veterans
<p>Abstract</p> <p>Background</p> <p>Older adults who live in rural areas experience significant disparities in health status and access to mental health care. "Telepsychology," (also referred to as "telepsychiatry," or "telemental health") represents a potential strategy towards addressing this longstanding problem. Older adults may benefit from telepsychology due to its: (1) utility to address existing problematic access to care for rural residents; (2) capacity to reduce stigma associated with traditional mental health care; and (3) utility to overcome significant age-related problems in ambulation and transportation. Moreover, preliminary evidence indicates that telepsychiatry programs are often less expensive for patients, and reduce travel time, travel costs, and time off from work. Thus, telepsychology may provide a cost-efficient solution to access-to-care problems in rural areas.</p> <p>Methods</p> <p>We describe an ongoing four-year prospective, randomized clinical trial comparing the effectiveness of an empirically supported treatment for major depressive disorder, Behavioral Activation, delivered either via in-home videoconferencing technology ("Telepsychology") or traditional face-to-face services ("Same-Room"). Our hypothesis is that in-homeTelepsychology service delivery will be equally effective as the traditional mode (Same-Room). Two-hundred twenty-four (224) male and female elderly participants will be administered protocol-driven individual Behavioral Activation therapy for depression over an 8-week period; and subjects will be followed for 12-months to ascertain longer-term effects of the treatment on three outcomes domains: (1) clinical outcomes (symptom severity, social functioning); (2) process variables (patient satisfaction, treatment credibility, attendance, adherence, dropout); and (3) economic outcomes (cost and resource use).</p> <p>Discussion</p> <p>Results from the proposed study will provide important insight into whether telepsychology service delivery is as effective as the traditional mode of service delivery, defined in terms of clinical, process, and economic outcomes, for elderly patients with depression residing in rural areas without adequate access to mental health services.</p> <p>Trial registration</p> <p>National Institutes of Health Clinical Trials Registry (ClinicalTrials.gov identifier# NCT00324701).</p
A Cryogenic Silicon Interferometer for Gravitational-wave Detection
The detection of gravitational waves from compact binary mergers by LIGO has
opened the era of gravitational wave astronomy, revealing a previously hidden
side of the cosmos. To maximize the reach of the existing LIGO observatory
facilities, we have designed a new instrument that will have 5 times the range
of Advanced LIGO, or greater than 100 times the event rate. Observations with
this new instrument will make possible dramatic steps toward understanding the
physics of the nearby universe, as well as observing the universe out to
cosmological distances by the detection of binary black hole coalescences. This
article presents the instrument design and a quantitative analysis of the
anticipated noise floor
Phenotypic Characterization of EIF2AK4 Mutation Carriers in a Large Cohort of Patients Diagnosed Clinically With Pulmonary Arterial Hypertension.
BACKGROUND: Pulmonary arterial hypertension (PAH) is a rare disease with an emerging genetic basis. Heterozygous mutations in the gene encoding the bone morphogenetic protein receptor type 2 (BMPR2) are the commonest genetic cause of PAH, whereas biallelic mutations in the eukaryotic translation initiation factor 2 alpha kinase 4 gene (EIF2AK4) are described in pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis. Here, we determine the frequency of these mutations and define the genotype-phenotype characteristics in a large cohort of patients diagnosed clinically with PAH. METHODS: Whole-genome sequencing was performed on DNA from patients with idiopathic and heritable PAH and with pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis recruited to the National Institute of Health Research BioResource-Rare Diseases study. Heterozygous variants in BMPR2 and biallelic EIF2AK4 variants with a minor allele frequency of <1:10 000 in control data sets and predicted to be deleterious (by combined annotation-dependent depletion, PolyPhen-2, and sorting intolerant from tolerant predictions) were identified as potentially causal. Phenotype data from the time of diagnosis were also captured. RESULTS: Eight hundred sixty-four patients with idiopathic or heritable PAH and 16 with pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis were recruited. Mutations in BMPR2 were identified in 130 patients (14.8%). Biallelic mutations in EIF2AK4 were identified in 5 patients with a clinical diagnosis of pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis. Furthermore, 9 patients with a clinical diagnosis of PAH carried biallelic EIF2AK4 mutations. These patients had a reduced transfer coefficient for carbon monoxide (Kco; 33% [interquartile range, 30%-35%] predicted) and younger age at diagnosis (29 years; interquartile range, 23-38 years) and more interlobular septal thickening and mediastinal lymphadenopathy on computed tomography of the chest compared with patients with PAH without EIF2AK4 mutations. However, radiological assessment alone could not accurately identify biallelic EIF2AK4 mutation carriers. Patients with PAH with biallelic EIF2AK4 mutations had a shorter survival. CONCLUSIONS: Biallelic EIF2AK4 mutations are found in patients classified clinically as having idiopathic and heritable PAH. These patients cannot be identified reliably by computed tomography, but a low Kco and a young age at diagnosis suggests the underlying molecular diagnosis. Genetic testing can identify these misclassified patients, allowing appropriate management and early referral for lung transplantation
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