83 research outputs found
New Lower Bounds on the Self-Avoiding-Walk Connective Constant
We give an elementary new method for obtaining rigorous lower bounds on the
connective constant for self-avoiding walks on the hypercubic lattice .
The method is based on loop erasure and restoration, and does not require exact
enumeration data. Our bounds are best for high , and in fact agree with the
first four terms of the expansion for the connective constant. The bounds
are the best to date for dimensions , but do not produce good results
in two dimensions. For , respectively, our lower bound is within
2.4\%, 0.43\%, 0.12\%, 0.044\% of the value estimated by series extrapolation.Comment: 35 pages, 388480 bytes Postscript, NYU-TH-93/02/0
BigBrain 3D atlas of cortical layers: Cortical and laminar thickness gradients diverge in sensory and motor cortices.
Histological atlases of the cerebral cortex, such as those made famous by Brodmann and von Economo, are invaluable for understanding human brain microstructure and its relationship with functional organization in the brain. However, these existing atlases are limited to small numbers of manually annotated samples from a single cerebral hemisphere, measured from 2D histological sections. We present the first whole-brain quantitative 3D laminar atlas of the human cerebral cortex. It was derived from a 3D histological atlas of the human brain at 20-micrometer isotropic resolution (BigBrain), using a convolutional neural network to segment, automatically, the cortical layers in both hemispheres. Our approach overcomes many of the historical challenges with measurement of histological thickness in 2D, and the resultant laminar atlas provides an unprecedented level of precision and detail. We utilized this BigBrain cortical atlas to test whether previously reported thickness gradients, as measured by MRI in sensory and motor processing cortices, were present in a histological atlas of cortical thickness and which cortical layers were contributing to these gradients. Cortical thickness increased across sensory processing hierarchies, primarily driven by layers III, V, and VI. In contrast, motor-frontal cortices showed the opposite pattern, with decreases in total and pyramidal layer thickness from motor to frontal association cortices. These findings illustrate how this laminar atlas will provide a link between single-neuron morphology, mesoscale cortical layering, macroscopic cortical thickness, and, ultimately, functional neuroanatomy
JAK2/IDH-mutant–driven myeloproliferative neoplasm is sensitive to combined targeted inhibition
Patients with myeloproliferative neoplasms (MPNs) frequently progress to bone marrow failure or acute myeloid leukemia (AML), and mutations in epigenetic regulators such as the metabolic enzyme isocitrate dehydrogenase (IDH) are associated with poor outcomes. Here, we showed that combined expression of Jak2V617Fand mutant IDH1R132Hor Idh2R140Q induces MPN progression, alters stem/progenitor cell function, and impairs differentiation in mice. Jak2V617FIdh2R140Q–mutant MPNs were sensitive to small-molecule inhibition of IDH. Combined inhibition of JAK2 and IDH2 normalized the stem and progenitor cell compartments in the murine model and reduced disease burden to a greater extent than was seen with JAK inhibition alone. In addition, combined JAK2 and IDH2 inhibitor treatment also reversed aberrant gene expression in MPN stem cells and reversed the metabolite perturbations induced by concurrent JAK2 and IDH2 mutations. Combined JAK2 and IDH2 inhibitor therapy also showed cooperative efficacy in cells from MPN patients with both JAK2mutand IDH2mutmutations. Taken together, these data suggest that combined JAK and IDH inhibition May offer a therapeutic advantage in this high-risk MPN subtype.Damon Runyon Cancer Research Foundation (DRG-2241-15)Howard Hughes Medical Institute (Faculty Scholars Award)Stand Up To CancerNational Cancer Institute (U.S.) (P50CA165962)National Cancer Institute (U.S.) (P30CA14051)Koch Institute for Integrative Cancer Research ( Dana-Farber Harvard Cancer Center Bridge Project)Leukemia & Lymphoma Society of America. Specialized Center of Research (SCOR) ProgramNational Institutes of Health (U.S.) (grant U54OD020355-01)National Institutes of Health (U.S.) (grant NCI R01CA172636)National Institutes of Health (U.S.) (grant R35CA197594)National Cancer Institute (U.S.) (Cancer Center Support Grant (P30 CA008747)
Effectiveness and cost-effectiveness of a telehealth intervention to support the management of long-term conditions: study protocol for two linked randomized controlled trials
Background: As the population ages, more people are suffering from long-term health conditions (LTCs). Health
services around the world are exploring new ways of supporting people with LTCs and there is great interest in the
use of telehealth: technologies such as the Internet, telephone and home self-monitoring.
Methods/Design: This study aims to evaluate the effectiveness and cost-effectiveness of a telehealth intervention
delivered by NHS Direct to support patients with LTCs. Two randomized controlled trials will be conducted in parallel,
recruiting patients with two exemplar LTCs: depression or raised cardiovascular disease (CVD) risk. A total of 1,200
patients will be recruited from approximately 42 general practices near Bristol, Sheffield and Southampton, UK.
Participants will be randomly allocated to either usual care (control group) or usual care plus the NHS Direct
Healthlines Service (intervention group). The intervention is based on a conceptual model incorporating promotion of
self-management, optimisation of treatment, coordination of care and engagement of patients and general
practitioners. Participants will be provided with tailored help, combining telephone advice from health information
advisors with support to use a range of online resources. Participants will access the service for 12 months. Outcomes
will be collected at baseline, four, eight and 12 months for the depression trial and baseline, six and 12 months for
the CVD risk trial. The primary outcome will be the proportion of patients responding to treatment, defined in the
depression trial as a PHQ-9 score <10 and an absolute reduction in PHQ-9 ≥5 after 4 months, and in the CVD risk
trial as maintenance or reduction of 10-year CVD risk after 12 months. The study will also assess whether the
intervention is cost-effective from the perspective of the NHS and personal social services. An embedded qualitative
interview study will explore healthcare professionals’ and patients’ views of the intervention.
Discussion: This study evaluates a complex telehealth intervention which combines evidence-based components and
is delivered by an established healthcare organisation. The study will also analyse health economic information. In
doing so, the study hopes to address some of the limitations of previous research by demonstrating the effectiveness
and cost-effectiveness of a real world telehealth interventio
Do pain, anxiety and depression influence quality of life for people with amyotrophic lateral sclerosis/motor neuron disease? A national study reconciling previous conflicting literature
The original version of this article unfortunately contained a mistake. Oliver Hanemann name was incorrect in the in the acknowledgements section of this paper
Professions and the French State, 1700–1900. Edited by Gerald L. Geison. Philadelphia: University of Pennsylvania Press, 1984. Pp. 319. $35.00.
Professions and the French State, 1700–1900. Edited by Gerald L. Geison. Philadelphia: University of Pennsylvania Press, 1984. Pp. 319. $35.00.
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