Local connectivity and synaptic dynamics in mouse and human neocortex.

We present a unique, extensive, and open synaptic physiology analysis platform and dataset. Through its application, we reveal principles that relate cell type to synaptic properties and intralaminar circuit organization in the mouse and human cortex. The dynamics of excitatory synapses align with the postsynaptic cell subclass, whereas inhibitory synapse dynamics partly align with presynaptic cell subclass but with considerable overlap. Synaptic properties are heterogeneous in most subclass-to-subclass connections. The two main axes of heterogeneity are strength and variability. Cell subclasses divide along the variability axis, whereas the strength axis accounts for substantial heterogeneity within the subclass. In the human cortex, excitatory-to-excitatory synaptic dynamics are distinct from those in the mouse cortex and vary with depth across layers 2 and 3.

An anatomic transcriptional atlas of human glioblastoma.

Glioblastoma is an aggressive brain tumor that carries a poor prognosis. The tumor's molecular and cellular landscapes are complex, and their relationships to histologic features routinely used for diagnosis are unclear. We present the Ivy Glioblastoma Atlas, an anatomically based transcriptional atlas of human glioblastoma that aligns individual histologic features with genomic alterations and gene expression patterns, thus assigning molecular information to the most important morphologic hallmarks of the tumor. The atlas and its clinical and genomic database are freely accessible online data resources that will serve as a valuable platform for future investigations of glioblastoma pathogenesis, diagnosis, and treatment.

Comprehensive cellular-resolution atlas of the adult human brain.

Detailed anatomical understanding of the human brain is essential for unraveling its functional architecture, yet current reference atlases have major limitations such as lack of whole-brain coverage, relatively low image resolution, and sparse structural annotation. We present the first digital human brain atlas to incorporate neuroimaging, high-resolution histology, and chemoarchitecture across a complete adult female brain, consisting of magnetic resonance imaging (MRI), diffusion-weighted imaging (DWI), and 1,356 large-format cellular resolution (1 µm/pixel) Nissl and immunohistochemistry anatomical plates. The atlas is comprehensively annotated for 862 structures, including 117 white matter tracts and several novel cyto- and chemoarchitecturally defined structures, and these annotations were transferred onto the matching MRI dataset. Neocortical delineations were done for sulci, gyri, and modified Brodmann areas to link macroscopic anatomical and microscopic cytoarchitectural parcellations. Correlated neuroimaging and histological structural delineation allowed fine feature identification in MRI data and subsequent structural identification in MRI data from other brains. This interactive online digital atlas is integrated with existing Allen Institute for Brain Science gene expression atlases and is publicly accessible as a resource for the neuroscience community. J. Comp. Neurol. 524:3127-3481, 2016. © 2016 The Authors The Journal of Comparative Neurology Published by Wiley Periodicals, Inc.

Bone marrow changes related to disuse.

OBJECTIVES: To evaluate bone marrow changes on knee magnetic resonance imaging (MRI) in patients with 3- to 6-week-long period of unloading. METHODS: MRI knee examinations were performed in 30 patients (14 men, 16 women; aged 20-53 years) at baseline and 5-10 weeks after immobilisation of the ipsilateral lower extremity; subsets of patients were examined at additional time-points. Ten volunteers (4 men, 6 women; aged 20-50 years) were studied as control cohort at two time-points. Bone marrow signal abnormalities were analysed according to: (1) severity, (2) signal alteration relative to hyaline cartilage, (3) morphology, (4) increased vascularity in the knee joint and (5) T1-signal alteration. Spearman's rank correlation test (SRC) and Kendall's tau (KT) were used to compare individual scores. RESULTS: All 30 patients presented abnormal bone marrow findings after unloading, which reached a peak at 10-25 weeks (P <0.001). These findings decreased within 1 year (P < 0.001). High scores of severity were associated with confluent and patchy patterns of bone marrow (SCR = 0.923, P < 0.001 and KT = 0.877, P <0.001). CONCLUSIONS: Signal abnormalities of the bone marrow related to unloading are consistent findings and most prominent 10-25 weeks following immobilisation when both confluent and patchy hyperintense patterns are present.

New York State Health Foundation grant helps health centers win federal expansion funds.

With approximately 1.2 million New Yorkers poised to gain health insurance coverage as a result of federal health reform, demand for primary care services is likely to increase greatly. The Affordable Care Act includes $11 billion in funding to enhance primary care access at community health centers. Recognizing a need and an opportunity, in August 2010 the New York State Health Foundation made a grant of nearly $400,000 to the Community Health Care Association of New York State to work with twelve health centers to develop successful proposals for obtaining and using these federal funds. Ultimately, eleven of the twelve sites are expected to receive $25.6 million in federal grants over a five-year period-a sixty-four-fold return on the foundation's investment. This article describes the strategy for investing in community health centers; identifies key project activities, challenges, and lessons; and highlights its next steps for strengthening primary care.

Evaluation of a metal artifact reduction technique in tonsillar cancer delineation.

PURPOSE: Metal artifacts can degrade computed tomographic (CT) simulation imaging and impair accurate delineation of tumors for radiation treatment planning purposes. We investigated a Digital Imaging and Communications in Medicine-based metal artifact reduction technique in tonsillar cancer delineation. METHODS AND MATERIALS: Eight patients with significant artifact and tonsil cancer were evaluated. Each patient had a positron emission tomography (PET)-CT and a contrast-enhanced CT obtained at the same setting during radiotherapy simulation. The CTs were corrected for artifact using the metal deletion technique (MDT). Two radiation oncologists independently delineated primary gross tumor volumes (GTVs) for each patient on native (CTnonMDT), metal corrected (CTMDT), and reference standard (CTPET/nonMDT) imaging, 1 week apart. Mixed effects models were used to determine if differences among GTVs were statistically significant. Two diagnostic radiologists and 2 radiation oncologists independently qualitatively evaluated CTs for each patient. Ratings were on an ordinal scale from -3 to +3, denoting that CTMDT was markedly, moderately, or slightly worse or better than CTnonMDT. Scores were compared with a Wilcoxon signed-rank test. RESULTS: The GTVPET/nonMDT were significantly smaller than GTVnonMDT (P = .004) and trended to be smaller than GTVMDT (P = .084). The GTVnonMDT and GTVMDT were not significantly different (P = .93). There was no significant difference in the extent to which GTVnonMDT or GTVMDT encompassed GTVPET/nonMDT (P = .33). In the subjective assessment of image quality, CTMDT did not significantly outperform CTnonMDT. In the majority of cases, the observer rated the CTMDT equivalent to (53%) or slightly superior (41%) to the corresponding CTnonMDT. CONCLUSIONS: The MTD modified images did not produce GTVMDT that more closely reproduced GTVPET/nonMDT than did GTVnonMDT. Moreover, the MTD modified images were not judged to be significantly superior when compared to the uncorrected images in terms of subjective ability to visualize the tonsilar tumors. This study failed to demonstrate value of the adjunctive use of a CT corrected for artifacts in the tumor delineation process. Artifacts do make tumor delineation challenging, and further investigation of other body sites is warranted.

A philanthropy tackles growth in health costs at the state level.

Slowing the rate of growth of health spending is as critical a goal at the state level as it is at the national level. Philanthropy can hardly address this issue alone, yet it has an obligation to take on big and seemingly intractable problems. The New York State Health Foundation is committed to stimulating innovative and replicable approaches to bending the cost curve. This article describes how the foundation recently awarded six grants to support efforts related to payment reform, hospital readmissions, medical malpractice reform, palliative care, and the quantification of other cost containment approaches that could be pursued at the state level.

Loudness adaptation: fact or artifact?

In the present study, the authors tested the hypothesis that contrast effects confound the Ipsilateral Comparison Paradigm (ICP). Bidirectional referents were used in which base tones of 50 or 70 dB alternated with referents of greater or lesser intensity in a 3.5-min listening period. The contrast hypothesis leads to the expectation that the bidirectional referents would produce opposing effects that should nullify time-based loudness changes in the common base tone. Contrary to that expectation, base-tone loudness declined significantly over time in the context of the bidirectional referents, and the loudness of the referents also declined significantly over time. Thus, the results of the study testified to the validity of the ICP as a contrast-free measure of broad-based loudness adaptation.