Transcript regulation is essential for cell function, and misregulation can lead to disease. Despite technologies to survey the transcriptome, we lack a comprehensive understanding of transcript ...kinetics, which limits quantitative biology. This is an acute challenge in embryonic development, where rapid changes in gene expression dictate cell fate decisions. By ultra-high-frequency sampling of Xenopus embryos and absolute normalization of sequence reads, we present smooth gene expression trajectories in absolute transcript numbers. During a developmental period approximating the first 8 weeks of human gestation, transcript kinetics vary by eight orders of magnitude. Ordering genes by expression dynamics, we find that “temporal synexpression” predicts common gene function. Remarkably, a single parameter, the characteristic timescale, can classify transcript kinetics globally and distinguish genes regulating development from those involved in cellular metabolism. Overall, our analysis provides unprecedented insight into the reorganization of maternal and embryonic transcripts and redefines our ability to perform quantitative biology.
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•Ultra-high temporal resolution RNA-seq reveals smooth expression trajectories•Absolute transcript measurements enable calculation of transcriptome kinetics•Transcript accumulation rates vary over eight orders of magnitude during development•Temporal synexpression and timescales distinguish gene functions
Owens et al. present an ultra-high-resolution RNA-seq time course during embryonic development. Using spike-ins to calibrate transcript reads, they measure absolute mRNA transcript numbers and calculate transcriptome kinetics, in some cases, in kilobases per minute per allele. With these data, they find that temporal synexpression and characteristic timescales distinguish gene functions across the transcriptome.
Clinical practice guideline.
To develop evidence-based recommendations on use of interventional diagnostic tests and therapies, surgeries, and interdisciplinary rehabilitation for low back pain of ...any duration, with or without leg pain.
Management of patients with persistent and disabling low back pain remains a clinical challenge. A number of interventional diagnostic tests and therapies and surgery are available and their use is increasing, but in some cases their utility remains uncertain or controversial. Interdisciplinary rehabilitation has also been proposed as a potentially effective noninvasive intervention for persistent and disabling low back pain.
A multidisciplinary panel was convened by the American Pain Society. Its recommendations were based on a systematic review that focused on evidence from randomized controlled trials. Recommendations were graded using methods adapted from the US Preventive Services Task Force and the Grading of Recommendations, Assessment, Development, and Evaluation Working Group.
Investigators reviewed 3348 abstracts. A total of 161 randomized trials were deemed relevant to the recommendations in this guideline. The panel developed a total of 8 recommendations.
Recommendations on use of interventional diagnostic tests and therapies, surgery, and interdisciplinary rehabilitation are presented. Due to important trade-offs between potential benefits, harms, costs, and burdens of alternative therapies, shared decision-making is an important component of a number of the recommendations.
The rapid increase in the performance of graphics hardware, coupled with recent improvements in its programmability, have made graphics hardware a compelling platform for computationally demanding ...tasks in a wide variety of application domains. In this report, we describe, summarize, and analyze the latest research in mapping general‐purpose computation to graphics hardware.
We begin with the technical motivations that underlie general‐purpose computation on graphics processors (GPGPU) and describe the hardware and software developments that have led to the recent interest in this field. We then aim the main body of this report at two separate audiences. First, we describe the techniques used in mapping general‐purpose computation to graphics hardware. We believe these techniques will be generally useful for researchers who plan to develop the next generation of GPGPU algorithms and techniques. Second, we survey and categorize the latest developments in general‐purpose application development on graphics hardware.
On-chip interconnection networks are rapidly becoming a key enabling technology for commodity multicore processors and SoCs common in consumer embedded systems, the National Science Foundation ...initiated a workshop that addressed upcoming research issues in OCIN technology, design, and implementation and set a direction for researchers in the field.
We provide a simple algorithm and data structures for d‐dimensional unbiased maximal Poisson‐disk sampling. We use an order of magnitude less memory and time than the alternatives. Our results become ...more favorable as the dimension increases. This allows us to produce bigger samplings. Domains may be non‐convex with holes. The generated point cloud is maximal up to round‐off error. The serial algorithm is provably bias‐free. For an output sampling of size n in fixed dimension d, we use a linear memory budget and empirical θ(n) runtime. No known methods scale well with dimension, due to the “curse of dimensionality.” The serial algorithm is practical in dimensions up to 5, and has been demonstrated in 6d. We have efficient GPU implementations in 2d and 3d. The algorithm proceeds through a finite sequence of uniform grids. The grids guide the dart throwing and track the remaining disk‐free area. The top‐level grid provides an efficient way to test if a candidate dart is disk‐free. Our uniform grids are like quadtrees, except we delay splits and refine all leaves at once. Since the quadtree is flat it can be represented using very little memory: we just need the indices of the active leaves and a global level. Also it is very simple to sample from leaves with uniform probability.
The membrane glycoprotein MRC OX-2 (CD200) is expressed in several lymphoid malignancies. However, the diagnostic usefulness and potential prognostic importance of CD200 expression have not been ...rigorously examined. We show that CD200 is uniformly expressed in chronic lymphocytic leukemia (CLL) and absent in mantle cell lymphoma (MCL). It is important to note that expression of CD200 is retained even in CLLs with immunophenotypic aberrancies, making CD200 a particularly useful marker for discrimination between these cases and MCL. CD200 is expressed in nearly all precursor B-lymphoblastic leukemias, with aberrant overexpression or underexpression compared with normal B-cell progenitors in 55% of cases. More than 70% of plasma cell myelomas (PCMs) expressed CD200, and loss of CD200 expression in PCM may be associated with more clinically aggressive disease. CD200 is expressed in several hematolymphoid neoplasms. Analysis of its expression has several diagnostic and potentially prognostic applications in the flow cytometric evaluation of lymphoid malignancies.
Background:
Most surgeons believe that graft choice for anterior cruciate ligament (ACL) reconstruction is an important factor related to outcome; however, graft choice for revision may be limited ...due to previously used grafts.
Hypotheses:
Autograft use would result in increased sports function, increased activity level, and decreased osteoarthritis symptoms (as measured by validated patient-reported outcome instruments). Autograft use would result in decreased graft failure and reoperation rate 2 years after revision ACL reconstruction.
Study Design:
Cohort study; Level of evidence, 2.
Methods:
Patients undergoing revision ACL reconstruction were identified and prospectively enrolled by 83 surgeons at 52 sites. Data collected included baseline demographics, surgical technique, pathologic abnormalities, and the results of a series of validated, patient-reported outcome instruments (International Knee Documentation Committee IKDC, Knee injury and Osteoarthritis Outcome Score KOOS, Western Ontario and McMaster Universities Osteoarthritis Index WOMAC, and Marx activity rating score). Patients were followed up at 2 years and asked to complete the identical set of outcome instruments. Incidences of additional surgery and reoperation due to graft failure were also recorded. Multivariate regression models were used to determine the predictors (risk factors) of IKDC, KOOS, WOMAC, Marx scores, graft rerupture, and reoperation rate at 2 years after revision surgery.
Results:
A total of 1205 patients (697 58% males) were enrolled. The median age was 26 years. In 88% of patients, this was their first revision, and 341 patients (28%) were undergoing revision by the surgeon who had performed the previous reconstruction. The median time since last ACL reconstruction was 3.4 years. Revision using an autograft was performed in 583 patients (48%), allograft was used in 590 (49%), and both types were used in 32 (3%). Questionnaire follow-up was obtained for 989 subjects (82%), while telephone follow-up was obtained for 1112 (92%). The IKDC, KOOS, and WOMAC scores (with the exception of the WOMAC stiffness subscale) all significantly improved at 2-year follow-up (P < .001). In contrast, the 2-year Marx activity score demonstrated a significant decrease from the initial score at enrollment (P < .001). Graft choice proved to be a significant predictor of 2-year IKDC scores (P = .017). Specifically, the use of an autograft for revision reconstruction predicted improved score on the IKDC (P = .045; odds ratio OR = 1.31; 95% CI, 1.01-1.70). The use of an autograft predicted an improved score on the KOOS sports and recreation subscale (P = .037; OR = 1.33; 95% CI, 1.02-1.73). Use of an autograft also predicted improved scores on the KOOS quality of life subscale (P = .031; OR = 1.33; 95% CI, 1.03-1.73). For the KOOS symptoms and KOOS activities of daily living subscales, graft choice did not predict outcome score. Graft choice was a significant predictor of 2-year Marx activity level scores (P = .012). Graft rerupture was reported in 37 of 1112 patients (3.3%) by their 2-year follow-up: 24 allografts, 12 autografts, and 1 allograft and autograft. Use of an autograft for revision resulted in patients being 2.78 times less likely to sustain a subsequent graft rupture compared with allograft (P = .047; 95% CI, 1.01-7.69).
Conclusion:
Improved sports function and patient-reported outcome measures are obtained when an autograft is used. Additionally, use of an autograft shows a decreased risk in graft rerupture at 2-year follow-up. No differences were noted in rerupture or patient-reported outcomes between soft tissue and bone–patellar tendon–bone grafts. Surgeon education regarding the findings of this study has the potential to improve the results of revision ACL reconstruction.
A task-parallel approach to programming commodity graphics hardware is useful for implementing irregular parallel workloads with dependencies, particularly for applications such as video encoding and ...backtracking algorithms
The advent of readily available temporal imaging or time series volumetric (4D) imaging has become an indispensable component of treatment planning and adaptive radiotherapy (ART) at many ...radiotherapy centers. Deformable image registration (DIR) is also used in other areas of medical imaging, including motion corrected image reconstruction. Due to long computation time, clinical applications of DIR in radiation therapy and elsewhere have been limited and consequently relegated to offline analysis. With the recent advances in hardware and software, graphics processing unit (GPU) based computing is an emerging technology for general purpose computation, including DIR, and is suitable for highly parallelized computing. However, traditional general purpose computation on the GPU is limited because the constraints of the available programming platforms. As well, compared to CPU programming, the GPU currently has reduced dedicated processor memory, which can limit the useful working data set for parallelized processing. We present an implementation of the demons algorithm using the NVIDIA 8800 GTX GPU and the new CUDA programming language. The GPU performance will be compared with single threading and multithreading CPU implementations on an Intel dual core
2.4
GHz
CPU using the C programming language. CUDA provides a C-like language programming interface, and allows for direct access to the highly parallel compute units in the GPU. Comparisons for volumetric clinical lung images acquired using 4DCT were carried out. Computation time for 100 iterations in the range of
1.8
–
13.5
s
was observed for the GPU with image size ranging from
2.0
×
10
6
to
14.2
×
10
6
pixels
. The GPU registration was 55–61 times faster than the CPU for the single threading implementation, and 34–39 times faster for the multithreading implementation. For CPU based computing, the computational time generally has a linear dependence on image size for medical imaging data. Computational efficiency is characterized in terms of time per megapixels per iteration (TPMI) with units of seconds per megapixels per iteration (or spmi). For the demons algorithm, our CPU implementation yielded largely invariant values of TPMI. The mean TPMIs were
0.527
spmi
and
0.335
spmi
for the single threading and multithreading cases, respectively, with
<
2
%
variation over the considered image data range. For GPU computing, we achieved
TPMI
=
0.00916
spmi with 3.7% variation, indicating optimized memory handling under CUDA. The paradigm of GPU based real-time DIR opens up a host of clinical applications for medical imaging.
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