Gray-matter volume, midbrain dopamine D2/D3 receptors and drug craving in methamphetamine users.

Dysfunction of the mesocorticolimbic system has a critical role in clinical features of addiction. Despite evidence suggesting that midbrain dopamine receptors influence amphetamine-induced dopamine release and that dopamine is involved in methamphetamine-induced neurotoxicity, associations between dopamine receptors and gray-matter volume have been unexplored in methamphetamine users. Here we used magnetic resonance imaging and [(18)F]fallypride positron emission tomography, respectively, to measure gray-matter volume (in 58 methamphetamine users) and dopamine D2/D3 receptor availability (binding potential relative to nondisplaceable uptake of the radiotracer, BPnd) (in 31 methamphetamine users and 37 control participants). Relationships between these measures and self-reported drug craving were examined. Although no difference in midbrain D2/D3 BPnd was detected between methamphetamine and control groups, midbrain D2/D3 BPnd was positively correlated with gray-matter volume in the striatum, prefrontal cortex, insula, hippocampus and temporal cortex in methamphetamine users, but not in control participants (group-by-midbrain D2/D3 BPnd interaction, P<0.05 corrected for multiple comparisons). Craving for methamphetamine was negatively associated with gray-matter volume in the insula, prefrontal cortex, amygdala, temporal cortex, occipital cortex, cerebellum and thalamus (P<0.05 corrected for multiple comparisons). A relationship between midbrain D2/D3 BPnd and methamphetamine craving was not detected. Lower midbrain D2/D3 BPnd may increase vulnerability to deficits in gray-matter volume in mesocorticolimbic circuitry in methamphetamine users, possibly reflecting greater dopamine-induced toxicity. Identifying factors that influence prefrontal and limbic volume, such as midbrain BPnd, may be important for understanding the basis of drug craving, a key factor in the maintenance of substance-use disorders

eXCloud: Transparent runtime support for scaling mobile applications in cloud

Cloud computing augments applications with ease-of-access to the enormous resources on the Internet. Combined with mobile computing technologies, mobile applications can exploit the Cloud everywhere by statically distributing code segments or dynamically migrating running processes onto cloud services. Existing migration techniques are however too coarse-grained for mobile devices, so the overheads often offset the benefits of migration. To build a truly elastic mobile cloud computing infrastructure, we introduce eXCloud (eXtensible Cloud) - a middleware system with multi-level mobility support, ranging from as coarse as a VM instance to as fine as a runtime stack frame, and allows resources to be integrated and used dynamically. In eXCloud, a stack-on-demand (SOD) approach is used to support computation mobility throughout the mobile cloud environment. The approach is fully adaptive, goal-driven and transparent. By downward task migration, applications running on the cloud nodes can exploit or take control of special resources in mobile devices such as GPS and cameras. With a restorable MPI layer, task migrations of MPI parallel programs can happen between cloud nodes or be initiated from a mobile device. Our evaluation shows that SOD outperforms several existing migration mechanisms in terms of migration overhead and latency. All our techniques result in better resource utilization through task migrations among cloud nodes and mobile nodes.published_or_final_versionThe 2011 International Conference on Cloud and Service Computing (CSC), Hong Kong, China, 12-14 December 2011. In Proceedings of CSC, 2011, p. 103-11

Cluster Computing with Single Thread Space

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Prolonged survival of patients receiving trastuzumab beyond disease progression for HER2 overexpressing metastatic breast cancer (MBC)

Background: The aim of this retrospective analysis was to evaluate the impact of trastuzumab-based regimens on the survival of patients with HER2-overexpressing metastatic breast cancer (MBC). The study specifically focussed on the influence of the continuation of trastuzumab-based treatment despite tumor progression on survival. Patients and Methods: Patients with HER2 overexpressing MBC were included in this retrospective analysis. HER2 overexpression was determined by the immunohistochemical staining score (DAKO Hercep Test (TM)). Trastuzumab was applied at a loading dose of 4 mg/kg and a maintenance dose of 2 mg/kg. Results: Among 136 HER2 overexpressing patients (DAKO score 3+), 66 patients received first-line trastuzumab, 47 patients received trastuzumab as second-line therapy and 23 patients received trastuzumab beyond disease progression. There was no significant difference regarding the duration of trastuzumab-based treatment (first-line: 29.5 weeks vs. second-line: 25 weeks). Moreover, there was no difference in the response rate (first-line: 37.9% vs. second-line: 35.7%) or the median survival (p = 0.47 log rank). Patients who received >= 2 trastuzumab-based regimens for MBC survived significantly longer compared to those who had received only 1 regimen (>= 2 regimens: 62.4 months vs. 1 regimen: 38.5 months; p = 0.01 log rank). Conclusions: Trastuzumab is highly effective in the treatment of HER2 overexpressing MBC. Compared to historical controls, overall survival appears to be markedly prolonged, particularly in patients who received sequential trastuzumab-based treatment beyond disease progression

Probiotic administration in congenital heart disease: a pilot study.

ObjectiveTo investigate the impact of probiotic Bifidobacterium longum ssp. infantis on the fecal microbiota and plasma cytokines in neonates with congenital heart disease.Study designSixteen infants with congenital heart disease were randomly assigned to receive either B. infantis (4.2 × 10(9) colony-forming units two times daily) or placebo for 8 weeks. Stool specimens from enrolled infants and from six term infants without heart disease were analyzed for microbial composition. Plasma cytokines were analyzed weekly in the infants with heart disease.ResultsHealthy control infants had increased total bacteria, total Bacteroidetes and total bifidobacteria compared to the infants with heart disease, but there were no significant differences between the placebo and probiotic groups. Plasma interleukin (IL)10, interferon (IFN)γ and IL1β levels were transiently higher in the probiotic group.ConclusionCongenital heart disease in infants is associated with dysbiosis. Probiotic B. infantis did not significantly alter the fecal microbiota. Alterations in plasma cytokines were found to be inconsistent

Retinal thickness in eyes with mild nonproliferative retinopathy in patients with type 2 diabetes mellitus: comparison of measurements obtained by retinal thickness analysis and optical coherence tomography

OBJECTIVE: To compare measurements of retinal thickness in eyes with mild nonproliferative retinopathy in patients with type 2 diabetes mellitus using 2 different techniques: the retinal thickness analyzer (RTA) and optical coherence tomography (OCT). METHODS: Twenty-eight eyes from 28 patients with type 2 diabetes mellitus and mild nonproliferative retinopathy were classified according to the Wisconsin grading system by 7-field stereoscopic fundus photography. Ten eyes were classified as level 10 (absence of visible lesions) and 18 as level 20 or 35 (minimal retinopathy). All eyes were examined by the RTA and OCT. Healthy populations were used to establish reference maps for the RTA (n = 14; mean age, 48 years; age range, 42-55 years) and OCT (n = 10; mean age, 56 years; age range, 43-68 years). Reference maps were computed using the means + 2 SDs of the values obtained for each location. Increases in thickness were computed as a percentage of increase over these reference maps. RESULTS: The RTA detected increases in thickness in 1 or more locations in 24 of the 28 diabetic eyes examined, whereas OCT detected increases in only 3 eyes. The percentages of increase detected by the RTA ranged from 0.3% to 73.5%, whereas OCT detected percentages of increase of 0.3% to 4.8%. CONCLUSION: Optical coherence tomography is less sensitive than the RTA in detecting localized increases in retinal thickness in the initial stages of diabetic retinal disease

Effect of pulsed methylprednisolone on pain, in patients with HTLV-1-associated myelopathy

HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is an immune mediated myelopathy caused by the human T-lymphotropic virus type 1 (HTLV-1). The efficacy of treatments used for patients with HAM/TSP is uncertain. The aim of this study is to document the efficacy of pulsed methylprednisolone in patients with HAM/TSP. Data from an open cohort of 26 patients with HAM/TSP was retrospectively analysed. 1g IV methylprednisolone was infused on three consecutive days. The outcomes were pain, gait, urinary frequency and nocturia, a range of inflammatory markers and HTLV-1 proviral load. Treatment was well tolerated in all but one patient. Significant improvements in pain were: observed immediately, unrelated to duration of disease and maintained for three months. Improvement in gait was only seen on Day 3 of treatment. Baseline cytokine concentrations did not correlate to baseline pain or gait impairment but a decrease in tumour necrosis factor-alpha (TNF-α) concentration after pulsed methylprednisolone was associated with improvements in both. Until compared with placebo, treatment with pulsed methylprednisolone should be offered to patients with HAM/TSP for the treatment of pain present despite regular analgesia

Run Generation Revisited: What Goes Up May or May Not Come Down

In this paper, we revisit the classic problem of run generation. Run generation is the first phase of external-memory sorting, where the objective is to scan through the data, reorder elements using a small buffer of size M , and output runs (contiguously sorted chunks of elements) that are as long as possible. We develop algorithms for minimizing the total number of runs (or equivalently, maximizing the average run length) when the runs are allowed to be sorted or reverse sorted. We study the problem in the online setting, both with and without resource augmentation, and in the offline setting. (1) We analyze alternating-up-down replacement selection (runs alternate between sorted and reverse sorted), which was studied by Knuth as far back as 1963. We show that this simple policy is asymptotically optimal. Specifically, we show that alternating-up-down replacement selection is 2-competitive and no deterministic online algorithm can perform better. (2) We give online algorithms having smaller competitive ratios with resource augmentation. Specifically, we exhibit a deterministic algorithm that, when given a buffer of size 4M , is able to match or beat any optimal algorithm having a buffer of size M . Furthermore, we present a randomized online algorithm which is 7/4-competitive when given a buffer twice that of the optimal. (3) We demonstrate that performance can also be improved with a small amount of foresight. We give an algorithm, which is 3/2-competitive, with foreknowledge of the next 3M elements of the input stream. For the extreme case where all future elements are known, we design a PTAS for computing the optimal strategy a run generation algorithm must follow. (4) Finally, we present algorithms tailored for nearly sorted inputs which are guaranteed to have optimal solutions with sufficiently long runs

ciliaFA : a research tool for automated, high-throughput measurement of ciliary beat frequency using freely available software

Background: Analysis of ciliary function for assessment of patients suspected of primary ciliary dyskinesia (PCD) and for research studies of respiratory and ependymal cilia requires assessment of both ciliary beat pattern and beat frequency. While direct measurement of beat frequency from high-speed video recordings is the most accurate and reproducible technique it is extremely time consuming. The aim of this study was to develop a freely available automated method of ciliary beat frequency analysis from digital video (AVI) files that runs on open-source software (ImageJ) coupled to Microsoft Excel, and to validate this by comparison to the direct measuring high-speed video recordings of respiratory and ependymal cilia. These models allowed comparison to cilia beating between 3 and 52 Hz. Methods: Digital video files of motile ciliated ependymal (frequency range 34 to 52 Hz) and respiratory epithelial cells (frequency 3 to 18 Hz) were captured using a high-speed digital video recorder. To cover the range above between 18 and 37 Hz the frequency of ependymal cilia were slowed by the addition of the pneumococcal toxin pneumolysin. Measurements made directly by timing a given number of individual ciliary beat cycles were compared with those obtained using the automated ciliaFA system. Results: The overall mean difference (± SD) between the ciliaFA and direct measurement high-speed digital imaging methods was −0.05 ± 1.25 Hz, the correlation coefficient was shown to be 0.991 and the Bland-Altman limits of agreement were from −1.99 to 1.49 Hz for respiratory and from −2.55 to 3.25 Hz for ependymal cilia. Conclusions: A plugin for ImageJ was developed that extracts pixel intensities and performs fast Fourier transformation (FFT) using Microsoft Excel. The ciliaFA software allowed automated, high throughput measurement of respiratory and ependymal ciliary beat frequency (range 3 to 52 Hz) and avoids operator error due to selection bias. We have included free access to the ciliaFA plugin and installation instructions in Additional file 1 accompanying this manuscript that other researchers may use

Endothelial cell processing and alternatively spliced transcripts of factor VIII: potential implications for coagulation cascades and pulmonary hypertension.

BACKGROUND: Coagulation factor VIII (FVIII) deficiency leads to haemophilia A. Conversely, elevated plasma levels are a strong predictor of recurrent venous thromboemboli and pulmonary hypertension phenotypes in which in situ thromboses are implicated. Extrahepatic sources of plasma FVIII are implicated, but have remained elusive. METHODOLOGY/PRINCIPAL FINDINGS: Immunohistochemistry of normal human lung tissue, and confocal microscopy, flow cytometry, and ELISA quantification of conditioned media from normal primary endothelial cells were used to examine endothelial expression of FVIII and coexpression with von Willebrand Factor (vWF), which protects secreted FVIII heavy chain from rapid proteloysis. FVIII transcripts predicted from database mining were identified by RT-PCR and sequencing. FVIII mAb-reactive material was demonstrated in CD31+ endothelial cells in normal human lung tissue, and in primary pulmonary artery, pulmonary microvascular, and dermal microvascular endothelial cells. In pulmonary endothelial cells, this protein occasionally colocalized with vWF, centered on Weibel Palade bodies. Pulmonary artery and pulmonary microvascular endothelial cells secreted low levels of FVIII and vWF to conditioned media, and demonstrated cell surface expression of FVIII and vWF Ab-reacting proteins compared to an isotype control. Four endothelial splice isoforms were identified. Two utilize transcription start sites in alternate 5 exons within the int22h-1 repeat responsible for intron 22 inversions in 40% of severe haemophiliacs. A reciprocal relationship between the presence of short isoforms and full-length FVIII transcript suggested potential splice-switching mechanisms. CONCLUSIONS/SIGNIFICANCE: The pulmonary endothelium is confirmed as a site of FVIII secretion, with evidence of synthesis, cell surface expression, and coexpression with vWF. There is complex alternate transcription initiation from the FVIII gene. These findings provide a framework for future research on the regulation and perturbation of FVIII synthesis, and of potential relevance to haemophilia, thromboses, and pulmonary hypertensive states