The MVA Priority Approximation

A Mean Value Analysis (MVA) approximation is presented for computing the average performance measures of closed-, open-, and mixed-type multiclass queuing networks containing Preemptive Resume (PR) and nonpreemptive Head-Of-Line (HOL) priority service centers. The approximation has essentially the same storage and computational requirements as MVA, thus allowing computationally efficient solutions of large priority queuing networks. The accuracy of the MVA approximation is systematically investigated and presented. It is shown that the approximation can compute the average performance measures of priority networks to within an accuracy of 5 percent for a large range of network parameter values. Accuracy of the method is shown to be superior to that of Sevcik's shadow approximation

UC: a language for the connection machine

n designing parallel languages, the concern for defining a simple virtual machine must be balanced against the need to efficiently map a program on a specific architecture. UC addresses this problem by separating the programming task from efficiency considerations. UC programs are designed using a small set of constructs that include reduction, parallel assignment, and fixed-point computation. The language also provides a map section that may optionally be used by a programmer to specify data mappings for the program. The authors describe the UC constructs and their implementation on the Connection Machine. They also present measurements of the compiler for simple benchmarks

Comparison of Risk of Recrudescent Fever in Children With Kawasaki Disease Treated With Intravenous Immunoglobulin and Low-Dose vs High-Dose Aspirin

Importance: Timely initiation of intravenous immunoglobulin plus aspirin is necessary for decreasing the risk of recrudescent fever and coronary artery abnormalities in children with Kawasaki disease (KD). The optimal dose of aspirin, however, remains unclear. Objective: To evaluate whether initial treatment with low-dose compared with high-dose aspirin in children with KD is associated with an increase in fever recrudescence. Design, Setting, and Participants: A retrospective cohort study of 260 children with KD at Riley Hospital for Children, Indianapolis, Indiana, between January 1, 2007, and December 31, 2018, was conducted. Children aged 0 to 18 years with a first episode of KD, identified by International Classification of Diseases, Ninth Revision and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision diagnosis codes treated within 10 days of symptom onset with high-dose intravenous immunoglobulin plus aspirin were eligible. Patients who received an alternative diagnosis, experienced a second episode of KD, did not receive intravenous immunoglobulin plus aspirin for initial treatment, were not treated within 10 days of symptoms, or had incomplete records were excluded. Exposures: High-dose (≥10 mg/kg/d) or low-dose (<10 mg/kg/d) aspirin therapy. Main Outcomes and Measures: The primary outcome was recrudescent fever necessitating retreatment of KD. The secondary outcomes were coronary artery abnormalities and hospital length of stay. Results: Among the 260 patients included, the median (interquartile range) age was 2.5 (1.6-4.3) years, 103 (39.6%) were girls, 166 (63.8%) were non-Hispanic white, 57 (21.9%) were African American, 22 (8.5%) were Asian, 11 (4.2%) were Hispanic, and 4 (1.5%) were of unknown race/ethnicity. One hundred-forty-two patients (54.6%) were treated with low-dose aspirin. There was no association between recrudescent fever and aspirin dose, with 39 children (27.5%) having recrudescent fever in the low-dose group compared with 26 children (22.0%) in the high-dose group (odds ratio [OR], 1.34; 95% CI, 0.76-2.37; P = .31), with similar results after adjusting for potential confounding variables (OR, 1.63; 95% CI, 0.89-2.97; P = .11). In a subset analysis of 167 children with complete KD, however, there was nearly a 2-fold difference in the odds of recrudescent fever with low-dose aspirin (OR, 1.87; 95% CI, 0.82-4.23; P = .14), although this difference did not reach statistical significance. In addition, no association was identified between treatment group and coronary artery abnormalities (low-dose, 7.4% vs high-dose, 9.4%; OR, 0.86; 95% CI, 0.48-1.55; P = .62) or median (interquartile range) length of stay (3 [3-5] days for both groups; P = .27). Conclusions and Relevance: In this study, low-dose aspirin for the initial treatment of children with KD was not associated with fever recrudescence or coronary artery abnormalities. Given the potential benefits, further study of low-dose aspirin to detect potentially clinically relevant outcome differences is warranted to inform treatment decisions and guideline development

Novel use Of Hydroxyurea in an African Region with Malaria (NOHARM): a trial for children with sickle cell anemia

Hydroxyurea treatment is recommended for children with sickle cell anemia (SCA) living in high-resource malaria-free regions, but its safety and efficacy in malaria-endemic sub-Saharan Africa, where the greatest sickle-cell burden exists, remain unknown. In vitro studies suggest hydroxyurea could increase malaria severity, and hydroxyurea-associated neutropenia could worsen infections. NOHARM (Novel use Of Hydroxyurea in an African Region with Malaria) was a randomized, double-blinded, placebo-controlled trial conducted in malaria-endemic Uganda, comparing hydroxyurea to placebo at 20 ± 2.5 mg/kg per day for 12 months. The primary outcome was incidence of clinical malaria. Secondary outcomes included SCA-related adverse events (AEs), clinical and laboratory effects, and hematological toxicities. Children received either hydroxyurea (N = 104) or placebo (N = 103). Malaria incidence did not differ between children on hydroxyurea (0.05 episodes per child per year; 95% confidence interval [0.02, 0.13]) vs placebo (0.07 episodes per child per year [0.03, 0.16]); the hydroxyurea/placebo malaria incidence rate ratio was 0.7 ([0.2, 2.7]; P = .61). Time to infection also did not differ significantly between treatment arms. A composite SCA-related clinical outcome (vaso-occlusive painful crisis, dactylitis, acute chest syndrome, splenic sequestration, or blood transfusion) was less frequent with hydroxyurea (45%) than placebo (69%; P = .001). Children receiving hydroxyurea had significantly increased hemoglobin concentration and fetal hemoglobin, with decreased leukocytes and reticulocytes. Serious AEs, sepsis episodes, and dose-limiting toxicities were similar between treatment arms. Three deaths occurred (2 hydroxyurea, 1 placebo, and none from malaria). Hydroxyurea treatment appears safe for children with SCA living in malaria-endemic sub-Saharan Africa, without increased severe malaria, infections, or AEs. Hydroxyurea provides SCA-related laboratory and clinical efficacy, but optimal dosing and monitoring regimens for Africa remain undefined. This trial was registered at www.clinicaltrials.gov as #NCT01976416

A multichannel feature-based approach for longitudinal lung CT registration in the presence of radiation induced lung damage

Quantifying parenchymal tissue changes in the lungs is imperative in furthering the study of radiation-induced lung damage (RILD). Registering lung images from different time-points is a key step of this process. Traditional intensity-based registration approaches fail this task due to the considerable anatomical changes that occur between timepoints. This work proposes a novel method to successfully register longitudinal pre- and post-radiotherapy (RT) lung CT scans that exhibit large changes due to RILD, by extracting consistent anatomical features from CT (lung boundaries, main airways, vessels) and using these features to optimise the registrations. Pre-RT and 12-month post-RT CT pairs from fifteen lung cancer patients were used for this study, all with varying degrees of RILD, ranging from mild parenchymal change to extensive consolidation and collapse. For each CT, signed distance transforms from segmentations of the lungs and main airways were generated, and the Frangi vesselness map was calculated. These were concatenated into multi-channel images and diffeomorphic multichannel registration was performed for each image pair using NiftyReg. Traditional intensity-based registrations were also performed for comparison purposes. For the evaluation, the pre- and post-registration landmark distance was calculated for all patients, using an average of 44 manually identified landmark pairs per patient. The mean (standard deviation) distance for all datasets decreased from 15.95 (8.09) mm pre-registration to 4.56 (5.70) mm post-registration, compared to 7.90 (8.97) mm for the intensity-based registrations. Qualitative improvements in image alignment were observed for all patient datasets. For four representative subjects, registrations were performed for 3 additional follow-up timepoints up to 48-months post-RT and similar accuracy was achieved. We have demonstrated that our novel multichannel registration method can successfully align longitudinal scans from RILD patients in the presence of large anatomical changes such as consolidation and atelectasis, outperforming the traditional registration approach both quantitatively and through thorough visual inspection

Determination of the breakpoint and molecular diagnosis of a common α-thalassaemia-1 deletion in the Indian population

The previously described South African type α-thalassaemia-1 mutation was identified in Indian HbH patients using a polymerase chain reaction (PCR) strategy. A multiplex PCR assay was devised to detect heterozygotes and homozygotes. This α-thalassaemia-1 mutation was found to be the commonest determinant causing HbH disease in this population. In one family this mutation was found in combination with a novel splice donor mutation α2 IVS I-1 (G→A). Characterization of the breakpoint junction sequence revealed, in addition to a 23 kb deletion, that there was an addition of ~160 bp bridging the breakpoints. Similar to other deletions in the α-globin gene cluster, there is an Alu repeat-mediated mechanism for the origin of the deletion

Salmonella choleraesuis subsp. indica serovar bornheim causing urinary tract infection

An unusual Salmonella species, S. choleraesuis subsp. indica serovar bornheim, was isolated from the urine of a patient with aplastic anemia, diabetes mellitus, and a healed urethral injury. An immune response to this isolate was demonstrated by whole-bacterial-cell agglutination

Investigation of the evolution of radiation-induced lung damage using serial CT imaging and pulmonary function tests

Background and purpose: Radiation-induced lung damage (RILD) is a common consequence of lung cancer radiotherapy (RT) with unclear evolution over time. We quantify radiological RILD longitudinally and correlate it with dosimetry and respiratory morbidity. Materials and methods: CTs were available pre-RT and at 3, 6, 12 and 24-months post-RT for forty-five subjects enrolled in a phase 1/2 clinical trial of isotoxic, dose-escalated chemoradiotherapy for locally advanced non-small cell lung cancer. Fifteen CT-based measures of parenchymal, pleural and lung volume change, and anatomical distortions, were calculated. Respiratory morbidity was assessed with the Medical Research Council (MRC) dyspnoea score and spirometric pulmonary function tests (PFTs): FVC, FEV1, FEV1/FVC and DLCO. Results: FEV1, FEV1/FVC and MRC scores progressively declined post-RT; FVC decreased by 6-months before partially recovering. Radiologically, an early phase (3–6 months) of acute inflammation was characterised by reversible parenchymal change and non-progressive anatomical distortion. A phase of chronic scarring followed (6–24 months) with irreversible parenchymal change, progressive volume loss and anatomical distortion. Post-RT increase in contralateral lung volume was common. Normal lung volume shrinkage correlated longitudinally with mean lung dose (r = 0.30–0.40, p = 0.01–0.04). Radiological findings allowed separation of patients with predominant acute versus chronic RILD; subjects with predominantly chronic RILD had poorer pre-RT lung function. Conclusions: CT-based measures enable detailed quantification of the longitudinal evolution of RILD. The majority of patients developed progressive lung damage, even when the early phase was absent or mild. Pre-RT lung function and RT dosimetry may allow to identify subjects at increased risk of RILD

The combinatorics of resource sharing

We discuss general models of resource-sharing computations, with emphasis on the combinatorial structures and concepts that underlie the various deadlock models that have been proposed, the design of algorithms and deadlock-handling policies, and concurrency issues. These structures are mostly graph-theoretic in nature, or partially ordered sets for the establishment of priorities among processes and acquisition orders on resources. We also discuss graph-coloring concepts as they relate to resource sharing.Comment: R. Correa et alii (eds.), Models for Parallel and Distributed Computation, pp. 27-52. Kluwer Academic Publishers, Dordrecht, The Netherlands, 200