Optimal discrete stopping times for reliability growth tests

Often, the duration of a reliability growth development test is specified in advance and the decision to terminate or continue testing is conducted at discrete time intervals. These features are normally not captured by reliability growth models. This paper adapts a standard reliability growth model to determine the optimal time for which to plan to terminate testing. The underlying stochastic process is developed from an Order Statistic argument with Bayesian inference used to estimate the number of faults within the design and classical inference procedures used to assess the rate of fault detection. Inference procedures within this framework are explored where it is shown the Maximum Likelihood Estimators possess a small bias and converges to the Minimum Variance Unbiased Estimator after few tests for designs with moderate number of faults. It is shown that the Likelihood function can be bimodal when there is conflict between the observed rate of fault detection and the prior distribution describing the number of faults in the design. An illustrative example is provided

Secondary schooling and rural youth transitions in Lesotho and Zimbabwe

Based on case studies centred on two rural secondary schools in Lesotho and Zimbabwe, this paper examines the gendered impacts of schooling on young people’s transitions to adulthood. School attendance is shown, first, to disrupt the conventional pathways to adulthood: young people attending school may leave home sooner than they otherwise would, and take responsibility for their day-to-day survival, while marriage and childbearing are often delayed. More significantly, secondary schooling reflects, and contributes to, a growing sense that adulthood itself is not fixed. An alternative version of adulthood is promoted through schools in which formal sector employment is central. Yet while young people are encouraged to opt for, and work towards, this goal, only a minority are able to obtain paid employment. The apparent possibility of determining one’s own lifecourse serves to cast the majority of young people as failures in their transitions to adulthood

Improved high modulus carbon fibers

Carbon fibers which are electrically insulating but still maintain the mechanical properties of the original carbon fibers were investigated. Three approaches were taken to increase the electrical resistance of carbon fibers: (1) boron nitride (BN) coatings; (2) doping of carbon fibers to alter their electrical properties; and (3) low temperature final heat treatment. The structure of carbon fibers and its effect upon properties was also studied. Results are presented

Genome-wide DNA methylation analysis for diabetic nephropathy in type 1 diabetes mellitus

BACKGROUND: Diabetic nephropathy is a serious complication of diabetes mellitus and is associated with considerable morbidity and high mortality. There is increasing evidence to suggest that dysregulation of the epigenome is involved in diabetic nephropathy. We assessed whether epigenetic modification of DNA methylation is associated with diabetic nephropathy in a case-control study of 192 Irish patients with type 1 diabetes mellitus (T1D). Cases had T1D and nephropathy whereas controls had T1D but no evidence of renal disease. METHODS: We performed DNA methylation profiling in bisulphite converted DNA from cases and controls using the recently developed Illumina Infinium(R) HumanMethylation27 BeadChip, that enables the direct investigation of 27,578 individual cytosines at CpG loci throughout the genome, which are focused on the promoter regions of 14,495 genes. RESULTS: Singular Value Decomposition (SVD) analysis indicated that significant components of DNA methylation variation correlated with patient age, time to onset of diabetic nephropathy, and sex. Adjusting for confounding factors using multivariate Cox-regression analyses, and with a false discovery rate (FDR) of 0.05, we observed 19 CpG sites that demonstrated correlations with time to development of diabetic nephropathy. Of note, this included one CpG site located 18 bp upstream of the transcription start site of UNC13B, a gene in which the first intronic SNP rs13293564 has recently been reported to be associated with diabetic nephropathy. CONCLUSION: This high throughput platform was able to successfully interrogate the methylation state of individual cytosines and identified 19 prospective CpG sites associated with risk of diabetic nephropathy. These differences in DNA methylation are worthy of further follow-up in replication studies using larger cohorts of diabetic patients with and without nephropathy

Thermodynamic Behavior of a Model Covalent Material Described by the Environment-Dependent Interatomic Potential

Using molecular dynamics simulations we study the thermodynamic behavior of a single-component covalent material described by the recently proposed Environment-Dependent Interatomic Potential (EDIP). The parameterization of EDIP for silicon exhibits a range of unusual properties typically found in more complex materials, such as the existence of two structurally distinct disordered phases, a density decrease upon melting of the low-temperature amorphous phase, and negative thermal expansion coefficients for both the crystal (at high temperatures) and the amorphous phase (at all temperatures). Structural differences between the two disordered phases also lead to a first-order transition between them, which suggests the existence of a second critical point, as is believed to exist for amorphous forms of frozen water. For EDIP-Si, however, the unusual behavior is associated not only with the open nature of tetrahedral bonding but also with a competition between four-fold (covalent) and five-fold (metallic) coordination. The unusual behavior of the model and its unique ability to simulation the liquid/amorphous transition on molecular-dynamics time scales make it a suitable prototype for fundamental studies of anomalous thermodynamics in disordeered systems.Comment: 48 pages (double-spaced), 13 figure

Heat and moisture transfer behaviour in Phyllostachys edulis (Moso bamboo) based panels

This study focuses on the heat and moisture transfer behaviours in the Phyllostachys edulis (Moso bamboo) panels in various temperature and relative humidity (RH) conditions. Moso bamboo panels with different lamination methods were prepared by bamboo strips from different layers of bamboo culm wall. The dynamic coupled heat and moisture transfer experiments were conducted. Unsteady state numerical modelling was conducted by COMSOL MultiphysicsTM. A rigorous approach was adopted in this paper, firstly a series of parametric studies of numerical simulation are firstly presented in this paper and then validated by the experiments. Both experiment and simulation results appear to be consistent with the results of measurements of the basic hygrothermal parameters, which demonstrates the robustness of the results. The temperature and RH results indicated that although the layer of panel made by the internal part of bamboo culm wall can provide good insulation performance, its ability to resist high RH variation is inferior to the layer from the external part of bamboo culm wall. The parametric study found that density is the most critical parameters to influence the temperature distributions in the transient state. The thermal conductivity dominates the temperature variation at the steady states. The water vapour diffusion resistance factor is the key parameter which influences the RH simulation results. Numerical simulation with moisture transfer shows better consistency than the simulation without moisture in both equilibrium and transient states. The results of this study demonstrated that the external part of the bamboo culm wall can be utilised to minimise the RH variation of the panel while the internal part is suitable for increasing the thermal insulation performance of the panel

Taming the snake in paradise: combining institutional design and leadership to enhance collaborative innovation

The growing expectations to public services and the pervasiveness of wicked problems in times characterized by growing fiscal constraints call for the enhancement of public innovation, and new research suggests that multi-actor collaboration in networks and partnerships is superior to hierarchical and market-based strategies when it comes to spurring such innovation. Collaborative innovation seems ideal as it builds on diversity to generate innovative public value outcomes, but there is a catch since diversity may clash with the need for constructing a common ground that allows participating actors to agree on a joint and innovative solution. The challenge for collaborative innovation – taming the snake in paradise – is to nurture the diversity of views, ideas and forms of knowledge while still establishing a common ground for joint learning. While we know a great deal about the dynamics of the mutually supportive processes of collaboration, learning and innovation, we have yet to understand the role of institutional design and leadership in spurring collaborative innovation and dealing with this tension. Building on extant research, the article draws suitable cases from the Collaborative Governance Data Bank and uses Qualitative Comparative Analysis to explore how multiple constellations of institutional design and leadership spur collaborative innovation. The main finding is that, even though certain institutional design features reduce the need for certain leadership roles, the exercise of hands-on leadership is more important for securing collaborative innovation outcomes than hands-off institutional design

Evaluation of an electronic warfarin nomogram for anticoagulation of hemodialysis patients

<p>Abstract</p> <p>Background</p> <p>Warfarin nomograms to guide dosing have been shown to improve control of the international normalized ratio (INR) in the general outpatient setting. However, the effectiveness of these nomograms in hemodialysis patients is unknown. We evaluated the effectiveness of anticoagulation using an electronic warfarin nomogram administered by nurses in outpatient hemodialysis patients, compared to physician directed therapy.</p> <p>Methods</p> <p>Hemodialysis patients at any of the six outpatient clinics in Calgary, Alberta, treated with warfarin anticoagulation were included. Two five-month time periods were compared: prior to and post implementation of the nomogram. The primary endpoint was adequacy of anticoagulation (proportion of INR measurements within range ± 0.5 units).</p> <p>Results</p> <p>Overall, 67 patients were included in the pre- and 55 in the post-period (with 40 patients in both periods). Using generalized linear mixed models, the adequacy of INR control was similar in both periods for all range INR levels: in detail, range INR 1.5 to 2.5 (pre 93.6% (95% CI: 88.6% - 96.5%); post 95.6% (95% CI: 89.4% - 98.3%); p = 0.95); INR 2.0 to 3.0 (pre 82.2% (95% CI: 77.9% - 85.8%); post 77.4% (95% CI: 72.0% - 82.0%); p = 0.20); and, INR 2.5 to 3.5 (pre 84.3% (95% CI: 59.4% - 95.1%); post 66.8% (95% CI: 39.9% - 86.0%); p = 0.29). The mean number of INR measurements per patient decreased significantly between the pre- (30.5, 95% CI: 27.0 - 34.0) and post- (22.3, 95% CI: 18.4 - 26.1) (p = 0.003) period. There were 3 bleeding events in each of the periods.</p> <p>Conclusions</p> <p>An electronic warfarin anticoagulation nomogram administered by nurses achieved INR control similar to that of physician directed therapy among hemodialysis patients in an outpatient setting, with a significant reduction in frequency of testing. Future controlled trials are required to confirm the efficacy of this nomogram.</p

Nivolumab for relapsed/refractory classical Hodgkin lymphoma: 5-year survival from the pivotal phase 2 CheckMate 205 study

Patients with relapsed/refractory (R/R) classical Hodgkin lymphoma (cHL) for whom autologous hematopoietic cell transplantation (auto-HCT) had failed experienced frequent and durable responses to nivolumab in the phase 2 CheckMate 205 trial. We present updated results (median follow-up, ~5 years). Patients with R/R cHL who were brentuximab vedotin (BV)–naive (cohort A), received BV after auto-HCT (cohort B), or received BV before and/or after auto-HCT (cohort C) were administered with nivolumab 3 mg/kg IV every 2 weeks until progression or unacceptable toxicity. Patients in cohort C with complete remission (CR) for 1 year could discontinue nivolumab and resume upon relapse. Among 243 patients (cohort A, n = 63; B, n = 80; and C, n = 100), the objective response rate (ORR) was 71.2% (95% confidence interval [CI], 65.1-76.8); the CR rate was 21.4% (95% CI, 16.4-27.1). Median duration of response, CR, and partial remission were 18.2 (95% CI, 14.7-26.1), 30.3, and 13.5 months, respectively. Median progression-free survival was 15.1 months (95% CI, 11.3-18.5). Median overall survival (OS) was not reached; OS at 5 years was 71.4% (95% CI, 64.8-77.1). In cohort C, all 3 patients who discontinued in CR and were subsequently re-treated achieved objective response. No new or unexpected safety signals were identified. This 5-year follow-up of CheckMate 205 demonstrated favorable OS and confirmed efficacy and safety of nivolumab in R/R cHL after auto-HCT failure. Results suggest patients may discontinue treatment after persistent CR and reinitiate upon progression. This trial was registered at www.clinicaltrials.gov as #NCT02181713