Efficient design of CMOS TSC checkers

This paper considers the design of an efficient, robustly testable, CMOS Totally Self-Checking (TSC) Checker for k-out-of-2k codes. Most existing implementations use primitive gates and assume the single stuck-at fault model. The self-testing property has been found to fail for CMOS TSC checkers under the stuck-open fault model due to timing skews and arbitrary delays in the circuit. A new four level design using CMOS primitive gates (NAND, NOR, INVERTERS) is presented. This design retains its properties under the stuck-open fault model. Additionally, this method offers an impressive reduction (greater than 70 percent) in gate count, gate inputs, and test set size when compared to the existing method. This implementation is easily realizable and is based on Anderson's technique. A thorough comparative study has been made on the proposed implementation and Kundu's implementation and the results indicate that the proposed one is better than Kundu's in all respects for k-out-of-2k codes

On Virtual Displacement and Virtual Work in Lagrangian Dynamics

The confusion and ambiguity encountered by students, in understanding virtual displacement and virtual work, is discussed in this article. A definition of virtual displacement is presented that allows one to express them explicitly for holonomic (velocity independent), non-holonomic (velocity dependent), scleronomous (time independent) and rheonomous (time dependent) constraints. It is observed that for holonomic, scleronomous constraints, the virtual displacements are the displacements allowed by the constraints. However, this is not so for a general class of constraints. For simple physical systems, it is shown that, the work done by the constraint forces on virtual displacements is zero. This motivates Lagrange's extension of d'Alembert's principle to system of particles in constrained motion. However a similar zero work principle does not hold for the allowed displacements. It is also demonstrated that d'Alembert's principle of zero virtual work is necessary for the solvability of a constrained mechanical problem. We identify this special class of constraints, physically realized and solvable, as {\it the ideal constraints}. The concept of virtual displacement and the principle of zero virtual work by constraint forces are central to both Lagrange's method of undetermined multipliers, and Lagrange's equations in generalized coordinates.Comment: 12 pages, 10 figures. This article is based on an earlier article physics/0410123. It includes new figures, equations and logical conten

Protocol for process evaluation of a randomised controlled trial of family-led rehabilitation post stroke (ATTEND) in India

Introduction We are undertaking a randomised controlled trial (fAmily led rehabiliTaTion aftEr stroke in INDia, ATTEND) evaluating training a family carer to enable maximal rehabilitation of patients with stroke-related disability; as a potentially affordable, culturally acceptable and effective intervention for use in India. A process evaluation is needed to understand how and why this complex intervention may be effective, and to capture important barriers and facilitators to its implementation. We describe the protocol for our process evaluation to encourage the development of in-process evaluation methodology and transparency in reporting. Methods and analysis The realist and RE-AIM (Reach, Effectiveness, Adoption, Implementation and Maintenance) frameworks informed the design. Mixed methods include semistructured interviews with health providers, patients and their carers, analysis of quantitative process data describing fidelity and dose of intervention, observations of trial set up and implementation, and the analysis of the cost data from the patients and their families perspective and programme budgets. These qualitative and quantitative data will be analysed iteratively prior to knowing the quantitative outcomes of the trial, and then triangulated with the results from the primary outcome evaluation. Ethics and dissemination The process evaluation has received ethical approval for all sites in India. In low-income and middle-income countries, the available human capital can form an approach to reducing the evidence practice gap, compared with the high cost alternatives available in established market economies. This process evaluation will provide insights into how such a programme can be implemented in practice and brought to scale. Through local stakeholder engagement and dissemination of findings globally we hope to build on patient-centred, cost-effective and sustainable models of stroke rehabilitation. Trial registration number CTRI/2013/04/003557

The complex genetic landscape of familial MDS and AML reveals pathogenic germline variants.

The inclusion of familial myeloid malignancies as a separate disease entity in the revised WHO classification has renewed efforts to improve the recognition and management of this group of at risk individuals. Here we report a cohort of 86 acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) families with 49 harboring germline variants in 16 previously defined loci (57%). Whole exome sequencing in a further 37 uncharacterized families (43%) allowed us to rationalize 65 new candidate loci, including genes mutated in rare hematological syndromes (ADA, GP6, IL17RA, PRF1 and SEC23B), reported in prior MDS/AML or inherited bone marrow failure series (DNAH9, NAPRT1 and SH2B3) or variants at novel loci (DHX34) that appear specific to inherited forms of myeloid malignancies. Altogether, our series of MDS/AML families offer novel insights into the etiology of myeloid malignancies and provide a framework to prioritize variants for inclusion into routine diagnostics and patient management

DDX5 plays essential transcriptional and post-transcriptional roles in the maintenance and function of spermatogonia

Mammalian spermatogenesis is sustained by mitotic germ cells with self-renewal potential known as undifferentiated spermatogonia. Maintenance of undifferentiated spermatogonia and spermatogenesis is dependent on tightly co-ordinated transcriptional and post-transcriptional mechanisms. The RNA helicase DDX5 is expressed by spermatogonia but roles in spermatogenesis are unexplored. Using an inducible knockout mouse model, we characterise an essential role for DDX5 in spermatogonial maintenance and show that Ddx5 is indispensable for male fertility. We demonstrate that DDX5 regulates appropriate splicing of key genes necessary for spermatogenesis. Moreover, DDX5 regulates expression of cell cycle genes in undifferentiated spermatogonia post-transcriptionally and is required for cell proliferation and survival. DDX5 can also act as a transcriptional co-activator and we demonstrate that DDX5 interacts with PLZF, a transcription factor required for germline maintenance, to co-regulate select target genes. Combined, our data reveal a critical multifunctional role for DDX5 in regulating gene expression programmes and activity of undifferentiated spermatogonia

Statistical analysis plan for the family-led rehabilitation after stroke in India (ATTEND) trial: A multicenter randomized controlled trial of a new model of stroke rehabilitation compared to usual care

Background In low- and middle-income countries, few patients receive organized rehabilitation after stroke, yet the burden of chronic diseases such as stroke is increasing in these countries. Affordable models of effective rehabilitation could have a major impact. The ATTEND trial is evaluating a family-led caregiver delivered rehabilitation program after stroke. Objective To publish the detailed statistical analysis plan for the ATTEND trial prior to trial unblinding. Methods Based upon the published registration and protocol, the blinded steering committee and management team, led by the trial statistician, have developed a statistical analysis plan. The plan has been informed by the chosen outcome measures, the data collection forms and knowledge of key baseline data. Results The resulting statistical analysis plan is consistent with best practice and will allow open and transparent reporting. Conclusions Publication of the trial statistical analysis plan reduces potential bias in trial reporting, and clearly outlines pre-specified analyses

Global diversity and antimicrobial resistance of typhoid fever pathogens: Insights from a meta-analysis of 13,000 Salmonella Typhi genomes

Background: The Global Typhoid Genomics Consortium was established to bring together the typhoid research community to aggregate and analyse Salmonella enterica serovar Typhi (Typhi) genomic data to inform public health action. This analysis, which marks 22 years since the publication of the first Typhi genome, represents the largest Typhi genome sequence collection to date (n=13,000). Methods: This is a meta-analysis of global genotype and antimicrobial resistance (AMR) determinants extracted from previously sequenced genome data and analysed using consistent methods implemented in open analysis platforms GenoTyphi and Pathogenwatch. Results: Compared with previous global snapshots, the data highlight that genotype 4.3.1 (H58) has not spread beyond Asia and Eastern/Southern Africa; in other regions, distinct genotypes dominate and have independently evolved AMR. Data gaps remain in many parts of the world, and we show the potential of travel-associated sequences to provide informal ‘sentinel’ surveillance for such locations. The data indicate that ciprofloxacin non-susceptibility (>1 resistance determinant) is widespread across geographies and genotypes, with high-level ciprofloxacin resistance (=3 determinants) reaching 20% prevalence in South Asia. Extensively drug-resistant (XDR) typhoid has becomedominant in Pakistan (70% in 2020) but has not yet become established elsewhere. Ceftriaxone resistance has emerged in eight non-XDR genotypes, including a ciprofloxacin-resistant lineage (4.3.1.2.1) in India. Azithromycin resistance mutations were detected at low prevalence in South Asia, including in two common ciprofloxacin-resistant genotypes. Conclusions: The consortium’s aim is to encourage continued data sharing and collaboration to monitor the emergence and global spread of AMR Typhi, and to inform decision-making around the introduction of typhoid conjugate vaccines (TCVs) and other prevention and control strategies

Improved functionalization of oleic acid-coated iron oxide nanoparticles for biomedical applications

Superparamagnetic iron oxide nanoparticles can providemultiple benefits for biomedical applications in aqueous environments such asmagnetic separation or magnetic resonance imaging. To increase the colloidal stability and allow subsequent reactions, the introduction of hydrophilic functional groups onto the particles’ surface is essential. During this process, the original coating is exchanged by preferably covalently bonded ligands such as trialkoxysilanes. The duration of the silane exchange reaction, which commonly takes more than 24 h, is an important drawback for this approach. In this paper, we present a novel method, which introduces ultrasonication as an energy source to dramatically accelerate this process, resulting in high-quality waterdispersible nanoparticles around 10 nmin size. To prove the generic character, different functional groups were introduced on the surface including polyethylene glycol chains, carboxylic acid, amine, and thiol groups. Their colloidal stability in various aqueous buffer solutions as well as human plasma and serum was investigated to allow implementation in biomedical and sensing applications.status: publishe