Multiplicity adjustments in parallel-group multi-arm trials sharing a control group: Clear guidance is needed

Multi-arm, parallel-group clinical trials are an efficient way of testing several new treatments, treatment regimens or doses. However, guidance on the requirement for statistical adjustment to control for multiple comparisons (type I error) using a shared control group is unclear. We argue, based on current evidence, that adjustment is not always necessary in such situations. We propose that adjustment should not be a requirement in multi-arm, parallel-group trials testing distinct treatments and sharing a control group, and we call for clearer guidance from stakeholders, such as regulators and scientific journals, on the appropriate settings for adjustment of multiplicity

Performance optimization of a leagility inspired supply chain model: a CFGTSA algorithm based approach

Lean and agile principles have attracted considerable interest in the past few decades. Industrial sectors throughout the world are upgrading to these principles to enhance their performance, since they have been proven to be efficient in handling supply chains. However, the present market trend demands a more robust strategy incorporating the salient features of both lean and agile principles. Inspired by these, the leagility principle has emerged, encapsulating both lean and agile features. The present work proposes a leagile supply chain based model for manufacturing industries. The paper emphasizes the various aspects of leagile supply chain modeling and implementation and proposes a new Hybrid Chaos-based Fast Genetic Tabu Simulated Annealing (CFGTSA) algorithm to solve the complex scheduling problem prevailing in the leagile environment. The proposed CFGTSA algorithm is compared with the GA, SA, TS and Hybrid Tabu SA algorithms to demonstrate its efficacy in handling complex scheduling problems

Multiplicity adjustments in parallel-group multi-arm trials sharing a control group: Clear guidance is needed

Multi-arm, parallel-group clinical trials are an efficient way of testing several new treatments, treatment regimens or doses. However, guidance on the requirement for statistical adjustment to control for multiple comparisons (type I error) using a shared control group is unclear. We argue, based on current evidence, that adjustment is not always necessary in such situations. We propose that adjustment should not be a requirement in multi-arm, parallel-group trials testing distinct treatments and sharing a control group, and we call for clearer guidance from stakeholders, such as regulators and scientific journals, on the appropriate settings for adjustment of multiplicity

"Obesity" and "Clinical Obesity" Men's understandings of obesity and its relation to the risk of diabetes: A qualitative study

<p>Abstract</p> <p>Background</p> <p>The 2007 Wanless report highlights the ever increasing problem of obesity and the consequent health problems. Obesity is a significant cause of diabetes. An increasing evidence base suggests that in terms of reducing diabetes and CVD risk, it is better to be "fit and fat" than unfit and of normal weight. There has been very little previous research into the understandings that men in the general population hold about the issues of weight, exercise and health; we therefore undertook this study in order to inform the process of health promotion and diabetes prevention in this group.</p> <p>Methods</p> <p>A qualitative study in North East England General Practice using a purposive sample of men aged 25 and 45 years (selection process designed to include 'normal', 'overweight' and 'obese' men). One to one audio-recorded semi structured interviews focused on: overweight and obesity, diet, physical activity and diabetes. Transcripts were initially analysed using framework analysis. Emerging themes interlinked.</p> <p>Results</p> <p>The men in this study (n = 17) understand the word obesity differently from the clinical definition; "obesity" was used as a description of those with fat in a central distribution, and understandings of the term commonly take into account fitness as well as weight. Men in their late 30s and early 40s described becoming more aware of health issues. Knowledge of what constitutes a 'healthy lifestyle' was generally good, but men described difficulty acting upon this knowledge for various reasons e.g. increasing responsibilities at home and at work. Knowledge of diabetes and the link between obesity and diabetes was poor.</p> <p>Conclusion</p> <p>Men in this study had a complex understanding of the interlinked importance of weight and fitness in relation to health. Obesity is understood as a description of people with centrally distributed fat, in association with low fitness levels. There is a need to increase understanding of the causes and consequences of diabetes. Discussion of increased health awareness by men round the age of 40 may indicate a window of opportunity to intervene at this time.</p

The FIELDS Instrument Suite for Solar Probe Plus: Measuring the Coronal Plasma and Magnetic Field, Plasma Waves and Turbulence, and Radio Signatures of Solar Transients.

NASA's Solar Probe Plus (SPP) mission will make the first in situ measurements of the solar corona and the birthplace of the solar wind. The FIELDS instrument suite on SPP will make direct measurements of electric and magnetic fields, the properties of in situ plasma waves, electron density and temperature profiles, and interplanetary radio emissions, amongst other things. Here, we describe the scientific objectives targeted by the SPP/FIELDS instrument, the instrument design itself, and the instrument concept of operations and planned data products

Adaptive remodeling of the bacterial proteome by specific ribosomal modification regulates Pseudomonas infection and niche colonisation

Post-transcriptional control of protein abundance is a highly important, underexplored regulatory process by which organisms respond to their environments. Here we describe an important and previously unidentified regulatory pathway involving the ribosomal modification protein RimK, its regulator proteins RimA and RimB, and the widespread bacterial second messenger cyclic-di-GMP (cdG). Disruption of rimK affects motility and surface attachment in pathogenic and commensal Pseudomonas species, with rimK deletion significantly compromising rhizosphere colonisation by the commensal soil bacterium P. fluorescens, and plant infection by the pathogens P. syringae and P. aeruginosa. RimK functions as an ATP-dependent glutamyl ligase, adding glutamate residues to the C-terminus of ribosomal protein RpsF and inducing specific effects on both ribosome protein complement and function. Deletion of rimK in P. fluorescens leads to markedly reduced levels of multiple ribosomal proteins, and also of the key translational regulator Hfq. In turn, reduced Hfq levels induce specific downstream proteomic changes, with significant increases in multiple ABC transporters, stress response proteins and non-ribosomal peptide synthetases seen for both ΔrimK and Δhfq mutants. The activity of RimK is itself controlled by interactions with RimA, RimB and cdG. We propose that control of RimK activity represents a novel regulatory mechanism that dynamically influences interactions between bacteria and their hosts; translating environmental pressures into dynamic ribosomal changes, and consequently to an adaptive remodeling of the bacterial proteome

Enriching Peptide Libraries for Binding Affinity and Specificity Through Computationally Directed Library Design

Peptide reagents with high affinity or specificity for their target protein interaction partner are of utility for many important applications. Optimization of peptide binding by screening large libraries is a proven and powerful approach. Libraries designed to be enriched in peptide sequences that are predicted to have desired affinity or specificity characteristics are more likely to yield success than random mutagenesis. We present a library optimization method in which the choice of amino acids to encode at each peptide position can be guided by available experimental data or structure-based predictions. We discuss how to use analysis of predicted library performance to inform rounds of library design. Finally, we include protocols for more complex library design procedures that consider the chemical diversity of the amino acids at each peptide position and optimize a library score based on a user-specified input model.National Institute of General Medical Sciences (U.S.) (Award R01 GM110048