Spatiotemporal neuromodulation therapies engaging muscle synergies improve motor control after spinal cord injury.

Electrical neuromodulation of lumbar segments improves motor control after spinal cord injury in animal models and humans. However, the physiological principles underlying the effect of this intervention remain poorly understood, which has limited the therapeutic approach to continuous stimulation applied to restricted spinal cord locations. Here we developed stimulation protocols that reproduce the natural dynamics of motoneuron activation during locomotion. For this, we computed the spatiotemporal activation pattern of muscle synergies during locomotion in healthy rats. Computer simulations identified optimal electrode locations to target each synergy through the recruitment of proprioceptive feedback circuits. This framework steered the design of spatially selective spinal implants and real-time control software that modulate extensor and flexor synergies with precise temporal resolution. Spatiotemporal neuromodulation therapies improved gait quality, weight-bearing capacity, endurance and skilled locomotion in several rodent models of spinal cord injury. These new concepts are directly translatable to strategies to improve motor control in humans.

Quality control and conduct of genome-wide association meta-analyses.

Rigorous organization and quality control (QC) are necessary to facilitate successful genome-wide association meta-analyses (GWAMAs) of statistics aggregated across multiple genome-wide association studies. This protocol provides guidelines for (i) organizational aspects of GWAMAs, and for (ii) QC at the study file level, the meta-level across studies and the meta-analysis output level. Real-world examples highlight issues experienced and solutions developed by the GIANT Consortium that has conducted meta-analyses including data from 125 studies comprising more than 330,000 individuals. We provide a general protocol for conducting GWAMAs and carrying out QC to minimize errors and to guarantee maximum use of the data. We also include details for the use of a powerful and flexible software package called EasyQC. Precise timings will be greatly influenced by consortium size. For consortia of comparable size to the GIANT Consortium, this protocol takes a minimum of about 10 months to complete.

MSight: an image analysis software for liquid chromatography-mass spectrometry.

Images obtained from high-throughput mass spectrometry (MS) contain information that remains hidden when looking at a single spectrum at a time. Image processing of liquid chromatography-MS datasets can be extremely useful for quality control, experimental monitoring and knowledge extraction. The importance of imaging in differential analysis of proteomic experiments has already been established through two-dimensional gels and can now be foreseen with MS images. We present MSight, a new software designed to construct and manipulate MS images, as well as to facilitate their analysis and comparison.

The appropriateness of renal angioplasty: the ANPARIA software: a multidisciplinary expert panel approach

Percutaneous transluminal renal angioplasty (PTRA) is an invasive technique that is costly and involves the risk of complications and renal failure. The ability of PTRA to reduce the administration of antihypertensive drugs has been demonstrated. A potentially greater benefit, which nevertheless remains to be proven, is the deferral of the need for chronic dialysis. The aim of the study (ANPARIA) was to assess the appropriateness of PTRA to impact on the evolution of renal function. A standardized expert panel method was used to assess the appropriateness of medical treatment alone or medical treatment with revascularization in various clinical situations. The choice of revascularization by either PTRA or surgery was examined for each clinical situation. Analysis was based on a detailed literature review and on systematically elicited expert opinion, which were obtained during a two-round modified Delphi process. The study provides detailed responses on the appropriateness of PTRA for 1848 distinct clinical scenarios. Depending on the major clinical presentation, appropriateness of revascularization varied from 32% to 75% for individual scenarios (overal 48%). Uncertainty as to revascularization was 41% overall. When revascularization was appropriate, PTRA was favored over surgery in 94% of the scenarios, except in certain cases of aortic atheroma where sugery was the preferred choice. Kidney size [7 cm, absence of coexisting disease, acute renal failure, a high degree of stenosis (C70%), and absence of multiple arteries were identified as predictive variables of favorable appropriateness ratings. Situations such as cardiac failure with pulmonary edema or acute thrombosis of the renal artery were defined as indications for PTRA. This study identified clinical situations in which PTRA or surgery are appropriate for renal artery disease. We built a decision tree which can be used via Internet: the ANPARIA software (http://www.chu-clermontferrand.fr/anparia/). In numerous clinical situations uncertainty remains as to whether PTRA prevents deterioration of renal function.

Improving globally distributed software development and support processes - A workflow view

We propose a new approach and related indicators for globally distributed software support and development based on a 3-year process improvement project in a globally distributed engineering company. The company develops, delivers and supports a complex software system with tailored hardware components and unique end-customer installations. By applying the domain knowledge from operations management on lead time reduction and its multiple benefits to process performance, the workflows of globally distributed software development and multitier support processes were measured and monitored throughout the company. The results show that the global end-to-end process visibility and centrally managed reporting at all levels of the organization catalyzed a change process toward significantly better performance. Due to the new performance indicators based on lead times and their variation with fixed control procedures, the case company was able to report faster bug-fixing cycle times, improved response times and generally better customer satisfaction in its global operations. In all, lead times to implement new features and to respond to customer issues and requests were reduced by 50%.