Magic Triangle – Human, Exoskeleton, and Collaborative Robot Scenario

The incidence of musculoskeletal disorders in workplaces with difficult ergonomic conditions is increasing. Today, there is a growing market for technical support systems that avoid repetitive strain on the musculoskeletal system. We have been observing two (parallel) lines of development: on the one hand, the development of exoskeletons supporting shop floor operators and, on the other hand, the development of collaborative robots for the creation of hybrid teams. The focus of our research is the combined application of exoskeletons AND collaborative robots for shop floor operators in the aerospace industry. Our approach is to analyze various scenarios to understand which tasks should preferably be executed either with a collaborative robot, with an exoskeleton, or by a human without assistance from any support systems such as an exoskeleton or robot. In order to pursue this idea of modular and selective support system solutions, tool availability has to be ensured without increasing the required infrastructure. In a first step, we have developed a prototype of a tool adapter that enables the application of a tool either by connection to a robot, an exoskeleton, or the tool being held by the operator, and allows very fast coupling and decoupling within seconds. This concept will enable the realization of the proposed simultaneous use of exoskeletons and robots

Crisponi syndrome/cold-induced sweating syndrome type 2: Reprogramming of CS/CISS2 individual derived fibroblasts into three clones of one iPSC line

Crisponi syndrome/cold-induced sweating syndrome type 2 (CS/CISS2) is a rare disease with severe dysfunctions of thermoregulatory processes. CS/CISS2 individuals suffer from recurrent episodes of hyperthermia in the neonatal period and paradoxical sweating at cold ambient temperatures in adolescence. Variants in CLCF1 (cardiotrophin-like-cytokine 1) cause CS/CISS2. Here, we summarize the generation of three clones of one stem cell line (iPSC) of a CS/CISS2 individual carrying the CLCF1 variant c.321C>G on both alleles. These patient derived iPSC clones show a normal karyotype, several pluripotency markers, and the ability to differentiate into the three germ layers

Long-term fluvastatin reduces the hazardous effect of renal impairment on four-year atherosclerotic outcomes (a LIPS substudy)

peer reviewedMild renal impairment is an important risk factor for late cardiovascular complications. This substudy of the Lescol Intervention Prevention Study (LIPS) assessed the effect of fluvastatin on outcome of patients who had renal dysfunction and those who did not. Complete data for creatinine clearance calculation. (Cockcroft=Gault formula) were available for 1,558 patients (92.9% of the LIPS population). Patients were randomized to fluvastatin or placebo after successful completion of a first percutaneous coronary intervention. Follow-up time was, 3 to 4 years. The effect of baseline creatinine clearance on coronary atherosclerotic events (cardiac death, non-fatal myocardial infarction, and coronary reinterventions not related to restenosis) was evaluated. Baseline creatinine clearance (logarithmic transformation) was inversely associated with an incidence of adverse events among patients who received, placebo. (hazard ratio 0.99, 95% confidence interval 0.982 to 0.998, p = 0.01). However, no association was noted between creatinine clearance and the incidence of adverse events among patients who received fluvastatin (hazard ratio 1.0, 95% confidence interval 0.99 to 1.0, p = 0.63). No further deterioration in creatinine clearance was observed during follow-up; regardless of baseline renal function or allocated treatment. Occurrence of adverse events was not related to changes in renal function during follow-up. Fluvastatin therapy markedly decreased the risk of coronary atherosclerotic events after percutaneous intervention in: patients who had lower values of creatinine clearance at baseline: The benefit of fluvastatin was unrelated to any effect on renal function. (C) 2005 by Excerpta Medica Inc

Metabolic control during the neonatal period in phenylketonuria:associations with childhood IQ

Background In phenylketonuria, treatment and subsequent lowering of phenylalanine levels usually occur within the first month of life. This study investigated whether different indicators of metabolic control during the neonatal period were associated with IQ during late childhood/early adolescence. Methods Overall phenylalanine concentration during the first month of life (total "area under the curve"), proportion of phenylalanine concentrations above upper target level (360 mu mol/L) and proportion below lower target level (120 mu mol/L) during this period, diagnostic phenylalanine levels, number of days until phenylalanine levels were 360 mu mol/L during the first month of life negatively correlated with IQ in late childhood/early adolescence. Separately, phenylalanine concentrations during different periods within the first month of life (0-10 days, 11-20 days, 21-30 days) were negatively correlated with later IQ as well, but correlation strengths did not differ significantly. No further significant associations were found. Conclusions In phenylketonuria, achievement of target-range phenylalanine levels during the neonatal period is important for cognition later in life, also when compared to other indicators of metabolic control. Impact In phenylketonuria, it remains unclear during which age periods or developmental stages metabolic control is most important for later cognitive outcomes. Phenylalanine levels during the neonatal period were clearly and negatively related to later IQ, whereas no significant associations were observed for other indices of metabolic control. This emphasizes the relative importance of this period for cognitive development in phenylketonuria. No further distinctions were observed in strength of associations with later IQ between different indicators of metabolic control during the neonatal period. Thus, achievement of good metabolic control within 1 month after birth appears "safe" with respect to later cognitive outcomes

Recoil following Wiktor stent implantation for restenotic lesions of coronary arteries

The purpose of this study was to determine acute recoil of the vessel wall immediately after Wiktor stent implantation in native coronary arteries of 77 consecutive patients and to assess whether there was compression or “late recoil” of the stent itself at long-term follow-up. Furthermore, the relationship between recoil and a number of clinical, angiographic, and procedural variables was studied in addition to the relation between acute recoil renarrowing or restenosis was assessed. All angiograms were analyzed with the Cardiovascular Angiography Analysis System using automated edge detection. Acute recoil was defined by the difference between the mean diameter of the fully expanded balloon on which the stent was mounted and the mean diameter of the stented segment. Late recoil was calculated by comparing the mean diameter of the stent itself immediately after implantation and at follow-up without opacification of the vessel. Acute recoil amounted to 0.25 ± 0.32 mm or 8.2%. Multivariate analysis identified sex (coefficient = –0.20, p = 0.04) and stent/artery ratio (coefficient = 0.99, p = 0.0001) as the only independent predictors of acute recoil. “Late recoil” of the stent itself was not observed. The overall difference between the mean diameter of the stent itself immediately after implantation and at follow-up was –0.15 ± 0.33 mm, suggesting an overall increase in diameter of 5.0%. There was no relation between acute recoil and late restenosis. On the contrary, there was a trend towards a greater degree of recoil in patients without restenosis. Moreover, linear regression analysis disclosed a weak but negative correlation between acute recoil and a loss in minimal luminal diameter (coefficient: –0.55, p = 0.04). The Wiktor stent effectively scaffolds the instrumented vessel. Only a minimal amount of acute recoil was noted, which did not contribute to late luminal renarrowing or restenosis. In addition, no late compression of the stent itself was observed. These data suggest that tissue ingrowth into the lumen of the stented segment is the main cause of late luminal renarrowing after stent implantation. © 1994 Wiley-Liss,Inc.

Angiographic predictors of recurrence of restenosis after Wiktor stent implantation in native coronary arteries

Intracoronary stenting has been proposed as an adjunct to balloon angioplasty to improve the immediate and long-term results. However, late luminal narrowing has been reported following the implantation of a variety of stents. One of the studies conducted with the Wiktor stent is a prospective registry designed to evaluate the feasibility, safety and efficacy of elective stent implantation in patients with documented restenosis of a native coronary artery. To identify angiographic variables predicting recurrence of restenosis, the angiograms of the first 91 patients with successful stent implantation and without clinical evidence of (sub)acute thrombotic stent occlusion were analyzed with the Computer Assisted Angiographic Analysis System using automated edge detection. The incidence of restenosis was 44% by patient and 45% by stent according to the 0.72 mm criterion, and 30% by patient and 29% by stent according to the 50% diameter stenosis criterion. The risk for restenosis for several angiographic variables was determined using an univariate analysis and is expressed as odds ratio with corresponding confidence interval. The only statistically significant predictor of restenosis was the relative gain when it exceeded 0.48 using the 0.72 mm criterion (odds ratio 2.7, 95% confidence interval 1.1-6.4). Furthermore, the relation between the relative gain (increase in minimal luminal diameter normalized to vessel size) as angiographic index of vessel wall injury and relative loss (decrease in minimal luminal diameter normalized to vessel size) as index of neointimal thickening was analyzed using a linear regression analysis. When using the categorical approach to address restenosis, there is an increased risk for recurrent restenosis when the relative gain exceeds 0.48. The continuous approach underscores this concept by indicating a weak but positive relation between the relative gain and relative loss

Future treatments for the arteriopathy of ectopic calcification disorders

Ectopic calcification disorders, including Generalized Arterial Calcification of Infancy (GACI) and Pseudoxanthoma Elasticum are rare but impactful on individuals, healthcare and society, with significant associated morbidity, mortality and healthcare costs. Available therapies are not curative and focus on reducing extracellular calcification to limit progression of the arteriopathy that is responsible for much of the morbidity and, in the case of GACI, significant early mortality (approximately 50% in infancy). In this article, current and emerging medical approaches are reviewed and critiqued, including dietary manipulation, phosphate binders, bisphosphonates, tissue nonspecific alkaline phosphatase inhibitors, ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) enzyme replacement, allele-specific therapies, gene therapies, and antibody targeted treatment. Available therapies may limit further arterial calcification, but in GACI in particular, significant calcification can be present at birth, contributing to high infant mortality. This highlights the need for new approaches that aim to reverse established calcification, rather than merely slow its progression. Recently, a promising new class of antibody-targeted nanoparticle therapeutics has emerged that can reverse established arterial calcification in animals, restoring arterial elasticity. In one realization, nanoparticles carry established chelators, such as ethylenediaminetetraacetic disodium acid, to sites of arterial damage, concentrating the impact of the chelator where it is needed and limiting off-target effects. Such drugs would complement existing and emerging therapies, such as ENPP1 enzyme replacement, that slow or prevent progression of calcification, by offering an opportunity to “reset” arterial health in ectopic calcification disorders. At present, ectopic calcification disorders are challenging to treat effectively and carry a high burden of morbidity and mortality, particularly in GACI. Recent drug developments offer good reason to be hopeful for a new era of effective therapeutics that may reverse established arterial disease as well as halt its progression

Cross-sectional observational study of 208 patients with non-classical urea cycle disorders.

Urea cycle disorders (UCDs) are inherited disorders of ammonia detoxification often regarded as mainly of relevance to pediatricians. Based on an increasing number of case studies it has become obvious that a significant number of UCD patients are affected by their disease in a non-classical way: presenting outside the newborn period, following a mild course, presenting with unusual clinical features, or asymptomatic patients with only biochemical signs of a UCD. These patients are surviving into adolescence and adulthood, rendering this group of diseases clinically relevant to adult physicians as well as pediatricians. In preparation for an international workshop we collected data on all patients with non-classical UCDs treated by the participants in 20 European metabolic centres. Information was collected on a cohort of 208 patients 50% of which were ≥ 16 years old. The largest subgroup (121 patients) had X-linked ornithine transcarbamylase deficiency (OTCD) of whom 83 were female and 29% of these were asymptomatic. In index patients, there was a mean delay from first symptoms to diagnosis of 1.6 years. Cognitive impairment was present in 36% of all patients including female OTCD patients (in 31%) and those 41 patients identified presymptomatically following positive newborn screening (in 12%). In conclusion, UCD patients with non-classical clinical presentations require the interest and care of adult physicians and have a high risk of neurological complications. To improve the outcome of UCDs, a greater awareness by health professionals of the importance of hyperammonemia and UCDs, and ultimately avoidance of the still long delay to correctly diagnose the patients, is crucial