An Innovative Approach to the Integrated Management System Development: SIMPRO-IMS Web Based Environment

The purpose of this paper is to contribute to learning, knowledge creation and knowledge transfer for building organization innovability by integrating the management systems in the SIMPRO-IMS web based environment. The paper content consists of the interpretation of role-play simulation, role-play simulation process description, methodology, and the employment of role-play simulation outcomes, as well as the discussion of the knowledge thus obtained. Primary the model of the SIMPRO-Q education environment has been developed and tested during a period of 15 years in several industrial organizations as well as service organizations such as Higher Education Institution (HEI) and Healthcare Organization (HCO). The newest version SIMPRO-IMS has recently been developed to support a need of integration of management systems and information archiving. With the last development, SIMPRO-IMS web based environment, processes of five ISO systems are integrated for parallel development, implementation, auditing, maintaining and leading. SIMPRO-IMS provides management with the apparatus necessary to realize a systematic and verifiable approach to the creation and control of IMS documentation. At the same time contributes to the preservation of organization memory in response to the growing challenges of globalization and digitalization. The research is limited by the complexity of a real system and possible empiric results verification. The results achieved are verified when people really overcome the resistance to change. This can be assessed thoughtfully only after some period of time. Another limitation is presented by measurability of real enhancement achieved in quality, safety and environmentality of production, and business continuity and social responsibility of an organization. Development and progress in the methodology of SIMPRO-IMS web based environment is encoded in upgrading the SIMPRO database by processes of the environmental management, occupational health & safety management, information security management, energy management, service management, business continuity management and social responsibility management into one cohesive system with a holistic set of documentation, policies, procedures and processes, and a preserving knowledge for learning, new knowledge creation and knowledge transfer for building organization innovability

Putting Back the Welcome Mat: A Neighborhood Guide for Turning Vacant Houses into Homes

http://deepblue.lib.umich.edu/bitstream/2027.42/110970/1/puttingbackwelcomemata_neighborhood_guide_for_turning_vacant_houses_into_homesopt2007.pd

Growth characteristics in individuals with osteogenesis imperfecta in North America: results from a multicenter study.

PurposeOsteogenesis imperfecta (OI) predisposes people to recurrent fractures, bone deformities, and short stature. There is a lack of large-scale systematic studies that have investigated growth parameters in OI.MethodsUsing data from the Linked Clinical Research Centers, we compared height, growth velocity, weight, and body mass index (BMI) in 552 individuals with OI. Height, weight, and BMI were plotted on Centers for Disease Control and Prevention normative curves.ResultsIn children, the median z-scores for height in OI types I, III, and IV were -0.66, -6.91, and -2.79, respectively. Growth velocity was diminished in OI types III and IV. The median z-score for weight in children with OI type III was -4.55. The median z-scores for BMI in children with OI types I, III, and IV were 0.10, 0.91, and 0.67, respectively. Generalized linear model analyses demonstrated that the height z-score was positively correlated with the severity of the OI subtype (P < 0.001), age, bisphosphonate use, and rodding (P < 0.05).ConclusionFrom the largest cohort of individuals with OI, we provide median values for height, weight, and BMI z-scores that can aid the evaluation of overall growth in the clinic setting. This study is an important first step in the generation of OI-specific growth curves

Infigratinib in children with achondroplasia:the PROPEL and PROPEL 2 studies

BACKGROUND: Achondroplasia is the most common short-limbed skeletal dysplasia resulting from gain-of-function pathogenic variants in fibroblast growth factor receptor 3 (FGFR3) gene, a negative regulator of endochondral bone formation. Most treatment options are symptomatic, targeting medical complications. Infigratinib is an orally bioavailable, FGFR1–3 selective tyrosine kinase inhibitor being investigated as a direct therapeutic strategy to counteract FGFR3 overactivity in achondroplasia. OBJECTIVES: The main objective of PROPEL is to collect baseline data of children with achondroplasia being considered for future enrollment in interventional studies sponsored by QED Therapeutics. The objectives of PROPEL 2 are to obtain preliminary evidence of safety and efficacy of oral infigratinib in children with achondroplasia, to identify the infigratinib dose to be explored in future studies, and to characterize the pharmacokinetic (PK) profile of infigratinib and major metabolites. DESIGN: PROPEL (NCT04035811) is a prospective, noninterventional clinical study designed to characterize the natural history and collect baseline data of children with achondroplasia over 6−24 months. PROPEL 2 (NCT04265651), a prospective, phase II, open-label study of infigratinib in children with achondroplasia, consists of a dose-escalation, dose-finding, and dose-expansion phase to confirm the selected dose, and a PK substudy. METHODS AND ANALYSIS: Children aged 3−11 years with achondroplasia who completed ⩾6 months in PROPEL are eligible for PROPEL 2. Primary endpoints include treatment-emergent adverse events and change from baseline in annualized height velocity. Four cohorts at ascending dose levels are planned for dose escalation. The selected dose will be confirmed in the dose-expansion phase. ETHICS: PROPEL and PROPEL 2 are being conducted in accordance with the International Conference on Harmonization Good Clinical Practice guidelines, principles of the Declaration of Helsinki, and relevant human clinical research and data privacy regulations. Protocols have been approved by local health authorities, ethics committees, and institutions as applicable. Parents/legally authorized representatives are required to provide signed informed consent; signed informed assent by the child is also required, where applicable. DISCUSSION: PROPEL and PROPEL 2 will provide preliminary evidence of the safety and efficacy of infigratinib as precision treatment of children with achondroplasia and will inform the design of future studies of FGFR-targeted agents in achondroplasia. REGISTRATION: ClinicalTrials.gov: NCT04035811; NCT04265651

The Cardiac Atlas Project—an imaging database for computational modeling and statistical atlases of the heart

Motivation: Integrative mathematical and statistical models of cardiac anatomy and physiology can play a vital role in understanding cardiac disease phenotype and planning therapeutic strategies. However, the accuracy and predictive power of such models is dependent upon the breadth and depth of noninvasive imaging datasets. The Cardiac Atlas Project (CAP) has established a large-scale database of cardiac imaging examinations and associated clinical data in order to develop a shareable, web-accessible, structural and functional atlas of the normal and pathological heart for clinical, research and educational purposes. A goal of CAP is to facilitate collaborative statistical analysis of regional heart shape and wall motion and characterize cardiac function among and within population groups

Clinical and Functional Characterization of a Patient Carrying a Compound Heterozygous Pericentrin Mutation and a Heterozygous IGF1 Receptor Mutation

Intrauterine and postnatal longitudinal growth is controlled by a strong genetic component that regulates a complex network of endocrine factors integrating them with cellular proliferation, differentiation and apoptotic processes in target tissues, particularly the growth centers of the long bones. Here we report on a patient born small for gestational age (SGA) with severe, proportionate postnatal growth retardation, discreet signs of skeletal dysplasia, microcephaly and moyamoya disease. Initial genetic evaluation revealed a novel heterozygous IGF1R p.Leu1361Arg mutation affecting a highly conserved residue with the insulin-like growth factor type 1 receptor suggestive for a disturbance within the somatotropic axis. However, because the mutation did not co-segregate with the phenotype and functional characterization did not reveal an obvious impairment of the ligand depending major IGF1R signaling capabilities a second-site mutation was assumed. Mutational screening of components of the somatotropic axis, constituents of the IGF signaling system and factors involved in cellular proliferation, which are described or suggested to provoke syndromic dwarfism phenotypes, was performed. Two compound heterozygous PCNT mutations (p.[Arg585X];[Glu1774X]) were identified leading to the specification of the diagnosis to MOPD II. These investigations underline the need for careful assessment of all available information to derive a firm diagnosis from a sequence aberration

Early Markers of Glycaemic Control in Children with Type 1 Diabetes Mellitus

Background: Type 1 diabetes mellitus (T1DM) may lead to severe long-term health consequences. In a longitudinal study, we aimed to identify factors present at diagnosis and 6 months later that were associated with glycosylated haemoglobin (HbA 1c) levels at 24 months after T1DM diagnosis, so that diabetic children at risk of poor glycaemic control may be identified. Methods: 229 children,15 years of age diagnosed with T1DM in the Auckland region were studied. Data collected at diagnosis were: age, sex, weight, height, ethnicity, family living arrangement, socio-economic status (SES), T1DM antibody titre, venous pH and bicarbonate. At 6 and 24 months after diagnosis we collected data on weight, height, HbA 1c level, and insulin dose. Results: Factors at diagnosis that were associated with higher HbA1c levels at 6 months: female sex (p,0.05), lower SES (p,0.01), non-European ethnicity (p,0.01) and younger age (p,0.05). At 24 months, higher HbA1c was associated with lower SES (p,0.001), Pacific Island ethnicity (p,0.001), not living with both biological parents (p,0.05), and greater BMI SDS (p,0.05). A regression equation to predict HbA1c at 24 months was consequently developed. Conclusions: Deterioration in glycaemic control shortly after diagnosis in diabetic children is particularly marked in Pacific Island children and in those not living with both biological parents. Clinicians need to be aware of factors associated wit

TRAIP promotes DNA damage response during genome replication and is mutated in primordial dwarfism.

DNA lesions encountered by replicative polymerases threaten genome stability and cell cycle progression. Here we report the identification of mutations in TRAIP, encoding an E3 RING ubiquitin ligase, in patients with microcephalic primordial dwarfism. We establish that TRAIP relocalizes to sites of DNA damage, where it is required for optimal phosphorylation of H2AX and RPA2 during S-phase in response to ultraviolet (UV) irradiation, as well as fork progression through UV-induced DNA lesions. TRAIP is necessary for efficient cell cycle progression and mutations in TRAIP therefore limit cellular proliferation, providing a potential mechanism for microcephaly and dwarfism phenotypes. Human genetics thus identifies TRAIP as a component of the DNA damage response to replication-blocking DNA lesions.This work was supported by funding from the Medical Research Council and the European Research Council (ERC, 281847) (A.P.J.), the Lister Institute for Preventative Medicine (A.P.J. and G.S.S.), Medical Research Scotland (L.S.B.), German Federal Ministry of Education and Research (BMBF, 01GM1404) and E-RARE network EuroMicro (B.W), Wellcome Trust (M. Hurles), CMMC (P.N.), Cancer Research UK (C17183/A13030) (G.S.S. and M.R.H), Swiss National Science Foundation (P2ZHP3_158709) (O.M.), AIRC (12710) and ERC/EU FP7 (CIG_303806) (S.S.), Cancer Research UK (C6/A11224) and ERC/EU FP7 (HEALTH-F2- 2010-259893) (A.N.B. and S.P.J.).This is the author accepted manuscript. The final version is available from NPG via http://dx.doi.org/10.1038/ng.345

Apnea of prematurity: from cause to treatment

Apnea of prematurity (AOP) is a common problem affecting premature infants, likely secondary to a “physiologic” immaturity of respiratory control that may be exacerbated by neonatal disease. These include altered ventilatory responses to hypoxia, hypercapnia, and altered sleep states, while the roles of gastroesophageal reflux and anemia remain controversial. Standard clinical management of the obstructive subtype of AOP includes prone positioning and continuous positive or nasal intermittent positive pressure ventilation to prevent pharyngeal collapse and alveolar atelectasis, while methylxanthine therapy is a mainstay of treatment of central apnea by stimulating the central nervous system and respiratory muscle function. Other therapies, including kangaroo care, red blood cell transfusions, and CO2 inhalation, require further study. The physiology and pathophysiology behind AOP are discussed, including the laryngeal chemoreflex and sensitivity to inhibitory neurotransmitters, as are the mechanisms by which different therapies may work and the potential long-term neurodevelopmental consequences of AOP and its treatment