Pilot study of the safety and effect of adalimumab on pain, physical function, and musculoskeletal disease in mucopolysaccharidosis types I and II.

Mucopolysaccharidosis I and II are lysosomal storage disorders that, despite treatment with hematopoietic cell transplantation (HCT) and/or enzyme replacement therapy (ERT), continue to cause significant skeletal abnormalities leading to pain, stiffness, physical dysfunction, and short stature. Tumor necrosis factor - alpha (TNF-α) is elevated in individuals with MPS I and II and associated with pain and physical dysfunction. Therefore, we evaluated the safety and effects of the TNF-α inhibitor adalimumab in patients with MPS I and II in a 32-week, randomized, double blind, placebo-controlled, crossover study of adalimumab at a dose of 20 mg (weight 15-<30 kg) or 40 mg (weight ≥ 30 kg) administered subcutaneously every other week or saline placebo for 16 weeks. Participants were evaluated at baseline, week 16, and week 32 with the Children's Health Questionnaire - Parent Form 50 (CHQ-PF50), the Pediatric Pain Questionnaire (PPQ), range-of-motion (ROM) measurements, anthropometry, six-minute walk test (6MWT), hand dynamometer, and laboratory evaluations for safety. The primary outcome was safety and primary efficacy outcome was bodily pain (BP) measured by the CHQ-PF50. Two subjects, one with MPS I and one with MPS II, completed the study. Adalimumab was well tolerated and there were no serious adverse events. Standardized BP scores for age and gender were higher (i.e. less pain) at the end of the treatment versus placebo phase for both subjects. Subject #1 became unblinded during treatment due to skin erythema. Behavior measured by both CHQ-PF50 and parental report improved during treatment compared to placebo in both subjects. ROM improved by > 5° in seven of eight joints in Subject #1 and five of eight joints in Subject #2 (range 7.0° to 52.8°). There was no change in the PPQ, 6MWT, or hand dynamometer. Data from this small pilot study suggest that treatment with adalimumab is safe, tolerable, and may improve ROM, physical function, and possibly pain, in children with MPS I or II. However, additional clinical trials are needed before this therapy should be recommended as part of clinical care

Space Station Freedom environmental control and life support system phase 3 simplified integrated test detailed report

A description of the phase 3 simplified integrated test (SIT) conducted at the Marshall Space Flight Center (MSFC) Core Module Integration Facility (CMIF) in 1989 is presented. This was the first test in the phase 3 series integrated environmental control and life support systems (ECLSS) tests. The basic goal of the SIT was to achieve full integration of the baseline air revitalization (AR) subsystems for Space Station Freedom. Included is a description of the SIT configuration, a performance analysis of each subsystem, results from air and water sampling, and a discussion of lessons learned from the test. Also included is a full description of the preprototype ECLSS hardware used in the test

Aphrati and Kato Syme: Pottery, Continuity, and Cult in Late Archaic and Classical Crete

The analysis of ceramics from Aphrati sheds valuable new light on the history of this Cretan settlement and on its relationship with a nearby rural sanctuary at Kato Syme in the Late Archaic and Classical periods. It has long been held that Aphrati was deserted from ca. 600 to 400 B.C. A pottery deposit from the domestic quarter, however, now supports occupation of the city during this period. A ceramic classification system is presented and the morphological development and absolute chronology of several key shapes at Aphrati and Kato Syme are plotted. Historical implications of the ceramic evidence are also explored

ACVIM consensus statement on the treatment of immune-mediated hemolytic anemia in dogs

Immune‐mediated hemolytic anemia (IMHA) causes severe anemia in dogs and is associated with considerable morbidity and mortality. Treatment with various immunosuppressive and antithrombotic drugs has been described anecdotally and in previous studies, but little consensus exists among veterinarians as to the optimal regimen to employ and maintain after diagnosis of the disease. To address this inconsistency and provide evidence‐based guidelines for treatment of IMHA in dogs, we identified and extracted data from studies published in the veterinary literature. We developed a novel tool for evaluation of evidence quality, using it to assess study design, diagnostic criteria, explanation of treatment regimens, and validity of statistical methods. In combination with our clinical experience and comparable guidelines for humans afflicted with autoimmune hemolytic anemia, we used the conclusions of this process to make a set of clinical recommendations regarding treatment of IMHA in dogs, which we refined subsequently by conducting several iterations of Delphi review. Additionally, we considered emerging treatments for IMHA in dogs and highlighted areas deserving of future research. Comments were solicited from several professional bodies to maximize clinical applicability before the recommendations were submitted for publication. The resulting document is intended to provide clinical guidelines for management of IMHA in dogs. These guidelines should be implemented pragmatically, with consideration of animal, owner, and veterinary factors that may vary among cases

Actors and networks or agents and structures: towards a realist view of information systems

Actor-network theory (ANT) has achieved a measure of popularity in the analysis of information systems. This paper looks at ANT from the perspective of the social realism of Margaret Archer. It argues that the main issue with ANT from a realist perspective is its adoption of a `flat' ontology, particularly with regard to human beings. It explores the value of incorporating concepts from ANT into a social realist approach, but argues that the latter offers a more productive way of approaching information systems

Plasma-sprayed coatings for fusion reactor applications

A series of plasma-sprayed coatings has been given a preliminary evaluation to assess the potential of this class of materials in fusion reactor applications. TiC, TiB/sub 2/, Be and VBe/sub 12/ coatings on copper and stainless steel were tested for coating adherence, ion erosion resistance and susceptability to arc erosion. The coatings, in general, display a good resistance to thermal shock failure. The TiC and TiB/sub 2/ coatings exhibit favorable ion erosion characteristics and the resistance of the coatings to arc erosion was, in general, superior to that of stainless steel

Comprehensive behavioral and biochemical outcomes of novel murine models of GM1-gangliosidosis and Morquio syndrome type B

Deficiencies in the lysosomal hydrolase β-galactosidase (β-gal) lead to two distinct diseases: the skeletal disease Morquio syndrome type B, and the neurodegenerative disease GM1-gangliosidosis. Utilizing CRISPR-Cas9 genome editing, the mouse β-gal encoding gene, Glb1, was targeted to generate both models of β-gal deficiency in a single experiment. For Morquio syndrome type B, the common human missense mutation W273L (position 274 in mice) was introduced into the Glb1 gene (Glb

Experts' Judgments of Management Journal Quality:An Identity Concerns Model

Many lists that purport to gauge the quality of journals in management and organization studies (MOS) are based on the judgments of experts in the field. This article develops an identity concerns model (ICM) that suggests that such judgments are likely to be shaped by the personal and social identities of evaluators. The model was tested in a study in which 168 editorial board members rated 44 MOS journals. In line with the ICM, respondents rated journal quality more highly to the extent that a given journal reflected their personal concerns (associated with having published more articles in that journal) and the concerns of a relevant ingroup (associated with membership of the journal’s editorial board or a particular disciplinary or geographical background). However, judges’ ratings of journals in which they had published were more favorable when those journals had a low-quality reputation, and their ratings of journals that reflected their geographical and disciplinary affiliations were more favorable when those journals had a high-quality reputation. The findings are thus consistent with the view that identity concerns come to the fore in journal ratings when there is either a need to protect against personal identity threat or a meaningful opportunity to promote social identity

Physical Electronics

Contains reports on three research projects