Discriminating long myelitis of neuromyelitis optica from sarcoidosis

Objective To compare longitudinally extensive myelitis in neuromyelitis optica spectrum disorders (NMOSD) and spinal cord sarcoidosis (SCS). Methods We identified adult patients evaluated between 1996 and 2015 with SCS or NMOSD whose first myelitis episode was accompanied by a spinal cord lesion spanning 653 vertebral segments. All NMOSD patients were positive for aquaporin-4-immunoglobulin G, and all sarcoidosis cases were pathologically confirmed. Clinical characteristics were evaluated. Spine magnetic resonance imaging was reviewed by 2 neuroradiologists. Results We studied 71 patients (NMOSD, 37; SCS, 34). Sixteen (47%) SCS cases were initially diagnosed as NMOSD or idiopathic transverse myelitis. Median delay to diagnosis was longer for SCS than NMOSD (5 vs 1.5 months, p < 0.01). NMOSD myelitis patients were more commonly women, had concurrent or prior optic neuritis or intractable vomiting episodes more frequently, had shorter time to maximum deficit, and had systemic autoimmunity more often than SCS (p < 0.05). SCS patients had constitutional symptoms, cerebrospinal fluid (CSF) pleocytosis, and hilar adenopathy more frequently than NMOSD (p < 0.05); CSF hypoglycorrhachia (11%, p = 0.25) and elevated angiotensin-converting enzyme (18%, p = 0.30) were exclusive to SCS. Dorsal cord subpial gadolinium enhancement extending 652 vertebral segments and persistent enhancement >2 months favored SCS, and ringlike enhancement favored NMOSD (p < 0.05). Maximum disability was similar in both disorders. Interpretation SCS is an under-recognized cause of longitudinally extensive myelitis that commonly mimics NMOSD. We identified clinical, laboratory, systemic, and radiologic features that, taken together, help discriminate SCS from NMOSD

Managing the tension between performance measurement and strategy : coping strategies

Purpose - The aim of this paper is to explore an important but relatively uncharted territory: the actual functioning of performance measurement systems (PMS) in their organisational context. The objective of the paper is to document the ways in which managers go about aligning operational measures with their organisation's strategy in practice. Design/methodology/approach - This research adopts an interpretive multiple-case approach in order to gather rich data on the strategies used in managing operational PMS. Data were collected from detailed interviews with managers and supervisors in four government agencies. Findings - The expectations were that the operations managers would adjust their performance measures to support the changes in strategy. This was not the case. All the interviewees employed one or more tactics to cope with the tensions between strategy and performance measures. The ten tactics identified are collected into three strategies; do-nothing strategy, pseudo-realigning strategy, and distracting strategy. Research limitations/implications - This paper casts some doubt on the practice, rather than the principle, of strategy-aligned performance management. More work needs to be carried out to ascertain how other, both for profit and public sector, organisations deal with these tensions in practice. Practical implications - From a practitioner point of view it raises the question as to whether senior managers are exerting sufficient control over the alignment issue or providing suitable tools, methods or indeed incentives to bring alignment about. Originality/value - The paper highlights a gap between theory and practice and suggests that the way to ensure implementation of "modern management methods," might be to deal firstly with the issues of relevance, timeliness, structure, integration, and symmetry

1,4-Benzodiazepines as inhibitors of respiratory syncytial virus

Respiratory syncytial virus (RSV) is the cause of one-fifth of all lower respiratory tract infections worldwide and is increasingly being recognized as a serious threat to patient groups with poorly functioning immune systems. Our approach to finding a novel inhibitor of this virus was to screen a 20 000-member diverse library in a whole cell XTT assay. Parallel assays were carried out in the absence of virus in order to quantify any associated cell toxicity. This identified 100 compounds with IC50's less than 50 μM. A-33903 (18), a 1,4-benzodiazepine analogue, was chosen as the starting point for lead optimization. This molecule was moderately active and demonstrated good pharmacokinetic properties. The most potent compounds identified from this work were A-58568 (47), A-58569 (44), and A-62066 (46), where modifications to the aromatic substitution enhanced potency, and A-58175 (42), where the amide linker was modified

Metal ion interpretation in resurfacing versus conventional hip arthroplasty and in whole blood versus serum. How should we interpret metal ion data

Contains fulltext : 96098.pdf (publisher's version ) (Closed access)Metal ions generated from joint replacements are a cause for concern. There is no consensus on the best surrogate measure of metal ion exposure, and both serum and whole blood measurements are used in clinical practice. This study provides a guideline for interpretation of metal ion analysis in clinical practice. In a prospective trial comparing hip resurfacing (HR) with a conventional metal-on-metal (MoM) total hip arthroplasty (THA) cobalt and chromium levels were determined for whole blood and serum in 343 paired samples at regular intervals up to 24 months postoperatively. Cobalt whole blood and serum levels increased significantly after both procedures. Cobalt concentrations were significantly higher for the HR group compared to the THA group, at 3, 6 and 12 months, for whole blood and serum. At 24 months cobalt levels decreased and differences between HR and THA were no longer significant. In contrast, chromium whole blood levels remained significantly higher for HR until 24 months. Whole blood and serum levels could not be used interchangeably. The mean differences for cobalt and chromium between blood and serum values were +0.13 microg/L and -0.91 microg/L respectively. Regression analysis provided a formula for conversion from serum to blood of 0.34+[0.88*Co serum] for cobalt and 0.14 + [0.58*Cr serum] for chromium, with an acceptable prediction error below +/-1.0 microg/L. Cobalt and chromium levels were significantly higher for HR versus THA, especially during the run-in phase of one year. Overall, the metal ion levels were well below 5 microg/L. We cannot recommend the use of whole blood over serum measurements or vice versa. The provided conversion formula between whole blood and serum in combination with the presented practical guidelines may be useful for clinical practice