Agreement between telehealth and in-person assessment of patients with chronic musculoskeletal conditions presenting to an advanced-practice physiotherapy screening clinic

Objective: To determine the level of agreement between a telehealth and in-person assessment of a representative sample of patients with chronic musculoskeletal conditions referred to an advanced-practice physiotherapy screening clinic. Design: Repeated-measures study design. Participants: 42 patients referred to the Neurosurgical & Orthopaedic Physiotherapy Screening Clinic (Queensland, Australia) for assessment of their chronic lumbar spine, knee or shoulder condition. Intervention: Participants underwent two consecutive assessments by different physiotherapists within a single clinic session. In-person assessments were conducted as per standard clinical practice. Telehealth assessments took place remotely via videoconferencing. Six Musculoskeletal Physiotherapists were paired together to perform both assessment types. Main outcome measures: Clinical management decisions including (i) recommended management pathways, (ii) referral to allied health professions, (iii) clinical diagnostics, and (iv) requirement for further investigations were compared using reliability and agreement statistics. Results: There was substantial agreement (83.3%; 35/42 cases) between in-person and telehealth assessments for recommended management pathways. Moderate to near perfect agreement (AC1 = 0.58–0.9) was reached for referral to individual allied health professionals. Diagnostic agreement was 83.3% between the two delivery mediums, whilst there was substantial agreement (81%; AC1 = 0.74) when requesting further investigations. Overall, participants were satisfied with the telehealth assessment. Conclusion: There is a high level of agreement between telehealth and in-person assessments with respect to clinical management decisions and diagnosis of patients with chronic musculoskeletal conditions managed in an advanced-practice physiotherapy screening clinic. Telehealth can be considered as a viable and effective medium to assess those patients who are unable to attend these services in person

Pragmatists versus dogmatists: Explaining the failure of power-sharing in Northern Ireland during the 1970s

This article argues that the failure of Northern Ireland’s first power-sharing executive, and subsequent attempts to restore power-sharing during the 1970s, was the result of conflicting attitudes towards devolution among Northern Ireland’s politicians. Traditional ideological divisions between nationalists and unionists were not the primary barrier to creating and sustaining cross-community institutions, as stressed in accounts of this period premised on consociational theory. Drawing extensively from archival sources, it argues that the split between the pragmatists from both communities, who were prepared to compromise their core principles and accept power-sharing devolution within a UK framework, and the dogmatists (both nationalists and unionists) who refused to contemplate any compromise to their core position, prevented a consensual political settlement emerging during the 1970s

Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes

Mass Spectrometry and Thiotemplate Assembly: Unique Insights Into the Production of Natural Products on >100 kDa Enzymes

190 p.Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 2005.This work further extends initial studies into using FTMS to examine NRP/PK synthetases and provides the most detailed insights into pyochelin, yersiniabactin and FK520 biosynthesis achieved to date. This study also represents the first observation of multiple covalently modified active site peptides in parallel using robust digestion protocols. It is hoped that further refinement of this mass spectrometry-based platform will bolster NRP/PK reengineering efforts towards the design of "unnatural" natural products that combat modern antibiotic-resistant pathogens.U of I OnlyRestricted to the U of I community idenfinitely during batch ingest of legacy ETD

Mass Spectrometry and Thiotemplate Assembly: Unique Insights Into the Production of Natural Products on >100 kDa Enzymes

190 p.Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 2005.This work further extends initial studies into using FTMS to examine NRP/PK synthetases and provides the most detailed insights into pyochelin, yersiniabactin and FK520 biosynthesis achieved to date. This study also represents the first observation of multiple covalently modified active site peptides in parallel using robust digestion protocols. It is hoped that further refinement of this mass spectrometry-based platform will bolster NRP/PK reengineering efforts towards the design of "unnatural" natural products that combat modern antibiotic-resistant pathogens.U of I OnlyRestricted to the U of I community idenfinitely during batch ingest of legacy ETD

Parallel interrogation of covalent intermediates in the biosynthesis of gramicidin S using high-resolution mass spectrometry

For determination of multiple covalent intermediates bound to the ultra-large enzymes responsible for biosynthesis via nonribosomal peptide synthesis, mass spectrometry (MS) is a promising method to provide new mechanistic insight. Application of a quadrupole-Fourier-transform instrument (Q-FTMS) for direct analysis of aminoacyl intermediates is demonstrated for the first two modules (127 and 120 kDa) involved in the nonribosomal synthesis of gramicidin S. Cyanogen bromide digestions of recombinant proteins afforded detection of two active site peptides (both ~13 kDa) that provided direct evidence for modules copurifying with their preferred amino acid substrates. Given the ability to detect multiple covalent intermediates in tandem, a competition experiment among several nonnatural substrates in parallel was performed using the first module. This defined mixture of acyl-enzyme intermediates was used to probe the selectivity of the condensation step producing a diversity of noncognate dipeptides on the second module

Bcl-XL represents a druggable molecular vulnerability during aurora B inhibitor-mediated polyploidization

Aurora kinase B inhibitors induce apoptosis secondary to polyploidization and have entered clinical trials as an emerging class of neocytotoxic chemotherapeutics. We demonstrate here that polyploidization neutralizes Mcl-1 function, rendering cancer cells exquisitely dependent on Bcl-XL/-2. This “addiction” can be exploited therapeutically by combining aurora kinase inhibitors and the orally bioavailable BH3 mimetic, ABT-263, which inhibits Bcl-XL, Bcl-2, and Bcl-w. The combination of ABT-263 with aurora B inhibitors produces a synergistic loss of viability in a range of cell lines of divergent tumor origin and exhibits more sustained tumor growth inhibition in vivo compared with aurora B inhibitor monotherapy. These data demonstrate that Bcl-XL/-2 is necessary to support viability during polyploidization in a variety of tumor models and represents a druggable molecular vulnerability with potential therapeutic utility