Prospective Environmental Analyses of Emerging Technology: A Critique, a Proposed Methodology, and a Case Study on Incremental Sheet Forming

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154436/1/jiec12748-sup-0001-SuppMat.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154436/2/jiec12748_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154436/3/jiec12748.pd

Accelerated Calvarial Healing in Mice Lacking Toll-Like Receptor 4

The bone and immune systems are closely interconnected. The immediate inflammatory response after fracture is known to trigger a healing cascade which plays an important role in bone repair. Toll-like receptor 4 (TLR4) is a member of a highly conserved receptor family and is a critical activator of the innate immune response after tissue injury. TLR4 signaling has been shown to regulate the systemic inflammatory response induced by exposed bone components during long-bone fracture. Here we tested the hypothesis that TLR4 activation affects the healing of calvarial defects. A 1.8 mm diameter calvarial defect was created in wild-type (WT) and TLR4 knockout (TLR4-/-) mice. Bone healing was tested using radiographic, histologic and gene expression analyses. Radiographic and histomorphometric analyses revealed that calvarial healing was accelerated in TLR4-/- mice. More bone was observed in TLR4-/- mice compared to WT mice at postoperative days 7 and 14, although comparable healing was achieved in both groups by day 21. Bone remodeling was detected in both groups on postoperative day 28. In TLR4-/- mice compared to WT mice, gene expression analysis revealed that higher expression levels of IL-1β, IL-6, TNF-α,TGF-β1, TGF-β3, PDGF and RANKL and lower expression level of RANK were detected at earlier time points (≤ postoperative 4 days); while higher expression levels of IL-1β and lower expression levels of VEGF, RANK, RANKL and OPG were detected at late time points (> postoperative 4 days). This study provides evidence of accelerated bone healing in TLR4-/- mice with earlier and higher expression of inflammatory cytokines and with increased osteoclastic activity. Further work is required to determine if this is due to inflammation driven by TLR4 activation. © 2012 Wang et al

The silence of self-knowledge

Gareth Evans famously affirmed an explanatory connection between answering the question whether p and knowing whether one believes that p. This is commonly interpreted in terms of the idea that judging that p constitutes an adequate basis for the belief that one believes that p. This paper formulates and defends an alternative, more modest interpretation, which develops from the suggestion that one can know that one believes that p in judging that p

The multiple sclerosis risk sharing scheme monitoring study - early results and lessons for the future

Background: Risk sharing schemes represent an innovative and important approach to the problems of rationing and achieving cost-effectiveness in high cost or controversial health interventions. This study aimed to assess the feasibility of risk sharing schemes, looking at long term clinical outcomes, to determine the price at which high cost treatments would be acceptable to the NHS. Methods: This case study of the first NHS risk sharing scheme, a long term prospective cohort study of beta interferon and glatiramer acetate in multiple sclerosis ( MS) patients in 71 specialist MS centres in UK NHS hospitals, recruited adults with relapsing forms of MS, meeting Association of British Neurologists (ABN) criteria for disease modifying therapy. Outcome measures were: success of recruitment and follow up over the first three years, analysis of baseline and initial follow up data and the prospect of estimating the long term cost-effectiveness of these treatments. Results: Centres consented 5560 patients. Of the 4240 patients who had been in the study for a least one year, annual review data were available for 3730 (88.0%). Of the patients who had been in the study for at least two years and three years, subsequent annual review data were available for 2055 (78.5%) and 265 (71.8%) patients respectively. Baseline characteristics and a small but statistically significant progression of disease were similar to those reported in previous pivotal studies. Conclusion: Successful recruitment, follow up and early data analysis suggest that risk sharing schemes should be able to deliver their objectives. However, important issues of analysis, and political and commercial conflicts of interest still need to be addressed

Can we accurately report PTEN status in advanced colorectal cancer?

BACKGROUND: Loss of phosphatase and tensin homologue (PTEN) function evaluated by loss of PTEN protein expression on immunohistochemistry (IHC) has been reported as both prognostic in metastatic colorectal cancer and predictive of response to anti-EGFR monoclonal antibodies although results remain uncertain. Difficulties in the methodological assessment of PTEN are likely to be a major contributor to recent conflicting results. METHODS: We assessed loss of PTEN function in 51 colorectal cancer specimens using Taqman® copy number variation (CNV) and IHC. Two blinded pathologists performed independent IHC assessment on each specimen and inter-observer variability of IHC assessment and concordance of IHC versus Taqman® CNV was assessed. RESULTS: Concordance between pathologists (PTEN loss vs no loss) on IHC assessment was 37/51 (73%). In specimens with concordant IHC assessment, concordance between IHC and Taqman® copy number in PTEN loss assessment was 25/37 (68%). CONCLUSION: Assessment PTEN loss in colorectal cancer is limited by the inter-observer variability of IHC, and discordance of CNV with loss of protein expression. An understanding of the genetic mechanisms of PTEN loss and implementation of improved and standardized methodologies of PTEN assessment are required to clarify the role of PTEN as a biomarker in colorectal cancer

The design, development and evaluation of an array-based FES system with automated setup for the correction of drop foot

Functional electrical stimulation has been shown to be a safe and effective means of correcting drop foot of central neurological origin. However, despite recent technological advances, the set-up of surface stimulators remains a challenge for many users with drop foot. The automation of the setup process through the use of electrode arrays has been proposed as a way to address this problem. This paper describes a series of research and clinical studies which have led to the first demonstration of unsupervised automated setup of an electrode-array based drop foot stimulator. Finally, future research plans are discussed

Cross-over study of novice intubators performing endotracheal intubation in an upright versus supine position

There are a number of potential physical advantages to performing orotracheal intubation in an upright position. The objective of this study was to measure the success of intubation of a simulated patient in an upright versus supine position by novice intubators after brief training. This was a cross-over design study in which learners (medical students, physician assistant students, and paramedic students) intubated mannequins in both a supine (head of the bed at 0°) and upright (head of bed elevated at 45°) position. The primary outcome of interest was successful intubation of the trachea. Secondary outcomes included log time to intubation, Cormack–Lehane view obtained, Percent of Glottic Opening score, provider assessment of difficulty, and overall provider satisfaction with the position. There were a total of 126 participants: 34 medical students, 84 physician assistant students, and 8 paramedic students. Successful tracheal intubation was achieved in 114 supine attempts (90.5 %) and 123 upright attempts (97.6 %; P = 0.283). Upright positioning was associated with significantly faster log time to intubation, higher likelihood of achieving Grade I Cormack–Lehane view, higher Percent of Glottic Opening score, lower perceived difficulty, and higher provider satisfaction. A subset of 74 participants had no previous intubation training or experience. For these providers, there was a non-significant trend toward improved intubation success with upright positioning vs supine positioning (98.6 % vs. 87.8 %, P = 0.283). For all secondary outcomes in this group, upright positioning significantly outperformed supine positioning