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1.  Developing a Hetero-Alkali-Metal Chemistry of 2,2,6,6-Tetramethyl-piperidide (TMP): Stoichiometric and Structural Diversity within a Series of Lithium/Sodium, Lithium/Potassium and Sodium/Potassium TMP Compounds 
Studied extensively in solution and in the solid state, Li(TMP) (TMP=2,2,6,6-tetramethylpiperidide) is an important utility reagent popular as a strongly basic, weakly nucleophilic tool for C–H metallation. Recently, there has been a surge in interest in mixed metal derivatives containing the bulky TMP anion. Herein, we start to develop hetero (alkali metal) TMP chemistry by reporting the N,N,N′,N′-tetramethylethylenediamine (TMEDA)-hemisolvated sodium–lithium cycloheterodimer [(tmeda)Na(μ-tmp)2Li], and its TMEDA-free variant [{Na(μ-tmp)Li(μ-tmp)}∞], which provides a rare example of a crystallographically authenticated polymeric alkali metal amide. Experimental observations suggest that the former is a kinetic intermediate en route to the latter thermodynamic product. Furthermore, a third modification, the mixed potassium–lithium-rich cycloheterotrimer [(tmeda)K(μ-tmp)Li(μ-tmp)Li(μ-tmp)], has also been synthesised and crystallographically characterised. On moving to the bulkier tridentate donor N,N,N′,N′′,N′′-pentamethyldiethylenediamine (PMDETA), the additional ligation forces the sodium–lithium and potassium–dilithium ring species to open giving the acyclic arc-shaped complexes [(pmdeta)Na(μ-tmp)Li(tmp)] and [(pmdeta)K(μ-tmp)Li(μ-tmp)Li(tmp)], respectively. Completing the series, the potassium–lithium and potassium–sodium derivatives [(pmdeta)K(μ-tmp)2M] (M=Li, Na) have also been isolated as closed structures with a distinctly asymmetric central MN2K ring. Collectively, these seven new bimetallic compounds display five distinct structural motifs, four of which have never hitherto been witnessed in TMP chemistry and three of which are unprecedented in the vast structural library of alkali metal amide chemistry.
PMCID: PMC3761191  PMID: 21766365
aggregation; alkali metals; amides; heterometallic complexes; X-ray diffraction
2.  A literature review of quality in lower gastrointestinal endoscopy from the patient perspective 
Colorectal cancer (CRC) is the third most frequently diagnosed cancer, and the second leading cause of cancer death among men and women in Canada. Prompted by nationally accepted CRC guidelines, the use of colonoscopy – widely regarded to be the optimal method of CRC screening – has increased dramatically in recent years. However, when evaluating colonoscopy performance and the delivery of high-quality care, it is important to also consider factors relevant to the patients who require colonoscopy services. Understanding the patient perspective on what comprises quality in colonoscopy/endoscopy is essential to tailoring improvements in the standards of practice and quality of care. Accordingly, this study systematically reviewed the literature pertaining to aspects of colonoscopy and endoscopy that may be considered to be important to patients.
Given the limited state of health care resources, increased demand for colorectal cancer (CRC) screening raises concerns about the quality of endoscopy services. Little is known about quality in colonoscopy and endoscopy from the patient perspective.
To systematically review the literature on quality that is relevant to patients who require colonoscopy or endoscopy services.
A systematic PubMed search was performed on articles that were published between January 2000 and February 2011. Keywords included “colonoscopy” or “sigmoidoscopy” or “endoscopy” AND “quality”; “colonoscopy” or “sigmoidoscopy” or “endoscopy” AND “patient satisfaction” or “willingness to return”. The included articles were qualitative and quantitative English language studies regarding aspects of colonoscopy and/or endoscopy services that were evaluated by patients in which data were collected within one year of the colonoscopy/endoscopy procedure.
In total, 28 quantitative studies were identified, of which eight (28.6%) met the inclusion criteria (four cross-sectional, three prospective cohort and one single-blinded controlled study). Aspects of quality included comfort, management of pain and anxiety, endoscopy unit staff manner, skills and specialty, procedure and results discussion with the doctor, physical environment, wait times for the appointment and procedure, and discharge. Qualitative studies eliciting the patient perspective on what constituted quality in colonoscopy/endoscopy were not found.
Factors related to comfort, staff, communication and the service environment were evaluated from the patient perspective using closed-ended questions that were designed by clinicians and researchers. Future research using qualitative methodology to elicit the patient perspective on quality in colonoscopy and/or endoscopy services is needed.
PMCID: PMC3266160  PMID: 22175059
Colonoscopy; Endoscopy; Patient perspective; Quality; Review
3.  Diabetic Foot Ulcers and Vascular Insufficiency: Our Population Has Changed, but Our Methods Have Not 
Diabetic foot complications are increasing in prevalence worldwide. Care and attention to these complications have improved greatly. Many advanced therapies are now being investigated or taken through final stages of clinical studies worldwide. However, the data upon which assumptions regarding morbidity, healing, and mortality have been based are grossly outdated. The purpose of this brief article is to report on current data regarding neuropathic and neuroischemic wounds and to propose that the latter category of advanced-stage diabetic foot wound may now be emerging as the most commonly encountered lesion in the developed world. Unfortunately, it is still systematically excluded from most clinical study criteria. Additionally, just as in the care of cancer, we call for therapy of these advanced-stage diabetic foot ulcers to be managed in similarly interdisciplinary centers where patients may have access to potentially beneficial clinical trials.
PMCID: PMC3262731  PMID: 22226282
amputation; diabetic foot ulcers; infection; ischemia; wound healing
4.  The Charcot Foot in Diabetes 
Diabetes Care  2011;34(9):2123-2129.
The diabetic Charcot foot syndrome is a serious and potentially limb-threatening lower-extremity complication of diabetes. First described in 1883, this enigmatic condition continues to challenge even the most experienced practitioners. Now considered an inflammatory syndrome, the diabetic Charcot foot is characterized by varying degrees of bone and joint disorganization secondary to underlying neuropathy, trauma, and perturbations of bone metabolism. An international task force of experts was convened by the American Diabetes Association and the American Podiatric Medical Association in January 2011 to summarize available evidence on the pathophysiology, natural history, presentations, and treatment recommendations for this entity.
PMCID: PMC3161273  PMID: 21868781
5.  Plasmalemmal vesicle associated protein (PV1) modulates SV40 virus infectivity in CV-1 cells 
Plasmalemmal vesicle associated protein (Plvap/PV1) is a structural protein required for the formation of the stomatal diaphragms of caveolae. Caveolae are plasma membrane invaginations that were implicated in SV40 virus entry in primate cells. Here we show that de novo Plvap/PV1 expression in CV-1 green monkey epithelial cells significantly reduces the ability of SV40 virus to establish productive infection, when cells are incubated with low concentrations of the virus. However, in presence of high viral titers PV1 has no effect on SV40 virus infectivity. Mechanistically, PV1 expression does not reduce the cell surface expression of known SV40 receptors such as GM1 ganglioside and MHC class I proteins. Furthermore, PV1 does not reduce the binding of virus-like particles made by SV40 VP1 protein to the CV-1 cell surface and does not impact their internalization when cells are incubated with either high or low VLP concentrations. These results suggest that PV1 protein is able to block SV40 infectivity at low but not at high viral concentration either by interfering with the infective internalization pathway at the cell surface or at a post internalization step.
PMCID: PMC3171970  PMID: 21827737
6.  Testing for gluten-related disorders in clinical practice: The role of serology in managing the spectrum of gluten sensitivity 
Immunoglobulin A tissue transglutaminase is the single most efficient serological test for the diagnosis of celiac disease. It is well known that immunoglobulin A tissue transglutaminase levels correlate with the degree of intestinal damage, and that values can fluctuate in patients over time. Serological testing can be used to identify symptomatic individuals that need a confirmatory biopsy, to screen at-risk populations or to monitor diet compliance in patients previously diagnosed with celiac disease. Thus, interpretation of serological testing requires consideration of the full clinical scenario. Antigliadin tests are no longer recommended for the diagnosis of classical celiac disease. However, our understanding of the pathogenesis and spectrum of gluten sensitivity has improved, and gluten-sensitive irritable bowel syndrome patients are increasingly being recognized. Studies are needed to determine the clinical utility of antigliadin serology in the diagnosis of gluten sensitivity.
PMCID: PMC3088693  PMID: 21523259
Antigliadin antibodies; Antitissue transglutaminase; Celiac disease; Diagnosis; Gluten intolerance; Serology
7.  Point-of-care, peer-comparator colonoscopy practice audit: The Canadian Association of Gastroenterology Quality Program – Endoscopy 
Point-of-care practice audits allow documentation of procedural outcomes to support quality improvement in endoscopic practice.
To evaluate a colonoscopists’ practice audit tool that provides point-of-care data collection and peer-comparator feedback.
A prospective, observational colonoscopy practice audit was conducted in academic and community endoscopy units for unselected patients undergoing colonoscopy. Anonymized colonoscopist, patient and practice data were collected using touchscreen smart-phones with automated data upload for data analysis and review by participants. The main outcome measures were the following colonoscopy quality indicators: colonoscope insertion and withdrawal times, bowel preparation quality, sedation, immediate complications and polypectomy, and biopsy rates.
Over a span of 16 months, 62 endoscopists reported on 1279 colonoscopy procedures. The mean cecal intubation rate was 94.9% (10th centile 84.2%). The mean withdrawal time was 8.8 min and, for nonpolypectomy colonoscopies, 41.9% of colonoscopists reported a mean withdrawal time of less than 6 min. Polypectomy was performed in 37% of colonoscopies. Independent predictors of polypectomy included the following: endoscopy unit type, patient age, interval since previous colonoscopy, bowel preparation quality, stable inflammatory bowel disease, previous colon polyps and withdrawal time. Withdrawal times of less than 6 min were associated with lower polyp removal rates (mean difference −11.3% [95% CI −2.8% to −19.9%]; P=0.01).
Cecal intubation rates exceeded 90% and polypectomy rates exceeded 30%, but withdrawal times were frequently shorter than recommended. There are marked practice variations consistent with previous observations.
Real-time, point-of-care practice audits with prompt, confidential access to outcome data provide a basis for targeted educational programs to improve quality in colonoscopy practice.
PMCID: PMC3027329  PMID: 21258663
Colonoscopy; Health care; Practice audit; Quality assurance; Quality indicators
8.  Comparison of a Sleep Item From the General Health Questionnaire-12 With the Jenkins Sleep Questionnaire as Measures of Sleep Disturbance 
Journal of Epidemiology  2011;21(6):474-480.
The objective of this study was to examine whether a widely available single-item measure of sleep disturbances is an acceptable alternative to a multi-item sleep questionnaire.
Data were derived from Finnish Helsinki Health Study postal questionnaires administered in 2000–2002 (n = 7777, response rate 67%). The measures were the 4-item Jenkins Sleep Questionnaire (JSQ) on difficulties initiating and maintaining sleep, and nonrestorative sleep, and an item on sleep loss due to worry, from the General Health Questionnaire-12 (GHQ-12). Receiver operating characteristics (ROC) curve analyses were done to compare the predictive performance of the GHQ-12 item with the JSQ scale. Using the above 2 measures of sleep, logistic regression models were used to examine associations between sociodemographic factors, working conditions, health-related factors, and sleep disturbance.
The estimated area under the ROC curve was 0.68 among both women and men, which suggests that the ability of the GHQ-12 item to discriminate true positives from false positives was modest. However, the associations of sleep disturbance with its key determinants were largely similar using the GHQ-12 and the JSQ.
A widely available, GHQ-12-based, single-item sleep measure was not an adequate substitute for a multi-item measure of overall sleep disturbance. Although the measures produced largely similar associations for key determinants of poor sleep, the discrepancies between responses must be considered when analyzing data from a measure that uses a single sleep item.
PMCID: PMC3899464  PMID: 21986193
sleep; validation; GHQ-12; JSQ; single-item; multi-item
9.  FaceTime for Physicians: Using Real Time Mobile Phone–Based Videoconferencing to Augment Diagnosis and Care in Telemedicine 
Eplasty  2011;11:e23.
Objective/Background: Telemedicine has, even in its infancy, had an impact on the provision of healthcare, particularly in rural communities. However, this often relies on an expensive and ponderous infrastructure that reduces the rapid use and spontaneity for consultations. Methods: Using postoperative and intraoperative examples, we describe the use of one rapid and widely available technology (iPhone FaceTime, Cupertino, California). Results: The device, in allowing “one button connection” similar to making a phone call, reduced the need for preplanning that is generally required for real-time telemedicine consultation. Conclusions: The ability to communicate quickly with something that is an afterthought has the potential to alter how we work with our colleagues and patients. Just as with the iPod in music and the laptop in computing, it is not the change in technology, but the change in form factor and ubiquity that alters this landscape.
PMCID: PMC3087505  PMID: 21559249
10.  Neurologists' understanding and management of conversion disorder 
Conversion disorder is largely managed by neurologists, for whom it presents great challenges to understanding and management. This study aimed to quantify these challenges, examining how neurologists understand conversion disorder, and what they tell their patients.
A postal survey of all consultant neurologists in the UK registered with the Association of British Neurologists.
349 of 591 practising consultant neurologists completed the survey. They saw conversion disorder commonly. While they endorsed psychological models for conversion, they diagnosed it according to features of the clinical presentation, most importantly inconsistency and abnormal illness behaviour. Most of the respondents saw feigning as entangled with conversion disorder, with a minority seeing one as a variant of the other. They were quite willing to discuss psychological factors as long as the patient was receptive but were generally unwilling to discuss feigning even though they saw it as their responsibility. Those who favoured models in terms of feigning were older, while younger, female neurologists preferred psychological models, believed conversion would one day be understood neurologically and found communicating with their conversion patients easier than it had been in the past.
Neurologists accept psychological models for conversion disorder but do not employ them in their diagnosis; they do not see conversion as clearly different from feigning. This may be changing as younger, female neurologists endorse psychological views more clearly and find it easier to discuss with their patients.
PMCID: PMC3191819  PMID: 21325661
11.  Trial Protocol: Communicating DNA-based risk assessments for Crohn's disease: a randomised controlled trial assessing impact upon stopping smoking 
BMC Public Health  2011;11:44.
Estimates of the risk of developing Crohn's disease (CD) can be made using DNA testing for mutations in the NOD2 (CARD15) gene, family history, and smoking status. Smoking doubles the risk of CD, a risk that is reduced by stopping. CD therefore serves as a timely and novel paradigm within which to assess the utility of predictive genetic testing to motivate behaviour change to reduce the risk of disease. The aim of the study is to describe the impact upon stopping smoking of communicating a risk of developing CD that incorporates DNA analysis. We will test the following main hypothesis:
Smokers who are first degree relatives (FDRs) of CD probands are more likely to make smoking cessation attempts following communication of risk estimates of developing CD that incorporate DNA analysis, compared with an equivalent communication that does not incorporate DNA analysis.
A parallel groups randomised controlled trial in which smokers who are FDRs of probands with CD are randomly allocated in families to undergo one of two types of assessment of risk for developing CD based on either:
i. DNA analysis, family history of CD and smoking status, or
ii. Family history of CD and smoking status
The primary outcome is stopping smoking for 24 hours or longer in the six months following provision of risk information. The secondary outcomes are seven-day smoking abstinence at one week and six month follow-ups. Randomisation of 470 smoking FDRs of CD probands, with 400 followed up (85%), provides 80% power to detect a difference in the primary outcome of 14% between randomised arms, at the 5% significance level.
This trial provides one of the strongest tests to date of the impact of communicating DNA-based risk assessment on risk-reducing behaviour change. Specific issues regarding the choice of trial design are discussed.
Trial Registration
PMCID: PMC3036624  PMID: 21247480

Results 1-11 (11)