Drug therapies in severe asthma - the era of stratified medicine

Difficult-to-treat asthma affects up to 20% of patients with asthma and is associated with significant healthcare cost. It is an umbrella term that defines a heterogeneous clinical problem including incorrect diagnosis, comorbid conditions and treatment non-adherence; when these are effectively addressed, good symptom control is frequently achieved. However, in 3–5% of adults with difficult-to-treat asthma, the problem is severe disease that is unresponsive to currently available treatments. Current treatment guidelines advise the ‘stepwise’ increase of corticosteroids, but it is now recognised that many aspects of asthma are not corticosteroid responsive, and that this ‘one size fits all’ approach does not deliver clinical benefit in many patients and can also lead to side effects. The future of management of severe asthma will involve optimisation with currently available treatments, particularly corticosteroids, including addressing non-adherence and defining an ‘optimised’ corticosteroid dose, allied with the use of ‘add-on’ target-specific novel treatments. This review examines the current status of novel treatments and research efforts to identify novel targets in the era of stratified medicines in severe asthma.

Epidemiology of painful procedures performed in neonates: A systematic review of observational studies

Procedural pain in neonates has been a concern in the last two decades. The purpose of this review was to provide a critical appraisal and a synthesis of the published epidemiological studies about procedural pain in neonates admitted to intensive care units. The aims were to determine the frequency of painful procedures and pain management interventions as well as to identify their predictors. Academic Search, CINAHL, LILACS, Medic Latina, MEDLINE and SciELO databases were searched for observational studies on procedural pain in neonates admitted to intensive care units. Studies in which neonatal data could not be extracted from the paediatric population were excluded. Eighteen studies were included in the review. Six studies with the same study duration, the first 14 days of the neonate life or admission in the unit of care, identified 6832 to 42,413 invasive procedures, with an average of 7.5-17.3 per neonate per day. The most frequent procedures were heel lance, suctioning, venepuncture and insertion of peripheral venous catheter. Pharmacological and nonpharmacological approaches were inconsistently applied. Predictors of the frequency of procedures and analgesic use included the neonate's clinical condition, day of unit stay, type of procedure, parental presence and pain assessment. The existence of pain protocols was not a predictor of analgesia. Painful procedures were performed frequently and often with inadequate pain management. Unlike neonate clinical factors, organizational factors may be modified to promote a context of care more favourable to pain management. © 2015 European Pain Federation - EFIC®

Development of CBCT-based prostate setup correction strategies and impact of rectal distension.

BACKGROUND: Cone-beam computed tomography (CBCT) image-guided radiotherapy (IGRT) systems are widely used tools to verify and correct the target position before each fraction, allowing to maximize treatment accuracy and precision. In this study, we evaluate automatic three-dimensional intensity-based rigid registration (RR) methods for prostate setup correction using CBCT scans and study the impact of rectal distension on registration quality. METHODS: We retrospectively analyzed 115 CBCT scans of 10 prostate patients. CT-to-CBCT registration was performed using (a) global RR, (b) bony RR, or (c) bony RR refined by a local prostate RR using the CT clinical target volume (CTV) expanded with 1-to-20-mm varying margins. After propagation of the manual CT contours, automatic CBCT contours were generated. For evaluation, a radiation oncologist manually delineated the CTV on the CBCT scans. The propagated and manual CBCT contours were compared using the Dice similarity and a measure based on the bidirectional local distance (BLD). We also conducted a blind visual assessment of the quality of the propagated segmentations. Moreover, we automatically quantified rectal distension between the CT and CBCT scans without using the manual CBCT contours and we investigated its correlation with the registration failures. To improve the registration quality, the air in the rectum was replaced with soft tissue using a filter. The results with and without filtering were compared. RESULTS: The statistical analysis of the Dice coefficients and the BLD values resulted in highly significant differences (p<10(-6)) for the 5-mm and 8-mm local RRs vs the global, bony and 1-mm local RRs. The 8-mm local RR provided the best compromise between accuracy and robustness (Dice median of 0.814 and 97% of success with filtering the air in the rectum). We observed that all failures were due to high rectal distension. Moreover, the visual assessment confirmed the superiority of the 8-mm local RR over the bony RR. CONCLUSION: The most successful CT-to-CBCT RR method proved to be the 8-mm local RR. We have shown the correlation between its registration failures and rectal distension. Furthermore, we have provided a simple (easily applicable in routine) and automatic method to quantify rectal distension and to predict registration failure using only the manual CT contours.

Cost evaluation and comparison of three decision strategies for cardiac revascularization : results of the suspected CAD protocol of the European CMR registry

Background: The public health burden of coronary artery disease (CAD) is important. Perfusion cardiac magnetic resonance (CMR) is generally accepted to detect and monitor CAD. Few studies have so far addressed its costs and costeffectiveness. Objectives: To compare in a large CMR registry the costs of a CMR-guided strategy vs two hypothetical invasive strategies for the diagnosis and the treatment of patients with suspected CAD. Methods: In 3'647 patients with suspected CAD included prospectively in the EuroCMR Registry (59 centers; 18 countries) costs were calculated for diagnostic examinations, revascularizations as well as for complication management over a 1-year follow-up. Patients with ischemia-positive CMR underwent an invasive X-ray coronary angiography (CXA) and revascularization at the discretion of the treating physician (=CMR+CXA strategy). Ischemia was found in 20.9% of patients and 17.4% of them were revascularized. In ischemia-negative patients by CMR, cardiac death and non-fatal myocardial infarctions occurred in 0.38%/y. In a hypothetical invasive arm the costs were calculated for an initial CXA followed by FFR testing in vessels with ≥50% diameter stenoses (=CXA+FFR strategy). To model this hypothetical arm, the same proportion of ischemic patients and outcome was assumed as for the CMR+CXA strategy. The coronary stenosis - FFR relationship reported in the literature was used to derive the proportion of patients with ≥50% diameter stenoses (Psten) in the study cohort. The costs of a CXA-only strategy were also calculated. Calculations were performed from a third payer perspective for the German, UK, Swiss, and US healthcare systems.

Worldwide trends in diabetes since 1980: a pooled analysis of 751 population-based studies with 4.4 million participants.

One of the global targets for non-communicable diseases is to halt, by 2025, the rise in the age-standardised adult prevalence of diabetes at its 2010 levels. We aimed to estimate worldwide trends in diabetes, how likely it is for countries to achieve the global target, and how changes in prevalence, together with population growth and ageing, are affecting the number of adults with diabetes. We pooled data from population-based studies that had collected data on diabetes through measurement of its biomarkers. We used a Bayesian hierarchical model to estimate trends in diabetes prevalence-defined as fasting plasma glucose of 7.0 mmol/L or higher, or history of diagnosis with diabetes, or use of insulin or oral hypoglycaemic drugs-in 200 countries and territories in 21 regions, by sex and from 1980 to 2014. We also calculated the posterior probability of meeting the global diabetes target if post-2000 trends continue. We used data from 751 studies including 4,372,000 adults from 146 of the 200 countries we make estimates for. Global age-standardised diabetes prevalence increased from 4.3% (95% credible interval 2.4-7.0) in 1980 to 9.0% (7.2-11.1) in 2014 in men, and from 5.0% (2.9-7.9) to 7.9% (6.4-9.7) in women. The number of adults with diabetes in the world increased from 108 million in 1980 to 422 million in 2014 (28.5% due to the rise in prevalence, 39.7% due to population growth and ageing, and 31.8% due to interaction of these two factors). Age-standardised adult diabetes prevalence in 2014 was lowest in northwestern Europe, and highest in Polynesia and Micronesia, at nearly 25%, followed by Melanesia and the Middle East and north Africa. Between 1980 and 2014 there was little change in age-standardised diabetes prevalence in adult women in continental western Europe, although crude prevalence rose because of ageing of the population. By contrast, age-standardised adult prevalence rose by 15 percentage points in men and women in Polynesia and Micronesia. In 2014, American Samoa had the highest national prevalence of diabetes (>30% in both sexes), with age-standardised adult prevalence also higher than 25% in some other islands in Polynesia and Micronesia. If post-2000 trends continue, the probability of meeting the global target of halting the rise in the prevalence of diabetes by 2025 at the 2010 level worldwide is lower than 1% for men and is 1% for women. Only nine countries for men and 29 countries for women, mostly in western Europe, have a 50% or higher probability of meeting the global target. Since 1980, age-standardised diabetes prevalence in adults has increased, or at best remained unchanged, in every country. Together with population growth and ageing, this rise has led to a near quadrupling of the number of adults with diabetes worldwide. The burden of diabetes, both in terms of prevalence and number of adults affected, has increased faster in low-income and middle-income countries than in high-income countries. Wellcome Trust.

Recreational Development and the Lake Erie Shore Photographs,1967

John N. Jackson was born and raised in London England. He served in the Royal Navy, acquired a B.A. and a Ph.D, conducted research for a city planning office and lectured at the University of Manchester. He joined Brock University’s faculty in 1965 as a Professor of Applied Geography. Since his retirement in 1991 he has been Professor Emeritus to Brock. Throughout his time in academia Jackson has focused his research on the history of the modern city, both throughout Europe and Canada. Jackson has also completed specific research on the Niagara Peninsula; including industrial geography, recreation along the Lake Erie shore, St. Catharines early history, the Welland Canals, railway development, comparisons across the Niagara River. While living in the Niagara region Jackson has become involved in many community events. He has been the Director for the Bruce Trail Association, President of the Welland Canals Foundation, and been involved in local historical groups throughout the Niagara region.

The New-York Weekly Museum Newspaper, Vol. II, No.24- October 16, 1813

A weekly paper that was published from 1805 to 1814. War related news includes: Page 95 - Weekly Retrospect: relief effort in London, England for those affected by the war in British North America; naval battles on Lake Ontario by Commodore Chauncey in late September; movements of Major Grant, De Rottenburgh's regiment, General Wilkinson, Commodore Yoe's fleet, General Hampton; the capture of Fort Malden by William Harrison. The rest of the newspaper contains literary works (poems and translations), marriages, deaths and other anecdotes. The motto on the front page states: "Visiting Every Flower with Labour Meet, and Gathering all its Treasures, Sweet by Sweet."

Colin Duquemin fonds, 1935, 1968-2001, n.d.

Colin Duquemin was born in 1932 in Guernsey, British Channel Islands, and came to Canada as a young adult. He attended McMaster University (B.A.), the University of Toronto (B.Ed.), the State University of New York at Buffalo (M.A.) and the University of London, London, England (M.Sc.). He began his career as a tea taster and tea buyer in Colombo, Ceylon (Sri Lanka), but later became a teacher. He spent most of his teaching career as a manager of the St. Johns Outdoor Studies Centre, north of Fonthill, Ontario, developing environmentally related programmes for elementary and secondary school students. He was also active in many local organizations, serving as Associate Director of the St. Catharines Grape and Wine Festival Board, Chairman of the St. Catharines Historical Museum Board, President of the Niagara Military Institute and President of the Canadian Canal Society. In addition to the numerous curriculum materials he authored, Colin wrote the Driver’s Guide Series, highlighting the many points of interest in the Niagara region, including the Welland Canal, battlefields of the War of 1812, and the Niagara Parkway. He also wrote A Guide to the Grand River Canal (1980) with Daniel Glenney, The Fur Trade in Rupert’s Land: Opening up the Canadian Northwest (1992), Stick to the Guns! A short history of the 10th field battery, Royal Regiment of Canadian Artillery (1996), Niagara Rebels: the Niagara Frontier Incidents in the Upper Canada Rebellion, 1837-1838 ( 2001), and edited and contributed to A Lodge of Friendship: the History of Niagara Lodge, No. 2, A.F. & A.M, Niagara-on-the-Lake, Ontario, Canada, 1792-1992 (1991). He died in December 2012.

Photograph - Portrait Col. Frank Case McCordick

A portrait photograph of Col. Frank Case McCordick in his military uniform. undated. The photographers are Elliott & Fry and are located at 55 Baker street London W.

Bulloch, Lade & Co. Order Form, 31 August 1870

An order form for the exportation of scotch pure malt whiskies, distilled by Bulloch, Lade & Co.

Compendium of Festive and Seasonable Stingo Recipes

A recipe booklet with the full title "Compendium of Festive and Seasonable Stingo recipes for the Delectation of the Nobility and Gentry, our esteemed Patrons". The inside sentiment reads "Presented to you with Good wishes all Seasonable Cheer by Watneys Brewers of the Very Best Beers at Stag Brewery, Pimlico, London, S.W.I"

Act for Laying a Duty on the Retailers of Spirits and Liquors

An act to charge duty to retailers of liquor and for licensing retailers of liquor. The document beings "At the Parliament begun and holden at Westminster, the Fourteenth Day of January, Anno Dom. 1734 in the Eighth Year of the Reign of our Sovereign Lord George the Second, by the Grace of God, of Great Britain, France, and Ireland, Kind, Defender of the Faith, And from thence continued by federal Prorogation to the Fifteenth Day of January, 1735. being the Second Session of this present Parliament."

Wine for Sale at Garraway's Coffee-House in Cornhill

A list of wines for sale "by the candle at Garraway's Coffee-house in Exchange Alley, Cornhill..." six pages in length. The list begins with four conditions of sale and then lists types of wines, lot numbers and how many dozen are available. The wines available are: Excellent Old Hock, Old Hock, Rich Hungarian White Wine, Hungarian White Wine, Curious French Claret, White Perfian Wine, and Curious Rich Perfian Red Wine. The broker listed on the final page is Peter Fearon.

Hedges & Butler Advertisement

An advertisement for Hedges & Butler, Wine Merchants to the Queen, in London, England. The advertisement lists the prices for: Sherries, Ports, Clarets, Champagnes, Burgundies, and Madeiras.

The New Testament of Our Lord and Saviour Jesus Christ

This book was presented by the Canadian Bible Society (British & Foreign Bible Society) to the Canadian Soldiers in the war of 1914. There is an inscription which reads "Niagara-on-the-Lake, August 15th 1915 Presented to the 35th overseas Battalion Draft. P.C. Band to his father before his departure for the front". The word "confirmed" is written below this but the rest of the page is torn out. There is also a book plate that reads "Presented by the Canadian Bible Society (British & Foreign Bible Society) to the Canadian Soldiers in the War of 1914. 'Be strong and of a Good Courage'". See the full text in the Brock University Special Collections and Archives.