An informal evaluation of a planned phonics program in grade one

Thesis (Ed.M.)--Boston Universit

Barriers in phase I cancer clinical trials referrals and enrollment: five-year experience at the Princess Margaret Hospital

BACKGROUND: There is a paucity of literature on the referral outcome of patients seen in phase I trial clinics in academic oncology centres. This study aims to provide information on the accrual rate and to identify obstacles in the recruitment process. METHODS: A retrospective chart review was performed for all new patients referred and seen in the phase I clinic at the Princess Margaret Hospital between January 2000 and June 2005. Data on their demographics, medical history, and details of trial participation or non-entry were recorded. RESULTS: A total of 667 new phase I referrals were seen during the stated period. Of these patients, 197 (29.5%) patients were enrolled into a phase I trial, and 64.5% of them started trial within 1 month of the initial visit. About a quarter (165 of 667) of the patients referred were deemed ineligible at their first visit, with the most frequent reasons for ineligibility being poor performance status, unacceptable bloodwork, too many prior treatments and rapid disease progression. The remaining 305 patients (45.7%) were potentially eligible at their initial visit, but never entered a phase I trial. The main reasons for their non-entry were patient refusal, other treatment recommended first, and lack of available trials or trial spots. CONCLUSION: This study provides information on the clinical realities underlying a referral to a phase I clinic and eventual trial enrollment. Better selection of patients, appropriate education of referring physicians, and opening phase I trials with fewer restrictions on some criteria such as prior therapy may enhance their recruitment rates

Cardiovascular disease, chronic kidney disease, and diabetes mortality burden of cardiometabolic risk factors from 1980 to 2010: A comparative risk assessment

Background: High blood pressure, blood glucose, serum cholesterol, and BMI are risk factors for cardiovascular diseases and some of these factors also increase the risk of chronic kidney disease and diabetes. We estimated mortality from cardiovascular diseases, chronic kidney disease, and diabetes that was attributable to these four cardiometabolic risk factors for all countries and regions from 1980 to 2010. Methods: We used data for exposure to risk factors by country, age group, and sex from pooled analyses of population-based health surveys. We obtained relative risks for the effects of risk factors on cause-specific mortality from meta-analyses of large prospective studies. We calculated the population attributable fractions for each risk factor alone, and for the combination of all risk factors, accounting for multicausality and for mediation of the effects of BMI by the other three risks. We calculated attributable deaths by multiplying the cause-specific population attributable fractions by the number of disease-specific deaths. We obtained cause-specific mortality from the Global Burden of Diseases, Injuries, and Risk Factors 2010 Study. We propagated the uncertainties of all the inputs to the final estimates. Findings: In 2010, high blood pressure was the leading risk factor for deaths due to cardiovascular diseases, chronic kidney disease, and diabetes in every region, causing more than 40% of worldwide deaths from these diseases; high BMI and glucose were each responsible for about 15% of deaths, and high cholesterol for more than 10%. After accounting for multicausality, 63% (10·8 million deaths, 95% CI 10·1-11·5) of deaths from these diseases in 2010 were attributable to the combined effect of these four metabolic risk factors, compared with 67% (7·1 million deaths, 6·6-7·6) in 1980. The mortality burden of high BMI and glucose nearly doubled from 1980 to 2010. At the country level, age-standardised death rates from these diseases attributable to the combined effects of these four risk factors surpassed 925 deaths per 100 000 for men in Belarus, Kazakhstan, and Mongolia, but were less than 130 deaths per 100 000 for women and less than 200 for men in some high-income countries including Australia, Canada, France, Japan, the Netherlands, Singapore, South Korea, and Spain. Interpretation: The salient features of the cardiometabolic disease and risk factor epidemic at the beginning of the 21st century are high blood pressure and an increasing effect of obesity and diabetes. The mortality burden of cardiometabolic risk factors has shifted from high-income to low-income and middle-income countries. Lowering cardiometabolic risks through dietary, behavioural, and pharmacological interventions should be a part of the global response to non-communicable diseases. Funding: UK Medical Research Council, US National Institutes of Health. © 2014 Elsevier Ltd

Reconciling autonomy and beneficence in treatment decision-making for animal patients

This article explores how the concept of consent to medical treatment applies in the veterinary context, and aims to evaluate normative justifications for owner consent to treatment of animal patients. We trace the evolution of the test for valid consent in human health decision-making, against a backdrop of increased recognition of the importance of patient rights and a gradual judicial espousal of a doctrine of informed consent grounded in a particular understanding of autonomy. We argue that, notwithstanding the adoption of a similar discourse of informed consent in professional veterinary codes, notions of autonomy and informed consent are not easily transferrable to the veterinary medicine context, given inter alia the tripartite relationship between veterinary professional, owner and animal patient. We suggest that a more appropriate, albeit inexact, analogy may be drawn with paediatric practice which is premised on a similarly tripartite relationship and where decisions must be reached in the best interests of the child. However, acknowledging the legal status of animals as property and how consent to veterinary treatment is predicated on the animal owner’s willingness and ability to pay, we propose that the appropriate response is for veterinary professionals generally to accept the client’s choice, provided this is informed. Yet such client autonomy must be limited where animal welfare concerns exist, so that beneficence continues to play an important role in the veterinary context. We suggest that this ‘middle road’ should be reflected in professional veterinary guidance

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Light-based technologies for management of COVID-19 pandemic crisis.

The global dissemination of the novel coronavirus disease (COVID-19) has accelerated the need for the implementation of effective antimicrobial strategies to target the causative agent SARS-CoV-2. Light-based technologies have a demonstrable broad range of activity over standard chemotherapeutic antimicrobials and conventional disinfectants, negligible emergence of resistance, and the capability to modulate the host immune response. This perspective article identifies the benefits, challenges, and pitfalls of repurposing light-based strategies to combat the emergence of COVID-19 pandemic

Gastrulation-stage gene expression in Nipbl+/- mouse embryos foreshadows the development of syndromic birth defects.

In animal models, Nipbl deficiency phenocopies gene expression changes and birth defects seen in Cornelia de Lange syndrome, the most common cause of which is Nipbl haploinsufficiency. Previous studies in Nipbl+/- mice suggested that heart development is abnormal as soon as cardiogenic tissue is formed. To investigate this, we performed single-cell RNA sequencing on wild-type and Nipbl+/- mouse embryos at gastrulation and early cardiac crescent stages. Nipbl+/- embryos had fewer mesoderm cells than wild-type and altered proportions of mesodermal cell subpopulations. These findings were associated with underexpression of genes implicated in driving specific mesodermal lineages. In addition, Nanog was found to be overexpressed in all germ layers, and many gene expression changes observed in Nipbl+/- embryos could be attributed to Nanog overexpression. These findings establish a link between Nipbl deficiency, Nanog overexpression, and gene expression dysregulation/lineage misallocation, which ultimately manifest as birth defects in Nipbl+/- animals and Cornelia de Lange syndrome

Synthetic studies related to diketopyrrolopyrrole (DPP) pigments. Part 1: The search for alkenyl-DPPs. Unsaturated nitriles in standard DPP syntheses: a novel cyclopenta[<i>c</i>]pyrrolone chromophore

Reactions of the anion of ethyl 4,5-dihydro-5-oxo-2-phenylpyrrole-3-carboxylate with the Diels-Alder adducts of acrylonitrile and various dienes rarely yield the expected DPP derivatives. The reaction with cyclohex-3-enecarbonitrile provides a noteworthy exception: thermolysis of the resulting cyclohexenyl-DPP gives butadiene and impure 3-ethenyl-6-phenyl-DPP, the latter being thermally unstable. Michael additions predominate when the above anion reacts with alpha,beta-unsaturated nitriles: acrylonitrile and methacrylonitrile give 4,4-bis(cyanoethyl) and 4,4-bis(2-cyanopropyl) derivatives, and cinnamonitrile, substituted cinnamonitriles and 3-(2-thienyl)acrylonitrile give deep red 3-aryl-5-cyano-4-hydroxy-2H-cyclopenta[c]pyrrol-1-ones. These ambident nucleophiles may undergo N- and either O- or C-alkylation according to the alkylating agent used. (C) 2002 Elsevier Science Ltd. All rights reserved.</p