Alkaloid inspired spirocyclic oxindoles from 1,3-dipolar cycloaddition of pyridinium ylides

Cycloaddition reactions between pyridinium ylides and 3-alkenyl oxindoles that proceed in high yield and with very good regio- and diastereoselectivity are reported. The resulting cycloadducts have the same stereochemistry of biologically active oxindole alkaloids, such as strychnofoline

Early Detection and Monitoring of Cancer with the Anti-Malignin Antibody Test "

ABSTRACT: The serum anti-malignin antibody (AMA) test determines the antibody to malignin. a IO,OOO-Da peptide present in patients with a wide variety of cancers.l~ A total of 3315 double-blind tests demonstrated that AMA is a general transformation antibody, elevated in active no.nterminal cancer, regardless of the site or tissue type, with sensitivity and specificity of95% on the flTst determination and >99% on repeat determinations. - 9 Data have not however been published yet that indicate whether, in daily clinical practice, the AMA test provides accurate prospective and predictive information. Fony-two physicians from II states, who ordered the AMA test, performed blind, report here on their results on 208 determinations in the first consecutive 181 patients and controls. Used in monitoring treatment in 56 patients, the test predicted or agreed 94.1 % overall with the clinical status. Used in early detection in 125 patients and controls, of which 118 now have confirmed diagnoses. AMA was elevated in 21, all of whom were proven to have cancer; AMA was normal in 97, none of whom had cancer. Transient elevated AMA occurred in 3%, followed by normal values. Seven patients with still uncertain diagnosis who have had elevated AMA on repeated tests for I year or longer include six who are symptomatic, and three whose families have a high frequency of cancer. The conditions of these 7 may include undetected cancer because of the 118 with now certain diagnosis the AMA test predicted all correctly. From our experience, the AMA test should be used together with other routine procedures whenever signs and symptoms suggest cancer to facilitate early detection

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

Curriculum integration for early adolescent schooling in Aotearoa New Zealand : worthy of a serious trial : a thesis presented in partial fulfilment of the requirements for the degree of Doctor of Education at Massey University, Palmerston North, New Zealand

The concept of curriculum integration has long held seductive appeal as a way to unite knowledge and meet the educational needs of young people. However, researchers have largely dismissed the concept as a romantic but unworkable idea. Nonetheless in the short history of education in Aotearoa New Zealand (NZ), notions of integration have persistently reappeared in the national curriculum. In the 1930s, innovative teachers implemented world-class examples of curriculum integration in rural schools. Later, the Freyberg Project (1986-1991) demonstrated that curriculum integration admirably meets the needs of young people. Recently, the Ministry of Education trialled curriculum integration in several schools but, since the literature indicates that curriculum integration is represented by a plethora of models, this raised an important question: which model is preferable? This thesis combines historical and theoretical methodology to conduct an investigation of the concept of curriculum integration with respect to the needs of early adolescents in NZ. The historical investigation demonstrates that curriculum integration is best described by two broad traditions which stem from nineteenth century USA: the 'student-centred' approach based on Dewey's 'organic' education and the 'subject-centred' approach based on the Herbartian notion of 'correlation'. These two approaches are represented in current practice by the student-centred integrative model (Beane, 1990/1993) and the subject-centred multidisciplinary model (Jacobs, 1989). The theoretical investigation draws from American experience to examine the respective claims of the integrative and multidisciplinary models as the preferred model of curriculum integration for middle schooling. It finds that the 'thick' ethics associated with the politics of the integrative model ensures that it meets the needs of all early adolescents whereas the 'thin' ethics of the multidisciplinary model is indifferent to the needs of young people. The thesis concludes that the integrative model should be seriously considered in the middle years in NZ. It also concludes that historical understandings of curriculum integration are vital to further research, policy-making and teacher education. Moreover, attention to political and ethical issues would enhance implementation of the integrative model in NZ and would help avoid a set of problems which have impeded implementation of the model in the USA

On the connexion between the origin and localization of diseases, whether usual or epidemical and the over-crowding of buildings in our cities

Room to be healthy is, then, one of the great wants of cities and towns, and no greater boon could be offered, to the working classes especially, than houses of two stories high being, at least in front and rear, freed from the obstructing injury of any other buildings to the full breadth of their own height. One point more must be put in this prayer for the poorer householders, which is this, that all frontages should receive the light and heat, the dryness and cleanliness, which a south or an eastern aspect would confer and maintain. Groups of houses round areas separated by their own height at least, and three-sided, leaving the south open, would be wholesome hamlets for the working classes. No doubt, if a grass-plot or flagged square of a moderate size, and without trees or shrubs, could be bestowed as a centre-piece,it would add greatly to the pleasure of the residents and the health of the children; and by inducing the population to live much in the open air, it would improve the physical, moral, and mental strength of the occupying tenants. Such are some of the reasons, statistical and constitutional, for a great increase of street-roominess

Transumbilical Breast Augmentation Is Safe and Effective

Transumbilical breast augmentation (TUBA) has proved to be safe and effective. This article highlights the advantages, disadvantages, gives an overview of the technique, discusses complications, and provides factual information to counter false negative information about the procedure