Debility and/or Loss of Weight the Diagnostic Approach

These last few decades have given us greatly increased precision of diagnosis and therapeutic power, and we, no longer merit Matthew Arnold's rebuke. These revolutionary changes have been produced as a result of a great spirit of free enquiry, a search for facts and their explanation. Such a search is dependent initially on the development of a working hypothesis, and this is just what a tentative diagnosis is. From this point our search is for facts uncoloured by accepted authority, popular opinion or personal prejudice.In medicine Galen of Pergamum was the "Master" for many centuries, and from 200 A.D. the dead hand of Galen's authority lay upon medicine for over 1300 years. The mighty Leonardo da Vinci first questioned Galen's views and in England in 1620 Francis Bacon in his "Novum Organum" urged men to abandon their four idols-accepted authority, popular opinion, legal bias and personal prejudice. Yet, despite Leonardo da Vinci and Bacon and even the revolutionary work of Harvey in 1628, it was not until the time of Lister (186o) that medicine ceased to be a traditional empirical art bound to the words of the Master and accepted authority.There are for us three kinds of facts, viz. symptoms, signs and the results of investigations, and upon these we base our diagnosis. It is because of the difficulty in setting down an accurate account of the first of these that medicine will be for ever an art

Far Ultraviolet Spectroscopic Explorer Survey of Magellanic Cloud Supernova Remnants

We report the progress to date from an ongoing unbiased ultraviolet survey of supernova remnants in the Magellanic Clouds using the Far Ultraviolet Spectroscopic Explorer (FUSE) satellite. This survey is obtaining spectra of a random large sample of Magellanic Cloud supernova remnants with a broad range of radio, optical, and X-ray properties. To date, 39 objects have been observed in the survey (38 in the LMC and one in the SMC) and 15 have been detected, a detection rate of nearly 40%. Our survey has nearly tripled the number of UV-detected SNRs in the Magellanic Clouds (from 8 to 22). Because of the diffuse source sensitivity of FUSE, upper limits on non-detected objects are quite sensitive in many cases. Estimated total luminosities in O~VI span a broad range from considerably brighter to many times fainter than the inferred soft X-ray luminosities, indicating that O~VI can be an important and largely unrecognized coolant in certain objects. We compare the optical and X-ray properties of the detected and non-detected objects but do not find a simple indicator for ultraviolet detectability. Non-detections may be due to clumpiness of the emission, high foreground extinction, slow shocks whose emission gets attenuated by the Magellanic interstellar medium, or a combination of these effects.Comment: 34 pages, 26 figures in 8 separate JPG figure files; the characteristics of individual detected supernova remnants are summarized in an Appendi

Res Medica, May 1961, Volume II, Number 4

TABLE OF CONTENTSDEBILITY AND / OR LOSS OF WEIGHT Charles W. Seward, M.D., F.R.C.P.E.LEUKAEMIA James A. Barrowman, B.Sc.POISONING BY BRITISH PLANTS R. W. Corner, Esq.RES MEDICAAUSCULTATION OF THE HEART: Ill R. W. D. Turner, O.B.E., M.A., M.D., F.R.C.P.Ed., F.R.C.P.Lond. PARRY AND PARRY'S DISEASE R. I. Legge NUTRITIONAL BLINDNESS D. S. McLaren, M.D., Ph.D., D.T.M. & H.ACCIDENTAL HAEMORRHAGE James MowatEYE CHANGES IN DISSEMINATED SCLEROSIS A. D. ChalmersBOOK REVIEWSREFLECTIONS

Genome-Wide Mutagenesis Reveals That ORF7 Is a Novel VZV Skin-Tropic Factor

The Varicella Zoster Virus (VZV) is a ubiquitous human alpha-herpesvirus that is the causative agent of chicken pox and shingles. Although an attenuated VZV vaccine (v-Oka) has been widely used in children in the United States, chicken pox outbreaks are still seen, and the shingles vaccine only reduces the risk of shingles by 50%. Therefore, VZV still remains an important public health concern. Knowledge of VZV replication and pathogenesis remains limited due to its highly cell-associated nature in cultured cells, the difficulty of generating recombinant viruses, and VZV's almost exclusive tropism for human cells and tissues. In order to circumvent these hurdles, we cloned the entire VZV (p-Oka) genome into a bacterial artificial chromosome that included a dual-reporter system (GFP and luciferase reporter genes). We used PCR-based mutagenesis and the homologous recombination system in the E. coli to individually delete each of the genome's 70 unique ORFs. The collection of viral mutants obtained was systematically examined both in MeWo cells and in cultured human fetal skin organ samples. We use our genome-wide deletion library to provide novel functional annotations to 51% of the VZV proteome. We found 44 out of 70 VZV ORFs to be essential for viral replication. Among the 26 non-essential ORF deletion mutants, eight have discernable growth defects in MeWo. Interestingly, four ORFs were found to be required for viral replication in skin organ cultures, but not in MeWo cells, suggesting their potential roles as skin tropism factors. One of the genes (ORF7) has never been described as a skin tropic factor. The global profiling of the VZV genome gives further insights into the replication and pathogenesis of this virus, which can lead to improved prevention and therapy of chicken pox and shingles

Supernova remnants: the X-ray perspective

Supernova remnants are beautiful astronomical objects that are also of high scientific interest, because they provide insights into supernova explosion mechanisms, and because they are the likely sources of Galactic cosmic rays. X-ray observations are an important means to study these objects.And in particular the advances made in X-ray imaging spectroscopy over the last two decades has greatly increased our knowledge about supernova remnants. It has made it possible to map the products of fresh nucleosynthesis, and resulted in the identification of regions near shock fronts that emit X-ray synchrotron radiation. In this text all the relevant aspects of X-ray emission from supernova remnants are reviewed and put into the context of supernova explosion properties and the physics and evolution of supernova remnants. The first half of this review has a more tutorial style and discusses the basics of supernova remnant physics and thermal and non-thermal X-ray emission. The second half offers a review of the recent advances.The topics addressed there are core collapse and thermonuclear supernova remnants, SN 1987A, mature supernova remnants, mixed-morphology remnants, including a discussion of the recent finding of overionization in some of them, and finally X-ray synchrotron radiation and its consequences for particle acceleration and magnetic fields.Comment: Published in Astronomy and Astrophysics Reviews. This version has 2 column-layout. 78 pages, 42 figures. This replaced version has some minor language edits and several references have been correcte

Breast cancer management pathways during the COVID-19 pandemic: outcomes from the UK ‘Alert Level 4’ phase of the B-MaP-C study

Abstract: Background: The B-MaP-C study aimed to determine alterations to breast cancer (BC) management during the peak transmission period of the UK COVID-19 pandemic and the potential impact of these treatment decisions. Methods: This was a national cohort study of patients with early BC undergoing multidisciplinary team (MDT)-guided treatment recommendations during the pandemic, designated ‘standard’ or ‘COVID-altered’, in the preoperative, operative and post-operative setting. Findings: Of 3776 patients (from 64 UK units) in the study, 2246 (59%) had ‘COVID-altered’ management. ‘Bridging’ endocrine therapy was used (n = 951) where theatre capacity was reduced. There was increasing access to COVID-19 low-risk theatres during the study period (59%). In line with national guidance, immediate breast reconstruction was avoided (n = 299). Where adjuvant chemotherapy was omitted (n = 81), the median benefit was only 3% (IQR 2–9%) using ‘NHS Predict’. There was the rapid adoption of new evidence-based hypofractionated radiotherapy (n = 781, from 46 units). Only 14 patients (1%) tested positive for SARS-CoV-2 during their treatment journey. Conclusions: The majority of ‘COVID-altered’ management decisions were largely in line with pre-COVID evidence-based guidelines, implying that breast cancer survival outcomes are unlikely to be negatively impacted by the pandemic. However, in this study, the potential impact of delays to BC presentation or diagnosis remains unknown