Multiphase smoothed-particle hydrodynamics

We adapt the smoothed-particle hydrodynamics (SPH) technique to allow a multiphase fluid in which SPH particles of widely differing density may be freely intermixed. Applications include modelling of galaxy formation and cooling flows

Interleukin-17 is required for control of chronic lung infection caused by Pseudomonas aeruginosa

Chronic pulmonary infection with Pseudomonas aeruginosa is a feature of cystic fibrosis (CF) and other chronic lung diseases. Cytokines of the IL-17 family have been proposed as important in the host response to P. aeruginosa infection through augmenting antibacterial immune responses, although their pro-inflammatory effect may contribute to lung damage that occurs as a result of chronic infection. We set out to explore the role of IL-17 in the host response to chronic P. aeruginosa infection. We used a murine model of chronic pulmonary infection with CF-related strains of P. aeruginosa. We demonstrate that IL-17 cytokine signaling is essential for survival and prevention of chronic infection at 2 weeks post-inoculation using two different P. aeruginosa strains. Following infection, there was a marked expansion of cells within mediastinal lymph nodes, comprised mainly of innate lymphoid cells (ILCs); ∼90% of IL-17 producing cells had markers consistent with Group 3 ILCs. A smaller percentage of IL-17+ cells had markers consistent with a B1 phenotype. In lung homogenates 14 days following infection, there was a significant expansion of IL-17+ cells – about 50% of these were CD3+, split equally between CD4+ Th17 cells and γδ T cells, while the CD3- IL-17+ cells were almost exclusively Group 3 ILCs. Further experiments with B cell deficient mice showed that B cell production of IL-17 or natural antibodies did not provide any defence against chronic P. aeruginosa infection. Thus, IL-17 rather than antibody is a key element in host defence against chronic pulmonary infection with P. aeruginosa

Veratrone in the treatment of eclampsia

It is not so long since authorities were agreed that eclampsia was due to an acute nephritis, that we knew all there was to know about it, and that no further progress either in prophylaxis or treatment would ever be made. We believe now that eclampsia is a profound toxic disturbance of the whole system somehow dependent on the existence of pregnancy, and as this toxic change arises from changes produced in the body itself, and not as the result of substances introduced from without, it is an "autointoxication”. The disturbances are produced by products of metabolism that have been formed within the tissues of the body. The term metabolism must be understood in its widest sense, and to indicate any form of chemical or biochemical cell-activity - normal or otherwise. Eclampsia is intimately associated with abnormal cellactivity. During the course of metabolism innumerable organic compounds are formed, some of which are of a more or less poisonous nature. As long as the body is in a normal condition, and as long as the compounds themselves are not too abnormal, either in quantity or quality, no harmful accumulation results. This is accomplished in the following ways:- (1) Elimination from the body in the urine, sweat, faeces, etc. (2) Combination with other substances into harmless or relatively harmless substances. (3) Chemical alterations into compounds that are nontoxic or relatively innocuous. A harmful accumulation of metabolic products or an intoxication may result from any of the following conditions (Wells: Chem. Pathology):- (1) Failure of elimination, because of abnormal conditions in the eliminating organs; e.g., uraemia. (2) Failure of neutralization by chemical combination, presumably due to abnormalities in the organs or tissues through whose activities the neutralization is normally accomplished; e.g., diseases of the liver. (3) Failure of the chemical transformation of the metabolic products: this may result either from abnormalities in the functionating tissues or through a checking of the normal Bteps of metabolism by the failure of the elimination of the endproducts. (4) Excessive formation of toxic chemical substances; e.g., autolytic changes in an organ, such as the liver, or the intoxication following superfacial burns. Eclampsia does not fall into any one of the above groups, but so complex and far-reaching are the anatomical and chemical changes that, according to Eardley Holland, it may be said to present a combination of all four. But though the majority are convinced that eclampsia is an autointoxication, no observer has yet been able to prove what the primary cause of the condition is. Our ignorance of the pathology of the disease is so great that naturally from time to time widely divergent theories as to the etiology have been brought forward - theories, many of which are interesting, all of which may possibly be sometimes true, but in regard to none of which have we any absolute knowledge. All then that we can fairly claim is that eclampsia is due to an autointoxication in some way dependent on pregnancy. Though we do not know the nature or origin of the "eclamptic toxin", or what is more probably correct - the "eclmaptic toxins", we can recognise the Physical lesions which they produce. We can also recognise the symptoms which they call forth, and any treatment to be intelligent must take cognizance of both of these factors, but owing to the poverty of our knowledge of the pathology of the disease the treatment must be based on speculation and experience rather than on scientific grounds. In order to treat any condition intelligently, it is necessary to have a clear conception of what the treatment is designed to accomplish. In eclampsia we have a morbid condition to contend with which is in some way dependent on the pregnant state, which usually gives marked premonitory warnings, as albuminuria and diminution in the amount of urine excreted, headache, muscae volitantes and dimness of vision, vomiting etc., and which is caused by some substance or substances circulating in the blood which produce marked inflammatory changes in the various internal organs. This toxaemia is characterized by a high blood pressure whicl: throws undue strain on any weakened vessels and on the heart which is probably always weakened by the degenerative action of the toxins. The disease is moreover characterized in its more severe type by convulsive attacks during which the strain on the arteries and heart is greatly increased, thus markedly increasing the tendency to rupture of the cerebral vessels on the one hand, or acute cardiac dilatation on the other, and one or other of these conditions is the ultimate cause of death in a large number of patientB. Additional dangers which may be caused by the fits and which account for a certain proportion of deaths are pulmonary complications as aspiration pneumonia and oedema of the lungs. Furthermore a certain number of patients die from the damage done directly by the toxins, a not uncommon result in cases in which adequate treatment is long deferred. The treatment of such a condition must be directed to stopping the absorption of the toxins, to securing their elimination and to neutralizing their, effects meanwhile, and must be divided into (a) prophylaxis and (b) the treatment of the disease. (a) Prophylaxis. I do not propose to enter into the discussion of the prophylactic treatment. All authorities are agreed as to the tremendous importance of sue treatment, and there is also general agreement as to the best method for carrying it out. Within the laet few years the duty of the practitioner to his patients during pregnancy has been emphasized, and it has been made clear how much suffering and ill-health can be prevented by proper and careful treatment of the expectant mother. This is especially the case in eclampsia. It is probable that very few threatening cases would ever develop into the severe form of the disease were careful supervision of the mother's health carried out from the very commencement of pregnancy. It is to be hoped that the next few years will see a still wider employment of efficient prophylactic treatment, and con sequently a great diminution in the ravages of this dire disease. (b) Treatment of the Disease. When however we come to consider the treatment of the disease itself, after the fits have commenced, we find ourselves in the midst of a bewildering maze of divergent and even conflicting opinions. It is agreed that the purpose of treatment is threefold: (l) to control the convulsions; (2) to eliminate the toxins; (5) to terminate labour. The chief divergence is as to the relative importance of these indications, whilst there are further differences as to the best way of achieving each

Object Identity: Deconstructing the 'Hartree Differential Analyser' and Reconstructing a Meccano Analogue Computer

In 1934, a child's construction toy - Meccano - was used to build the first differential analyser in the UK. Initially intended as a proof-of-concept model, the original Meccano differential analyser proved so successful at resolving equations that many subsequent Meccano and non-Meccano analogue computers were built in the UK. These machines were used before, during, and after the Second World War as research instruments and teaching devices. Despite this, the part of the original Meccano differential analyser that has sat in the Science Museum since 1949 has been used to tell a Whiggish history of computers that focuses on digital machines at the expense of analogue mechanisms. While historians of computing today define their work in opposition to this linear-progressive account of computing, this approach featured prominently in academic literature until the turn of the millennium. This thesis explores Hartree and Porter's original Meccano differential analyser as an analogue computer, using it as a case study to explore the complex relationships between Meccano, play, science, and engineering. In doing so, it considers the object as an assemblage of its Meccano materiality, its instrumentality as an analogue computer, and its career as a collected object in the Science Museum. It deconstructs these different elements of the assemblage and explores how they are part of wider, external assemblages that have their own public histories. The thesis considers the changing materiality of Meccano as an object from 1901 to the present day, analysing marketing materials, the Meccano Magazine, and the voices of the Meccanomen to challenge the conventional, synchronic history of the toy as an unchanged engineering tool. It uses the Meccanomen's popular publications together with archival sources and interviews to historicise the 'alternative' version of the Meccanomen's movement, making it possible to see how individuals attached a variety of personalised meanings to their Meccano hobby. It also explores the object's instrumentality as an analogue computer, beginning with a detailed 'nuts and bolts' comparison of how the original Meccano differential analyser worked with how it was presented in academic and popular publications in 1934. It then brings together the stories and applications of other differential analysers constructed in Britain during this period, to provide further case studies about the role of these computers during the Second World War, and how they have been displayed in museums. The thesis then draws on these analyses by telling the story of the 'Trainbox' object that was collected by the Science Museum in 1949. The 'Trainbox' was comprised of parts of the original Meccano differential analyser that Hartree used to teach the principles of differential equations and integration after the Second World War. Through exploring how the public history and voices of the object have been changed in different exhibits in the museum, this thesis demonstrates the complex relationship between different parts of object's assemblage in a variety of contexts over time. The final part of the thesis builds on these deconstructed elements by reconstructing the original object as the Kent machine, a historical reproduction designed to recover elements of the tacit knowledge used to build it in 1934. It finishes by exploring how these new understandings of Meccano and analogue computers were used to co-curate a new public history for this curious object, using the 'shared authority' of myself, the Meccanomen, and audiences we engaged with the Kent machine

Andy Thomas Ritchie, Jr. Papers, 1930-1970

Finding aid for the Andy Thomas Ritchie, Jr. Papers, 1930-1970

Lung cancer treatment rates and the role of the lung cancer nurse specialist : a qualitative study

Objectives: This qualitative study examines how the Lung Cancer Nurse Specialist (LCNS) role operates and why they may be able to increase access to treatment. Setting: 4 Hospital NHS Foundation Trusts in England. Design: A multiple case study design using semistructured interviews, observation and Framework Analysis techniques. Participants: Four LCNSs, comprised the ‘cases’. Twenty four clinicians who worked with the LCNS participated in individual interviews. Six LCNSs took part in a group interview and 60 lung cancer multidisciplinary team (MDT) members and co-ordinators were observed in the MDT meeting. Results: The LCNS is crucial within the MDT and can act as a catalyst to patient access to treatment. The study identified the clinical activity (assessment, managing symptoms, psychological support and information provision) and role characteristics that can facilitate treatment access. These characteristics are the LCNS's presence across the patient pathway, acting as the ‘hub’ of the MDT, maintaining a holistic patient focus and working to an advanced level of practice. The findings indicate how factors may have a cumulative impact on treatment access. Conclusions: If UK patient with lung cancer survival rates are to improve in line with comparable countries, we need to employ every advantage. This study demonstrates how the LCNS role may open doors to positive patient outcomes, including treatment. Further research is required to explore patients’ experiences, decision-making and attitudes to treatment