14 research outputs found
High hereditary transthyretin-related amyloidosis prevalence in Crete genetic heterogeneity and distinct phenotypes
No full textBackground and Objectives Our goal was to study hereditary transthyretin-related amyloidosis (hATTR) in Crete, Greece. Methods We aimed at ascertaining all hATTR cases in Crete, an island of 0.62 million people. For this, we evaluated patients with polyneuropathy, autonomic involvement, cardiomyopathy, and/or ophthalmopathy suggestive of hATTR, who presented to the physicians of this study or were referred to them by other physicians. Genetic analyses were performed on all patients suspected of suffering from hATTR. We included in our observational longitudinal cohort study all individuals, residents of Crete, who, during the study period (1993–2019), were found to carry a pathogenic TTR variant. Results Over the past 27 years, 30 individuals (15 female patients, 15 male patients), from 12 apparently unrelated families, were diagnosed with hATTR, whereas evaluation of their offspring identified 5 asymptomatic TTR pathogenic variant carriers. The most prevalent TTR variant detected was p.Val50Met, affecting 19 patients (11 female patients, 8 male patients) and causing a rather consistent phenotype characterized by predominant polyneuropathy of early adult onset (median age of symptom onset: 30 years; range: 18–37 years). Specifically, patients affected by the p.Val50Met TTR variant experienced progressive sensorimotor disturbances, involving mainly the lower extremities, associated with autonomic and/or gastrointestinal dysfunction. The second most frequent TTR variant was p.Val114Ala, found in 10 patients (4 female patients, 6 male patients) who were affected at an older age (median age of symptom onset: 70 years; range: 54–78 years). This variant caused a predominantly cardiomyopathic phenotype, manifested by congestive heart failure and associated with peripheral neuropathy, carpal tunnel syndrome, and/or autonomic involvement. In these patients, cardiac amyloid deposition was detected on 99m-technetium pyrophosphate scintigraphy and/or heart biopsy. The third TTR variant (p.Arg54Gly) was found in a 50-year-old male patient with ophthalmopathy due to vitreous opacities and positive family history for visual loss. As 22 patients were alive at the end of the study, we calculated the hATTR prevalence in Crete to be 35 cases per 1 million inhabitants. Copyright © 2022 The Author(s)
Talactoferrin alfa versus placebo in patients with refractory advanced non-small-cell lung cancer (FORTIS-M trial)
No full textBackground: Talactoferrin alfa is an oral dendritic cell (DC)-mediated immunotherapy (DCMI). We tested whether talactoferrin was superior to placebo in advanced non-small-cell lung cancer (NSCLC). Patients and methods: An FORTIS-M trial was an international, multicenter, randomized, double-blind comparison of talactoferrin (1.5 g p.o. BID) versus placebo BID, in patients with stage IIIB/IV NSCLC whose disease had failed two or more prior regimens. Treatment was administered for a maximum of five 14-week cycles. The primary efficacy end point was overall survival (OS); secondary end points included 6- and 12-month survival, progression-free survival (PFS), and disease control rate (DCR). Results: Seven hundred and forty-two patients were randomly assigned (2:1) to talactoferrin (497) or placebo (245). The median OS in the intent-to-treat (ITT) population was 7.66 months in the placebo arm and 7.49 months in the talactoferrin arm [hazard ratio (HR), 1.04; 95% CI, 0.873-1.24; P = 0.6602]. The 6-month survival rates were 59.9% (95% CI, 53.4% to 65.8%) and 55.7% (95% CI, 51.1% to 59.9%), respectively. The 12-month survival rates were 32.2% (95% CI, 26.3% to 38.2%) and 30.9% (95% CI, 26.8% to 35%), respectively. The median PFS rates were 1.64 months and 1.68 months, respectively (HR, 0.99; 95% CI, 0.835-1.16; P = 0.8073). The DCRs were 38.4 and 37.6%, respectively [stratified odds ratio (OR), 0.96; 95% CI, 0.698-1.33; P = 0.8336]. The safety profiles were comparable between arms. Conclusions: There was no improvement in efficacy with talactoferrin alfa in patients with advanced NSCLC whose disease had failed two or more previous regimens. © The Author 2013. Published by Oxford University Press on behalf of the European Society for Medical Oncology All rights reserved
La semántica biopolítica. Foucault y sus recepciones
No full textHace prácticamente cuarenta años Michel Foucault comenzó a plasmar una serie de investigaciones sobre lo que llamaba “las tecnologías de poder” biopolíticas. Es decir, sobre los modos concretos en los que se ejerce el poder sobre la vida de los individuos. En estos cuarenta años son muchas las investigaciones que han asumido esta perspectiva de análisis y sin embargo apenas se ha tocado el que parece el punto neurálgico de toda la cuestión, que es la relación de estas biopolíticas con el desarrollo del neoliberalismo.
En este libro se presentan las investigaciones de Foucault sobre la materia, como si se tratara de un puzle que se va armando paso a paso, a través de los cursos del Colegio de Francia. De modo que es posible atestiguar el desarrollo de la Investigación de Foucault y la serie de transformaciones que sus ideas sobre la biopolítica van experimentando.
Además se presentan de manera detallada los proyectos teóricos que han recepcionado estas ideas sobre el biopoder y la biopolítica. Así, se pasa revista a los Studies in governmentality, a partir de sus primeros trabajos en 1979; al proyecto delHomo sacer, inaugurado por Agamben en 1995; a la trilogía de Imperio inaugurada el 2000 por Hardt y Negri; y también al proyecto de Immunitas que Esposito ha dado comienzo en 2002. De modo que se puede analizar cronológicamente el despliegue de estos discursos y así transitar hasta los últimos textos de estos respectivos proyectos. A estas recepciones de los análisis foucaulteanos, se suma la revisión de algunas perspectivas propuestas por Deleuze entre 1986 y 1990.
El libro finaliza revisando algunas señales de una nueva etapa en estos análisis de las cuales el propio libro pretende ser part
Investigating grammatical complexity in Gulf Arabic speaking children with specific language impairment (SLI)
No full textThis is the first investigation of Specific Language Impairment (SLI) in Gulf-Arabic (GA) speaking children. The thesis consists of two main sections, in the first one, I discuss the definitions of SLI and the various theories put forward to account for the deficits seen in this population. I also discuss the importance of cross-linguistic investigations of SLI and why studying SLI in GA may prove useful in testing the accounts of SLI that argue for a general processing deficit vs. those that argue for a domain specific account of SLI. The remaining section of the first part is dedicated to describing the various language tests developed to identify children with SLI in GA. These tests were conducted with approximately 88 typically developing children and 26 children with SLI between the age of 4;6 and 9;4 years old. In the second part of the thesis, I report on two experiments investigating syntactic and phonological complexity in GA speaking children with SLI. The first experiment investigates the comprehension of three types of word orders: a canonical SVO, and two word orders that involve fronting of the direct object (OSV and OVS). Results showed that children with SLI differed from the TD groups on the sentences with fronted NP's, but not on the canonical word order. The second experiment involves a nonword repetition test where syllable length and consonant clusters are systematically controlled to contrast the influence of both phonological short-term memory and phonological complexity. The results are consistent with accounts that argue for a significant role of phonological complexity in NWR and question the “centrality” of phonological capacity in nonword repetition. The final chapter summarises the findings of the thesis and its contribution to theories of SLI in general, and to the study of SLI in Arabic in particular
Complicated intra-abdominal infections in Europe: preliminary data from the first three months of the CIAO Study
No full textContains fulltext :
110654.pdf (Publisher’s version ) (Open Access)ABSTRACT: The CIAO Study is a multicenter observational study currently underway in 66 European medical institutions over the course of a six-month study period (January-June 2012).This preliminary report overviews the findings of the first half of the study, which includes all data from the first three months of the six-month study period.Patients with either community-acquired or healthcare-associated complicated intra-abdominal infections (IAIs) were included in the study.912 patients with a mean age of 54.4 years (range 4-98) were enrolled in the study during the first three-month period. 47.7% of the patients were women and 52.3% were men. Among these patients, 83.3% were affected by community-acquired IAIs while the remaining 16.7% presented with healthcare-associated infections. Intraperitoneal specimens were collected from 64.2% of the enrolled patients, and from these samples, 825 microorganisms were collectively identified.The overall mortality rate was 6.4% (58/912). According to univariate statistical analysis of the data, critical clinical condition of the patient upon hospital admission (defined by severe sepsis and septic shock) as well as healthcare-associated infections, non-appendicular origin, generalized peritonitis, and serious comorbidities such as malignancy and severe cardiovascular disease were all significant risk factors for patient mortality.White Blood Cell counts (WBCs) greater than 12,000 or less than 4,000 and core body temperatures exceeding 38 degrees C or less than 36 degrees C by the third post-operative day were statistically significant indicators of patient mortality
Post-larval development in deep-sea echinoderms
No full textThe post-larval phase is an essential period in the life history of marine invertebrates; vulnerable to high mortality, it ultimately influences the distribution and abundance of adult populations. The post metamorphic ontogenesis of thirty species of deep-sea echinoderms, belonging to three classes (Ophiuroidea, Asteroidea and Echinoidea), is described using scanning electron microscopy. The life history of Ophiocten gracilis is also examined as a case study for future research on post-larval organisms. The analysis of development in ophiuroids reveals that species can be identified from a very early post metamorphic stage, even in congeneric species, contrary to the findings of other authors. The ontogeny of homologous structures is similar within related groups, but may give rise to different adult structures indifferent taxa. The mouth papillae within the ophiurids are serially homologous, originating from the jaw, but the fourth mouth papilla may have a different origin. In the families Ophiactidae, Ophiacanthidae and Amphilepididae examined, the mouth papillae have different origins, as, for instance, the adoral shieldspine or tentacle scale. Data on the post-larval development of Ophiura affinis suggest that this species is more closely related to the genus Ophiocten and a change in the generic status is proposed. Ophiocten gracilis is a bathyal brittle star occurring on both sides of the North Atlantic and its life history is studied in the eastern side of the North Atlantic. In this area, O. gracilis spawns in February/March of each year producing a large number of eggs. Fecundity is estimated to be around 40,000 eggs/ind, with the population of the Hebridean Slope being able to produce probably up to 16 million eggs/m2. Post-larvae start settling in May and numbers settling reached over 3,200 post-larvae/m2. The settling speed of post-larvae in the water column is estimated to be around 500 m/day, settling faster in warmer than colder water. Settling speeds appear to be similar for post-larvae ranging from 0.6 to 0.9 mm in disk diameter. Size at settlement is around 0.6 mm in disk diameter and 5-6 arm segments. The settlement of post-larval O. gracilis on the bottom of the Hebridean Slope also represented a considerable fraction of the particulate organic carbon (POC) flux in the area, reaching over 7% of the total daily flux. This is likely to have a considerable impact in the benthic community as competition and predation and as an additional food source for demersal and benthic organisms. The occurrence of post-larvae of O. gracilis in sediment traps also represented a large problem for POC flux measurements, with ophiuroids consuming part of the flux. In future works with sediment traps, such errors must be taken into account and ophiuroids must be included in the total POC flux. The deep-sea juvenile asteroids of the NE Atlantic could be distinguished to species level from a very early stage of development. The ontogenesis of Porcellanaster ceruleus shows that this species is likely to undergo a shift in habitat and diet during the juvenile phase. This is evidenced by the appearance of the epiproctal cone, the changing of the furrow and apical spines, the early development of the cribriform organ adjacent to the madreporite and the appearance of sediment in the stomach. P. ceruleus is probably a predator on meiofauna and small macrofaunal organisms during the early stages of life, changing to a burrowed life style ingesting sediment particles. Most juvenile sea stars analysed during the present study showed wider bathymetric distribution than their adult counterparts, suggesting that events occurring during the early stages of life are important for the maintenance of the local population structure and diversity in the deep NE Atlantic.The post-metamorphic development of three deep-sea spatangoid echinoids is very similar, but the morphology and formation of fascioles facilitate the distinction of the species examined. Whereas in Hemiaster expergitus and Spatangus raschi the fascioles present in the post-larvae develop to form the adult fascioles, in Brissopsis lyrifera post-larvae there is a juvenile fasciole, which disappears during ontogenesis giving way to the adult fascioles. The function of the juvenile fasciole is unknown in B.lyrifera. The development of the periproct in all spatangoids examined is similar to that described by other authors, with the periproct being initially endocyclic and migrating towards the rear of the animal as development progresses. Post-larvae of the genus Echinus could not be separated into different species, which may be linked to the recent diversification of the genus in the North Atlantic. The widespread settlement of echinoderm post-larvae reported in the present thesis and in other works is thought to have been very important for the colonization of the deep-sea through the supply of stages to deeper areas and selection of pressure adapted animals and subsequent speciation
'Riot', 'Revolution' and 'Rape': The theatre relationship and performance breakdown
No full textThis thesis considers theories about the relationship between theatre makers and audience members in theatre – how this relationship is established and how it can break down. The thesis posits that the breakdown of a theatre relationship is manifested in audience behaviour which, when it is severe enough, can lead to interventions in performance and, potentially, the breakdown of that performance. The thesis argues that audience intervention in a performance constitutes a seizure of ‘performance power’ from the theatre makers, which is sufficiently difficult to achieve that successful and sustained interventions can only be carried out by groups of audience members and, probably, organized in advance. Further, the thesis suggests that in its most extreme form, such interventions may bring about a transfer of roles and power between audience members and theatre makers such that a new quasi-theatrical ‘performance of protest’ is created.
The thesis surveys three historical cases in which theatre performances were disrupted by deliberate audience interventions. In each case the nature of the intervention was slightly different and the effect upon the performance was also different. In the first example, the Plough and the Stars riots (Dublin, 1926) a preplanned protest occurred in the playhouse and, despite interruption, the performance continued. In the second instance, the audience at Living Theatre’s Paradise Now (California 1969) erupted in spontaneous protest within the theatre and the performance was almost entirely subsumed. In the final study, the Mervyn Thompson case (Auckland 1984) the protest took two forms: first there was a vigilante-style attack on Thompson himself which took place well away from any theatre event but had strong theatrical references; then several of his performances were affected by organized lobbying, pickets and interruptions. The thesis asks why the rupture in the theatre relationship occurred in each case and considers what these instances have to tell us about the breakdown of theatre performance as a social phenomenon.
The thesis finds that in all three cases the audience members carrying out the interventions belonged to pre-existing groups with prior experience in protest action. The thesis also finds that the protesters had all had direct experience of some other ‘dramatic’ or ‘theatrical’ event in their own lives; experiences that made the performance seem less relevant. Given this, the thesis argues that, in these cases, the propensity to disrupt was brought to the theatre relationship by the audience members rather than being a direct response to the performance, even where that performance was confrontational.
These findings have implications for theatre study and practice: in particular, the thesis raises questions about how we look at performance breakdown. Rather than assuming audience protest is a simple response to the performance, the findings suggest that such events must be considered in the light of the wider social and political context of the performance, most particularly the audience members’ pre-occupations. Finally, the thesis asks whether audience protest, however theatrical it appears, can ever become substitute theatre in the true sense of that word
Accessible theatre: the application of human ethology and innate neurobiological systems to full-masked devised theatre practice
No full textThis thesis is concerned with the challenges of devising a full-masked theatre performance that is largely accessible to audiences of every age, social background and culture. The study is original and contributes to knowledge in two distinct ways; it is to this researcher’s knowledge the only such research that examines the relationship between the devising processes of a full-masked performance, neurobiology, human ethology and the accessibility of audience reception (Bennett, 1994). Secondly, this is the first study to investigate how universal innate neurological processes can be used in the making and reception of stage performance to help ensure wide accessibility of information and meaning. The thesis addresses the concept of accessibility by taking a phenomenological approach to devising and audience reception, with particular focus on the role of neurobiological systems and structures, in particular the mirror neuron system, the pleasure-reward system, and pattern recognition systems, in the communication and reception of performance meaning (McConachie, 2008). The research is framed by the concept of a universal theatrical language proposed by practitioners Peter Brook and Tadeshi Suzuki, which has the potential to connect people ‘at the deepest levels of their humanity’ (Pavis, 1996: 6). Practical approaches adopted in the research are informed and supported by anthropological and human ethological claims of universality (Ekman, 1975; Brown, 1991; Eibl-Eibesfeldt; 2007 [1989]; Schmitt et al. 1997). This thesis theorizes that human beings possess innate neurobiological systems that interact with culturally specific concepts, conditions and knowledge in such a way that when deployed appropriately, these innate neurobiological systems can be a platform for human cognition and for the designing of performances accessible to an audience of different ages, social backgrounds and cultures. It also proposes that innate neurobiological systems create a universal framework that makes it possible for the said broad-based audience to read and receive a performance using similar codes of cognition and aesthetic reference irrespective of age, social and cultural backgrounds. The research process led to the creation of an original full-masked theatrical performance and eighteen performances of this piece were given to different audiences in a range of venues and locations in Northamptonshire. Qualitative and quantitative data analysis of how the various audiences received the performance suggest that the devising methods employed did contribute to making the performance accessible to an audience with a ‘broader constituency than theaters normally envision’ (Pitts-Walker, 1994: 9-10). This research enables practitioners for whom a wide audience and accessibility are an explicit focus to adopt devising approaches that will help to achieve the desired wide-ranging reception and accessibility in mixed audiences irrespective of race, age, gender and culture
A rapid and systematic review of the clinical effectiveness and cost-effectiveness of paclitaxel, docetaxel, gemcitabine and vinorelbine in non-small-cell lung cancer
No full textBACKGROUND:
The incidence of lung cancer is declining following a drop in smoking rates, but it is still the leading cause of death from cancer in England and Wales, with about 30,000 deaths a year. Survival rates for lung cancer are poor everywhere, but they appear to be better in the rest of the European Community and the USA than in the UK. Only about 5 per cent of people with lung cancer survive for 5 years, and nearly all of these are cured by surgery after fortuitously early diagnosis. At present, only a small proportion of patients (probably about 5 per cent) with non-small-cell lung cancer are being given chemotherapy. Some centres treat a greater proportion.
OBJECTIVES:
This review examines the clinical effectiveness and cost-effectiveness of four of the newer drugs - vinorelbine, gemcitabine, paclitaxel and docetaxel - used for treating the most common type of lung cancer (non-small-cell lung cancer). The first three drugs are used for first-line treatment, but at present docetaxel is used only after first-line chemotherapy has failed.
METHODS:
This report was based on a systematic literature review and economic modelling, supplemented by cost data. RESULTS - NUMBER AND QUALITY OF STUDIES: A reasonable number of randomised trials were found - three for docetaxel, six for gemcitabine, five for paclitaxel and 13 for vinorelbine. The quality of the trials was variable but good overall. There was a wide range of comparators. Some trials compared chemotherapy with best supportive care (BSC), which involves care that aims to control symptoms, with palliative radiotherapy if needed, but not to prolong life. Others compared the newer drugs against previous drugs or combinations. RESULTS - SUMMARY OF BENEFITS: The gains in duration of survival with the new drugs are modest - a few months - but worthwhile in a condition for which the untreated survival is only about 5 months. There are also gains in quality of life compared with BSC, because on balance the side-effects of some forms of chemotherapy have less effect on quality of life than the effects of uncontrolled spread of cancer. RESULTS - COSTS: The total cost to the NHS of using these new drugs in England and Wales might be about GBP 10 million per annum, but is subject to a number of factors. There would be non-financial constraints on any increase in chemotherapy for the next few years, such as staffing; the number of patients choosing to have the newer forms of chemotherapy is not yet known; and the costs of the drugs may fall, for example, as generic forms appear. RESULTS - COST PER LIFE-YEAR GAINED: The available data did not provide an entirely satisfactory basis for cost-effectiveness calculations. The main problem was the lack of direct comparisons of the new drugs. In order to strengthen the analysis, three different modelling approaches were used: pairwise comparisons using trial data; cost-minimisation analysis, as if all the new regimens were of equal efficacy; and cost-effectiveness analysis pooling the results of several trials with different comparators, giving indirect comparisons of the new drugs by using BSC as the common comparator. A number of different scenarios were explored through extensive sensitivity analysis in each model. Outcomes were expressed in incremental cost per life-year saved or incremental cost, versus BSC. There was insufficient evidence from which to derive cost per quality-adjusted life-year. In first-line treatment, vinorelbine, gemcitabine, and the lower-dose paclitaxel plus cisplatin combinations generally performed well against BSC under a range of different scenarios and especially when given as a maximum of 3 cycles. Incremental cost per life-year gained (LYG) versus BSC varied depending on scenario, but baseline figures based on trial data and protocols were: single-agent vinorelbine, pound 2194 per LYG; vinorelbine plus cisplatin, pound 5206; single-agent gemcitabine, pound 5690; gemcitabine plus cisplatin, pound 10,041; and paclitaxel plus cisplatin, pound 8537. In second-line chemotherapy, docetaxel gave a cost per LYG of pound 17,546, again well within the range usually accepted as cost-effective. However, in routine care, the impact of therapy would be regularly reviewed, and continuation would depend on response, side-effects, patient choice and clinical judgement. Chemotherapy would be stopped in non-responders, making chemotherapy more cost-effective. A 'real-life' scenario in which 60 per cent of patients receive only 1 or 2 cycles of chemotherapy gives much lower costs per LYG, with single-agent gemcitabine, single-agent vinorelbine, and paclitaxel plus platinum appearing to be cost-saving compared with BSC; the incremental cost of gemcitabine plus cisplatin would be pound 2478 per LYG, and of vinorelbine plus cisplatin, pound 2808. At the very least, gains in duration of survival were achieved without diminution of quality of life (at best, they improved quality) and with relatively low incremental cost. Comparisons among the individual drugs should be viewed with caution because they have had to be based on indirect comparisons. RESULTS - LIMITATIONS OF THE ANALYSIS: Each of the three models had limitations. The cost-effectiveness estimates from the pairwise comparisons were based on single studies. The cost-minimisation analysis assumed that the regimens have equal efficacy in practice. The cost-effectiveness analysis had to be based on pooling data from individual trials. The costs of BSC, inpatient stay and outpatient visits were from Scottish data. Median rather than mean data on duration of survival have been used in the analysis, because most of the trials reported only median data. Median survival and number of drug cycles were calculated by averaging across a number of studies, rather than being reliant on one particular study. The costs of the less expensive antiemetics cited in the trials were omitted. The use of more modern and costly antiemetics would have a modest detrimental effect on cost-effectiveness. In the absence of published data, an estimate was made of the cost of side-effects of chemotherapy, in particular hospital admissions, and applied to all the new regimens. In practice, admissions related to side-effects and their respective costs are likely to vary by regimen.
CONCLUSIONS:
The new drugs for non-small-cell lung cancer extend life by only a few months compared with BSC, but appear to do so without net loss in quality of life and at a cost per LYG that is much lower than for many other NHS activities. Depending on assumptions used, these new drugs range from being cost-effective, as conventionally accepted, to being cost-saving. CONCLUSIONS - IMPLICATIONS OF THE NEWER DRUGS: One of the present constraints on chemotherapy is availability of inpatient beds. The advent of newer and gentler forms of chemotherapy given on an outpatient basis would not only overcome this, but it would allow more patients to be treated. This might apply particularly to older patients. The treatment of more patients would increase workload for oncologists, cancer nurses and pharmacists. The Government has already announced increased expenditure on staff for cancer care. The previously pessimistic attitudes to chemotherapy in non-small-cell lung cancer are changing in the wake of the newer agents, and this shift is likely to increase referral. CONCLUSIONS - NEED FOR FURTHER RESEARCH: Recent advances in chemotherapy are welcome, but their effects remain small for patients with non-small-cell lung cancer. Much more research is needed into better drugs, better combinations, new ways of assessing the likelihood of response and especially direct comparisons between the new regimens. This research would be aided by having a greater proportion of patients involved in trials, but there will be infrastructure implications of increased participation
Theatre/drama in education in the United Kingdom, Italy and Poland.
No full textIn 2 volsAvailable from British Library Document Supply Centre- DSC:DX188333 / BLDSC - British Library Document Supply CentreSIGLEGBUnited Kingdo
