A text become provisional: revisiting the capital of the ruins

This essay is a reexamination of Samuel Beckett's The Capital of the Ruins, the untransmitted radio script written for Raidió Éireann (now Raidió Teilifís Éireann) in 1946 following his work with the Irish Red Cross in Saint Lô. The first half of this essay is concerned with the archival and publishing history of the text. This section examines the variants introduced by various editors or publishers and makes a case for a definitive edition of the text based on the edited photocopy of the typescript held in the Beckett International Foundation archive at the University of Reading. The second half of this essay then uses this close attention to the text to reconsider the focus of The Capital of the Ruins and the extent to which the piece is more firmly directed towards socio-political aspects of post-neutrality Ireland than has previously been identified

The Alzheimer's Disease Neuroimaging Initiative 3: Continued innovation for clinical trial improvement

INTRODUCTION: The overall goal of the Alzheimer's Disease Neuroimaging Initiative (ADNI) is to validate biomarkers for Alzheimer's disease (AD) clinical trials. ADNI-3, which began on August 1, 2016, is a 5-year renewal of the current ADNI-2 study. METHODS: ADNI-3 will follow current and additional subjects with normal cognition, mild cognitive impairment, and AD using innovative technologies such as tau imaging, magnetic resonance imaging sequences for connectivity analyses, and a highly automated immunoassay platform and mass spectroscopy approach for cerebrospinal fluid biomarker analysis. A Systems Biology/pathway approach will be used to identify genetic factors for subject selection/enrichment. Amyloid positron emission tomography scanning will be standardized using the Centiloid method. The Brain Health Registry will help recruit subjects and monitor subject cognition. RESULTS: Multimodal analyses will provide insight into AD pathophysiology and disease progression. DISCUSSION: ADNI-3 will aim to inform AD treatment trials and facilitate development of AD disease-modifying treatments

Impact of the Alzheimer's Disease Neuroimaging Initiative, 2004 to 2014

INTRODUCTION: The Alzheimer's Disease Neuroimaging Initiative (ADNI) was established in 2004 to facilitate the development of effective treatments for Alzheimer's disease (AD) by validating biomarkers for AD clinical trials. METHODS: We searched for ADNI publications using established methods. RESULTS: ADNI has (1) developed standardized biomarkers for use in clinical trial subject selection and as surrogate outcome measures; (2) standardized protocols for use across multiple centers; (3) initiated worldwide ADNI; (4) inspired initiatives investigating traumatic brain injury and post-traumatic stress disorder in military populations, and depression, respectively, as an AD risk factor; (5) acted as a data-sharing model; (6) generated data used in over 600 publications, leading to the identification of novel AD risk alleles, and an understanding of the relationship between biomarkers and AD progression; and (7) inspired other public-private partnerships developing biomarkers for Parkinson's disease and multiple sclerosis. DISCUSSION: ADNI has made myriad impacts in its first decade. A competitive renewal of the project in 2015 would see the use of newly developed tau imaging ligands, and the continued development of recruitment strategies and outcome measures for clinical trials

Deriving utility scores for co-morbid conditions: a test of the multiplicative model for combining individual condition scores

BACKGROUND: The co-morbidity of health conditions is becoming a significant health issue, particularly as populations age, and presents important methodological challenges for population health research. For example, the calculation of summary measures of population health (SMPH) can be compromised if co-morbidity is not taken into account. One popular co-morbidity adjustment used in SMPH computations relies on a straightforward multiplicative combination of the severity weights for the individual conditions involved. While the convenience and simplicity of the multiplicative model are attractive, its appropriateness has yet to be formally tested. The primary objective of the current study was therefore to examine the empirical evidence in support of this approach. METHODS: The present study drew on information on the prevalence of chronic conditions and a utility-based measure of health-related quality of life (HRQoL), namely the Health Utilities Index Mark 3 (HUI3), available from Cycle 1.1 of the Canadian Community Health Survey (CCHS; 2000–01). Average HUI3 scores were computed for both single and co-morbid conditions, and were also purified by statistically removing the loss of functional health due to health problems other than the chronic conditions reported. The co-morbidity rule was specified as a multiplicative combination of the purified average observed HUI3 utility scores for the individual conditions involved, with the addition of a synergy coefficient s for capturing any interaction between the conditions not explained by the product of their utilities. The fit of the model to the purified average observed utilities for the co-morbid conditions was optimized using ordinary least squares regression to estimate s. Replicability of the results was assessed by applying the method to triple co-morbidities from the CCHS cycle 1.1 database, as well as to double and triple co-morbidities from cycle 2.1 of the CCHS (2003–04). RESULTS: Model fit was optimized at s = .99 (i.e., essentially a straightforward multiplicative model). These results were closely replicated with triple co-morbidities reported on CCHS 2000–01, as well as with double and triple co-morbidities reported on CCHS 2003–04. CONCLUSION: The findings support the simple multiplicative model for computing utilities for co-morbid conditions from the utilities for the individual conditions involved. Future work using a wider variety of conditions and data sources could serve to further evaluate and refine the approach

The facilitating factors and barriers encountered in the adoption of a humanized birth care approach in a highly specialized university affiliated hospital

<p>Abstract</p> <p>Background</p> <p>Considering the fact that a significant proportion of high-risk pregnancies are currently referred to tertiary level hospitals; and that a large proportion of low obstetric risk women still seek care in these hospitals, it is important to explore the factors that influence the childbirth experience in these hospitals, particularly, the concept of humanized birth care.</p> <p>The aim of this study was to explore the organizational and cultural factors, which act as barriers or facilitators in the provision of humanized obstetrical care in a highly specialized, university-affiliated hospital in Quebec province, in Canada.</p> <p>Methods</p> <p>A single case study design was chosen. The study sample included 17 professionals and administrators from different disciplines, and 157 women who gave birth in the hospital during the study. The data was collected through semi-structured interviews, field notes, participant observations, a self-administered questionnaire, documents, and archives. Both descriptive and qualitative deductive content analyses were performed and ethical considerations were respected.</p> <p>Results</p> <p>Both external and internal dimensions of a highly specialized hospital can facilitate or be a barrier to the humanization of birth care practices in such institutions, whether independently, or altogether. The greatest facilitating factors found were: caring and family- centered model of care, professionals' and administrators' ambient for the provision of humanized birth care besides the medical interventional care which is tailored to improve safety, assurance, and comfort for women and their children, facilities to provide a pain-free birth, companionship and visiting rules, dealing with the patients' spiritual and religious beliefs. The most cited barriers were: the shortage of health care professionals, the lack of sufficient communication among the professionals, the stakeholders' desire for specialization rather than humanization, over estimation of medical performance, finally the training environment of the hospital leading to the presence of too many health care professionals, and consequently, a lack of privacy and continuity of care.</p> <p>Conclusion</p> <p>The argument of medical intervention and technology at birth being an opposing factor to the humanization of birth was not seen to be an issue in the studied highly specialized university affiliated hospital.</p

Autosomal dominant and sporadic late onset Alzheimer's disease share a common in vivo pathophysiology

The extent to which the pathophysiology of autosomal dominant Alzheimer's disease corresponds to the pathophysiology of 'sporadic' late onset Alzheimer's disease is unknown, thus limiting the extrapolation of study findings and clinical trial results in autosomal dominant Alzheimer's disease to late onset Alzheimer's disease. We compared brain MRI and amyloid PET data, as well as CSF concentrations of amyloid-β42, amyloid-β40, tau and tau phosphorylated at position 181, in 292 carriers of pathogenic variants for Alzheimer's disease from the Dominantly Inherited Alzheimer Network, with corresponding data from 559 participants from the Alzheimer's Disease Neuroimaging Initiative. Imaging data and CSF samples were reprocessed as appropriate to guarantee uniform pipelines and assays. Data analyses yielded rates of change before and after symptomatic onset of Alzheimer's disease, allowing the alignment of the ∼30-year age difference between the cohorts on a clinically meaningful anchor point, namely the participant age at symptomatic onset. Biomarker profiles were similar for both autosomal dominant Alzheimer's disease and late onset Alzheimer's disease. Both groups demonstrated accelerated rates of decline in cognitive performance and in regional brain volume loss after symptomatic onset. Although amyloid burden accumulation as determined by PET was greater after symptomatic onset in autosomal dominant Alzheimer's disease than in late onset Alzheimer's disease participants, CSF assays of amyloid-β42, amyloid-β40, tau and p-tau181 were largely overlapping in both groups. Rates of change in cognitive performance and hippocampal volume loss after symptomatic onset were more aggressive for autosomal dominant Alzheimer's disease participants. These findings suggest a similar pathophysiology of autosomal dominant Alzheimer's disease and late onset Alzheimer's disease, supporting a shared pathobiological construct