Psychological distress after stroke and aphasia: the first six months

Objective: We explored the factors that predicted psychological distress in the first six months post stroke in a sample including people with aphasia. Design: Prospective longitudinal observational study. Setting and subjects: Participants with a first stroke from two acute stroke units were assessed while still in hospital (baseline) and at three and six months post stroke. Main measures: Distress was assessed with the General Health Questionnaire-12. Other measures included: NIH Stroke Scale, Barthel Index, Frenchay Aphasia Screening Test, Frenchay Activities Index, MOS Social Support Scale and social network indicators. Logistic regression was used to identify predictors of distress at each stage post stroke; and to determine what baseline factors predicted distress at six months. Results: Eighty-seven participants were able to self-report on measures used, of whom 32 (37%) had aphasia. 71 (82%) were seen at six months, including 11 (16%) with aphasia. Predictors of distress were: stroke severity at baseline; low social support at three months; and loneliness and low satisfaction with social network at six months. The baseline factors that predicted distress at six months were psychological distress, loneliness and low satisfaction with social network (Nagelkerke R2 = 0.49). Aphasia was not a predictor of distress at any time point. Yet, at three months post stroke 93% of those with aphasia experienced high distress, as opposed to 50% of those without aphasia (χ2 (1) = 8.61, P<0.01). Conclusions: Factors contributing to distress after stroke vary across time. Loneliness and low satisfaction with one’s social network are particularly important and contribute to long-term psychological distress

The Peak Brightness and Spatial Distribution of AGB Stars Near the Nucleus of M32

The bright stellar content near the center of the Local Group elliptical galaxy M32 is investigated with 0.12 arcsec FWHM H and K images obtained with the Gemini Mauna Kea telescope. Stars with K = 15.5, which are likely evolving near the tip of the asymptotic giant branch (AGB), are resolved to within 2 arcsec of the nucleus, and it is concluded that the peak stellar brightness near the center of M32 is similar to that in the outer regions of the galaxy. Moreover, the projected density of bright AGB stars follows the visible light profile to within 2 arcsec of the nucleus, indicating that the brightest stars are well mixed throughout the galaxy. Thus, there is no evidence for an age gradient, and the radial variations in spectroscopic indices and ultraviolet colors that have been detected previously must be due to metallicity and/or some other parameter. We suggest that either the bright AGB stars formed as part of a highly uniform and coherent galaxy-wide episode of star formation, or they originated in a separate system that merged with M32.Comment: 9 pages of text, 3 figures. ApJ (Letters) in pres

Rapid, reliable, and reproducible molecular sub-grouping of clinical medulloblastoma samples

The diagnosis of medulloblastoma likely encompasses several distinct entities, with recent evidence for the existence of at least four unique molecular subgroups that exhibit distinct genetic, transcriptional, demographic, and clinical features. Assignment of molecular subgroup through routine profiling of high-quality RNA on expression microarrays is likely impractical in the clinical setting. The planning and execution of medulloblastoma clinical trials that stratify by subgroup, or which are targeted to a specific subgroup requires technologies that can be economically, rapidly, reliably, and reproducibly applied to formalin-fixed paraffin embedded (FFPE) specimens. In the current study, we have developed an assay that accurately measures the expression level of 22 medulloblastoma subgroup-specific signature genes (CodeSet) using nanoString nCounter Technology. Comparison of the nanoString assay with Affymetrix expression array data on a training series of 101 medulloblastomas of known subgroup demonstrated a high concordance (Pearson correlation r = 0.86). The assay was validated on a second set of 130 non-overlapping medulloblastomas of known subgroup, correctly assigning 98% (127/130) of tumors to the appropriate subgroup. Reproducibility was demonstrated by repeating the assay in three independent laboratories in Canada, the United States, and Switzerland. Finally, the nanoString assay could confidently predict subgroup in 88% of recent FFPE cases, of which 100% had accurate subgroup assignment. We present an assay based on nanoString technology that is capable of rapidly, reliably, and reproducibly assigning clinical FFPE medulloblastoma samples to their molecular subgroup, and which is highly suited for future medulloblastoma clinical trials

East Midlands Research into Ageing Network (EMRAN) Discussion Paper Series

Academic geriatric medicine in Leicester . There has never been a better time to consider joining us. We have recently appointed a Professor in Geriatric Medicine, alongside Tom Robinson in stroke and Victoria Haunton, who has just joined as a Senior Lecturer in Geriatric Medicine. We have fantastic opportunities to support students in their academic pursuits through a well-established intercalated BSc programme, and routes on through such as ACF posts, and a successful track-record in delivering higher degrees leading to ACL post. We collaborate strongly with Health Sciences, including academic primary care. See below for more detail on our existing academic set-up. Leicester Academy for the Study of Ageing We are also collaborating on a grander scale, through a joint academic venture focusing on ageing, the ‘Leicester Academy for the Study of Ageing’ (LASA), which involves the local health service providers (acute and community), De Montfort University; University of Leicester; Leicester City Council; Leicestershire County Council and Leicester Age UK. Professors Jayne Brown and Simon Conroy jointly Chair LASA and have recently been joined by two further Chairs, Professors Kay de Vries and Bertha Ochieng. Karen Harrison Dening has also recently been appointed an Honorary Chair. LASA aims to improve outcomes for older people and those that care for them that takes a person-centred, whole system perspective. Our research will take a global perspective, but will seek to maximise benefits for the people of Leicester, Leicestershire and Rutland, including building capacity. We are undertaking applied, translational, interdisciplinary research, focused on older people, which will deliver research outcomes that address domains from: physical/medical; functional ability, cognitive/psychological; social or environmental factors. LASA also seeks to support commissioners and providers alike for advice on how to improve care for older people, whether by research, education or service delivery. Examples of recent research projects include: ‘Local History Café’ project specifically undertaking an evaluation on loneliness and social isolation; ‘Better Visits’ project focused on improving visiting for family members of people with dementia resident in care homes; and a study on health issues for older LGBT people in Leicester. Clinical Geriatric Medicine in Leicester We have developed a service which recognises the complexity of managing frail older people at the interface (acute care, emergency care and links with community services). There are presently 17 consultant geriatricians supported by existing multidisciplinary teams, including the largest complement of Advance Nurse Practitioners in the country. Together we deliver Comprehensive Geriatric Assessment to frail older people with urgent care needs in acute and community settings. The acute and emergency frailty units – Leicester Royal Infirmary This development aims at delivering Comprehensive Geriatric Assessment to frail older people in the acute setting. Patients are screened for frailty in the Emergency Department and then undergo a multidisciplinary assessment including a consultant geriatrician, before being triaged to the most appropriate setting. This might include admission to in-patient care in the acute or community setting, intermediate care (residential or home based), or occasionally other specialist care (e.g. cardiorespiratory). Our new emergency department is the county’s first frail friendly build and includes fantastic facilities aimed at promoting early recovering and reducing the risk of hospital associated harms. There is also a daily liaison service jointly run with the psychogeriatricians (FOPAL); we have been examining geriatric outreach to oncology and surgery as part of an NIHR funded study. We are home to the Acute Frailty Network, and those interested in service developments at the national scale would be welcome to get involved. Orthogeriatrics There are now dedicated hip fracture wards and joint care with anaesthetists, orthopaedic surgeons and geriatricians. There are also consultants in metabolic bone disease that run clinics. Community work Community work will consist of reviewing patients in clinic who have been triaged to return to the community setting following an acute assessment described above. Additionally, primary care colleagues refer to outpatients for sub-acute reviews. You will work closely with local GPs with support from consultants to deliver post-acute, subacute, intermediate and rehabilitation care services. Stroke Medicine 24/7 thrombolysis and TIA services. The latter is considered one of the best in the UK and along with the high standard of vascular surgery locally means one of the best performances regarding carotid intervention

'A habitual disposition to the good': on reason, virtue and realism

Amidst the crisis of instrumental reason, a number of contemporary political philosophers including Jürgen Habermas have sought to rescue the project of a reasonable humanism from the twin threats of religious fundamentalism and secular naturalism. In his recent work, Habermas defends a post-metaphysical politics that aims to protect rationality against encroachment while also accommodating religious faith within the public sphere. This paper contends that Habermas’ post-metaphysical project fails to provide a robust alternative either to the double challenge of secular naturalism and religious fundamentalism or to the ruthless instrumentalism that underpins capitalism. By contrast with Habermas and also with the ‘new realism’ of contemporary political philosophers such as Raymond Geuss or Bernard Williams, realism in the tradition of Plato and Aristotle can defend reason against instrumental rationality and blind belief by integrating it with habit, feeling and even faith. Such metaphysical–political realism can help develop a politics of virtue that goes beyond communitarian thinking by emphasising plural modes of association (not merely ‘community’), substantive ties of sympathy and the importance of pursuing goodness and mutual flourishing

On certain infinite extensions of the rationals with Northcott property

A set of algebraic numbers has the Northcott property if each of its subsets of bounded Weil height is finite. Northcott's Theorem, which has many Diophantine applications, states that sets of bounded degree have the Northcott property. Bombieri, Dvornicich and Zannier raised the problem of finding fields of infinite degree with this property. Bombieri and Zannier have shown that \IQ_{ab}^{(d)}, the maximal abelian subfield of the field generated by all algebraic numbers of degree at most $d$, is such a field. In this note we give a simple criterion for the Northcott property and, as an application, we deduce several new examples, e.g. \IQ(2^{1/d_1},3^{1/d_2},5^{1/d_3},7^{1/d_4},11^{1/d_5},...) has the Northcott property if and only if $2^{1/d_1},3^{1/d_2},5^{1/d_3},7^{1/d_4},11^{1/d_5},...$ tends to infinity

Metrics to evaluate research performance in academic institutions: A critique of ERA 2010 as applied in forestry and the indirect H2 index as a possible alternative

Excellence for Research in Australia (ERA) is an attempt by the Australian Research Council to rate Australian universities on a 5-point scale within 180 Fields of Research using metrics and peer evaluation by an evaluation committee. Some of the bibliometric data contributing to this ranking suffer statistical issues associated with skewed distributions. Other data are standardised year-by-year, placing undue emphasis on the most recent publications which may not yet have reliable citation patterns. The bibliometric data offered to the evaluation committees is extensive, but lacks effective syntheses such as the h-index and its variants. The indirect H2 index is objective, can be computed automatically and efficiently, is resistant to manipulation, and a good indicator of impact to assist the ERA evaluation committees and to similar evaluations internationally.Comment: 19 pages, 6 figures, 7 tables, appendice

Proteomic profiling of high risk medulloblastoma reveals functional biology

Genomic characterization of medulloblastoma has improved molecular risk classification but struggles to define functional biological processes, particularly for the most aggressive subgroups. We present here a novel proteomic approach to this problem using a reference library of stable isotope labeled medulloblastoma-specific proteins as a spike-in standard for accurate quantification of the tumor proteome. Utilizing high-resolution mass spectrometry, we quantified the tumor proteome of group 3 medulloblastoma cells and demonstrate that high-risk MYC amplified tumors can be segregated based on protein expression patterns. We cross-validated the differentially expressed protein candidates using an independent transcriptomic data set and further confirmed them in a separate cohort of medulloblastoma tissue samples to identify the most robust proteogenomic differences. Interestingly, highly expressed proteins associated with MYC-amplified tumors were significantly related to glycolytic metabolic pathways via alternative splicing of pyruvate kinase (PKM) by heterogeneous ribonucleoproteins (HNRNPs). Furthermore, when maintained under hypoxic conditions, these MYC-amplified tumors demonstrated increased viability compared to non-amplified tumors within the same subgroup. Taken together, these findings highlight the power of proteomics as an integrative platform to help prioritize genetic and molecular drivers of cancer biology and behavior