Medical graduate views on statistical learning needs for clinical practice: a comprehensive survey

BACKGROUND: This paper seeks to contribute to a reputable evidence base for required competencies across different topics in statistics and probability (statistical topics) in preparing medical graduates for clinical practice. This is in order to inform the prioritization of statistical topics within future undergraduate medical curricula, while exploring the need for preparing tomorrow's doctors to be producers, and not merely consumers, of statistics. METHODS: We conducted a comprehensive online survey from July 2013 to August 2014 for a target group of 462 medical graduates with current or prior experience of teaching undergraduate medical students of the University of Edinburgh of whom 278 (60.2%) responded. Statistical topics were ranked by proportion of respondents who identified the practice of statistics, performing statistical procedures or calculations using appropriate data, as a required competency for medical schools to provide in preparing undergraduate medical students for clinical practice. Mixed effects analyses were used to identify potential predictors for selection of the above competency and to compare the likelihood of this selection for a range of statistical topics versus critical appraisal. RESULTS: Evidence was gleaned from medical graduates' experiences of clinical practice for the need for, not only a theoretical understanding of statistics and probability but also, the ability to practice statistics. Nature of employment and statistical topic were highly significant predictors of choice of the practice of statistics as a required competency ((F = 3.777, p < 0.0005) and (F = 45.834, p < 0.0005), respectively). The most popular topic for this competency was graphical presentation of data (84.3% of respondents) in contrast to cross-over trials for the competency understanding the theory only (70.5% of respondents). Several topics were found to be more popular than critical appraisal for competency in the practice of statistics. CONCLUSIONS: The model of medical graduates as mere consumers of statistics is oversimplified. Contrary to what has been suggested elsewhere, statistical learning opportunities in undergraduate medicine should not be restricted to development of critical appraisal skills. Indeed, our findings support development of learning opportunities for undergraduate medical students as producers of statistics across a wide range of statistical topics

Finding binaries from phase modulation of pulsating stars with Kepler: V. Orbital parameters, with eccentricity and mass-ratio distributions of 341 new binaries

The orbital parameters of binaries at intermediate periods (102–103 d) are difficult to measure with conventional methods and are very incomplete. We have undertaken a new survey, applying our pulsation timing method to Kepler light curves of 2224 main-sequence A/F stars and found 341 non-eclipsing binaries. We calculate the orbital parameters for 317 PB1 systems (single-pulsator binaries) and 24 PB2s (double-pulsators), tripling the number of intermediate-mass binaries with full orbital solutions. The method reaches down to small mass ratios q ≈ 0.02 and yields a highly homogeneous sample. We parametrize the mass- ratio distribution using both inversion and Markov-Chain Monte Carlo forward-modelling techniques, and find it to be skewed towards low-mass companions, peaking at q ≈ 0.2. While solar-type primaries exhibit a brown dwarf desert across short and intermediate periods, we find a small but statistically significant (2.6σ ) population of extreme-mass-ratio companions (q 0.1, we measure the binary fraction of current A/F primaries to be 15.4 per cent ± 1.4 per cent, though we find that a large fraction of the companions (21 per cent ± 6 per cent) are white dwarfs in post-mass-transfer systems with primaries that are now blue stragglers, some of which are the progenitors of Type Ia supernovae, barium stars, symbiotics, and related phenomena. Excluding these white dwarfs, we determine the binary fraction of original A/F primaries to be 13.9 per cent ± 2.1 per cent over the same parameter space. Combining our measurements with those in the literature, we find the binary fraction across these periods is a constant 5 per cent for primaries M1 < 0.8 M , but then increases linearly with log M1, demonstrating that natal discs around more massive protostars M1 2: 1M become increasingly more prone to fragmentation. Finally, we find the eccentricity distribution of the main-sequence pairs to be much less eccentric than the thermal distribution

Speech and communication in Parkinson’s disease: a cross-sectional exploratory study in the UK

Objective: To assess associations between cognitive status, intelligibility, acoustics and functional communication in PD. Design: Cross-sectional exploratory study of functional communication, including a within-participants experimental design for listener assessment. Setting: A major academic medical centre in the East of England, UK. Participants: Questionnaire data were assessed for 45 people with Parkinson’s disease (PD), who had self-reported speech or communication difficulties and did not have clinical dementia. Acoustic and listener analyses were conducted on read and conversational speech for 20 people with PD and 20 familiar conversation partner controls without speech, language or cognitive difficulties. Main outcome measures: Functional communication assessed by the Communicative Participation Item Bank (CPIB) and Communicative Effectiveness Survey (CES). Results: People with PD had lower intelligibility than controls for both the read (mean difference 13.7%, p=0.009) and conversational (mean difference 16.2%, p=0.04) sentences. Intensity and pause were statistically significant predictors of intelligibility in read sentences. Listeners were less accurate identifying the intended emotion in the speech of people with PD (14.8% point difference across conditions, p=0.02) and this was associated with worse speaker cognitive status (16.7% point difference, p=0.04). Cognitive status was a significant predictor of functional communication using CPIB (F=8.99, p=0.005, η2 = 0.15) but not CES. Intelligibility in conversation sentences was a statistically significant predictor of CPIB (F=4.96, p=0.04, η2 = 0.19) and CES (F=13.65, p=0.002, η2 = 0.43). Read sentence intelligibility was not a significant predictor of either outcome. Conclusions: Cognitive status was an important predictor of functional communication—the role of intelligibility was modest and limited to conversational and not read speech. Our results highlight the importance of focusing on functional communication as well as physical speech impairment in speech and language therapy (SLT) for PD. Our results could inform future trials of SLT techniques for PD

Light-driven molecular motors embedded in covalent organic frameworks

The incorporation of molecular machines into the backbone of porous framework structures will facilitate nano actuation, enhanced molecular transport, and other out-of-equilibrium host-guest phenomena in well-defined 3D solid materials. In this work, we detail the synthesis of a diamine-based light-driven molecular motor and its incorporation into a series of imine-based polymers and covalent organic frameworks (COF). We study structural and dynamic properties of the molecular building blocks and derived self-assembled solids with a series of spectroscopic, diffraction, and theoretical methods. Using an acid-catalyzed synthesis approach, we are able to obtain the first crystalline 2D COF with stacked hexagonal layers that contains 20 mol% molecular motors. The COF features a specific pore volume and surface area of up to 0.45 cm(3) g(-1) and 604 m(2) g(-1), respectively. Given the molecular structure and bulkiness of the diamine motor, we study the supramolecular assembly of the COF layers and detail stacking disorders between adjacent layers. We finally probe the motor dynamics with in situ spectroscopic techniques revealing current limitations in the analysis of these new materials and derive important analysis and design criteria as well as synthetic access to new generations of motorized porous framework materials

Key Learning Outcomes for Clinical Pharmacology and Therapeutics Education in Europe:A Modified Delphi Study

Harmonizing clinical pharmacology and therapeutics (CPT) education in Europe is necessary to ensure that the prescribing competency of future doctors is of a uniform high standard. As there are currently no uniform requirements, our aim was to achieve consensus on key learning outcomes for undergraduate CPT education in Europe. We used a modified Delphi method consisting of three questionnaire rounds and a panel meeting. A total of 129 experts from 27 European countries were asked to rate 307 learning outcomes. In all, 92 experts (71%) completed all three questionnaire rounds, and 33 experts (26%) attended the meeting. 232 learning outcomes from the original list, 15 newly suggested and 5 rephrased outcomes were included. These 252 learning outcomes should be included in undergraduate CPT curricula to ensure that European graduates are able to prescribe safely and effectively. We provide a blueprint of a European core curriculum describing when and how the learning outcomes might be acquired.</p

Solid State Physics

Contains reports on three research projects

Finding binaries from phase modulation of pulsating stars with Kepler: V. Orbital parameters, with eccentricity and mass-ratio distributions of 341 new binaries

The orbital parameters of binaries at intermediate periods (102-103 d) are difficult to measure with conventional methods and are very incomplete. We have undertaken a new survey, applying our pulsation timing method to Kepler light curves of 2224 main-sequence A/F stars and found 341 non-eclipsing binaries. We calculate the orbital parameters for 317 PB1 systems (single-pulsator binaries) and 24 PB2s (double-pulsators), tripling the number of intermediate-mass binaries with full orbital solutions. The method reaches down to small mass ratios q ≈ 0.02 and yields a highly homogeneous sample. We parametrize the massratio distribution using both inversion and Markov-Chain Monte Carlo forward-modelling techniques, and find it to be skewed towards low-mass companions, peaking at q ≈ 0.2. While solar-type primaries exhibit a brown dwarf desert across short and intermediate periods, we find a small but statistically significant (2.6σ) population of extreme-mass-ratio companions (q [removed] 0.1, we measure the binary fraction of current A/F primaries to be 15.4 percent ± 1.4 per cent, though we find that a large fraction of the companions (21 percent ± 6 per cent) are white dwarfs in post-mass-transfer systems with primaries that are now blue stragglers, some of which are the progenitors of Type Ia supernovae, barium stars, symbiotics, and related phenomena. Excluding these white dwarfs, we determine the binary fraction of original A/F primaries to be 13.9 percent ± 2.1 per cent over the same parameter space. Combining our measurements with those in the literature, we find the binary fraction across these periods is a constant 5 per cent for primaries M1 < 0.8M⊙, but then increases linearly with log M1, demonstrating that natal discs around more massive protostars M1 ≳ 1M⊙ become increasingly more prone to fragmentation. Finally, we find the eccentricity distribution of the main-sequence pairs to be much less eccentric than the thermal distribution

Predictive blood biomarkers and brain changes associated with age-related cognitive decline

Growing evidence supports the use of plasma levels of tau phosphorylated at threonine 181, amyloid-β, neurofilament light and glial fibrillary acidic protein as promising biomarkers for Alzheimer's disease. While these blood biomarkers are promising for distinguishing people with Alzheimer's disease from healthy controls, their predictive validity for age-related cognitive decline without dementia remains unclear. Further, while tau phosphorylated at threonine 181 is a promising biomarker, the distribution of this phospho-epitope of tau in the brain is unknown. Here, we tested whether plasma levels of tau phosphorylated at threonine 181, amyloid-β, neurofilament light and fibrillary acidic protein predict cognitive decline between ages 72 and 82 in 195 participants in the Lothian birth cohorts 1936 study of cognitive ageing. We further examined post-mortem brain samples from temporal cortex to determine the distribution of tau phosphorylated at threonine 181 in the brain. Several forms of tau phosphorylated at threonine 181 have been shown to contribute to synapse degeneration in Alzheimer's disease, which correlates closely with cognitive decline in this form of dementia, but to date, there have not been investigations of whether tau phosphorylated at threonine 181 is found in synapses in Alzheimer's disease or healthy ageing brain. It was also previously unclear whether tau phosphorylated at threonine 181 accumulated in dystrophic neurites around plaques, which could contribute to tau leakage to the periphery due to impaired membrane integrity in dystrophies. Brain homogenate and biochemically enriched synaptic fractions were examined with western blot to examine tau phosphorylated at threonine 181 levels between groups (n = 10-12 per group), and synaptic and astrocytic localization of tau phosphorylated at threonine 181 were examined using array tomography (n = 6-15 per group), and localization of tau phosphorylated at threonine 181 in plaque-associated dystrophic neurites with associated gliosis were examined with standard immunofluorescence (n = 8-9 per group). Elevated baseline plasma tau phosphorylated at threonine 181, neurofilament light and fibrillary acidic protein predicted steeper general cognitive decline during ageing. Further, increasing tau phosphorylated at threonine 181 over time predicted general cognitive decline in females only. Change in plasma tau phosphorylated at threonine 181 remained a significant predictor of g factor decline when taking into account Alzheimer's disease polygenic risk score, indicating that the increase of blood tau phosphorylated at threonine 181 in this cohort was not only due to incipient Alzheimer's disease. Tau phosphorylated at threonine 181 was observed in synapses and astrocytes in both healthy ageing and Alzheimer's disease brain. We observed that a significantly higher proportion of synapses contain tau phosphorylated at threonine 181 in Alzheimer's disease relative to aged controls. Aged controls with pre-morbid lifetime cognitive resilience had significantly more tau phosphorylated at threonine 181 in fibrillary acidic protein-positive astrocytes than those with pre-morbid lifetime cognitive decline. Further, tau phosphorylated at threonine 181 was found in dystrophic neurites around plaques and in some neurofibrillary tangles. The presence of tau phosphorylated at threonine 181 in plaque-associated dystrophies may be a source of leakage of tau out of neurons that eventually enters the blood. Together, these data indicate that plasma tau phosphorylated at threonine 181, neurofilament light and fibrillary acidic protein may be useful biomarkers of age-related cognitive decline, and that efficient clearance of tau phosphorylated at threonine 181 by astrocytes may promote cognitive resilience