BREXIT and the battle for the past. A study of historian's involvement in the Brexit debate

Master's ThesisMAHF-HISHIS35

Predicting, Preparing for, and Creating the Future: What Will Happen to Internal Medicine?

It is the year 2025. During the past 20 years, internal medicine as a discipline continued to become less prestigious, less respected, and more fragmented. As fewer medical students chose internal medicine as a career, residency programs began to close. Those that remained open filled with fewer graduates of US medical schools but filled with more US citizens who graduated from international medical schools, more graduates of osteopathic medical schools, and more foreign graduates of international medical schools. Due to lack of adequate remuneration and a shift of primary care provision from generalist physicians to nurse practitioners and physician assistants, training in general internal medicine as a patient care specialty ceased. Generalist internal medicine careers have been replaced by tracks designed to foster health services research or academic careers; internal medicine training graduates subspecialty physicians. Although the projected collapse of Medicare in 2019 was avoided, severe cuts in federal funding for undergraduate and graduate medical education programs forced medical schools and residency programs to compete for federal funds. As a result, medical school tuition became prohibitive, for-profit health care systems viewed medical education as a significant cost center and chose to limit the size of their residency programs, and community-based training programs could not withstand the financial pressures and closed. The result was a reduced supply of internists. Furthermore, compliance with the regulatory burden imposed by accrediting organizations—such as the Accreditation Council for Graduate Medical Education—drove individuals from sustained careers in education, further impacting the viability of training programs

contribution of individual amino acids within mhc molecule or antigenic peptide to tcr ligand potency

The TCR recognition of peptides bound to MHC class II molecules is highly flexible in some T cells. Although progress has been made in understanding the interactions within the trimolecular complex, to what extent the individual components and their amino acid composition contribute to ligand recognition by individual T cells is not completely understood. We investigated how single amino acid residues influence Ag recognition of T cells by combining several experimental approaches. We defined TCR motifs for CD4+ T cells using peptide synthetic combinatorial libraries in the positional scanning format (PS-SCL) and single amino acid-modified peptide analogues. The similarity of the TCR motifs defined by both methods and the identification of stimulatory antigenic peptides by the PS-SCL approach argue for a contribution of each amino acid residue to the overall potency of the antigenic peptide ligand. In some instances, however, motifs are formed by adjacent amino acids, and their combined influence is superimposed on the overall contribution of each amino acid within the peptide epitope. In contrast to the flexibility of the TCR to interact with different peptides, recognition was very sensitive toward modifications of the MHC-restriction element. Exchanges of just one amino acid of the MHC molecule drastically reduced the number of peptides recognized. The results indicate that a specific MHC molecule not only selects certain peptides, but also is crucial for setting an affinity threshold for TCR recognition, which determines the flexibility in peptide recognition for a given TCR

Understanding context specificity:the effect of contextual factors on clinical reasoning

Background: Situated cognition theory argues that thinking is inextricably situated in a context. In clinical reasoning, this can lead to context specificity: a physician arriving at two different diagnoses for two patients with the same symptoms, findings, and diagnosis but different contextual factors (something beyond case content potentially influencing reasoning). This paper experimentally investigates the presence of and mechanisms behind context specificity by measuring differences in clinical reasoning performance in cases with and without contextual factors. Methods: An experimental study was conducted in 2018-2019 with 39 resident and attending physicians in internal medicine. Participants viewed two outpatient clinic video cases (unstable angina and diabetes mellitus), one with distracting contextual factors and one without. After viewing each case, participants responded to six open-ended diagnostic items (e.g. problem list, leading diagnosis) and rated their cognitive load. Results: Multivariate analysis of covariance (MANCOVA) results revealed significant differences in angina case performance with and without contextual factors [Pillai's trace = 0.72, F=12.4, df=(6, 29), p Conclusions: Using typical presentations of common diagnoses, and contextual factors typical for clinical practice, we provide ecologically valid evidence for the theoretically predicted negative effects of context specificity (i.e. for the angina case), with large effect sizes, offering insight into the persistence of diagnostic error

Fatigue in multiple sclerosis: Associations with clinical, MRI and CSF parameters

Background: Damage of different brain structures has been related to fatigue. Alternatively, functional alterations of central nervous system (CNS) cells by the inflammatory milieu within the CNS may be responsible for the development of fatigue. Aim: To investigate the effect of structural brain damage and inflammatory cerebrospinal fluid (CSF) changes on fatigue in multiple sclerosis (MS). Methods: We determined the association of different clinical, CSF and magnetic resonance imaging (MRI) parameters with prevalence and severity of fatigue, as measured by the Fatigue Scale for Motor and Cognitive Functions in 68 early MS patients (discovery cohort). We validated our findings in two MS cohorts: the MRI validation cohort (N=233) for the clinical and MRI parameters, and the CSF validation cohort (N=81) for the clinical and CSF parameters. Results: Fatigue was associated with clinical disability. Fatigue did not correlate with any CSF parameter but correlated negatively with total and cortical grey matter volume. However, when controlling for Expanded Disability Status Scale (EDSS) in a multivariate model, these associations lost significance. Conclusion: Disability and disease duration best explain fatigue severity but none of the tested MRI or CSF parameter was reliably associated with fatigue

Lesion location across diagnostic regions in multiple sclerosis

Background: Lesions in the periventricular, (juxta)cortical, and infratentorial region, as visible on brain MRI, are part of the diagnostic criteria for Multiple sclerosis (MS) whereas lesions in the subcortical region are currently only a marker of disease activity. It is unknown whether MS lesions follow individual spatial patterns or whether they occur in a random manner across diagnostic regions.Aim: First, to describe cross-sectionally the spatial lesion patterns in patients with MS. Second, to investigate the spatial association of new lesions and lesions at baseline across diagnostic regions. Methods: Experienced neuroradiologists analyzed brain MRI (3D, 3T) in a cohort of 330 early MS patients. Le-sions at baseline and new solitary lesions after two years were segmented (manually and by consensus) and classified as periventricular, (juxta)cortical, or infratentorial (diagnostic regions) or subcortical-with or without Gadolinium-enhancement. Gadolinium enhancement of lesions in the different regions was compared by Chi square test. New lesions in the four regions served as dependent variable in four zero-inflated Poisson models each with the six independent variables of lesions in the four regions at baseline, age and gender.Results: At baseline, lesions were most often observed in the subcortical region (mean 13.0 lesions/patient), while lesion volume was highest in the periventricular region (mean 2287 mu l/patient). Subcortical lesions were less likely to show gadolinium enhancement (3.1 %) than juxtacortical (4.3 %), periventricular (5.3 %) or infra-tentorial lesions (7.2 %). Age was inversely correlated with new periventricular, juxtacortical and subcortical lesions. New lesions in the periventricular, juxtacortical and infratentorial region showed a significant auto -correlative behavior being positively related to the number of lesions in the respective regions at baseline. New lesions in the subcortical region showed a different behavior with a positive association with baseline peri-ventricular lesions and a negative association with baseline infratentorial lesions.Conclusion: Across regions, new lesions do not occur randomly;instead, new lesions in the periventricular, juxtacortical and infratentorial diagnostic region are associated with that at baseline. Lesions in the subcortical regions are more closely related to periventricular lesions. Moreover, subcortical lesions substantially contribute to lesion burden in MS but are less likely to show gadolinium enhancement (than lesions in the diagnostic regions)

Fluorescence and spin properties of defects in single digit nanodiamonds

International audienceThis article reports stable photoluminescence and high-contrast optically detected electron spin resonance (ODESR) from single nitrogen-vacancy (NV) defect centers created within ultrasmall, disperse nanodiamonds of radius less than 4 nm. Unexpectedly, the efficiency for the production of NV fluorescent defects by electron irradiation is found to be independent of the size of the nanocrystals. Fluorescence lifetime imaging shows lifetimes with a mean value of around 17 ns, only slightly longer than the bulk value of the defects. After proper surface cleaning, the dephasing times of the electron spin resonance in the nanocrystals approach values of some microseconds, which is typical for the type Ib diamond from which the nanoparticle is made. We conclude that despite the tiny size of these nanodiamonds the photoactive nitrogen-vacancy color centers retain their bulk properties to the benefit of numerous exciting potential applications in photonics, biomedical labeling, and imaging

Automated segmentation of changes in FLAIR-hyperintense white matter lesions in multiple sclerosis on serial magnetic resonance imaging

Longitudinal analysis of white matter lesion changes on serial MRI has become an important parameter to study diseases with white-matter lesions. Here, we build on earlier work on cross-sectional lesion segmentation;we present a fully automatic pipeline for serial analysis of FLAIR-hyperintense white matter lesions. Our algorithm requires three-dimensional gradient echo T1- and FLAIR- weighted images at 3 Tesla as well as available cross-sectional lesion segmentations of both time points. Preprocessing steps include lesion filling and intrasubject registration. For segmentation of lesion changes, initial lesion maps of different time points are fused;herein changes in intensity are analyzed at the voxel level. Significance of lesion change is estimated by comparison with the difference distribution of FLAIR intensities within normal appearing white matter. The method is validated on MRI data of two time points from 40 subjects with multiple sclerosis derived from two different scanners (20 subjects per scanner). Manual segmentation of lesion increases served as gold standard. Across all lesion increases, voxel-wise Dice coefficient (0.7) as well as lesion-wise detection rate (0.8) and false-discovery rate (0.2) indicate good overall performance. Analysis of scans from a repositioning experiment in a single patient with multiple sclerosis did not yield a single false positive lesion. We also introduce the lesion change plot as a descriptive tool for the lesion change of individual patients with regard to both number and volume. An open source implementation of the algorithm is available at http//www.satastical-modeling.de/lst.html