•We propose a generic pipeline for estimating movement impairment severity scores using body or hand skeletons and classify them into clinical scores.•We assess the inter-rater reliability of ...multiple ratings from 3 different raters and propose a pipeline to learn clinical score estimation under uncertainty.•We extend our model via the Rater Confusion Estimation framework trained by our novel ordinal focal loss, with the addition of an explicit simplex projection for learning.•We present saliency visualizations to stratify the contribution of separate body joints to the estimation of MDS-UPDRS scores.
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Parkinson’s disease (PD) is a brain disorder that primarily affects motor function, leading to slow movement, tremor, and stiffness, as well as postural instability and difficulty with walking/balance. The severity of PD motor impairments is clinically assessed by part III of the Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), a universally-accepted rating scale. However, experts often disagree on the exact scoring of individuals. In the presence of label noise, training a machine learning model using only scores from a single rater may introduce bias, while training models with multiple noisy ratings is a challenging task due to the inter-rater variabilities. In this paper, we introduce an ordinal focal neural network to estimate the MDS-UPDRS scores from input videos, to leverage the ordinal nature of MDS-UPDRS scores and combat class imbalance. To handle multiple noisy labels per exam, the training of the network is regularized via rater confusion estimation (RCE), which encodes the rating habits and skills of raters via a confusion matrix. We apply our pipeline to estimate MDS-UPDRS test scores from their video recordings including gait (with multiple Raters, R=3) and finger tapping scores (single rater). On a sizable clinical dataset for the gait test (N=55), we obtained a classification accuracy of 72% with majority vote as ground-truth, and an accuracy of ∼84% of our model predicting at least one of the raters’ scores. Our work demonstrates how computer-assisted technologies can be used to track patients and their motor impairments, even when there is uncertainty in the clinical ratings. The latest version of the code will be available at https://github.com/mlu355/PD-Motor-Severity-Estimation.
Neuronal circuit asymmetries are important components of brain circuits, but the molecular pathways leading to their establishment remain unknown. Here we found that the mutation of FRMD7, a gene ...that is defective in human congenital nystagmus, leads to the selective loss of the horizontal optokinetic reflex in mice, as it does in humans. This is accompanied by the selective loss of horizontal direction selectivity in retinal ganglion cells and the transition from asymmetric to symmetric inhibitory input to horizontal direction-selective ganglion cells. In wild-type retinas, we found FRMD7 specifically expressed in starburst amacrine cells, the interneuron type that provides asymmetric inhibition to direction-selective retinal ganglion cells. This work identifies FRMD7 as a key regulator in establishing a neuronal circuit asymmetry, and it suggests the involvement of a specific inhibitory neuron type in the pathophysiology of a neurological disease.
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•FRMD7 is required for the horizontal optokinetic reflex in mice as in humans•Horizontal direction selectivity is lost in the retina of FRMD7 mutant mice•Asymmetry of inhibitory inputs to horizontal DS cells is lost in FRMD7 mutant mice•FRMD7 is expressed in ChAT-expressing cells in the retina of mice and primates
Yonehara et al. show that FRMD7, a gene that is defective in human congenital nystagmus, is required in the mouse retina to establish spatially asymmetric inhibitory inputs from starburst cells to horizontal direction-selective ganglion cells.
1255 cases of leukemia-lymphoma were tested between 1972 and 1984 by multiple marker analysis. Routine leukemia phenotyping was performed using standard morphological and cytochemical techniques in ...combination with clinical and histo-pathological information; the main emphasis was put on immunological surface marker analysis using erythrocyte rosette assays, TdT and a large panel of poly- and monoclonal antibody tests. The 1255 cases were divided into these major types and subtypes: 349 cases of ALL and related immature T- and Burkitt-lymphomas (cALL, pre B-ALL, B-ALL and Burkitt-lymphomas, T-ALL and immature, mostly leukemic T-lymphomas, Null-ALL), 454 cases of mature T- and B-cell malignancies (T-CLL, mycosis fungoides, Sezary-syndrome, T-lymphomas, B-CLL, hairy cell leukemia, multiple myeloma, B-lymphomas), 263 cases of acute myeloid leukemias (AML, AMMoL/AMoL), 182 cases of chronic myeloid leukemias (CML in chronic phase, CMoL, CML in blast crisis), 6 cases of erythroleukemia and 1 case of megakaryoblastic leukemia. A simplified classification scheme which has been used in our laboratories is presented. Phenotyping is of diagnostic, prognostic and therapeutic relevance, most evidently for patients with ALL. Routine leukemia phenotyping should be performed with highly standardized techniques and reagents and by combining information from several fields in the multiple marker analysis. New areas of leukemia research might become very useful for the routine procedure of phenotyping.
Medical residents are key figures in delivering care and an important target group for patient safety education. The objective of this study was to assess residents' intentions and actions concerning ...patient safety improvement after patient safety education.
Four multi-specialty 2-day patient safety courses were organized, in which residents from five Dutch hospitals participated. At the end of these courses participants were asked to formulate an action point to improve patient safety. Three months later semi-structured interviews were conducted to reveal actions that were taken, factors that had influenced their behaviour and reactions concerning the education. An inductive theory approach was used to analyze transcriptions.
Out of 71 participants, sixty-nine (97%) residents were interviewed. In total they had formulated 91 action points, which mainly focused on: 'Improving organization of own work/Follow policies' and 'Improving culture/Educating colleagues about patient safety'. Sixty-two (90%) residents declared to have taken action, and 50 (55%) action points were fully carried out. Most actions taken were at the level of the individual professional, rather than at the level of their social or organizational context. Results of actions included adjusting the structure of their own work, organizing patient safety education for colleagues, communicating more efficiently and in a more structured way with colleagues, and reporting incidents. Promoters for action included: 'Awareness of the importance of the action to be taken', 'Supportive attitude of colleagues' and 'Having received patient safety education'. Barriers included: 'Impeding attitude of colleagues', 'High work-pressure', 'Hierarchy' and 'Switching of work stations'.
After patient safety training, residents reported various intentions to contribute to patient safety improvement. Numerous actions were taken, but there still is a discrepancy between intentions and actual behaviour. To increase residents' participation in patient safety improvement, educational efforts should be supplemented with actions to remove experienced barriers, most of which are related to the residents' social and organizational context.
A well-characterized monoclonal antibody against human lysosomal alpha-glucosidase has been used for the immunohistochemical localization of the enzyme in cultured human skin fibroblasts. Under ...conditions that are routinely used for the preparation of cells for immunocytochemistry, this monoclonal antibody does not react with acid alpha-glucosidase but in contrast with components of the cytoskeleton. Double-labelling experiments with the monoclonal antibody and rabbit anti-vimentin antiserum identified the cytoskeletal components as intermediate filaments. The implications of this observation for the use of monoclonal antibodies in immunocytochemistry in general are discussed.
The authors compared leg stiffness (K
VERT
), muscle activation, and joint movement patterns between 11 men and 10 women during hopping. Physically active and healthy men and women performed ...continuous 2-legged hopping at their preferred rate and at 3.0 Hz. Compared with men, women demonstrated decreased K
VERT
; however, after the authors normalized for body mass, gender differences in K
VERT
were eliminated. In comparison with men, women also demonstrated increased quadriceps and soleus activity, as well as greater quadriceps-to-hamstrings coactivation ratios. There were no significant gender differences for joint movement patterns (p >.05). The relationship between the observed gender differences in muscle recruitment and the increased risk of anterior cruciate ligament injury in women requires further study.
To identify rate-limiting steps in T cell-independent type 2 antibody production against polysaccharide antigens, we performed a genome-wide screen by immunizing several hundred pedigrees of C57BL/6 ...mice segregating N-ethyl-N-nitrosurea-induced mis-sense mutations. Two independent mutations, Tilcara and Untied, were isolated that semi-dominantly diminished antibody against polysaccharide but not protein antigens. Both mutations resulted from single-amino-acid substitutions within the kinase domain of protein kinase C-β (PKCβ). In Tilcara, a Ser552>Pro mutation occurred in helix G, in close proximity to a docking site for the inhibitory N-terminal pseudosubstrate domain of the enzyme, resulting in almost complete loss of active, autophosphorylated PKCβI, whereas the amount of alternatively spliced PKCβII protein was not markedly reduced. Circulating B cell subsets were normal and acute responses to B-cell receptor stimulation such as CD25 induction and initiation of DNA synthesis were only measurably diminished in Tilcara homozygotes, whereas the fraction of cells that had divided multiple times was decreased to an intermediate degree in heterozygotes. These results, coupled with evidence of numerous mis-sense PRKCB mutations in the human genome, identify Prkcb as a genetically sensitive step likely to contribute substantially to population variability in anti-polysaccharide antibody levels.
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