Regression models for analyzing radiological visual grading studies – an empirical comparison

Background: For optimizing and evaluating image quality in medical imaging, one can use visual grading experiments, where observers rate some aspect of image quality on an ordinal scale. To analyze the grading data, several regression methods are available, and this study aimed at empirically comparing such techniques, in particular when including random effects in the models, which is appropriate for observers and patients. Methods: Data were taken from a previous study where 6 observers graded or ranked in 40 patients the image quality of four imaging protocols, differing in radiation dose and image reconstruction method. The models tested included linear regression, the proportional odds model for ordinal logistic regression, the partial proportional odds model, the stereotype logistic regression model and rank-order logistic regression (for ranking data). In the first two models, random effects as well as fixed effects could be included; in the remaining three, only fixed effects. Results: In general, the goodness of fit (AIC and McFaddens Pseudo R-2) showed small differences between the models with fixed effects only. For the mixed-effects models, higher AIC and lower Pseudo R-2 was obtained, which may be related to the different number of parameters in these models. The estimated potential for dose reduction by new image reconstruction methods varied only slightly between models. Conclusions: The authors suggest that the most suitable approach may be to use ordinal logistic regression, which can handle ordinal data and random effects appropriately

Machine Learning Models that Remember Too Much

Machine learning (ML) is becoming a commodity. Numerous ML frameworks and services are available to data holders who are not ML experts but want to train predictive models on their data. It is important that ML models trained on sensitive inputs (e.g., personal images or documents) not leak too much information about the training data. We consider a malicious ML provider who supplies model-training code to the data holder, does not observe the training, but then obtains white- or black-box access to the resulting model. In this setting, we design and implement practical algorithms, some of them very similar to standard ML techniques such as regularization and data augmentation, that "memorize" information about the training dataset in the model yet the model is as accurate and predictive as a conventionally trained model. We then explain how the adversary can extract memorized information from the model. We evaluate our techniques on standard ML tasks for image classification (CIFAR10), face recognition (LFW and FaceScrub), and text analysis (20 Newsgroups and IMDB). In all cases, we show how our algorithms create models that have high predictive power yet allow accurate extraction of subsets of their training data

Brief International Cognitive Assessment for MS (BICAMS): International Standards for Validation

An international expert consensus committee recently recommended a brief battery of tests for cognitive evaluation in multiple sclerosis. The Brief International Cognitive Assessment for MS (BICAMS) battery includes tests of mental processing speed and memory. Recognizing that resources for validation will vary internationally, the committee identified validation priorities, to facilitate international acceptance of BICAMS. Practical matters pertaining to implementation across different languages and countries were discussed. Five steps to achieve optimal psychometric validation were proposed. In Step 1, test stimuli should be standardized for the target culture or language under consideration. In Step 2, examiner instructions must be standardized and translated, including all information from manuals necessary for administration and interpretation. In Step 3, samples of at least 65 healthy persons should be studied for normalization, matched to patients on demographics such as age, gender and education. The objective of Step 4 is test-retest reliability, which can be investigated in a small sample of MS and/or healthy volunteers over 1–3 weeks. Finally, in Step 5, criterion validity should be established by comparing MS and healthy controls. At this time, preliminary studies are underway in a number of countries as we move forward with this international assessment tool for cognition in MS

Association between amygdala reactivity and a dopamine transporter gene polymorphism

Essential for detection of relevant external stimuli and for fear processing, the amygdala is under modulatory influence of dopamine (DA). The DA transporter (DAT) is of fundamental importance for the regulation of DA transmission by mediating reuptake inactivation of extracellular DA. This study examined if a common functional variable number tandem repeat polymorphism in the 3′ untranslated region of the DAT gene (SLC6A3) influences amygdala function during the processing of aversive emotional stimuli. Amygdala reactivity was examined by comparing regional cerebral blood flow, measured with positron emission tomography and [15O]water, during exposure to angry and neutral faces, respectively, in a Swedish sample comprising 32 patients with social anxiety disorder and 17 healthy volunteers. In a separate US sample, comprising 85 healthy volunteers studied with blood oxygen level-dependent functional magnetic resonance imaging, amygdala reactivity was assessed by comparing the activity during exposure to threatening faces and neutral geometric shapes, respectively. In both the Swedish and the US sample, 9-repeat carriers displayed higher amygdala reactivity than 10-repeat homozygotes. The results suggest that this polymorphism contributes to individual variability in amygdala reactivity

Assessment of low-dose cisplatin as a model of nausea and emesis in beagle dogs, potential for repeated administration

Cisplatin is a highly emetogenic cancer chemotherapy agent, which is often used to induce nausea and emesis in animal models. The cytotoxic properties of cisplatin also cause adverse events that negatively impact on animal welfare preventing repeated administration of cisplatin. In this study, we assessed whether a low (subclinical) dose of cisplatin could be utilized as a model of nausea and emesis in the dog while decreasing the severity of adverse events to allow repeated administration. The emetic, nausea-like behavior and potential biomarker response to both the clinical dose (70 mg/m2) and low dose (15 mg/m2) of cisplatin was assessed. Plasma creatinine concentrations and granulocyte counts were used to assess adverse effects on the kidneys and bone marrow, respectively. Nausea-like behavior and emesis was induced by both doses of cisplatin, but the latency to onset was greater in the low-dose group. No significant change in plasma creatinine was detected for either dose groups. Granulocytes were significantly reduced compared with baseline (P = 0.000) following the clinical, but not the low-dose cisplatin group. Tolerability of repeated administration was assessed with 4 administrations of an 18 mg/m2 dose cisplatin. Plasma creatinine did not change significantly. Cumulative effects on the granulocytes occurred, they were significantly decreased (P = 0.03) from baseline at 3 weeks following cisplatin for the 4th administration only. Our results suggest that subclinical doses (15 and 18 mg/m2) of cisplatin induce nausea-like behavior and emesis but have reduced adverse effects compared with the clinical dose allowing for repeated administration in crossover studies

Metabolically exaggerated cardiac reactions to acute psychological stress: The effects of resting blood pressure status and possible underlying mechanisms

The study aimed to: confirm that acute stress elicits metabolically exaggerated increases in cardiac activity; test whether individuals with elevated resting blood pressure show more exaggerated cardiac reactions to stress than those who are clearly normotensive; and explore the underlying mechanisms. Cardiovascular activity and oxygen consumption were measured pre-, during, and post- mental stress, and during graded submaximal cycling exercise in 11 young men with moderately elevated resting blood pressure and 11 normotensives. Stress provoked increases in cardiac output that were much greater than would be expected from contemporary levels of oxygen consumption. Exaggerated cardiac reactions were larger in the relatively elevated blood pressure group. They also had greater reductions in total peripheral resistance, but not heart rate variability, implying that their more exaggerated cardiac reactions reflected greater β-adrenergic activation

Система дистанційної освіти та її захист

BACKGROUND: It is currently unknown whether early immunomodulatory treatment in relapsing-remitting MS (RRMS) can delay the transition to secondary progression (SP). OBJECTIVE: To compare the time interval from onset to SP in patients with RRMS between a contemporary cohort, treated with first generation disease modifying drugs (DMDs), and a historical control cohort. METHODS: We included a cohort of contemporary RRMS patients treated with DMDs, obtained from the Swedish National MS Registry (disease onset between 1995-2004, n = 730) and a historical population-based incidence cohort (onset 1950-64, n = 186). We retrospectively analyzed the difference in time to SP, termed the "period effect" within a 12-year survival analysis, using Kaplan-Meier and Cox regression analysis. RESULTS: We found that the "period" affected the entire severity spectrum. After adjusting for onset features, which were weaker in the contemporary material, as well as the therapy initiation time, the DMD-treated patients still exhibited a longer time to SP than the controls (hazard ratios: men, 0.32; women, 0.53). CONCLUSION: Our results showed there was a longer time to SP in the contemporary subjects given DMD. Our analyses suggested that this effect was not solely driven by the inclusion of benign cases, and it was at least partly due to the long-term immunomodulating therapy given

Association between renin and atherosclerotic burden in subjects with and without type 2 diabetes.

Published onlineJournal ArticleThis is the final version of the article. Available from BioMed Central via the DOI in this record.BACKGROUND: Activation of the renin-angiotensin-aldosterone-system (RAAS) has been proposed to contribute to development of vascular complications in type 2 diabetes (T2D). The aim of the present study was to determine if plasma renin levels are associated with the severity of vascular changes in subjects with and without T2D. METHODS: Renin was analyzed by the Proximity Extension Assay in subjects with (n = 985) and without (n = 515) T2D participating in the SUMMIT (SUrrogate markers for Micro- and Macro-vascular hard endpoints for Innovative diabetes Tools) study and in 205 carotid endarterectomy patients. Vascular changes were assessed by determining ankle-brachial pressure index (ABPI), carotid intima-media thickness (IMT), carotid plaque area, pulse wave velocity (PWV) and the reactivity hyperemia index (RHI). RESULTS: Plasma renin was elevated in subjects with T2D and demonstrated risk factor-independent association with prevalent cardiovascular disease both in subjects with and without T2D. Renin levels increased with age, body mass index, HbA1c and correlated inversely with HDL. Subjects with T2D had more severe carotid disease, increased arterial stiffness, and impaired endothelial function. Risk factor-independent associations between renin and APBI, bulb IMT, carotid plaque area were observed in both T2D and non-T2D subjects. These associations were independent of treatment with RAAS inhibitors. Only weak associations existed between plasma renin and the expression of pro-inflammatory and fibrous components in plaques from 205 endarterectomy patients. CONCLUSIONS: Our findings provide clinical evidence for associations between systemic RAAS activation and atherosclerotic burden and suggest that this association is of particular importance in T2D.Innovative Medicines Initiative (the SUMMIT consortium, IMI-2008/115006, the Swedish Heart-Lung Foundation, the Swedish Research Council and Marianne and Marcus Wallenberg Foundation)