Predictive Modeling for Diagnostic Tests with High Specificity, but Low Sensitivity: A Study of the Glycerol Test in Patients with Suspected Menière’s Disease

A high specificity does not ensure that the expected benefit of a diagnostic test outweighs its cost. Problems arise, in particular, when the investigation is expensive, the prevalence of a positive test result is relatively small for the candidate patients, and the sensitivity of the test is low so that the information provided by a negative result is virtually negligible. The consequence may be that a potentially useful test does not gain broader acceptance. Here we show how predictive modeling can help to identify patients for whom the ratio of expected benefit and cost reaches an acceptable level so that testing these patients is reasonable even though testing all patients might be considered wasteful. Our application example is based on a retrospective study of the glycerol test, which is used to corroborate a suspected diagnosis of Menière’s disease. Using the pretest hearing thresholds at up to 10 frequencies, predictions were made by K-nearest neighbor classification or logistic regression. Both methods estimate, based on results from previous patients, the posterior probability that performing the considered test in a new patient will have a positive outcome. The quality of the prediction was evaluated using leave-one-out cross-validation, making various assumptions about the costs and benefits of testing. With reference to all 356 cases, the probability of a positive test result was almost 0.4. For subpopulations selected by K-nearest neighbor classification, which was clearly superior to logistic regression, this probability could be increased up to about 0.6. Thus, the odds of a positive test result were more than doubled

Thermodynamic Model of a Very High Efficiency Power Plant Based on a Biomass Gasifier, SOFCs, and a Gas Turbine

Thermodynamic calculations with a power plant based on a biomass gasifier, SOFCs and a gas turbine are presented. The SOFC anode off-gas which mainly consists of steam and carbon dioxides used as a gasifying agent leading to an allothermal gasification process for which heat is required. Implementation of heat pipes between the SOFC and the gasifier using two SOFC stacks and intercooling the fuel and the cathode streams in between them has shown to be a solution on one hand to drive the allothermal gasification process and on the other hand to cool down the SOFC. It is seen that this helps to reduce the exergy losses in the system significantly. With such a system, electrical efficiency around 73% is shown as achievable

Musculoskeletal sonography in juvenile systemic lupus erythematosus

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Mimicking human neuronal pathways in silico: an emergent model on the effective connectivity

International audienceWe present a novel computational model that detects temporal configurations of a given human neuronal pathway and constructs its artificial replication. This poses a great challenge since direct recordings from individual neurons are impossible in the human central nervous system and therefore the underlying neuronal pathway has to be considered as a black box. For tackling this challenge, we used a branch of complex systems modeling called artificial self-organization in which large sets of software entities interacting locally give rise to bottom-up collective behaviors. The result is an emergent model where each software entity represents an integrate-and-fire neuron. We then applied the model to the reflex responses of single motor units obtained from conscious human subjects. Experimental results show that the model recovers functionality of real human neuronal pathways by comparing it to appropriate surrogate data. What makes the model promising is the fact that, to the best of our knowledge, it is the first realistic model to self-wire an artificial neuronal network by efficiently combining neuroscience with artificial self-organization. Although there is no evidence yet of the model's connectivity mapping onto the human connectivity, we anticipate this model will help neuroscientists to learn much more about human neuronal networks, and could also be used for predicting hypotheses to lead future experiments

Window opening effects on structural behaviour of historical masonry Fatih Mosque

YesStructural walls of old historical structures are either blind or have openings for functional requirements. It is well known that in and out of plane responses of structural walls are affected by the size, locations, and arrangements of such openings. The purpose of this investigation is to study the window opening effects on static and seismic behaviors of historical masonry old mosques. Fatih Mosque, which was converted from a church, constructed in 914 in Trabzon, Turkey, is selected for this purpose. The mosque is being restored. Structural exterior walls of the mosque were made using stone and mortar materials. When the plaster on the walls was removed during the restoration, 12 window openings were found as blind on the exterior structural walls of the mosque. Within the scope of restoration works, it is aimed to open such blind windows. In order to investigate the effects of the window openings on the structural behavior of the mosque, 3D solid and finite elements models of the mosque with and without window openings are initially developed. The experimental dynamic characteristics such as frequency, damping ratio, and mode shapes of the current situation of the mosque, where some windows openings are blind, are determined using Ambient Vibration Testing. Then, the finite element model of the current situation of the mosque is updated using the experimental dynamic characteristics. The static and seismic time history analyses of the updated finite element model with and without window openings are carried out. Structural behaviors of the mosque with and without window openings are compared considering displacement and stress propagations

Elevated levels of MMP12 sourced from macrophages are associated with poor prognosis in urothelial bladder cancer

Abstract Background Urothelial bladder cancer is most frequently diagnosed at the non-muscle-invasive stage (NMIBC). However, recurrences and interventions for intermediate and high-risk NMIBC patients impact the quality of life. Biomarkers for patient stratification could help to avoid unnecessary interventions whilst indicating aggressive measures when required. Methods In this study, immuno-oncology focused, multiplexed proximity extension assays were utilised to analyse plasma (n = 90) and urine (n = 40) samples from 90 newly-diagnosed and treatment-naïve bladder cancer patients. Public single-cell RNA-sequencing and microarray data from patient tumour tissues and murine OH-BBN-induced urothelial carcinomas were also explored to further corroborate the proteomic findings. Results Plasma from muscle-invasive, urothelial bladder cancer patients displayed higher levels of MMP7 (p = 0.028) and CCL23 (p = 0.03) compared to NMIBC patients, whereas urine displayed higher levels of CD27 (p = 0.044) and CD40 (p = 0.04) in the NMIBC group by two-sided Wilcoxon rank-sum tests. Random forest survival and multivariable regression analyses identified increased MMP12 plasma levels as an independent marker (p < 0.001) associated with shorter overall survival (HR = 1.8, p < 0.001, 95% CI:1.3–2.5); this finding was validated in an independent patient OLINK cohort, but could not be established using a transcriptomic microarray dataset. Single-cell transcriptomics analyses indicated tumour-infiltrating macrophages as a putative source of MMP12. Conclusions The measurable levels of tumour-localised, immune-cell-derived MMP12 in blood suggest MMP12 as an important biomarker that could complement histopathology-based risk stratification. As MMP12 stems from infiltrating immune cells rather than the tumor cells themselves, analyses performed on tissue biopsy material risk a biased selection of biomarkers produced by the tumour, while ignoring the surrounding microenvironment

Lifli Betonun Çekme Dayanımı Üzerindeki Boyut Etkisinin Üçgen Plaka Deney Yöntemi İle Belirlenmesi

Boyut etkisi betonun kırılma mekaniğinin önemli bir uygulamasıdır. Yapılan çalışmaların çoğu tek eksenli gerilme durumunu veren numuneler kullanılarak gerçekleştirilmiştir. Ancak döşeme, kaldırım ve beton yol gibi yaygın olarak kullanılan beton yapılar genellikle çok eksenli gerilme durumlarına maruz kalmaktadır. Dolayısıyla yapı malzemelerinin çok eksenli çekme dayanımlarının belirlenmesi yapı elemanlarının tasarımında önemli rol oynamaktadır. Bu çalışmada çelik lifli betonların iki eksenli eğilmede çekme dayanımı üzerinde boyut etkisinin üçgen plaka yöntemi kullanılarak belirlenmasi amaçlanmıştır. Bu amaç doğrultusunda, 0,42 su çimento oranına sahip ve numune kalınlık/kenarortay (t/r) oranı sabit tutularak farklı boyutlarda çelik lif içeren harç numuneleri hazırlanmıştır. Karışımda hacimce %1 oranında iki ucu kancalı çelik lif katılarak toplamda 5 farklı boyutta 15 adet üçgen plaka kalıpları içinde üretilmiştir. Üretilen numuneler 28 gün standart koşullarda kür edilmiştir. Kürlenen numuneler üzerinde üçgen plaka deneyleri yapılmıştır. Deneylerden elde edilen veriler üzerinde boyut etkisi analizleri yapılmış olup boyut etkisi eğrileri çizilmiştir. Sonuç olarak üçgen plaka numunelerin kalınlığı (t) arttığında kırılma yükleri artarken gerilmelerin azaldığı gözlemlenmiştir. Üçgen plaka yönteminin çelik lifli betonların iki yönlü çekme dayanımı üzerindeki boyut etkisini ve kırılma davranışını belirlemede alternatif bir deney yönetimi olarak kullanılabileceği sonucuna ulaşılmıştır

Exploring the receptor origin of vibration-induced reflexes

STUDY DESIGN: An experimental design. OBJECTIVES: The aim of this study was to determine the latencies of vibration-induced reflexes in individuals with and without spinal cord injury (SCI), and to compare these latencies to identify differences in reflex circuitries. SETTING: A tertiary rehabilitation center in Istanbul. METHODS: Seventeen individuals with chronic SCI (SCI group) and 23 participants without SCI (Control group) were included in this study. Latency of tonic vibration reflex (TVR) and whole-body vibration-induced muscular reflex (WBV-IMR) of the left soleus muscle was tested for estimating the reflex origins. The local tendon vibration was applied at six different vibration frequencies (50, 85, 140, 185, 235, and 265 Hz), each lasting for 15 s with 3-s rest intervals. The WBV was applied at six different vibration frequencies (35, 37, 39, 41, 43, and 45 Hz), each lasting for 15 s with 3-s rest intervals. RESULTS: Mean (SD) TVR latency was 39.7 (5.3) ms in the SCI group and 35.9 (2.7) ms in the Control group with a mean (95% CI) difference of -3.8 (-6.7 to -0.9) ms. Mean (SD) WBV-IMR latency was 45.8 (7.4) ms in the SCI group and 43.3 (3.0) ms in the Control group with a mean (95% CI) difference of -2.5 (-6.5 to 1.4) ms. There were significant differences between TVR latency and WBV-IMR latency in both the groups (mean (95% CI) difference; -6.2 (-9.3 to -3.0) ms, p = 0.0001 for the SCI group and -7.4 (-9.3 to -5.6) ms, p = 0.011 for Control group). CONCLUSIONS: The results suggest that the receptor of origin of TVR and WBV-IMR may be different

Does primary brachial plexus surgery alter palliative tendon transfer surgery outcomes in children with obstetric paralysis?

<p>Abstract</p> <p>Background</p> <p>The surgical management of obstetrical brachial plexus palsy can generally be divided into two groups; early reconstructions in which the plexus or affected nerves are addressed and late or palliative reconstructions in which the residual deformities are addressed. Tendon transfers are the mainstay of palliative surgery. Occasionally, surgeons are required to utilise already denervated and subsequently reinnervated muscles as motors. This study aimed to compare the outcomes of tendon transfers for residual shoulder dysfunction in patients who had undergone early nerve surgery to the outcomes in patients who had not.</p> <p>Methods</p> <p>A total of 91 patients with obstetric paralysis-related shoulder abduction and external rotation deficits who underwent a modified Hoffer transfer of the latissimus dorsi/teres major to the greater tubercle of the humerus tendon between 2002 and 2009 were retrospectively analysed. The patients who had undergone neural surgery during infancy were compared to those who had not in terms of their preoperative and postoperative shoulder abduction and external rotation active ranges of motion.</p> <p>Results</p> <p>In the early surgery groups, only the postoperative external rotation angles showed statistically significant differences (25 degrees and 75 degrees for total and upper type palsies, respectively). Within the palliative surgery-only groups, there were no significant differences between the preoperative and postoperative abduction and external rotation angles. The significant differences between the early surgery groups and the palliative surgery groups with total palsy during the preoperative period diminished postoperatively (p < 0.05 and p > 0.05, respectively) for abduction but not for external rotation. Within the upper type palsy groups, there were no significant differences between the preoperative and postoperative abduction and external rotation angles.</p> <p>Conclusions</p> <p>In this study, it was found that in patients with total paralysis, satisfactory shoulder abduction values can be achieved with tendon transfers regardless of a previous history of neural surgery even if the preoperative values differ.</p