DNA Methylation-Guided Prediction of Clinical Failure in High-Risk Prostate Cancer.

BACKGROUND Prostate cancer (PCa) is a very heterogeneous disease with respect to clinical outcome. This study explored differential DNA methylation in a priori selected genes to diagnose PCa and predict clinical failure (CF) in high-risk patients. METHODS A quantitative multiplex, methylation-specific PCR assay was developed to assess promoter methylation of the APC, CCND2, GSTP1, PTGS2 and RARB genes in formalin-fixed, paraffin-embedded tissue samples from 42 patients with benign prostatic hyperplasia and radical prostatectomy specimens of patients with high-risk PCa, encompassing training and validation cohorts of 147 and 71 patients, respectively. Log-rank tests, univariate and multivariate Cox models were used to investigate the prognostic value of the DNA methylation. RESULTS Hypermethylation of APC, CCND2, GSTP1, PTGS2 and RARB was highly cancer-specific. However, only GSTP1 methylation was significantly associated with CF in both independent high-risk PCa cohorts. Importantly, trichotomization into low, moderate and high GSTP1 methylation level subgroups was highly predictive for CF. Patients with either a low or high GSTP1 methylation level, as compared to the moderate methylation groups, were at a higher risk for CF in both the training (Hazard ratio [HR], 3.65; 95% CI, 1.65 to 8.07) and validation sets (HR, 4.27; 95% CI, 1.03 to 17.72) as well as in the combined cohort (HR, 2.74; 95% CI, 1.42 to 5.27) in multivariate analysis. CONCLUSIONS Classification of primary high-risk tumors into three subtypes based on DNA methylation can be combined with clinico-pathological parameters for a more informative risk-stratification of these PCa patients.

Registration And Visualisation Of Deformation Maps From Terrestrial Radar Interferometry Using Photogrammetry And Structure From Motion

This paper describes a general workflow for the registration of terrestrial radar interferometric data with 3D point clouds derived from terrestrial photogrammetry and structure from motion. After the determination of intrinsic and extrinsic orientation parameters, data obtained by terrestrial radar interferometry were projected on point clouds and then on the initial photographs. Visualisation of slope deformation measurements on photographs provides an easily understandable and distributable information product, especially of inaccessible target areas such as steep rock walls or in rockfall run-out zones. The suitability and error propagation of the referencing steps and final visualisation of four approaches are compared: (a) the classic approach using a metric camera and stereo-image photogrammetry; (b) images acquired with a metric camera, automatically processed using structure from motion; (c) images acquired with a digital compact camera, processed with structure from motion; and (d) a markerless approach, using images acquired with a digital compact camera using structure from motion without artificial ground control points. The usability of the completely markerless approach for the visualisation of high-resolution radar interferometry assists the production of visualisation products for interpretation.

Consciousness and choking in visually-guided actions

Choking under pressure describes the phenomenon of people performing well below their expected standard under circumstances where optimal performance is crucial. One of the prevailing explanations for choking is that pressure increases the conscious attention to the underlying processes of the performer's task execution, thereby disrupting what would normally be a relatively automatic process. However, research on choking has focused mainly on the influence of pressure on motor performance, typically overlooking how it might alter the way that vision is controlled when performing these motor actions. In this article we ask whether the visual component of expert motor-skill execution is susceptible to choking much like the motor component is thought to be. To do so, we draw heavily on empirical findings from studies of sporting expertise, in particular focussing on the role of gaze in three types of visually-guided actions: interceptive actions, aiming tasks, and anticipatory skill. For each of these skills we evaluate the nature of the expert advantage, discuss the role of consciousness in their control, examine the potential impact of pressure on task performance, and consider interventions designed to reduce the likelihood of choking when performing these tasks

A Neuromonitoring Approach to Facial Nerve Preservation During Image-guided Robotic Cochlear Implantation.

HYPOTHESIS A multielectrode probe in combination with an optimized stimulation protocol could provide sufficient sensitivity and specificity to act as an effective safety mechanism for preservation of the facial nerve in case of an unsafe drill distance during image-guided cochlear implantation. BACKGROUND A minimally invasive cochlear implantation is enabled by image-guided and robotic-assisted drilling of an access tunnel to the middle ear cavity. The approach requires the drill to pass at distances below 1 mm from the facial nerve and thus safety mechanisms for protecting this critical structure are required. Neuromonitoring is currently used to determine facial nerve proximity in mastoidectomy but lacks sensitivity and specificity necessaries to effectively distinguish the close distance ranges experienced in the minimally invasive approach, possibly because of current shunting of uninsulated stimulating drilling tools in the drill tunnel and because of nonoptimized stimulation parameters. To this end, we propose an advanced neuromonitoring approach using varying levels of stimulation parameters together with an integrated bipolar and monopolar stimulating probe. MATERIALS AND METHODS An in vivo study (sheep model) was conducted in which measurements at specifically planned and navigated lateral distances from the facial nerve were performed to determine if specific sets of stimulation parameters in combination with the proposed neuromonitoring system could reliably detect an imminent collision with the facial nerve. For the accurate positioning of the neuromonitoring probe, a dedicated robotic system for image-guided cochlear implantation was used and drilling accuracy was corrected on postoperative microcomputed tomographic images. RESULTS From 29 trajectories analyzed in five different subjects, a correlation between stimulus threshold and drill-to-facial nerve distance was found in trajectories colliding with the facial nerve (distance <0.1 mm). The shortest pulse duration that provided the highest linear correlation between stimulation intensity and drill-to-facial nerve distance was 250 μs. Only at low stimulus intensity values (≤0.3 mA) and with the bipolar configurations of the probe did the neuromonitoring system enable sufficient lateral specificity (>95%) at distances to the facial nerve below 0.5 mm. However, reduction in stimulus threshold to 0.3 mA or lower resulted in a decrease of facial nerve distance detection range below 0.1 mm (>95% sensitivity). Subsequent histopathology follow-up of three representative cases where the neuromonitoring system could reliably detect a collision with the facial nerve (distance <0.1 mm) revealed either mild or inexistent damage to the nerve fascicles. CONCLUSION Our findings suggest that although no general correlation between facial nerve distance and stimulation threshold existed, possibly because of variances in patient-specific anatomy, correlations at very close distances to the facial nerve and high levels of specificity would enable a binary response warning system to be developed using the proposed probe at low stimulation currents.

Synergistic action of image-guided radiotherapy and androgen deprivation therapy.

The combined use of androgen deprivation therapy (ADT) and image-guided radiotherapy (IGRT) can improve overall survival in aggressive, localized prostate cancer. However, owing to the adverse effects of prolonged ADT, it is imperative to identify the patients who would benefit from this combined-modality therapy relative to the use of IGRT alone. Opportunities exist for more personalized approaches in treating aggressive, locally advanced prostate cancer. Biomarkers--such as disseminated tumour cells, circulating tumour cells, genomic signatures and molecular imaging techniques--could identify the patients who are at greatest risk for systemic metastases and who would benefit from the addition of systemic ADT. By contrast, when biomarkers of systemic disease are not present, treatment could proceed using local IGRT alone. The choice of drug, treatment duration and timing of ADT relative to IGRT could be predicated on these personalized approaches to prostate cancer medicine. These novel treatment intensification and reduction strategies could result in improved prostate-cancer-specific survival and overall survival, without incurring the added expense of metabolic syndrome and other adverse effects of ADT in all patients.

Biomechanical Role of Bone Anisotropy Estimated on Clinical CT Scans by Image Registration

Image-based modeling is a popular approach to perform patient-specific biomechanical simulations. Accurate modeling is critical for orthopedic application to evaluate implant design and surgical planning. It has been shown that bone strength can be estimated from the bone mineral density (BMD) and trabecular bone architecture. However, these findings cannot be directly and fully transferred to patient-specific modeling since only BMD can be derived from clinical CT. Therefore, the objective of this study was to propose a method to predict the trabecular bone structure using a µCT atlas and an image registration technique. The approach has been evaluated on femurs and patellae under physiological loading. The displacement and ultimate force for femurs loaded in stance position were predicted with an error of 2.5% and 3.7%, respectively, while predictions obtained with an isotropic material resulted in errors of 7.3% and 6.9%. Similar results were obtained for the patella, where the strain predicted using the registration approach resulted in an improved mean squared error compared to the isotropic model. We conclude that the registration of anisotropic information from of a single template bone enables more accurate patient-specific simulations from clinical image datasets than isotropic model.

Sudden cardiac arrest in sports - need for uniform registration: A Position Paper from the Sport Cardiology Section of the European Association for Cardiovascular Prevention and Rehabilitation

There are large variations in the incidence, registration methods and reported causes of sudden cardiac arrest/sudden cardiac death (SCA/SCD) in competitive and recreational athletes. A crucial question is to which degree these variations are genuine or partly due to methodological incongruities. This paper discusses the uncertainties about available data and provides comprehensive suggestions for standard definitions and a guide for uniform registration parameters of SCA/SCD. The parameters include a definition of what constitutes an 'athlete', incidence calculations, enrolment of cases, the importance of gender, ethnicity and age of the athlete, as well as the type and level of sporting activity. A precise instruction for autopsy practice in the case of a SCD of athletes is given, including the role of molecular samples and evaluation of possible doping. Rational decisions about cardiac preparticipation screening and cardiac safety at sport facilities requires increased data quality concerning incidence, aetiology and management of SCA/SCD in sports. Uniform standard registration of SCA/SCD in athletes and leisure sportsmen would be a first step towards this goal.

Pemphigus. S2 Guideline for diagnosis and treatment--guided by the European Dermatology Forum (EDF) in cooperation with the European Academy of Dermatology and Venereology (EADV)

BACKGROUND Pemphigus encompasses a group of life-threatening autoimmune bullous diseases characterized by blisters and erosions of the mucous membranes and skin. Before the era of immunosuppressive treatment, the prognosis of pemphigus was almost fatal. Due to its rarity, only few prospective controlled therapeutic trials are available. OBJECTIVES For this reason, a group of European dermatologists with a long-standing interest and expertise in basic and clinical pemphigus research has sought to define diagnostic and therapeutic guidelines for the management of patients with pemphigus. RESULTS This group identified the statements of major agreement or disagreement regarding the diagnostic and therapeutic management of pemphigus. The revised final version of the pemphigus guideline was finally passed on to the European Dermatology Forum (EDF) for a final consensus with the European Academy of Dermatology and Venereology (EADV) and the European Union of Medical Specialists (UEMS).

Non-rigid Free-Form 2D-3D Registration Using Statistical Deformation Model

This paper presents a non-rigid free-from 2D-3D registration approach using statistical deformation model (SDM). In our approach the SDM is first constructed from a set of training data using a non-rigid registration algorithm based on b-spline free-form deformation to encode a priori information about the underlying anatomy. A novel intensity-based non-rigid 2D-3D registration algorithm is then presented to iteratively fit the 3D b-spline-based SDM to the 2D X-ray images of an unseen subject, which requires a computationally expensive inversion of the instantiated deformation in each iteration. In this paper, we propose to solve this challenge with a fast B-spline pseudo-inversion algorithm that is implemented on graphics processing unit (GPU). Experiments conducted on C-arm and X-ray images of cadaveric femurs demonstrate the efficacy of the present approach.

CT-guided infiltration saves surgical intervention and fastens return to work compared to anatomical landmark-guided infiltration in patients with lumbosciatica

BACKGROUND Infiltration procedures are a common treatment of lumbar radiculopathy. There is a wide variety of infiltration techniques without an established gold standard. Therefore, we compared the effectiveness of CT-guided transforaminal infiltrations versus anatomical landmark-guided transforaminal infiltrations at the lower lumbar spine in case of acute sciatica at L3-L5. METHODS A retrospective chart review was conducted of 107 outpatients treated between 2009 and 2011. All patients were diagnosed with lumbar radiculopathic pain secondary to disc herniation in L3-L5. A total of 52 patients received CT-guided transforaminal infiltrations; 55 patients received non-imaging-guided nerve root infiltrations. The therapeutic success was evaluated regarding number of physician contacts, duration of treatment, type of analgesics used and loss of work days. Defined endpoint was surgery at the lower lumbar spine. RESULTS In the CT group, patients needed significantly less oral analgesics (p < 0.001). Overall treatment duration and physician contacts were significantly lower in the CT group (p < 0.001 and 0.002) either. In the CT group, patients lost significant fewer work days due to incapacity (p < 0.001). Surgery had to be performed in 18.2 % of the non-imaging group patients (CT group: 1.9 %; p = 0.008). CONCLUSION This study shows that CT-guided periradicular infiltration in lumbosciatica caused by intervertebral disc herniation is significantly superior to non-imaging, anatomical landmark-guided infiltration, regarding the parameters investigated. The high number of treatment failures in the non-imaging group underlines the inferiority of this treatment concept.