Requirements for dose calculation on an active scanned proton beamline for small, shallow fields.

INTRODUCTION: A growing interest in using proton pencil beam scanning in combination with collimators for the treatment of small, shallow targets, such as ocular melanoma or pre-clinical research emerged recently. This study aims at demonstrating that the dose of a synchrotron-based PBS system with a dedicated small, shallow field nozzle can be accurately predicted by a commercial treatment planning system (TPS) following appropriate tuning of both, nozzle and TPS. MATERIALS: A removable extension to the clinical nozzle was developed to modify the beam shape passively. Five circular apertures with diameters between 5 to 34mm, mounted 72cm downstream of a range shifter were used. For each collimator treatment plans with spread-out Bragg peaks (SOBP) with a modulation of 3 to 30mm were measured and calculated with GATE/Geant4 and the research TPS RayStation (RS11B-R). The dose grid, multiple coulomb scattering and block discretization resolution were varied to find the optimal balance between accuracy and performance. RESULTS: For SOBPs deeper than 10mm, the dose in the target agreed within 1% between RS11B-R, GATE/Geant4 and measurements for aperture diameters between 8 to 34mm, but deviated up to 5% for smaller apertures. A plastic taper was introduced reducing scatter contributions to the patient (from the pipe) and improving the dose calculation accuracy of the TPS to a 5% level in the entrance region for large apertures. CONCLUSION: The commercial TPS and GATE/Geant4 can accurately calculate the dose for shallow, small proton fields using a collimator and pencil beam scanning.

Does choice change preferences? An incentivized test of the mere choice effect.

Widespread evidence from psychology and neuroscience documents that previous choices unconditionally increase the later desirability of chosen objects, even if those choices were uninformative. This is problematic for economists who use choice data to estimate latent preferences, demand functions, and social welfare. The evidence on this mere choice effect, however, exhibits serious shortcomings which prevent evaluating its possible relevance for economics. In this paper, we present a novel, parsimonious experimental design to test for the economic validity of the mere choice effect addressing these shortcomings. Our design uses well-defined, monetary lotteries, all decisions are incentivized, and we effectively randomize participants' initial choices without relying on deception. Results from a large, pre-registered online experiment find no support for the mere choice effect. Our results challenge conventional wisdom outside economics. The mere choice effect does not seem to be a concern for economics, at least in the domain of decision making under risk. Supplementary Information: The online version contains supplementary material available at 10.1007/s10683-021-09728-5.

Combined use of magnetic microbeads for endothelial cell isolation and enhanced cell engraftment in myocardial repair.

Background: The regenerative potential of the heart after injury is limited. Therefore, cell replacement strategies have been developed. However, the engraftment of transplanted cells in the myocardium is very inefficient. In addition, the use of heterogeneous cell populations precludes the reproducibility of the outcome. Methods: To address both issues, in this proof of principle study, we applied magnetic microbeads for combined isolation of eGFP+ embryonic cardiac endothelial cells (CECs) by antigen-specific magnet-associated cell sorting (MACS) and improved engraftment of these cells in myocardial infarction by magnetic fields. Results: MACS provided CECs of high purity decorated with magnetic microbeads. In vitro experiments revealed that the angiogenic potential of microbead-labeled CECs was preserved and the magnetic moment of the cells was strong enough for site-specific positioning by a magnetic field. After myocardial infarction in mice, intramyocardial CEC injection in the presence of a magnet resulted in a strong improvement of cell engraftment and eGFP+ vascular network formation in the hearts. Hemodynamic and morphometric analysis demonstrated augmented heart function and reduced infarct size only when a magnetic field was applied. Conclusion: Thus, the combined use of magnetic microbeads for cell isolation and enhanced cell engraftment in the presence of a magnetic field is a powerful approach to improve cell transplantation strategies in the heart.

Drilling- and withdrawing-related thermal effects of implant site preparation for ceramic and stainless steel twist drills in standardized bovine bone.

INTRODUCTION: Excessive surgical trauma is believed to be among the most important causes for early implant losses. As thermal injury to the bone is not only dependent on the amount of generated heat but also on the tissue exposure time, and the greatest temperature increase was found within the withdrawing period, the entire osteotomy procedure with the parameters contributing to thermal damage is of particular clinical relevance. The aim of this study was to investigate the thermal performance of metal-based and ceramic implant drills regarding the temperature exposure time during the whole osteotomy process. MATERIALS AND METHODS: This investigation consisted of 240 individual preparations in total, comprising two different drilling depths (10 and 16 mm), two irrigation methods (external and without irrigation), two implant drill materials (stainless steel and zirconia), and three consecutive drill diameters per material (2.0/2.2, 2.8, and 3.5 mm) with 10 identical repetitions. Real-time multichannel temperature measurement was conducted during automated drilling procedures in standardized bovine bone specimens. RESULTS: The maximum temperature changes were highly associated with the time period of passive drill withdrawing (p ≤ 0.05), irrespective of drill material, drilling depth, or drill diameter. Statistically significant differences in temperature generation between stainless steel and ceramic drills were observed in irrigated testing sites at both drilling depths with smaller drill diameters (2.0/2.2 and 2.8 mm, p ≤ 0.05). CONCLUSION: Results of this in vitro study could demonstrate a strong association between the highest temperature increase and the passive withdrawing time period in both investigated drill materials. Considering these findings and the resulting thermal bone damage due to the whole surgical procedure, high overall temperatures in combination with a prolonged heat exposure time may impact the future osseointegration process.

University Students' Well-Being and Engagement in Activities in the Early Days of Covid-19.

Governments worldwide took measures to contain the spread of the coronavirus COVID-19. Universities moved to online teaching almost overnight. This paper explores Belgian university students' perceptions, behaviors, and emotional well-being during the first weeks of strict preventive measures. We conducted a survey with 614 business administration students at the University of Antwerp. The results indicate that, in comparison to the pre-lockdown period, students feel less productive, engage less in healthy behaviors (e.g., healthy snacking, exercising alone), and report more study problems. Based on the emotional quality of their everyday experience, students can be clustered into two groups. One group (54.5%) experiences mostly negative affect, while the other reports experiencing mostly positive affect and personal optimism. The "negative affect" group consists of more women and students in the early years of their bachelor's. This group experiences more financial difficulties and spends more time on social media. These students seem to have a more challenging time coping with the lockdown: they perceive higher study load increase and more significant reduction of social contacts while facing more study problems, studying fewer hours, and perceiving a lower study efficiency. They also engage in less healthy behaviors (e.g., unhealthy snacking more, drinking more alcohol, and exercising alone less) to a greater extent than the positive affect group. These results confirm previous research, demonstrating a positive relationship between emotional well-being and the engagement in and the intensity of productive and healthy activities. Several recommendations are provided in light of these findings.

Improved access to the bone marrow space by multiple perforations of the alveolar bundle bone after tooth extraction-A case report.

OBJECTIVES: The dental alveolus is lined by a thin cortical layer ("bundle bone", "alveolar bone proper", "cribriform plate", "lamina dura"), that can impede access to the bone marrow and its vasculature. During unassisted socket healing, the alveolar bundle bone is gradually resorbed allowing tissue resources from the bone marrow to enter into the socket space. An optimized wound healing process, either during unassisted socket healing or during ridge preservation procedures, with autogenous bone and/or any bone/collagen substitute material, depends at least partly on an adequate vascularization of the socket space. This ensures sufficient recruitment of osteoblast and osteoclast precursor cells and facilitates fast bone regeneration and/or uneventful integration of the augmentation material. METHODS: The present technical note describes an easy treatment step after tooth extraction aiming to improve socket healing with or without any ridge preservation procedure, by facilitating an increased blood inflow into the dental alveolus. Specifically, after tooth extraction the alveolar bundle bone is perforated several times - mainly in a palatally/lingually - by a small round bur (diameter < 1 mm) extending into the trabecular bone. RESULTS AND CONCLUSIONS: By means of this relatively simple treatment step, an increased blood inflow into the alveolus is achieved after tooth extraction, which might enhance socket healing and corticalization of the entrance, and in turn result in a lower complication rate (e.g., dry socket), in an enhanced graft incorporation, and/or in a reduced loss of alveolar ridge volume.

Cardiac MRI in Patients with Prolonged Cardiorespiratory Symptoms after Mild to Moderate COVID-19.

Background Myocardial injury and inflammation at cardiac MRI in patients with COVID-19 have been described in recent publications. Concurrently, a chronic COVID-19 syndrome (CCS) after SARS-CoV-2 infection has been observed and manifests with symptoms such as fatigue and exertional dyspnea. Purpose To explore the relationship between CCS and myocardial injury and inflammation as an underlying cause of the persistent complaints in previously healthy individuals. Materials and Methods In this prospective study from January 2021 to April 2021, study participants without known cardiac or pulmonary diseases prior to SARS-CoV-2 infection who had persistent CCS symptoms such as fatigue or exertional dyspnea after convalescence and healthy control participants underwent cardiac MRI. The cardiac MRI protocol included evaluating the T1 and T2 relaxation times, extracellular volume, T2 signal intensity ratio, and late gadolinium enhancement (LGE). Student t tests, Mann-Whitney U tests, and χ2 tests were used for statistical analysis. Results Forty-one participants with CCS (mean age, 39 years ± 13 [standard deviation]; 18 men) and 42 control participants (mean age, 39 years ± 16; 26 men) were evaluated. The median time between the initial incidence of mild to moderate COVID-19 not requiring hospitalization and undergoing cardiac MRI was 103 days (interquartile range, 88-158 days). Troponin T levels were normal. Parameters indicating myocardial inflammation and edema were comparable between participants with CCS and control participants (T1 relaxation times: 978 msec ± 23 vs 971 msec ± 25 [P = .17]; T2 relaxation times: 53 msec ± 2 vs 52 msec ± 2 [P = .47]; T2 signal intensity ratios: 1.6 ± 0.2 vs 1.6 ± 0.3 [P = .10]). Visible myocardial edema was present in none of the participants. Three of 41 (7%) participants with CCS demonstrated nonischemic LGE, whereas no participants in the control group demonstrated nonischemic LGE (0 of 42 [0%]; P = .07). None of the participants fulfilled the 2018 Lake Louise criteria for the diagnosis of myocarditis. Conclusion Individuals with chronic COVID-19 syndrome who did not undergo hospitalization for COVID-19 did not demonstrate signs of active myocardial injury or inflammation at cardiac MRI. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Lima and Bluemke in this issue.

Cardiac MRI in Suspected Acute COVID-19 Myocarditis.

Keywords: COVID-19; coronavirus; myocarditis; cardiac MRI; T1 mapping; T2 mapping.

Thermal effects of various drill materials during implant site preparation-Ceramic vs. stainless steel drills: A comparative in vitro study in a standardised bovine bone model.

OBJECTIVES: The aim of this study was to evaluate thermal effects of ceramic and metal implant drills during implant site preparation using a standardised bovine model. MATERIAL AND METHODS: A total of 320 automated intermittent osteotomies of 10- and 16-mm drilling depths were performed using zirconium dioxide-based and stainless steel drills. Various drill diameters (2.0/ 2.2, 2.8, 3.5, 4.2 mm ∅) and different cooling methods (without/ with external saline irrigation) were investigated at room temperature (21 ± 1°C). Temperature changes were recorded in real time using two custom-built multichannel thermoprobes in 1- and 2-mm distance to the osteotomy site. For comparisons, a linear mixed model was estimated. RESULTS: Comparing thermal effects, significantly lower temperatures could be detected with steel-based drills in various drill diameters, regardless of drilling depth or irrigation method. Recorded temperatures for metal drills of all diameters and drilling depths using external irrigation were below the defined critical temperature threshold of 47°C, whereas ceramic drills of smaller diameters reached or exceeded the harmful temperature threshold at 16-mm drilling depths, regardless of whether irrigation was applied or not. The results of this study suggest that the highest temperature changes were not found at the deepest point of the osteotomy site but were observed at subcortical and deeper layers of bone, depending on drill material, drill diameter, drilling depth and irrigation method. CONCLUSIONS: This standardised investigation revealed drill material and geometry to have a substantial impact on heat generation, as well as external irrigation, drilling depth and drill diameter.

The practical radius of a pencil beam in proton therapy.

The central Gaussian shaped high dose region of a pencil beam (PB) in light ion beam therapy (LIBT) is enveloped by a low dose region causing non-negligible field size effects and impairs the dose calculation accuracy considerably if the low dose envelope is not well modeled. The purpose of this study was to calculate the practical radius, Rc, at which a PB does not influence a field more than a certain accuracy level. Lateral dose profiles of proton beams in water were simulated using GATE/Geant4. Those lateral dose profiles were integrated numerically and used to calculate field size factors (FSFs). The Rc was then determined such, that the lateral dose at radii exceeding Rc can be neglected without compromising the FSF of a 20cm×20cm field more than a desired accuracy level c. The practical radius Rc yielding c=0.5% was compared to the frequently applied concept of full width at a ratio x of the maximum (FWxM). The sensitivity to variations of the beam width was tested by increasing the initial beam width σC of the clinical beam model by 0.5 and 1mm, respectively. Neglecting the dose at radii exceeding Rc resulted in the desired FSF accuracy, whereas using the FW0.01%M cut resulted in varying accuracy. In order to yield a constant FSF accuracy, the ratio x in FWxM ranged from 0.003% to 0.065% of the maximum. In contrast to Rc, FWxM was sensitive to variations of the initial beam width. The maximum Rc over all depths was less than 7cm for the low(62.4MeV) and medium(148.2MeV) proton energy beam, which suggests that a plane parallel ionization chamber exceeding that radius is sufficient to acquire laterally integrated depth dose distributions for those energies. However, this holds not true for the highest energy (252.7MeV) or when including a range shifter (RaShi). The values of Rc are specific to our beam line configuration as the maximum Rc was depending on both, the scattering material in the Nozzle as well as the distance of the air-gap between Nozzle and phantom.

Investigation of the Bragg peak degradation caused by homogeneous and heterogeneous lung tissue substitutes: proton beam experiments and comparison to current clinical dose calculation.

Submillimetre structures of lung tissue are not represented in computed tomography images used for radiotherapeutic dose calculation. In order to study the effect experimentally, lung substitutes with properties similar to lung tissue were chosen, namely two types of commercial lung tissue equivalent plates (LTEPs) (CIRS, USA), two types of cork, balsawood, floral foam and konjac sponge. Laterally integrated dose profiles were measured as a function of depth for proton pencil beams (PBs) with an initial nominal energy of 97.4 and 148.2 MeV, respectively. The obtained dose profiles were investigated for their shifting and degradation of the Bragg peak (BP) caused by the materials, expressed as water equivalent thickness (WET) and full width half maximum. The set-up was simulated in the treatment planning system (TPS) RayStation using the Monte Carlo (MC) dose calculation algorithm. While the WET between experiment and dose calculation agreed within 0.5 mm, except for floral foam, the full width half maximum was underestimated in the TPS by up to 2.3 mm. Normalisation to the same mass thickness of the lung substitutes allowed to classify LTEPs and balsawood as homogeneous and cork, floral foam and konjac sponge as heterogeneous materials. The material specific BP degradation was up to 3.4 times higher for the heterogeneous samples. The modulation power as a measure for the heterogeneity was compared to the spectrum of Hounsfield units (HU) of the materials. A clear correlation was not found, but with further improvements the HU spectrum may serve as an indicator for the material heterogeneity. Further, MC simulations of binary voxel models using GATE/Geant4 were performed to investigate the influence of grain size and mass density. For mass densities similar to lung tissue the BP degradation had a maximum at 3 and 7 mm grain size.

Guided Osteotomy and Guided Autotransplantation for Treatment of Severely Impacted Teeth: A Proof-of-Concept Report.

INTRODUCTION: The aim was to present a novel surgical technique using virtually preplanned 3-dimensional (3D)-printed templates for guided osteotomies. These were to ensure atraumatic uncovering of a severely impacted donor tooth including guided drilling of the recipient alveolus followed by a secure autotransplantation procedure. METHODS: This report presents an autotransplantation procedure of a 14-year-old patient with a severely impacted second premolar and extensive contact to the roots of the adjacent teeth and the inferior alveolar nerve. Autotransplantation of the impacted premolar was virtually performed using modified methods from guided implant surgery in order to prefabricate 3D-printed templates with the aid of a fully digital workflow. RESULTS: Satisfactory treatment could be achieved using surgical templates for guided osteotomies of the surgical access, guided drilling of the recipient site, and occlusal reference template ensuring autotransplantation in the appropriate 3D location of the graft. An atraumatic approach could be ensured with an extraoral time of 46 seconds by 1 fitting attempt; no injuries or altered sensation of the inferior alveolar nerve were present. A vital natural tooth could be observed. CONCLUSIONS: This innovative technique uses for the first time a fully implemented digital workflow for guided osteotomies, guided drilling, and guided autotransplantation of a severely impacted tooth. 3D-printed templates could ensure a guided atraumatic approach and facilitate highly complex treatments by virtually implementing recommended guidelines in future autotransplantations.

Guided Lateral Sinus Lift Procedure Using 3-Dimensionally Printed Templates for a Safe Surgical Approach: A Proof-of-Concept Case Report.

The purpose of this article was to present a guided lateral window sinus lift procedure with the aid of a fully digital workflow using surgical templates for window osteotomy preparation and implant placement. A 22-year-old patient with insufficient residual bone height in the posterior maxilla was treated with a maxillary sinus augmentation procedure with a lateral window technique and simultaneous implant installation using 3-dimensionally printed surgical guides. The surgical guides, used for the preparation of both the lateral window and the implant site according to the optimal prosthodontic and anatomic position, were based on a fully digital workflow and virtual pre-planning with modified implant-planning software. Successful functional and esthetic rehabilitation of the patient was accomplished using standard surgical techniques and instruments but an innovative method for the production and application of surgical templates ensured a precise and safe approach for the lateral window osteotomy preparation. This guided lateral window sinus lift technique may reduce the incidence of surgical complications and failures and enhance patient-related outcomes.

Time-resolved dosimetry for validation of 4D dose calculation in PBS proton therapy.

Four-dimensional dose calculation (4D-DC) is crucial for predicting the dosimetric outcome in the presence of intra-fractional organ motion. Time-resolved dosimetry can provide significant insights into 4D pencil beam scanning dose accumulation and is therefore irreplaceable for benchmarking 4D-DC. In this study a novel approach of time-resolved dosimetry using five PinPoint ionization chambers (ICs) embedded in an anthropomorphic dynamic phantom was employed and validated against beam delivery details. Beam intensity variations as well as the beam delivery time structure were well reflected with an accuracy comparable to the temporal resolution of the IC measurements. The 4D dosimetry approach was further applied for benchmarking the 4D-DC implemented in the RayStation 6.99 treatment planning system. Agreement between computed values and measurements was investigated for (i) partial doses based on individual breathing phases, and (ii) temporally distributed cumulative doses. For varied beam delivery and patient-related parameters the average unsigned dose difference for (i) was 0.04 ± 0.03 Gy over all considered IC measurement values, while the prescribed physical dose was 2 Gy. By implementing (ii), a strong effect of the dose gradient on measurement accuracy was observed. The gradient originated from scanned beam energy modulation and target motion transversal to the beam. Excluding measurements in the high gradient the relative dose difference between measurements and 4D-DCs for a given treatment plan at the end of delivery was 3.5% on average and 6.6% at maximum over measurement points inside the target. Overall, the agreement between 4D dose measurements in the moving phantom and retrospective 4D-DC was found to be comparable to the static dose differences for all delivery scenarios. The presented 4D-DC has been proven to be suitable for simulating treatment deliveries with various beam- as well as patient-specific parameters and can therefore be employed for dosimetric validation of different motion mitigation techniques.

Dynamic lung phantom commissioning for 4D dose assessment in proton therapy.

Anthropomorphic phantoms mimicking organ and tumor motion of patients are essential for end-to-end testing of motion mitigation techniques in ion beam therapy. In this work a commissioning procedure developed with the in-house designed respiratory phantom ARDOS (Advanced Radiation DOSimetry system) is presented. The phantom was tested and benchmarked for 4D dose verification in proton therapy, which included: characterization of the tissue equivalent materials from computed tomography (CT) imaging, assessment of dose calculation accuracy in critical structures of the phantom, and testing various detectors for proton dosimetry in the ARDOS phantom. To prove the validity of the CT calibration curve, measured relative stopping powers (RSP) of the ARDOS materials were compared with values from CTs: original and overwritten with known material parameters. Override of rib- and soft-tissue phantom components improved RSP accuracy while inhomogeneous lung tissue, represented by the balsa wood, was better modelled by the CT Hounsfield units. Monte Carlo (MC) dose calculations were benchmarked against measurements with a reference Farmer chamber embedded in ARDOS material samples showing less than 3% relative dose difference. Differences between MC calculated dose distributions and those calculated by analytical algorithms for the ARDOS geometry were higher than 20% of the prescribed dose, depending on the position in the phantom. Pinpoint ionization chambers and thermoluminescence dosimeters showed differences of up to 5.5% compared to MC dose calculations for all lung setups in the static phantom. They were also able to detect dose distortions due to motion. EBT3 film dosimetry was shown to be suitable for 2D relative dose characterization, which could provide extended information on dose distributions in the penumbra area. The presented methodology and results can be used for drafting general recommendations for dynamic phantom commissioning, which is an essential step towards end-to-end evaluation of motion mitigation techniques in ion beam therapy.

Image guidance: past and future of radiotherapy.

Image guidance has been playing a decisive role throughout the history of radiotherapy, but developments in 3D-and 4D imaging data acquisition using computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET) have significantly boosted the precision of conformal radiotherapy. An overarching aim of radiotherapy is conforming the treatment dose to the tumor in order to optimally limit a high radiation dose outside the target. Stereotactic, intensity modulated, and adaptive radiotherapy are all largely based on appropriately using imaging information both before and during treatment delivery using on-board imaging devices. While pretreatment imaging for planning has reached a very high level in the past two decades, the next step will be to further refine and accelerate imaging during treatment delivery, resulting in adaptation of the dose fluence during a patient's treatment in various scenarios, some of which are discussed in this article.

Myocardial maladaptation to pressure overload in CB2 receptor-deficient mice.

BACKGROUND: Adaptation to aortic valve stenosis leads to myocardial hypertrophy, which has been associated with inflammation, fibrosis and activation of the endocannabinoid system. Since the endocannabinoid system and the CB2 receptor provide cardioprotection and modulate immune response in experimental ischemia, we investigated the role of CB2 in a mouse model of cardiac pressure overload. METHODS: Transverse aortic constriction was performed in CB2 receptor-deficient (Cnr2-/-) mice and their wild-type littermates (Cnr2+/+). After echocardiography and Millar left heart catheter hemodynamic evaluation hearts were processed for histological, cellular and molecular analyses. RESULTS: The endocannabinoid system showed significantly higher anandamide production and CB2 receptor expression in Cnr2+/+ mice. Histology showed non-confluent, interstitial fibrosis with rare small areas of cardiomyocyte loss in Cnr2+/+ mice. In contrast, extensive cardiomyocyte loss and confluent scar formation were found in Cnr2-/- mice accompanied by significantly increased apoptosis and left ventricular dysfunction when compared with Cnr2+/+ mice. The underlying cardiac maladaptation in Cnr2-/- mice was associated with significantly reduced expression of myosin heavy chain isoform beta and less production of heme oxygenase-1. Cnr2-/- hearts presented after 7 days with stronger proinflammatory response including significantly higher TNF-alpha expression and macrophage density, but lower density of CD4+ and B220+ cells. At the same time, we found increased apoptosis of macrophages and adaptive immune cells. Higher myofibroblast accumulation and imbalance in MMP/TIMP-regulation indicated adverse remodeling in Cnr2-/- mice. CONCLUSIONS: Our study provides mechanistic evidence for the role of the endocannabinoid system in myocardial adaptation to pressure overload in mice. The underlying mechanisms include production of anandamide, adaptation of contractile elements and antioxidative enzymes, and selective modulation of immune cells action and apoptosis in order to prevent the loss of cardiomyocytes.

Impact of androgen deprivation therapy on apparent diffusion coefficient and T2w MRI for histogram and texture analysis with respect to focal radiotherapy of prostate cancer.

PURPOSE: Accurate prostate cancer (PCa) detection is essential for planning focal external beam radiotherapy (EBRT). While biparametric MRI (bpMRI) including T2-weighted (T2w) and diffusion-weighted images (DWI) is an accurate tool to localize PCa, its value is less clear in the case of additional androgen deprivation therapy (ADT). The aim of this study was to investigate the value of a textural feature (TF) approach on bpMRI analysis in prostate cancer patients with and without neoadjuvant ADT with respect to future dose-painting applications. METHODS: 28 PCa patients (54-80 years) with (n = 14) and without (n = 14) ADT who underwent bpMRI with T2w and DWI were analyzed retrospectively. Lesions, central gland (CG), and peripheral zone (PZ) were delineated by an experienced urogenital radiologist based on localized pre-therapeutic histopathology. Histogram parameters and 20 Haralick TF were calculated. Regional differences (i. e., tumor vs. PZ, tumor vs. CG) were analyzed for all imaging parameters. Receiver-operating characteristic (ROC) analysis was performed to measure diagnostic performance to distinguish PCa from benign prostate tissue and to identify the features with best discriminative power in both patient groups. RESULTS: The obtained sensitivities were equivalent or superior when utilizing the TF in the no-ADT group, while specificity was higher for the histogram parameters. However, in the ADT group, TF outperformed the conventional histogram parameters in both specificity and sensitivity. Rule-in and rule-out criteria for ADT patients could exclusively be defined with the aid of TF. CONCLUSIONS: The TF approach has the potential for quantitative image-assisted boost volume delineation in PCa patients even if they are undergoing neoadjuvant ADT.

Association between maxillary lateral incisors' root volume and palatally displaced canines: An instrumental variables approach to the guidance theory.

OBJECTIVES:: To evaluate association and causation between maxillary lateral incisors' (MxI2) apical root volume (ARV) and palatally displaced canines (PDC). MATERIALS AND METHODS:: In a retrospective cross-sectional study, computed tomography scans of 179 patients with unilateral PDC were analyzed. MxI2 root length and volume on the impaction and eruption side were measured. A mixed logit model was used to infer the association between ARV and PDC and an instrumental variables approach to interpret causality. RESULTS:: MxI2 root length on the impaction side was shorter in 42%, equal in 33% and longer in 25% of the patients. ARV amounted for 13.5% of total root volume on the impaction and 14.9% on the eruption side. Reduced ARV was significantly associated with the impaction side ( P < .001). The causal effect of ARV on PDC in the instrumental variable approach amounted to less than half of the association in a standard noncausal approach. CONCLUSIONS:: An association between PDC and reduced MxI2 root length and volume was confirmed. However, the lack of causality did not allow the researchers to draw a conclusion as to whether a reduced ARV is causing PDC or resulting from it; this should be considered in etiologic theories.

Overexpression of Cx43 in cells of the myocardial scar: Correction of post-infarct arrhythmias through heterotypic cell-cell coupling.

Ventricular tachycardia (VT) is the most common and potentially lethal complication following myocardial infarction (MI). Biological correction of the conduction inhomogeneity that underlies re-entry could be a major advance in infarction therapy. As minimal increases in conduction of infarcted tissue markedly influence VT susceptibility, we reasoned that enhanced propagation of the electrical signal between non-excitable cells within a resolving infarct might comprise a simple means to decrease post-infarction arrhythmia risk. We therefore tested lentivirus-mediated delivery of the gap-junction protein Connexin 43 (Cx43) into acute myocardial lesions. Cx43 was expressed in (myo)fibroblasts and CD45+ cells within the scar and provided prominent and long lasting arrhythmia protection in vivo. Optical mapping of Cx43 injected hearts revealed enhanced conduction velocity within the scar, indicating Cx43-mediated electrical coupling between myocytes and (myo)fibroblasts. Thus, Cx43 gene therapy, by direct in vivo transduction of non-cardiomyocytes, comprises a simple and clinically applicable biological therapy that markedly reduces post-infarction VT.