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The assessment of bone mineral density (BMD) is essential to skeletal health, and dual-energy x-ray absorptiometry (DXA) is a type of bone densitometer that is extensively used in both clinical and research settings. When changing a DXA system during longitudinal monitoring or multicenter studies, it is important to conduct cross-calibration between the new and reference scanners to ensure that BMD values measured by the two systems are as close as possible. Purpose: To properly cross calibrate between the GE Lunar iDXA and Prodigy in healthy young adults. Methods: Thirty college students, ten males and twenty females, participated in the study. The BMD at the lumbar spine and dual femurs were measured using the GE iDXA and Prodigy by the same licensed technician on the same day. A paired sample t-test and linear regression analysis were utilized to compare the BMD values between the two systems. Limits of agreement were obtained by Bland-Altman analyses. Results: Although strong correlations were found between the two systems (r = 0.985 – 0.998), the iDXA had significantly higher lumbar spine (1.54%) and dual femur (1.28 - 1.56%) BMD values compared to the Prodigy. Conclusion: Our results suggest that calibration equations should be considered to examine data across densitometers to reduce system differences in the young adult population.

Penile adhesions may cause pain, bleeding, disfigurement and distress. In the setting of lichen sclerosus (LS), they often recur but current treatment options are limited. We present a novel surgical technique for treatment of recurrent penile adhesions using sub-coronal buccal mucosal graft (BMG) resurfacing. A retrospective, international multi-institutional study was conducted to include patients with refractory penile adhesions who were treated with this technique. Patients with > 12-month follow-up were included in analysis. The procedure involved circumferential excision of the diseased skin and replacement with a BMG. The primary outcomes were recurrence and surgical complications. Secondary outcomes were patient-reported outcome measures (PROMs) including Sexual Health Inventory for Men (SHIM) questionnaire and Global Response Assessment (GRA) questionnaire measuring functional and esthetic outcomes. Twenty-five men underwent the procedure across six institutions between 3/2014 and 11/2019. Twenty-one men met inclusion criteria. Mean operative time and hospital stay for sub-coronal resurfacing were 40 min (25–50) and 0.76 days (1–2), respectively. At the mean follow-up of 18 months (12–61), no patients developed recurrence. All patients who presented with pain and postcoital bleeding saw improvement on follow-up (18/18). There was a significant improvement in SHIM scores after the operation (14.4 pre-op, 17.0 post-op; p = 0.003). Overall improvement of symptoms was reported by all patients: 57% GRA + 3; 29% GRA + 2; 14% GRA + 1. Baseline penile sensation was preserved in 17/21 (81%) patients. Recurrent penile adhesions in the setting of LS are notoriously difficult to treat. A sub-coronal BMG resurfacing is feasible. This initial patient cohort demonstrated no recurrence and overall high satisfaction.

Objective: To outline our step-by-step surgical technique using a subcoronal buccal mucosal graft (BMG) resurfacing technique for the treatment of recurrent penile adhesions. Methods: To perform the 'buccal belt' procedure a subcoronal circumferential segment of diseased skin was excised. An appropriately sized BMG was circumferentially secured subcoronally with a proximal and distal anastomosis to the edges of the wound. Quilting stitches were also placed to allow proper graft fixation. A petroleum jelly bolster was secured as a tie-over dressing. Patients were discharged with a Foley catheter and the bolster dressing in place. The bolster and Foley catheter were removed 7 days postoperatively. The patients were then seen for follow-up at 4- to 6-month intervals. A retrospective, international multi-institutional review was conducted to include all patients who underwent this procedure. Surgical complications, evidence of recurrence, and patient-reported outcome measures including visual analogue scale (VAS) and global response assessment (GRA) questionnaires were reviewed. Results: Thirty-one men underwent the procedure across six institutions between March 2014 and September 2020. The mean (range) surgical time was 59 (25-95) min. At the mean (range) follow-up of 27 (4-79) months all patients reported resolution of presenting symptoms and no recurrence of adhesions. The mean VAS score was 8.9 and 9.0 for aesthetics and functional outcomes, respectively. On GRA, overall improvement was reported by all patients (61%, +3; 25%, +2; 14%, +1). Conclusion: There are limited options for the treatment of recurrent penile adhesions. A subcoronal BMG resurfacing is feasible, with no recurrence and overall high satisfaction seen in an initial patient cohort. Sin financiación 1.472 SJR (2021) Q1, 6/108 Urology No data IDR 2021 5.969 JCR (2021) Q1, 15/90 Urology & Nephrology 1.472 SJR (2021) Q1, 6/108 Urology No data IDR 2021 UEM

INTRODUCTION AND OBJECTIVE:Radiation-associated strictures occurring after radiotherapy for prostate cancer usually affect the bulbomembranous urethra. These strictures are more challenging to repa...

INTRODUCTION AND OBJECTIVE:Reconstruction of membranous urethral stenosis in patients with previous transurethral resection of the prostate (TURP) or other endoscopic prostate ablative procedures i...

The Gamer’s Dilemma challenges us to find a distinction between virtual murder and virtual pedophilia. Without such a distinction, we are forced to conclude that either both actions are morally acceptable or that both should be morally illicit. This paper argues that the best way to solve the dilemma is, in one sense, to dissolve it. The Gamer’s Dilemma rests on a misunderstanding in the sense that it does not distinguish between the effects that the form of a simulation can have on moral judgment apart from its surface content. A greater appreciation of the way structural features of a simulation affect subject experience will help us see why only simulations of murder and pedophilia generating virtually real experiences are likely to be seen as wrong. I argue that a simulation’s structural elements powerfully affect how subjects experience simulated content and hence is an important, and previously neglected, variable necessary to dissolve the Gamer’s Dilemma. Properly understood, virtually real simulations of murder and pedophilia are both likely to be treated by players as morally wrong. Similarly, virtually unreal murder and pedophilia will be less likely to be judged as wrong. Subject judgments are thus consistent once a simulation’s structural variables are accounted for. The Gamer’s Dilemma dissolves as a dilemma once we acknowledge these structural features of simulations and how they affect experience and moral judgment.

Monte Carlo modelling of SPECT imaging in Molecular Radiotherapy can improve activity quantification. Until now, SPECT modelling with GATE only considered circular orbit (CO) acquisitions. This cannot reproduce auto-contour acquisitions, where the detector head moves close to the patient to improve image resolution. The aim of this work is to develop and validate an auto-contouring step-and-shoot acquisition mode for GATE SPECT modelling.Experimental and simulated SPECT images were compared using the gamma index, and were in good agreement with gamma index passing rate (GIPR) and gammaThis work thereby justifies the need for auto-contouring modelling for isotopes with high septal penetration.

Background The aim of this study was to compare a commercial dosimetry workstation (PLANET® Dose) and the dosimetry approach (GE Dosimetry Toolkit® and OLINDA/EXM® V1.0) currently used in our department for quantification of the absorbed dose (AD) to organs at risk after peptide receptor radionuclide therapy with [177Lu]Lu-DOTA-TATE. Methods An evaluation on phantom was performed to determine the SPECT calibration factor variations over time and to compare the Time Integrated Activity Coefficients (TIACs) obtained with the two approaches. Then, dosimetry was carried out with the two tools in 21 patients with neuroendocrine tumours after the first and second injection of 7.2 ± 0.2 GBq of [177Lu]Lu-DOTA-TATE (40 dosimetry analyses with each software). SPECT/CT images were acquired at 4 h, 24 h, 72 h and 192 h post-injection and were reconstructed using the Xeleris software (General Electric). The liver, spleen and kidneys masses and TIACs were determined using Dosimetry Toolkit® (DTK) and PLANET® Dose. The ADs were calculated using OLINDA/EXM® V1.0 and the Local Deposition Method (LDM) or Dose voxel-Kernel convolution (DK) on PLANET® Dose. Results With the phantom, the 3D calibration factors showed a slight variation (0.8% and 3.3%) over time, and TIACs of 225.19 h and 217.52 h were obtained with DTK and PLANET® Dose, respectively. In patients, the root mean square deviation value was 8.9% for the organ masses, 8.1% for the TIACs, and 9.1% and 7.8% for the ADs calculated with LDM and DK, respectively. The Lin’s concordance correlation coefficient was 0.99 and the Bland–Altman plot analysis estimated that the AD value difference between methods ranged from − 0.75 to 0.49 Gy, from − 0.20 to 0.64 Gy, and from − 0.43 to 1.03 Gy for 95% of the 40 liver, kidneys and spleen dosimetry analyses. The dosimetry method had a minor influence on AD differences compared with the image registration and organ segmentation steps. Conclusions The ADs to organs at risk obtained with the new workstation PLANET® Dose are concordant with those calculated with the currently used software and in agreement with the literature. These results validate the use of PLANET® Dose in clinical routine for patient dosimetry after targeted radiotherapy with [177Lu]Lu-DOTA-TATE.

Background: Recently, commercial software tools have become available for dosimetry evaluations in clinical settings. The aim of this study was to compare a commercial dosimetry workstation (PLANETâDose) and the dosimetry approach (GE Dosimetry Toolkit® and OLINDA/EXM® V1.0) currently used in our department for quantification of the absorbed dose in organs at risk after peptide receptor radionuclide therapy with 177Lu-DOTATATE.Methods: First, an evaluation on phantom, with data acquisition at 5 time points, was performed to determine the SPECT calibration factor variations over time and to compare the Time Integrated Activity Coefficients (TIACs) and absorbed doses obtained with the two tools. Then, the two tools were used for dosimetry evaluation in 21 patients with neuroendocrine tumours after the first and second injection of 7.2 ± 0.2 GBq of 177Lu-DOTATATE (40 dosimetry analyses with each software). SPECT/CT images were acquired at 4h, 24h, 72h and 192h after 177Lu-DOTATATE injection and were reconstructed using the Xeleris software (General Electric). The liver, spleen and kidney masses, TIACs and absorbed doses were calculated using i) GE Dosimetry Toolkit® (DTK) and OLINDA/EXM® V1.0 and ii) the Local Deposition Method (LDM) or Dose voxel-Kernel convolution (DK) on PLANETâDose. Results: With the phantom, the 3D calibration factors showed a slight variation (0.8% and 3.3%) over time and TIACs of 225.19h and 217.52h were obtained with DTK and PLANETâDose, respectively. In patients, the mean of the relative standard deviations was -1% for the organ masses, 5.6%, for the TIACs, and 4.4% for the absorbed doses. The Lin’s concordance correlation coefficient was 0.99 and the Bland-Altman plot analysis estimated that the difference of absorbed dose values between methods ranged from -0.58 Gy to 0.84 Gy for approximately 95% of the 40 dosimetry analyses. A difference of 2.2% was obtained between the absorbed doses to organs at risk calculated with LDM and DK (PLANETâDose). Conclusions: The absorbed doses to organs at risk obtained with the new workstation are concordant with those calculated with the currently used software and in agreement with the literature. These results validate the use of PLANETâDose in clinical routine for patient dosimetry after targeted radiotherapy with 177Lu-DOTATATE.

We argue that moral judgment studies currently conducted utilizing virtual reality (VR) devices must confront a dilemma as a result of how virtual environments are designed and how those en...

Introduction The aim of this work was to study the biodistribution, metabolism and radiation dosimetry of rats injected with [18F]FNM using PET/CT images. This novel radiotracer targeting NMDA receptor has potential for investigation for neurological and psychiatric diseases. Methods Free fraction and stability in fresh human plasma were determined in vitro. PET/CT was performed on anesthetized rats. Organs were identified and 3D volumes of interest (VOIs) were manually drawn on the CT in the center of each organ. Time activity curves (TACs) were created with these VOIs, enabling the calculation of residence times. To confirm these values, ex vivo measurements of organs were performed. Plasma and urine were also collected to study in vivo metabolism. Data was extrapolated to humans, effective doses were estimated using ICRP-60 and ICRP-89 dosimetric models and absorbed doses were estimated using OLINDA/EXM V1.0 and OLINDA/EXM V2.0 (which use weighting factors from ICRP-103 to do the calculations). Results The [18F]FNM was stable in human plasma and the diffusible free fraction was 53%. As with memantine, this tracer is poorly metabolized in vivo. Ex vivo distributions validated PET/CT data as well as demonstrating a decrease of radiotracer uptake in the brain due to anesthesia. Total effective dose was around 6.11 μSv/MBq and 4.65 μSv/MBq for female and male human dosimetric models, respectively. Conclusions This study shows that the presented compound exhibits stability in plasma and plasma protein binding very similar to memantine. Its dosimetry shows that it is suitable for use in humans due to a low total effective dose compared to other PET radiotracers.

Purpose The aim of this study was to quantitatively compare five commercial dosimetric software platforms based on the analysis of clinical datasets of patients who benefited from peptide receptor radionuclide therapy (PRRT) with 177Lu‐DOTATATE (LUTATHERA®). Methods The dosimetric analysis was performed on two patients during two cycles of PRRT with 177Lu. Single photon emission computed tomography/computed tomography images were acquired at 4, 24, 72, and 192 h post injection. Reconstructed images were generated using Dosimetry Toolkit® (DTK) from Xeleris™ and HybridRecon‐Oncology version_1.3_Dicom (HROD) from HERMES. Reconstructed images using DTK were analyzed using the same software to calculate time‐integrated activity coefficients (TIAC), and mean absorbed doses were estimated using OLINDA/EXM V1.0 with mass correction. Reconstructed images from HROD were uploaded into PLANET® OncoDose from DOSIsoft, STRATOS from Phillips, Hybrid Dosimetry Module™ from HERMES, and SurePlan™ MRT from MIM. Organ masses, TIACs, and mean absorbed doses were calculated from each application using their recommendations. Results The majority of organ mass estimates varied by

Purpose Small-scale dosimetry studies generally consider an artificial environment where the tumors are spherical and the radionuclides are homogeneously biodistributed. However, tumor shapes are irregular and radiopharmaceutical biodistributions are heterogeneous, impacting the energy deposition in targeted radionuclide therapy. To bring realism, we developed a dosimetric methodology based on a three-dimensional in vitro model of follicular lymphoma incubated with rituximab, an anti-CD20 monoclonal antibody used in the treatment of non-Hodgkin lymphomas, which might be combined with a radionuclide. The effects of the realistic geometry and biodistribution on the absorbed dose were highlighted by comparison with literature data. Additionally, to illustrate the possibilities of this methodology, the effect of different radionuclides on the absorbed dose distribution delivered to the in vitro tumor were compared. Methods The starting point was a model named multicellular aggregates of lymphoma cells (MALC). Three MALCs of different dimensions and their rituximab biodistribution were considered. Geometry, antibody location and concentration were extracted from selective plane illumination microscopy. Assuming antibody radiolabeling with Auger electron (125 I and 111 In) and β- particle emitters (177 Lu, 131 I and 90 Y), we simulated energy deposition in MALCs using two Monte Carlo codes: Geant4-DNA with "CPA100" physics models for Auger electron emitters and Geant4 with "Livermore" physics models for β- particle emitters. Results MALCs had ellipsoid-like shapes with major radii, r, of ~0.25, ~0.5 and ~1.3 mm. Rituximab was concentrated in the periphery of the MALCs. The absorbed doses delivered by 177 Lu, 131 I and 90 Y in MALCs were compared with literature data for spheres with two types of homogeneous biodistributions (on the surface or throughout the volume). Compared to the MALCs, the mean absorbed doses delivered in spheres with surface biodistributions were between 18% and 38% lower, while with volume biodistribution they were between 15% and 29% higher. Regarding the radionuclides comparison, the relationship between MALC dimensions, rituximab biodistribution and energy released per decay impacted the absorbed doses. Despite releasing less energy, 125 I delivered a greater absorbed dose per decay than 111 In in the r ~ 0.25 mm MALC (6.78·10-2 vs 6.26·10-2 µGy·Bq-1 ·s-1 ). Similarly, the absorbed doses per decay in the r ~ 0.5 mm MALC for 177 Lu (2.41·10-2 µGy·Bq-1 ·s-1 ) and 131 I (2.46·10-2 µGy·Bq-1 ·s-1 ) are higher than for 90 Y (1.98·10-2 µGy·Bq-1 ·s-1 ). Furthermore, radionuclides releasing more energy per decay delivered absorbed dose more uniformly through the MALCs. Finally, when considering the radiopharmaceutical effective half-life, due to the biological half-life of rituximab being best matched by the physical half-life of 177 Lu and 131 I compared to 90 Y, the first two radionuclides delivered higher absorbed doses. Conclusion In the simulated configurations, β- emitters delivered higher and more uniform absorbed dose than Auger electron emitters. When considering radiopharmaceutical half-lives, 177 Lu and 131 I delivered absorbed doses higher than 90 Y. In view of real irradiation of MALCs, such a work may be useful to select suited radionuclides and to help explain the biological effects.

Radiopharmaceutical dosimetry depends on the localization in space and time of radioactive sources and requires the estimation of the amount of energy emitted by the sources deposited within targets. In particular, when computing resources are not accessible, this task can be performed using precomputed tables of specific absorbed fractions (SAFs) or S values based on dosimetric models. The aim of the OpenDose collaboration is to generate and make freely available a range of dosimetric data and tools. Methods: OpenDose brings together resources and expertise from 18 international teams to produce and compare traceable dosimetric data using 6 of the most popular Monte Carlo codes in radiation transport (EGSnrc/EGS++, FLUKA, GATE, Geant4, MCNP/MCNPX, and PENELOPE). SAFs are uploaded, together with their associated statistical uncertainties, in a relational database. S values are then calculated from monoenergetic SAFs on the basis of the radioisotope decay data presented in International Commission on Radiological Protection Publication 107. Results: The OpenDose collaboration produced SAFs for all source region and target combinations of the 2 International Commission on Radiological Protection Publication 110 adult reference models. SAFs computed from the different Monte Carlo codes were in good agreement at all energies, with SDs below individual statistical uncertainties. Calculated S values were in good agreement with OLINDA/EXM 2.0 (commercial) and IDAC-Dose 2.1 (free) software. A dedicated website (www.opendose.org) has been developed to provide easy and open access to all data. Conclusion: The OpenDose website allows the display and downloading of SAFs and the corresponding S values for 1,252 radionuclides. The OpenDose collaboration, open to new research teams, will extend data production to other dosimetric models and implement new free features, such as online dosimetric tools and patient-specific absorbed dose calculation software, together with educational resources.

International audience; Purpose: The aim of this study was to quantitatively compare five commercial dosimetric software platforms based on the analysis of clinical datasets of patients who benefited from peptide receptor radionuclide therapy (PRRT) with 177 Lu-DOTATATE (LUTATHERA® ).Methods: The dosimetric analysis was performed on two patients during two cycles of PRRT with 177 Lu. Single photon emission computed tomography/computed tomography images were acquired at 4, 24, 72, and 192 h post injection. Reconstructed images were generated using Dosimetry Toolkit® (DTK) from Xeleris™ and HybridRecon-Oncology version_1.3_Dicom (HROD) from HERMES. Reconstructed images using DTK were analyzed using the same software to calculate time-integrated activity coefficients (TIAC), and mean absorbed doses were estimated using OLINDA/EXM V1.0 with mass correction. Reconstructed images from HROD were uploaded into PLANET® OncoDose from DOSIsoft, STRATOS from Phillips, Hybrid Dosimetry Module™ from HERMES, and SurePlan™ MRT from MIM. Organ masses, TIACs, and mean absorbed doses were calculated from each application using their recommendations.Results: The majority of organ mass estimates varied by

Background: The SR101 N-(3-[18F]Fluoropropyl) sulfonamide ([18F]SRF101) is a Sulforhodamine 101 derivative that was previously synthesised by our group. The fluorescent dye SR101 has been reported as a marker of astroglia in the neocortex of rodents in vivo. Objective: The aim of this study was to perform a toxicological evaluation of [18F]SRF101 and to estimate human radiation dosimetry based on preclinical studies. Methods: Radiation dosimetry studies were conducted based on biokinetic data obtained from a mouse model. A single-dose toxicity study was carried out. The toxicological limit chosen was Results: The absorbed and effective dose estimated using OLINDA/EXM V2.0 for male and female dosimetric models presented the same tendency. The highest total absorbed dose values were for different sections of the intestines. The mean effective dose was 4.03 x10-3 mSv/MBq and 5.08 x10-3 mSv/MBq for the male and female dosimetric models, respectively, using tissue-weighting factors from ICRP-89. The toxicity study detected no changes in the organ or whole-body weight, food consumption, haematologic or clinical chemistry parameters. Moreover, lesions or abnormalities were not found during the histopathological examination. Conclusion: The toxicological evaluation of SRF101 verified the biosafety of the radiotracer for human administration. The dosimetry calculations revealed that the radiation-associated risk of [18F]SRF101 would be of the same order as other 18F radiopharmaceuticals used in clinical applications. These study findings confirm that the novel radiotracer would be safe for use in human PET imaging.

To evaluate the outcomes and factors affecting success of urethroplasty in patients with stricture recurrence after Urolume urethral stent. Material and Methods: This is a retrospective international multicenter study on patients treated with urethral reconstruction after Urolume stent. Stricture and stent length, time between urethral stent insertion and urethroplasty, age, mode of stent retrieval, type of urethroplasty, complications and baseline, and posturethroplasty voiding parameters were analyzed. Successful outcome was defined as standard voiding, without need of any postoperative adjunctive procedure. Results: Sixty-three patients were included. Stent was removed at urethroplasty in 61 patients. Reconstruction technique was excision and primary anastomosis in 14 (22.2%), dorsal onlay buccal mucosa graft (BMG) in 9 (14.3%), ventral onlay BMG in 6 (9.5%), dorsolateral onlay BMG in 9 (14.3%), ventral onlay plus dorsal inlay BMG in 3 (4.8%), augmented anastomosis in 5 (7.9%), pedicled flap urethroplasty in 6 (9.5%), 2-stage procedure in 4 (6.4%), and perineal urethrostomy in 7(11.1%). Success rate was 81% at a mean 59.7 ± 63.4 months. Dilatation or internal urethrotomy was performed in 10 (15.9%) and redo-urethroplasty in 5 (7.9%). Total International Prostate Symptom Score, quality of life, urine maximum flow, and postvoid residual significantly improved (P

Dietmar Hubner and Lucie White (2016) argue, persuasively, that deep brain stimulation (DBS) would be unethical as a treatment for imprisoned psychopaths. Although I agree with this conclusion, I w...

International audience; BACKGROUND: This study's aim was to develop our dosimetric methodology using a commercial workstation for the routine evaluation of the organs at risk during peptide receptor radionuclide therapy (PRRT) with 177Lu.METHODS: First, planar and SPECT sensitivity factors were determined on phantoms. The reconstruction parameters were optimized by SPECT/CT image acquisition using a NEMA IEC phantom containing a 500 ml bottle of 177Lu, to simulate a kidney. The recovery coefficients were determined on various phantoms. For the red marrow, this was calculated using a NEMA IEC phantom that contained a centrally placed bottle of 80 ml of 177Lu (to model the L2-L4 red marrow) flanked by two 200 ml bottles with 177Lu to simulate the kidneys. Then, SPECT/CT images were acquired at 4, 24, 72, and 192 h after injection in 12 patients with neuroendocrine tumors who underwent PRRT with 177Lu-DOTATATE. SPECT data were reconstructed using the iterative ordered subset expectation maximization (OSEM) method, with six iterations and ten subsets, attenuation, scatter, recovery resolution corrections, and a Gaussian post-filter of 0.11 cm. The liver, spleen, kidneys, and red marrow dose per administered activity (AD/A admin) values were calculated with the Medical Internal Radiation Dose (MIRD) formalism and the residence times (Dosimetry toolkit® application) using standard and CT imaging-based organ masses (OLINDA/EXM® V1.0 software).RESULTS: Sensitivity factors of 6.11 ± 0.01 and 5.67 ± 0.08 counts/s/MBq were obtained with planar and SPECT/CT acquisitions, respectively. A recovery coefficient of 0.78 was obtained for the modeled L2-L4 red marrow. The mean AD/A admin values were 0.43 ± 0.13 mGy/MBq [0.27-0.91] for kidneys, 0.54 ± 0.58 mGy/MBq [0.12-2.26] for liver, 0.61 ± 0.13 mGy/MBq [0.42-0.89] for spleen, and 0.04 ± 0.02 mGy/MBq [0.01-0.09] for red marrow. The AD/A admin values varied when calculated using the personalized and standard organ mass, particularly for kidneys (p = 1 × 10-7), spleen (p = 0.0069), and red marrow (p = 0.0027). Intra-patient differences were observed especially in organs close to or including tumor cells or metastases.CONCLUSIONS: The obtained AD/A admin values were in agreement with the literature data. This study shows the technical feasibility of patient dosimetry in clinical practice and the need to obtain patient-specific information.

I argue that psychopathy undermines three common assumptions typically invoked in favor of moderate reasons responsive theories of moral responsibility. First, I propose a theory of psychopathic agency and claim that psychopathic agency suggests that the systems underlying receptivity to reason bifurcate into at least two sub-systems of receptivity. Next, I claim that the bifurcation of systems for receptivity suggests that reactivity is not “all of a piece” but that it too decomposes into at least two sub-systems. Lastly, I argue that prior attempts by Fischer and Ravizza to address these concerns contain an appeal to internalism. Since Fischer and Ravizza want their theory to remain agnostic about the nature of reasons for action, this appeal to internalism is problematic for their view. I close by suggesting that if we are to make sense of when and why psychopaths are responsible then a mechanism-based theory of responsibility must be able to explain how different systems of receptivity and reactivity ...

The aim of this work was to study the biodistribution, metabolism and radiation dosimetry of rats injected with [Free fraction and stability in fresh human plasma were determined in vitro. PET/CT was performed on anesthetized rats. Organs were identified and 3D volumes of interest (VOIs) were manually drawn on the CT in the center of each organ. Time activity curves (TACs) were created with these VOIs, enabling the calculation of residence times. To confirm these values, ex vivo measurements of organs were performed. Plasma and urine were also collected to study in vivo metabolism. Data was extrapolated to humans, effective doses were estimated using ICRP-60 and ICRP-89 dosimetric models and absorbed doses were estimated using OLINDA/EXM V1.0 and OLINDA/EXM V2.0 (which use weighting factors from ICRP-103 to do the calculations).The [This study shows that the presented compound exhibits stability in plasma and plasma protein binding very similar to memantine. Its dosimetry shows that it is suitable for use in humans due to a low total effective dose compared to other PET radiotracers.