Dopamine Beta Hydroxylase Genotype Identifies Individuals Less Susceptible to Bias in Computer-Assisted Decision Making

Computerized aiding systems can assist human decision makers in complex tasks but can impair performance when they provide incorrect advice that humans erroneously follow, a phenomenon known as “automation bias.” The extent to which people exhibit automation bias varies significantly and may reflect inter-individual variation in the capacity of working memory and the efficiency of executive function, both of which are highly heritable and under dopaminergic and noradrenergic control in prefrontal cortex. The dopamine beta hydroxylase (DBH) gene is thought to regulate the differential availability of dopamine and norepinephrine in prefrontal cortex. We therefore examined decision-making performance under imperfect computer aiding in 100 participants performing a simulated command and control task. Based on two single nucleotide polymorphism (SNPs) of the DBH gene, −1041 C/T (rs1611115) and 444 G/A (rs1108580), participants were divided into groups of low and high DBH enzyme activity, where low enzyme activity is associated with greater dopamine relative to norepinephrine levels in cortex. Compared to those in the high DBH enzyme activity group, individuals in the low DBH enzyme activity group were more accurate and speedier in their decisions when incorrect advice was given and verified automation recommendations more frequently. These results indicate that a gene that regulates relative prefrontal cortex dopamine availability, DBH, can identify those individuals who are less susceptible to bias in using computerized decision-aiding systems

Combination of searches for heavy spin-1 resonances using 139 fb−1 of proton-proton collision data at s = 13 TeV with the ATLAS detector

A combination of searches for new heavy spin-1 resonances decaying into different pairings of W, Z, or Higgs bosons, as well as directly into leptons or quarks, is presented. The data sample used corresponds to 139 fb−1 of proton-proton collisions at = 13 TeV collected during 2015–2018 with the ATLAS detector at the CERN Large Hadron Collider. Analyses selecting quark pairs (qq, bb, , and tb) or third-generation leptons (τν and ττ) are included in this kind of combination for the first time. A simplified model predicting a spin-1 heavy vector-boson triplet is used. Cross-section limits are set at the 95% confidence level and are compared with predictions for the benchmark model. These limits are also expressed in terms of constraints on couplings of the heavy vector-boson triplet to quarks, leptons, and the Higgs boson. The complementarity of the various analyses increases the sensitivity to new physics, and the resulting constraints are stronger than those from any individual analysis considered. The data exclude a heavy vector-boson triplet with mass below 5.8 TeV in a weakly coupled scenario, below 4.4 TeV in a strongly coupled scenario, and up to 1.5 TeV in the case of production via vector-boson fusion

Stereotactic radiation therapy of liver metastases

Purpose. A number of minimal-invasive methods have been developed for the treatment of non-resectable liver metastases. A focused high dose can be delivered to a liver tumor with sparing of surrounding normal liver tissue using non-invasive stereotactic techniques. Methods. Sixty-six metastases were treated stereotactically in 43 patients during a phase 2 trial. Results. There were no major side effects observed. The actuarial local control was 82% after 18 months. The median actuarial survival was 24 months. However, there was a significantly improved survival in patients without additional extrahepatic tumor manifestation at the time of treatment compared to those, who were treated in palliative intention (87% vs. 24% after 18 months, p=0.001 (log-rank). Conclusion. Stereotactic single dose irradiation is a non-invasive and safe treatment option for patients with inoperable liver metastases. Phase III studies will further evaluate this new approach

Extracranial stereotactic radiation therapy: Set-up accuracy of patients treated for liver metastases

Purpose: Patients with liver metastases might benefit from high-dose conformal radiation therapy. A high accuracy of repositioning and a reduction of target movement are necessary for such an approach. The set-up accuracy of patients with liver metastases treated with stereotactic single dose radiation was evaluated. Methods and Materials: Twenty-four patients with liver metastases were treated with single dose radiation therapy on 26 occasions using a self-developed stereotactic frame. Liver movement was reduced by abdominal pressure, The effectiveness was evaluated under fluoroscopy, CT scans were performed on the planning day and directly before treatment. Representative reference marks were chosen and the coordinates were calculated. In addition, the target displacement was quantitatively evaluated after treatment. Results: Diaphragmal movement was reduced to median 7 mm (range: 3-13 mm). The final set-up accuracy of the body was limited to all of median 1.8 mm in latero-lateral direction (range: 0.3-5.0 mm) and 2.0 mm in anterior-posterior direction (0.8-3.8 mm), Deviations of the body in cranio-caudal direction were always less than the thickness of one CT slice (<5 mm). However, a repositioning was necessary in 16 occasions. The final target shift was median 1.6 mm (0.2-7.0 mm) in latero-lateral and 2.3 mm in anterior-posterior direction (0.0-6.3 mm), The median shift in cranio-caudal direction was 4.4 mm (0.0-10.0 mm), Conclusions: In patients with liver metastases, a high set-up accuracy of the body and the target can be achieved. This allows a high-dose focal radiotherapy of these lesions. However, a control CT scan should be performed directly before therapy to confirm set-up accuracy and possibly prompt necessary corrections. (C) 2000 Elsevier Science Inc

Assessment of focal liver reaction by multiphasic CT after stereotactic single-dose radiotherapy of liver tumors

Purpose: To characterize and quantitatively assess focal radiation reactions in the liver after stereotactic single-dose radiotherapy for liver malignancies. Methods and Materials: A total of 131 multiphasic CT scans were performed in 36 patients before and after stereotactic radiotherapy for liver tumors. The examination protocol included a nonenhanced scan and contrast-enhanced scans at different times after contrast injection. The volume of the reaction was determined in each scan and the threshold dose calculated using the dose-volume histogram of the treatment plan. Results: Every patient showed a focal radiation reaction on at least one follow-up examination. In 74% of the posttherapeutic scans, a sharply demarcated hypodense area surrounded the treated tumor in the nonenhanced scans. The reaction occurred at a median of 1.8 months (range 1.2-4.6) after radiotherapy. The median threshold dose was 13.7 Gy (range 8.9=19.2). The threshold dose strongly correlated with the time of detection after therapy (r = 0.7). Radiologically, three reaction types were found on the enhanced scans: type 1, portal-venous phase: hypodense and late phase: isodense; type 2, portal-venous phase: hypodense and late phase: hyperdense; and type 3, portal-venous phase: isodense/hyperdense and late phase: hyperdense. Type 1 or 2 reactions were observed significantly earlier than type 3 (p <0.05). The median threshold dose for type 1 or 2 reactions was significantly lower than for type 3 (p <0.05). The reaction volume decreased with longer follow-up (2-4 months: median 40% of initial volume). The reaction types shifted with follow-up: 58% were of type 1 at the initial manifestation and 58% were of type 3 at the next examination thereafter. Conclusion: A focal radiation reaction occurs after stereotactic single-dose therapy in the liver. The volume of the reaction decreases and changes its radiologic appearance during follow-up. This reaction has to be differentiated from recurrent tumor. (C) 2003 Elsevier Inc

Noninvasive patient fixation for extracranial stereotactic radiotherapy

Purpose: To evaluate the setup accuracy that can be achieved with a novel noninvasive patient fixation technique based on a body cast attached to a recently developed stereotactic body frame during fractionated extracranial stereotactic radiotherapy. Methods and Materials: Thirty-one CT studies (greater than or equal to 20 slices, thickness: 3 mm) from 5 patients who were immobilized in a body cast attached to a stereotactic body frame for treatment of paramedullary tumors in the thoracic or lumbar spine were evaluated with respect to setup accuracy. The immobilization device consisted of a custom-made wrap-around body cast that extended from the neck to the thighs and a separate head mask, both made from Scotchcast. Each CT study was performed immediately before or after every second or third actual treatment fraction without repositioning the patient between CT and treatment. The stereotactic localization system was mounted and the isocenter as initially located stereotactically was marked with fiducials for each CT study. Deviation of the treated isocenter as compared to the planned position was measured in all three dimensions. Results: The immobilization device can be easily handled, attached to and removed from the stereotactic frame and thus enables treatment of multiple patients with the same stereotactic frame each day. Mean patient movements of 1.6 mm +/- 1.2 mm (laterolateral [LL]), 1.4 mm +/- 1.0 mm (anterior-posterior [AP]), 2.3 mm +/- 1.3 mm (transversal vectorial error [VE]) and < slice thickness = 3 mm (craniocaudal [CC]) were recorded for the targets in the thoracic spine and 1.4 mm +/- 1.0 mm (LL), 1.2 mm +/- 0.7 mm (AP), 1.8 mm +/- 1.2 mm (VE), and < 3 mm (CC) for the lumbar spine. The worst case deviation was 3.9 mm for the first patient with the target in the thoracic spine tin the LL direction). Combining those numbers (mean transversal VE for both locations and maximum CC error of 3 mm), the mean three-dimensional vectorial patient movement and thus the mean overall accuracy can be safely estimated to be less than or equal to 3.6 mm. Conclusion: The presented combination of a body cast and head mask system in a rigid stereotactic body frame ensures reliable noninvasive patient fixation for fractionated extracranial stereotactic radiotherapy and may enable dose escalation for less radioresponsive tumors that are near the spinal cord or otherwise critically located while minimizing the risk of late sequelae. (C) 1999 Elsevier Science Inc

Stereotactic single-dose radiation therapy of liver tumors: Results of a phase I/II trial

Purpose: To investigate the feasibility and the clinical response of a stereotactic single-dose radiation treatment for liver rumors. Patients and Methods: Between April 1997 and September 1999, a stereotactic single-dose radiation treatment of 60 liver tumors (four primary tumors, 56 metastases) in 37 patients was performed. Patients were positioned in an individually shaped vacuum pillow. The applied dose was escalated from 14 to 26 Gy (reference point), with the 80% isodose surrounding the planning target volume. Median tumor size was 10 cm(3) (range, 1 to 132 cm(3)). The morbidity, clinical outcome, laboratory findings, and response as seen on computed tomography (CT) scan were evaluated. Results: Follow-up data could be obtained from 55 treated tumors (35 patients). The median follow-up period was 5.7 months (range, 1.0 to 26.1 months; mean, 9.5 months). The treatment was well tolerated by all patients. There were no major side effects. Fifty-four (98%) of 55 tumors were locally controlled after 6 weeks at the initial follow-up based on the CT findings (22 cases of stable disease, 28 partial responses, and four complete responses). After a dose-escalating and learning phase, the actuarial local tumor control rate was 81% at 18 months after therapy. A total of 12 local failures were observed during follow-up. So far, the longest local tumor control is 26.1 months. Conclusion: Stereotactic single-dose radiation therapy is a feasible method for the treatment of singular inoperable liver metastases with the potential of a high local tumor control rate and low morbidity. J Clin Oncol 19:164-170. (C) 2001 by American Society of Clinical Oncology