Tri-Modality therapy with I-125 brachytherapy, external beam radiation therapy, and short- or long-term hormone therapy for high-risk localized prostate cancer (TRIP): study protocol for a phase III, multicenter, randomized, controlled trial

<p>Abstract</p> <p>Background</p> <p>Patients with high Gleason score, elevated prostate specific antigen (PSA) level, and advanced clinical stage are at increased risk for both local and systemic relapse. Recent data suggests higher radiation doses decrease local recurrence and may ultimately benefit biochemical, metastasis-free and disease-specific survival. No randomized data is available on the benefits of long-term hormonal therapy (HT) in these patients. A prospective study on the efficacy and safety of trimodality treatment consisting of HT, external beam radiation therapy (EBRT), and brachytherapy (BT) for high-risk prostate cancer (PCa) is strongly required.</p> <p>Methods/Design</p> <p>This is a phase III, multicenter, randomized controlled trial (RCT) of trimodality with BT, EBRT, and HT for high-risk PCa (TRIP) that will investigate the impact of adjuvant HT following BT using iodine-125 (¹²⁵I-BT) and supplemental EBRT with neoadjuvant and concurrent HT. Prior to the end of September 2012, a total of 340 patients with high-risk PCa will be enrolled and randomized to one of two treatment arms. These patients will be recruited from more than 41 institutions, all of which have broad experience with ¹²⁵I-BT. Pathological slides will be centrally reviewed to confirm patient eligibility. The patients will commonly undergo 6-month HT with combined androgen blockade (CAB) before and during ¹²⁵I-BT and supplemental EBRT. Those randomly assigned to the long-term HT group will subsequently undergo 2 years of adjuvant HT with luteinizing hormone-releasing hormone agonist. All participants will be assessed at baseline and every 3 months for the first 30 months, then every 6 months until 84 months from the beginning of CAB.</p> <p>The primary endpoint is biochemical progression-free survival. Secondary endpoints are overall survival, clinical progression-free survival, disease-specific survival, salvage therapy non-adaptive interval, and adverse events.</p> <p>Discussion</p> <p>To our knowledge, there have been no prospective studies documenting the efficacy and safety of trimodality therapy for high-risk PCa. The present RCT is expected to provide additional insight regarding the potency and limitations of the addition of 2 years of adjuvant HT to this trimodality approach, and to establish an appropriate treatment strategy for high-risk PCa.</p> <p>Trial registration</p> <p>UMIN000003992</p

Peer-Victimization and Mental Health Problems in Adolescents: Are Parental and School Support Protective?

The aim of this study was to investigate the frequency and effects of peer-victimization on mental health problems among adolescents. Parental and school support were assumed as protective factors that might interact with one another in acting as buffers for adolescents against the risk of peer-victimization. Besides these protective factors, age and gender were additionally considered as moderating factors. The Social and Health Assessment survey was conducted among 986 students aged 11–18 years in order to assess peer-victimization, risk and protective factors and mental health problems. For mental health problems, the Strengths and Difficulties Questionnaire (SDQ) was used. Effects of peer-victimization on mental health problems were additionally compared with normative SDQ data in order to obtain information about clinically relevant psychopathology in our study sample. Results of this study show that peer-victimization carries a serious risk for mental health problems in adolescents. School support is effective in both male and female adolescents by acting as a buffer against the effect of victimization, and school support gains increasing importance in more senior students. Parental support seems to be protective against maladjustment, especially in peer-victimized girls entering secondary school. Since the effect of peer-victimization can be reduced by parental and school support, educational interventions are of great importance in cases of peer-victimization

Association between infection early in life and mental disorders among youth in the community: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>The objective of this study was to examine the association between infection early in life and mental disorders among youth in the community.</p> <p>Methods</p> <p>Data were drawn from the MECA (Methods in Epidemiology of Child and Adolescent psychopathology), a community-based study of 1,285 youth in the United States conducted in 1992. Multiple logistic regression analyses were used to investigate the association between parent/caregiver-reported infection early in life and DSM/DISC diagnoses of mental disorders at ages 9-17.</p> <p>Results</p> <p>Infection early in life was associated with a significantly increased odds of major depression (OR = 3.9), social phobia (OR = 5.8), overanxious disorder (OR = 6.1), panic disorder (OR = 12.1), and oppositional defiant disorder (OR = 3.7).</p> <p>Conclusions</p> <p>These findings are consistent with and extend previous results by providing new evidence suggesting a link between infection early in life and increased risk of depression and anxiety disorders among youth. These results should be considered preliminary. Replication of these findings with longitudinal epidemiologic data is needed. Possible mechanisms are discussed.</p

Molecular and cellular mechanisms underlying the evolution of form and function in the amniote jaw.

The amniote jaw complex is a remarkable amalgamation of derivatives from distinct embryonic cell lineages. During development, the cells in these lineages experience concerted movements, migrations, and signaling interactions that take them from their initial origins to their final destinations and imbue their derivatives with aspects of form including their axial orientation, anatomical identity, size, and shape. Perturbations along the way can produce defects and disease, but also generate the variation necessary for jaw evolution and adaptation. We focus on molecular and cellular mechanisms that regulate form in the amniote jaw complex, and that enable structural and functional integration. Special emphasis is placed on the role of cranial neural crest mesenchyme (NCM) during the species-specific patterning of bone, cartilage, tendon, muscle, and other jaw tissues. We also address the effects of biomechanical forces during jaw development and discuss ways in which certain molecular and cellular responses add adaptive and evolutionary plasticity to jaw morphology. Overall, we highlight how variation in molecular and cellular programs can promote the phenomenal diversity and functional morphology achieved during amniote jaw evolution or lead to the range of jaw defects and disease that affect the human condition

Evaluation of a robotic technique for transrectal MRI-guided prostate biopsies

Item does not contain fulltextOBJECTIVES: To evaluate the accuracy and speed of a novel robotic technique as an aid to perform magnetic resonance image (MRI)-guided prostate biopsies on patients with cancer suspicious regions. METHODS: A pneumatic controlled MR-compatible manipulator with 5 degrees of freedom was developed in-house to guide biopsies under real-time imaging. From 13 consecutive biopsy procedures, the targeting error, biopsy error and target displacement were calculated to evaluate the accuracy. The time was recorded to evaluate manipulation and procedure time. RESULTS: The robotic and manual techniques demonstrated comparable results regarding mean targeting error (5.7 vs 5.8 mm, respectively) and mean target displacement (6.6 vs 6.0 mm, respectively). The mean biopsy error was larger (6.5 vs 4.4 mm) when using the robotic technique, although not significant. Mean procedure and manipulation time were 76 min and 6 min, respectively using the robotic technique and 61 and 8 min with the manual technique. CONCLUSIONS: Although comparable results regarding accuracy and speed were found, the extended technical effort of the robotic technique make the manual technique - currently - more suitable to perform MRI-guided biopsies. Furthermore, this study provided a better insight in displacement of the target during in vivo biopsy procedures.01 februari 201

Benchmarking Materials Property Prediction Methods: The Matbench Test Set and Automatminer Reference Algorithm

We present a benchmark test suite and an automated machine learning procedure for evaluating supervised machine learning (ML) models for predicting properties of inorganic bulk materials. The test suite, Matbench, is a set of 13 ML tasks that range in size from 312 to 132k samples and contain data from 10 density functional theory-derived and experimental sources. Tasks include predicting optical, thermal, electronic, thermodynamic, tensile, and elastic properties given a materials composition and/or crystal structure. The reference algorithm, Automatminer, is a highly-extensible, fully-automated ML pipeline for predicting materials properties from materials primitives (such as composition and crystal structure) without user intervention or hyperparameter tuning. We test Automatminer on the Matbench test suite and compare its predictive power with state-of-the-art crystal graph neural networks and a traditional descriptor-based Random Forest model. We find Automatminer achieves the best performance on 8 of 13 tasks in the benchmark. We also show our test suite is capable of exposing predictive advantages of each algorithm - namely, that crystal graph methods appear to outperform traditional machine learning methods given ~10^4 or greater data points. The pre-processed, ready-to-use Matbench tasks and the Automatminer source code are open source and available online (http://hackingmaterials.lbl.gov/automatminer/). We encourage evaluating new materials ML algorithms on the MatBench benchmark and comparing them against the latest version of Automatminer.Comment: Main text, supplemental inf

Incidence of seed migration to the chest, abdomen, and pelvis after transperineal interstitial prostate brachytherapy with loose 125I seeds

<p>Abstract</p> <p>Background</p> <p>The aim was to determine the incidence of seed migration not only to the chest, but also to the abdomen and pelvis after transperineal interstitial prostate brachytherapy with loose ¹²⁵I seeds.</p> <p>Methods</p> <p>We reviewed the records of 267 patients who underwent prostate brachytherapy with loose ¹²⁵I seeds. After seed implantation, orthogonal chest radiographs, an abdominal radiograph, and a pelvic radiograph were undertaken routinely to document the occurrence and sites of seed migration. The incidence of seed migration to the chest, abdomen, and pelvis was calculated. All patients who had seed migration to the abdomen and pelvis subsequently underwent a computed tomography scan to identify the exact location of the migrated seeds. Postimplant dosimetric analysis was undertaken, and dosimetric results were compared between patients with and without seed migration.</p> <p>Results</p> <p>A total of 19,236 seeds were implanted in 267 patients. Overall, 91 of 19,236 (0.47%) seeds migrated in 66 of 267 (24.7%) patients. Sixty-nine (0.36%) seeds migrated to the chest in 54 (20.2%) patients. Seven (0.036%) seeds migrated to the abdomen in six (2.2%) patients. Fifteen (0.078%) seeds migrated to the pelvis in 15 (5.6%) patients. Seed migration occurred predominantly within two weeks after seed implantation. None of the 66 patients had symptoms related to the migrated seeds. Postimplant prostate D90 was not significantly different between patients with and without seed migration.</p> <p>Conclusion</p> <p>We showed the incidence of seed migration to the chest, abdomen and pelvis. Seed migration did not have a significant effect on postimplant prostate D90.</p

Elevated basal serum tryptase identifies a multisystem disorder associated with increased TPSAB1 copy number

Elevated basal serum tryptase levels are present in 4-6% of the general population, but the cause and relevance of such increases are unknown. Previously, we described subjects with dominantly inherited elevated basal serum tryptase levels associated with multisystem complaints including cutaneous flushing and pruritus, dysautonomia, functional gastrointestinal symptoms, chronic pain, and connective tissue abnormalities, including joint hypermobility. Here we report the identification of germline duplications and triplications in the TPSAB1 gene encoding α-tryptase that segregate with inherited increases in basal serum tryptase levels in 35 families presenting with associated multisystem complaints. Individuals harboring alleles encoding three copies of α-tryptase had higher basal serum levels of tryptase and were more symptomatic than those with alleles encoding two copies, suggesting a gene-dose effect. Further, we found in two additional cohorts (172 individuals) that elevated basal serum tryptase levels were exclusively associated with duplication of α-tryptase-encoding sequence in TPSAB1, and affected individuals reported symptom complexes seen in our initial familial cohort. Thus, our findings link duplications in TPSAB1 with irritable bowel syndrome, cutaneous complaints, connective tissue abnormalities, and dysautonomia