Incorporating characteristics of human creativity into an evolutionary art algorithm (journal article)

A perceived limitation of evolutionary art and design algorithms is that they rely on human intervention; the artist selects the most aesthetically pleasing variants of one generation to produce the next. This paper discusses how computer generated art and design can become more creatively human-like with respect to both process and outcome. As an example of a step in this direction, we present an algorithm that overcomes the above limitation by employing an automatic fitness function. The goal is to evolve abstract portraits of Darwin, using our 2nd generation fitness function which rewards genomes that not just produce a likeness of Darwin but exhibit certain strategies characteristic of human artists. We note that in human creativity, change is less choosing amongst randomly generated variants and more capitalizing on the associative structure of a conceptual network to hone in on a vision. We discuss how to achieve this fluidity algorithmically

Validation of a new prognostic model to easily predict outcome in renal cell carcinoma: The GRANT score applied to the ASSURE trial population

Background: Prognostic scores have been developed to estimate the risk of recurrence and the probability of survival after nephrectomy for renal cell carcinoma (RCC). The use of these tools, despite being helpful to plan a customized schedule of follow-up, to the patient's tailored counselling and to select individuals who could potentially benefit from adjuvant treatment, currently is not routine, due to their relative complexity and to the lack of histological data (i.e. necrosis).Patients and methods: We developed a simple score called GRade, Age, Nodes and Tumor (GRANT) based on four easily obtained parameters: Fuhrman grade, age, pathological nodal status and pathological tumor size. Patients with 0 or 1 factor are classified as favorable risk, whereas patients with two or more risk factors as unfavorable risk. The large population of RCC patients from the ASSURE adjuvant trial was used as independent dataset for this external validation, to investigate the prognostic value of the new score in terms of disease-free survival and overall survival and to evaluate its possible application as predictive tool. Statistical analyses were carried out by the Department of Biostatistics & Computational Biology, Dana-Farber Cancer Institute (Boston, USA) for the ASSURE trial patients' population.Results: The performance of the new model is similar to that of the already validated score systems, but its strength, compared with the others already available, is the ease and clarity of its calculation, with great speed of use during the clinical practice. Limitations are the use of the Fuhrman nuclear grade, not valid for rare histologies, and the TNM classification modifications over time.Conclusion: The GRANT score demonstrated its potential usefulness for clinical practice

The structural properties and star formation history of Leo T from deep LBT photometry

We present deep, wide-field g and r photometry of the transition type dwarf galaxy Leo T, obtained with the blue arm of the Large Binocular Telescope. The data confirm the presence of both very young (5 Gyr) stars. We study the structural properties of the old and young stellar populations by preferentially selecting either population based on their color and magnitude. The young population is significantly more concentrated than the old population, with half-light radii of 104+-8 and 148+-16 pc respectively, and their centers are slightly offset. Approximately 10% of the total stellar mass is estimated to be represented by the young stellar population. Comparison of the color-magnitude diagram (CMD) with theoretical isochrones as well as numerical CMD-fitting suggest that star formation began over 10 Gyr ago and continued in recent times until at least a few hundred Myr ago. The CMD-fitting results are indicative of two distinct star formation bursts, with a quiescent period around 3 Gyr ago, albeit at low significance. The results are consistent with no metallicity evolution and [Fe/H] ~ -1.5 over the entire age of the system. Finally, the data show little if any sign of tidal distortion of Leo T.Comment: 8 pages, 9 figures, some small textual changes, accepted for publication in the Astrophysical Journa

A randomized phase II trial of mitoxantrone, estramustine and vinorelbine or bcl-2 modulation with 13-cis retinoic acid, interferon and paclitaxel in patients with metastatic castrate-resistant prostate cancer: ECOG 3899

<p>Abstract</p> <p>Background</p> <p>To test the hypothesis that modulation of Bcl-2 with 13-cis retinoic acid (CRA)/interferon-alpha2b (IFN) with paclitaxel (TAX), or mitoxantrone, estramustine and vinorelbine (MEV) will have clinical activity in men with metastatic castrate-resistant prostate cancer (CRPC).</p> <p>Methods</p> <p>70 patients were treated with either MEV (Arm A) in a 3-week cycle or CRA/IFN/TAX with an 8-week cycle (Arm B). Patients were assessed for response, toxicity, quality of life (QOL), and the effect of treatment on Bcl-2 levels in peripheral blood mononuclear cells (PBMC).</p> <p>Results</p> <p>The PSA response rates were 50% and 23%, measurable disease response rates (CR+PR) 14% and 15%, and median overall survival 19.4 months and 13.9 months on Arm A and Arm B respectively. Transient grade 4 neutropenia occurred in 18 and 2 patients, and grade 3 to 4 thrombosis in 7 patients and 1 patient in Arm A and Arm B respectively. Patients on Arm B reported a clinically significant decline in QOL between baseline and week 9/10 (.71 s.d.), and a significantly lower level of QOL than Arm A (p = 0.01). As hypothesized, Bcl-2 levels decreased with CRA/IFN therapy only in Arm B (p = 0.03).</p> <p>Conclusions</p> <p>Treatment with MEV was well tolerated and demonstrated clinical activity in patients with CRPC. Given the adverse effect of CRA/IFN/TAX on QOL, the study of other novel agents that target Bcl-2 family proteins is warranted. The feasibility of measuring Bcl-2 protein in a cooperative group setting is hypothesis generating and supports further study as a marker for Bcl-2 targeted therapy.</p> <p>Trial Registration</p> <p><b>Clinical Trials Registration number</b>: CDR0000067865</p

Use of the Spine AdVerse Events Severity (SAVES) System to Categorize and Report Adverse Events in Spine Surgery.

Introduction: Analysis of adverse events (AEs) in spine surgery has historically been retrospective, utilizing hospital administrative data. Our objective was to determine the incidence, severity and effect on hospital length of stay (LOS) for AEs in spine surgery using the Spine AdVerse Events Severity (SAVES V2) system. Methods: AEs for all surgical spine patients at our institution were prospectively collected for 18 months and correlated with retrospective data from operative reports and H&Ps. Statistical analyses compared patient demographics, diagnoses, and surgical characteristics to hospital length of stay and likelihood of adverse events. Results: This system captured 75% (765/977) of surgical cases for all indications over the study period. 73% (541/743) of patients experienced at least one AE, with an average of 1.2 AEs per patient (range 0-5). The most common AEs were pain control (31%), urinary retention (9.7%), wound infection (6.3%), and incidental durotomy (5.8%). For patients experiencing at least one AE, 30% had no effect on LOS, 48% increased LOS by 1-2 days, 15% increased LOS by 3-7 days, and 7% had prolonged LOS greater than 8 days. Our system captured 25.4% more adverse events (60.0% vs. 34.6%) than hospital administrative data. Univariate analysis revealed patient age, emergent surgery, diagnostic and surgical categories, and spine region to be predictors of both AEs and LOS. Instrumentation was predictive of increased LOS but not AEs. The type of AE was strongly associated with LOS. Multivariable analysis of AE likelihood demonstrated emergent surgery to be the strongest independent predictor with an adjusted odds ratio of 8.5 versus elective surgery. Discussion: Spine surgery is associated with a high incidence of adverse events, which often prolong hospital length of stay. Better characterization of adverse events and their predictors could lead to improved management strategies that reduce patient morbidity and mortality

U.S. Inhibitor Pilot Project: Study Design And Methods Validation

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106090/1/jth01876.pd

Clinical actionability of comprehensive genomic profiling for management of rare or refractory cancers

Background. The frequency with which targeted tumor sequencing results will lead to implemented change in care is unclear. Prospective assessment of the feasibility and limitations of using genomic sequencing is critically important. Methods. A prospective clinical study was conducted on 100 patients with diverse-histology, rare, or poor-prognosis cancers to evaluate the clinical actionability of a Clinical Laboratory Improvement Amendments (CLIA)-certified, comprehensive genomic profiling assay (FoundationOne), using formalin-fixed, paraffin-embedded tumors. The primary objectives were to assess utility, feasibility, and limitations of genomic sequencing for genomically guided therapy or other clinical purpose in the setting of a multidisciplinary molecular tumor board. Results. Of the tumors from the 92 patients with sufficient tissue, 88 (96%) had at least one genomic alteration (average 3.6, range 0–10). Commonly altered pathways included p53 (46%), RAS/RAF/MAPK (rat sarcoma; rapidly accelerated fibrosarcoma; mitogen-activated protein kinase) (45%), receptor tyrosine kinases/ligand (44%), PI3K/AKT/mTOR (phosphatidylinositol-4,5-bisphosphate 3-kinase; protein kinase B; mammalian target of rapamycin) (35%), transcription factors/regulators (31%), and cell cycle regulators (30%). Many low frequency but potentially actionable alterations were identified in diverse histologies. Use of comprehensive profiling led to implementable clinical action in 35% of tumors with genomic alterations, including genomically guided therapy, diagnostic modification, and trigger for germline genetic testing. Conclusion. Use of targeted next-generation sequencing in the setting of an institutional molecular tumor board led to implementable clinical action in more than one third of patients with rare and poor-prognosis cancers. Major barriers to implementation of genomically guided therapy were clinical status of the patient and drug access. Early and serial sequencing in the clinical course and expanded access to genomically guided early-phase clinical trials and targeted agents may increase actionability. Implications for Practice: Identification of key factors that facilitate use of genomic tumor testing results and implementation of genomically guided therapy may lead to enhanced benefit for patients with rare or difficult to treat cancers. Clinical use of a targeted next-generation sequencing assay in the setting of an institutional molecular tumor board led to implementable clinical action in over one third of patients with rare and poor prognosis cancers. The major barriers to implementation of genomically guided therapy were clinical status of the patient and drug access both on trial and off label. Approaches to increase actionability include early and serial sequencing in the clinical course and expanded access to genomically guided early phase clinical trials and targeted agents

Atrial and placental melanoma metastasis: a case report and literature review

Malignant melanoma can metastasize to virtually any organ of the body. The aggressiveness is determined by the primary site, depth of dermal invasion, presence or absence of ulceration, lymphovascular infiltration and regional lymph node involvement. We report a case of a pregnant woman with a previous history of stage 3 melanoma who presented with cardiac metastasis and placental melanoma infiltration. A review of literature on cardiac and placental involvement of melanoma is also provided

Effects of clockwise and counterclockwise job shift work rotation on sleep and work-life balance on hospital nurses

Rotational shift work is associated with sleep disturbances, increased risk of cardiovascular and psychological disorders, and may negatively impact work\u2013life balance. The direction of shift rotation (Clockwise, CW or counterclockwise, CCW) and its role in these disorders are poorly understood. The aim of the study was to investigate the effect of the shift schedule direction on sleep quantity and quality, alertness and work performance, and on work\u2013life balance on hospital nurses. One-hundred female nurses, working a continuous rapid shift schedule in hospitals in the north of Italy, participated in this cross-sectional study. Fifty worked on CW rotation schedule (Morning: 6 a.m.\u20132 p.m., Afternoon: 2 p.m.\u201310 p.m., Night: 10 p.m.\u20136 a.m., 2 rest days) and fifty on CCW rotation (Afternoon, Morning, Morning, Night, 3 rest days). Data were collected by ad hoc questionnaire and daily diary. During the shift cycle CW nurses slept longer (7.40 \ub1 2.24 h) than CCW (6.09 \ub1 1.73; p < 0.001). CW nurses reported less frequently than CCW awakening during sleep (40% vs. 80%; p < 0.001), attention disturbance during work (20% vs. 64%; p < 0.001), and interference with social and family life (60% vs. 96% and 20% vs. 70%, respectively; p < 0.001). CCW rotating shift schedule seems to be characterized by higher sleep disturbances and a worse work\u2013life balance