Path planning for sailboat robots is a challenging task particularly due to the kinematics and dynamics modelling of such kinds of wind propelled boats. The problem is divided into two layers. The ...first one is global were a general trajectory composed of waypoints is planned, which can be done automatically based on some variables such as weather conditions or defined by hand using some human-robot interface (a ground-station). In the second local layer, at execution time, the global route should be followed by making the sailboat proceed between each pair of consecutive waypoints. Our proposal in this paper is an algorithm for the global, path generation layer, which has been developed for the N-Boat (The Sailboat Robot project), in order to compute feasible sailing routes between a start and a target point while avoiding dangerous situations such as obstacles and borders. A reinforcement learning approach (Q-Learning) is used based on a reward matrix and a set of actions that changes according to wind directions to account for the dead zone, which is the region against the wind where the sailboat can not gain velocity. Our algorithm generates straight and zigzag paths accounting for wind direction. The path generated also guarantees the sailboat safety and robustness, enabling it to sail for long periods of time, depending only on the start and target points defined for this global planning. The result is the development of a complete path planner algorithm that, together with the local planner solved in previous work, can be used to allow the final developments of an N-Boat making it a fully autonomous sailboat.
Prostate cancer is a heterogeneous disease where the previous concept of "hormone resistance" has been changed by a new generation of hormonal therapies that have proven efficacy in the ...castration-resistant setting. The fact is that androgens play a crucial role in the whole clinical course of prostate cancer, even when a patient meets castration-resistance criteria. The development of abiraterone showed how important and clinically meaningful can be to achieve the lowest possible levels of testosterone, and androgen receptor overexpression, mutation, or enhanced crosstalk with other pathways, which can also be targeted with new agents tested in the last few years. New androgen biosynthesis inhibitors have been developed, such as orteronel (TAK-700), but also new antiandrogens (enzalutamide, ARN-509, ODM-201) or even agents with a dual mechanism of action (galeterone). In this review the development of new hormonal therapies following the arrival of abiraterone for the treatment of prostate cancer will be summarized.
The landscape of castration-resistant prostate carcinoma has changed completely in the last few years, with the approval of four new agents with proven benefit in overall survival. Abiraterone, ...cabazitaxel, enzalutamide and radium-223 dichloride have been added to the armamentarium of available agents for the treatment of these patients. We still lack information about which agent works best in an individual patient and how to optimally use them in a sequential strategy. Cabozantinib, a targeted agent against MET and vascular endothelial growth factor receptor-2, has shown promising results and could become the first targeted therapy to be approved for castration-resistant prostate carcinoma. This paper reviews the clinical development of cabozantinib in prostate cancer and future research possibilities for this drug.
Safety of pregnancy in women with history of estrogen receptor (ER)-positive breast cancer remains controversial. In this multicenter case-control study, 333 patients with pregnancy after breast ...cancer were matched (1:3) to 874 nonpregnant patients of similar characteristics, adjusting for guaranteed time bias. Survival estimates were calculated using the Kaplan-Meier analysis; groups were compared with the log-rank test. All reported P values were two-sided. At a median follow-up of 7.2 years after pregnancy, no difference in disease-free survival was observed between pregnant and nonpregnant patients with ER-positive (hazard ratio HR = 0.94, 95% confidence interval CI = 0.70 to 1.26, P = .68) or ER-negative (HR = 0.75, 95% CI = 0.53 to 1.06, P = .10) disease. No overall survival (OS) difference was observed in ER-positive patients (HR = 0.84, 95% CI = 0.60 to 1.18, P = .32); ER-negative patients in the pregnant cohort had better OS (HR = 0.57, 95% CI = 0.36 to 0.90, P = .01). Abortion, time to pregnancy, breastfeeding, and type of adjuvant therapy had no impact on patients' outcomes. This study provides reassuring evidence on the long-term safety of pregnancy in breast cancer survivors, including those with ER-positive disease.
We questioned the impact of pregnancy on disease-free survival (DFS) in women with history of breast cancer (BC) according to estrogen receptor (ER) status.
A multicenter, retrospective cohort study ...in which patients who became pregnant any time after BC were matched (1:3) to patients with BC with similar ER, nodal status, adjuvant therapy, age, and year of diagnosis. To adjust for guaranteed time bias, each nonpregnant patient had to have a disease-free interval at least equal to the time elapsing between BC diagnosis and date of conception of the matched pregnant one. The primary objective was DFS in patients with ER-positive BC. DFS in the ER-negative cohort, whole population, and overall survival (OS) were secondary objectives. Subgroup analyses included DFS according to pregnancy outcome and BC-pregnancy interval. With a two-sided α = 5% and β = 20%, 645 ER-positive patients were required to detect a hazard ratio (HR) = 0.65.
A total of 333 pregnant patients and 874 matched nonpregnant patients were analyzed, of whom 686 patients had an ER-positive disease. No difference in DFS was observed between pregnant and nonpregnant patients in the ER-positive (HR = 0.91; 95% CI, 0.67 to 1.24, P = .55) or the ER-negative (HR = 0.75; 95% CI, 0.51 to 1.08, P = .12) cohorts. However, the pregnant group had better OS (HR = 0.72; 95% CI, 0.54 to 0.97, P = .03), with no interaction according to ER status (P = .11). Pregnancy outcome and BC-pregnancy interval did not seem to impact the risk of relapse.
Pregnancy after ER-positive BC does not seem to reduce the risk of BC recurrence.
Muscle-invasive bladder tumors are associated with a high risk of relapse and metastasis even after neoadjuvant chemotherapy and radical cystectomy. Therefore, further therapeutic options are needed ...and molecular characterization of the disease may help to identify new targets. The aim of this study was to characterize muscle-invasive bladder tumors at the molecular level using computational analyses.
The TCGA cohort of muscle-invasive bladder cancer patients was used to describe these tumors. Probabilistic graphical models, layer analyses based on sparse k-means coupled with Consensus Cluster, and Flux Balance Analysis were applied to characterize muscle-invasive bladder tumors at a functional level.
Luminal and Basal groups were identified, and an immune molecular layer with independent value was also described. Luminal tumors showed decreased activity in the nodes of epidermis development and extracellular matrix, and increased activity in the node of steroid metabolism leading to a higher expression of the androgen receptor. This fact points to the androgen receptor as a therapeutic target in this group. Basal tumors were highly proliferative according to Flux Balance Analysis, which makes these tumors good candidates for neoadjuvant chemotherapy. The Immune-high group showed a higher degree of expression of immune biomarkers, suggesting that this group may benefit from immune therapy.
Our approach, based on layer analyses, established a Luminal group candidate for therapy with androgen receptor inhibitors, a proliferative Basal group which seems to be a good candidate for chemotherapy, and an immune-high group candidate for immunotherapy.
Pazopanib is indicated in the first-line treatment of metastatic renal cell cancer (mRCC). The aim of this study was to review the efficacy, safety, and pharmacokinetics of pazopanib and see how ...these aspects are linked to clinical practice.
A non-exhaustive systematic review was conducted according to the three topics. No publication restrictions were imposed and the selected languages were Spanish and English. After that, a summary of the main results and findings of the review was presented and discussed during three meetings (one for each topic) with 13 medical oncologists that usually treat mRCC. At these meetings, a questionnaire on the first-line use of pazopanib in clinical practice was also drawn up. After the meetings, the questionnaire was completed by 60 specialist medical oncologists in renal cancer.
The efficacy and safety of pazopanib have been demonstrated in several clinical trials, and subsequently confirmed in studies in real-world clinical practice. In addition to its clinical benefit and good safety profile, quality of life results for pazopanib, which compare favorably to sunitinib, make it a good option in the first-line treatment of patients. Special populations have been included in studies conducted with pazopanib, and it is safe for use in elderly patients, poor functional status, kidney failure, and mild or moderate hepatic impairment, and in patients with concomitant cardiovascular disease. The results of the questionnaire have shown that pazopanib is perceived as an effective drug, in which quality of life (QoL) outcomes are valued above all.
This paper offers a comprehensive and critical summary of efficacy, tolerability, and pharmacokinetics of pazopanib in the treatment of mRCC. Pazopanib is an effective treatment with an acceptable safety profile. Its QoL and tolerability results offer certain advantages when compared with other therapeutic alternatives, and its use appears to be safe in different patient profiles.
Differentiated vulvar intraepithelial neoplasia is a unique precursor to vulvar squamous cell carcinoma that is typically HPV-negative and frequently associated with nuclear p53 staining. These ...features imply a mode of pathogenesis involving somatic mutations. However, the genetic relationship of differentiated vulvar intraepithelial neoplasm and vulvar squamous cell carcinoma and the role of Tp53 mutations in this process have not been resolved. We analyzed 11 differentiated vulvar intraepithelial neoplasms and 6 associated vulvar squamous cell carcinomas. Sections were stained for p53 and p63 and DNA from multiple epithelial sites, representing normal control tissues (n=10), differentiated vulvar intraepithelial neoplasias (n=18), and vulvar squamous cell carcinomas (n=6), were obtained by laser capture microdissection, and sequenced for exons 2-11 of Tp53. Six of 10 cases contained at least one Tp53 mutation-positive differentiated vulvar intraepithelial neoplasia focus; 4 strongly p53 immuno-positive and 2 negative. Staining for p53 and p63 co-localized, targeting the immature epithelium, but surface epithelium was Tp53 mutation-positive. Four of five vulvar squamous cell carcinomas were Tp53 mutation-positive; two shared identical Tp53 mutation with adjacent differentiated vulvar intraepithelial neoplasia. Disparate foci of differentiated vulvar intraepithelial neoplasia often showed different mutations consistent with multiple neoplastic clones. Differentiated vulvar intraepithelial neoplasia is, with few exceptions, associated with Tp53 mutations and will be p53 immunopositive when missense mutations (versus some nonsense and all deletion mutations) are present. Multiple Tp53 mutations in different sites supports the presence of multiple independent genetic events, but shared Tp53 mutations in both differentiated vulvar intraepithelial neoplasia and vulvar squamous cell carcinoma support a genetic relationship between the two. The confinement of p53 staining to immature cell nuclei is consistent with maturation-dependent degradation of mutant p53 protein.
•In-depth characterisation of different mine waste materials from the same tailing pond.•Sources of metals of interest (Pb and Zn) are different mineral and slag phases.•Low abundance of Pb/Zn phases ...causes a nugget effect.•The chemical heterogeneity of slags exacerbates the nugget effect.•The approach is applicable to different mine waste deposits around the globe.
The exploitation of mine waste materials as secondary resources requires in-depth mineralogical analyses, with metal deportment being of particular relevance for metal recovery. Using a combination of the Scanning Electron Microscope (SEM)-based Mineral Liberation Analyser (MLA) and Electron Probe Micro-Analyser (EPMA) methods, the deportment of lead and zinc in the historic Plombières mine site (East Belgium) was investigated. The mine site comprises four different materials: soil, metallurgical waste, brown and yellow tailings. The integration of the MLA and EPMA data allowed the identification and quantification of Pb- and Zn-bearing phases, including minerals present in low abundances as well as slag phases. Different slag types and Pb oxides phases are the main sources of lead in Plombières mine waste samples. These phases host 65 to 99 % of the Pb, the rest is distributed between cerussite (0 to 37 %), and/or anglesite (0 to 17 %). Approximately 95 % of Zn is hosted by different types of slags or by fraipontite, with minor amounts contributed by sphalerite (0.1 to 3 %), gahnite (1.0 to 2.4 %), willemite (0.1 to 2.9 %), and bannisterite (0 to 3 %). The MLA/EPMA measurements were validated by comparing calculated Pb and Zn grades with bulk grades measured by X-ray fluorescence spectroscopy. The coefficients of correlation between the measured and calculated values were found to be 0.89 for lead and 0.80 for zinc. Uncertainties on the metal deportments were estimated by bootstrap resampling and are typically low. The highest uncertainties are observed when the metal-bearing phases are present in low abundances, which is particularly noticeable in the yellow tailings. Considering the promising results, the integrated approach applied in this study should be applicable to other metals and waste deposits across the globe.
Renal cell carcinoma comprises a variety of entities, the most common being the clear-cell, papillary and chromophobe subtypes. These subtypes are related to different clinical evolution; however, ...most therapies have been developed for clear-cell carcinoma and there is not a specific treatment based on different subtypes. In this study, one hundred and sixty-four paraffin samples from primary nephrectomies for localized tumors were analyzed. MiRNAs were isolated and measured by microRNA arrays. Significance Analysis of Microarrays and Consensus Cluster algorithm were used to characterize different renal subtypes. The analyses showed that chromophobe renal tumors are a homogeneous group characterized by an overexpression of miR 1229, miR 10a, miR 182, miR 1208, miR 222, miR 221, miR 891b, miR 629-5p and miR 221-5p. On the other hand, clear cell renal carcinomas presented two different groups inside this histological subtype, with differences in miRNAs that regulate focal adhesion, transcription, apoptosis and angiogenesis processes. Specifically, one of the defined groups had an overexpression of proangiogenic microRNAs miR185, miR126 and miR130a. In conclusion, differences in miRNA expression profiles between histological renal subtypes were established. In addition, clear cell renal carcinomas had different expression of proangiogenic miRNAs. With the emergence of antiangiogenic drugs, these differences could be used as therapeutic targets in the future or as a selection method for tailoring personalized treatments.
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