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Heat management is crucial in the design of nanoscale devices as the operating temperature determines their efficiency and lifetime. Past experimental and theoretical works exploring nanoscale heat transport in semiconductors addressed known deviations from Fourier's law modeling by including effective parameters, such as a size-dependent thermal conductivity. However, recent experiments have qualitatively shown behavior that cannot be modeled in this way. Here, we combine advanced experiment and theory to show that the cooling of 1D- and 2D-confined nanoscale hot spots on silicon can be described using a general hydrodynamic heat transport model, contrary to previous understanding of heat flow in bulk silicon. We use a comprehensive set of extreme ultraviolet scatterometry measurements of nondiffusive transport from transiently heated nanolines and nanodots to validate and generalize our ab initio model, that does not need any geometry-dependent fitting parameters. This allows us to uncover the existence of two distinct time scales and heat transport mechanisms: an interface resistance regime that dominates on short time scales and a hydrodynamic-like phonon transport regime that dominates on longer time scales. Moreover, our model can predict the full thermomechanical response on nanometer length scales and picosecond time scales for arbitrary geometries, providing an advanced practical tool for thermal management of nanoscale technologies. Furthermore, we derive analytical expressions for the transport time scales, valid for a subset of geometries, supplying a route for optimizing heat dissipation.

This paper presents a multi-user mobile learning system—specifically designed to enhance collaborative language learning through mobile devices. The system delivers an app version of a paper-based learning task, called Terminkalender, which has successfully been used for several years with students from an A1-level German language course (CEFR). The learning task requires students to interact with each other via text messages in order to jointly plan different activities and record them in an appointment calendar. While the paper-based version already had a great potential for engaging students to interact in the target language, the app not only facilitates students’ interaction, but also allows teachers to easily trace back and analyse learners’ interaction. To this end, specific software implementing several features was developed: a web-based platform for system administration, an in-app text chat function, real-time feedback on learner performance as well as a log function for storage and assessment of learners’ interaction. The experiment sheds some light on the potential of the designed system for analysing learners’ behaviour and interaction patterns as well as assessing different indicators with regard to the student use and competencies in the target language.

Bladder cancer (BC), the most frequent malignancy of the urinary system, is ranked the sixth most prevalent cancer worldwide. Of all newly diagnosed patients with BC, 70–75% will present disease confined to the mucosa or submucosa, the non-muscle-invasive BC (NMIBC) subtype. Of those, approximately 70% will recur after transurethral resection (TUR). Due to high rate of recurrence, patients are submitted to an intensive follow-up program maintained throughout many years, or even throughout life, resulting in an expensive follow-up, with cystoscopy being the most cost-effective procedure for NMIBC screening. Currently, the gold standard procedure for detection and follow-up of NMIBC is based on the association of cystoscopy and urine cytology. As cystoscopy is a very invasive approach, over the years, many different noninvasive assays (both based in serum and urine samples) have been developed in order to search genetic and protein alterations related to the development, progression, and recurrence of BC. TERT promoter mutations and FGFR3 hotspot mutations are the most frequent somatic alterations in BC and constitute the most reliable biomarkers for BC. Based on these, we developed an ultra-sensitive, urine-based assay called Uromonitor®, capable of detecting trace amounts of TERT promoter (c.1-124C > T and c.1-146C > T) and FGFR3 (p.R248C and p.S249C) hotspot mutations, in tumor cells exfoliated to urine samples. Cells present in urine were concentrated by the filtration of urine through filters where tumor cells are trapped and stored until analysis, presenting long-term stability. Detection of the alterations was achieved through a custom-made, robust, and highly sensitive multiplex competitive allele-specific discrimination PCR allowing clear interpretation of results. In this study, we validate a test for NMIBC recurrence detection, using for technical validation a total of 331 urine samples and 41 formalin-fixed paraffin-embedded tissues of the primary tumor and recurrence lesions from a large cluster of urology centers. In the clinical validation, we used 185 samples to assess sensitivity/specificity in the detection of NMIBC recurrence vs. cystoscopy/cytology and in a smaller cohort its potential as a primary diagnostic tool for NMIBC. Our results show this test to be highly sensitive (73.5%) and specific (93.2%) in detecting recurrence of BC in patients under surveillance of NMIBC.

Leiomyosarcoma (LMS) is a rare malignant tumor of smooth muscle origin that generally stems from soft tissues and uterine tissue. Although, a small percentage of these may originate from the smooth muscle or vessel walls, most of which are of venous origin. Renal leiomyosarcomas may arise from the smooth muscle fibers of renal pelvis, renal capsule or renal vessels, last one is the most frequent. We report a case of renal LMS that could be originated in the renal capsule.

El carácter crónico de la cirrosis hepática y sus severas complicaciones, entre las que se incluyen la incapacidad del propio paciente para llevar a cabo sus autocuidados, hacen recomendable la identificación y asignación de un cuidador principal que conviva con el paciente y sepa reconocer la aparición de los trastornos propios de la enfermedad. Sin embargo, para ello es preciso que, tanto el cuidador principal como el propio paciente, dispongan de la información adecuada sobre los hábitos dietéticos y sobre las medidas de control y observación necesarias que se han de seguir, una vez que la enfermedad ha sido diagnosticada. El objetivo del presente estudio es determinar el grado de conocimiento que tiene el cuidador principal del paciente cirrótico sobre la enfermedad para, a partir de aquí, elaborar estrategias y protocolos de educación sanitaria, que permitan evitar innecesarias hospitalizaciones o frenar, en la medida de lo posible, las complicaciones que el curso de la citada patología conlleva. Y también determinar el cansancio en el rol del cuidador, como diagnóstico de la NANDA. Hemos hallado un porcentaje significativo de cuidadores principales que desconocen la correlación existente entre el estreñimiento y la encefalopatía hepática y algunos datos de una insuficiente información. Abstract The chronic character of the liver cirrhosis and its severe complications, including the patient inability to take care of himself, makes recommendable the availability of a caregiver living with the patient. This caregiver should be able to recognize the usual disorders associated to the cirrhosis. Additionally, an adequate information about the dietary habits and other recommended measures is mandatory for both the caregiver and patient to keep under control all the complications which appears once the illness has been diagnosed. The objective of the present study was to explore the knowledge of the cirrhotic patient’s caregiver regarding this illness. This was intended as a first step in order to develop education protocols that might reduce illness complications and the eventually avoidable hospital admissions. It also tried to explore and determine the fatigue of the personal caregiver in her role, as a diagnosis of the NANDA. We found a significant percentage of caregivers who were not aware of the relationship between constipation and encephalopaty as well as other data indicating insufficient education of the caregivers. Centro de Trabajo: (*) Diplomados Universitarios de Enfermería y (**) Supervisora de Enfermería. Servicio de Digestivo. Hospital Universitario Puerta del Mar. Cádiz. España Fecha del Trabajo: 15/06/2004 Palabra Clave: Cirrosis, cuidador, conocimientos, enfermería Key Words: Cirrhosis, caregiver, knowledge, nursing

The chronic character of the liver cirrhosis and its severe complications, including the patient inability to take care of himself, makes recommendable the availability of a caregiver living with the patient. This caregiver should be able to recognize the usual disorders associated to the cirrhosis. Additionally, an adequate information about the dietary habits and other recommended measures is mandatory for both the caregiver and patient to keep under control all the complications which appears once the illness has been diagnosed.The objective of the present study was to explore the knowledge of the cirrhotic patient’s caregiver regarding this illness. This was intended as a first step in order to develop education protocols that might reduce illness complications and the eventually avoidable hospital admissions. It also tried to explore and determine the fatigue of the personal caregiver in her role, as a diagnosis of the NANDA.We found a significant percentage of caregivers who were not aware of the relationship between constipation and encephalopaty as well as other data indicating insufficient education of the caregivers.

Background: Abiraterone acetate and enzalutamide are standard treatments for chemotherapy-naive metastatic castration-resistant prostate cancer (CN-mCRPC). The purpose of this study was to evaluate the effectiveness and safety of these medications in elderly (≥ 75 years old) compared with young CN-mCRPC patients in a real-world clinical setting. Secondarily, we explored the survival prognostic value of different anatomo-clinical factors in elderly group., Methods: In this retrospective observational multicentre study, we included 134 consecutive CN-mCRPC patients, 64 young and 70 elderly men, who had received AA or Enz., Results: We did not find significant differences in treatment duration [16.6 months, (95% CI 9-24.2 months) vs. 16.8 months (95% CI: 6.3-27.2 months); p = 0.926] and overall survival [median not reached vs. 23.3 months (95% CI 10.2-36.3 months); p = 0.131] between the young and elderly groups. In elderly group, the only predictors of overall survival with AA or Enz were good ECOG performance status and high G8 score. Adverse events of grade ≥3 was similar in elderly group (12.9%) and in the young group (15.6%). Treatment was discontinued due to AEs in 6.3% of young group and 18.6% of elderly group., Conclusions: Effectiveness and safety of treatment of CN-mRCPC with Abiraterone acetate and enzalutamide were similar in older and younger patients, although treatment discontinuation due to AEs was more frequent in the older age group. In addition to ECOG PS, assessment using specific geriatric scales as G8 screening tool could help to identify patients aged ≥75 who would most benefit from treatment with new-generation hormone therapy., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Bacillus Calmette-Guérin (BCG) maintenance therapy for 3 yr following BCG induction can reduce the progression of urothelial bladder carcinoma versus BCG induction alone, but is associated with high toxicity., Objective: To investigate whether a modified 3-yr BCG maintenance regimen following induction therapy is more effective than standard BCG induction therapy alone and exhibits a low toxicity profile., Design, Setting, and Participants: Patients from the outpatient clinics of the participating centres with high-risk non-muscle-invasive bladder carcinoma (NMIBC) were randomised between October 1999 and April 2007., Intervention: Participants received BCG induction once-weekly for 6 wk (no maintenance arm) or BCG induction followed by one BCG instillation every 3 mo for 3 yr (maintenance arm)., Outcome Measurements and Statistical Analysis: Primary endpoints were disease-free interval (DFI) and time to progression (TTP). Secondary endpoints included survival duration and toxicity. Differences between treatment arms were tested using Student's t test and χ(2) and log-rank tests., Results and Limitations: A total of 397 patients were randomised, 195 to the no-maintenance and 202 to the maintenance arm. A median time to recurrence was not reached in either treatment arm. DFI was similar between the arms (hazard ration [HR] 0.83; 95% CI 0.61-1.13; p=0.2) with disease relapse at 5 yr of 33.5% and 38.5%, respectively. TTP was also similar between the treatment arms (HR 0.79; 95% CI 0.50-1.26; p=0.3), with a progression rate at 5 yr of 16% and 19.5%, respectively. There were no significant differences between the treatment groups for overall survival and cancer-specific survival at 5 yr. Twenty and five patients in the maintenance and no-maintenance arms, respectively, stopped treatment because of toxicity. The most common local side effects were frequency (65% of patients), dysuria (63%), and haematuria (43%); the most frequent systemic side effects were general malaise (7.2%) and fever (34%)., Conclusions: In NMIBC patients treated with maintenance therapy comprising a single BCG instillation every 3 mo for 3 yr following standard induction BCG, we did not observe a decrease in recurrence and progression rates versus induction therapy alone., Patient Summary: Patients who undergo surgery to remove bladder cancer are usually treated with bacillus Calmette-Guérin (BCG) for 6 wk if there is a high risk of disease recurrence. Extending BCG therapy by 3 yr can further minimise disease recurrence and progression, but is associated with more side effects. We report that a modified 3-yr BCG treatment regimen showed low toxicity, but seemed to be no more effective than 6-wk treatment., Trial Registration: CUETO 98013., (Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Intravesical bacillus Calmette-Guérin (BCG) is an effective therapy in non-muscle-invasive bladder cancer (NMIBC), but it has limitations in terms of recurrence and toxicity., Objective: To determine whether the sequential combination of mitomycin C (MMC) and BCG is superior to BCG alone in increasing a disease-free interval (DFI)., Design, Setting, and Participants: We conducted a prospective randomized trial including 407 patients with intermediate- to high-risk NMIBC and allocated 211 to the MMC and BCG arm and 196 to the BCG-alone arm., Outcome Measurements and Statistical Analysis: The trial was designed to provide concurrently a power of 80% for the detection of a relative risk reduction of 35% (hazard ratio [HR]: 0.65) of disease relapse with a type I error of 0.05. Times to events were estimated using cumulative incidence functions and compared using the Cox regression model. We used the Kaplan-Meier technique to estimate survival curves., Results and Limitations: In the intention-to-treat analysis at 5 yr, DFI was significantly improved by the sequential scheme (HR: 0.57; 95% confidence interval [CI], 0.39-0.83; p=0.003), reducing the disease relapse rate from 33.9% to 20.6%. Higher toxicity was observed with the combination, even reducing the MMC dose, especially in G3 local toxicity compared with BCG with a difference of 17.4% (95% CI, 7.6-27.2; p<0.001). In recurrent T1 tumors, the potential benefit of the sequential scheme was more evident than in the remaining subgroup (18.8% vs 12.8%), with a number needed to treat of five versus eight to avoid an event and with similar toxicity., Conclusions: Although the sequential scheme is more effective than BCG alone in reducing disease relapse, due to higher toxicity it could be offered only to patients with a high likelihood of recurrence, such as those with recurrent T1 tumors., Patient Summary: We analyzed the outcomes of a randomized trial demonstrating that in intermediate- to high-risk non-muscle-invasive bladder cancer, mitomycin C and bacillus Calmette-Guérin (BCG) reduced disease relapse compared with BCG alone but was more toxic. Consequently, it could be offered only to patients with recurrent T1 tumors., Trial Registration: CUETO 93009., (Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Aim: Hepatic metabolism of sildenafil uses the same metabolic pathway as the calcineurin inhibitors (cyclosporine/tacrolimus), through the CYP3A4 isoenzyme. The aim of this pilot study was to evaluate the potential interaction between sildenafil therapy and circulating levels of cyclosporine and tacrolimus in a group of steady-state renal transplant recipients with erectile dysfunction., Material and Methods: A prospective pilot study of sildenafil interactions was carried out in 9 stable male renal transplant recipients with severe erectile dysfunction (mean age 50 +/- 8 years, range 38-64). All patients were receiving therapy with calcineurin inhibitors (5 with cyclosporine and 4 with tacrolimus). Erectile dysfunction was evaluated by clinical history, physical examination, International Index of Erectile Function (IIEF) questionnaire and the nocturnal penile tumescence test (RigiScan). Each patient received a first dose of 50 mg of sildenafil, one hour before sexual activity and a second dose at 72 hours of 50 or 100 mg according to the clinical response to the first dose. We evaluated the efficacy and safety of sildenafil and the evolution of cyclosporine-tacrolimus levels. Cyclosporine and tacrolimus trough whole blood concentrations were determined in basal conditions (before starting sildenafil) and on days 1, 4 and 7 after sildenafil therapy., Results: Eighty-nine percent of patients (n = 8) required a complete 100 mg dose of sildenafil. There was a positive clinical response in two-thirds of cases (6 patients). In 5 patients (55%) sildenafil administration produced a complete response, in one patient the response was incomplete, and in the remaining 3 cases (33%) no clinical response was observed. Associated side effects included self-limited tachycardia in one patient and mild visual disturbances in another. Cyclosporine and tacrolimus levels remained stable in all patients. There were no significant differences in circulating levels of cyclosporine (basal 120 +/- 47; day 1: 116 +/- 55; day 4: 123 +/- 56 and day 7: 121 +/- 56 ng/ml p = NS) or tacrolimus (basal 11.6 +/- 1.3; day 1: 11.9 +/- 1.3; day 4: 11.1 +/- 1.0 and day 7: 11.8 +/- 0.9 ng/ml p = NS) over the study period., Conclusions: Sildenafil therapy is safe and effective for the treatment of erectile dysfunction in renal transplant recipients. Recommended therapeutic doses of sildenafil did not modify cyclosporine and tacrolimus trough blood levels.

Background: The description of the different forms of circulating PSA has opened a new strategy in the diagnosis of prostate cancer. The aim of our study was to assess the diagnostic potential of PSA and the PSA fractions in the diagnosis of benign prostate hyperplasia (BPH) and prostate cancer., Patients and Methods: We measured the serum levels of PSA (Elecsys 2010, Roche Diagnostics, Mannheim, Germany), complexed PSA (Immuno 1 system, Bayer, Tarrytown, NY USA) and free PSA (Elecsys 2010, Roche Diagnostics, Mannheim, Germany) in 178 patients with BPH and 44 patients with prostate cancer., Results: ROC curves were used for comparison of the diagnostic utility of the tests assessed. The biggest areas under the curve were obtained for the ratios between free/complexed PSA and free/total PSA (0.887 and 0.872, respectively). When choosing the cut-off values to obtain a 90% sensibility, we found that the specificity for the free/total PSA ratio was 59% and for the free/complexed PSA ratio 72%., Conclusion: Our results suggest that replacement of the measurement of total PSA by complexed PSA in prostate cancer diagnosis may be interesting. Nevertheless, as this is a retrospective study limited to a small number of patients, it is obvious that we need more data to make a final decision with regard to this subject.

Background: It has been proposed that a dysregulation in the balance between type T1 (IL-2, IFN-gamma) and type T2 (IL-4, IL-10) cytokines may be implicated in the development of cancer., Methods: We determined the expression of IL-2, IL-4, IL-10, and IFN-gamma in CD4 and CD8 lymphocytes by flow cytometry in 12 patients with prostate cancer and in 7 healthy subjects. In addition to the basal expression of these cytokines, their expression was also determined, following stimulation of lymphocytes with PMA (phorbol 12-mystirate 13 acetate) and ionomycin., Results: The basal expression of cytokines was scarce, while following stimulation this increased markedly. On the other hand, there was a dysregulation in the balance between T1 and T2 lymphocytes in patients with prostate cancer. To this effect, in relation to healthy subjects, we observed an increase in IL-10 expression and a decrease in IL-2 expression., Conclusions: The disequilibrium observed in the balance between type T1 and type T2 cytokines may be implicated in the evolution of neoplastic disease., (Copyright 2000 Wiley-Liss, Inc.)