The cyclin D1 (CCND1) rs9344 G>A polymorphism predicts clinical outcome in colon cancer patients treated with adjuvant 5-FU-based chemotherapy

Recent evidence indicates a potential prognostic and predictive value for germline polymorphisms in genes involved in cell cycle control. We investigated the effect of cyclin D1 (CCND1) rs9344 G>A in stage II/III colon cancer patients and validated the findings in an independent study cohort. For evaluation and validation set, a total of 264 and 234 patients were included. Patients treated with 5-fluorouracil-based chemotherapy, carrying the CCND1 rs9344 A/A genotype had significantly decreased time-to-tumor recurrence (TTR) in univariate analysis and multivariate analysis (hazard ratio (HR) 2.47; 95% confidence interval (CI) 1.16-5.29; P=0.019). There was no significant association between CCND1 rs9344 G>A and TTR in patients with curative surgery alone. In the validation set, the A allele of CCND1 rs9344 G>A remained significantly associated with decreased TTR in univariate and multivariate analyses (HR 1.94; 95% CI 1.05-3.58; P=0.035). CCND1 rs9344 G>A may be a predictive and/or prognostic biomarker in stage II/III colon cancer patients, however, prospective trials are warranted to confirm our findings.

EGF61 polymorphism predicts complete pathologic response to cetuximab-based chemoradiation independent of KRAS status in locally advanced rectal cancer patients

BACKGROUND: Cetuximab has shown significant clinical activity in metastatic colon cancer. However, cetuximab-containing neoadjuvant chemoradiation has not been shown to improve tumor response in locally advanced rectal cancer patients in recent phase I/II trials. We evaluated functional germline polymorphisms of genes involved in epidermal growth factor receptor pathway, angiogenesis, antibody-dependent cell-mediated cytotoxicity, DNA repair, and drug metabolism, for their potential role as molecular predictors for clinical outcome in locally advanced rectal cancer patients treated with preoperative cetuximab-based chemoradiation.

METHODS: 130 patients (74 men and 56 women) with locally advanced rectal cancer (4 with stage II, 109 with stage III, and 15 with stage IV, 2 unknown) who were enrolled in phase I/II clinical trials treated with cetuximab-based chemoradiation in European cancer centers were included. Genomic DNA was extracted from formalin-fixed paraffin-embedded tumor samples and genotyping was done by using PCR-RFLP assays. Fisher's exact test was used to examine associations between polymorphisms and complete pathologic response (pCR) that was determined by a modified Dworak classification system (grade III vs. grade IV: complete response).

RESULTS: Patients with the epidermal growth factor (EGF) 61 G/G genotype had pCR of 45% (5/11), compared with 21% (11/53) in patients heterozygous, and 2% (1/54) in patients homozygous for the A/A allele (P < 0.001). In addition, this association between EGF 61 G allele and pCR remained significant (P = 0.019) in the 59 patients with wild-type KRAS.

CONCLUSION: This study suggested EGF A+61G polymorphism to be a predictive marker for pCR, independent of KRAS mutation status, to cetuximab-based neoadjuvant chemoradiation of patients with locally advanced rectal cancer.

Design, analysis and performance of a polymer-carbon nanotubes based economic solar collector

A low cost flat plate solar collector was developed by using polymeric components as opposed to metal and glass components of traditional flat plate solar collectors. In order to improve the thermal and optical properties of the polymer absorber of the solar collector, Carbon Nanotubes (CNT) were added as a filler. The solar collector was designed as a multi-layer construction with an emphasis on low manufacturing costs. Through the mathematical heat transfer analysis, the thermal performance of the collector and the characteristics of the design parameters were analyzed. Furthermore, the prototypes of the proposed collector were built and tested at a state-of-the-art solar simulator facility to evaluate its actual performance. The inclusion of CNT improved significantly the properties of the polymer absorber. The key design parameters and their effects on the thermal performance were identified via the heat transfer analysis. Based on the experimental and analytical results, the cost-effective polymer-CNT solar collector, which achieved a high thermal efficiency similar to that of a conventional glazed flat plate solar panel, was successfully developed.

Analgesia em modelo animal superior para ortopedia

O teste de novos biomateriais para aplicações clínicas em ortopedia, ou noutras áreas da medicina, em modelos animais vivos e sencientes, em prol do benefício humano, deve ser objecto de planeamento cuidado e ponderado, dado o conflito ético que se coloca. Compete-nos, enquanto investigadores, garantir que as condições de vida, saúde e bem-estar são asseguradas. O uso de ovinos como modelo superior pré-clínico, para investigação em Ortopedia, tem-se evidenciado devido às suas características translacionais para a espécie humana. Neste estudo retrospectivo deu-se ênfase ao plano anestésico/ analgésico instituído em três tipos de técnicas cirúrgicas ortopédicas, realizadas em ovinos. Os animais intervencionados foram adquiridos com 2 meses de antecedência em relação às cirurgias e mantidos em rebanho, com condições adequadas de abrigo, alimentação e maneio. As técnicas cirúrgicas inovadoras foram treinadas previamente em peças anatómicas adquiridas no matadouro. Todas as cirurgias e anestesias foram realizadas por médicos veterinários devidamente qualificados. Durante os períodos pós-operatórios os animais foram mantidos no Hospital Veterinário, sob vigilância e tratamento, após o que regressaram ao pasto. Considera-se que os protocolos anestésico e analgésico instituídos foram suficientes para eliminar a dor ortopédica/ neuropática causada pelas técnicas cirúrgicas referidas.

Telaprevir or boceprevir based therapy for chronic hepatitis C infection: Development of resistance-associated variants in treatment failure

The use of triple-therapy, pegylated-interferon, ribavirin and either of the first generation hepatitis C virus (HCV) protease inhibitors telaprevir or boceprevir, is the new standard of care for treating genotype 1 chronic HCV. Clinical trials have shown response rates of around 70–80%, but there is limited data from the use of this combination outside this setting. Through an expanded access programme, we treated 59 patients, treatment naïve and experienced, with triple therapy. Baseline factors predicting treatment response or failure during triple therapy phase were identified in 58 patients. Thirty seven (63.8%) of 58 patients had undetectable HCV RNA 12 weeks after the end of treatment. Genotype 1a (p = 0.053), null-response to previous treatment (p = 0.034), the rate of viral load decline after 12 weeks of previous interferon-based treatment (p = 0.033) were all associated with triple-therapy failure. The most common cause of on-treatment failure for telaprevir-based regimens was the development of resistance-associated variants (RAVs) at amino acids 36 and/or 155 of HCV protease (p = 0.027) whereas in boceprevir-based regimens mutations at amino acid 54 were significant (p = 0.015). SVR12 rates approaching 64% were achieved using triple therapy outside the clinical trial setting, in a patient cohort that included cirrhotics.

Post awakening salivary cortisol secretion and trait well-being: The importance of sample timing accuracy

Indices of post awakening cortisol secretion (PACS), include the rise in cortisol(cortisol awakening response: CAR) and overall cortisol concentrations (e.g. area under the curve with reference to ground: AUCg) in the first 30—45 min. Both are commonly investigated in relation to psychosocial variables. Although sampling within the domestic setting is ecologically valid, participant non-adherence to the required timing protocol results in erroneous measurement of PACS and this may explain discrepancies in the literature linking these measures to trait well-being (TWB). We have previously shown that delays of little over 5 min(between awakening and the start of sampling) to result in erroneous CAR estimates. In this study, we report for the first time on the negative impact of sample timing inaccuracy (verified by electronic-monitoring) on the efficacy to detect significant relationships between PACS and TWB when measured in the domestic setting.Healthy females (N = 49, 20.5 ± 2.8 years) selected for differences in TWB collected saliva samples (S1—4) on 4 days at 0, 15, 30, 45 min post awakening, to determine PACS. Adherence to the sampling protocol was objectively monitored using a combination of electronic estimates of awakening (actigraphy) and sampling times (track caps).Relationships between PACS and TWB were found to depend on sample timing accuracy. Lower TWB was associated with higher post awakening cortisol AUCg in proportion to the mean sample timing accuracy (p < .005). There was no association between TWB and the CAR even taking into account sample timing accuracy. These results highlight the importance of careful electronic monitoring of participant adherence for measurement of PACS in the domestic setting. Mean sample timing inaccuracy, mainly associated with delays of >5 min between awakening and collection of sample 1 (median = 8 min delay), negatively impacts on the sensitivity of analysis to detect associations between PACS and TWB.

How women use and experience western herbal practice for distress: implications for health care and self-management approaches.

Introduction: In the UK, common mental health disorders account for one in five of all work days lost, and cost employers £25bn each year. Herbal medicine has been shown to potentially be of use for mental distress, including conditions like anxiety. In 2008, 35% of British adults surveyed claimed to have used herbal medicine at some stage, the majority of whom were women. However, there is little research into how the users of western herbal medicine (WHM) experience the practice of herbal medicine, or how these experiences may change over time. Our research is studying women in the south-east of the UK who are suffering from distress (either as a primary complaint, or associated with another condition) who are seeking the services of a herbalist who practices WHM. Aim: To investigate the experiences of western herbal practice by women who are suffering with distress. Methods: The study is using semi-structured interviews of around thirty women, to elicit patient narratives at two time points. Thematic analysis is being used to consider how distressed women perceive and experience their distress, their reasons for using WHM, what contribution the women perceive the consultation and treatment with WHM may or may not make to their wellbeing, and whether their experiences change over time. Currently, sixteen women have been interviewed, and a preliminary thematic analysis has commenced. Results: Preliminary finding suggest that not only do women internalise their distress, but that they are surprisingly isolated in how they deal with it, whilst some also express social embarrassment about their experiences. The women perceived that their distress is not always considered seriously from their medical practitioners’ point of view. These women are drawn to herbalists not only in a search for effective treatment, but also to be given time to have their story heard, to form a collaborative relationship, and to attempt to regain some control of their life. The herbal treatment is valued due to its perceived naturalness, and reduced risk of adverse side effects. Nevertheless, WHM is just one of a number of self-care strategies that women utilise to help manage their distress. Discussion: Effective treatment is not only dependent upon the herbs, but also upon an effective therapeutic relationship. Feeling that the herbalist hears their story, provides a treatment plan that is individually tailored to the patient, and is available (even outside of the consultation) are all important in helping to establish this relationship.

DNA-based biosensor for the electrocatalytic determination of antioxidant capacity in beverages

Reactive oxygen species (ROS) are produced as a consequence of normal aerobic metabolism and are able to induce DNA oxidative damage. At the cellular level, the evaluation of the protective effect of antioxidants can be achieved by examining the integrity of the DNA nucleobases using electrochemical techniques. Herein, the use of an adenine-rich oligonucleotide (dA21) adsorbed on carbon paste electrodes for the assessment of the antioxidant capacity is proposed. The method was based on the partial damage of a DNA layer adsorbed on the electrode surface by OH• radicals generated by Fenton reaction and the subsequent electrochemical oxidation of the intact adenine bases to generate an oxidation product that was able to catalyze the oxidation of NADH. The presence of antioxidant compounds scavenged hydroxyl radicals leaving more adenines unoxidized, and thus, increasing the electrocatalytic current of NADHmeasured by differential pulse voltammetry (DPV). Using ascorbic acid (AA) as a model antioxidant species, the detection of as low as 50nMof AA in aqueous solution was possible. The protection efficiency was evaluated for several antioxidant compounds. The biosensor was applied to the determination of the total antioxidant capacity (TAC) in beverages.

Distribution system operation supported by contextual energy resource management based on intelligent SCADA

Future distribution systems will have to deal with an intensive penetration of distributed energy resources ensuring reliable and secure operation according to the smart grid paradigm. SCADA (Supervisory Control and Data Acquisition) is an essential infrastructure for this evolution. This paper proposes a new conceptual design of an intelligent SCADA with a decentralized, flexible, and intelligent approach, adaptive to the context (context awareness). This SCADA model is used to support the energy resource management undertaken by a distribution network operator (DNO). Resource management considers all the involved costs, power flows, and electricity prices, allowing the use of network reconfiguration and load curtailment. Locational Marginal Prices (LMP) are evaluated and used in specific situations to apply Demand Response (DR) programs on a global or a local basis. The paper includes a case study using a 114 bus distribution network and load demand based on real data.

On the development of an automatic voice pleasantness classification and intensity estimation system

In the last few years, the number of systems and devices that use voice based interaction has grown significantly. For a continued use of these systems, the interface must be reliable and pleasant in order to provide an optimal user experience. However there are currently very few studies that try to evaluate how pleasant is a voice from a perceptual point of view when the final application is a speech based interface. In this paper we present an objective definition for voice pleasantness based on the composition of a representative feature subset and a new automatic voice pleasantness classification and intensity estimation system. Our study is based on a database composed by European Portuguese female voices but the methodology can be extended to male voices or to other languages. In the objective performance evaluation the system achieved a 9.1% error rate for voice pleasantness classification and a 15.7% error rate for voice pleasantness intensity estimation.

LNT: a logical neighbor tree secure group communication scheme for wireless sensor networks

Secure group communication is a paradigm that primarily designates one-to-many communication security. The proposed works relevant to secure group communication have predominantly considered the whole network as being a single group managed by a central powerful node capable of supporting heavy communication, computation and storage cost. However, a typical Wireless Sensor Network (WSN) may contain several groups, and each one is maintained by a sensor node (the group controller) with constrained resources. Moreover, the previously proposed schemes require a multicast routing support to deliver the rekeying messages. Nevertheless, multicast routing can incur heavy storage and communication overheads in the case of a wireless sensor network. Due to these two major limitations, we have reckoned it necessary to propose a new secure group communication with a lightweight rekeying process. Our proposal overcomes the two limitations mentioned above, and can be applied to a homogeneous WSN with resource-constrained nodes with no need for a multicast routing support. Actually, the analysis and simulation results have clearly demonstrated that our scheme outperforms the previous well-known solutions.

A sensitivity study of the WRF model in wind simulation for an area of high wind energy

The performance of the Weather Research and Forecast (WRF) model in wind simulation was evaluated under different numerical and physical options for an area of Portugal, located in complex terrain and characterized by its significant wind energy resource. The grid nudging and integration time of the simulations were the tested numerical options. Since the goal is to simulate the near-surface wind, the physical parameterization schemes regarding the boundary layer were the ones under evaluation. Also, the influences of the local terrain complexity and simulation domain resolution on the model results were also studied. Data from three wind measuring stations located within the chosen area were compared with the model results, in terms of Root Mean Square Error, Standard Deviation Error and Bias. Wind speed histograms, occurrences and energy wind roses were also used for model evaluation. Globally, the model accurately reproduced the local wind regime, despite a significant underestimation of the wind speed. The wind direction is reasonably simulated by the model especially in wind regimes where there is a clear dominant sector, but in the presence of low wind speeds the characterization of the wind direction (observed and simulated) is very subjective and led to higher deviations between simulations and observations. Within the tested options, results show that the use of grid nudging in simulations that should not exceed an integration time of 2 days is the best numerical configuration, and the parameterization set composed by the physical schemes MM5–Yonsei University–Noah are the most suitable for this site. Results were poorer in sites with higher terrain complexity, mainly due to limitations of the terrain data supplied to the model. The increase of the simulation domain resolution alone is not enough to significantly improve the model performance. Results suggest that error minimization in the wind simulation can be achieved by testing and choosing a suitable numerical and physical configuration for the region of interest together with the use of high resolution terrain data, if available.

Fractional dynamics of a system with particles subjected to impacts

This paper studies the dynamics of a system composed of a collection of particles that exhibit collisions between them. Several entropy measures and different impact conditions of the particles are tested. The results reveal a Power Law evolution both of the system energy and the entropy measures, typical in systems having fractional dynamics.

Mode III interlaminar fracture of carbon/epoxy laminates using the edge crack torsion (ECT) test

The mode III interlaminar fracture of carbon/epoxy laminates was evaluated with the edge crack torsion (ECT) test. Three-dimensional finite element analyses were performed in order to select two specimen geometries and an experimental data reduction scheme. Test results showed considerable non-linearity before the maximum load point and a significant R-curve effect. These features prevented an accurate definition of the initiation point. Nevertheless, analyses of non-linearity zones showed two likely initiation points corresponding to GIIIc values between 850 and 1100 J/m2 for both specimen geometries. Although any of these values is realistic, the range is too broad, thus showing the limitations of the ECT test and the need for further research.