Respecting and fulfilling the right of post-primary pupils to consent to participate in trials and evaluative research: A discussion paper

This paper provides an introduction to issues surrounding the participation rights of young people in research and the implications of their growing involvement in research as well as providing a discourse on the ethical implications related to consent. The unique contribution of this paper is that it considers children’s rights in respect to the increasing opportunities for young people to take part in evaluation research. The aim of this paper, therefore, is to acknowledge the growing involvement for young people in research and the implications of ensuring that their rights of participation are respected. Secondly we will consider the children’s rights legislation and our obligations as researchers to implement this. Finally we will explore consent as an issue in its own right as well as the practicalities of accessing participants. This paper will postulate that any research about young people should involve and prioritise at all stages of the research process; including participation in decision-making. We conclude by identifying five key principles, which we believe can help to facilitate the fulfilment of post-primary pupils’ ability to consent to participate in trials and evaluative research.

Phonic skills mediate improved literacy outcomes in at-risk primary school children: results from the Ready-to-Learn Programme

Background
Learning to read is a key goal during primary school: reading difficulties may curtail children’s learning trajectories. Controversy remains regarding what types of interventions are effective for children at risk for academic failure, such as children in disadvantaged areas. We present data from a complex intervention to test the hypothesis that phonic skills and word recognition abilities are a pivotal and specific causal mechanism for the development of reading skills in children at risk for poorer literacy outcomes.
Method
Over 500 pupils across 16 primary schools took part in a Cluster Randomised Controlled Trial from school year 1 to year 3. Schools were randomly allocated to the intervention or the control arm. The intervention involved a literacy-rich after-school programme. Children attending schools in the control arm of the study received the curriculum normally provided. Children in both arms completed batteries of language, phonic skills, and reading tests every year. We used multilevel mediation models to investigate mediating processes between intervention and outcomes.
Findings
Children who took part in the intervention displayed improvements in reading skills compared to those in the control arm. Results indicated a significant indirect effect of the intervention via phonics encoding.
Discussion
The results suggest that the intervention was effective in improving reading abilities of children at risk, and this effect was mediated by improving children’s phonic skills. This has relevance for designing interventions aimed at improving literacy skills of children exposed to socio-economic disadvantage. Results also highlight the importance of methods to investigate causal pathways from intervention to outcomes.

Health in Ireland: Key Trends 2015

Health in Ireland Key Trends gives us insights into trends in demographics, population health, hospital and primary care and health service employment and expenditure. The presentation of trend data over the last decade in the 2015 report highlights the many significant achievements that Ireland has made in terms of key outcomes relating to the health and wellbeing of the population. However, it also highlights the challenges that persist in terms of the accessibility of timely healthcare and in the context of financial constraints. In the last decade alone, there has been an increase of two and a half years in life expectancy. These gains are driven largely by reductions in mortality rates from principal causes of deaths such as those from heart disease and cancer. Another striking feature is the growth in the number of people aged over 65. Each year this cohort increases by 20,000 people. This trend is set to continue into the future and will have implications for future planning and health service delivery. Ireland will see the largest proportional increases in the population aged 85 years and older. Ageing of the population in conjunction with lifestyle-related health threats continue to present major challenges now and into the future in sustaining and further improving health and health services in Ireland. Although difficult to quantify, the contribution of modern health services to these improvements in health outcomes and in life expectancy have been significant. Ireland’s fertility rates are still among the highest in Europe but the birth rate has fallen to its lowest rate for the last decade.  However, Ireland currently has the highest proportion of children and young people in our population among EU countries.  

Social representations of nursing students about hospital assistance and primary health care

Objective: To analyze how social representations of hospital and community care are structured in two groups of nursing students – 1st and 4th years. Method: Qualitative research oriented by the Theory of Social Representations. We used a questionnaire with Free Association of Words. Data were analyzed in the Software IRaMuTeQ 0.6 alpha 3. Results: We applied the method of Descending Hierarchical Classifi cation and obtained four classes. Class 4 has the largest social representation (30.41%) within the corpus. The two organizational axes are nurse and disease/patient in the central core. On the periphery are the care and help related to the nurse and the treatment and prevention associated with the disease. Conclusion: Social representations focus on disease/patient and on the role of nurses in the treatment, prevention, and care. Health promotion and the social determinants of health are absent from the social representations of students.

Mineral stress response of Vitis cell wall transcriptome: identification, characterization and expression of genes from key families involved in wall biosynthesis and modification

Doutoramento em Engenharia Agronómica - Instituto Superior de Agronomia - UL

Primary Joint Arthroplasty Surgery: Is the Risk of Major Bleeding Higher in Elderly Patients? A Retrospective Cohort Study

Increased risk of bleeding after major orthopedic surgery (MOS) has been widely documented in general population. However, this complication has not been studied in elderly patients. The purpose of this study is to determine whether the risk of major bleeding after MOS is higher in elderly patients, compared with those operated at a younger age. Methods: This retrospective cohort study included total hip and total knee arthroplasty patients operated during 5 consecutive years. The main outcome was the occurrence of major bleeding. Patients with other causes of bleeding were excluded. Relative risks (RRs) and confidence intervals (CIs) were calculated, anda multivariate analysis was performed. Results: A total of 1048 patients were included, 56% of patients were hip arthroplasties. At the time of surgery, 553 (53%) patients were older than 70 years. Patients aged >70 years showed an increased risk of major bleeding (RR: 2.42 [95% CI: 1.54-3.81]). For hip arthroplasty, the RR of bleeding was 2.61 (95%CI: 1.50-4.53) and 2.25 (95% CI: 1.03-4.94) for knee arthroplasty. After multivariate analysis, age was found to be independently associated with higher risk of major bleeding. Conclusion: According to European Medicines Agency criteria, patients aged 70 years are at a higher risk of major bleeding after MOS, result of a higher frequency of blood transfusions in this group of patients. Standardized protocols for blood transfusion in these patients are still required.

Sequential alcohol oxidation/putative homo Claisen-Tishchenko-type reaction to give esters: a key process in accessing novel biologically active lactone macrocycles

We report an efficient methodology for the direct oxidative esterification of primary alcohols to diether-esters using pyridinium chlorochromate (PCC). Numerous studies were carried out to probe the reaction mechanism and at the same time optimize the reaction conditions. The reaction could be conducted with 1 equivalent of PCC and 1 equivalent of BF3 center dot OEt2. Indications based on literature precedent were that the reaction may proceed via a sequential alcohol oxidation to the aldehyde followed by a putative Cr or boron catalyzed Claisen-Tishchenko-type reaction. Using this efficient methodology, we synthesized a family of novel diether-esters in very good yields; some of these molecules were subsequently tested against both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). In addition, we also disclose a new synthetic strategy for the synthesis of lactam macrocycles with potential biological activity. This methodology included the regioselective borylation of the ester substrate and a subsequent Suzuki-Miyaura coupling to obtain the desired lactam macrocycle.

Ikkε Is Key To Induction Of Insulin Resistance In The Hypothalamus, And Its Inhibition Reverses Obesity.

IKK epsilon (IKKε) is induced by the activation of nuclear factor-κB (NF-κB). Whole-body IKKε knockout mice on a high-fat diet (HFD) were protected from insulin resistance and showed altered energy balance. We demonstrate that IKKε is expressed in neurons and is upregulated in the hypothalamus of obese mice, contributing to insulin and leptin resistance. Blocking IKKε in the hypothalamus of obese mice with CAYMAN10576 or small interfering RNA decreased NF-κB activation in this tissue, relieving the inflammatory environment. Inhibition of IKKε activity, but not TBK1, reduced IRS-1(Ser307) phosphorylation and insulin and leptin resistance by an improvement of the IR/IRS-1/Akt and JAK2/STAT3 pathways in the hypothalamus. These improvements were independent of body weight and food intake. Increased insulin and leptin action/signaling in the hypothalamus may contribute to a decrease in adiposity and hypophagia and an enhancement of energy expenditure accompanied by lower NPY and increased POMC mRNA levels. Improvement of hypothalamic insulin action decreases fasting glycemia, glycemia after pyruvate injection, and PEPCK protein expression in the liver of HFD-fed and db/db mice, suggesting a reduction in hepatic glucose production. We suggest that IKKε may be a key inflammatory mediator in the hypothalamus of obese mice, and its hypothalamic inhibition improves energy and glucose metabolism.

Advancing Bag-of-visual-words Representations For Lesion Classification In Retinal Images.

Diabetic Retinopathy (DR) is a complication of diabetes that can lead to blindness if not readily discovered. Automated screening algorithms have the potential to improve identification of patients who need further medical attention. However, the identification of lesions must be accurate to be useful for clinical application. The bag-of-visual-words (BoVW) algorithm employs a maximum-margin classifier in a flexible framework that is able to detect the most common DR-related lesions such as microaneurysms, cotton-wool spots and hard exudates. BoVW allows to bypass the need for pre- and post-processing of the retinographic images, as well as the need of specific ad hoc techniques for identification of each type of lesion. An extensive evaluation of the BoVW model, using three large retinograph datasets (DR1, DR2 and Messidor) with different resolution and collected by different healthcare personnel, was performed. The results demonstrate that the BoVW classification approach can identify different lesions within an image without having to utilize different algorithms for each lesion reducing processing time and providing a more flexible diagnostic system. Our BoVW scheme is based on sparse low-level feature detection with a Speeded-Up Robust Features (SURF) local descriptor, and mid-level features based on semi-soft coding with max pooling. The best BoVW representation for retinal image classification was an area under the receiver operating characteristic curve (AUC-ROC) of 97.8% (exudates) and 93.5% (red lesions), applying a cross-dataset validation protocol. To assess the accuracy for detecting cases that require referral within one year, the sparse extraction technique associated with semi-soft coding and max pooling obtained an AUC of 94.2 ± 2.0%, outperforming current methods. Those results indicate that, for retinal image classification tasks in clinical practice, BoVW is equal and, in some instances, surpasses results obtained using dense detection (widely believed to be the best choice in many vision problems) for the low-level descriptors.

Primary Relapse Site Pattern In Women With Triple-negative Breast Cancer.

Despite the remarkable improvements in breast cancer (BC) characterization, accurate prediction of BC clinical behavior is often still difficult to achieve. Some studies have investigated the association between the molecular subtype, namely the basal-like BC and the pattern of relapse, however only few investigated the association between relapse pattern and immunohistochemical defined triple-negative breast cancers (TNBCs). The aim of this study was to evaluate the pattern of relapse in patients with TNBC, namely the primary distant relapse site. One-hundred twenty nine (129) invasive breast carcinomas with follow-up information were classified according to the molecular subtype using immunohistochemistry for ER, PgR and Her2. The association between TNBC and distant relapse primary site was analyzed by logistic regression. Using multivariate logistic regression analysis patients with TNBC displayed only 0.09 (95% CI: 0.00-0.74; p=0.02) the odds of the non-TNBC patients of developing bone primary relapse. Regarding visceral and lymph-node relapse, no differences between in this cohort were found. Though classically regarded as aggressive tumors, TNBCs rarely development primary relapse in bone when compared to non-TNBC, a clinical relevant fact when investigating a metastasis of an occult or non-sampled primary BC.

Homozygous Inactivating Mutation In Nanos3 In Two Sisters With Primary Ovarian Insufficiency.

Despite the increasing understanding of female reproduction, the molecular diagnosis of primary ovarian insufficiency (POI) is seldom obtained. The RNA-binding protein NANOS3 poses as an interesting candidate gene for POI since members of the Nanos family have an evolutionarily conserved function in germ cell development and maintenance by repressing apoptosis. We performed mutational analysis of NANOS3 in a cohort of 85 Brazilian women with familial or isolated POI, presenting with primary or secondary amenorrhea, and in ethnically-matched control women. A homozygous p.Glu120Lys mutation in NANOS3 was identified in two sisters with primary amenorrhea. The substituted amino acid is located within the second C2HC motif in the conserved zinc finger domain of NANOS3 and in silico molecular modelling suggests destabilization of protein-RNA interaction. In vitro analyses of apoptosis through flow cytometry and confocal microscopy show that NANOS3 capacity to prevent apoptosis was impaired by this mutation. The identification of an inactivating missense mutation in NANOS3 suggests a mechanism for POI involving increased primordial germ cells (PGCs) apoptosis during embryonic cell migration and highlights the importance of NANOS proteins in human ovarian biology.

Analysis Of The Contribution Of Immunologically-detectable Her2, Steroid Receptors And Of The Triple-negative" Tumor Status To Disease-free And Overall Survival Of Women With Epithelial Ovarian Cancer."

We assessed associations between steroid receptors including: estrogen-alpha, estrogen-beta, androgen receptor, progesterone receptor, the HER2 status and triple-negative epithelial ovarian cancer (ERα-/PR-/HER2-; TNEOC) status and survival in women with epithelial ovarian cancer. The study included 152 women with primary epithelial ovarian cancer. The status of steroid receptor and HER2 was determined by immunohistochemistry. Disease-free and overall survival were calculated and compared with steroid receptor and HER2 status as well as clinicopathological features using the Cox Proportional Hazards model. A mean follow-up period of 43.6 months (interquartile range=41.4 months) was achieved where 44% of patients had serous tumor, followed by mucinous (23%), endometrioid (9%), mixed (9%), undifferentiated (8.5%) and clear cell tumors (5.3%). ER-alpha staining was associated with grade II-III tumors. Progesterone receptor staining was positively associated with a Body Mass Index≥25. Androgen receptor positivity was higher in serous tumors. In stand-alone analysis of receptor contribution to survival, estrogen-alpha positivity was associated with greater disease-free survival. However, there was no significant association between steroid receptor expression, HER2 status, or TNEOC status, and overall survival. Although estrogen-alpha, androgen receptor, progesterone receptor and the HER2 status were associated with key clinical features of the women and pathological characteristics of the tumors, these associations were not implicated in survival. Interestingly, women with TNEOC seem to fare the same way as their counterparts with non-TNEOC.

Infratentorial Gray Matter Atrophy And Excess In Primary Craniocervical Dystonia.

Primary craniocervical dystonia (CCD) is generally attributed to functional abnormalities in the cortico-striato-pallido-thalamocortical loops, but cerebellar pathways have also been implicated in neuroimaging studies. Hence, our purpose was to perform a volumetric evaluation of the infratentorial structures in CCD. We compared 35 DYT1/DYT6 negative patients with CCD and 35 healthy controls. Cerebellar volume was evaluated using manual volumetry (DISPLAY software) and infratentorial volume by voxel based morphometry of gray matter (GM) segments derived from T1 weighted 3 T MRI using the SUIT tool (SPM8/Dartel). We used t-tests to compare infratentorial volumes between groups. Cerebellar volume was (1.14 ± 0.17) × 10(2) cm(3) for controls and (1.13 ± 0.14) × 10(2) cm(3) for patients; p = 0.74. VBM demonstrated GM increase in the left I-IV cerebellar lobules and GM decrease in the left lobules VI and Crus I and in the right lobules VI, Crus I and VIIIb. In a secondary analysis, VBM demonstrated GM increase also in the brainstem, mostly in the pons. While gray matter increase is observed in the anterior lobe of the cerebellum and in the brainstem, the atrophy is concentrated in the posterior lobe of the cerebellum, demonstrating a differential pattern of infratentorial involvement in CCD. This study shows subtle structural abnormalities of the cerebellum and brainstem in primary CCD.

Biased Random-key Genetic Algorithms For The Winner Determination Problem In Combinatorial Auctions.

Abstract In this paper, we address the problem of picking a subset of bids in a general combinatorial auction so as to maximize the overall profit using the first-price model. This winner determination problem assumes that a single bidding round is held to determine both the winners and prices to be paid. We introduce six variants of biased random-key genetic algorithms for this problem. Three of them use a novel initialization technique that makes use of solutions of intermediate linear programming relaxations of an exact mixed integer-linear programming model as initial chromosomes of the population. An experimental evaluation compares the effectiveness of the proposed algorithms with the standard mixed linear integer programming formulation, a specialized exact algorithm, and the best-performing heuristics proposed for this problem. The proposed algorithms are competitive and offer strong results, mainly for large-scale auctions.

Root Canal Content From Primary Endodontic Infection And Upregulation Of Gelatinases In Fibroblast Cells.

To investigate endotoxin levels from primary endodontic infections before and after chemomechanical preparation (CMP) and to determine their antigenicity against 3T3 fibroblasts through gelatinolytic activity of matrix metalloproteinases (MMPs). Twenty-four root canals with primary endodontic infection and apical periodontitis were selected. Samples were collected using paper points before (S1) and after chemomechanical preparation (CMP) (S2). The limulus amebocyte lysate assay was used for endotoxin measurement. Fibroblasts were stimulated with root canal contents for 24 h. Supernatants of cell cultures stimulated with root canal contents were collected after 24 h to determine the levels of MMP-2 and MMP-9 gelatinolytic activity using the zymography technique. Friedman and Wilcoxon tests were used to compare the amount of endotoxin before (S1) and after CMP (S2) (P < 0.05). Data obtained from gelatinolytic activity were analysed using anova and Tukey's tests (P < 0.05). Endotoxin was recovered in 100% of the samples. There was a significant reduction in endotoxin levels after CMP (P < 0.05). A correlation was found between the levels of endotoxins and MMP-2 expression (P < 0.05). Root canal contents of initial samples (S1) induced significantly greater MMP-2 expression by fibroblasts when compared to S2 and the nonstimulated group (P < 0.05). No gelatinolytic activity of MMP-9 was observed in S1, S2 and control group. Root canal contents from primary endodontic infections had gelatinolytic activity for MMP-2. Moreover, CMP was effective in reducing endotoxin levels and their antigenicity against fibroblasts on gelatinolytic activity.