Germline variation in RASAL2 may predict survival in patients with RAS-activated colorectal cancer.

Background: Therapeutic agents that specifically target patients with RAS mutant colorectal cancer (CRC) are needed. We sought potential drug targets by relating genome-wide association study and survival data in patients with advanced CRC profiled for mitogen-activated protein kinase (MAPK) pathway mutations.

Methods: In total, 694 patients from the clinical trials COIN and COIN-B had MAPK-activated CRCs (assigned as KRAS, NRAS, or BRAF mutant).

Relationship between 233 colorectal cancer risk loci and survival in 1926 patients with advanced disease.

Background: Genome, transcriptome and methylome-wide association studies have identified single-nucleotide polymorphisms (SNPs) or genes at 258 loci associated with colorectal cancer (CRC) risk. We studied the relationship between these and patient outcome.

Methods: We studied 1926 unrelated patients with advanced CRC from COIN and COIN-B.

Genetic variation in ST6GAL1 is a determinant of capecitabine and oxaliplatin induced hand-foot syndrome.

Cancer patients treated with capecitabine and oxaliplatin (XELOX) often develop hand-foot syndrome (HFS) or palmar-plantar erythrodysesthesia. Genetic variation in ST6GAL1 is a risk factor for type-2 diabetes (T2D), a disease also associated with HFS. We analysed genome-wide association data for 10 toxicities in advanced colorectal cancer (CRC) patients from the COIN and COIN-B trials.

A genome-wide search for determinants of survival in 1926 patients with advanced colorectal cancer with follow-up in over 22,000 patients.

Background: While genome-wide association studies (GWAS) have identified germline variants influencing the risk of developing colorectal cancer (CRC), there has been limited examination of the possible role of inherited variation as a determinant of patient outcome.

Patients And Methods: We performed a GWAS for overall survival (OS) in 1926 patients with advanced CRC from the COIN and COIN-B clinical trials. For single nucleotide polymorphisms (SNPs) showing an association with OS (P < 1.

Genome-wide association studies of toxicity to oxaliplatin and fluoropyrimidine chemotherapy with or without cetuximab in 1800 patients with advanced colorectal cancer.

Chemotherapies administered at normal therapeutic dosages can cause significant side-effects and may result in early treatment discontinuation. Inter-individual variation in toxicity highlights the need for biomarkers to personalise treatment. We sought to identify such biomarkers by conducting 40 genome-wide association studies, together with gene and gene set analyses, for any toxicity and 10 individual toxicities in 1800 patients with advanced colorectal cancer treated with oxaliplatin and fluoropyrimidine chemotherapy ± cetuximab from the MRC COIN and COIN-B trials (385 patients received FOLFOX, 360 FOLFOX + cetuximab, 707 XELOX and 348 XELOX + cetuximab).

Correction to: Persistent physical symptoms reduction intervention: a system change and evaluation in secondary care (PRINCE secondary) - a CBT-based transdiagnostic approach: study protocol for a randomised controlled trial.

An amendment to this paper has been published and can be accessed via the original article.

Persistent physical symptoms reduction intervention: a system change and evaluation in secondary care (PRINCE secondary) - a CBT-based transdiagnostic approach: study protocol for a randomised controlled trial.

Background: Persistent physical symptoms (PPS), also known as medically unexplained symptoms (MUS), affect approximately 50% of patients in secondary care and are often associated with disability, psychological distress and increased health care costs. Cognitive behavioural therapy (CBT) has demonstrated both short- and long-term efficacy with small to medium effect sizes for PPS, with larger treatment effects for specific PPS syndromes, including non-cardiac chest pain, irritable bowel syndrome (IBS) and chronic fatigue syndrome (CFS). Research indicates that PPS conditions share similar cognitive and behavioural responses to symptoms, such as avoidance and unhelpful beliefs.

Preliminary evaluation of a multimodal early intervention program for behaviorally inhibited preschoolers.

Objective: Approximately 15%-20% of young children can be classified as having a behaviorally inhibited (BI) temperament. Stable BI predicts the development of later anxiety disorders (particularly social anxiety), but not all inhibited children develop anxiety. Parenting characterized by inappropriate warmth/sensitivity and/or intrusive control predicts the stability of BI and moderates risk for anxiety among high-BI children.

Waist circumference predicts cardiovascular risk in young Australian children.

Aim: It has been shown that compared with healthyweight children, overweight and obese primary school-aged children have a higher incidence of hyperinsulinism, dyslipidaemia and hypertension. It is therefore important to investigate clinically relevant markers of cardiovascular risk in children. Waist circumference is a simple, non-invasive anthropometric measure, but its association with cardiovascular risk profile in young Australian children is not clear.

Resistance training and diastolic myocardial tissue velocities in obese children.

Purpose: The primary purpose of this study was to determine the effects of resistance exercise training on early diastolic myocardial velocities (E') in an obese pediatric population.

Methods: Twenty-three obese adolescents were selected to participate in either a resistance-based training program (RT; n = 13, 12.2 +/- 0.

Exercise alone reduces insulin resistance in obese children independently of changes in body composition.

Context: The number of obese children with insulin resistance and type 2 diabetes is increasing, but the best management strategy is not clear.

Objective: The objective of this study was to assess the effect of a structured 8-wk exercise training program on insulin resistance and changes in body composition in obese children.

Design: The study was 8 wk of structured supervised exercise intervention with outcome measures before and after the exercise period.

Do skinfolds accurately assess changes in body fat in obese children and adolescents?

Purpose: Obesity is epidemic in Western societies, with rapid rates of increase in the young. Various methods exist for the assessment of body composition, but these have not been compared in obese children and adolescents. This study compared methods of body composition assessment in obese young people to determine whether changes in various measures of body composition as a result of exercise training were correlated.

Exercise training in obese children and adolescents: current concepts.

Childhood obesity has reached epidemic proportions worldwide and is associated with increased cardiovascular mortality and morbidity in adult life. The increase in fat mass in children and adolescents has occurred concomitantly with a decline in reported time for exercise. Evidence suggests that non-physically active children are more likely to become non-physically active adults and that encouraging the development of physical activity habits in children helps establish patterns that continue into adulthood.

Exercise training normalizes vascular dysfunction and improves central adiposity in obese adolescents.

Objectives: We sought to characterize the impact of obesity on vascular function in adolescents and to determine whether an exercise program reverses abnormalities in endothelial function.

Background: Obesity, a major modifiable risk factor for cardiovascular disease, is epidemic in Western societies, with rapid rates of increase in the young. Atherosclerosis begins in childhood, and endothelial dysfunction is its earliest detectable manifestation.

Effects of exercise training on vascular function in obese children.

Objectives: Atherosclerosis is a disease that begins in childhood; endothelial dysfunction is its earliest detectable manifestation, and primary prevention strategies are likely to be most effective if instituted early. The aim of this study was to characterize the impact of obesity on vascular function in young children and to determine whether an exercise program improves abnormalities in vascular function.

Study Design: The influence of 8 weeks of exercise training was examined in 14 obese subjects, 8.

Lack of effect of oral glucose loading on conduit vessel endothelial function in healthy subjects.

The aim of the present study was to investigate the impact of an oral glucose load on circulating insulin and glucose levels and arterial function in healthy non-diabetic subjects. Thirty-nine non-obese, healthy subjects (24 female, 15 male), aged 21.0+/-1.

Effect of lower limb exercise on forearm vascular function: contribution of nitric oxide.

We examined vascular function in an inactive muscle bed, the forearm, during lower limb exercise and determined the contribution of endothelium-derived nitric oxide (NO) to the hyperemic response. Eight young males were randomized to participate in two studies, each consisting of two bouts of lower limb exercise, separated by a 30-min recovery. Peak forearm blood flow (PFBF) and mean blood flow (MFBF) were continuously recorded at baseline and during exercise using continuous high-resolution vascular ultrasound and Doppler flow velocity measurement.

Increased gyrification in Williams syndrome: evidence using 3D MRI methods.

Understanding patterns of gyrification in neurogenetic disorders helps to uncover the neurodevelopmental etiology underlying behavioral phenotypes. This is particularly true in Williams syndrome (WS), a condition caused by de novo deletion of approximately 1 to 2 Mb in the 7q11.23 region.