Misguided and Modest: Reflections of Our Youth Voice Research.

In recent years, Physical Education (PE) has seen a growth in the commitment to youth voice research. This approach foregrounds the practice of researching with young people, rather than conducting research on or about them. Whilst we are cognisant of the many possibilities youth voice research offers, we are also concerned that there is a tendency to overlook the challenges of supporting youth voice activities.

"I'm a Referee, Not a Female Referee": The Experiences of Women Involved in Football as Coaches and Referees.

The development of the Women's Super League (WSL) in English football, increased media coverage of the game, and an expansion of grassroots opportunities indicate a bright future for women and girls who want to play. Yet this vision must be tempered against compelling evidence of deep rooted and enduring gender inequalities within the game. This is the case for both players, and women who undertake non-playing roles, which is reflected in the relatively low numbers of women coaches and referees.

Generation of Doubled Haploid Wheat- Introgression Lines and Their Characterisation Using Chromosome-Specific KASP Markers.

Wheat is one of the most important food and protein sources in the world and although, in recent years wheat breeders have achieved yield gains, they are not sufficient to meet the demands of an ever-growing population. Development of high yielding wheat varieties, resilient to abiotic and biotic stress resulting from climate change, has been limited by wheat's narrow genetic base. In contrast to wheat, the wild relatives of wheat provide a vast reservoir of genetic variation for most, if not all, agronomic traits.

Development of Stable Homozygous Wheat/ () Introgression Lines and Their Cytogenetic and Molecular Characterization.

Wheat is one of the world's most important sources of food. However, due to its evolution its genetic base has narrowed, which is severely limiting the ability of breeders to develop new higher yielding varieties that can adapt to the changing environment. In contrast to wheat, its wild relatives provide a vast reservoir of genetic variability for most, if not all, agronomically important traits.

Cross-sectional and longitudinal studies suggest pharmacological treatment used in patients with glucokinase mutations does not alter glycaemia.

Aims/hypothesis: Heterozygous glucokinase (GCK) mutations cause mild, fasting hyperglycaemia from birth. Although patients are usually asymptomatic and have glycaemia within target ranges, some are put on pharmacological treatment. We aimed to investigate how many patients are on pharmacological treatment and the impact of treatment on glycaemic control.

Clinical heterogeneity in monogenic diabetes caused by mutations in the glucokinase gene (GCK-MODY).

Objective: To evaluate the heterogeneity in the clinical expression in a family with glucokinase mature-onset diabetes of the young (GCK-MODY).

Research Design And Methods: Members (three generations) of the same family presented either with overt neonatal hyperglycemia, marked postprandial hyperglycemia, or glucosuria. Homeostasis model assessment of insulin resistance (HOMA(IR)) and insulinogenic and disposition indexes were calculated.

Partial and whole gene deletion mutations of the GCK and HNF1A genes in maturity-onset diabetes of the young.

Aims/hypothesis: Heterozygous mutations of glucokinase (GCK) and hepatocyte nuclear factor-1 alpha (HNF1A; also known as hepatic transcription factor 1 [TCF1]) genes are the most common cause of MODY. Genomic deletions of the HNF1B (also known as TCF2) gene have recently been shown to account for one third of mutations causing renal cysts and diabetes syndrome. We investigated the prevalence of partial and whole gene deletions in UK patients meeting clinical criteria for GCK or HNF-1alpha/-4alpha MODY and in whom no mutation had been identified by sequence analysis.

Isomers of the TCF1 gene encoding hepatocyte nuclear factor-1 alpha show differential expression in the pancreas and define the relationship between mutation position and clinical phenotype in monogenic diabetes.

The generation of multiple transcripts by mRNA processing has the potential to moderate differences in gene expression both between tissues and at different stages of development. Where gene function is compromised by mutation, the presence of multiple isoforms may influence the resulting phenotype. Heterozygous mutations in the transcription factor hepatocyte nuclear factor-1 alpha (HNF1A or TCF1 gene) result in early-onset diabetes as a result of pancreatic beta-cell dysfunction.

Beta-cell dysfunction, insulin sensitivity, and glycosuria precede diabetes in hepatocyte nuclear factor-1alpha mutation carriers.

Objective: Patients with diabetes due to hepatocyte nuclear factor (HNF)-1alpha mutations have beta-cell deficiency, insulin sensitivity, altered proinsulin levels, and a low renal threshold for glucose. It is uncertain how many of these features precede the development of diabetes. The aim of our study was to test for these characteristics in young nondiabetic HNF-1alpha mutation carriers.

Insights into the structure and regulation of glucokinase from a novel mutation (V62M), which causes maturity-onset diabetes of the young.

Glucokinase (GCK) serves as the pancreatic glucose sensor. Heterozygous inactivating GCK mutations cause hyperglycemia, whereas activating mutations cause hypoglycemia. We studied the GCK V62M mutation identified in two families and co-segregating with hyperglycemia to understand how this mutation resulted in reduced function.

Microalbuminuria as a screening tool in cystic fibrosis-related diabetes.

The improving longevity of cystic fibrosis (CF) subjects has resulted in an increased prevalence and duration of cystic fibrosis-related diabetes (CFRD). Microvascular complications were reported in CFRD. Microalbuminuria is well-established as a sensitive indicator of progression to diabetic nephropathy in non-CF diabetes, but confounding factors may make it less sensitive for CF subjects.

Serum amino acids in patients with mutations in the hepatocyte nuclear factor-1 alpha gene.

Aims: Knockout mice lacking both copies of the hepatocyte nuclear factor 1 (HNF1) gene have altered serum levels of amino acids and generalized aminoaciduria. The aim of our study was to test whether alterations in serum amino acid levels were found in patients with mutations in the hepatocyte nuclear factor-1 alpha (HNF-1alpha) gene compared with controls.

Methods: Fasting serum from 20 patients with HNF-1alpha mutations and 20 age, sex and body mass index-matched controls was analysed for 16 amino acids.

Etiological investigation of diabetes in young adults presenting with apparent type 2 diabetes.

Objective: Young adults with newly diagnosed apparent type 2 diabetes present the clinician with a wide differential diagnosis of possible etiology, including autoimmune and genetic causes as well as young-onset type 2 diabetes (YT2D). The characteristics of these groups have been described, but it is not known in which subjects investigation for etiology may be beneficial.

Research Design And Methods: A total of 268 unselected U.

Atypical familial juvenile hyperuricemic nephropathy associated with a hepatocyte nuclear factor-1beta gene mutation.

Background: Familial juvenile hyperuricemic nephropathy (FJHN) is a dominantly inherited condition characterized by young-onset hyperuricemia, gout, and renal disease. The etiologic genes are unknown, although a locus on chromosome 16 has been identified in some kindreds. Mutations in the gene encoding hepatocyte nuclear factor (HNF)-1beta have been associated with dominant inheritance of a variety of disorders of renal development, particularly renal cystic disease and early onset diabetes; hyperuricemia has been reported in some kindreds.

Intrauterine hyperglycemia is associated with an earlier diagnosis of diabetes in HNF-1alpha gene mutation carriers.

Objective: In animals, experimentally induced maternal hyperglycemia during pregnancy results in hyperglycemic offspring. Similarly, Pima Indian offspring with mothers who are diabetic at the time of pregnancy have increased risk of early-onset diabetes. We hypothesized that exposure to hyperglycemia in utero would decrease the age at diagnosis of diabetes in patients with maturity-onset diabetes of the young (MODY) due to a mutation in the hepatocyte nuclear factor 1alpha (HNF-1alpha) gene.

Heterogeneity in young adult onset diabetes: aetiology alters clinical characteristics.

Aims: To describe the characteristics of hepatocyte nuclear factor (HNF) 1 alpha mutation carriers diagnosed with diabetes after 25 years and compare them with young-onset Type 2 diabetic patients (YT2D) diagnosed at the same age.

Subjects And Methods: We studied 44 (21 male, 23 female) patients with HNF-1 alpha mutations diagnosed with diabetes at ages 25-45 years and 44 YT2D subjects matched for sex and age of diagnosis.

Results: Median age of onset of diabetes was 35 years in both groups.

Different genes, different diabetes: lessons from maturity-onset diabetes of the young.

Maturity-onset diabetes of the young (MODY) is a genetic subgroup of diabetes characterised by an autosomal dominant inheritance and early onset, non-insulin dependent diabetes. This results from a monogenic defect causing beta-cell dysfunction. The defining of five genes in which mutations cause MODY has allowed us to understand the clinical heterogeneity seen in this condition and can guide clinical management.

The genetic abnormality in the beta cell determines the response to an oral glucose load.

Aims/hypothesis: We assessed how the role of genes genetic causation in causing maturity-onset diabetes of the young (MODY) alters the response to an oral glucose tolerance test (OGTT).

Methods: We studied OGTT in 362 MODY subjects, from seven European centres; 245 had glucokinase gene mutations and 117 had Hepatocyte Nuclear Factor -1 alpha ( HNF-1alpha) gene mutations.

Results: BMI and age were similar in the genetically defined groups.

beta-cell genes and diabetes: quantitative and qualitative differences in the pathophysiology of hepatic nuclear factor-1alpha and glucokinase mutations.

Mutations in the beta-cell genes encoding the glycolytic enzyme glucokinase (GCK) and the transcription factor hepatocyte nuclear factor (HNF)-1alpha are the most common causes of maturity-onset diabetes of the young (MODY). Studying patients with mutations in these genes gives insights into the functions of these two critical beta-cell genes in humans. We studied 178 U.

Continental margin of Western europe: slope progradation and erosion.

Reflection profiling of the continental margin off western Europe shows seaward-dipping continental-slope deposits that have been dissected by submarine canyons west of the English Channel. These records refute previous interpretation of structural benches of older, nearly horizontal strata outcropping on the slope face.