The prevalence of type 2 diabetes mellitus (T2DM) has been increasing, owing to increases in overweight and obesity, decreasing physical activity and the changing demographic structure of the ...population. People can develop T2DM without symptoms and up to 20% may be undiagnosed. They may have diabetic complications, such as retinopathy, by the time they are diagnosed, or may suffer a heart attack, without warning. Undiagnosed diabetes can be detected by raised blood glucose levels.
The aim of this review was to provide an update for the UK National Screening Committee (NSC) on screening for T2DM.
As this review was undertaken to update a previous Health Technology Assessment review published in 2007, and a more recent Scottish Public Health Network review, searches for evidence were restricted from 2009 to end of January 2012, with selected later studies added. The databases searched were MEDLINE, EMBASE, MEDLINE-in-Process & Other Non-Indexed Citations, Science Citation Index and Conference Proceedings Citation Index. The case for screening was considered against the criteria used by the NSC to assess proposed population screening programmes.
Population screening for T2DM does not meet all of the NSC criteria. Criterion 12, on optimisation of existing management, has not been met. A report by the National Audit Office (NAO) gives details of shortcomings. Criterion 13 requires evidence from high-quality randomised controlled trials that screening is beneficial. This has not been met. The Ely trial of screening showed no benefit. The ADDITION trial was not a trial of screening, but showed no benefit in cardiovascular outcomes from intensive management in people with screen-detected T2DM. Criterion 18 on staffing and facilities does not appear to have been met, according to the NAO report. Criterion 19 requires that all other options, including prevention, should have been considered. A large proportion of cases of T2DM could be prevented if people avoided becoming overweight or obese. The first stage of selection would use risk factors, using data held on general practitioner computer systems, using the QDiabetes Risk Score, or by sending out questionnaires, using the Finnish Diabetes Risk Score (FINDRISC). Those at high risk would have a measure of blood glucose. There is no perfect screening test. Glycated haemoglobin (HbA1c) testing has advantages in not requiring a fasting sample, and because it is a predictor of vascular disease across a wider range than just the diabetic one. However, it lacks sensitivity and would miss some people with diabetes. Absolute values of HbA1c may be more useful as part of overall risk assessment than a dichotomous 'diabetes or not diabetes' diagnosis. The oral glucose tolerance test is more sensitive, but inconvenient, more costly, has imperfect reproducibility and is less popular, meaning that uptake would be lower.
When considered against the NSC criteria, the case for screening is less strong than it was in the 2007 review. The main reason is the absence of cardiovascular benefit in the two trials published since the previous review. There is a case for selective screening as part of overall vascular risk assessment. Population screening for T2DM does not meet all of the NSC criteria.
The National Institute for Health Research Health Technology Assessment programme.
The establishment of language as a focus of study took place over many centuries, and reflection on its nature emerged in relation to very different social and cultural practices. Written by a team ...of leading scholars, this volume provides an authoritative, chronological account of the history of the study of language from ancient times to the end of the 20th century (i.e., 'recent history', when modern linguistics greatly expanded). Comprised of 29 chapters, it is split into 3 parts, each with an introduction covering the larger context of interest in language, especially the different philosophical, religious, and/or political concerns and socio-cultural practices of the times. At the end of the volume, there is a combined list of all references cited and a comprehensive index of topics, languages, major figures, etc. Comprehensive in its scope, it is an essential reference for researchers, teachers and students alike in linguistics and related disciplines.
Candida albicans cells are often detected with Streptococcus mutans in plaque biofilms from children affected with early childhood caries. The coadhesion between these 2 organisms appears to be ...largely mediated by the S. mutans–derived exoenzyme glucosyltransferase B (GtfB); GtfB readily binds to C. albicans cells in an active form, producing glucans locally that provide enhanced binding sites for S. mutans. However, knowledge is limited about the mechanisms by which the bacterial exoenzyme binds to and functions on the fungal surface to promote this unique cross-kingdom interaction. In this study, we use atomic force microscopy to understand the strength and binding dynamics modulating GtfB–C. albicans adhesive interactions in situ. Single-molecule force spectroscopy with GtfB-functionalized atomic force microscopy tips demonstrated that the enzyme binds with remarkable strength to the C. albicans cell surface (~2 nN) and showed a low dissociation rate, suggesting a highly stable bond. Strikingly, the binding strength of GtfB to the C. albicans surface was ~2.5-fold higher and the binding stability, ~20 times higher, as compared with the enzyme adhesion to S. mutans. Furthermore, adhesion force maps showed an intriguing pattern of GtfB binding. GtfB adhered heterogeneously on the surface of C. albicans, showing a higher frequency of adhesion failure but large sections of remarkably strong binding forces, suggesting the presence of GtfB binding domains unevenly distributed on the fungal surface. In contrast, GtfB bound uniformly across the S. mutans cell surface with less adhesion failure and a narrower range of binding forces (vs. the C. albicans surface). The data provide the first insights into the mechanisms underlying the adhesive and mechanical properties governing GtfB interactions with C. albicans. The strong and highly stable GtfB binding to C. albicans could explain, at least in part, why this bacterially derived exoenzyme effectively modulates this virulent cross-kingdom interaction.
This paper explores the underlying drivers of steel production to predict the fate of the blast furnace as a steelmaking route. Steel production is driven by demand for stocks of steel products and ...increases in steel stocks are driven by population growth and economic development. However, per-capita steel stocks are expected to saturate with economic development leading to the long-term saturation of steel demand. Combined with an increase in the availability of end-of-life scrap, this suggests that the electric arc furnace route will be increasingly dominant. Furthermore, with an increasingly resource and carbon constrained world, material efficiency strategies will be required to provide the same services with less liquid steel. These factors may usher in the end of the blast furnace era within the next 50 years. This paper is based on research undertaken as part of the WellMet2050 project, and was delivered at the Cleveland Institution of Engineers debate in December 2014.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Many plants dramatically elongate their stems during flowering, yet how this response is coordinated with the reproductive phase is unclear. We demonstrate that microRNA (miRNA) control of
(
) is ...required for rapid, complete elongation of stem internodes in barley, especially of the final 'peduncle' internode directly underneath the inflorescence. Disrupted miR172 targeting of
in the
barley mutant caused lower mitotic activity, delayed growth dynamics and premature lignification in the peduncle leading to fewer and shorter cells. Stage- and tissue-specific comparative transcriptomics between
and its parent cultivar showed reduced expression of proliferation-associated genes, ectopic expression of maturation-related genes and persistent, elevated expression of genes associated with jasmonate and stress responses. We further show that applying methyl jasmonate (MeJA) phenocopied the stem elongation of
, and that
itself was hypersensitive to inhibition by MeJA but less responsive to promotion by gibberellin. Taken together, we propose that miR172-mediated restriction of
may modulate the jasmonate pathway to facilitate gibberellin-promoted stem growth during flowering.
Preeclampsia is a complication of pregnancy with significant morbidity and mortality for the mother and the fetus. Presumptions are made that placental hypoxia has a causative role in the clinical ...syndrome. Furthermore, soluble fms-like tyrosine kinase 1 (sFLT-1) has been shown to have a role in the maternal syndrome of preeclampsia. We investigated the relationship between uteroplacental ischemia (UPI), the maternal clinical syndrome of preeclampsia and sFLT-1 in non-human primates. The induction of UPI in a pregnant non-human primate resulted in the development of a clinical entity analogous to human preeclampsia. This was illustrated by the increase in blood pressure, development of proteinuria, and renal histological changes identical to human preeclampsia. A significant elevation in the placental and peripheral blood mononuclear cell sFLT-1 mRNA expression was noted, translating to a significant elevation in circulating sFLT-1. Thus, this sequence suggests that a pathogenic reduction in placental perfusion results in the development of the maternal syndrome of preeclampsia and an increase in circulating sFLT-1, which is derived both from placental and extra-placental sources.
The capability of molecular markers to provide information of genetic structure is influenced by their number and the way they are chosen. This study evaluates the effects of single nucleotide ...polymorphism (SNP) number and selection strategy on estimates of germplasm diversity and population structure for different types of barley germplasm, namely cultivar and landrace. One hundred and sixty-nine barley landraces from Syria and Jordan and 171 European barley cultivars were genotyped with 1536 SNPs. Different subsets of 384 and 96 SNPs were selected from the 1536 set, based on their ability to detect diversity in landraces or cultivated barley in addition to corresponding randomly chosen subsets. All SNP sets except the landrace-optimised subsets underestimated the diversity present in the landrace germplasm, and all subsets of SNP gave similar estimates for cultivar germplasm. All marker subsets gave qualitatively similar estimates of the population structure in both germplasm sets, but the 96 SNP sets showed much lower data resolution values than the larger SNP sets. From these data we deduce that pre-selecting markers for their diversity in a germplasm set is very worthwhile in terms of the quality of data obtained. Second, we suggest that a properly chosen 384 SNP subset gives a good combination of power and economy for germplasm characterization, whereas the rather modest gain from using 1536 SNPs does not justify the increased cost and 96 markers give unacceptably low performance. Lastly, we propose a specific 384 SNP subset as a standard genotyping tool for middle-eastern landrace barley.
Elite cultivated crop gene pools of the Triticeae tribe (wheat, barley and rye) exhibit limited genetic diversity, raising concerns about our ability to increase or simply sustain crop yield and ...quality in the face of dynamic environmental and biotic threats. Although exploiting their wild relatives as a source of novel alleles is challenging, it has provided notable successes in cereal improvement for >100 years. Increasingly facile gene discovery, improved enabling technologies for genetics and breeding and a better understanding of the factors limiting practical exploitation of exotic germplasm promise to transform existing, and accelerate the development of new, strategies for efficient and directed germplasm utilization.
Although ischaemic heart disease is the predominant cause of mortality in older people with diabetes, age-specific mortality rates have not been published for patients with Type 1 diabetes. The ...Diabetes UK cohort, essentially one of patients with Type 1 diabetes, now has sufficient follow-up to report all heart disease, and specifically ischaemic heart disease, mortality rates by age.
A cohort of 23,751 patients with insulin-treated diabetes, diagnosed under the age of 30 years and from throughout the United Kingdom, was identified during the period 1972 to 1993 and followed for mortality until December 2000. Age- and sex-specific heart disease mortality rates and standardised mortality ratios were calculated.
There were 1437 deaths during the follow-up, 536 from cardiovascular disease, and of those, 369 from ischaemic heart disease. At all ages the ischaemic heart disease mortality rates in the cohort were higher than in the general population. Mortality rates within the cohort were similar for men and women under the age of 40. The standardised mortality ratios were higher in women than men at all ages, and in women were 44.8 (95%CI 20.5-85.0) at ages 20-29 and 41.6 (26.7-61.9) at ages 30-39.
The risk of mortality from ischaemic heart disease is exceptionally high in young adult women with Type 1 diabetes, with rates similar to those in men with Type 1 diabetes under the age of 40. These observations emphasise the need to identify and treat coronary risk factors in these young patients.
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