Clinicians' caseload management behaviours as explanatory factors in patients' length of time on caseloads : a predictive multilevel study in paediatric community occupational therapy

Peer reviewedPublisher PD

Glucose-lowering therapies in type 2 diabetes: Opportunities and challenges for peptides

This overview considers the opportunities and challenges that face the use of gluco-regulatory peptides to treat type 2 diabetes. New insulin analogues and formulations are being developed with pharmacokinetic properties to speed-up or prolong transfer from a subcutaneous injection site to the target tissues, or to selectively favour effects on the liver. Alternative routes of insulin administration continue to attract attention, and advances in the integration of glucose monitoring with insulin pump devices are improving miniaturised ‘closed loop’ artificial pancreas systems. Proof of concept has been established for non-cellular glucose-responsive insulin delivery (‘smart insulins’) to release insulin from implants or circulating depots in proportion to circulating glucose. The many peptides involved in blood glucose control offer diverse therapeutic opportunities. Exploitation of multiple selected receptor targets using constructs of hybrid and chimeric peptides, especially those based on glucagon and gastrointestinal hormones, has gained much credence from initial preclinical studies. Peptide templates identified from comparative endocrine studies have also provided valuable insights in this respect and indicated novel approaches to address associated conditions such as obesity and infections at the same time. Nevertheless, there are many challenges to the use of therapeutic peptides that impose on every step in the complex pathway from design and testing through to making a fully characterised therapeutic product, and optimising administration, tissue targeting and degradation. Stability of peptides and immunological uncertainties of novel structures require particular consideration as well as the need to avoid over-reduction of blood glucose into hypoglycaemia

Twenty years of satellite and in situ observations of surface chlorophyll-a from the northern Bay of Biscay to the eastern English Channel. Is the water quality improving?

Thevariabilityofthephytoplanktonbiomassderivedfromdailychlorophyll-a(Chl-a)satelliteimageswasinvestigated over the period 1998–2017 in the surface waters of the English Channel and the northern Bay of Biscay. Merged satellite (SeaWiFS-MODIS/Aqua-MERIS-VIIRS) Chl-a wascalculated using the OC5 Ifremeralgorithm which is optimized for moderately-turbid waters. The seasonal cycle in satellite-derived Chl-a was comparedwithinsitumeasurementsmadeatsevencoastalstationslocatedinthesouthernsideoftheEnglish ChannelandinthenorthernBayofBiscay.TheresultsfirstlyshowedthatthesatelliteChl-aproduct,derived from a suite of space-borne marine reflectance data, is in agreement with the coastal observations. For compliancewiththedirectivesoftheEuropeanUniononwaterquality,time-seriesof6-yearmovingaverageofChlawereassessedovertheregion.Acleardeclinewasobservedinthemeanand90thpercentileofChl-aatstations locatedinthemixedwatersoftheEnglishChannel.Thetime-seriesatthestationslocatedintheBayofBiscay showedyearlyfluctuationswhichcorrelatedwellwithriverdischarge,butnooverallChl-atrendwasobserved. IntheEnglishChannel,theshapeoftheseasonalcycleinChl-achangedovertime.Narrowerpeakswereobservedinspringattheendofthestudiedperiod,indicatinganearlierlimitationbynutrients.Monthlyaverages of satellite Chl-a, over theperiods 1998–2003and2012–2017,exhibitedspatial andtemporalpatternsin the evolutionofthephytoplanktonbiomasssimilartotheseobservedatthesevencoastalstations.Boththeinsitu andsatelliteChl-atimes-seriesshowedadecreaseinChl-aintheEnglishChannelinMay,JuneandJuly.This trendinphytoplanktonbiomassiscorrelatedwithlowerriverdischargesattheendoftheperiodandaconstant reduction in the riverine input of phosphorus through improvements in the water quality of the surrounding rivercatchments

Genomic Landscape of a Three-Generation Pedigree Segregating Affective Disorder

Bipolar disorder (BPD) is a common psychiatric illness with a complex mode of inheritance. Besides traditional linkage and association studies, which require large sample sizes, analysis of common and rare chromosomal copy number variants (CNVs) in extended families may provide novel insights into the genetic susceptibility of complex disorders. Using the Illumina HumanHap550 BeadChip with over 550,000 SNP markers, we genotyped 46 individuals in a three-generation Old Order Amish pedigree with 19 affected (16 BPD and three major depression) and 27 unaffected subjects. Using the PennCNV algorithm, we identified 50 CNV regions that ranged in size from 12 to 885 kb and encompassed at least 10 single nucleotide polymorphisms (SNPs). Of 19 well characterized CNV regions that were available for combined genotype-expression analysis 11 (58%) were associated with expression changes of genes within, partially within or near these CNV regions in fibroblasts or lymphoblastoid cell lines at a nominal P value <0.05. To further investigate the mode of inheritance of CNVs in the large pedigree, we analyzed a set of four CNVs, located at 6q27, 9q21.11, 12p13.31 and 15q11, all of which were enriched in subjects with affective disorders. We additionally show that these variants affect the expression of neuronal genes within or near the rearrangement. Our analysis suggests that family based studies of the combined effect of common and rare CNVs at many loci may represent a useful approach in the genetic analysis of disease susceptibility of mental disorders

SAQC: SNP Array Quality Control

<p>Abstract</p> <p>Background</p> <p>Genome-wide single-nucleotide polymorphism (SNP) arrays containing hundreds of thousands of SNPs from the human genome have proven useful for studying important human genome questions. Data quality of SNP arrays plays a key role in the accuracy and precision of downstream data analyses. However, good indices for assessing data quality of SNP arrays have not yet been developed.</p> <p>Results</p> <p>We developed new quality indices to measure the quality of SNP arrays and/or DNA samples and investigated their statistical properties. The indices quantify a departure of estimated individual-level allele frequencies (AFs) from expected frequencies via standardized distances. The proposed quality indices followed lognormal distributions in several large genomic studies that we empirically evaluated. AF reference data and quality index reference data for different SNP array platforms were established based on samples from various reference populations. Furthermore, a confidence interval method based on the underlying empirical distributions of quality indices was developed to identify poor-quality SNP arrays and/or DNA samples. Analyses of authentic biological data and simulated data show that this new method is sensitive and specific for the detection of poor-quality SNP arrays and/or DNA samples.</p> <p>Conclusions</p> <p>This study introduces new quality indices, establishes references for AFs and quality indices, and develops a detection method for poor-quality SNP arrays and/or DNA samples. We have developed a new computer program that utilizes these methods called SNP Array Quality Control (SAQC). SAQC software is written in R and R-GUI and was developed as a user-friendly tool for the visualization and evaluation of data quality of genome-wide SNP arrays. The program is available online (<url>http://www.stat.sinica.edu.tw/hsinchou/genetics/quality/SAQC.htm</url>).</p

Influence of the ion bombardment on the growth and moisture permeation barrier properties of SiO2-like films deposited by remote plasma

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High-rate anisotropic silicon etching with the expanding thermal plasma technique

Deep anisotropic silicon etching with the expanding thermal plasma (ETP) technique using fluorine-based chemistries was demonstrated. The ETP technique makes use of a remote high-d. plasma source and it has a good control of the downstream plasma chem. Both a cryogenic etching process and a time-multiplexed etching process were developed. Etch rates up to 12 micro m min-1 and selectivities higher than 300 were obtained while feature profiles were comparable to those obtained with the widely used inductively coupled plasma reactors. Therefore, this deep anisotropic silicon etching technique is an attractive alternative for the fabrication of microstructures with high-aspect-ratio features. [on SciFinder (R)