Visual Perceptual Difficulties and Under-Achievement at School in a Large Community-Based Sample of Children

Difficulties with visual perception (VP) are often described in children with neurological or developmental problems. However, there are few data regarding the range of visual perceptual abilities in populations of normal children, or on the impact of these abilities on children's day-to-day functioning. Methods Data were obtained for 4512 participants in an ongoing birth cohort study (Avon Longitudinal Study of Parents and Children; ALSPAC). The children's mothers responded to questions designed to elicit indications of visual perceptual difficulties or immaturity, when their children were aged 13 years. We examined associations with standardised school test results in reading and in mathematics at age 1314 years (SATS-KS3), accounting for potential confounders including IQ. Results Three underlying factors explained half the variance in the VP question responses. These correlated best with questions on interpreting cluttered scenes; guidance of movement and face recognition. The adjusted parameter estimates (95% CI) for the cluttered-scenes factor (0.05; 0.02 to 0.08; p<0.001) suggested positive associations with the reading test results whilst that for the guidance-of-movement factor (0.03; 0.00 to 0.06; p = 0.026) suggested positive association with the mathematics results. The raw scores were associated with both test results. Discussion VP abilities were widely distributed in this sample of 13-year old children. Lower levels of VP function were associated with under-achievement in reading and in mathematics. Simple interventions can help children with VP difficulties, so research is needed into practicable, cost-effective strategies for identification and assessment, so that support can be targeted appropriately

Effects of concentrate crude protein content on nutrient digestibility, energy utilization, and methane emissions in lactating dairy cows fed fresh-cut perennial grass

Although many studies have investigated mitigation strategies for methane (CH4) output from dairy cows fed a wide variety of diets, research on effects of concentrate crude protein (CP) content on CH4 emissions from dairy cows offered fresh grass is limited. The present study was therefore designed to evaluate effects of cow genotype and concentrate CP level on nutrient digestibility, energy utilization and CH4 emissions of dairy cows offered fresh grass based diets. Twelve multiparous lactating dairy cows (6 Holstein and 6 Holstein × Swedish Red) were blocked into 3 groups within each breed and assigned to low, medium or high CP concentrate diet (14.1, 16.1 and 18.1 % on dry matter (DM) basis), respectively, in a 3-period changeover study (25-d / period). Total diets contained (DM basis) 32.8 % concentrates and 67.2 % perennial ryegrass, which was harvested daily. All measurements were undertaken during the final 6-d of each period; digestibility measurements for 6-d and calorimetric measurements in respiration chambers for 3-d. Feed intake and milk production data were reported in a previous paper. No significant interaction between concentrate CP level and cow genotype on any parameter was observed. Concentrate CP level had no significant effect on any energy utilization parameter, except for urinary energy output which was positively related to concentrate CP level. Similarly concentrate CP content had no effect on CH4 emission (g/d), CH4 per kg feed intake or nutrient digestibility. The crossbreeding of Holstein cows significantly reduced gross energy, digestible energy and metabolizable energy intake, heat production and milk energy output. However, cow genotype had no significant effects on energy utilization efficiency or CH4 parameters. Furthermore, the present study yielded a value for gross energy lost as CH4 (5.6 %) on fresh grass-based diets that is lower than the widely accepted value of 6.5 %. The present findings indicate reducing concentrate CP content from 18.1 to 14.1 % may not be a successful approach to alleviate CH4 emissions from lactating dairy cows offered good quality fresh grass, however grazing cows could be offered a low CP concentrate without compromising energy utilization efficiency. Further research is needed to investigate whether larger differences in dietary CP content may yield positive results

How Well has Land-Use Planning Worked Under Different Governance Regimes? A Case Study in the Portland, OR-Vancouver, WA Metropolitan Area, USA

We examine land use planning outcomes over a 30-year period in the Portland, OR-Vancouver, WA (USA) metropolitan area. The four-county study region enables comparisons between three Oregon counties subject to Oregon’s 1973 Land Use Act (Senate Bill 100) and Clark County, WA which implemented land use planning under Washington’s 1990 Growth Management Act. We describe county-level historical land uses from the mid-1970s to the mid-2000s, including low-density residential and urban development, both outside and inside of current urban growth boundaries. We use difference-in-differences models to test whether differences in the proportions of developed land resulting from implementation of urban growth boundaries are statistically significant and whether they vary between Oregon and Washington. Our results suggest that land use planning and urban growth boundaries now mandated both in Oregon and Washington portions of the study area have had a measurable and statistically significant effect in containing development and conserving forest and agricultural lands in the Portland-Vancouver metropolitan area. Our results also suggest, however, that these effects differ across the four study-area counties, likely owing in part to differences in counties’ initial levels of development, distinctly different land use planning histories, and how restrictive their urban growth boundaries were drawn

What is the current significance of low birthweight pigs on commercial farms in Northern Ireland in terms of impaired growth and mortality?

Publication history: Accepted - 25 July 2020; Published - 31 July 2020.There is little modern data addressing the differential lifetime growth of commercially reared low and average birthweight pigs born into large litters (>14 piglets). As such, the main aim of this study was to quantify the lifetime growth and mortality rate of low and average birthweight pigs on commercial farms in Northern Ireland. It was also aimed to analyse the level, stage and cause of mortality within each birthweight category. A total of 328 low birthweight (LOW BW; 0.05). The alimentary tract (27%) and respiratory tract (27%) were the most commonly implicated body systems following post-mortem examination of post-weaning deaths. In conclusion, this study quantified the inferior weight, growth rate and mortality of Low BW pigs, identifying the lactation and immediate post-weaning periods as having greatest potential in reducing this birthweight associated growth differential

Proteomic Alterations of HDL in Youth with Type 1 Diabetes and their Associations with Glycemic Control: A Case-Control Study

Background: Patients with type 1 diabetes (T1DM) typically have normal or even elevated plasma high density lipoprotein (HDL) cholesterol concentrations; however, HDL protein composition can be altered without a change in cholesterol content. Alteration of the HDL proteome can result in dysfunctional HDL particles with reduced ability to protect against cardiovascular disease (CVD). The objective of this study was to compare the HDL proteomes of youth with T1DM and healthy controls (HC) and to evaluate the influence of glycemic control on HDL protein composition. Methods: This was a cross-sectional case–control study. Blood samples were obtained from patients with T1DM and HC. HDL was isolated from plasma by size-exclusion chromatography and further purified using a lipid binding resin. The HDL proteome was analyzed by mass spectrometry using label-free SWATH peptide quantification. Results: Samples from 26 patients with T1DM and 13 HC were analyzed and 78 HDL-bound proteins were measured. Youth with T1DM had significantly increased amounts of complement factor H related protein 2 (FHR2; adjusted P \u3c 0.05), compared to HC. When patients were analyzed based on glucose control, several trends emerged. Some proteins were altered in T1DM and not influenced by glycemic control (e.g. FHR2) while others were partially or completely corrected with optimal glucose control (e.g. alpha-1-beta glycoprotein, A1BG). In a subgroup of poorly controlled T1DM patients, inter alpha trypsin inhibitor 4 (ITIH4) was dramatically elevated (P \u3c 0.0001) and this was partially reversed in patients with optimal glucose control. Some proteins including complement component C3 (CO3) and albumin (ALB) were significantly different only in T1DM patients with optimal glucose control, suggesting a possible effect of exogenous insulin. Conclusions: Youth with T1DM have proteomic alterations of their HDL compared to HC, despite similar concentration of HDL cholesterol. The influence of these compositional changes on HDL function are not yet known. Future efforts should focus on investigating the role of these HDL associated proteins in regard to HDL function and their role in CVD risk in patients with T1DM. Trial registration NCT0227509

Effect of Metformin on the High-Density Lipoprotein Proteome in Youth with Type 1 Diabetes

Background: Youth with type 1 diabetes (T1D) have normal or elevated High-Density Lipoprotein Cholesterol (HDL-C), however, the function of HDL, partly mediated by the HDL proteome, may be impaired. Metformin can be used as an adjunct therapy in youth with T1D, but its effects on the HDL proteome are unknown. Objective: To determine the effect of metformin on the HDL proteome. Subjects: Youth (12-20 years old) with T1D who had a BMI \u3e 90th percentile, HbA1c \u3e 8.0% and Tanner stage 5. Methods: Double-blinded, placebo-controlled randomized sub-study. We examined the effects of metformin (n = 25) or placebo (n = 10) after 6 months on HDL proteome. Changes in HDL proteins were measured by data-independent acquisition (DIA) mass spectrometry and compared between treatment groups. As a secondary outcome, associations between proteins of interest and the most studied function of HDL, the cholesterol efflux capacity (CEC), was examined. Results: The relative abundance of 84 HDL-associated proteins were measured. Two proteins were significantly affected by metformin treatment, peptidoglycan recognition protein 2 (PGRP2; +23.4%, p = .0058) and alpha-2-macroglobulin (A2MG; +29.8%, p = .049). Metformin did not significantly affect CEC. Changes in affected HDL proteins did not correlate with CEC. Conclusions: Despite having little effect on HDL-C, metformin increased PGRP2 and A2MG protein on HDL in youth with T1D, but had no significant effect on CEC. Further studies are needed to understand the impact of PGRP2 and A2MG on other HDL functions

Effect of Niacin Monotherapy on High Density Lipoprotein Composition and Function

BACKGROUND: Niacin has modest but overall favorable effects on plasma lipids by increasing high density lipoprotein cholesterol (HDL-C) and lowering triglycerides. Clinical trials, however, evaluating niacin therapy for prevention of cardiovascular outcomes have returned mixed results. Recent evidence suggests that the HDL proteome may be a better indicator of HDL\u27s cardioprotective function than HDL-C. The objective of this study was to evaluate the effect of niacin monotherapy on HDL protein composition and function. METHODS: A 20-week investigational study was performed with 11 participants receiving extended-release niacin (target dose = 2 g/day) for 16-weeks followed by a 4-week washout period. HDL was isolated from participants at weeks: 0, 16, and 20. The HDL proteome was analyzed at each time point by mass spectrometry and relative protein quantification was performed by label-free precursor ion intensity measurement. RESULTS: In this cohort, niacin therapy had typical effects on routine clinical lipids (HDL-C + 16%, q \u3c 0.01; LDL-C - 20%, q \u3c 0.01; and triglyceride - 15%, q = 0.1). HDL proteomics revealed significant effects of niacin on 5 proteins: serum amyloid A (SAA), angiotensinogen (AGT), apolipoprotein A-II (APOA2), clusterin (CLUS), and apolipoprotein L1 (APOL1). SAA was the most prominently affected protein, increasing 3-fold in response to niacin (q = 0.008). Cholesterol efflux capacity was not significantly affected by niacin compared to baseline, however, stopping niacin resulted in a 9% increase in efflux (q \u3c 0.05). Niacin did not impact HDL\u27s ability to influence endothelial function. CONCLUSION: Extended-release niacin therapy, in the absence of other lipid-modifying medications, can increase HDL-associated SAA, an acute phase protein associated with HDL dysfunction

High-throughput clone library analysis of the mucosa-associated microbiota reveals dysbiosis and differences between inflamed and non-inflamed regions of the intestine in inflammatory bowel disease.

BACKGROUND: The gut microbiota is thought to play a key role in the development of the inflammatory bowel diseases Crohn's disease (CD) and ulcerative colitis (UC). Shifts in the composition of resident bacteria have been postulated to drive the chronic inflammation seen in both diseases (the "dysbiosis" hypothesis). We therefore specifically sought to compare the mucosa-associated microbiota from both inflamed and non-inflamed sites of the colon in CD and UC patients to that from non-IBD controls and to detect disease-specific profiles. RESULTS: Paired mucosal biopsies of inflamed and non-inflamed intestinal tissue from 6 CD (n = 12) and 6 UC (n = 12) patients were compared to biopsies from 5 healthy controls (n = 5) by in-depth sequencing of over 10,000 near full-length bacterial 16S rRNA genes. The results indicate that mucosal microbial diversity is reduced in IBD, particularly in CD, and that the species composition is disturbed. Firmicutes were reduced in IBD samples and there were concurrent increases in Bacteroidetes, and in CD only, Enterobacteriaceae. There were also significant differences in microbial community structure between inflamed and non-inflamed mucosal sites. However, these differences varied greatly between individuals, meaning there was no obvious bacterial signature that was positively associated with the inflamed gut. CONCLUSIONS: These results may support the hypothesis that the overall dysbiosis observed in inflammatory bowel disease patients relative to non-IBD controls might to some extent be a result of the disturbed gut environment rather than the direct cause of disease. Nonetheless, the observed shifts in microbiota composition may be important factors in disease maintenance and severity

Are braneworlds born isotropic?

It has recently been suggested that an isotropic singularity may be a generic feature of brane cosmologies, even in the inhomogeneous case. Using the covariant and gauge-invariant approach we present a detailed analysis of linear perturbations of the isotropic model ${\cal F}_b$ which is a past attractor in the phase space of homogeneous Bianchi models on the brane. We find that for matter with an equation of state parameter $\gamma > 1$, the dimensionless variables representing generic anisotropic and inhomogeneous perturbations decay as $t\to 0$, showing that the model ${\cal F}_b$ is asymptotically stable in the past. We conclude that brane universes are born with isotropy naturally built-in, contrary to standard cosmology. The observed large-scale homogeneity and isotropy of the universe can therefore be explained as a consequence of the initial conditions if the brane-world paradigm represents a description of the very early universe.Comment: Changed to match published versio

Structure of Tagatose-1,6-bisphosphate Aldolase. Insight into chiral discrimination, mechanism, and specificity of class II aldolases

Tagatose-1,6-bisphosphate aldolase (TBPA) is a tetrameric class II aldolase that catalyzes the reversible condensation of dihydroxyacetone phosphate with glyceraldehyde 3-phosphate to produce tagatose 1,6-bisphosphate. The high resolution (1.45 Å) crystal structure of the Escherichia coli enzyme, encoded by the agaY gene, complexed with phosphoglycolohydroxamate (PGH) has been determined. Two subunits comprise the asymmetric unit, and a crystallographic 2-fold axis generates the functional tetramer. A complex network of hydrogen bonds position side chains in the active site that is occupied by two cations. An unusual Na(+) binding site is created using a interaction with Tyr(183) in addition to five oxygen ligands. The catalytic Zn(2+) is five-coordinate using three histidine nitrogens and two PGH oxygens. Comparisons of TBPA with the related fructose-1,6-bisphosphate aldolase (FBPA) identifies common features with implications for the mechanism. Because the major product of the condensation catalyzed by the enzymes differs in the chirality at a single position, models of FBPA and TBPA with their cognate bisphosphate products provide insight into chiral discrimination by these aldolases. The TBPA active site is more open on one side than FBPA, and this contributes to a less specific enzyme. The availability of more space and a wider range of aldehyde partners used by TBPA together with the highly specific nature of FBPA suggest that TBPA might be a preferred enzyme to modify for use in biotransformation chemistry