Type 1 diabetes affects over 200,000 children in the United States and is associated with an increased risk of cognitive dysfunction. Prior single-site, single-voxel MRS case reports and studies have ...identified associations between reduced NAA/Cr, a marker of neuroaxonal loss, and type 1 diabetes. However, NAA/Cr differences among children with various disease complications or across different brain tissues remain unclear. To better understand this phenomenon and the role of MRS in characterizing it, we conducted a multisite pilot study.
In 25 children, 6-14 years of age, with type 1 diabetes across 3 sites, we acquired T1WI and axial 2D MRSI along with phantom studies to calibrate scanner effects. We quantified tissue-weighted NAA/Cr in WM and deep GM and modeled them against study covariates.
We found that MRSI differentiated WM and deep GM by NAA/Cr on the individual level. On the population level, we found significant negative associations of WM NAA/Cr with chronic hyperglycemia quantified by hemoglobin A1c (
< .005) and a history of diabetic ketoacidosis at disease onset (
< .05). We found a statistical interaction (
< .05) between A1c and ketoacidosis, suggesting that neuroaxonal loss from ketoacidosis may outweigh that from poor glucose control. These associations were not present in deep GM.
Our pilot study suggests that MRSI differentiates GM and WM by NAA/Cr in this population, disease complications may lead to neuroaxonal loss in WM in children, and deeper investigation is warranted to further untangle how diabetic ketoacidosis and chronic hyperglycemia affect brain health and cognition in type 1 diabetes.
Context
Oil and gas activity is increasing in the western boreal forest of North America. To manage cumulative effects of this industry, a better quantification of footprint effects on wildlife is ...needed.
Objectives
We used point-count surveys to evaluate how well footprint amounts within 150 m, and proximity to seismic lines, pipelines, well sites, roads, and energy facilities predicted the abundance of 48 bird species.
Methods
We developed models for each species, evaluating the best functional forms for different footprint effects, then predicted how different model structures influenced estimates of regional population size.
Results
Most species exhibited at least one nonlinear response to footprint amount (79% of species) or distance (88%). Species associated with older coniferous forests decreased more often with increased footprint amount and closer proximity to footprint, while species associated with open lands and young forests increased with greater footprint and closer proximity. In one-third of species, bird abundance versus distance changed from a positive to negative relationship (or reverse) at a threshold distance from at least one footprint. Models based on footprint proximity had better fit than those based on footprint amount for 29 of 48 species, but both model types produced similar population estimates.
Conclusions
Both footprint amount and proximity models were useful for assessing cumulative effects on wildlife and mechanisms causing change. Models of distance to footprint can provide evidence of positive or negative edge effects for developing management buffers. Models of footprint amount provide important information on functional changes in habitat.
Both maternal 25-hydroxyvitamin D (25(OH)D) concentrations during pregnancy and
placental amino acid transporter gene expression have been associated with
development of the offspring in terms of ...body composition and bone structure.
Several amino acid transporter genes have vitamin D response elements in their
promoters suggesting the possible linkage of these two mechanisms. We aimed to
establish whether maternal 25(OH)D and vitamin D-binding protein (VDBP) levels
relate to expression of placental amino acid transporters. RNA was extracted
from 102 placental samples collected in the Southampton Women's Survey,
and gene expression was analysed using quantitative real-time PCR. Gene
expression data were normalised to the geometric mean of three housekeeping
genes, and related to maternal factors and childhood body composition. Maternal
serum 25(OH)D and VDBP levels were measured by radioimmunoassay. Maternal
25(OH)D and VDBP levels were positively associated with placental expression of
specific genes involved in amino acid transport. Maternal 25(OH)D and VDBP
concentrations were correlated with the expression of specific placental amino
acid transporters, and thus may be involved in the regulation of amino acid
transfer to the fetus. The positive correlation of VDBP levels and placental
transporter expression suggests that delivery of vitamin D to the placenta may
be important. This exploratory study identifies placental amino acid
transporters which may be altered in response to modifiable maternal factors and
provides a basis for further studies.
A range of N-heterocyclic carbene-supported copper diphenylphosphides (NHC = IPr, 6-Dipp, SIMes and 6-Mes) were synthesised. These include the first reports of ring-expanded NHC-copper(
i
) ...phosphides. The compounds were characterised by NMR spectroscopy and X-ray crystallography. Reaction of (6-Dipp)CuPPh
2
with isocyanates, isothiocyanates and carbon disulfide results in the insertion of the heterocumulene into the Cu-P bond. The NHC-copper phosphides were found to be the most selective catalysts yet reported for the hydrophosphination of isocyanates. They provide access to a broad range of phosphinocarboxamides in excellent conversion and good yield.
The first copper(
i
) phosphides supported by ring-expanded N-heterocyclic carbenes have been synthesised and react readily with heterocumulenes. These copper(
i
) phosphides are highly active and selective in the hydrophosphination of isocyanates.
Epicardial adipose tissue (EAT) volume is a marker of visceral obesity that can be measured in coronary computed tomography angiograms (CCTA). The clinical value of integrating this measurement in ...routine CCTA interpretation has not been documented.
This study sought to develop a deep-learning network for automated quantification of EAT volume from CCTA, test it in patients who are technically challenging, and validate its prognostic value in routine clinical care.
The deep-learning network was trained and validated to autosegment EAT volume in 3,720 CCTA scans from the ORFAN (Oxford Risk Factors and Noninvasive Imaging Study) cohort. The model was tested in patients with challenging anatomy and scan artifacts and applied to a longitudinal cohort of 253 patients post-cardiac surgery and 1,558 patients from the SCOT-HEART (Scottish Computed Tomography of the Heart) Trial, to investigate its prognostic value.
External validation of the deep-learning network yielded a concordance correlation coefficient of 0.970 for machine vs human. EAT volume was associated with coronary artery disease (odds ratio OR per SD increase in EAT volume: 1.13 95% CI: 1.04-1.30; P = 0.01), and atrial fibrillation (OR: 1.25 95% CI: 1.08-1.40; P = 0.03), after correction for risk factors (including body mass index). EAT volume predicted all-cause mortality (HR per SD: 1.28 95% CI: 1.10-1.37; P = 0.02), myocardial infarction (HR: 1.26 95% CI:1.09-1.38; P = 0.001), and stroke (HR: 1.20 95% CI: 1.09-1.38; P = 0.02) independently of risk factors in SCOT-HEART (5-year follow-up). It also predicted in-hospital (HR: 2.67 95% CI: 1.26-3.73; P ≤ 0.01) and long-term post-cardiac surgery atrial fibrillation (7-year follow-up; HR: 2.14 95% CI: 1.19-2.97; P ≤ 0.01).
Automated assessment of EAT volume is possible in CCTA, including in patients who are technically challenging; it forms a powerful marker of metabolically unhealthy visceral obesity, which could be used for cardiovascular risk stratification.
Distributions of landbirds in Canadian northern forests are expected to be affected by climate change, but it remains unclear which pathways are responsible for projected climate effects. Determining ...whether climate change acts indirectly through changing fire regimes and/or vegetation dynamics, or directly through changes in climatic suitability may allow land managers to address negative trajectories via forest management. We used SpaDES, a novel toolkit built in R that facilitates the implementation of simulation models from different areas of knowledge to develop a simulation experiment for a study area comprising 50 million ha in the Northwest Territories, Canada. Our factorial experiment was designed to contrast climate effects pathways on 64 landbird species using climate-sensitive and non-climate sensitive models for tree growth and mortality, wildfire, and landbirds. Climate-change effects were predicted to increase suitable habitat for 73% of species, resulting in average net gain of 7.49 million ha across species. We observed higher species turnover in the northeastern, south-central (species loss), and western regions (species gain). Importantly, we found that most of the predicted differences in net area of occupancy across models were attributed to direct climate effects rather than simulated vegetation change, despite a similar relative importance of vegetation and climate variables in landbird models. Even with close to a doubling of annual area burned by 2100, and a 600 kg/ha increase in aboveground tree biomass predicted in this region, differences in landbird net occupancy across models attributed to climate-driven forest growth were very small, likely resulting from differences in the pace of vegetation and climate changes, or vegetation lags. The effect of vegetation lags (i.e., differences from climatic equilibrium) varied across species, resulting in a wide range of changes in landbird distribution, and consequently predicted occupancy, due to climate effects. These findings suggest that hybrid approaches using statistical models and landscape simulation tools could improve wildlife forecasts when future uncoupling of vegetation and climate is anticipated. This study lays some of the methodological groundwork for ecological adaptive management using the new platform SpaDES, which allows for iterative forecasting, mixing of modeling paradigms, and tightening connections between data, parameterization, and simulation.
To determine if a structured transition program for young adults with type 1 diabetes improves clinic attendance, glycemic control, diabetes-related distress, quality of life, and satisfaction with ...care.
In this multicenter randomized controlled trial, young adults (17-20 years) with type 1 diabetes were randomly assigned to a transition program with a transition coordinator or to standard care. The intervention lasted 18 months (6 in pediatric and 12 in adult care). The primary outcome was the proportion of participants who failed to attend at least one adult diabetes clinic visit during the 12-month follow-up after completion of the intervention.
We randomized 205 participants, 104 to the transition program and 101 to standard care. Clinic attendance was improved in the transition program (mean SD number of visits 4.1 1.1 vs. 3.6 1.2,
= 0.002), and there was greater satisfaction with care (mean SD score 29.0 2.7 vs. 27.9 3.4,
= 0.032) and less diabetes-related distress (mean SD score 1.9 0.8 vs. 2.1 0.8,
= 0.049) reported than in standard care. There was a trend toward improvement in mean HbA
(8.33% 68 mmol/mol vs. 8.80% 73 mmol/mol,
= 0.057). During the 12-month follow-up, there was no difference in those failing to attend at least one clinic visit (
= 0.846), and the mean change in HbA
did not differ between the groups (
= 0.073). At completion of follow-up, the groups did not differ with respect to satisfaction with care or diabetes-related distress and quality of life.
Transition support during this 18-month intervention was associated with increased clinic attendance, improved satisfaction with care, and decreased diabetes-related distress, but these benefits were not sustained 12 months after completion of the intervention.
Results of studies in animals and human beings suggest that type 1 diabetes is preventable. Nicotinamide prevents autoimmune diabetes in animal models, possibly through inhibition of the DNA repair ...enzyme poly-ADP-ribose polymerase and prevention of β-cell NAD depletion. We aimed to assess whether high dose nicotinamide prevents or delays clinical onset of diabetes in people with a first-degree family history of type 1 diabetes.
We did a randomised double-blind placebo-controlled trial of nicotinamide in 552 relatives with confirmed islet cell antibody (ICA) levels of 20 Juvenile Diabetes Federation (JDF) units or more, and a non-diabetic oral glucose tolerance test. Participants were recruited from 18 European countries, Canada, and the USA, and were randomly allocated oral modified release nicotinamide (1·2 g/m2) or placebo for 5 years. Random allocation was done with a pseudorandom number generator and we used size balanced blocks of four and stratified by age and national group. Primary outcome was development of diabetes, as defined by WHO criteria. Analysis was done on an intention-to-treat basis.
There was no difference in the development of diabetes between the treatment groups. Of 159 participants who developed diabetes in the course of the trial, 82 were taking nicotinamide and 77 were on placebo. The unadjusted hazard ratio for development of diabetes was 1·07 (95% CI 0·78–1·45; p=0·69), and the hazard ratio adjusted for age-at-entry, baseline glucose tolerance, and number of islet autoantibodies detected was 1·01 (0·73–1·38; p=0·97). Of 168 (30·4%) participants who withdrew from the trial, 83 were on placebo. The number of serious adverse events did not differ between treatment groups. Nicotinamide treatment did not affect growth in children or first-phase insulin secretion.
Large-scale controlled trials of interventions designed to prevent the onset of type 1 diabetes are feasible, but nicotinamide was ineffective at the dose we used.
Chronic myelogenous leukemia (CML) is caused by expression of the BCR-ABL tyrosine kinase oncogene, the product of the t(9;22) Philadelphia translocation. Patients with CML in accelerated phase have ...rapidly progressive disease and are characteristically unresponsive to existing therapies. Imatinib (formerly STI571) is a rationally developed, orally administered inhibitor of the Bcr-Abl kinase. A total of 235 CML patients were enrolled in this study, of whom 181 had a confirmed diagnosis of accelerated phase. Patients were treated with imatinib at 400 or 600 mg/d and were evaluated for hematologic and cytogenetic response, time to progression, survival, and toxicity. Imatinib induced hematologic response in 82% of patients and sustained hematologic responses lasting at least 4 weeks in 69% (complete in 34%). The rate of major cytogenetic response was 24% (complete in 17%). Estimated 12-month progression-free and overall survival rates were 59% and 74%, respectively. Nonhematologic toxicity was usually mild or moderate, and hematologic toxicity was manageable. In comparison to 400 mg, imatinib doses of 600 mg/d led to more cytogenetic responses (28% compared to 16%), longer duration of response (79% compared to 57% at 12 months), time to disease progression (67% compared to 44% at 12 months), and overall survival (78% compared to 65% at 12 months), with no clinically relevant increase in toxicity. Orally administered imatinib is an effective and well-tolerated treatment for patients with CML in accelerated phase. A daily dose of 600 mg is more effective than 400 mg, with similar toxicity.
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