Theoretical and experimental analysis of the photoluminescence and photoluminescence excitation spectroscopy spectra of m\textit{m}-plane InGaN/GaN quantum wells

We present a combined theoretical and experimental analysis of the optical properties of $\textit{m}$-plane InGaN/GaN quantum wells. The sample was studied by photoluminescence and photoluminescence excitation spectroscopy at low temperature. The spectra show a large Stokes shift between the lowest exciton peak in the excitation spectra and the peak of the photoluminescence spectrum. This behavior is indicative of strong carrier localization effects. These experimental results are complemented by tight-binding calculations, accounting for random alloy fluctuations and Coulomb effects. The theoretical data explain the main features of the experimental spectra. Moreover, by comparison with calculations based on a virtual crystal approximation, the importance of carrier localization effects due to random alloy fluctuations is explicitly shown.This work was supported by Science Foundation Ireland (Project No. 13/SIRG/2210) and the United Kingdom Engineering and Physical Sciences Research Council (Grant Agreement Nos. EP\J001627\1 and EP\J003603\1). S.S. acknowledges computing resources provided by the SFI/HEA Irish Centre for High-End Computing. R.A.O. and F.T. acknowledge the support of the European Research Council under the European Community's 7th Framework Programme (FP7/2007–2013)/ERC Grant Agreement No. 279361 (MACONS)

A comparative study of Tam3 and Ac transposition in transgenic tobacco and petunia plants

Transposition of the Anthirrinum majus Tam3 element and the Zea mays Ac element has been monitored in petunia and tobacco plants. Plant vectors were constructed with the transposable elements cloned into the leader sequence of a marker gene. Agrobacterium tumefaciens-mediated leaf disc transformation was used to introduce the transposable element constructs into plant cells. In transgenic plants, excision of the transposable element restores gene expression and results in a clearly distinguishable phenotype. Based on restored expression of the hygromycin phosphotransferase II (HPTII) gene, we established that Tam3 excises in 30% of the transformed petunia plants and in 60% of the transformed tobacco plants. Ac excises from the HPTII gene with comparable frequencies (30%) in both plant species. When the β-glucuronidase (GUS) gene was used to detect transposition of Tam3, a significantly lower excision frequency (13%) was found in both plant species. It could be shown that deletion of parts of the transposable elements Tam3 and Ac, removing either one of the terminal inverted repeats (TIR) or part of the presumptive transposase coding region, abolished the excision from the marker genes. This demonstrates that excision of the transposable element Tam3 in heterologous plant species, as documented for the autonomous element Ac, also depends on both properties. Southern blot hybridization shows the expected excision pattern and the reintegration of Tam3 and Ac elements into the genome of tobacco plants.

Individualizing therapy – in search of approaches to maximize the benefit of drug treatment (II)

Adjusting drug therapy to the individual, a common approach in clinical practice, has evolved from 1) dose adjustments based on clinical effects to 2) dose adjustments made in response to drug levels and, more recently, to 3) dose adjustments based on deoxyribonucleic acid (DNA) sequencing of drug-metabolizing enzyme genes, suggesting a slow drug metabolism phenotype. This development dates back to the middle of the 20(th )century, when several different drugs were administered on the basis of individual plasma concentration measurements. Genetic control of drug metabolism was well established by the 1960s, and pharmakokinetic-based individualized therapy was in use by 1973

Trajectories in chronic disease accrual and mortality across the lifespan in Wales, UK (2005–2019), by area deprivation profile: linked electronic health records cohort study on 965,905 individuals

BACKGROUND: Understanding and quantifying the differences in disease development in different socioeconomic groups of people across the lifespan is important for planning healthcare and preventive services. The study aimed to measure chronic disease accrual, and examine the differences in time to individual morbidities, multimorbidity, and mortality between socioeconomic groups in Wales, UK. METHODS: Population-wide electronic linked cohort study, following Welsh residents for up to 20 years (2000–2019). Chronic disease diagnoses were obtained from general practice and hospitalisation records using the CALIBER disease phenotype register. Multi-state models were used to examine trajectories of accrual of 132 diseases and mortality, adjusted for sex, age and area-level deprivation. Restricted mean survival time was calculated to measure time spent free of chronic disease(s) or mortality between socioeconomic groups. FINDINGS: In total, 965,905 individuals aged 5–104 were included, from a possible 2.9 m individuals following a 5-year clearance period, with an average follow-up of 13.2 years (12.7 million person-years). Some 673,189 (69.7%) individuals developed at least one chronic disease or died within the study period. From ages 10 years upwards, the individuals living in the most deprived areas consistently experienced reduced time between health states, demonstrating accelerated transitions to first and subsequent morbidities and death compared to their demographic equivalent living in the least deprived areas. The largest difference were observed in 10 and 20 year old males developing multimorbidity (−0.45 years (99% CI: −0.45, −0.44)) and in 70 year old males dying after developing multimorbidity (−1.98 years (99% CI: −2.01, −1.95)). INTERPRETATION: This study adds to the existing literature on health inequalities by demonstrating that individuals living in more deprived areas consistently experience accelerated time to diagnosis of chronic disease and death across all ages, accounting for competing risks. FUNDING: UK Medical Research Council, Health Data Research UK, and Administrative Data Research Wales

Feasibility of using quadriceps-strengthening exercise to improve pain and sleep in a severely demented elder with osteoarthritis – a case report

BACKGROUND: Osteoarthritis (OA) of the knee, which is prevalent among older adults in nursing homes, causes significant pain and suffering, including disturbance of nocturnal sleep. One nonpharmacologic treatment option is quadriceps-strengthening exercise, however, the feasibility of such a treatment for reducing pain from OA in severely demented elders has not been studied. This report describes our test of the feasibility of such an exercise program, together with its effects on pain and sleep, in a severely demented nursing home resident. CASE PRESENTATION: The subject was an elderly man with severe cognitive impairment (Mini-Mental Status Exam score 4) and knee OA (Kellgren-Lawrence radiographic grade 4). He was enrolled in a 5-week, 10-session standardized progressive-resistance training program to strengthen the quadriceps, and completed all sessions. Pain was assessed with the Western Ontario and MacMaster OA Index (WOMAC) pain subscale, and sleep was assessed by actigraphy. The patient was able to perform the exercises, with a revision to the protocol. However, the WOMAC OA pain subscale proved inadequate for measuring pain in a patient with low cognitive functioning, and therefore the effects on pain were inconclusive. Although his sleep improved after the intervention, the influence of his medications and the amount of daytime sleep on his nighttime sleep need to be considered. CONCLUSIONS: A quadriceps-strengthening exercise program for treating OA of the knee is feasible in severely demented elders, although a better outcome measure is needed for pain

Identifying differential exon splicing using linear models and correlation coefficients

Background: With the availability of the Affymetrix exon arrays a number of tools have been developed to enable the analysis. These however can be expensive or have several pre-installation requirements. This led us to develop an analysis workflow for analysing differential splicing using freely available software packages that are already being widely used for gene expression analysis. The workflow uses the packages in the standard installation of R and Bioconductor (BiocLite) to identify differential splicing. We use the splice index method with the LIMMA framework. The main drawback with this approach is that it relies on accurate estimates of gene expression from the probe-level data. Methods such as RMA and PLIER may misestimate when a large proportion of exons are spliced. We therefore present the novel concept of a gene correlation coefficient calculated using only the probeset expression pattern within a gene. We show that genes with lower correlation coefficients are likely to be differentially spliced.Results: The LIMMA approach was used to identify several tissue-specific transcripts and splicing events that are supported by previous experimental studies. Filtering the data is necessary, particularly removing exons and genes that are not expressed in all samples and cross-hybridising probesets, in order to reduce the false positive rate. The LIMMA approach ranked genes containing single or few differentially spliced exons much higher than genes containing several differentially spliced exons. On the other hand we found the gene correlation coefficient approach better for identifying genes with a large number of differentially spliced exons.Conclusion: We show that LIMMA can be used to identify differential exon splicing from Affymetrix exon array data. Though further work would be necessary to develop the use of correlation coefficients into a complete analysis approach, the preliminary results demonstrate their usefulness for identifying differentially spliced genes. The two approaches work complementary as they can potentially identify different subsets of genes (single/few spliced exons vs. large transcript structure differences)

Paradoxical euthyroid hormone profile in a case of Graves' disease with cardiac failure

Cardiac failure is an uncommon complication of juvenile hyperthyroidism. We describe an adolescent boy with Graves' disease who developed manifestations of heart failure while on antithyroid medications. There was no evidence of any underlying cardiac disease. He had paradoxical euthyroid hormone profile which rose to hyperthyroid range when the manifestations of the cardiac failure subsided. The case highlights several unusual features of Graves' disease