Psychotropic drug use following venous thromboembolism versus diabetes mellitus in adolescence or young adulthood: A Danish nationwide cohort study

© Author(s) (or their employer(s)) 2018. Objectives Critical and chronic illness in youth such as diabetes can lead to impaired mental health. Despite the potentially traumatic and life-Threatening nature of venous thromboembolism (VTE), the long-Term mental health of adolescents and young adults with VTE is unclear. We compared the long-Term mental health of adolescents and young adults with VTE versus adolescents and young adults with insulin-dependent diabetes mellitus (IDDM) using psychotropic drug purchase as proxy for mental health. Design Nationwide registry-based cohort study. Setting Denmark 1997-2015. Participants All patients aged 13-33 years with an incident diagnosis of VTE (n=5065) or IDDM (n=6609). Exposure First time primary hospital diagnosis of VTE or IDDM. Primary and secondary outcome measures Adjusted absolute risk and risk difference at 1 and 5 years follow-up for first psychotropic drug purchase comparing patients with VTE and patients with IDDM. Results The absolute 1 year risk of psychotropic drug use was 6.2% among VTE patients versus 3.6% among patients with IDDM, at 5 years this was 19.3%-14.7%, respectively. After adjusting for the effect of sex, age and risk factors for VTE this corresponded to a 1 year risk differences of 1.9% (95 % CI 0.1% to 3.3%). At 5 years follow-up the risk difference was 1.9% (95% CI 0.5% to 3.3%). Conclusion One-fifth of adolescents and young adults with incident VTE had claimed a prescription for a psychotropic drug within 5 years, a risk comparable to that of young patients with IDDM

Bottom mixed layer oxygen dynamics in the Celtic Sea

The seasonally stratified continental shelf seas are highly productive, economically important environments which are under considerable pressure from human activity. Global dissolved oxygen concentrations have shown rapid reductions in response to anthropogenic forcing since at least the middle of the twentieth century. Oxygen consumption is at the same time linked to the cycling of atmospheric carbon, with oxygen being a proxy for carbon remineralisation and the release of CO2. In the seasonally stratified seas the bottom mixed layer (BML) is partially isolated from the atmosphere and is thus controlled by interplay between oxygen consumption processes, vertical and horizontal advection. Oxygen consumption rates can be both spatially and temporally dynamic, but these dynamics are often missed with incubation based techniques. Here we adopt a Bayesian approach to determining total BML oxygen consumption rates from a high resolution oxygen time-series. This incorporates both our knowledge and our uncertainty of the various processes which control the oxygen inventory. Total BML rates integrate both processes in the water column and at the sediment interface. These observations span the stratified period of the Celtic Sea and across both sandy and muddy sediment types. We show how horizontal advection, tidal forcing and vertical mixing together control the bottom mixed layer oxygen concentrations at various times over the stratified period. Our muddy-sand site shows cyclic spring-neap mediated changes in oxygen consumption driven by the frequent resuspension or ventilation of the seabed. We see evidence for prolonged periods of increased vertical mixing which provide the ventilation necessary to support the high rates of consumption observed

The interpretative value of transformed tephra sequences

Financial support was provided by the National Science Foundation of America through grants 1202692 and 1249313, the Carnegie Trust for the Universities of Scotland through a grant to RTS, and the NERC Doctoral Training Partnership PhD studentship NE/L002558/1 to PT.We explore developments in tephra science that consider more than chronology, using case studies. Volcanic processes and prevailing weather conditions determine the distribution of tephra deposits immediately after an eruption, but as these freshly fallen tephra become part of the stratigraphic record, the thickness, morphology and definition of the layers they form changes, reflecting the interplay of the tephra, Earth surface processes, topography and vegetation structure, plus direct or indirect modification caused by people and animals. Once part of the stratigraphic record, further diagnostic changes can happen to the morphology of tephra layers, such as the creation of over folds by cryoturbation. Thus, tephra layers may contain proxy evidence of both past surface environments and subsurface processes. Transformations of tephra deposits can complicate the reconstruction of past volcanic processes and make the application of classical tephrochronology as pioneered by Thorarinsson (Sigurður Þórarinsson in Icelandic) challenging. However, as Thorarinsson also noted, novel sources of environmental data can exist within transformed tephra sequences that include the spread or removal of tephra, variations in layer thickness and internal structures, the nature of contact surfaces and the orientation of layers.PostprintPeer reviewe

Universal contributions to scalar masses from five dimensional supergravity

We compute the effective Kahler potential for matter fields in warped compactifications, starting from five dimensional gauged supergravity, as a function of the matter fields localization. We show that truncation to zero modes is inconsistent and the tree-level exchange of the massive gravitational multiplet is needed for consistency of the four-dimensional theory. In addition to the standard Kahler coming from dimensional reduction, we find the quartic correction coming from integrating out the gravity multiplet. We apply our result to the computation of scalar masses, by assuming that the SUSY breaking field is a bulk hypermultiplet. In the limit of extreme opposite localization of the matter and the spurion fields, we find zero scalar masses, consistent with sequestering arguments. Surprisingly enough, for all the other cases the scalar masses are tachyonic. This suggests the holographic interpretation that a CFT sector always generates operators contributing in a tachyonic way to scalar masses. Viability of warped su- persymmetric compactifications necessarily asks then for additional contributions. We discuss the case of additional bulk vector multiplets with mixed boundary conditions, which is a partic- ularly simple and attractive way to generate large positive scalar masses. We show that in this case successful fermion mass matrices implies highly degenerate scalar masses for the first two generations of squarks and sleptons.Comment: 23 pages. v2: References added, new section on effect of additional bulk vector multiplets and phenomenolog

Characterisation of Gut Microbiota in Ossabaw and Göttingen Minipigs as Models of Obesity and Metabolic Syndrome

Recent evidence suggests that the gut microbiota is an important contributing factor to obesity and obesity related metabolic disorders, known as the metabolic syndrome. The aim of this study was to characterise the intestinal microbiota in two pig models of obesity namely Göttingen minipigs and the Ossabaw minipigs.The cecal, ileal and colonic microbiota from lean and obese Osabaw and Göttingen minipigs were investigated by Illumina-based sequencing and by high throughput qPCR, targeting the 16S rRNA gene in different phylogenetic groups of bacteria. The weight gain through the study was significant in obese Göttingen and Ossabaw minipigs. The lean Göttingen minipigs' cecal microbiota contained significantly higher abundance of Firmicutes (P<0.006), Akkermensia (P<0.01) and Methanovibribacter (P<0.01) than obese Göttingen minipigs. The obese Göttingen cecum had higher abundances of the phyla Spirochaetes (P<0.03), Tenericutes (P<0.004), Verrucomicrobia (P<0.005) and the genus Bacteroides (P<0.001) compared to lean minipigs. The relative proportion of Clostridium cluster XIV was 7.6-fold higher in cecal microbiota of obese Göttingen minipigs as compared to lean. Obese Ossabaw minipigs had a higher abundance of Firmicutes in terminal ileum and lower abundance of Bacteroidetes in colon than lean Ossabaw minipigs (P<0.01). Obese Ossabaws had significantly lower abundances of the genera Prevotella and Lactobacillus and higher abundance of Clostridium in their colon than the lean Ossabaws. Overall, the Göttingen and Ossabaw minipigs displayed different microbial communities in response to diet-induced obesity in the different sections of their intestine.Obesity-related changes in the composition of the gut microbiota were found in lean versus obese Göttingen and Ossabaw minipigs. In both pig models diet seems to be the defining factor that shapes the gut microbiota as observed by changes in different bacteria divisions between lean and obese minipigs

Imidazoacridinone-dependent lysosomal photodestruction: a pharmacological Trojan horse approach to eradicate multidrug-resistant cancers

Multidrug resistance (MDR) remains a primary hindrance to curative cancer therapy. Thus, introduction of novel strategies to overcome MDR is of paramount therapeutic significance. Sequestration of chemotherapeutics in lysosomes is an established mechanism of drug resistance. Here, we show that MDR cells display a marked increase in lysosome number. We further demonstrate that imidazoacridinones (IAs), which are cytotoxic fluorochromes, undergo a dramatic compartmentalization in lysosomes because of their hydrophobic weak base nature. We hence developed a novel photoactivation-based pharmacological Trojan horse approach to target and eradicate MDR cancer cells based on photo-rupture of IA-loaded lysosomes and tumor cell lysis via formation of reactive oxygen species. Illumination of IA-loaded cells resulted in lysosomal photodestruction and restoration of parental cell drug sensitivity. Lysosomal photodestruction of MDR cells overexpressing the key MDR efflux transporters ABCG2, ABCB1 or ABCC1 resulted in 10- to 52-fold lower IC(50) values of various IAs, thereby restoring parental cell sensitivity. Finally, in vivo application of this photodynamic therapy strategy after i.v. injection of IAs in human ovarian tumor xenografts in the chorioallantoic membrane model revealed selective destruction of tumors and their associated vasculature. These findings identify lysosomal sequestration of IAs as an Achilles heel of MDR cells that can be harnessed to eradicate MDR tumor cells via lysosomal photodestruction

The evolution of galaxies from primeval irregulars to present-day ellipticals

The current understanding of galaxy formation is that it proceeds in a 'bottom up' way, with the formation of small clumps of gas and stars that merge hierarchically until giant galaxies are built up. The baryonic gas loses the thermal energy by radiative cooling and falls towards the centres of the new galaxies, while supernovae (SNe) blow gas out. Any realistic model therefore requires a proper treatment of these processes, but hitherto this has been far from satisfactory. Here we report an ultra-high-resolution simulation that follows evolution from the earliest stages of galaxy formation through the period of dynamical relaxation. The bubble structures of gas revealed in our simulation ($< 3\times10^8$ years) resemble closely the high-redshift Lyman $\alpha$ emitters (LAEs). After $10^9$ years these bodies are dominated by stellar continuum radiation and look like the Lyman break galaxies (LBGs) known as the high-redshift star-forming galaxies at which point the abundance of elements heavier than helium ("metallicity") appears to be solar. After $1.3\times10^{10}$ years, these galaxies resemble present-day ellipticals.Comment: 27 pages and 4 figures, Supplementary Information included, movie available on http://www.isc.senshu-u.ac.jp/~thj0613/natur