An online acceptance, commitment, and self-compassion based treatment to decrease psychological distress in people with type 2 diabetes: A feasibility randomised-controlled trial

BACKGROUND AND PURPOSE: This study explored the feasibility and acceptability of conducting a larger trial of a self-guided, online self-compassion and acceptance and commitment therapy (ACT) focused treatment among people with type 2 diabetes (T2D) to decrease psychological distress. MATERIALS AND METHODS: This study was a two-arm, parallel, feasibility randomised controlled trial with nested qualitative methods. UK adults with T2D were randomly (1:1) allocated to a five-week online self-compassion and ACT treatment or waitlist control. Information regarding recruitment, trial retention, and treatment completion was collected, and post-treatment semi-structured interviews were conducted to assess feasibility and acceptability. Self-report measures of psychological distress (depression, anxiety, diabetes distress) and potential treatment processes (self-compassion and psychological flexibility) were completed as secondary feasibility outcomes. RESULTS: Fifty-five (60.44 %) out of 91 people who accessed the study link were eligible to participate. Of these, 33 eligible participants (60 %) were randomly assigned to treatment (n = 19) or control arms (waitlist; n = 14). While treatment completion was 47.37 %, trial retention rates were 39.39 % (5-week follow-up) and 21.2 % (9-week follow-up). Secondary feasibility outcomes of treatment effect estimates are difficult to interpret in light of low treatment completion and trial retention rates. CONCLUSION: A larger trial of the self-guided, online self-compassion treatment to decrease psychological distress in people with T2D may be beneficial, but it has limited feasibility in its current form. Further efforts are needed to improve treatment acceptability of online self-compassion and ACT focused treatment and trial procedures

Critical Micronutrients in Pregnancy, Lactation, and Infancy: Considerations on Vitamin D, Folic Acid, and Iron, and Priorities for Future Research

The Early Nutrition Academy and the European Commission-funded EURRECA Network of Excellence jointly sponsored a scientific workshop on critical micronutrients in pregnancy, lactation, and infancy. Current knowledge and unresolved questions on the supply of vitamin D, folic acid, and iron for pregnant women, lactating women, and infants, and their health effects were discussed. The question was addressed of whether, and under which circumstances, supplementation with these micronutrients in addition to usual dietary intakes is advisable. The workshop participants concluded that public health strategies for improving supplementation with these micronutrients in pregnancy, lactation, and infancy are required. Further research priorities should focus on adequately powered human intervention trials to obtain a stronger evidence base for the amounts of vitamin D, folic acid, and iron that have optimal effects on health. The conclusions of the workshop should help to inform the scientific community as well as public health policy strategies. Copyright (C) 2011 S. Karger AG, Base

Gravitational waves from merging compact binaries

Largely motivated by the development of highly sensitive gravitational-wave detectors, our understanding of merging compact binaries and the gravitational waves they generate has improved dramatically in recent years. Breakthroughs in numerical relativity now allow us to model the coalescence of two black holes with no approximations or simplifications. There has also been outstanding progress in our analytical understanding of binaries. We review these developments, examining merging binaries using black hole perturbation theory, post-Newtonian expansions, and direct numerical integration of the field equations. We summarize these approaches and what they have taught us about gravitational waves from compact binaries. We place these results in the context of gravitational-wave generating systems, analyzing the impact gravitational wave emission has on their sources, as well as what we can learn about them from direct gravitational-wave measurements.Comment: 90 pages, 12 figures. Invited review to appear in Annual Reviews of Astronomy and Astrophysics. Further minor tweaks in response to reader feedbac

Comparing distribution of harbour porpoise using generalized additive models and hierarchical Bayesian models with integrated nested laplace approximation

Species Distribution Models (SDMs) are used regularly to develop management strategies, but many modelling methods ignore the spatial nature of data. To address this, we compared fine-scale spatial distribution predictions of harbour porpoise (Phocoena phocoena) using empirical aerial-video-survey data collected along the east coast of Scotland in August and September 2010 and 2014. Incorporating environmental covariates that cover habitat preferences and prey proxies, we used a traditional (and commonly implemented) Generalized Additive Model (GAM), and two Hierarchical Bayesian Modelling (HBM) approaches using Integrated Nested Laplace Approxi�mation (INLA) model-fitting methodology. One HBM-INLA modelled gridded space (similar to the GAM), and the other dealt more explicitly in continuous space using a Log-Gaussian Cox Process (LGCP). Overall, predicted distributions in the three models were similar; however, HBMs had twice the level of certainty, showed much finer-scale patterns in porpoise distribution, and identified some areas of high relative density that were not apparent in the GAM. Spatial differences were due to how the two methods accounted for autocorrelation, spatial clustering of animals, and differences between modelling in discrete vs. continuous space; consequently, methods for spatial analyses likely depend on scale at which results, and certainty, are needed. For large-scale analysis (>5–10 km resolution, e.g. initial impact assessment), there was little difference be�tween results; however, insights into fine-scale (<1 km) distribution of porpoise from the HBM model using LGCP, while more computationally costly, offered potential benefits for refining conservation management or mitigation measures within offshore developments or protected areas

Molecular Valves for Controlling Gas Phase Transport Made from Discrete Angstrom-Sized Pores in Graphene

An ability to precisely regulate the quantity and location of molecular flux is of value in applications such as nanoscale 3D printing, catalysis, and sensor design. Barrier materials containing pores with molecular dimensions have previously been used to manipulate molecular compositions in the gas phase, but have so far been unable to offer controlled gas transport through individual pores. Here, we show that gas flux through discrete angstrom-sized pores in monolayer graphene can be detected and then controlled using nanometer-sized gold clusters, which are formed on the surface of the graphene and can migrate and partially block a pore. In samples without gold clusters, we observe stochastic switching of the magnitude of the gas permeance, which we attribute to molecular rearrangements of the pore. Our molecular valves could be used, for example, to develop unique approaches to molecular synthesis that are based on the controllable switching of a molecular gas flux, reminiscent of ion channels in biological cell membranes and solid state nanopores.Comment: to appear in Nature Nanotechnolog

Targeting metabolic activity in high-risk neuroblastoma through Monocarboxylate Transporter 1 (MCT1) inhibition

Amplification of the MYCN oncogene occurs in ~25% of primary neuroblastomas and is the single most powerful biological marker of poor prognosis in this disease. MYCN transcriptionally regulates a range of biological processes important for cancer, including cell metabolism. The MYCN-regulated metabolic gene SLC16A1, encoding the lactate transporter monocarboxylate transporter 1 (MCT1), is a potential therapeutic target. Treatment of neuroblastoma cells with the MCT1 inhibitor SR13800 increased intracellular lactate levels, disrupted the nicotinamide adenine dinucleotide (NADH/NAD+) ratio, and decreased intracellular glutathione levels. Metabolite tracing with 13C-glucose and 13C-glutamine following MCT1 inhibitor treatment revealed increased quantities of tricarboxylic acid (TCA) cycle intermediates and increased oxygen consumption rate. MCT1 inhibition was highly synergistic with vincristine and LDHA inhibition under cell culture conditions, but this combination was ineffective against neuroblastoma xenografts. Posttreatment xenograft tumors had increased synthesis of the MCT1 homolog MCT4/SLC16A, a known resistance factor to MCT1 inhibition. We found that MCT4 was negatively regulated by MYCN in luciferase reporter assays and its synthesis in neuroblastoma cells was increased under hypoxic conditions and following hypoxia-inducible factor (HIF1) induction, suggesting that MCT4 may contribute to resistance to MCT1 inhibitor treatment in hypoxic neuroblastoma tumors. Co-treatment of neuroblastoma cells with inhibitors of MCT1 and LDHA, the enzyme responsible for lactate production, resulted in a large increase in intracellular pyruvate and was highly synergistic in decreasing neuroblastoma cell viability. These results highlight the potential of targeting MCT1 in neuroblastoma in conjunction with strategies that involve disruption of pyruvate homeostasis and indicate possible resistance mechanisms

Simultaneous quantification of 12 different nucleotides and nucleosides released from renal epithelium and in human urine samples using ion-pair reversed-phase HPLC

Nucleotides and nucleosides are not only involved in cellular metabolism but also act extracellularly via P1 and P2 receptors, to elicit a wide variety of physiological and pathophysiological responses through paracrine and autocrine signalling pathways. For the first time, we have used an ion-pair reversed-phase high-performance liquid chromatography ultraviolet (UV)-coupled method to rapidly and simultaneously quantify 12 different nucleotides and nucleosides (adenosine triphosphate, adenosine diphosphate, adenosine monophosphate, adenosine, uridine triphosphate, uridine diphosphate, uridine monophosphate, uridine, guanosine triphosphate, guanosine diphosphate, guanosine monophosphate, guanosine): (1) released from a mouse renal cell line (M1 cortical collecting duct) and (2) in human biological samples (i.e., urine). To facilitate analysis of urine samples, a solid-phase extraction step was incorporated (overall recovery rate ? 98 %). All samples were analyzed following injection (100 ?l) into a Synergi Polar-RP 80 Å (250 × 4.6 mm) reversed-phase column with a particle size of 10 ?m, protected with a guard column. A gradient elution profile was run with a mobile phase (phosphate buffer plus ion-pairing agent tetrabutylammonium hydrogen sulfate; pH 6) in 2-30 % acetonitrile (v/v) for 35 min (including equilibration time) at 1 ml min(-1) flow rate. Eluted compounds were detected by UV absorbance at 254 nm and quantified using standard curves for nucleotide and nucleoside mixtures of known concentration. Following validation (specificity, linearity, limits of detection and quantitation, system precision, accuracy, and intermediate precision parameters), this protocol was successfully and reproducibly used to quantify picomolar to nanomolar concentrations of nucleosides and nucleotides in isotonic and hypotonic cell buffers that transiently bathed M1 cells, and urine samples from normal subjects and overactive bladder patients

Asymmetric triplex metallohelices with high and selective activity against cancer cells

Small cationic amphiphilic α-helical peptides are emerging as agents for the treatment of cancer and infection, but they are costly and display unfavourable pharmacokinetics. Helical coordination complexes may offer a three-dimensional scaffold for the synthesis of mimetic architectures. However, the high symmetry and modest functionality of current systems offer little scope to tailor the structure to interact with specific biomolecular targets, or to create libraries for phenotypic screens. Here, we report the highly stereoselective asymmetric self-assembly of very stable, functionalized metallohelices. Their anti-parallel head-to-head-to-tail ‘triplex’ strand arrangement creates an amphipathic functional topology akin to that of the active sub-units of, for example, host-defence peptides and ​p53. The metallohelices display high, structure-dependent toxicity to the human colon carcinoma cell-line HCT116 ​p53++, causing dramatic changes in the cell cycle without DNA damage. They have lower toxicity to human breast adenocarcinoma cells (MDA-MB-468) and, most remarkably, they show no significant toxicity to the bacteria methicillin-resistant Staphylococcus aureus and Escherichia coli. At a glanc

Symmetric informationally complete positive operator valued measure and probability representation of quantum mechanics

Symmetric informationally complete positive operator valued measures (SIC-POVMs) are studied within the framework of the probability representation of quantum mechanics. A SIC-POVM is shown to be a special case of the probability representation. The problem of SIC-POVM existence is formulated in terms of symbols of operators associated with a star-product quantization scheme. We show that SIC-POVMs (if they do exist) must obey general rules of the star product, and, starting from this fact, we derive new relations on SIC-projectors. The case of qubits is considered in detail, in particular, the relation between the SIC probability representation and other probability representations is established, the connection with mutually unbiased bases is discussed, and comments to the Lie algebraic structure of SIC-POVMs are presented.Comment: 22 pages, 1 figure, LaTeX, partially presented at the Workshop "Nonlinearity and Coherence in Classical and Quantum Systems" held at the University "Federico II" in Naples, Italy on December 4, 2009 in honor of Prof. Margarita A. Man'ko in connection with her 70th birthday, minor misprints are corrected in the second versio