Mindfulness-based interventions in epilepsy: a systematic review

Mindfulness based interventions (MBIs) are increasingly used to help patients cope with physical and mental long-term conditions (LTCs). Epilepsy is associated with a range of mental and physical comorbidities that have a detrimental effect on quality of life (QOL), but it is not clear whether MBIs can help. We systematically reviewed the literature to determine the effectiveness of MBIs in people with epilepsy. Medline, Cochrane Central Register of Controlled Trials, EMBASE, CINAHL, Allied and Complimentary Medicine Database, and PsychInfo were searched in March 2016. These databases were searched using a combination of subject headings where available and keywords in the title and abstracts. We also searched the reference lists of related reviews. Study quality was assessed using the Cochrane Collaboration risk of bias tool. Three randomised controlled trials (RCTs) with a total of 231 participants were included. The interventions were tested in the USA (n = 171) and China (Hong Kong) (n = 60). Significant improvements were reported in depression symptoms, quality of life, anxiety, and depression knowledge and skills. Two of the included studies were assessed as being at unclear/high risk of bias - with randomisation and allocation procedures, as well as adverse events and reasons for drop-outs poorly reported. There was no reporting on intervention costs/benefits or how they affected health service utilisation. This systematic review found limited evidence for the effectiveness of MBIs in epilepsy, however preliminary evidence suggests it may lead to some improvement in anxiety, depression and quality of life. Further trials with larger sample sizes, active control groups and longer follow-ups are needed before the evidence for MBIs in epilepsy can be conclusively determined

Bang-bang control of fullerene qubits using ultra-fast phase gates

Quantum mechanics permits an entity, such as an atom, to exist in a superposition of multiple states simultaneously. Quantum information processing (QIP) harnesses this profound phenomenon to manipulate information in radically new ways. A fundamental challenge in all QIP technologies is the corruption of superposition in a quantum bit (qubit) through interaction with its environment. Quantum bang-bang control provides a solution by repeatedly applying `kicks' to a qubit, thus disrupting an environmental interaction. However, the speed and precision required for the kick operations has presented an obstacle to experimental realization. Here we demonstrate a phase gate of unprecedented speed on a nuclear spin qubit in a fullerene molecule (N@C60), and use it to bang-bang decouple the qubit from a strong environmental interaction. We can thus trap the qubit in closed cycles on the Bloch sphere, or lock it in a given state for an arbitrary period. Our procedure uses operations on a second qubit, an electron spin, in order to generate an arbitrary phase on the nuclear qubit. We anticipate the approach will be vital for QIP technologies, especially at the molecular scale where other strategies, such as electrode switching, are unfeasible

Assessment of a Dedicated Transplant Low Clearance Clinic and Patient Outcomes on Dialysis After Renal Allograft Loss at 2 UK Transplant Centers.

Background Low clearance transplant clinics (LCTCs) are recommended for the management of recipients with a failing kidney transplant (RFKT) but data to support their use is limited. We conducted a retrospective study to assess management of RFKT at 2 transplant centers, 1 with a LCTC (center A) and 1 without (center B). Methods Patients who transitioned to an alternative form of renal replacement therapy (RRT) between January 1, 2012, and November 30, 2016, were included. Patients with graft failure within a year of transplantation or due to an unpredictable acute event were excluded. Clinical data were collected after review of medical records. Results One hundred seventy-nine patients (age, 48.6 ± 13.4 years, 99 [55.3%] male, and mean transplant duration 10.3 ± 7.8 years) were included. RRT counseling occurred in 79 (91%) and 68 (74%) patients at centers A and B (P = 0.003), at median 135 (61-319) and 133 (69-260) days before dialysis after graft loss (P = 0.92). Sixty-one (34.1%) patients were waitlisted for retransplantation; 18 (32.7%) nonwaitlisted patients were still undergoing workup at center A compared with 37 (58.7%) at center B (P = 0.028). Preemptive retransplantation occurred in 4 (4.6%) and 5 (5.4%) patients at centers A and B (P = 0.35). At 1 year after initiation of dialysis after graft loss, 11 (15.3%) and 11 (17.2%) patients were retransplanted (P = 0.12), and mortality was 6.6% overall. Conclusions A dedicated LCTC improved RRT counseling and transplant work-up but did not lead to improved rates of retransplantation. Earlier consideration of retransplantation in LCTCs is required to improve RFKT outcomes

Clinical Implication of Targeting of Cancer Stem Cells

The existence of cancer stem cells (CSCs) is receiving increasing interest particularly due to its potential ability to enter clinical routine. Rapid advances in the CSC field have provided evidence for the development of more reliable anticancer therapies in the future. CSCs typically only constitute a small fraction of the total tumor burden; however, they harbor self-renewal capacity and appear to be relatively resistant to conventional therapies. Recent therapeutic approaches aim to eliminate or differentiate CSCs or to disrupt the niches in which they reside. Better understanding of the biological characteristics of CSCs as well as improved preclinical and clinical trials targeting CSCs may revolutionize the treatment of many cancers. Copyright (c) 2012 S. Karger AG, Base

Tendinopathy—from basic science to treatment

Chronic tendon pathology (tendinopathy), although common, is difficult to treat. Tendons possess a highly organized fibrillar matrix, consisting of type I collagen and various 'minor' collagens, proteoglycans and glycoproteins. The tendon matrix is maintained by the resident tenocytes, and there is evidence of a continuous process of matrix remodeling, although the rate of turnover varies at different sites. A change in remodeling activity is associated with the onset of tendinopathy. Major molecular changes include increased expression of type III collagen, fibronectin, tenascin C, aggrecan and biglycan. These changes are consistent with repair, but they might also be an adaptive response to changes in mechanical loading. Repeated minor strain is thought to be the major precipitating factor in tendinopathy, although further work is required to determine whether it is mechanical overstimulation or understimulation that leads to the change in tenocyte activity. Metalloproteinase enzymes have an important role in the tendon matrix, being responsible for the degradation of collagen and proteoglycan in both healthy patients and those with disease. Metalloproteinases that show increased expression in painful tendinopathy include ADAM (a disintegrin and metalloproteinase)-12 and MMP (matrix metalloproteinase)-23. The role of these enzymes in tendon pathology is unknown, and further work is required to identify novel and specific molecular targets for therapy

Two novel human cytomegalovirus NK cell evasion functions target MICA for lysosomal degradation

NKG2D plays a major role in controlling immune responses through the regulation of natural killer (NK) cells, αβ and γδ T-cell function. This activating receptor recognizes eight distinct ligands (the MHC Class I polypeptide-related sequences (MIC) A andB, and UL16-binding proteins (ULBP)1–6) induced by cellular stress to promote recognition cells perturbed by malignant transformation or microbial infection. Studies into human cytomegalovirus (HCMV) have aided both the identification and characterization of NKG2D ligands (NKG2DLs). HCMV immediate early (IE) gene up regulates NKGDLs, and we now describe the differential activation of ULBP2 and MICA/B by IE1 and IE2 respectively. Despite activation by IE functions, HCMV effectively suppressed cell surface expression of NKGDLs through both the early and late phases of infection. The immune evasion functions UL16, UL142, and microRNA(miR)-UL112 are known to target NKG2DLs. While infection with a UL16 deletion mutant caused the expected increase in MICB and ULBP2 cell surface expression, deletion of UL142 did not have a similar impact on its target, MICA. We therefore performed a systematic screen of the viral genome to search of addition functions that targeted MICA. US18 and US20 were identified as novel NK cell evasion functions capable of acting independently to promote MICA degradation by lysosomal degradation. The most dramatic effect on MICA expression was achieved when US18 and US20 acted in concert. US18 and US20 are the first members of the US12 gene family to have been assigned a function. The US12 family has 10 members encoded sequentially through US12–US21; a genetic arrangement, which is suggestive of an ‘accordion’ expansion of an ancestral gene in response to a selective pressure. This expansion must have be an ancient event as the whole family is conserved across simian cytomegaloviruses from old world monkeys. The evolutionary benefit bestowed by the combinatorial effect of US18 and US20 on MICA may have contributed to sustaining the US12 gene family

The use of carboxymethylcellulose gel to increase non-viral gene transfer in mouse airways

We have assessed whether viscoelastic gels known to inhibit mucociliary clearance can increase lipid-mediated gene transfer. Methylcellulose or carboxymethylcellulose (0.25 to 1.5%) were mixed with complexes of the cationic lipid GL67A and plasmids encoding luciferase and perfused onto the nasal epithelium of mice. Survival after perfusion with 1% CMC or1% MC was 90 and 100%, respectively. In contrast 1.5% CMC was uniformly lethal likely due to the viscous solution blocking the airways. Perfusion with 0.5% CMC containing lipid/DNA complexes reproducibly increased gene expression by approximately 3-fold (n= 16, p<0.05). Given this benefit, likely related to increased duration of contact, we also assessed the effect of prolonging contact time of the liposome/DNA complexes by delivering our standard 80 μg DNA dose over either approximately 22 or 60 min of perfusion. This independently increased gene transfer by 6-fold (n=8, p<0.05) and could be further enhanced by the addition of 0.5% CMC, leading to an overall 25-fold enhancement (n=8, p<0.001) in gene expression. As a result of these interventions CFTR transgene mRNA transgene levels were increased several logs above background. Interestingly, this did not lead to correction of the ion transport defects in the nasal epithelium of cystic fibrosis mice nor for immunohistochemical quantification of CFTR expression. To assess if 0.5% CMC also increased gene transfer in the mouse lung, we used whole body nebulisation chambers. CMC was nebulised for 1 hr immediately before, or simultaneously with GL67A/pCIKLux. The former did not increase gene transfer, whereas co-administration significantly increased gene transfer by 4-fold (p<0.0001, n=18). This study suggests that contact time of non-viral gene transfer agents is a key factor for gene delivery, and suggests two methods which may be translatable for use in man

Design of Experiments for Screening

The aim of this paper is to review methods of designing screening experiments, ranging from designs originally developed for physical experiments to those especially tailored to experiments on numerical models. The strengths and weaknesses of the various designs for screening variables in numerical models are discussed. First, classes of factorial designs for experiments to estimate main effects and interactions through a linear statistical model are described, specifically regular and nonregular fractional factorial designs, supersaturated designs and systematic fractional replicate designs. Generic issues of aliasing, bias and cancellation of factorial effects are discussed. Second, group screening experiments are considered including factorial group screening and sequential bifurcation. Third, random sampling plans are discussed including Latin hypercube sampling and sampling plans to estimate elementary effects. Fourth, a variety of modelling methods commonly employed with screening designs are briefly described. Finally, a novel study demonstrates six screening methods on two frequently-used exemplars, and their performances are compared

Two Stellar Components in the Halo of the Milky Way

The halo of the Milky Way provides unique elemental abundance and kinematic information on the first objects to form in the Universe, which can be used to tightly constrain models of galaxy formation and evolution. Although the halo was once considered a single component, evidence for its dichotomy has slowly emerged in recent years from inspection of small samples of halo objects. Here we show that the halo is indeed clearly divisible into two broadly overlapping structural components -- an inner and an outer halo -- that exhibit different spatial density profiles, stellar orbits and stellar metallicities (abundances of elements heavier than helium). The inner halo has a modest net prograde rotation, whereas the outer halo exhibits a net retrograde rotation and a peak metallicity one-third that of the inner halo. These properties indicate that the individual halo components probably formed in fundamentally different ways, through successive dissipational (inner) and dissipationless (outer) mergers and tidal disruption of proto-Galactic clumps.Comment: Two stand-alone files in manuscript, concatenated together. The first is for the main paper, the second for supplementary information. The version is consistent with the version published in Natur

Multiplicity of young brown dwarfs in Cha I

How frequent are brown dwarf binaries? Do brown dwarfs have planets? Are current theoretical pre-main-sequence evolutionary tracks valid down to the substellar regime? - Any detection of a companion to a brown dwarf takes us one step forward towards answering these basic questions of star formation. We report here on a search for spectroscopic and visual companions to young brown dwarfs in the Cha I star forming cloud. Based on spectra taken with UVES at the VLT, we found significant radial velocity (RV) variations for five bona-fide and candidate brown dwarfs in Cha I. They can be caused by either a (substellar or planetary) companion or stellar activity. A companion causing the detected RV variations would have about a few Jupiter masses. We are planning further UVES observations in order to explore the nature of the detected RV variations. We also found that the RV dispersion is only ~ 2km/s indicating that there is probably no run-away brown dwarf among them. Additionally a search for companions by direct imaging with the HST and SOFI (NTT) has yielded to the detection of a few companion candidates in larger orbits.Comment: Conference proceeding "Origins of stars and planets: The VLT view", ESO, Garching, April 24-27 200