Outcome measurement in functional neurological disorder: a systematic review and recommendations.

OBJECTIVES: We aimed to identify existing outcome measures for functional neurological disorder (FND), to inform the development of recommendations and to guide future research on FND outcomes. METHODS: A systematic review was conducted to identify existing FND-specific outcome measures and the most common measurement domains and measures in previous treatment studies. Searches of Embase, MEDLINE and PsycINFO were conducted between January 1965 and June 2019. The findings were discussed during two international meetings of the FND-Core Outcome Measures group. RESULTS: Five FND-specific measures were identified-three clinician-rated and two patient-rated-but their measurement properties have not been rigorously evaluated. No single measure was identified for use across the range of FND symptoms in adults. Across randomised controlled trials (k=40) and observational treatment studies (k=40), outcome measures most often assessed core FND symptom change. Other domains measured commonly were additional physical and psychological symptoms, life impact (ie, quality of life, disability and general functioning) and health economics/cost-utility (eg, healthcare resource use and quality-adjusted life years). CONCLUSIONS: There are few well-validated FND-specific outcome measures. Thus, at present, we recommend that existing outcome measures, known to be reliable, valid and responsive in FND or closely related populations, are used to capture key outcome domains. Increased consistency in outcome measurement will facilitate comparison of treatment effects across FND symptom types and treatment modalities. Future work needs to more rigorously validate outcome measures used in this population

Freeze-thaw treatment effects on the dynamic mechanical properties of articular cartilage

BACKGROUND: As a relatively non-regenerative tissue, articular cartilage has been targeted for cryopreservation as a method of mitigating a lack of donor tissue availability for transplant surgeries. In addition, subzero storage of articular cartilage has long been used in biomedical studies using various storage temperatures. The current investigation studies the potential for freeze-thaw to affect the mechanical properties of articular cartilage through direct comparison of various subzero storage temperatures. METHODS: Both subzero storage temperature as well as freezing rate were compared using control samples (4°C) and samples stored at either -20°C or -80°C as well as samples first snap frozen in liquid nitrogen (-196°C) prior to storage at -80°C. All samples were thawed at 37.5°C to testing temperature (22°C). Complex stiffness and hysteresis characterized load resistance and damping properties using a non-destructive, low force magnitude, dynamic indentation protocol spanning a broad loading rate range to identify the dynamic viscoelastic properties of cartilage. RESULTS: Stiffness levels remained unchanged with exposure to the various subzero temperatures. Hysteresis increased in samples snap frozen at -196°C and stored at -80°C, though remained unchanged with exposure to the other storage temperatures. CONCLUSIONS: Mechanical changes shown are likely due to ice lens creation, where frost heave effects may have caused collagen damage. That storage to -20°C and -80°C did not alter the mechanical properties of articular cartilage shows that when combined with a rapid thawing protocol to 37.5°C, the tissue may successfully be stored at subzero temperatures

The holographic principle

There is strong evidence that the area of any surface limits the information content of adjacent spacetime regions, at 10^(69) bits per square meter. We review the developments that have led to the recognition of this entropy bound, placing special emphasis on the quantum properties of black holes. The construction of light-sheets, which associate relevant spacetime regions to any given surface, is discussed in detail. We explain how the bound is tested and demonstrate its validity in a wide range of examples. A universal relation between geometry and information is thus uncovered. It has yet to be explained. The holographic principle asserts that its origin must lie in the number of fundamental degrees of freedom involved in a unified description of spacetime and matter. It must be manifest in an underlying quantum theory of gravity. We survey some successes and challenges in implementing the holographic principle.Comment: 52 pages, 10 figures, invited review for Rev. Mod. Phys; v2: reference adde

Variations in Mre11/Rad50/Nbs1 status and DNA damage-induced S-phase arrest in the cell lines of the NCI60 panel

<p>Abstract</p> <p>Background</p> <p>The Mre11/Rad50/Nbs1 (MRN) complex is a regulator of cell cycle checkpoints and DNA repair. Defects in MRN can lead to defective S-phase arrest when cells are damaged. Such defects may elicit sensitivity to selected drugs providing a chemical synthetic lethal interaction that could be used to target therapy to tumors with these defects. The goal of this study was to identify these defects in the NCI60 panel of cell lines and identify compounds that might elicit selective cytotoxicity.</p> <p>Methods</p> <p>We screened the NCI60 panel in search of cell lines that express low levels of MRN proteins, or that fail to arrest in S-phase in response to the topisomerase I inhibitor SN38. The NCI COMPARE program was used to discover compounds that preferentially target cells with these phenotypes.</p> <p>Results</p> <p>HCT116 cells were initially identified as defective in MRN and S phase arrest. Transfection with Mre11 also elevated Rad50 and Nbs1, and rescued the defective S-phase arrest. Cells of the NCI60 panel exhibited a large range of protein expression but a strong correlation existed between Mre11, Rad50 and Nbs1 consistent with complex formation determining protein stability. Mre11 mRNA correlated best with protein level suggesting it was the primary determinant of the overall level of the complex. Three other cell lines failed to arrest in response to SN38, two of which also had low MRN. However, other cell lines with low MRN still arrested suggesting low MRN does not predict an inability to arrest. Many compounds, including a family of benzothiazoles, correlated with the failure to arrest in S phase. The activity of benzothiazoles has been attributed to metabolic activation and DNA alkylation, but we note several cell lines in which sensitivity does not correlate with metabolism. We propose that the checkpoint defect imposes an additional mechanism of sensitivity on cells.</p> <p>Conclusions</p> <p>We have identified cells with possible defects in the MRN complex and S phase arrest, and a series of compounds that may preferentially target S phase-defective cells. We discuss limitations of the COMPARE program when attempting to identify compounds that selectively inhibit only a few cell lines.</p

Oil Palm Research in Context: Identifying the Need for Biodiversity Assessment

Oil palm cultivation is frequently cited as a major threat to tropical biodiversity as it is centered on some of the world's most biodiverse regions. In this report, Web of Science was used to find papers on oil palm published since 1970, which were assigned to different subject categories to visualize their research focus. Recent years have seen a broadening in the scope of research, with a slight growth in publications on the environment and a dramatic increase in those on biofuel. Despite this, less than 1% of publications are related to biodiversity and species conservation. In the context of global vegetable oil markets, palm oil and soyabean account for over 60% of production but are the subject of less than 10% of research. Much more work must be done to establish the impacts of habitat conversion to oil palm plantation on biodiversity. Results from such studies are crucial for informing conservation strategies and ensuring sustainable management of plantations

High recombination rates and hotspots in a Plasmodium falciparum genetic cross

Using the universal P2/P8 primers, we were able to obtain the gene segments of chromo-helicase-DNA binding protein (CHD)-Z and CHD-W from ten species of ardeid birds including Chinese egret (Egretta eulophotes), little egret (E. garzetta), eastern reef egret (E. sacra), great egret (Ardea alba), grey heron (A. cinerea), Chinese pond-heron (Ardeola bacchus), cattle egret (Bubulcus ibis), black-crowned night-heron (Nycticorax nycticorax), cinnamon bittern (Ixobrychus cinnamomeus) and yellow bittern (I. sinensis). Based on conserved regions inside the P2/P8-derived sequences, we designed new PCR primers for sex identification in these ardeid species. Using agarose gel electrophoresis, the PCR products showed two bands for females (140 bp derived from CHD-W and the other 250 bp from CHD-ZW), whereas the males showed only the 250 bp band. The results indicated that our new primers could be used for accurate and convenient sex identification in ardeid species.National Natural Science Foundation of China[30970380, 40876077]; Fujian Natural Science Foundation of China[2008S0007, 2009J01195

Dynamical Boson Stars

The idea of stable, localized bundles of energy has strong appeal as a model for particles. In the 1950s John Wheeler envisioned such bundles as smooth configurations of electromagnetic energy that he called {\em geons}, but none were found. Instead, particle-like solutions were found in the late 1960s with the addition of a scalar field, and these were given the name {\em boson stars}. Since then, boson stars find use in a wide variety of models as sources of dark matter, as black hole mimickers, in simple models of binary systems, and as a tool in finding black holes in higher dimensions with only a single killing vector. We discuss important varieties of boson stars, their dynamic properties, and some of their uses, concentrating on recent efforts.Comment: 79 pages, 25 figures, invited review for Living Reviews in Relativity; major revision in 201

Genetic structure of sigmodontine rodents (Cricetidae) along an altitudinal gradient of the Atlantic Rain Forest in southern Brazil

The population genetic structure of two sympatric species of sigmodontine rodents (Oligoryzomys nigripes and Euryoryzomys russatus) was examined for mitochondrial DNA (mtDNA) sequence haplotypes of the control region. Samples were taken from three localities in the Atlantic Rain Forest in southern Brazil, along an altitudinal gradient with different types of habitat. In both species there was no genetic structure throughout their distribution, although levels of genetic variability and gene flow were high