Chronic kidney disease is common in the general population and associated with excess cardiovascular disease (CVD), but kidney function does not feature in current CVD risk-prediction models. We ...tested three formulae for estimated glomerular filtration rate (eGFR) to determine which was the most clinically informative for predicting CVD and mortality. Using data from 440,526 participants from UK Biobank, eGFR was calculated using serum creatinine, cystatin C (eGFRcys) and creatinine-cystatin C. Associations of each eGFR with CVD outcome and mortality were compared using Cox models and adjusting for atherosclerotic risk factors (per relevant risk scores), and the predictive utility was determined by the C-statistic and categorical net reclassification index. We show that eGFRcys is most strongly associated with CVD and mortality, and, along with albuminuria, adds predictive discrimination to current CVD risk scores, whilst traditional creatinine-based measures are weakly associated with risk. Clinicians should consider measuring eGFRcys as part of cardiovascular risk assessment.
Spinal cord injury (SCI) is a devastating condition that causes substantial morbidity and mortality and for which no treatments are available. Stem cells offer some promise in the restoration of ...neurological function. We used systematic review, meta-analysis, and meta-regression to study the impact of stem cell biology and experimental design on motor and sensory outcomes following stem cell treatments in animal models of SCI. One hundred and fifty-six publications using 45 different stem cell preparations met our prespecified inclusion criteria. Only one publication used autologous stem cells. Overall, allogeneic stem cell treatment appears to improve both motor (effect size, 27.2%; 95% Confidence Interval CI, 25.0%-29.4%; 312 comparisons in 5,628 animals) and sensory (effect size, 26.3%; 95% CI, 7.9%-44.7%; 23 comparisons in 473 animals) outcome. For sensory outcome, most heterogeneity between experiments was accounted for by facets of stem cell biology. Differentiation before implantation and intravenous route of delivery favoured better outcome. Stem cell implantation did not appear to improve sensory outcome in female animals and appeared to be enhanced by isoflurane anaesthesia. Biological plausibility was supported by the presence of a dose-response relationship. For motor outcome, facets of stem cell biology had little detectable effect. Instead most heterogeneity could be explained by the experimental modelling and the outcome measure used. The location of injury, method of injury induction, and presence of immunosuppression all had an impact. Reporting of measures to reduce bias was higher than has been seen in other neuroscience domains but were still suboptimal. Motor outcomes studies that did not report the blinded assessment of outcome gave inflated estimates of efficacy. Extensive recent preclinical literature suggests that stem-cell-based therapies may offer promise, however the impact of compromised internal validity and publication bias mean that efficacy is likely to be somewhat lower than reported here.
Depersonalization and derealization can occur not just from psychiatric causes but also from various organic etiologies, such as seizures and intracerebral structural abnormalities. However, there ...have been no previous reported cases to the authors' knowledge detailing isolated depersonalization and derealization in the absence of clinical seizure activity or other psychiatric pathology, as sequelae of structural intracerebral lesions.
In this case report, we detail the unique presentation of a 68-year-old woman under the care of palliative medicine who experienced depersonalization and derealization secondary to a metastatic lesion in her temporal lobe, in the parahippocampal gyrus to medial occipitotemporal gyrus region. These symptoms were present in the absence of any clinical seizure activity or other psychiatric symptomatology and largely resolved with the use of steroidal therapy, before returning secondary to disease progression.
We discuss the relationship among isolated depersonalization and derealization with pathology of the left posterior temporal lobe in the context of this interesting case. This case expands our knowledge of the neurobiology of these phenomena, given the specific localization of the intracerebral pathology and temporal specificity of symptoms relative to tumor growth and treatment course.
DNA double strand breaks (DSB) are the most serious form of DNA damage. If not repaired they can lead to cell death. If misrepaired DSBs contribute to chromosomal aberrations and genomic instability. ...Non-homologous end joining (NHEJ) is one of two major pathways for the repair of DSBs in human cells. Proteins known to be required for NHEJ include the DNA-dependent protein kinase (DNA-PK), XRCC4, DNA ligase IV, and Artemis. This review discusses how these and other accessory proteins may function in the repair of DSBs produced by ionizing radiation (IR) and by V(D)J recombination.
Vector control interventions play a fundamental role in the control and elimination of vector-borne diseases. The evaluation of vector control products relies on bioassays, laboratory and semi-field ...tests using live insects to assess the product's effectiveness. Bioassay method development requires a rigorous validation process to ensure that relevant methods are used to capture appropriate entomological endpoints which accurately and precisely describe likely efficacy against disease vectors as well as product characteristics within the manufacturing tolerance ranges for insecticide content specified by the World Health Organization. Currently, there are no standardized guidelines for bioassay method validation in vector control. This report presents a framework for bioassay validation that draws on accepted validation processes from the chemical and healthcare fields and which can be applied for evaluating bioassays and semi-field tests in vector control. The validation process has been categorized into four stages: preliminary development; feasibility experiments; internal validation, and external validation. A properly validated method combined with an appropriate experimental design and data analyses that account for both the variability of the method and the product is needed to generate reliable estimates of product efficacy to ensure that at-risk communities have timely access to safe and reliable vector control products.
We present a new module of
micrOMEGAs devoted to the computation of indirect signals from dark matter annihilation in any new model with a stable weakly interacting particle. The code provides the ...mass spectrum, cross-sections, relic density and exotic fluxes of gamma rays, positrons and antiprotons. The propagation of charged particles in the Galactic halo is handled with a new module that allows to easily modify the propagation parameters.
Program title: micrOMEGAs2.4
Catalogue identifier: ADQR_v2_3
Program summary URL:
http://cpc.cs.qub.ac.uk/summaries/ADQR_v2_3.html
Program obtainable from: CPC Program Library, Queen's University, Belfast, N. Ireland
Licensing provisions: Standard CPC licence,
http://cpc.cs.qub.ac.uk/licence/licence.html
No. of lines in distributed program, including test data, etc.: 401 126
No. of bytes in distributed program, including test data, etc.: 6 583 596
Distribution format: tar.gz
Programming language: C and Fortran
Computer: PC, Alpha, Mac, Sun
Operating system: UNIX (Linux, OSF1, SunOS, Darwin, Cygwin)
RAM: 50 MB depending on the number of processes required
Classification: 1.9, 11.6
Catalogue identifier of previous version: ADQR_v2_3
Journal reference of previous version: Comput. Phys. Comm. 180 (2009) 747
Does the new version supersede the previous version?: Yes
Nature of problem: Calculation of the relic density and detection rates of the lightest stable particle in a generic new model of particle physics.
Solution method: In numerically solving the evolution equation for the density of dark matter, relativistic formulas for the thermal average are used. All tree-level processes for annihilation and coannihilation of new particles in the model are included. The cross-sections for all processes are calculated exactly with CalcHEP after definition of a model file. The propagation of the charged cosmic rays is solved within a semi-analytical two-zone model.
Reasons for new version: There are many experiments that are currently searching for the remnants of dark matter annihilation. In this version we perform the computation of indirect signals from dark matter annihilation in any new model with a stable weakly interacting particle. We include the propagation of charged particles in the Galactic halo.
Summary of revisions:
•
Annihilation cross-sections for all 2-body tree-level processes and for radiative emission of a photon for all models.
•
Annihilation cross-sections into polarised gauge bosons.
•
Annihilation cross-sections for the loop induced processes
γγ and
γ
Z
0
in the MSSM.
•
Modelling of the DM halo with a general parameterization and with the possibility of including DM clumps.
•
Computation of the propagation of charged particles through the Galaxy, including the possibility of modifying the propagation parameters.
•
Effect of solar modulation on the charged particle spectrum.
•
Model independent predictions of the indirect detection signals.
Unusual features: Depending on the parameters of the model, the program generates additional new code, compiles it and loads it dynamically.
Running time: 3 sec
Dengue and dengue hemorrhagic fever are increasing public health problems with an estimated 50–100 million new infections each year. Aedes aegypti is the major vector of dengue viruses in its range ...and control of this mosquito would reduce significantly human morbidity and mortality. Present mosquito control methods are not sufficiently effective and new approaches are needed urgently. A "sterile-male-release" strategy based on the release of mosquitoes carrying a conditional dominant lethal gene is an attractive new control methodology. Transgenic strains of Aedes aegypti were engineered to have a repressible female-specific flightless phenotype using either two separate transgenes or a single transgene, based on the use of a female-specific indirect flight muscle promoter from the Aedes aegypti Actin-4 gene. These strains eliminate the need for sterilization by irradiation, permit male-only release ("genetic sexing"), and enable the release of eggs instead of adults. Furthermore, these strains are expected to facilitate area-wide control or elimination of dengue if adopted as part of an integrated pest management strategy.
Dengue is the most important mosquito-borne viral disease. In the absence of specific drugs or vaccines, control focuses on suppressing the principal mosquito vector, Aedes aegypti, yet current ...methods have not proven adequate to control the disease. New methods are therefore urgently needed, for example genetics-based sterile-male-release methods. However, this requires that lab-reared, modified mosquitoes be able to survive and disperse adequately in the field.
Adult male mosquitoes were released into an uninhabited forested area of Pahang, Malaysia. Their survival and dispersal was assessed by use of a network of traps. Two strains were used, an engineered 'genetically sterile' (OX513A) and a wild-type laboratory strain, to give both absolute and relative data about the performance of the modified mosquitoes. The two strains had similar maximum dispersal distances (220 m), but mean distance travelled of the OX513A strain was lower (52 vs. 100 m). Life expectancy was similar (2.0 vs. 2.2 days). Recapture rates were high for both strains, possibly because of the uninhabited nature of the site.
After extensive contained studies and regulatory scrutiny, a field release of engineered mosquitoes was safely and successfully conducted in Malaysia. The engineered strain showed similar field longevity to an unmodified counterpart, though in this setting dispersal was reduced relative to the unmodified strain. These data are encouraging for the future testing and implementation of genetic control strategies and will help guide future field use of this and other engineered strains.
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