230 research outputs found
Predictors of adolescents’ consent to use health records for research and results from data collection in a Swedish twin cohort
INTRODUCTION: Non-random selection into a study population due to differences
between consenters and non-consenters may introduce participation bias. Past
investigations of factors predicting consent to collection of medical health
records for research imply that age, sex, health status, and education are of
importance for participation, but disagree on the direction of effects. Very
little is known about influences on consent from adolescents. METHODS: Two
cohorts of Swedish 15-year-old twins (total n = 4,611) previously invited to the
Child and Adolescent Twin Study in Sweden (CATSS) responded to a questionnaire
with information on sex, individual's health, height, weight, and parental
factors. The questionnaire included a question for consent to collection of
medical health records. Predictors for consent were analyzed using logistic
regression. Additionally, regional differences in the collection of health
records of consenters were evaluated. RESULTS: Males were significantly less
likely to consent compared to females (OR 0.74, 95% CI 0.64-0.85). The twin
siblings' decision to consent was strongly associated with consent (OR 10.9, 95%
CI 8.76-13.5), and individuals whose parents had responded to the original CATSS
study were more likely to consent to record collection at age 15 (OR 2.2, 95% CI
1.81-2.75). Results of the subsequent collection of consenters' medical health
records varied between geographical regions of Sweden. CONCLUSION: We identified
several predictors for adolescents' consent to collection of their medical health
records. Further selection was introduced through the subsequent record
collection. Whether this will induce participation bias in future studies depends
on the research questions' relationship to the identified predictors.NoneAccepte
First-principle solubilities of alkali and alkaline earth metals in Mg-B alloys
By devising a novel framework, we present a comprehensive theoretical study
of solubilities of alkali (Li, Na, K, Rb, Cs) and alkaline earth (Be, Ca, Sr,
Ba) metals in the he boron-rich Mg-B system. The study is based on
first-principle calculations of solutes formation energies in MgB, MgB,
MgB alloys and subsequent statistical-thermodynamical evaluation of
solubilities. The advantage of the approach consists in considering all the
known phase boundaries in the ternary phase diagram. Substitutional Na, Ca, and
Li demonstrate the largest solubilities, and Na has the highest (0.5-1 % in
MgB at K). All the considered interstitials have negligible
solubilities. The solubility of Be in MgB can not be determined because the
corresponding low-solubility formation energy is negative indicating the
existence of an unknown ternary ground state. We have performed a
high-throughput search of ground states in binary Mg-B, Mg-, and B-
systems, and we construct the ternary phase diagrams of Mg-B- alloys based
on the stable binary phases. Despite its high temperature observations, we find
that SrMg is not a low-temperature equilibrium structure. We also
determine two new possible ground states CaB and RbB, not yet
observed experimentally.Comment: 5 figure
Viral Perturbations of Host Networks Reflect Disease Etiology
Many human diseases, arising from mutations of disease susceptibility genes (genetic diseases), are also associated with viral infections (virally implicated diseases), either in a directly causal manner or by indirect associations. Here we examine whether viral perturbations of host interactome may underlie such virally implicated disease relationships. Using as models two different human viruses, Epstein-Barr virus (EBV) and human papillomavirus (HPV), we find that host targets of viral proteins reside in network proximity to products of disease susceptibility genes. Expression changes in virally implicated disease tissues and comorbidity patterns cluster significantly in the network vicinity of viral targets. The topological proximity found between cellular targets of viral proteins and disease genes was exploited to uncover a novel pathway linking HPV to Fanconi anemia
Tuning microtubule dynamics to enhance cancer therapy by modulating FER-mediated CRMP2 phosphorylation
Though used widely in cancer therapy, paclitaxel only elicits a response in a fraction of patients. A strong determinant of paclitaxel tumor response is the state of microtubule dynamic instability. However, whether the manipulation of this physiological process can be controlled to enhance paclitaxel response has not been tested. Here, we show a previously unrecognized role of the microtubule-associated protein CRMP2 in inducing microtubule bundling through its carboxy terminus. This activity is significantly decreased when the FER tyrosine kinase phosphorylates CRMP2 at Y479 and Y499. The crystal structures of wild-type CRMP2 and CRMP2-Y479E reveal how mimicking phosphorylation prevents tetramerization of CRMP2. Depletion of FER or reducing its catalytic activity using sub-therapeutic doses of inhibitors increases paclitaxel-induced microtubule stability and cytotoxicity in ovarian cancer cells and in vivo. This work provides a rationale for inhibiting FER-mediated CRMP2 phosphorylation to enhance paclitaxel on-target activity for cancer therapy
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