Utility of Plasma Protein Biomarkers and Mid-Infrared Spectroscopy for Diagnosing Fracture-Related Infections: A Pilot Study.

OBJECTIVES: To compare a large panel of plasma protein inflammatory biomarkers and mid-infrared (MIR) spectral patterns between patients with confirmed fracture related infections (FRIs) and controls without infection. DESIGN: Prospective case-control. SETTING: Academic, level 1 trauma center. PATIENTS: Thirteen patients meeting confirmatory FRI criteria were matched to 13 controls based on age, time after surgery, and fracture region. INTERVENTION: Plasma levels of 49 proteins were measured using enzyme-linked immunosorbent assay (ELISA) techniques. Fourier transform infrared (FTIR) spectroscopy of dried films was used to obtain MIR spectra of plasma samples. MAIN OUTCOME MEASUREMENTS: Plasma protein levels and MIR spectra of samples. RESULTS: Multivariate analysis-based predictive model developed utilizing ELISA-based biomarkers had sensitivity, specificity, and accuracy of 69.2±0.0%, 99.9±1.0%, and 84.5±0.6%, respectively, with PDGF-AB/BB, CRP, and MIG selected as the minimum number of variables explaining group differences (P CONCLUSIONS: This pilot study demonstrates the feasibility of using a select panel of plasma proteins and FTIR spectroscopy to diagnose FRI. The preliminary data suggest that measurement of these select proteins and MIR spectra may be potential clinical tools to detect FRI. Further investigation of these biomarkers in a larger cohort of patients is warranted. LEVEL OF EVIDENCE: Diagnostic Level III. See Instructions for Authors for a complete description of levels of evidence

Discovering joint associations between disease and gene pairs with a novel similarity test

Genes in a functional pathway can have complex interactions. A gene might activate or suppress another gene, so it is of interest to test joint associations of gene pairs. To simultaneously detect the joint association between disease and two genes (or two chromosomal regions), we propose a new test with the use of genomic similarities. Our test is designed to detect epistasis in the absence of main effects, main effects in the absence of epistasis, or the presence of both main effects and epistasis. Results: The simulation results show that our similarity test with the matching measure is more powerful than the Pearson's chi(2) test when the disease mutants were introduced at common haplotypes, but is less powerful when the disease mutants were introduced at rare haplotypes. Our similarity tests with the counting measures are more sensitive to marker informativity and linkage disequilibrium patterns, and thus are often inferior to the similarity test with the matching measure and the Pearson 's chi(2) test. Conclusions: In detecting joint associations between disease and gene pairs, our similarity test is a complementary method to the Pearson's chi(2) test

Deformation-related volcanism in the Pacific Ocean linked to the Hawaiian-Emperor bend

Ocean islands, seamounts and volcanic ridges are thought to form above mantle plumes. Yet, this mechanism cannot explain many volcanic features on the Pacific Ocean floor and some might instead be caused by cracks in the oceanic crust linked to the reorganization of plate motions. A distinctive bend in the Hawaiian–Emperor volcanic chain has been linked to changes in the direction of motion of the Pacific Plate, movement of the Hawaiian plume, or a combination of both. However, these links are uncertain because there is no independent record that precisely dates tectonic events that affected the Pacific Plate. Here we analyse the geochemical characteristics of lava samples collected from the Musicians Ridges, lines of volcanic seamounts formed close to the Hawaiian–Emperor bend. We find that the geochemical signature of these lavas is unlike typical ocean island basalts and instead resembles mid-ocean ridge basalts. We infer that the seamounts are unrelated to mantle plume activity and instead formed in an extensional setting, due to deformation of the Pacific Plate. 40Ar/39Ar dating reveals that the Musicians Ridges formed during two time windows that bracket the time of formation of the Hawaiian–Emperor bend, 53–52 and 48–47 million years ago. We conclude that the Hawaiian–Emperor bend was formed by plate–mantle reorganization, potentially triggered by a series of subduction events at the Pacific Plate margins

Earthquake source parameters and scaling relationships in Hungary (central Pannonian basin)

Abstract Fifty earthquakes that occurred in Hungary (central part of the Pannonian basin) with local magnitude ML ranging from 0.8 to 4.5 have been analyzed. The digital seismograms used in this study were recorded by six permanent broad-band stations and twenty short-period ones at hypocentral distances between 10 and 327 km. The displacement spectra for P- and SH-waves were analyzed according to Brune’s source model. Observed spectra were corrected for path-dependent attenuation effects using an independent regional estimate of the quality factor QS. To correct spectra for near-surface attenuation, the k parameterwas calculated, obtaining it fromwaveforms recorded at short epicentral distances. The values of the k parameter vary between 0.01 to 0.06 s with a mean of 0.03 s for P-waves and between 0.01 to 0.09 s with a mean of 0.04 s for SH-waves. After correction for attenuation effects, spectral parameters (corner frequency and low-frequency spectral level) were estimated by a grid search algorithm. The obtained seismic moments range from4.21×1011 to 3.41×1015 Nm (1.7≤Mw ≤4.3). The source radii are between 125 and 1343 m. Stress drop values vary between 0.14 and 32.4 bars with a logarithmic mean of 2.59 bars (1 bar = 105 Pa). From the results, a linear relationship between local andmomentmagnitudes has been established. The obtained scaling relations show slight evidence of self-similarity violation. However, due to the high scatter of our data, the existence of self-similarity cannot be excluded

Robustness and uncertainties in global multivariate wind-wave climate projections

Understanding climate-driven impacts on the multivariate global wind-wave climate is paramount to effective offshore/coastal climate adaptation planning. However, the use of single-method ensembles and variations arising from different methodologies has resulted in unquantified uncertainty amongst existing global wave climate projections. Here, assessing the first coherent, community-driven, multi-method ensemble of global wave climate projections, we demonstrate widespread ocean regions with robust changes in annual mean significant wave height and mean wave period of 5–15% and shifts in mean wave direction of 5–15°, under a high-emission scenario. Approximately 50% of the world’s coastline is at risk from wave climate change, with ~40% revealing robust changes in at least two variables. Furthermore, we find that uncertainty in current projections is dominated by climate model-driven uncertainty, and that single-method modelling studies are unable to capture up to ~50% of the total associated uncertainty

Dia2 Controls Transcription by Mediating Assembly of the RSC Complex

Background: Dia2 is an F-box protein found in the budding yeast, S. cerevisiae. Together with Skp1 and Cul1, Dia2 forms the substrate-determining part of an E3 ubiquitin ligase complex, otherwise known as the SCF. Dia2 has previously been implicated in the control of replication and genome stability via its interaction with the replisome progression complex. Principal Findings: We identified components of the RSC chromatin remodelling complex as genetic interactors with Dia2, suggesting an additional role for Dia2 in the regulation of transcription. We show that Dia2 is involved in controlling assembly of the RSC complex. RSC belongs to a group of ATP-dependent nucleosome-remodelling complexes that controls the repositioning of nucleosomes. The RSC complex is expressed abundantly and its 17 subunits are recruited to chromatin in response to both transcription activation and repression. In the absence of Dia2, RSC-mediated transcription regulation was impaired, with concomitant abnormalities in nucleosome positioning. Conclusions: Our findings imply that Dia2 is required for the correct assembly and function of the RSC complex. Dia2, by controlling the RSC chromatin remodeller, fine-tunes transcription by controlling nucleosome positioning during transcriptional activation and repression

DONSON and FANCM associate with different replisomes distinguished by replication timing and chromatin domain

Eukaryotic replisomes are multiprotein complexes. Here the authors reveal two distinct stressed replisomes, associated with DONSON and FANCM, displaying a bias in replication timing and chromatin domain

Future oriented group training for suicidal patients: a randomized clinical trial

<p>Abstract</p> <p>Background</p> <p>In routine psychiatric treatment most clinicians inquire about indicators of suicide risk, but once the risk is assessed not many clinicians systematically focus on suicidal thoughts. This may reflect a commonly held opinion that once the depressive or anxious symptoms are effectively treated the suicidal symptoms will wane. Consequently, many clients with suicidal thoughts do not receive systematic treatment of their suicidal thinking. There are many indications that specific attention to suicidal thinking is necessary to effectively decrease the intensity and recurrence of suicidal thinking. We therefore developed a group training for patients with suicidal thoughts that is easy to apply in clinical settings as an addition to regular treatment and that explicitly focuses on suicidal thinking. We hypothesize that such an additional training will decrease the frequency and intensity of suicidal thinking.</p> <p>We based the training on cognitive behavioural approaches of hopelessness, worrying, and future perspectives, given the theories of Beck, McLeod and others, concerning the lack of positive expectations characteristic for many suicidal patients. In collaboration with each participant in the training individual positive future possibilities and goals were challenged.</p> <p>Methods/Design</p> <p>We evaluate the effects of our program on suicide ideation (primary outcome measure). The study is conducted in a regular treatment setting with regular inpatients and outpatients representative for Dutch psychiatric treatment settings. The design is a RCT with two arms: TAU (Treatment as Usual) versus TAU plus the training. Follow up measurements are taken 12 months after the first assessment.</p> <p>Discussion</p> <p>There is a need for research on the effectiveness of interventions in suicidology, especially RCT's. In our treatment program we combine aspects and interventions that have been proven to be useful in the treatment of suicidal thinking and behavior.</p> <p>Trial registration</p> <p>ISRCTN56421759</p