Causes and prevention--(i) biomechanics

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/26051/1/0000125.pd

Coil-Assisted Retrograde Transvenous Obliteration (CARTO) for the Treatment of Portal Hypertensive Variceal Bleeding: Preliminary Results.

ObjectivesTo describe the technical feasibility, safety, and clinical outcomes of coil-assisted retrograde transvenous obliteration (CARTO) in treating portal hypertensive non-esophageal variceal hemorrhage.MethodsFrom October 2012 to December 2013, 20 patients who received CARTO for the treatment of portal hypertensive non-esophageal variceal bleeding were retrospectively evaluated. All 20 patients had at least 6-month follow-up. All patients had detachable coils placed to occlude the efferent shunt and retrograde gelfoam embolization to achieve complete thrombosis/obliteration of varices. Technical success, clinical success, rebleeding, and complications were evaluated at follow-up.ResultsA 100% technical success rate (defined as achieving complete occlusion of efferent shunt with complete thrombosis/obliteration of bleeding varices and/or stopping variceal bleeding) was demonstrated in all 20 patients. Clinical success rate (defined as no variceal rebleeding) was 100%. Follow-up computed tomography after CARTO demonstrated decrease in size with complete thrombosis and disappearance of the varices in all 20 patients. Thirteen out of the 20 had endoscopic confirmation of resolution of varices. Minor post-CARTO complications, including worsening of esophageal varices (not bleeding) and worsening of ascites/hydrothorax, were noted in 5 patients (25%). One patient passed away at 24 days after the CARTO due to systemic and portal venous thrombosis and multi-organ failure. Otherwise, no major complication was noted. No variceal rebleeding was noted in all 20 patients during mean follow-up of 384±154 days.ConclusionsCARTO appears to be a technically feasible and safe alternative to traditional balloon-occluded retrograde transvenous obliteration or transjugular intrahepatic portosystemic shunt, with excellent clinical outcomes in treating portal hypertensive non-esophageal variceal bleeding

Lumbar muscle size and locations from CT scans of 96 women of age 40 to 63 years

Computed tomography scans of 96 women aged between 40 and 63 years were systematically measured to determine torso muscle moment arms and cross-sectional areas at L2/L3, L3/L4 and L4/L5 disc levels. The major findings were as follows: (1) the mean muscle moment arm and area data were not different bilaterally; (2) psoas, quadratus lumborum, and latissimus dorsi muscle moment arms consistently changed at the three disc levels, while erector spinae, rectus abdominis, transverse abdominis and the oblique muscles remained about the same distance from the three disc centroids; (3) psoas and quadratus lumborum muscles increased in mean size at the lower levels and (4 gross torso anthropometry and body weight had a significant (P r2 from 0[middle dot]12 to 0[middle dot]65) with the size of the erector spinae and psoas muscles, and with the moment arms of the rectus abdominis, transverse abdominis, latissimus dorsi, and oblique muscles.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/28726/1/0000549.pd

The limitations of canine trabecular bone as a model for human: A biomechanical study

Distal canine femurs were sectioned into 8mm cubic specimens. Orthogonal compression tests were performed to preyield in two or three directions and to failure in a third. Apparent density and ash weight density were measured for a subset of specimens. The results were compared to the human distal femur results of Ciarelli et al. (Transactions of the 32nd Annual Meeting of the Orthopaedic Research Society, Vol. 11, p. 42, 1986). Quantitative similarities existed in the fraction of components comprising the trabecular tissue of the two species. Qualitative similarities were seen in the positional and anisotropic variation of the mechanical properties, and also in the form and strength of the relationships between the mean modulus and bone density, ultimate stress and density, and ultimate stress and modulus. However, significantly different regression equations resulted for the mean modulus-density, and ultimate stress-modulus relationships, indicating that for the same density, canine trabecular bone displays a lower modulus than human, and may achieve greater compressive strains before failure.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/28130/1/0000581.pd

The mechanical properties of human tibial trabecular bone as a function of metaphyseal location

Experimental determination of the elastic modulus and ultimate strength of human tibial trabecular bone as a function of metaphyseal location is presented.A 1 cm cubic matrix with planes parallel to the subchondral plate was defined on five fresh frozen cadaver tibias. Approximately 400, 7 mm x 10 mm cylindrical bone plugs were cut from the locations defined by the matrix and tested in uniaxial compressive stress at a strain rate of 0.1%s-1. Results of the study indicate that the trabecular bone properties vary as much as two orders of magnitude from one location to another. As might be predicted from Wolff's law, and noted by previous investigators, concentrations of strength arise from the medial and lateral metaphyseal cortices toward the major medial and lateral contact regions.These results may be valuable for improved analytical modeling and optimal prosthetic design.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/25447/1/0000897.pd

Trabecular bone remodeling: An experimental model

An experimental model, capable of inducing controlled stress fields to the distal femoral metaphyses of large dogs, is presented. This model utilized an implantable hydraulic device incorporating five loading cylinders and platens in direct contact with an exposed plane of trabecular bone. A microprocessor controls the loading characteristics, and finite element models were created to calculate the induced stress and strain fields. The trabecular remodeling response is measured using serial in vivo computed tomography, in vitro microcomputed tomography, and histologic analysis. The results of the experiment indicate that significant remodeling can be induced by the activated implant. An increase in trabecular orientation toward the loaded platens was observed, and a statistically significant decrease in connectivity was documented. The greatest effect was associated with a change in the loading rate. A fast rise time (70 ms) loading waveform induced significant bone ingrowth at the implant interface when compared to a slow rise time waveform (700 ms), and demonstrated high correlations with the calculated stress fields as remodeling approached an equilibrium state.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29555/1/0000643.pd

Analysis of cumulative strain in tendons and tendon sheaths

Twenty-five fresh frozen flexor digitorum profundus tendons stratified by sex were subjected to uniaxial step stress and cyclic loads in twelve intact human cadaver hands. By attaching specially designed clip strain gage transducers on tendons just proximal and distal to an undisrupted carpal tunnel, the interactions of the tendons, tendon sheath and retinacula were measured.The elastic and viscous response of the tendon composites to step stresses were found to fit fractional power functions of stress and time respectively. A significant and quantifiable decrease in strain from the proximal to the distal tendon segment was found to be a function of wrist deviation.The results indicate that an accumulation of strain does occur in tendinous tissues during physiologic loading.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/26842/1/0000402.pd

Evolution of Li, Be and B in the Galaxy

In this paper we study the production of Li, Be and B nuclei by Galactic cosmic ray spallation processes. We include three kinds of processes: (i) spallation by light cosmic rays impinging on interstellar CNO nuclei (direct processes); (ii) spallation by CNO cosmic ray nuclei impinging on interstellar p and 4He (inverse processes); and (iii) alpha-alpha fusion reactions. The latter dominate the production of 6Li and 7Li. We calculate production rates for a closed-box Galactic model, verifying the quadratic dependence of the Be and B abundances for low values of Z. These are quite general results and are known to disagree with observations. We then show that the multi-zone multi-population model we used previously for other aspects of Galactic evolution produces quite good agreement with the linear trend observed at low metallicities without fine tuning. We argue that reported discrepancies between theory and observations do not represent a nucleosynthetic problem, but instead are the consequences of inaccurate treatments of Galactic evolution.Comment: 26 pages, 5 figures, LaTeX. The Astrophysical Journal, in pres

In Vivo Emergence of a Novel Protease Inhibitor Resistance Signature in HIV-1 Matrix.

Protease inhibitors (PIs) are the second- and last-line therapy for the majority of HIV-infected patients worldwide. Only around 20% of individuals who fail PI regimens develop major resistance mutations in protease. We sought to explore the role of mutations in gag-pro genotypic and phenotypic changes in viruses from six Nigerian patients who failed PI-based regimens without known drug resistance-associated protease mutations in order to identify novel determinants of PI resistance. Target enrichment and next-generation sequencing (NGS) with the Illumina MiSeq system were followed by haplotype reconstruction. Full-length Gag-protease gene regions were amplified from baseline (pre-PI) and virologic failure (VF) samples, sequenced, and used to construct gag-pro-pseudotyped viruses. Phylogenetic analysis was performed using maximum-likelihood methods. Susceptibility to lopinavir (LPV) and darunavir (DRV) was measured using a single-cycle replication assay. Western blotting was used to analyze Gag cleavage. In one of six participants (subtype CRF02_AG), we found 4-fold-lower LPV susceptibility in viral clones during failure of second-line treatment. A combination of four mutations (S126del, H127del, T122A, and G123E) in the p17 matrix of baseline virus generated a similar 4-fold decrease in susceptibility to LPV but not darunavir. These four amino acid changes were also able to confer LPV resistance to a subtype B Gag-protease backbone. Western blotting demonstrated significant Gag cleavage differences between sensitive and resistant isolates in the presence of drug. Resistant viruses had around 2-fold-lower infectivity than sensitive clones in the absence of drug. NGS combined with haplotype reconstruction revealed that resistant, less fit clones emerged from a minority population at baseline and thereafter persisted alongside sensitive fitter viruses. We used a multipronged genotypic and phenotypic approach to document emergence and temporal dynamics of a novel protease inhibitor resistance signature in HIV-1 matrix, revealing the interplay between Gag-associated resistance and fitness