The Oregon Wolfe Barley mapping population is a resource for genetics research and instruction. Prior reports are based on a population of doubled haploid (DH) lines developed by the
Hordeum bulbosum
...(H.b.) method, which samples female gametes. We developed new DH lines from the same cross using anther culture (A.C.), which samples male gametes. Linkage maps were generated in each of the two subpopulations using the same 1,328 single nucleotide polymorphism markers. The linkage maps based on DH lines derived from the products of megasporogeneis and microsporogenesis revealed minor differences in terms of estimated recombination rates. There were no differences in locus ordering. There was greater segregation distortion in the A.C.-derived subpopulation than in the H.b.-derived subpopulation, but in the region showing the greatest distortion, the cause was more likely allelic variation at the
ZEO1
plant height locus rather than to DH production method. The effects of segregation distortion and pleiotropy had greater impacts on estimates of quantitative trait locus effect than population size for reproductive fitness traits assayed under greenhouse conditions. The Oregon Wolfe Barley (OWB) population and data are community resources. Seed is available from three distribution centers located in North America, Europe, and Asia. Details on ordering seed sets, as well as complete genotype and phenotype data files, are available at
http://wheat.pw.usda.gov/ggpages/maps/OWB/
.
Abstract Impulsivity and sensation seeking have been associated with substance use disorders, including opioid use disorders. This pilot study sought to examine whether impulsivity and sensation ...seeking, as measured by the Barratt Impulsiveness Scale (BIS) and Sensation Seeking Scale (SSS), were associated with opioid analgesic misuse risk in chronic, low-back pain patients prescribed opioid analgesics. Participants were 42 chronic, low-back pain patients enrolled in a larger study examining problematic opioid analgesic use. Impulsivity was assessed using the BIS, sensation seeking was measured using the SSS, and opioid analgesic misuse risk was assessed using the Current Opioid Misuse Measure (COMM). Significant bivariate associations were found between the COMM and the following predictor variables: age and the three BIS subscales: Attentional Impulsiveness, Non-planning Impulsiveness, and Motor Impulsiveness. Using a multivariate linear regression, after controlling for age, the BIS subscales accounted for 29.0% of the variance in the COMM. Attentional Impulsiveness was the only significant BIS subscale. These results suggest a potential relationship between impulsivity, but not sensation seeking, and risk for opioid analgesic misuse. Impulsivity is not a prominent trait observed in chronic pain patients; however, it may be an important risk factor for opioid analgesic misuse for a subset of individuals with chronic pain. As such, these findings suggest that additional exploration of this potential risk factor is warranted.
Abstract Background and aims A 12‐week placebo‐controlled, sequential parallel Accelerated Development of Additive Pharmacotherapy Treatment for Methamphetamine Use Disorder (ADAPT‐2) trial evaluated ...the effects of extended‐release injectable naltrexone plus extended‐release oral bupropion (NTX + BUPN) on methamphetamine (MA) use over two stages. This study reports on the previously unpublished stage 2 MA use in participants randomized at stage 1 to receive NTX + BUPN through both stages compared with those assigned to placebo. Design This is a secondary analysis of the US National Institute on Drug Abuse (NIDA) ADAPT‐2 network trial. Setting The parent ADAPT‐2 trial was carried out across multiple NIDA Clinical Trials Network (CTN) sites in the United States. Participants This analysis includes 403 people with MA use disorder who participated in the ADAPT‐2 CTN trial. Intervention and comparator NTX + BUPN was compared with placebo over the course of the trial. Measurement MA use was measured by urine drug screens conducted twice weekly for 12 weeks, then once in week 13 and once in week 16 post‐treatment follow‐up. Findings Participants on NTX + BUPN in stage 1 showed an additional 9.2% increase 95% confidence interval (CI), 0.09%–17.9%, P = 0.038 during stage 2 in their probability of testing negative for MA, with a total increase of 27.1% (95% CI, 13.2%–41.1%, P < 0.001) over the full 12 weeks of treatment. In contrast, participants on placebo in both stages increased in probability of testing MA‐negative by a total of 11.4% (95% CI, 4.1%–18.6%, P = 0.002) over all 12 weeks. The 12‐week increase among participants on NTX + BUPN was significantly greater—by 15.8% (95% CI, 4.5%–27.0%, P = 0.006)—than the increase among those on placebo. Conclusion For people with methamphetamine (MA) use disorder receiving treatment with extended‐release injectable naltrexone plus extended‐release oral bupropion (NTX + BUPN), continued treatment with NTX + BUPN after 6 weeks is associated with additional reductions in MA use up to 12 weeks.
The purpose of this study was to investigate whether post-ischemic left ventricular (LV) remodeling might be induced by regional contractile dysfunction per se (i.e., in the absence of transmural ...necrosis) and whether this phenomenon is potentially reversible after contractile recovery.
Formation of extensive scar tissue is thought to be chiefly responsible for post-infarction LV remodeling; however, myocardial necrosis also causes loss of contractility. We investigated LV geometry and shape in a setting in which contractile dysfunction occurs in the presence of preserved myocyte viability, and thus it is potentially reversible.
In 42 patients with chronically dysfunctional myocardium, we evaluated (by two-dimensional echocardiography) LV global and regional function, volumes, and sphericity index (SI), at baseline and 8 +/- 3 months after coronary revascularization. Myocardial viability before revascularization was evaluated by dobutamine echocardiography.
At baseline, regional and global function were depressed and LV dilation was present. Revascularization was followed by recovery of ejection fraction (from 33 +/- 6% to 45 +/- 10%, p < 0.0001) and wall motion score index (from 2.29 +/- 0.31 to 1.74 +/- 0.42, p < 0.0001). After revascularization, significant improvement of end-systolic volume index (from 78 +/- 23 ml/m2 to 56 +/- 23 ml/m2, p < 0.0001), end-diastolic volume index (from 118 +/- 26 ml/m2 to 99 +/- 26 ml/m2, p < 0.0001), and SI (from 0.69 +/- 0.14 to 0.52 +/- 0.11, p < 0.0001) was also observed. Improvement in LV volumes and SI were significantly correlated to the number of segments recovering function after revascularization.
Hibernating myocardium is associated with major alterations in LV volumes and shape, which significantly revert after revascularization. Thus, chronic dyssynergy per se is sufficient to induce ischemic LV remodeling in patients.
Full in-beam PET measurements of 62 MeV protons onto a PMMA target Sportelli, G; Straub, K; Aiello, M ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
08/2013, Letnik:
718
Journal Article
Recenzirano
Positron emission tomography (PET) is a valuable technique to monitor in situ and non-invasively the particle range in ion beam therapy exploiting the beta+ activity produced in nuclear interactions ...along the beam path within the target volume. Due to the high random rates and dead-time losses induced by the particle spills, as of to date data are usually acquired during beam pauses or after the irradiation. We have developed a new PET prototype with a faster photon discrimination component that reduces the front-end dead time, and a modularized acquisition system that parallelizes the sensitive detector area, so as to enable data acquisition also during therapeutic irradiation (full in-beam measurement). The PET system has been able to sustain the single photon count rates and acquire coincidences during the beam, in conditions of sub-clinical beam currents. A study on the paralyzation conditions and dead time losses under different beam currents is presented and the feasibility of a full in-beam PET scanner is discussed.
An innovative detector concept for hybrid 4D-PET/MRI imaging Cerello, P.; Pennazio, F.; Bisogni, M.G. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
02/2013, Letnik:
702
Journal Article
Recenzirano
The importance of a high-quality hybrid imaging, providing morphological and functional information with only one acquisition session, is widely acknowledged by the scientific community. The ...historical limitations to the quality of PET images are related to the unsatisfactory measurement of the depth of interaction (DOI) in the crystals and of the time of flight (TOF), that cause a parallax error and an unfavorable signal to background condition in the image reconstruction process, respectively. The 4DMPET project is developing a high performance PET block-detector featuring 4D image reconstruction capabilities. The detector module is based on a fast scintillating continuous crystal coupled on both sides to arrays of Silicon PhotoMultipliers (SiPM). The SiPMs collect the scintillation light and provide the trigger signal, the time and the energy released in the crystal at the pixel level. The photon depth of interaction (DOI) is reconstructed by measuring the cluster size asymmetry on the two faces of the crystal, thus obtaining a comparable spatial resolution in the three coordinates and removing the parallax error. The event position along the line of response can be measured with high precision by means of TOF techniques. We discuss the module design concept and the results of the detailed Monte Carlo detector simulation, which inspire the architectural solutions selected for the layout and the front-end The expected resolution for 3D spatial coordinates of the interaction point in the crystal (1mm) and the TOF (about 110ps) would provide a substantial improvement of the image quality. 4DMPET aims at building a prototype block detector demonstrating that the proposed layout meets the expected performance and is suitable for designing a detector focused on a specific application.
The azoxymethane (AOM)-induced mouse colon tumor model recapitulates many of the histopathological features associated with the multistage progression of human sporadic colorectal cancers (CRCs). To ...better define the genetic events associated with tumorigenesis in this murine model, we analysed tumors from A/J mice for chromosomal (CIN) and microsatellite (MSI) instabilities, two fundamental pathways of genomic instability that play a critical role in the pathogenesis of human CRCs. Male A/J mice, 6-week old, were injected with either AOM (n=5) (10 mg/kg b.w., i.p.) or vehicle (n=5) (0.9% NaCl solution) once a week for 6 weeks. At 32 weeks after the last dose, comparative genomic hybridization (CGH) was performed on 16 tumors harvested from five animals. Although 25% of the tumors displayed either a gain of chromosome 2 or loss of Y, the majority (75%) showed no genomic imbalances. Further analysis of chromosomal aberrations, using CGH and spectral karyotyping (SKY) was performed in our recently established A/J colon tumor-derived cell line, AJ02-NM0. Results showed a pseudotetraploid karyotype with loss of only the Y chromosome in these cultured cells, thereby providing additional evidence for the minimal role of CIN in the primary AOM-induced tumors. Interestingly, the majority (81%) of A/J tumors displayed low-level microsatellite instability (MSI-L) when analysed using mono- and dinucleotide repeat markers, and showed a significant expansion to high-level instability (MSI-H) in the AJ02-NM0 cells. This finding in cultured cells additionally provides evidence that a mild mutator pathway may contribute to the development of behaviorally benign carcinomas in situ in A/J mice. To better understand the tumorigenic process in the A/J colons, we screened for mutational alterations in key regions of the K-ras and Apc genes. Results showed a very low frequency (6%) of K-ras activating mutations, together with the absence of Apc truncation mutations in primary tumors and AJ02-NM0 cells. However, these tumors displayed intense nuclear accumulation of beta-catenin protein, indicating activation of the Wnt signaling pathway. Based on our molecular and cytogenetic findings, we propose that carcinogen-induced tumors may develop via mechanisms independent of the 'classical' CIN or MSI pathways.
...the atrial cavity has, in the past, been assigned the minimalistic role of a ‘transit chamber’, devoted exclusively to collecting and redirecting the reflux blood from the pulmonary district ...towards the systemic circulation. Left atrial cavity, in fact, is intimately related to ventricular function throughout the whole cardiac cycle.1 During ventricular systole, longitudinal fibre shortening forces the descent of the cardiac base, contributing to atrial filling from the pulmonary veins2 while, during diastole, the atrium passively and actively contributes to ventricular filling. Since the cavity, during early and mid-diastole, is directly exposed to the ventricular pressure through the open mitral valve, the atrial emptying pattern is obviously strongly influenced by the left heart diastolic properties.3 Atrial function can be best described by the relation between pressure and volume.4 Gathering this information, however, implies the use of a high-fidelity pressure catheter in the atrial chamber, a manoeuvre that is not performed routinely nowadays in clinical practice. Because cardiac MRI availability is limited, we employed 3D echocardiography to acquire complete and simultaneous left atrial and ventricular full-volume datasets to characterise the volume of both left-sided cardiac chambers at each time point during the cardiac cycle in order to quantify LACV (figure 1, modified from ref 8). Furthermore, those authors noticed that left atrioventricular coupling was impaired and chamber atrial compliance was reduced, in association with lower ventricular stroke volume. ...impaired atrial compliance could provide a plausible mechanism for the observed deranged atrial conduit strain and compromised peak VO2max in the Von Roeder’s study,19 advancing the concept of an early intrinsic atrial myopathy in the genesis of HFpEF.20 Atrial stiffness and its role in heart failure The physiological significance of atrial stiffness is not completely understood, but some indirect evidence does suggest that it is important in haemodynamics.
PDF
