The heart receives high radiation doses during radiation therapy of advanced-stage lung cancer. We have explored associations between overall survival, cardiac radiation doses, and ...electrocardiographic (ECG) changes in patients treated in IDEAL-CRT, a trial of isotoxically escalated concurrent chemoradiation delivering tumor doses of 63 to 73 Gy.
Dosimetric and survival data were analyzed for 78 patients. The whole heart, pericardium, AV node, and walls of left and right atria (LA/RA-Wall) and ventricles (LV/RV-Wall) were outlined on radiation therapy planning scans, and differential dose-volume histograms (dDVHs) were calculated. For each structure, dDVHs were approximated using the average dDVH and the 10 highest-ranked structure-specific principal components (PCs). ECGs at baseline and 6 months after radiation therapy were analyzed for 53 patients, dichotomizing patients according to presence or absence of “any ECG change” (conduction or ischemic/pericarditis-like change). All-cause death rate (DR) was analyzed from the start of treatment using Cox regression.
38% of patients had ECG changes at 6 months. On univariable analysis, higher scores for LA-Wall-PC6, Heart-PC6, “any ECG change,” and larger planning target volume (PTV) were significantly associated with higher DR (P=.003, .009, .029, and .037, respectively). Heart-PC6 and LA-Wall-PC6 represent larger volumes of whole heart and left atrial wall receiving 63 to 69 Gy. Cardiac doses ≥63 Gy were concentrated in the LA-Wall, and consequently Heart-PC6 was highly correlated with LA-Wall-PC6. “Any ECG change,” LA-Wall-PC6 scores, and PTV size were retained in the multivariable model.
We found associations between higher DR and conduction or ischemic/pericarditis-like changes on ECG at 6 months, and between higher DR and higher Heart-PC6 or LA-Wall-PC6 scores, which are closely related to heart or left atrial wall volumes receiving 63 to 69 Gy in this small cohort of patients.
To develop and validate a psoriatic arthritis (PsA) screening questionnaire: the Toronto Psoriatic Arthritis Screen (ToPAS).
The ToPAS was developed through review of items seen in patients with PsA ...and evaluation by patients with PsA and patients with other rheumatological conditions, and was administered to consecutive consenting patients attending five clinics: PsA, psoriasis, general dermatology, general rheumatology (excluding PsA patients) and family medicine. All patients were assessed by a rheumatologist according to a standard protocol. A three-step analysis strategy was adopted: a stepwise logistic regression to identify the questions most important in discriminating between those with and without PsA; a logistic model was fitted to three clinically relevant domains for PsA: skin, joints and nails; and a simpler weighting of each of the domains used in step 2. Receiver operating characteristic (ROC) curves were obtained based on these various models.
In all, there were 134 patients from the PsA clinic, 123 with psoriasis, 118 from dermatology, 135 from rheumatology and 178 from family medicine. A simplified discriminatory score based on the skin, joint and nail domains gave results comparable to other methods with an observed overall sensitivity and specificity, based on a single cut point, of 86.8% and 93.1%. When the patients with PsA were compared with each of the other four patient groups individually, the sensitivity and specificity of the ToPAS were: psoriasis 89.1%, 86.3%; dermatology 91.9%, 95.2%; rheumatology 92.6%, 85.7%; and family medicine 90.4%, 100%.
Our simplified index is very good at classifying those who are not diagnosed with PsA and those who are diagnosed with PsA.
We report on four radio-detected cosmic-ray (CR) or CR-like events observed with the Antarctic Impulsive Transient Antenna (ANITA), a NASA-sponsored long-duration balloon payload. Two of the four ...were previously identified as stratospheric CR air showers during the ANITA-I flight. A third stratospheric CR was detected during the ANITA-II flight. Here, we report on characteristics of these three unusual CR events, which develop nearly horizontally, 20-30 km above the surface of Earth. In addition, we report on a fourth steeply upward-pointing ANITA-I CR-like radio event which has characteristics consistent with a primary that emerged from the surface of the ice. This suggests a possible τ-lepton decay as the origin of this event, but such an interpretation would require significant suppression of the standard model τ-neutrino cross section.
Imaging CBF is important for managing pediatric moyamoya. Traditional arterial spin-labeling MR imaging detects delayed transit thorough diseased arteries but is inaccurate for measuring perfusion ...because of these delays. Velocity-selective arterial spin-labeling is insensitive to transit delay and well-suited for imaging Moyamoya perfusion. This study assesses the accuracy of a combined velocity-selective arterial spin-labeling and traditional pulsed arterial spin-labeling CBF approach in pediatric moyamoya, with comparison to blood flow patterns on conventional angiography.
Twenty-two neurologically stable pediatric patients with moyamoya and 5 asymptomatic siblings without frank moyamoya were imaged with velocity-selective arterial spin-labeling, pulsed arterial spin-labeling, and DSA (patients). Qualitative comparison was performed, followed by a systematic comparison using ASPECTS-based scoring. Quantitative pulsed arterial spin-labeling CBF and velocity-selective arterial spin-labeling CBF for the middle cerebral artery, anterior cerebral artery, and posterior cerebral artery territories were also compared.
Qualitatively, velocity-selective arterial spin-labeling perfusion maps reflect the DSA parenchymal phase, regardless of postinjection timing. Conversely, pulsed arterial spin-labeling maps reflect the DSA appearance at postinjection times closer to the arterial spin-labeling postlabeling delay, regardless of vascular phase. ASPECTS comparison showed excellent agreement (88%, κ = 0.77,
< .001) between arterial spin-labeling and DSA, suggesting velocity-selective arterial spin-labeling and pulsed arterial spin-labeling capture key perfusion and transit delay information, respectively. CBF coefficient of variation, a marker of perfusion variability, was similar for velocity-selective arterial spin-labeling in patient regions of delayed-but-preserved perfusion compared to healthy asymptomatic sibling regions (coefficient of variation = 0.30 versus 0.26, respectively, Δcoefficient of variation = 0.04), but it was significantly different for pulsed arterial spin-labeling (coefficient of variation = 0.64 versus 0.34, Δcoefficient of variation = 0.30,
< .001).
Velocity-selective arterial spin-labeling offers a powerful approach to image perfusion in pediatric moyamoya due to transit delay insensitivity. Coupled with pulsed arterial spin-labeling for transit delay information, a volumetric MR imaging approach capturing key DSA information is introduced.
Purpose
Wide variation in care and costs exists regarding the management of abdominal wall hernias, with unproven benefit for many therapies. This work establishes a specialty society-based solution ...to improve the quality and value of care delivered to hernia patients during routine clinical management on a national scale.
Methods
The Americas Hernia Society Quality Task Force was charged by the Americas Hernia Society leadership to develop an initiative that utilizes the concepts of continuous quality improvement (CQI). A disease-based registry was created to collect information for CQI incorporating real-time outcome reporting, patient reported outcomes, stakeholder engagement, and collaborative learning methods to form a comprehensive quality improvement effort.
Results
The Americas Hernia Society Quality Collaborative (AHSQC) was formed with the mission to provide health care professionals real-time information for maximizing value in hernia care. The initial disease areas selected for CQI were incisional and parastomal hernias with ten priorities encompassing the spectrum of care. A prospective registry was created with real-time analytic feedback to surgeons. A data assurance process was implemented to ensure maximal data quality and completeness. Four collaborative meetings per year were established to meet the goals of the AHSQC. As of the fourth quarter 2014, the AHSQC includes nearly 2377 patients at 38 institutions with 82 participating surgeons.
Conclusions
The AHSQC has been established as a quality improvement initiative utilizing concepts of CQI. This ongoing effort will continually refine its scope and goals based on stakeholder input to improve care delivered to hernia patients.
Abstract Neuroinflammation is associated with glial activation following a variety of brain injuries, including stroke. While activation of perilesional astrocytes and microglia following ischemic ...brain injury is well documented, the influence of age on these cellular responses after stroke is unclear. This study investigated the influence of advanced age on neuronal degeneration, neuroinflammation, and glial activation in female Sprague–Dawley rats after reversible embolic occlusion of the middle cerebral artery (MCAO). Results indicate that in comparison to young adult rats (3 months), aged rats (18 months) showed enhanced neuronal degeneration, altered microglial response, and a markedly increased expression of proinflammatory cytokines/chemokines following MCAO. In addition, the time-course for activation of signal transducers and activators of transcription 3 (STAT3), the signaling mechanism that regulates astrocyte reactivity, was truncated in the aged rats after MCAO. Moreover, the expression of suppressor of cytokine signaling 3 (SOCS3), which is associated with termination of astrogliosis, was enhanced as a function of age after MCAO. These findings are suggestive of an enhanced proinflammatory response and a truncated astroglial response as a function of advanced age following MCAO. These data provide further evidence of the prominent role played by age in the molecular and cellular responses to ischemic stroke and suggest that astrocytes may represent targets for future therapies aimed at improving stroke outcome.
The cattle reference genome assembly has underpinned major innovations in beef and dairy genetics through genome-enabled selection, including removal of deleterious recessive variants and selection ...for favorable alleles affecting quantitative production traits. The initial reference assemblies, up to and including UMD3.1 and Btau4.1, were based on a combination of clone-by-clone sequencing of bacterial artificial chromosome clones generated from blood DNA of a Hereford bull and whole-genome shotgun sequencing of blood DNA from his inbred daughter/granddaughter named L1 Dominette 01449 (Dominette). The approach introduced assembly gaps, misassemblies, and errors, and it limited the ability to assemble regions that undergo rearrangement in blood cells, such as immune gene clusters. Nonetheless, the reference supported the creation of genotyping tools and provided a basis for many studies of gene expression. Recently, long-read sequencing technologies have emerged that facilitated a re-assembly of the reference genome, using lung tissue from Dominette to resolve many of the problems and providing a bridge to place historical studies in common context. The new reference, ARS-UCD1.2, successfully assembled germline immune gene clusters and improved overall continuity (i.e., reduction of gaps and inversions) by over 250-fold. This reference properly places nearly all of the legacy genetic markers used for over a decade in the industry. In this review, we discuss the improvements made to the cattle reference; remaining issues present in the assembly; tools developed to support genome-based studies in beef and dairy cattle; and the emergence of newer genome assembly methods that are producing even higher-quality assemblies for other breeds of cattle at a fraction of the cost. The new frontier for cattle genomics research will likely include a transition from the individual Hereford reference genome, to a “pan-genome” reference, representing all the DNA segments existing in commonly used cattle breeds, bringing the cattle reference into line with the current direction of human genome research.
Microbial pathogens use a variety of mechanisms to disrupt the actin cytoskeleton during infection. Vibrio parahaemolyticus (V. para) is a Gram-negative bacterium that causes gastroenteritis, and new ...pandemic strains are emerging throughout the world. Analysis of the V. para genome revealed a type III secretion system effector, VopL, encoding three Wiskott-Aldrich homology 2 domains that are interspersed with three proline-rich motifs. Infection of HeLa cells with V. para induces the formation of long actin fibers in a VopL-dependent manner. Transfection of VopL promotes the assembly of actin stress fibers. In vitro, recombinant VopL potently induces assembly of actin filaments that grow at their barbed ends, independent of eukaryotic factors. Vibrio VopL is predicted to be a bacterial virulence factor that disrupts actin homeostasis during an enteric infection of the host.
Men and women use a variety of coping strategies to manage stress associated with infertility. Although previous research has helped us understand these coping processes, questions remain about ...gender differences in coping and the nature of the relationship between coping and specific types of infertility stress. METHODS: This study examined the coping behaviours of 1026 (520 women, 506 men) consecutively referred patients at a University-affiliated teaching hospital. Participants completed the Ways of Coping Questionnaire, Fertility Problem Inventory and the Dyadic Adjustment Scale. RESULTS: Women used proportionately greater amounts of confrontative coping, accepting responsibility, seeking social support and escape/avoidance when compared with men, whereas men used proportionately greater amounts of distancing, self-controlling and planful problem-solving. For men and women, infertility stress was positively related to escape/avoidance and accepting responsibility and negatively related to seeking social support, planful problem-solving and distancing. CONCLUSIONS: By analysing relative coping scores, this study identified key gender differences in how men and women cope with infertility. This was particularly true for men’s coping processes that had previously remained hidden because of less frequent use of coping strategies when compared with women.
Abstract Naked mole-rats are highly social rodents that live in large colonies characterized by a rigid social and reproductive hierarchy. Only one female, the queen, breeds. Most colony members are ...non-reproductive subordinates that work cooperatively to rear the young and maintain an underground burrow system. Little is known about the neurobiological basis of the complex sociality exhibited by this species. The neuropeptide oxytocin (Oxt) modulates social bonding and other social behaviors in many vertebrates. Here we examined the distribution of Oxt immunoreactivity in the brains of male and female naked mole-rats. As in other species, the majority of Oxt-immunoreactive (Oxt-ir) cells were found in the paraventricular and supraoptic nuclei, with additional labeled cells scattered throughout the preoptic and anterior hypothalamic areas. Oxt-ir fibers were found traveling toward and through the median eminence, as well as in the tenia tecta, septum, and nucleus of the diagonal band of Broca. A moderate network of fibers covered the bed nucleus of the stria terminalis and preoptic area, and a particularly dense fiber innervation of the nucleus accumbens and substantia innominata was observed. In the brainstem, Oxt-ir fibers were found in the periaqueductal gray, locus coeruleus, parabrachial nucleus, nucleus of the solitary tract, and nucleus ambiguus. The high levels of Oxt immunoreactivity in the nucleus accumbens and preoptic area are intriguing, given the link in other rodents between Oxt signaling in these regions and maternal behavior. Although only the queen gives birth or nurses pups in a naked mole-rat colony, most individuals actively participate in pup care.
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