Pathologic Features of the Intervertebral Disc in Young Nova Scotia Duck Tolling Retrievers Confirms Chondrodystrophy Degenerative Phenotype Associated With Genotype.

Chondrodystrophy results in predictable and progressive biochemical and structural changes to the intervertebral disc, resulting in early onset degeneration and dystrophic mineralization of the disc. Accelerated degeneration and mineralization of the intervertebral disc are common in multiple dog breeds and can result in compromised function, herniation, pain, and a variety of neurological sequelae. A mutation responsible for chondrodystrophy in dogs has been identified as an aberrant fibroblast growth factor 4 (FGF4) retrogene insertion on chromosome 12 (CFA12) and is associated with short stature of the Nova Scotia Duck Tolling Retriever. Segregation of the CFA12 FGF4 retrogene in this dog breed provides an opportunity to examine the effect of retrogene presence on radiographic and histologic appearance of chondrodystrophic disc degeneration within a single breed. Here we found that in the intervertebral discs isolated from 2 dogs with the CFA12 FGF4 genotype, the nucleus pulposus was largely replaced by cartilaginous tissue, and physaliferous notochordal cells were rarely if ever identified. These findings are in contrast to the normal histologic findings in 2 breed-matched dogs lacking the mutation. The findings are consistent with premature chondroid degeneration of the intervertebral disc and suggest that the presence of the CFA12 FGF4 retrogene is sufficient to cause the chondrodystrophic phenotype

Group cognitive analytic music therapy: a quasi-experimental feasibility study conducted in a high secure hospital

This study conducted a feasibility patient preference quasi-experimental study of group cognitive analytic music therapy (G-CAMT) for mentally disordered offenders. Participants either chose or were randomised to 16 sessions of manualised G-CAMT (N = 10) plus treatment as usual (TAU) or TAU alone (N = 10). Self-rated and staff-rated outcomes were assessed at baseline, post-intervention and 8-weeks post-intervention. Residency was assessed at 2-year follow-up. Results indicate that G-CAMT was easily implemented; 9/10 participants completed G-CAMT and attendees had high satisfaction with the approach. Session attendance was high; 4/10 participants attended all sessions. At the 8-week follow-up, 3/9 G-CAMT participants had reliable reductions (i.e. statistically reliable pre to 8-week follow-up change results) in intrusive/possessive behaviours and fear of separation/abandonment. On the staff-rated outcome measure G-CAMT participants as a group were statistically significantly friendlier compared to TAU at 8-week follow-up (U = 0.50, p = 0.009, d = 1.92, CI 0.44 to 3.11). There were no differences between the arms in terms of residency outcomes at 2-year follow-up. The study is discussed in terms of G-CAMT’s theoretical grounding and high acceptability. The study is limited by its small sample size, but indicates the possibility of progressing onto a full trial

The C-Band All-Sky Survey: Instrument design, status, and first-look data

The C-Band All-Sky Survey (C-BASS) aims to produce sensitive, all-sky maps of diffuse Galactic emission at 5 GHz in total intensity and linear polarization. These maps will be used (with other surveys) to separate the several astrophysical components contributing to microwave emission, and in particular will allow an accurate map of synchrotron emission to be produced for the subtraction of foregrounds from measurements of the polarized Cosmic Microwave Background. We describe the design of the analog instrument, the optics of our 6.1 m dish at the Owens Valley Radio Observatory, the status of observations, and first-look data.Comment: 10 pages, 11 figures, published in Proceedings of SPIE MIllimeter, Submillimeter, and Far-Infrared Detectors and Instrumentation for Astronomy V (2010), Vol. 7741, 77411I-1 - 77411I-1

A blind test of photometric redshift prediction

Results of a blind test of photometric redshift predictions against spectroscopic galaxy redshifts obtained in the Hubble Deep Field with the Keck Telescope are presented. The best photometric redshift schemes predict spectroscopic redshifts with a redshift accuracy of |Delta-z|<0.1 for more than 68 percent of sources and with |Delta-z|<0.3 for 100 percent, when single-feature spectroscopic redshifts are removed from consideration. This test shows that photometric redshift schemes work well at least when the photometric data are of high quality and when the sources are at moderate redshifts.Comment: 14 pp., accepted for publication in A

Durable Response After Tisagenlecleucel in Adults With Relapsed/Refractory Follicular Lymphoma: ELARA Trial Update

Tisagenlecleucel is approved for adults with relapsed/refractory (r/r) follicular lymphoma (FL) in the ≥3rd-line setting. The primary analysis (median follow-up: 17 months) of the Phase II ELARA trial (ClinicalTrials.gov identifier: NCT03568461) reported high response rates and excellent safety profile in extensively pretreated patients with r/r FL. Here we report longer-term efficacy, safety, pharmacokinetic, and exploratory biomarker analyses after a median follow-up of 29 months. As of March 29, 2022, 97 patients with r/r FL (grades 1-3A) after ≥2 lines of therapy or who relapsed after autologous stem cell transplant received tisagenlecleucel infusion (0.6-6×108 CAR+ viable T cells). Bridging chemotherapy was allowed. Baseline clinical factors, tumor microenvironment (TME), blood soluble factors, and circulating blood cells were correlated with clinical response. Cellular kinetics were assessed by quantitative polymerase chain reaction. Median progression-free survival (PFS), duration of response (DOR), and overall survival (OS) were not reached after 29 months median follow-up (IQR, 22.2-37.7). Estimated 24-month PFS, DOR, and OS rates in all patients were 57.4% (95% CI, 46.2-67), 66.4% (95% CI, 54.3-76), and 87.7% (95% CI, 78.3-93.2). Complete response rate and overall response rate were 68.1% (95% CI, 57.7-77.3) and 86.2% (95% CI, 77.5-92.4), respectively. No new safety signals or treatment-related deaths were reported. Low levels of tumor-infiltrating LAG3+CD3+ exhausted T-cells and higher baseline levels of naïve CD8+ T-cells were associated with improved outcomes. Tisagenlecleucel continued to demonstrate highly durable efficacy and a favorable safety profile in this extended follow-up of 29 months in patients with r/r FL enrolled in ELARA

STAT2 deficiency and susceptibility to viral illness in humans

Severe infectious disease in children may be a manifestation of primary immunodeficiency. These genetic disorders represent important experiments of nature with the capacity to elucidate nonredundant mechanisms of human immunity. We hypothesized that a primary defect of innate antiviral immunity was responsible for unusually severe viral illness in two siblings; the proband developed disseminated vaccine strain measles following routine immunization, whereas an infant brother died after a 2-d febrile illness from an unknown viral infection. Patient fibroblasts were indeed abnormally permissive for viral replication in vitro, associated with profound failure of type I IFN signaling and absence of STAT2 protein. Sequencing of genomic DNA and RNA revealed a homozygous mutation in intron 4 of STAT2 that prevented correct splicing in patient cells. Subsequently, other family members were identified with the same genetic lesion. Despite documented infection by known viral pathogens, some of which have been more severe than normal, surviving STAT2-deficient individuals have remained generally healthy, with no obvious defects in their adaptive immunity or developmental abnormalities. These findings imply that type I IFN signaling [through interferon-stimulated gene factor 3 (ISGF3)] is surprisingly not essential for host defense against the majority of common childhood viral infections

Clinical evaluation of magnetic resonance imaging in coronary heart disease: The CE-MARC study

<p>Abstract</p> <p>Background</p> <p>Several investigations are currently available to establish the diagnosis of coronary heart disease (CHD). Of these, cardiovascular magnetic resonance (CMR) offers the greatest information from a single test, allowing the assessment of myocardial function, perfusion, viability and coronary artery anatomy. However, data from large scale studies that prospectively evaluate the diagnostic accuracy of multi-parametric CMR for the detection of CHD in unselected populations are lacking, and there are few data on the performance of CMR compared with current diagnostic tests, its prognostic value and cost-effectiveness.</p> <p>Methods/design</p> <p>This is a prospective diagnostic accuracy cohort study of 750 patients referred to a cardiologist with suspected CHD. Exercise tolerance testing (ETT) will be preformed if patients are physically able. Recruited patients will then undergo CMR and single photon emission tomography (SPECT) followed in all patients by invasive X-ray coronary angiography. The order of the CMR and SPECT tests will be randomised. The CMR study will comprise rest and adenosine stress perfusion, cine imaging, late gadolinium enhancement and whole-heart MR coronary angiography. SPECT will use a gated stress/rest protocol. The primary objective of the study is to determine the diagnostic accuracy of CMR in detecting significant coronary stenosis, as defined by X-ray coronary angiography. Secondary objectives include an assessment of the prognostic value of CMR imaging, a comparison of its diagnostic accuracy against SPECT and ETT, and an assessment of cost-effectiveness.</p> <p>Discussion</p> <p>The CE-MARC study is a prospective, diagnostic accuracy cohort study of 750 patients assessing the performance of a multi-parametric CMR study in detecting CHD using invasive X-ray coronary angiography as the reference standard and comparing it with ETT and SPECT.</p> <p>Trial Registration</p> <p>Current Controlled Trials ISRCTN77246133</p