The Radiology Fellowship Application and Selection Process in the United States: Experiences and Perceptions from Both Sides

Objective. Our purpose was to investigate radiology fellowship directors\u27 and recent fellows\u27 experiences and perceptions with regard to the fellowship application and selection process and to compare these experiences and perceptions. Materials and Methods. Institutional review board approval was obtained. We conducted an online survey of the memberships of three radiology subspecialty societies between October 2009 and December 2009 to learn about radiologists\u27 views regarding various aspects of radiology fellowships. Results. In the process of selecting fellows, program directors and recent fellows consider performance during the radiology residency and the quality or prestige of the residency program as the most important objective factors, and the personal interview, letters of recommendation, and personality as the most important subjective factors. 25% of the program directors were in the match, and 41% of the recent fellows were in the match. Most (48%) of program directors favored a match, but most (56%) of the recent fellows disfavored participating in a match. Both program directors and recent fellows expressed satisfaction with the fellowship application and selection process. Conclusion. There was no majority support for a fellowship match among program directors and recent fellows and less support among recent fellows. Recent fellows appear more satisfied with the current selection and application process than program directors

Gain-of-function mutations in the UNC-2/CaV2α channel lead to excitation-dominant synaptic transmission in C. elegans

Mutations in pre-synaptic voltage gated calcium channels can lead to familial hemiplegic migraine type 1 (FHM1). While mammalian studies indicate that the migraine brain is hyperexcitable due to enhanced excitation or reduced inhibition, the molecular and cellular mechanisms underlying this excitatory/inhibitory (E/I) imbalance are poorly understood. We identified a gain-of-function (gf) mutation in the Caenorhabditis elegans CaV2 channel α1 subunit, UNC-2, which leads to increased calcium currents. unc-2(zf35gf) mutants exhibit hyperactivity and seizure-like motor behaviors. Expression of the unc-2 gene with FHM1 substitutions R192Q and S218L leads to hyperactivity similar to that of unc-2(zf35gf) mutants. unc-2(zf35gf) mutants display increased cholinergic-and decreased GABAergic-transmission. Moreover, increased cholinergic transmission in unc-2(zf35gf) mutants leads to an increase of cholinergic synapses and a TAX-6/calcineurin dependent reduction of GABA synapses. Our studies reveal mechanisms through which CaV2 gain-of-function mutations disrupt excitation-inhibition balance in the nervous system.Fil: Huang, Yung Chi. University of Massachussets; Estados UnidosFil: Pirri, Jennifer K.. University of Massachussets; Estados UnidosFil: Rayes, Diego Hernán. University of Massachussets; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; ArgentinaFil: Gao, Shangbang. Mount Sinai Hospital; Estados UnidosFil: Mulcahy, Ben. Mount Sinai Hospital; Estados UnidosFil: Grant, Jeff. University of Massachussets; Estados UnidosFil: Saheki, Yasunori. The Rockefeller University; Estados UnidosFil: Francis, Michael M.. University of Massachussets; Estados UnidosFil: Zhen, Mei. University of Toronto; Canadá. Mount Sinai Hospital; Estados UnidosFil: Alkema, Mark J.. University of Massachussets; Estados Unido

LOFAR MSSS: The Scaling Relation between AGN Cavity Power and Radio Luminosity at Low Radio Frequencies

This article has been accepted for publication in a forthcoming issue of Astronomy & Astrophysics. Reproduced with permission from Astronomy & Astrophysics. © 2018 ESO.We present a new analysis of the widely used relation between cavity power and radio luminosity in clusters of galaxies with evidence for strong AGN feedback. We study the correlation at low radio frequencies using two new surveys - the First Alternative Data Release of the TIFR GMRT Sky Survey (TGSS ADR1) at 148 MHz and LOFAR's first all-sky survey, the Multifrequency Snapshot Sky Survey (MSSS) at 140 MHz. We find a scaling relation $P_{\rm cav} \propto L_{148}^{\beta}$, with a logarithmic slope of $\beta = 0.51 \pm 0.14$, which is in good agreement with previous results based on data at 327 MHz. The large scatter present in this correlation confirms the conclusion reached at higher frequencies that the total radio luminosity at a single frequency is a poor predictor of the total jet power. We show that including measurements at 148 MHz alone is insufficient to reliably compute the bolometric radio luminosity and reduce the scatter in the correlation. For a subset of four well-resolved sources, we examine the detected extended structures at low frequencies and compare with the morphology known from higher frequency images and Chandra X-ray maps. In Perseus we discuss details in the structures of the radio mini-halo, while in the 2A 0335+096 cluster we observe new diffuse emission associated with multiple X-ray cavities and likely originating from past activity. For A2199 and MS 0735.6+7421, we confirm that the observed low-frequency radio lobes are confined to the extents known from higher frequencies. This new low-frequency analysis highlights the fact that existing cavity power to radio luminosity relations are based on a relatively narrow range of AGN outburst ages. We discuss how the correlation could be extended using low frequency data from the LOFAR Two-metre Sky Survey (LoTSS) in combination with future, complementary deeper X-ray observations.Peer reviewe

Dogs (Canis familiaris), but Not Chimpanzees (Pan troglodytes), Understand Imperative Pointing

Chimpanzees routinely follow the gaze of humans to outside targets. However, in most studies using object choice they fail to use communicative gestures (e.g. pointing) to find hidden food. Chimpanzees' failure to do this may be due to several difficulties with this paradigm. They may, for example, misinterpret the gesture as referring to the opaque cup instead of the hidden food. Or perhaps they do not understand informative communicative intentions. In contrast, dogs seem to be skilful in using human communicative cues in the context of finding food, but as of yet there is not much data showing whether they also use pointing in the context of finding non-food objects. Here we directly compare chimpanzees' (N = 20) and dogs' (N = 32) skills in using a communicative gesture directed at a visible object out of reach of the human but within reach of the subject. Pairs of objects were placed in view of and behind the subjects. The task was to retrieve the object the experimenter wanted. To indicate which one she desired, the experimenter pointed imperatively to it and directly rewarded the subject for handing over the correct one. While dogs performed well on this task, chimpanzees failed to identify the referent. Implications for great apes' and dogs' understanding of human communicative intentions are discussed

Detection of Prion Infectivity in Fat Tissues of Scrapie-Infected Mice

Distribution of prion infectivity in organs and tissues is important in understanding prion disease pathogenesis and designing strategies to prevent prion infection in animals and humans. Transmission of prion disease from cattle to humans resulted in banning human consumption of ruminant nervous system and certain other tissues. In the present study, we surveyed tissue distribution of prion infectivity in mice with prion disease. We show for the first time detection of infectivity in white and brown fat. Since high amounts of ruminant fat are consumed by humans and also incorporated into animal feed, fat-containing tissues may pose a previously unappreciated hazard for spread of prion infection

LOFAR discovery of a quiet emission mode in PSR B0823+26

15 pages, 8 figures, 2 tables, accepted for publication in MNRASInternational audiencePSR B0823+26, a 0.53-s radio pulsar, displays a host of emission phenomena over timescales of seconds to (at least) hours, including nulling, subpulse drifting, and mode-changing. Studying pulsars like PSR B0823+26 provides further insight into the relationship between these various emission phenomena and what they might teach us about pulsar magnetospheres. Here we report on the LOFAR discovery that PSR B0823+26 has a weak and sporadically emitting 'quiet' (Q) emission mode that is over 100 times weaker (on average) and has a nulling fraction forty-times greater than that of the more regularly-emitting 'bright' (B) mode. Previously, the pulsar has been undetected in the Q-mode, and was assumed to be nulling continuously. PSR B0823+26 shows a further decrease in average flux just before the transition into the B-mode, and perhaps truly turns off completely at these times. Furthermore, simultaneous observations taken with the LOFAR, Westerbork, Lovell, and Effelsberg telescopes between 110 MHz and 2.7 GHz demonstrate that the transition between the Q-mode and B-mode occurs within one single rotation of the neutron star, and that it is concurrent across the range of frequencies observed

Cholangiocyte organoids can repair bile ducts after transplantation in the human liver.

Organoid technology holds great promise for regenerative medicine but has not yet been applied to humans. We address this challenge using cholangiocyte organoids in the context of cholangiopathies, which represent a key reason for liver transplantation. Using single-cell RNA sequencing, we show that primary human cholangiocytes display transcriptional diversity that is lost in organoid culture. However, cholangiocyte organoids remain plastic and resume their in vivo signatures when transplanted back in the biliary tree. We then utilize a model of cell engraftment in human livers undergoing ex vivo normothermic perfusion to demonstrate that this property allows extrahepatic organoids to repair human intrahepatic ducts after transplantation. Our results provide proof of principle that cholangiocyte organoids can be used to repair human biliary epithelium

Multiple FadD Acyl-CoA Synthetases Contribute to Differential Fatty Acid Degradation and Virulence in Pseudomonas aeruginosa

A close interconnection between nutrient metabolism and virulence factor expression contributes to the pathophysiology of Pseudomonas aeruginosa as a successful pathogen. P. aeruginosa fatty acid (FA) degradation is complicated with multiple acyl-CoA synthetase homologs (FadDs) expressed in vivo in lung tissue during cystic fibrosis infections. The promoters of two genetically linked P. aeruginosa fadD genes (fadD1 and fadD2) were mapped and northern blot analysis indicated they could exist on two different transcripts. These FadDs contain ATP/AMP signature and FA-binding motifs highly homologous to those of the Escherichia coli FadD. Upon introduction into an E. coli fadD-/fadR- double mutant, both P. aeruginosa fadDs functionally complemented the E. coli fadD-/fadR- mutant, allowing degradation of different chain-length FAs. Chromosomal mutagenesis, growth analysis, induction studies, and determination of kinetic parameters suggested that FadD1 has a substrate preference for long-chain FAs while FadD2 prefers shorter-chain FAs. When compared to the wild type strain, the fadD2 mutant exhibited decreased production of lipase, protease, rhamnolipid and phospholipase, and retardation of both swimming and swarming motilities. Interestingly, fadD1 mutant showed only increased swarming motility. Growth analysis of the fadD mutants showed noticeable deficiencies in utilizing FAs and phosphatidylcholine (major components of lung surfactant) as the sole carbon source. This defect translated into decreased in vivo fitness of P. aeruginosa in a BALB/c mouse lung infection model, supporting the role of lipids as a significant nutrient source for this bacterium in vivo

Selinexor in Advanced, Metastatic Dedifferentiated Liposarcoma: A Multinational, Randomized, Double-Blind, Placebo-Controlled Trial

PURPOSE Antitumor activity in preclinical models and a phase I study of patients with dedifferentiated liposarcoma (DD-LPS) was observed with selinexor. We evaluated the clinical benefit of selinexor in patients with previously treated DD-LPS whose sarcoma progressed on approved agents. METHODS SEAL was a phase II-III, multicenter, randomized, double-blind, placebo-controlled study. Patients age 12 years or older with advanced DD-LPS who had received two-five lines of therapy were randomly assigned (2:1) to selinexor (60 mg) or placebo twice weekly in 6-week cycles (crossover permitted). The primary end point was progression-free survival (PFS). Patients who received at least one dose of study treatment were included for safety analysis (ClinicalTrials.gov identifier: ). RESULTS Two hundred eighty-five patients were enrolled (selinexor, n = 188; placebo, n = 97). PFS was significantly longer with selinexor versus placebo: hazard ratio (HR) 0.70 (95% CI, 0.52 to 0.95; one-sided P = .011; medians 2.8 v 2.1 months), as was time to next treatment: HR 0.50 (95% CI, 0.37 to 0.66; one-sided P < .0001; medians 5.8 v 3.2 months). With crossover, no difference was observed in overall survival. The most common treatment-emergent adverse events of any grade versus grade 3 or 4 with selinexor were nausea (151 [80.7%] v 11 [5.9]), decreased appetite (113 [60.4%] v 14 [7.5%]), and fatigue (96 [51.3%] v 12 [6.4%]). Four (2.1%) and three (3.1%) patients died in the selinexor and placebo arms, respectively. Exploratory RNA sequencing analysis identified that the absence of CALB1 expression was associated with longer PFS with selinexor compared with placebo (median 6.9 v 2.2 months; HR, 0.19; P = .001). CONCLUSION Patients with advanced, refractory DD-LPS showed improved PFS and time to next treatment with selinexor compared with placebo. Supportive care and dose reductions mitigated side effects of selinexor. Prospective validation of CALB1 expression as a predictive biomarker for selinexor in DD-LPS is warranted. (C) 2022 by American Society of Clinical Oncolog