The struggling infectious diseases fellow: Remediation challenges and opportunities

Remediation of struggling learners is a challenge faced by all educators. In recognition of this reality, and in light of contemporary challenges facing infectious diseases (ID) fellowship program directors, the Infectious Diseases Society of America Training Program Directors\u27 Committee focused the 2018 National Fellowship Program Directors\u27 Meeting at IDWeek on Remediation of the Struggling Fellow. Small group discussions addressed 7 core topics, including feedback and evaluations, performance management and remediation, knowledge deficits, fellow well-being, efficiency and time management, teaching skills, and career development. This manuscript synthesizes those discussions around a competency-based framework to provide program directors and other educators with a roadmap for addressing common contemporary remediation challenges

Constrictive pleuropericarditis: a dominant clinical manifestation in Whipple’s disease

Background: Whipple’s disease is a rare, multisystemic, chronic infectious disease which classically presents as a wasting illness characterized by polyarthralgia, diarrhea, fever, and lymphadenopathy. Pleuropericardial involvement is a common pathologic finding in patients with Whipple’s disease, but rarely causes clinical symptoms. We report the first case of severe fibrosing pleuropericarditis necessitating pleural decortication in a patient with Whipple’s disease. Case presentation: Our patient, an elderly gentleman, had a chronic inflammatory illness dominated by constrictive pericarditis and later severe fibrosing pleuritis associated with a mildly elevated serum IgG4 level. A pericardial biopsy showed dense fibrosis without IgG4 plasmacytic infiltration. The patient received immunosuppressive therapy for possible IgG4-related disease. His poor response to this therapy prompted a re-examination of the diagnosis, including a request for the pericardial biopsy tissue to be stained for Tropheryma whipplei. Conclusions: Despite a high prevalence of pleuropericardial involvement in Whipple’s disease, constrictive pleuropericarditis is rare, particularly as the dominant disease manifestation. The diagnosis of Whipple’s disease is often delayed in such atypical presentations since the etiologic agent, Tropheryma whipplei, is not routinely sought in histopathology specimens of pleura or pericardium. A diagnosis of Whipple’s disease should be considered in middle-aged or elderly men with polyarthralgia and constrictive pericarditis, even in the absence of gastrointestinal symptoms. Although Tropheryma whipplei PCR has limited sensitivity and specificity, especially in the analysis of peripheral blood samples, it may have diagnostic value in inflammatory disorders of uncertain etiology, including cases of polyserositis. The optimal approach to managing constrictive pericarditis in patients with Whipple’s disease is uncertain, but limited clinical experience suggests that a combination of pericardiectomy and antibiotic therapy is of benefit

The Formation of Broad Line Clouds in the Accretion Shocks of Active Galactic Nuclei

Recent work on the gas dynamics in the Galactic Center has improved our understanding of the accretion processes in galactic nuclei, particularly with regard to properties such as the specific angular momentum distribution, density, and temperature of the inflowing plasma. This information can be valuable in trying to determine the origin of the Broad Line Region (BLR) in Active Galactic Nuclei (AGNs). In this paper, we explore various scenarios for the cloud formation based on the underlying principle that the source of plasma is ultimately that portion of the gas trapped by the central black hole from the interstellar medium. Based on what we know about the Galactic Center, it is likely that in highly dynamic environments such as this, the supply of matter is due mostly to stellar winds from the central cluster. Winds accreting onto a central black hole are subjected to several disturbances capable of producing shocks, including a Bondi-Hoyle flow, stellar wind-wind collisions, and turbulence. Shocked gas is initially compressed and heated out of thermal equilibrium with the ambient radiation field; a cooling instability sets in as the gas is cooled via inverse-Compton and bremsstrahlung processes. If the cooling time is less than the dynamical flow time through the shock region, the gas may clump to form the clouds responsible for broad line emission seen in many AGN spectra. Clouds produced by this process display the correct range of densities and velocity fields seen in broad emission lines. Very importantly, the cloud distribution agrees with the results of reverberation studies, in which it is seen that the central line peak responds slower to continuum changes than the line wings.Comment: 22 pages, 5 figure

Safety, the Preface Paradox and Possible Worlds Semantics

This paper contains an argument to the effect that possible worlds semantics renders semantic knowledge impossible, no matter what ontological interpretation is given to possible worlds. The essential contention made is that possible worlds semantic knowledge is unsafe and this is shown by a parallel with the preface paradox

Shadowing of the Nascent Jet in NGC 4261 by a Line-Emitting Supersonic Accretion Disk

NGC 4261 (3C 270) is a low-luminosity radio galaxy with two symmetric kiloparsec-scale jets. Earlier Hubble Space Telescope observations indicated the presence of a hundred-parsec scale disk of cool dust and gas surrounding a central, supermassive (\sim 4.9\times 10^8\msun) black hole. The recent detection of free-free radio absorption by a small, geometrically-thin disk, combined with earlier studies of the disk's large scale properties, provide the strictest constraints to date on the nature of the accretion process in this system. We show here that a supersonic disk, illuminated by the active galactic nucleus (AGN), can not only account for the observed radio shadowing, but can also produce the optical broad lines emitted from this region. Beyond a critical radius $r_c$, line cooling dominates over gravitational dissipation and the gas is effectively cooled down to temperatures below $10^4$ K. Within $r_c$, however, heating due to the release of gravitational energy overwhelms line cooling and the plasma is heated very quickly to a temperature close to its virial value as it falls toward the central engine. The disk is optically-thin to UV and X-ray radiation within $r_c$, so the ionizing radiation from the AGN is preferentially absorbed near $r_c$, affecting the disk structure significantly. To include the ensuing photoionization effect, we have used the algorithm Cloudy with additional heating introduced by gravitational dissipation to calculate the temperature profile and line emission from the disk in a self-consistent manner. The results of our model calculation are consistent with current multiwavelength observations of the disk in this source.Comment: 28 pages, 9 figures. To appear in Ap

US Cosmic Visions: New Ideas in Dark Matter 2017: Community Report

This white paper summarizes the workshop "U.S. Cosmic Visions: New Ideas in Dark Matter" held at University of Maryland on March 23-25, 2017.Comment: 102 pages + reference

Summary of Lepton Photon 2011

In this lecture, I summarize developments presented at the Lepton Photon 2011 conference and give my perspective on the current situation in high-energy physics.Comment: 56 pages, 37 figures; v2: minor corrections to reference

Anastrozole versus tamoxifen for the prevention of locoregional and contralateral breast cancer in postmenopausal women with locally excised ductal carcinoma in situ (IBIS-II DCIS): a double-blind, randomised controlled trial

Background Third-generation aromatase inhibitors are more effective than tamoxifen for preventing recurrence in postmenopausal women with hormone-receptor-positive invasive breast cancer. However, it is not known whether anastrozole is more effective than tamoxifen for women with hormone-receptor-positive ductal carcinoma in situ (DCIS). Here, we compare the efficacy of anastrozole with that of tamoxifen in postmenopausal women with hormone-receptor-positive DCIS. Methods In a double-blind, multicentre, randomised placebo-controlled trial, we recruited women who had been diagnosed with locally excised, hormone-receptor-positive DCIS. Eligible women were randomly assigned in a 1:1 ratio by central computer allocation to receive 1 mg oral anastrozole or 20 mg oral tamoxifen every day for 5 years. Randomisation was stratified by major centre or hub and was done in blocks (six, eight, or ten). All trial personnel, participants, and clinicians were masked to treatment allocation and only the trial statistician had access to treatment allocation. The primary endpoint was all recurrence, including recurrent DCIS and new contralateral tumours. All analyses were done on a modified intention-to-treat basis (in all women who were randomised and did not revoke consent for their data to be included) and proportional hazard models were used to compute hazard ratios and corresponding confidence intervals. This trial is registered at the ISRCTN registry, number ISRCTN37546358. Results Between March 3, 2003, and Feb 8, 2012, we enrolled 2980 postmenopausal women from 236 centres in 14 countries and randomly assigned them to receive anastrozole (1449 analysed) or tamoxifen (1489 analysed). Median follow-up was 7·2 years (IQR 5·6–8·9), and 144 breast cancer recurrences were recorded. We noted no statistically significant difference in overall recurrence (67 recurrences for anastrozole vs 77 for tamoxifen; HR 0·89 [95% CI 0·64–1·23]). The non-inferiority of anastrozole was established (upper 95% CI <1·25), but its superiority to tamoxifen was not (p=0·49). A total of 69 deaths were recorded (33 for anastrozole vs 36 for tamoxifen; HR 0·93 [95% CI 0·58–1·50], p=0·78), and no specific cause was more common in one group than the other. The number of women reporting any adverse event was similar between anastrozole (1323 women, 91%) and tamoxifen (1379 women, 93%); the side-effect profiles of the two drugs differed, with more fractures, musculoskeletal events, hypercholesterolaemia, and strokes with anastrozole and more muscle spasm, gynaecological cancers and symptoms, vasomotor symptoms, and deep vein thromboses with tamoxifen. Conclusions No clear efficacy differences were seen between the two treatments. Anastrozole offers another treatment option for postmenopausal women with hormone-receptor-positive DCIS, which may be be more appropriate for some women with contraindications for tamoxifen. Longer follow-up will be necessary to fully evaluate treatment differences

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta