Sequence structure emission in The Red Rectangle Bands

We report high resolution (R~37,000) integral field spectroscopy of the central region (r<14arcsec) of the Red Rectangle nebula surrounding HD44179. The observations focus on the 5800A emission feature, the bluest of the yellow/red emission bands in the Red Rectangle. We propose that the emission feature, widely believed to be a molecular emission band, is not a molecular rotation contour, but a vibrational contour caused by overlapping sequence bands from a molecule with an extended chromophore. We model the feature as arising in a Polycyclic Aromatic Hydrocarbon (PAH) with 45-100 carbon atoms.Comment: 13 pages, 9 figures, accepted for publication in ApJ. A version of the paper with full resolution figures is available at: http://www.aao.gov.au/local/www/rgs/Sequence-Structure

Workplace learning from a socio-cultural perspective: creating developmental space during the general practice clerkship

Workplace learning in undergraduate medical education has predominantly been studied from a cognitive perspective, despite its complex contextual characteristics, which influence medical students’ learning experiences in such a way that explanation in terms of knowledge, skills, attitudes and single determinants of instructiveness is unlikely to suffice. There is also a paucity of research which, from a perspective other than the cognitive or descriptive one, investigates student learning in general practice settings, which are often characterised as powerful learning environments. In this study we took a socio-cultural perspective to clarify how students learn during a general practice clerkship and to construct a conceptual framework that captures this type of learning. Our analysis of group interviews with 44 fifth-year undergraduate medical students about their learning experiences in general practice showed that students needed developmental space to be able to learn and develop their professional identity. This space results from the intertwinement of workplace context, personal and professional interactions and emotions such as feeling respected and self-confident. These forces framed students’ participation in patient consultations, conversations with supervisors about consultations and students’ observation of supervisors, thereby determining the opportunities afforded to students to mind their learning. These findings resonate with other conceptual frameworks and learning theories. In order to refine our interpretation, we recommend that further research from a socio-cultural perspective should also explore other aspects of workplace learning in medical education

Unusually Weak Diffuse Interstellar Bands toward HD 62542

As part of an extensive survey of diffuse interstellar bands (DIBs), we have obtained optical spectra of the moderately reddened B5V star HD 62542, which is known to have an unusual UV extinction curve of the type usually identified with dark clouds. The typically strongest of the commonly catalogued DIBs covered by the spectra -- those at 5780, 5797, 6270, 6284, and 6614 A -- are essentially absent in this line of sight, in marked contrast with other lines of sight of similar reddening. We compare the HD 62542 line of sight with others exhibiting a range of extinction properties and molecular abundances and interpret the weakness of the DIBs as an extreme case of deficient DIB formation in a dense cloud whose more diffuse outer layers have been stripped away. We comment on the challenges these observations pose for identifying the carriers of the diffuse bands.Comment: 20 pages, 4 figures; aastex; accepted by Ap

Navigating the challenges: a case report on managing a complicated postpartum course in type 3 von Willebrand disease with alloantibodies

BACKGROUND: Von Willebrand disease (VWD) type 3 is characterized by a complete deficiency of von Willebrand factor (VWF), resulting in a severe bleeding phenotype. Treatment often requires administration of VWF concentrates/factor (F)VIII. However, the development of alloantibodies is a rare complication, resulting in ineffective recovery and allergic reactions. Emicizumab, a bispecific antibody mimicking FVIII function, has emerged as a potential alternative, with promising results reported in several case reports. KEY CLINICAL QUESTION: Description of multiple approaches to control highly severe postpartum hemorrhage in type 3 VWD with alloantibodies, including off-label use of emicizumab. CLINICAL APPROACH: Here we present a 28-year-old patient with type 3 VWD and alloantibodies, known to have arthropathy of the right elbow. Previous immune tolerance induction was unsuccessful. Despite receiving negative pregnancy advice during preconception counseling, the patient became pregnant. Delivery was induced at 38 4/7 weeks with prostaglandin, and recombinant FVIIa (rFVIIa) was administered every 2 hours. Despite administration of rFVIIa, bleeding persisted, requiring manual placental removal and insertion of a Bakri balloon. Since bleeding persisted, plasma-derived VWF was administered with an initial excellent recovery and successful embolization of the uterine artery. Twelve days postpartum, she developed endometritis and recurrent vaginal bleeding treated with antibiotics, rFVIIa every 2 hours, and multiple erythrocyte transfusions. Plasma-derived VWF was administered but was complicated by anaphylaxis and no recovery. Due to persistent vaginal bleeding, reembolization of uterine arteries was performed and off-label emicizumab was initiated. Twenty-nine days postpartum, she developed septic shock requiring an abdominal hysterectomy, again complicated by severe bleeding necessitating direct intraabdominal packing after rFVIIa. A computed tomography scan 9 days postsurgery revealed thrombosis in the left iliac vein and asymptomatic pulmonary embolisms. rFVIIa was stopped and prophylactic low-molecular-weight heparin was started. The patient was discharged 2 months after delivery on low-dose low-molecular-weight heparin, emicizumab, and antibiotics for an intra-abdominal abscess. During 2.5 years of emicizumab prophylaxis, she has had no rebleeding in her arthropathic right elbow. CONCLUSION: The current case emphasizes the postpartum clinical challenges of patients with type 3 VWD and alloantibodies. It underscores the potential role of emicizumab in maintaining hemostatic control

Occupational exposure to gases/fumes and mineral dust affect DNA methylation levels of genes regulating expression

Many workers are daily exposed to occupational agents like gases/fumes, mineral dust or biological dust, which could induce adverse health effects. Epigenetic mechanisms, such as DNA methylation, have been suggested to play a role. We therefore aimed to identify differentially methylated regions (DMRs) upon occupational exposures in never-smokers and investigated if these DMRs associated with gene expression levels. To determine the effects of occupational exposures independent of smoking, 903 never-smokers of the LifeLines cohort study were included. We performed three genome-wide methylation analyses (Illumina 450 K), one per occupational exposure being gases/fumes, mineral dust and biological dust, using robust linear regression adjusted for appropriate confounders. DMRs were identified using comb-p in Python. Results were validated in the Rotterdam Study (233 never-smokers) and methylation-expression associations were assessed using Biobank-based Integrative Omics Study data (n = 2802). Of the total 21 significant DMRs, 14 DMRs were associated with gases/fumes and 7 with mineral dust. Three of these DMRs were associated with both exposures (RPLP1 and LINC02169 (2x)) and 11 DMRs were located within transcript start sites of gene expression regulating genes. We replicated two DMRs with gases/fumes (VTRNA2-1 and GNAS) and one with mineral dust (CCDC144NL). In addition, nine gases/fumes DMRs and six mineral dust DMRs significantly associated with gene expression levels. Our data suggest that occupational exposures may induce differential methylation of gene expression regulating genes and thereby may induce adverse health effects. Given the millions of workers that are exposed daily to occupational exposures, further studies on this epigenetic mechanism and health outcomes are warranted

Infrared Emission from Interstellar Dust. II. The Diffuse Interstellar Medium

We present a quantitative model for the infrared emission from dust in the diffuse interstellar medium. The model consists of a mixture of amorphous silicate grains and carbonaceous grains, each with a wide size distribution ranging from molecules containing tens of atoms to large grains > 1 um in diameter. We assume that the carbonaceous grains have polycyclic aromatic hydrocarbon (PAH)-like properties at very small sizes, and graphitic properties for radii a > 50 A. On the basis of recent laboratory studies and guided by astronomical observations, we propose "astronomical" absorption cross sections for use in modeling neutral and ionized PAHs from the far ultraviolet to the far infrared. We also propose modifications to the far-infrared emissivity of "astronomical silicate". We calculate energy distribution functions for small grains undergoing "temperature spikes" due to stochastic absorption of starlight photons, using realistic heat capacities and optical properties. Using a grain size distribution consistent with the observed interstellar extinction, we are able to reproduce the near-IR to submillimeter emission spectrum of the diffuse interstellar medium, including the PAH emission features at 3.3, 6.2, 7.7, 8.6, and 11.3um. The model is compared with the observed emission at high Galactic latitudes as well as in the Galactic plane, as measured by COBE and IRTS. We calculate infrared emission spectra for our dust model heated by a range of starlight intensities, and we provide tabulated dust opacities (extended tables available at http://www.astro.princeton.edu/~draine/dust/dustmix.html)Comment: Final version published in ApJ, 554, 778 but with factor 1.086 error in Table 6 and Fig. 16 corrected. Main change from astro-ph version 1 is correction of typographical errors in Table 1, and correction of typo in eq. (A2). 51 pages, 16 figures, Late

Antimicrobial susceptibility profile of clinically relevant Bacteroides, Phocaeicola, Parabacteroides and Prevotella species, isolated by eight laboratories in the Netherlands

Objectives: Recently, reports on antimicrobial-resistant Bacteroides and Prevotella isolates have increased in the Netherlands. This urged the need for a surveillance study on the antimicrobial susceptibility profile of Bacteroides, Phocaeicola, Parabacteroides and Prevotella isolates consecutively isolated from human clinical specimens at eight different Dutch laboratories. Methods: Each laboratory collected 20–25 Bacteroides (including Phocaeicola and Parabacteroides) and 10–15 Prevotella isolates for 3 months. At the national reference laboratory, the MICs of amoxicillin, amoxicillin/clavulanic acid, piperacillin/tazobactam, meropenem, imipenem, metronidazole, clindamycin, tetracycline and moxifloxacin were determined using agar dilution. Isolates with a high MIC of metronidazole or a carbapenem, or harbouring cfiA, were subjected to WGS. Results: Bacteroides thetaiotaomicron/faecis isolates had the highest MIC 90 values, whereas Bacteroides fragilis had the lowest MIC 90 values for amoxicillin/clavulanic acid, piperacillin/tazobactam, meropenem, imipenem and moxifloxacin. The antimicrobial profiles of the different Prevotella species were similar, except for amoxicillin, for which the MIC 50 ranged from 0.125 to 16 mg/L for Prevotella bivia and Prevotella buccae, respectively. Three isolates with high metronidazole MICs were sequenced, of which one Bacteroides thetaiotaomicron isolate harboured a plasmid-located nimE gene and a Prevotella melaninogenica isolate harboured a nimA gene chromosomally. Five Bacteroides isolates harboured a cfiA gene and three had an IS element upstream, resulting in high MICs of carbapenems. The other two isolates harboured no IS element upstream of the cfiA gene and had low MICs of carbapenems. Conclusions: Variations in resistance between species were observed. To combat emerging resistance in anaerobes, monitoring resistance and conducting surveillance are essential.</p

Electron density and carriers of the diffuse interstellar bands

We have used the ionisation equilibrium equation to derive the electron density in interstellar clouds in the direction to 13 stars. A linear relation was found, that allows the determination of the electron density from the Mg I and Mg II column densities in diffuse clouds. The comparison of normalised equivalent width of 12 DIBs with the electron density shows that the DIBs equivalent width do not change with electron density varying in the range ne=0.01-2.5 cm^-3. Therefore the DIBs carriers (1) can be observed only in one ionisation stage, or (2) the DIBs are arising in cloud regions (eg. cores or cloud coronas) for which we can not determine the electron density

MAPK-ERK is a central pathway in T-cell acute lymphoblastic leukemia that drives steroid resistance

(Patho-)physiological activation of the IL7-receptor (IL7R) signaling contributes to steroid resistance in pediatric T-cell acute lymphoblastic leukemia (T-ALL). Here, we show that activating IL7R pathway mutations and physiological IL7R signaling activate MAPK-ERK signaling, which provokes steroid resistance by phosphorylation of BIM. By mass spectrometry, we demonstrate that phosphorylated BIM is impaired in binding to BCL2, BCLXL and MCL1, shifting the apoptotic balance toward survival. Treatment with MEK inhibitors abolishes this inactivating phosphorylation of BIM and restores its interaction with anti-apoptotic BCL2-protein family members. Importantly, the MEK inhibitor selumetinib synergizes with steroids in both IL7-dependent and IL7-independent steroid resistant pediatric T-ALL PDX samples. Despite the anti-MAPK-ERK activity of ruxolitinib in IL7-induced signaling and JAK1 mutant cells, ruxolitinib only synergizes with steroid treatment in IL7-dependent steroid resistant PDX samples but not in IL7-independent steroid resistant PDX samples. Our study highlights the central role for MAPK-ERK signaling in steroid resistance in T-ALL patients, and demonstrates the broader application of MEK inhibitors over ruxolitinib to resensitize steroid-resistant T-ALL cells. These findings strongly support the enrollment of T-ALL patients in the current phase I/II SeluDex trial (NCT03705507) and contributes to the optimization and stratification of newly designed T-ALL treatment regimens