Advancing the Provision of Pain Education and Learning (APPEAL) study

Objectives Unrelieved pain is a substantial public health concern necessitating improvements in medical education. The Advancing the Provision of Pain Education and Learning (APPEAL) study aimed to determine current levels and methods of undergraduate pain medicine education in Europe. Design and methods Using a cross-sectional design, publicly available curriculum information was sought from all medical schools in 15 representative European countries in 2012–2013. Descriptive analyses were performed on: the provision of pain teaching in dedicated pain modules, other modules or within the broader curriculum; whether pain teaching was compulsory or elective; the number of hours/credits spent teaching pain; pain topics; and teaching and assessment methods. Results Curriculum elements were publicly available from 242 of 249 identified schools (97%). In 55% (133/242) of schools, pain was taught only within compulsory non-pain-specific modules. The next most common approaches were for pain teaching to be provided wholly or in part via a dedicated pain module (74/242; 31%) or via a vertical or integrated approach to teaching through the broader curriculum, rather than within any specific module (17/242; 7%). The curricula of 17/242 schools (7%) showed no evidence of any pain teaching. Dedicated pain modules were most common in France (27/31 schools; 87%). Excluding France, only 22% (47/211 schools) provided a dedicated pain module and in only 9% (18/211) was this compulsory. Overall, the median number of hours spent teaching pain was 12.0 (range 4–56.0 h; IQR: 12.0) for compulsory dedicated pain modules and 9.0 (range 1.0–60.0 h; IQR: 10.5) for other compulsory (non-pain specific) modules. Pain medicine was principally taught in classrooms and assessed by conventional examinations. There was substantial international variation throughout. Conclusions Documented pain teaching in many European medical schools falls far short of what might be expected given the prevalence and public health burden of pain

Loss of Rnf31 and Vps4b sensitizes pancreatic cancer to T cell-mediated killing

Pancreatic ductal adenocarcinoma (PDA) is an inherently immune cell deprived tumor, characterized by desmoplastic stroma and suppressive immune cells. Here we systematically dissect PDA intrinsic mechanisms of immune evasion by in vitro and in vivo CRISPR screening, and identify Vps4b and Rnf31 as essential factors required for escaping CD8+ T cell killing. For Vps4b we find that inactivation impairs autophagy, resulting in increased accumulation of CD8+ T cell-derived granzyme B and subsequent tumor cell lysis. For Rnf31 we demonstrate that it protects tumor cells from TNF-mediated caspase 8 cleavage and subsequent apoptosis induction, a mechanism that is conserved in human PDA organoids. Orthotopic transplantation of Vps4b- or Rnf31 deficient pancreatic tumors into immune competent mice, moreover, reveals increased CD8+ T cell infiltration and effector function, and markedly reduced tumor growth. Our work uncovers vulnerabilities in PDA that might be exploited to render these tumors more susceptible to the immune system

Sample deposition onto cryo-EM grids: from sprays to jets and back

Despite the great strides made in the field of single-particle cryogenic electron microscopy (cryo-EM) in microscope design, direct electron detectors and new processing suites, the area of sample preparation is still far from ideal. Traditionally, sample preparation involves blotting, which has been used to achieve high resolution, particularly for well behaved samples such as apoferritin. However, this approach is flawed since the blotting process can have adverse effects on some proteins and protein complexes, and the long blot time increases exposure to the damaging air-water interface. To overcome these problems, new blotless approaches have been designed for the direct deposition of the sample on the grid. Here, different methods of producing droplets for sample deposition are compared. Using gas dynamic virtual nozzles, small and high-velocity droplets were deposited on cryo-EM grids, which spread sufficiently for high-resolution cryo-EM imaging. For those wishing to pursue a similar approach, an overview is given of the current use of spray technology for cryo-EM grid preparation and areas for enhancement are pointed out. It is further shown how the broad aspects of sprayer design and operation conditions can be utilized to improve grid quality reproducibly

Serum Metabolites Responding in a Dose-Dependent Manner to the Intake of a High-Fat Meal in Normal Weight Healthy Men Are Associated with Obesity

Although the composition of the human blood metabolome is influenced both by the health status of the organism and its dietary behavior, the interaction between these two factors has been poorly characterized. This study makes use of a previously published randomized controlled crossover acute intervention to investigate whether the blood metabolome of 15 healthy normal weight (NW) and 17 obese (OB) men having ingested three doses (500, 1000, 1500 kcal) of a high-fat (HF) meal can be used to identify metabolites differentiating these two groups. Among the 1024 features showing a postprandial response, measured between 0 h and 6 h, in the NW group, 135 were dose-dependent. Among these 135 features, 52 had fasting values that were significantly different between NW and OB men, and, strikingly, they were all significantly higher in OB men. A subset of the 52 features was identified as amino acids (e.g., branched-chain amino acids) and amino acid derivatives. As the fasting concentration of most of these metabolites has already been associated with metabolic dysfunction, we propose that challenging normal weight healthy subjects with increasing caloric doses of test meals might allow for the identification of new fasting markers associated with obesity

Fibroblast growth factor receptors 1 and 2 in keratinocytes control the epidermal barrier and cutaneous homeostasis

Loss of FGFRs results in skin abnormalities due to activation of keratinocytes and epidermal T cells

Ultrabroadband Polarization Insensitive Hybrid using Multiplane Light Conversion

We designed, fabricated and tested an optical hybrid that supports an octave of bandwidth (900-1800 nm) and below 4-dB insertion loss using multiplane light conversion. Measured phase errors are below 3-degree across a measurement bandwidth of 390 nm.Comment: 3 pages, 4 figures, accepted by OFC 202

Microscopic Selection of Fluid Fingering Pattern

We study the issue of the selection of viscous fingering patterns in the limit of small surface tension. Through detailed simulations of anisotropic fingering, we demonstrate conclusively that no selection independent of the small-scale cutoff (macroscopic selection) occurs in this system. Rather, the small-scale cutoff completely controls the pattern, even on short time scales, in accord with the theory of microscopic solvability. We demonstrate that ordered patterns are dynamically selected only for not too small surface tensions. For extremely small surface tensions, the system exhibits chaotic behavior and no regular pattern is realized.Comment: 6 pages, 5 figure

Recurrent failure of the continental slope as a key factor controlling reservoir potential in the South China Sea (Qiongdongnan Basin, South Hainan Island)

High-resolution multi-beam bathymetry, 3D and 2D seismic reflection profiles from the South China Sea are used to investigate the morphology, characteristics, origin and implications to petroleum systems of recurrent slope failure in the Qiongdongnan Basin, northern South China Sea. Seven Late Miocene-Holocene mass-transport deposits (MTDs) and numerous submarine canyons were identified on the continental slope and rise. Providing new insights on the evolution of an enigmatic region of the South China Sea, this paper defends that the interpreted MTDs were caused by a combination of high sedimentation rates and local tectonic uplift. By comparing the stratigraphy of the study area with local sea-level curves, we show that a significant portion of shelf-edge deposits effectively bypassed most of the continental slope during the Miocene-Quaternary to accumulate as large MTDs on its lower part (i.e. on the 'basin-floor'), independently of sea-level changes. Our work has implications to the current sequence stratigraphic models for continental margins, and sheds new light on the reservoir potential of Miocene units in the South China Sea. Hence, regions where base-of-slope fans are expected to occur are, in the study area, occupied by large-scale recurrent MTDs sourced from the shelf edge. Stratigraphically, recurrent slope instability resulted: a) in abrupt episodes of accommodation space creation on the shelf-edge, b) on a moderate reduction in accommodation space at the base of the continental slope, and c) in a complete separation between shelf and distal slope depositional systems, with most stratigraphic markers on 3D seismic data being diachronous across the continental margin. As MTDs also comprise the bulk of channel-fill deposits in large submarine canyons, we propose that the reservoir potential of channel-fill deposits in the South China Sea is closely dependent on the nature of the sediment (i.e. net-to-gross ratio) eroded and transported by these same MTDs

Offshore 1755 CE Lisbon Tsunami deposit in the southern portuguese continental shelf

The importance of tsunami hazard assessment is only possible if a complete dataset of events is available, allowing the determination of the recurrence intervals of the tsunamis adapted to local and regional conditions. One possible way to know these intervals is to study the offshore sedimentary record, looking for sediment remobilised and transported by the incoming tsunami waves and generated backwash currents. Even if these deposits are not of easy access (and not so well studied), the tsunami depositional signature has potential to be better preserved than those located onshore.info:eu-repo/semantics/publishedVersio