Automated detection and delineation of lymph nodes in haematoxylin & eosin stained digitised slides.

Treatment of patients with oesophageal and gastric cancer (OeGC) is guided by disease stage, patient performance status and preferences. Lymph node (LN) status is one of the strongest prognostic factors for OeGC patients. However, survival varies between patients with the same disease stage and LN status. We recently showed that LN size from patients with OeGC might also have prognostic value, thus making delineations of LNs essential for size estimation and the extraction of other imaging biomarkers. We hypothesized that a machine learning workflow is able to: (1) find digital H&E stained slides containing LNs, (2) create a scoring system providing degrees of certainty for the results, and (3) delineate LNs in those images. To train and validate the pipeline, we used 1695 H&E slides from the OE02 trial. The dataset was divided into training (80%) and validation (20%). The model was tested on an external dataset of 826 H&E slides from the OE05 trial. U-Net architecture was used to generate prediction maps from which predefined features were extracted. These features were subsequently used to train an XGBoost model to determine if a region truly contained a LN. With our innovative method, the balanced accuracies of the LN detection were 0.93 on the validation dataset (0.83 on the test dataset) compared to 0.81 (0.81) on the validation (test) datasets when using the standard method of thresholding U-Net predictions to arrive at a binary mask. Our method allowed for the creation of an "uncertain" category, and partly limited false-positive predictions on the external dataset. The mean Dice score was 0.73 (0.60) per-image and 0.66 (0.48) per-LN for the validation (test) datasets. Our pipeline detects images with LNs more accurately than conventional methods, and high-throughput delineation of LNs can facilitate future LN content analyses of large datasets

Automated detection and delineation of lymph nodes in haematoxylin & eosin stained digitised slides

Treatment of patients with oesophageal and gastric cancer (OeGC) is guided by disease stage, patient performance status and preferences. Lymph node (LN) status is one of the strongest prognostic factors for OeGC patients. However, survival varies between patients with the same disease stage and LN status. We recently showed that LN size from patients with OeGC might also have prognostic value, thus making delineations of LNs essential for size estimation and the extraction of other imaging biomarkers. We hypothesized that a machine learning workflow is able to: (1) find digital H&E stained slides containing LNs, (2) create a scoring system providing degrees of certainty for the results, and (3) delineate LNs in those images. To train and validate the pipeline, we used 1695 H&E slides from the OE02 trial. The dataset was divided into training (80%) and validation (20%). The model was tested on an external dataset of 826 H&E slides from the OE05 trial. U-Net architecture was used to generate prediction maps from which predefined features were extracted. These features were subsequently used to train an XGBoost model to determine if a region truly contained a LN. With our innovative method, the balanced accuracies of the LN detection were 0.93 on the validation dataset (0.83 on the test dataset) compared to 0.81 (0.81) on the validation (test) datasets when using the standard method of thresholding U-Net predictions to arrive at a binary mask. Our method allowed for the creation of an “uncertain” category, and partly limited false-positive predictions on the external dataset. The mean Dice score was 0.73 (0.60) per-image and 0.66 (0.48) per-LN for the validation (test) datasets. Our pipeline detects images with LNs more accurately than conventional methods, and high-throughput delineation of LNs can facilitate future LN content analyses of large datasets

Pointlike probes of superstring-theoretic superfluids

In analogy with an experimental setup used in liquid helium, we use a pointlike probe to study superfluids which have a gravity dual. In the gravity description, the probe is represented by a hanging string. We demonstrate that there is a critical velocity below which the probe particle feels neither drag nor stochastic forces. Above this critical velocity, there is power-law scaling for the drag force, and the stochastic forces are characterized by a finite, velocity-dependent temperature. This temperature participates in two simple and general relations between the drag force and stochastic forces. The formula we derive for the critical velocity indicates that the low-energy excitations are massless, and they demonstrate the power of stringy methods in describing strongly coupled superfluids.Comment: 17 pages, 2 figures, added a figure, a reference, and moved material to an appendi

ACL reconstruction with unicondylar replacement in knee with functional instability and osteoarthritis

Severe symptomatic osteoarthritis in young and active patients with pre-existing deficiency of the anterior cruciate ligament and severe functionally instability is a difficult subgroup to manage. There is considerable debate regarding management of young patients with isolated unicompartment osteoarthritis and concomitant ACL deficiency. A retrospective analysis of was done in 9 patients with symptomatic osteoarthritis with ACL deficiencies and functional instability that were treated with unicompartment knee arthroplasty and ACL reconstruction between April 2002 and June 2005. The average arc of flexion was 119° (range 85° to 135°) preoperatively and 125° (range 105° to 140°). There were no signs of instability during the follow up of patients. No patients in this group were reoperated. In this small series we have shown that instability can be corrected and pain relieved by this combined procedure

Breaking the superfluid speed limit in a fermionic condensate

Coherent condensates appear as emergent phenomena in many systems. They share the characteristic feature of an energy gap separating the lowest excitations from the condensate ground state. This implies that a scattering object, moving through the system with high enough velocity for the excitation spectrum in the scatterer frame to become gapless, can create excitations at no energy cost, initiating the breakdown of the condensate—the well-known Landau velocity. Whereas, for the neutral fermionic superfluid 3He-B in the T = 0 limit, flow around an oscillating body displays a very clear critical velocity for the onset of dissipation, here we show that for uniform linear motion there is no discontinuity whatsoever in the dissipation as the Landau critical velocity is passed and exceeded. Given the importance of the Landau velocity for our understanding of superfluidity, this result is unexpected, with implications for dissipative effects of moving objects in all coherent condensate systems

New coil concept for endoluminal MR imaging: Initial results in staging of gastric carcinoma in correlation with Histopathology

Our aim was to conduct a prospective study to evaluate staging accuracy of a new coil concept for endoluminal magnetic resonance imaging (MRI) on ex vivo gastric carcinomas. Twenty-eight consecutive patients referred to surgery with a clinically proven primary gastric malignancy were included. Surgical specimens were examined with a foldable and self-expanding loop coil (8-cm diameter) at 1.5 Tesla immediately after total gastrectomy. T1- and T2-weighted and opposed-phase sequences (axial, frontal sections; 3- to 4-mm slice thickness) were acquired. Investigators blinded to any patient information analyzed signal intensity of normal gastric wall, gastric tumor, and lymph nodes. Findings were compared with histopathological staging. On surgical specimens, 2–5 gastric wall layers could be visualized. All gastric tumors (26 carcinomas, two lymphomas) were identified on endoluminal MR data (100%). Overall accuracy for T staging was 75% (18/24); sensitivity to detect serosal involvement was 80% and specificity 89%. N staging correlated in 58% (14/24) with histopathology (N+ versus N−). The endoluminal coil concept is feasible and applicable for an ex vivo setting. Endoluminal MR data provided sufficient detail for gastric wall layer differentiation, and therefore, identification of T stages in gastric carcinoma is possible. Further investigations in in vivo settings should explore the potential of our coil concept for endoluminal MR imaging

Whole-Exome Sequencing Identifies Homozygous AFG3L2 Mutations in a Spastic Ataxia-Neuropathy Syndrome Linked to Mitochondrial m-AAA Proteases

We report an early onset spastic ataxia-neuropathy syndrome in two brothers of a consanguineous family characterized clinically by lower extremity spasticity, peripheral neuropathy, ptosis, oculomotor apraxia, dystonia, cerebellar atrophy, and progressive myoclonic epilepsy. Whole-exome sequencing identified a homozygous missense mutation (c.1847G>A; p.Y616C) in AFG3L2, encoding a subunit of an m-AAA protease. m-AAA proteases reside in the mitochondrial inner membrane and are responsible for removal of damaged or misfolded proteins and proteolytic activation of essential mitochondrial proteins. AFG3L2 forms either a homo-oligomeric isoenzyme or a hetero-oligomeric complex with paraplegin, a homologous protein mutated in hereditary spastic paraplegia type 7 (SPG7). Heterozygous loss-of-function mutations in AFG3L2 cause autosomal-dominant spinocerebellar ataxia type 28 (SCA28), a disorder whose phenotype is strikingly different from that of our patients. As defined in yeast complementation assays, the AFG3L2Y616C gene product is a hypomorphic variant that exhibited oligomerization defects in yeast as well as in patient fibroblasts. Specifically, the formation of AFG3L2Y616C complexes was impaired, both with itself and to a greater extent with paraplegin. This produced an early-onset clinical syndrome that combines the severe phenotypes of SPG7 and SCA28, in additional to other “mitochondrial” features such as oculomotor apraxia, extrapyramidal dysfunction, and myoclonic epilepsy. These findings expand the phenotype associated with AFG3L2 mutations and suggest that AFG3L2-related disease should be considered in the differential diagnosis of spastic ataxias

Consensus on the pathological definition and classification of poorly cohesive gastric carcinoma

Background and aims Clinicopathological characteristics of gastric cancer (GC) are changing, especially in the West with a decreasing incidence of distal, intestinal-type tumours and the corresponding increasing proportion of tumours with Laurén diffuse or WHO poorly cohesive (PC) including signet ring cell (SRC) histology. To accurately assess the behaviour and the prognosis of these GC subtypes, the standardization of pathological definitions is needed. Methods A multidisciplinary expert team belonging to the European Chapter of International Gastric Cancer Association (IGCA) identified 11 topics on pathological classifications used for PC and SRC GC. The topics were debated during a dedicated Workshop held in Verona in March 2017. Then, through a Delphi method, consensus statements for each topic were elaborated. Results A consensus was reached on the need to classify gastric carcinoma according to the most recent edition of the WHO classification which is currently WHO 2010. Moreover, to standardize the definition of SRC carcinomas, the proposal that only WHO PC carcinomas with more than 90% poorly cohesive cells having signet ring cell morphology have to be classified as SRC carcinomas was made. All other PC non-SRC types have to be further subdivided into PC carcinomas with SRC component ( 10% SRCs) and PC carcinomas not otherwise specified (< 10% SRCs). Conclusion The reported statements clarify some debated topics on pathological classifications used for PC and SRC GC. As such, this consensus classification would allow the generation of evidence on biological and prognostic differences between these GC subtypes

A new form of energy dissipation by a moving object in He II.

Despite the superfluid1 character of 4He below the lambda transition temperature, there are two distinct mechanisms by which an object moving through the liquid dissipates kinetic energy: (1) it can scatter the excitations (rotons, phonons, 3He isotopic impurities) that constitute the normal fluid component; and (2) for speeds in excess of the Landau critical velocity vL it can create rotons, apparently in pairs. The first process has been studied extensively, mostly by measurements of the zero-field mobilities of positive and negative ions. The second process, which is much rarer, has also been investigated in considerable detail by studies of the motion of negative ions in isotopically pure 4He at elevated pressures. Here, we report an attempt to extend the latter type of investigation to lower pressures. This yields unexpected results that can be accounted for satisfactorily only if we postulate the existence of a third dissipation mechanism