The histologic examination of endoscopic biopsies or resection specimens remains a key step in the work-up of affected inflammatory bowel disease (IBD) patients and can be used for diagnosis and ...differential diagnosis, particularly in the differentiation of UC from CD and other non-IBD related colitides. The introduction of new treatment strategies in inflammatory bowel disease (IBD) interfering with the patients' immune system may result in mucosal healing, making the pathologists aware of the impact of treatment upon diagnostic features. The European Crohn's and Colitis Organisation (ECCO) and the European Society of Pathology (ESP) jointly elaborated a consensus to establish standards for histopathology diagnosis in IBD. The consensus endeavors to address: (i) procedures required for a proper diagnosis, (ii) features which can be used for the analysis of endoscopic biopsies, (iii) features which can be used for the analysis of surgical samples, (iv) criteria for diagnosis and differential diagnosis, and (v) special situations including those inherent to therapy. Questions that were addressed include: how many features should be present for a firm diagnosis? What is the role of histology in patient management, including search for dysplasia? Which features if any, can be used for assessment of disease activity? The statements and general recommendations of this consensus are based on the highest level of evidence available, but significant gaps remain in certain areas.
Active galactic nuclei, which are powered by long-term accretion onto central supermassive black holes, produce relativistic jets with lifetimes of at least one million years, and the observation of ...the birth of such a jet is therefore unlikely. Transient accretion onto a supermassive black hole, for example through the tidal disruption of a stray star, thus offers a rare opportunity to study the birth of a relativistic jet. On 25 March 2011, an unusual transient source (Swift J164449.3+573451) was found, potentially representing such an accretion event. Here we report observations spanning centimetre to millimetre wavelengths and covering the first month of evolution of a luminous radio transient associated with Swift J164449.3+573451. The radio transient coincides with the nucleus of an inactive galaxy. We conclude that we are seeing a newly formed relativistic outflow, launched by transient accretion onto a million-solar-mass black hole. A relativistic outflow is not predicted in this situation, but we show that the tidal disruption of a star naturally explains the observed high-energy properties and radio luminosity and the inferred rate of such events. The weaker beaming in the radio-frequency spectrum relative to γ-rays or X-rays suggests that radio searches may uncover similar events out to redshifts of z ≈ 6.
Barrett's oesophagus (BE) is a premalignant condition that can progress to oesophageal adenocarcinoma. Endoscopic surveillance aims to identify potential progression at an early, treatable stage, but ...generates large numbers of tissue biopsies. Fourier transform infrared (FTIR) mapping was used to develop an automated histology tool for detection of BE and Barrett's neoplasia in tissue biopsies. 22 oesophageal tissue samples were collected from 19 patients. Contiguous frozen tissue sections were taken for pathology review and FTIR imaging. 45 mid-IR images were measured on an Agilent 620 FTIR microscope with an Agilent 670 spectrometer. Each image covering a 140 μm × 140 μm region was measured in 5 minutes, using a 1.1 μm
pixel size and 64 scans per pixel. Principal component fed linear discriminant analysis was used to build classification models based on spectral differences, which were then tested using leave-one-sample-out cross validation. Key biochemical differences were identified by their spectral signatures: high glycogen content was seen in normal squamous (NSQ) tissue, high glycoprotein content was observed in glandular BE tissue, and high DNA content in dysplasia/adenocarcinoma samples. Classification of normal squamous samples versus 'abnormal' samples (any stage of Barrett's) was performed with 100% sensitivity and specificity. Neoplastic Barrett's (dysplasia or adenocarcinoma) was identified with 95.6% sensitivity and 86.4% specificity. Highly accurate pathology classification can be achieved with FTIR measurement of frozen tissue sections in a clinically applicable timeframe.
Caring for a growing aging population using existing long-term care resources while simultaneously supporting and educating family caregivers, is a public health challenge. We describe the ...application of the Replicating Effective Programs (REP) framework, developed by the Centers for Disease Control Prevention and used in public health program implementation, to scale up an evidence-based family caregiver training intervention in the Veterans Affairs (VA) healthcare system.
From 2018 to 2020, clinicians at eight VA medical centers received REP-guided implementation including facilitation, technical assistance, and implementation tools to deliver the training program. The project team used the REP framework to develop activities across four distinct phases - (1) pre-conditions, (2) pre-implementation, (3) implementation, and (4) maintenance and evolution - and systematically tracked implementation facilitators, barriers, and adaptations.
Within the REP framework, results describe how each medical center adapted implementation approaches to fit local needs. We highlight examples of how sites balanced adaptations and intervention fidelity.
The REP framework shows promise for national expansion of the caregiver training intervention, including to non-VA systems of care, because it allows sites to adapt while maintaining intervention fidelity.
NCT03474380 . Date registered: March 22, 2018.
Legislative drivers for water quality and urban flood risk are driving a growing need to accurately determine the performance of urban drainage systems in near real time. Rainfall data are clearly a ...key input to urban drainage system models. Historically rain gauge data have been used, however radar rainfall data are now widely available and benefits from significantly higher spatial coverage than rain gauges in most UK urban catchments. This paper describes a detailed study based on a small (11km2) urban catchment in West Yorkshire, England. Radar and rain gauge data have been compared and used as the input to hydrodynamic sewer flow simulations, and the results of these simulations have been compared with measured flows in the sewer system. The results showed that for this size of catchment, there can be significant differences in simulated peak flows and combined sewer overflow spill volumes due to inherent uncertainties between the two rainfall estimates.
Lunar water is redistributed by various processes. Topographic diffusion affects the transport of water and contributes to its preservation in subsurface layers. Here, we analyze 16 complex craters ...(∼3.2 – ∼4.2 Ga) larger than 20 km in diameter near the lunar south pole to quantify their degradation states. The results show that the diffusive rates of late Imbrian craters are similar to those of similarly aged simple craters, while Nectarian and pre‐Nectarian craters are degraded less efficiently. Within a complex crater, the mass accumulation by topographic diffusion and ejecta blankets from other complex craters preserves water, ranging up to 1 wt% on average. However, impact mixing and internal heat further limit the stability of ancient water to subsurface regions with ages younger than 3.9 Ga and at depth from a few meters to 10s of meters.
Plain Language Summary
Water in lunar shadowed regions is redistributed by various processes. When small craters form on a large crater's wall, its topography gradually erodes. Surface materials and deposited water move downhill, leading to a mixture of these materials and accumulations on the complex crater's floor. Here, we analyze 16 complex craters older than 3.2 Ga and larger than 20 km in diameter near the lunar south pole to investigate how fast these complex craters are topographically eroded. The results show that the speeds of topographic degradation of craters with an age of ∼3.2 Ga are comparable to those of similarly aged simple craters, while older craters experience significant degradation but are diffused inefficiently. On a complex crater, water may be stored in accumulated mass by topographic diffusion and large ejecta blankets for a long time. Such accumulated regions may host water, ranging up to 1 wt%. However, impact mixing and internal heat compete against the water supply and storage, limiting the water existence in subsurface layers at 10s of meters but a few meters below the surface and younger than 3.9 Ga.
Key Points
Topographic degradation of 16 complex craters near the lunar south pole significantly varies with surface age and crater size
Mass wasting by topographic diffusion and ejecta blanketing mixes water with regolith, giving a water mass fraction of up to 1 wt%
Impact mixing and internal heat limit the existence of unaffected ancient water at 10s of meters in depth and younger than 3.9 Ga
There is an increasing burden upon diagnostic histopathologists to identify accurately factors of prognostic and therapeutic implication in gastrointestinal cancer. It is perhaps partly because of ...the use of rigid sequential staging systems, such as the Dukes' classification, that some factors, perhaps most notably involvement of surgical margins (especially in rectal cancer) and serosal involvement (particularly in oesophageal, colonic and rectal cancer), have been relatively neglected until more recently. This is surprising and concerning because both of these pathologically derived parameters strongly correlate with subsequent locoregional recurrence and, ultimately, with prognosis. Whilst the occurrence and significance of serosal involvement have been well recognized in gastric cancer for many years, relatively little attention has been paid to the phenomenon in oesophageal cancer and yet both pleural and peritoneal involvement may be comparatively commonly identified in oesophageal cancer. Serosal involvement and transperitoneal spread are also of considerable prognostic importance in primary appendiceal carcinoma. Only more recently has the significance of serosal involvement been appreciated in colonic and rectal cancer. In the colon, the phenomenon is now recognized to be one of the most important factors in predicting transperitoneal spread and overall prognosis. Furthermore, there is increasing interest in alternative novel strategies, including intraperitoneal chemotherapy and radical peritoneal surgery, as legitimate therapeutic options in many gastrointestinal cancers.
In obesity, improved muscle insulin sensitivity following exercise training has been linked to the lowering of diacylglycerol (DAG) and ceramide concentrations. Little is known, however, about how ...improved insulin action with exercise training in obese individuals relates to lipid droplet (LD) adaptations in skeletal muscle. In this study we investigated the hypothesis that short-term sprint interval training (SIT) and moderate-intensity continuous training (MICT) in obese individuals would increase perilipin (PLIN) expression, increase the proportion of LDs in contact with mitochondria and reduce muscle concentrations of DAGs and ceramides.
Sixteen sedentary obese males performed 4 weeks of either SIT (4-7 × 30 s sprints at 200% W
, 3 days week) or MICT (40-60 min cycling at ~65% VO
, 5 days per week), and muscle biopsies were obtained pre- and post-training.
Training increased PLIN2 (SIT 90%, MICT 68%) and PLIN5 (SIT 47%, MICT 34%) expression in type I fibres only, and increased PLIN3 expression in both type I (SIT 63%, MICT 67%) and type II fibres (SIT 70%, MICT 160%) (all P<0.05). Training did not change LD content but increased the proportion of LD in contact with mitochondria (SIT 12%, MICT 21%, P<0.01). Ceramides were reduced following training (SIT -10%, MICT -7%, P<0.05), but DAG was unchanged. No training × group interactions were observed for any variables.
These results confirm the hypothesis that SIT and MICT results in remodelling of LDs and lowers ceramide concentrations in skeletal muscle of sedentary obese males.
Viscoelastic properties of articular cartilage have been characterised at physiological frequencies. However, studies investigating the interaction between cartilage and subchondral bone and the ...influence of underlying bone histomorphometry on the viscoelasticity of cartilage are lacking.
Dynamic Mechanical Analysis (DMA) has been used to quantify the dynamic viscoelasticity of bovine tibial plateau osteochondral cores, over a frequency sweep from 1 to 88 Hz. Specimens (approximately aged between 18 and 30 months) were neither osteoarthritic nor otherwise compromised. A maximum nominal stress of 1.7 MPa was induced. Viscoelastic properties of cores have been compared with that of its components (cartilage and bone) in terms of the elastic and viscous components of both structural stiffness and material modulus. Micro-computed tomography scans were used to quantify the histomorphological properties of the subchondral bone.
Opposing frequency-dependent loss stiffness, and modulus, trends were witnessed for osteochondral tissues: for cartilage it increased logarithmically (P < 0.05); for bone it decreased logarithmically (P < 0.05). The storage stiffness of osteochondral cores was logarithmically frequency-dependent (P < 0.05), however, the loss stiffness was typically frequency-independent (P > 0.05). A linear relationship between the subchondral bone plate (SBP) thickness and cartilage thickness (P < 0.001) was identified. Cartilage loss modulus was linearly correlated to bone mineral density (BMD) (P < 0.05) and bone volume (P < 0.05).
The relationship between the subchondral bone histomorphometry and cartilage viscoelasticity (namely loss modulus) and thickness, have implications for the initiation and progression of osteoarthritis (OA) through an altered ability of cartilage to dissipate energy.
Summary
We conducted a single‐centre observational study of retrievals for severe respiratory failure over 12 months. Our intensivist‐delivered retrieval service has mobile extracorporeal membrane ...oxygenation capabilities. Sixty patients were analysed: 34 (57%) were female and the mean (SD) age was 44.1 (13.6) years. The mean (SD) PaO2/FIO2 ratio at referral was 10.2 (4.1) kPa and median (IQR range) Murray score was 3.25 (3.0–3.5 1.5–4.0). Forty‐eight patients (80%) required veno‐venous extracorporeal membrane oxygenation at the referring centre. There were no cannulation or extracorporeal membrane oxygenation‐related complications. The median (IQR range) retrieval distance was 47.2 (14.9–77.0 2.3–342.0) miles. There were no major adverse events during retrieval. Thirty‐seven patients (77%) who received extracorporeal membrane oxygenation survived to discharge from the intensive care unit and 36 patients (75%) were alive after six months. Senior intensivist‐initiated and delivered mobile extracorporeal membrane oxygenation is safe and associated with a high incidence of survival.
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