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Abstract Background Thoracotomy is considered one of the most painful surgical procedures and can cause debilitating chronic post-surgical pain lasting months or years postoperatively. Aggressive management of acute pain resulting from thoracotomy may reduce the likelihood of developing chronic pain. This trial compares the two most commonly used modes of acute analgesia provision at the time of thoracotomy (thoracic epidural blockade (TEB) and paravertebral blockade (PVB)) in terms of their clinical and cost-effectiveness in preventing chronic post-thoracotomy pain. Methods TOPIC 2 is a multi-centre, open-label, parallel group, superiority, randomised controlled trial, with an internal pilot investigating the use of TEB and PVB in 1026 adult (≥ 18 years old) patients undergoing thoracotomy in up to 20 thoracic centres throughout the UK. Patients (N = 1026) will be randomised in a 1:1 ratio to receive either TEB or PVB. During the first year, the trial will include an integrated QuinteT (Qualitative Research Integrated into Trials) Recruitment Intervention (QRI) with the aim of optimising recruitment and informed consent. The primary outcome is the incidence of chronic post-surgical pain at 6 months post-randomisation defined as ‘worst chest pain over the last week’ equating to a visual analogue score greater than or equal to 40 mm indicating at least a moderate level of pain. Secondary outcomes include acute pain, complications of regional analgesia and surgery, health-related quality of life, mortality and a health economic analysis. Discussion Both TEB and PVB have been demonstrated to be effective in the prevention of acute pain following thoracotomy and nationally practice is divided. Identification of which mode of analgesia is both clinically and cost-effective in preventing chronic post-thoracotomy pain could ameliorate the debilitating effects of chronic pain, improving health-related quality of life, facilitating return to work and caring responsibilities and resulting in a cost saving to the NHS. Trial registration NCT03677856 [ClinicalTrials.gov] registered September 19, 2018. https://clinicaltrials.gov/ct2/show/NCT03677856 . First patient recruited 8 January 2019.

BackgroundAspects of cognitive function decline with age. This phenomenon is referred to as age-related cognitive decline (ARCD). Improving the understanding of these changes that occur as part of the ageing process can serve to enhance the detection of the more incapacitating neurodegenerative disorders such as Alzheimer’s disease (AD). In this study, we employ novel methods to assess ARCD by exploring the utility of the alpha3/alpha2 electroencephalogram (EEG) power ratio – a marker of AD, and a novel virtual reality (VR) functional cognition task – VStore, in discriminating between young and ageing healthy adults.Materials and methodsTwenty young individuals aged 20–30, and 20 older adults aged 60–70 took part in the study. Participants underwent resting-state EEG and completed VStore and the Cogstate Computerised Cognitive Battery. The difference in alpha3/alpha2 power ratios between the age groups was tested using t-test. In addition, the discriminatory accuracy of VStore and Cogstate were compared using logistic regression and overlying receiver operating characteristic (ROC) curves. Youden’s J statistic was used to establish the optimal threshold for sensitivity and specificity and model performance was evaluated with the DeLong’s test. Finally, alpha3/alpha2 power ratios were correlated with VStote and Cogstate performance.ResultsThe difference in alpha3/alpha2 power ratios between age cohorts was not statistically significant. On the other hand, VStore discriminated between age groups with high sensitivity (94%) and specificity (95%) The Cogstate Pre-clinical Alzheimer’s Battery achieved a sensitivity of 89% and specificity of 60%, and Cogstate Composite Score achieved a sensitivity of 83% and specificity of 85%. The differences between the discriminatory accuracy of VStore and Cogstate models were statistically significant. Finally, high alpha3/alpha2 power ratios correlated strongly with VStore (r = 0.73), the Cogstate Pre-clinical Alzheimer’s Battery (r = -0.67), and Cogstate Composite Score (r = -0.76).ConclusionWhile we did not find evidence that the alpha3/alpha2 power ratio is elevated in healthy ageing individuals compared to young individuals, we demonstrated that VStore can classify age cohorts with high accuracy, supporting its utility in the assessment of ARCD. In addition, we found preliminary evidence that elevated alpha3/alpha2 power ratio may be linked to lower cognitive performance.

A 70-year old man had multiple lung nodules detected on a computed tomography (CT) performed as part of the work-up for an isolated episode of hematuria of several hours' duration. A CT-guided lung biopsy disclosed a morphologically undifferentiated neoplasm, that could not be further subclassified despite an extensive immunohistochemical panel.Four years previously the patient had undergone a left hemicolectomy in another institution to resect a 4.7 cm polypoid ulcerated area in the splenic flexure. The slides from that resection were retrieved for review at our institution. There was a variably cellular, diffuse spindle cell neoplastic proliferation involving the submucosa, muscularis propria and subserosa of the large bowel, composed of elongated spindle cells, with small, inconspicuous nucleoli, arranged in intersecting fascicles. Occasional areas of the tumor showed myxoid stroma. Mitotic activity was low.Immunohistochemistry showed strong and diffuse cytoplasmic staining for MUC4 in both the large bowel and lung tumors. Molecular profiling identified a FUS-CREB3L1 fusion gene.The constellation of morphological, immunohistochemical and molecular features are of low-grade fibromyxoid sarcoma (LGFMS) of the large bowel, with metastatic fibromyxoid sarcoma to the lung.LGFMS is a malignant, often late-metastasizing tumor, with a misleadingly bland histological appearance, that typically arises in the deep soft tissues of the proximal extremities or trunk of young adults. Accurate classification, requiring morphology and ancillary tests, is required for appropriate clinical follow-up and treatment of patients. Keywords: Colon, Low-grade fibromyxoid sarcoma, Metastasis, Lung

Objectives Thoracotomy is considered one of the most painful surgical procedures. The incidence of chronic post-thoracotomy pain (CPTP) is up to 50%. Paravertebral blockade (PVB) may be superior to thoracic epidural blockade (TEB) in preventing CPTP. The specific objective of this pilot study was to assess the feasibility of conducting a larger trial to determine whether PVB at thoracotomy is more effective in reducing CPTP compared with TEB.Design A randomised, parallel, external pilot study was conducted to assess whether a large randomised trial of TEB and PVB with CPTP as the primary outcome is feasible.Setting Two adult thoracic centres in the UK.Participants All adult patients admitted for elective open thoracotomy. Participants were excluded if they were American Society of Anesthesiologists physical status IV or V; or if there is contraindication to local anaesthetics; infection near the proposed puncture site; coagulation/thoracic spine disorders; required chest wall resection or emergency thoracic surgery or had a previous thoracotomy.Results All patients presenting for thoracotomy were screened over a 12-month period with 194 found to be eligible. Of these, 69 (36%) were randomised (95% CI 29% to 42%). Discounting five participants who died, 54 of 64 participants (84%) returned questionnaire booklets at 6 months. The number of participants indicating at least a moderate level of chest pain at 6 months was lower with PVB but with high levels of uncertainty (RR: 0.7; 95% CI 0.3 to 1.7 for worst pain; RR: 0.3; 95% CI 0.0 to 2.8 for average pain). There were no safety concerns.Conclusions A large, multicentre randomised controlled trial of PVB versus TEB is feasible as it is possible to randomise and follow up participants with high fidelity. Pain scores were lower on average with PVB compared with TEB but a much larger trial is required to confirm this reliably.Trial registration number ISRCTN45041624

Background: Thoracotomy is considered one of the most painful surgical procedures and can cause debilitating chronic post-surgical pain lasting months or years postoperatively. Aggressive management of acute pain resulting from thoracotomy may reduce the likelihood of developing chronic pain. This trial compares the two most commonly used modes of acute analgesia provision at the time of thoracotomy (thoracic epidural blockade (TEB) and paravertebral blockade (PVB)) in terms of their clinical and cost-effectiveness in preventing chronic post-thoracotomy pain. Methods: TOPIC 2 is a multi-centre, open-label, parallel group, superiority, randomised controlled trial, with an internal pilot investigating the use of TEB and PVB in 1026 adult (≥ 18 years old) patients undergoing thoracotomy in up to 20 thoracic centres throughout the UK. Patients (N = 1026) will be randomised in a 1:1 ratio to receive either TEB or PVB. During the first year, the trial will include an integrated QuinteT (Qualitative Research Integrated into Trials) Recruitment Intervention (QRI) with the aim of optimising recruitment and informed consent. The primary outcome is the incidence of chronic post-surgical pain at 6 months post-randomisation defined as 'worst chest pain over the last week' equating to a visual analogue score greater than or equal to 40 mm indicating at least a moderate level of pain. Secondary outcomes include acute pain, complications of regional analgesia and surgery, health-related quality of life, mortality and a health economic analysis. Discussion: Both TEB and PVB have been demonstrated to be effective in the prevention of acute pain following thoracotomy and nationally practice is divided. Identification of which mode of analgesia is both clinically and cost-effective in preventing chronic post-thoracotomy pain could ameliorate the debilitating effects of chronic pain, improving health-related quality of life, facilitating return to work and caring responsibilities and resulting in a cost saving to the NHS. Trial registration: NCT03677856 [ClinicalTrials.gov] registered September 19, 2018. https://clinicaltrials.gov/ct2/show/NCT03677856. First patient recruited 8 January 2019. [ABSTRACT FROM AUTHOR]

In this paper, we compare the chemistry and the emission spectra of nitrogen-dominated cool, warm, and hot ultra-short-period (USP) super-Earth atmospheres in and out of chemical equilibrium at various surface pressure scenarios ranging from 10−1 to 10 bar. We link the one-dimensional vulcan chemical kinetic code, in which thermochemical kinetic and vertical transport and photochemistry are taken into account, to the one-dimensional radiative transfer model, petitradtrans , to predict the emission spectra of these planets. The radiative–convective temperature–pressure profiles were computed with the helios code. Then, using pandexo noise simulator, we explore the observability of the differences produced by disequilibrium processes with the JWST. Our grids show how different surface pressures can significantly affect the temperature profiles, the atmospheric abundances, and consequently the emission spectra of these planets. We find that the divergences due to disequilibrium processes would be possible to observe in cooler planets by targeting HCN, C2H4, and CO, and in warmer planets by targeting CH4 with HCN, using the NIRSpec and MIRI LRS JWST instruments. These species are also found to be sensitive indicators of the existence of surfaces on nitrogen-dominated USP super-Earths, providing information regarding the thickness of these atmospheres. [ABSTRACT FROM AUTHOR]

A previously fit and well man developed acute respiratory failure due to environmental mould exposure from living in damp rental accommodation. Despite aggressive intensive care management he rapidly deteriorated and required respiratory and cardiac Extracorporeal Membrane Oxygenation. We hypothesize that poor domiciliary conditions may make an underestimated contribution to community respiratory disease. These conditions may present as acute and severe illness with non-typical pathogens identified.

Tumor recurrence following treatment remains a major clinical challenge. Evidence from xenograft models and human trials indicates selective enrichment of cancer-initiating cells (CICs) in tumors that survive therapy. Together with [...]

Every 8.5h, the star Kepler-78 (first known as TYC3147-188-1 and later designated KIC 8435766) presents to the Earth a shallow eclipse consistent (8) with the passage of an orbiting planet [...], Recent analyses (1-4) of data from the NASA Kepler spacecraft (5) have established that planets with radii within 25 per cent of the Earth's (R⊕) are commonplace throughout the Galaxy, orbiting at least 16.5 per cent of Sun-like stars (1). Because these studies were sensitive to the sizes of the planets but not their masses, the question remains whether these Earth-sized planets are indeed similar to the Earth in bulk composition. The smallest planets for which masses have been accurately determined (6, 7) are Kepler-10b (1.42R⊕) and Kepler-36b (1.49R⊕), which are both significantly larger than the Earth. Recently, the planet Kepler-78b was discovered (8) and found to have a radius of only 1.16R⊕. Here we report that the mass of this planet is 1.86 Earth masses. The resulting mean density of the planet is 5.57 g [cm.sup.-3], which is similar to that of the Earth and implies a composition of iron and rock.

BACKGROUND: Many consider histology to be the gold standard for Helicobacter pylori detection. Because the number and distribution of H pylori organisms vary, particularly in patients taking proton pump inhibitors (PPIs), the American Gastroenterological Association recommends discontinuing PPIs two weeks before endoscopy, and taking biopsies from both the body and antrum.