Endoscopic duodenal-jejunal bypass liner treatment of moderate obstructive sleep apnoea-A pilot study.

We aimed to assess the extent to which people with type 2 diabetes or pre-diabetes, obesity (BMI 30-45 kg/m2) and moderate obstructive sleep apnoea (OSA) requiring continuous positive airway pressure ventilation (CPAP) were able to discontinue CPAP following EndoBarrier-related weight loss. We assessed sleep and metabolic parameters before, during and after EndoBarrier in 12 participants with moderate OSA requiring CPAP (75% female, 8/12 [66%] type 2 diabetes, 4/12 [34%] prediabetes, mean ± SD age 52.6 ± 9.7 years, BMI 37.4 ± 3.5 kg/m2, median duration of OSA while on CPAP 9.0 [7.0-15.0] months). With EndoBarrier in-situ, mean ± SD Apnoea Hypopnoea Index (AHI) fell by 9.1 ± 5.0 events/h from 18.9 ± 3.8 to 9.7 ± 3.0 events/h (p < .001) with an associated reduction in symptoms of daytime sleepiness (mean Epworth Sleepiness Score) such that all the 12 participants no longer required CPAP according to National Institute for Health and Care Excellence criteria. After EndoBarrier removal, 10/12 (83%) patients attended follow-up and at 12 months after removal, AHI remained below 15 in 5/10 (50%) patients but in other five the AHI rose above 15 such that restarting CPAP was recommended as justified by their symptoms. Rather than restart CPAP, two patients lost the regained weight and their AHI dropped below 15 again. Thus, 7/10 (70%) of patients were able to remain off CPAP 12 or more months after EndoBarrier removal. These results demonstrate major benefit of EndoBarrier in moderate OSA, allowing all patients to discontinue CPAP during treatment, and with maintenance of improvement at follow-up in 70%. They confirm previously demonstrated metabolic improvements in diabetes and obesity.

Oculometric biomarkers of visuomotor deficits in clinically asymptomatic patients with systemic lupus erythematosus undergoing long-term hydroxychloroquine treatment.

Introduction: This study examines a set of oculomotor measurements, or "oculometric" biomarkers, as potential early indicators of visual and visuomotor deficits due to retinal toxicity in asymptomatic Systemic Lupus Erythematosus (SLE) patients on long-term hydroxychloroquine (HCQ) treatment. The aim is to identify subclinical functional impairments that are otherwise undetectable by standard clinical tests and to link them to structural retinal changes. Methods: We measured oculomotor responses in a cohort of SLE patients on chronic HCQ therapy using a previously established behavioral task and analysis technique. We also examined the relationship between oculometrics, OCT measures of retinal thickness, and standard clinical perimetry measures of visual function in our patient group using Bivariate Pearson Correlation and a Linear Mixed-Effects Model (LMM). Results: Significant visual and visuomotor deficits were found in 12 asymptomatic SLE patients on long-term HCQ therapy compared to a cohort of 17 age-matched healthy controls. Notably, six oculometrics were significantly different. The median initial pursuit acceleration was 22%, steady-state pursuit gain 16%, proportion smooth 7%, and target speed responsiveness 31% lower, while catch-up saccade amplitude was 46% and fixation error 46% larger. Excluding the two patients with diagnosed mild toxicity, four oculometrics, all but fixation error and proportion smooth, remained significantly impaired compared to controls. Across our population of 12 patients (24 retinae), we found that pursuit latency, initial acceleration, steady-state gain, and fixation error were linearly related to retinal thickness even when age was accounted for, while standard measures of clinical function (Mean Deviation and Pattern Standard Deviation) were not. Discussion: Our data show that specific oculometrics are sensitive early biomarkers of functional deficits in SLE patients on HCQ that could be harnessed to assist in the early detection of HCQ-induced retinal toxicity and other visual pathologies, potentially providing early diagnostic value beyond standard visual field and OCT evaluations.

Exploring a targeted approach for public health capacity restrictions during COVID-19 using a new computational model.

This work introduces the Queen's University Agent-Based Outbreak Outcome Model (QUABOOM). This tool is an agent-based Monte Carlo simulation for modelling epidemics and informing public health policy. We illustrate the use of the model by examining capacity restrictions during a lockdown. We find that public health measures should focus on the few locations where many people interact, such as grocery stores, rather than the many locations where few people interact, such as small businesses. We also discuss a case where the results of the simulation can be scaled to larger population sizes, thereby improving computational efficiency.

Performance of a convolutional autoencoder designed to remove electronic noise from p-type point contact germanium detector signals.

We present a convolutional autoencoder to denoise pulses from a p-type point contact high-purity germanium detector similar to those used in several rare event searches. While we focus on training procedures that rely on detailed detector physics simulations, we also present implementations requiring only noisy detector pulses to train the model. We validate our autoencoder on both simulated data and calibration data from an 241 Am source, the latter of which is used to show that the denoised pulses are statistically compatible with data pulses. We demonstrate that our denoising method is able to preserve the underlying shapes of the pulses well, offering improvement over traditional denoising methods. We also show that the shaping time used to calculate energy with a trapezoidal filter can be significantly reduced while maintaining a comparable energy resolution. Under certain circumstances, our denoising method can improve the overall energy resolution. The methods we developed to remove electronic noise are straightforward to extend to other detector technologies. Furthermore, the latent representation from the encoder is also of use in quantifying shape-based characteristics of the signals. Our work has great potential to be used in particle physics experiments and beyond.

Recurrent Pyroglutamic Acidosis in the Context of Undiagnosed Liver Cirrhosis-A Case Report.

Metabolic associated fatty liver disease, previously known as nonalcoholic fatty liver disease, is the most common cause of chronic liver disease across all ethnic groups; however, it remains enormously underestimated.1 , 2 Sepsis, hepatotoxic medications and malnutrition in the acute settings on top of unknown cirrhosis can lead to decompensation and various metabolic complications. Pyroglutamic acidosis is a rarely recognised cause for unexplained high anion gap metabolic acidosis that is felt to be frequently underdiagnosed. Particular patients at risk include women, the elderly, those on regular paracetamol and those suffering with malnourishment or sepsis. Other risk factors include alcohol abuse and chronic liver disease (3). We present the case of a patient with recurrent episodes of pyroglutamic acidosis and encephalopathy in the context of undiagnosed nonalcoholic fatty liver disease with cirrhosis.

Metastatic ampullary adenocarcinoma presenting as a hydrocele: a case report.

CONTEXT: Metastases from ampullary malignancies are common, but spread to the testicle and paratesticular tissue is exceedingly rare with only 2 reported cases in the literature. CASE REPORT: We report a case of a 70 year-old male with a history of ampullary adenocarcinoma status post pancreaticoduodenectomy who presented with a symptomatic right-sided hydrocele. Subsequent pathology revealed metastatic ampullary adenocarcinoma. CONCLUSIONS: Metastasis to the testicle and paratesticular tissue from ampullary malignancies is rare, but must be considered in the evaluation of scrotal masses in patients with a history of ampullary malignancy.

Perioperative intravesical chemotherapy in non-muscle-invasive bladder cancer: a systematic review and meta-analysis.

The role for a single dose of intravesical chemotherapy (IVC) after transurethral resection (TUR) remains unclear in patients with non-muscle-invasive bladder cancer (NMIBC). Several recent randomized clinical trials (RCTs) have evaluated its effect on recurrence, prompting this systematic review of RCTs comparing a single immediate postoperative dose of IVC versus placebo within 24 hours of TUR of NMIBC, and this meta-analysis using a random-effects model to predict the pooled relative risk (RR) of tumor recurrence. Subanalyses pooled studies by drug type and a meta-regression was performed to determine the effect of underlying patient risk factors on the efficacy of a single dose of IVC. A total of 3103 patients were randomized in the 18 RCTs that met inclusion criteria. The recurrence rate in patients receiving perioperative IVC and TUR was 37% versus 50% in the TUR-alone group. The pooled RR of recurrence for IVC and TUR was 0.67 (95% CI, 0.56-0.79), corresponding to a 13% absolute reduction and a number needed to treat of 7.2 patients to avoid 1 recurrence. The proportions of patients with tumor risk factors (T1, high-grade, multifocal, or recurrent) were not associated with IVC efficacy. A single dose of IVC administered within 24 hours of TUR of NMIBC was found to result in a reduction in tumor recurrence (RR, 0.67; 95% CI, 0.56-0.79). Patients with higher-risk tumor features seem to benefit at a similar rate.

Community-based information exchange. Community-based hies are a model of interoperability among clinical information systems.

Many health providers have focused on community-based health information exchanges (HIEs) as a useful platform to help them take the next steps in implementing electronic health information. Recent research by a healthcare technology advisory firm is an attempt to characterize various HIE models, with an eye on achieving that goal.

Potential driven deposition of polyelectrolytes onto the surface of cysteine monolayers assembled on gold.

Electrochemical impedance spectroscopy and the quartz crystal microbalance measurements are used to examine the ability of potential applied to a substrate to create, in situ, conditions favorable for the electrostatic deposition of polyelectrolytes onto a gold substrate modified by the self-assembly of cysteine. Cysteine is a zwitterionic compound that, when confined to a substrate, has the ability to establish either a net positive or a net negative interfacial charge, depending on the conditions. As such, cysteine modified interfaces could possibly be used as a versatile substrate for deposition of either cationic or anionic polyelectrolytes. The potential of zero charge of a gold electrode modified by self-assembly with cysteine in the presence of 0.10molL(-1) KCl and buffered at pH 5 is found by differential capacitance measurement to be -0.12(+/-0.02)V vs. Ag/AgCl. When -0.05V vs. Ag/AgCl is applied to the substrate (a potential positive of the PZC) in the presence of different polyelectrolytes, both impedance spectroscopy and quartz crystal microbalance data suggest the accumulation of anionic poly(sodium styrenesulfonate) along the cysteine modified interface. Conversely, when -0.40V vs. Ag/AgCl is applied to the substrate (a potential negative of the PZC), experimental results suggest the accumulation of cationic poly(diallydimethylammonium chloride).

Electrochemical glucose sensors--developments using electrostatic assembly and carbon nanotubes for biosensor construction.

In 1962, Clark and Lyons proposed incorporating the enzyme glucose oxidase in the construction of an electrochemical sensor for glucose in blood plasma. In their application, Clark and Lyons describe an electrode in which a membrane permeable to glucose traps a small volume of solution containing the enzyme adjacent to a pH electrode, and the presence of glucose is detected by the change in the electrode potential that occurs when glucose reacts with the enzyme in this volume of solution. Although described nearly 50 years ago, this seminal development provides the general structure for constructing electrochemical glucose sensors that is still used today. Despite the maturity of the field, new developments that explore solutions to the fundamental limitations of electrochemical glucose sensors continue to emerge. Here we discuss two developments of the last 15 years; confining the enzyme and a redox mediator to a very thin molecular films at electrode surfaces by electrostatic assembly, and the use of electrodes modified by carbon nanotubes (CNTs) to leverage the electrocatalytic effect of the CNTs to reduce the oxidation overpotential of the electrode reaction or for the direct electron transport to the enzyme.

Impedance differences found with n-alkanethiol monolayers prepared by contact printing and solution adsorption.

Self-assembled monolayers (SAMs) of n-octadecanethiol, n-dodecanethiol and n-pentanethiol formed by contact printing and solution adsorption are characterized by electrochemical impedance spectroscopy (EIS). Impedance measurements show that monolayers prepared by contact printing are on the order of 5 times less resistive to charge transfer and have greater defect density than monolayers prepared by solution adsorption. Modeling of the average defect size and density show that the size of monolayer defects stays relatively constant independent of the monolayer preparation conditions; however, the density of defects decreases with increasing concentration for the contact printed monolayers. The impedance data also show that monolayers prepared by solution adsorption have fewer defects than those prepared by contact printing.

The effect of ethnicity on the presentation and management of oesophageal and gastric cancers: a UK perspective.

BACKGROUND: Studies show disparities in the management of oesophageal and gastric cancers between different ethnic groups. Asian patients with gastric adenocarcinoma present with less advanced disease and are more likely to undergo curative resection. For oesophageal cancer, the rate of surgery in Black patients is half that of Caucasians. However, these studies originate from the United States where demographics differ from that of the UK. METHODS: We undertook a 5-year retrospective audit of patients diagnosed with oesophageal and gastric cancers at City Hospital, Birmingham (UK), which serves three major ethnic groups: Caucasians, Blacks and Asians. RESULTS: Data were extracted from 244 patients' records that included 133 gastric and 111 oesophageal cancers. Caucasians were more likely to present within 3 months of symptom onset than Asians or Blacks. Asians were less likely to be referred for urgent endoscopy than Caucasians or Blacks (P<0.05). Significant differences in reported symptoms were found between ethnic groups with Caucasians more likely to report dysphagia and less likely to describe abdominal pain than other ethnic groups. There was a lower rate of curative operation for Asians but this did not reach significance. CONCLUSION: Ethnicity seems to influence health-seeking behaviour, with Caucasians more likely to present earlier for medical attention and Asian patients less likely to be referred for urgent endoscopy. Improvements in symptom education amongst patients and health professionals alike may accelerate referral and improve outcome. The favourable disease patterns reported in the United States 'Asians' and the lower surgery rates reported in the United States 'Blacks' are not shown in this UK population.

Electrostatic deposition of polycations and polyanions onto cysteine monolayers.

Electrochemical impedance spectroscopy and the quartz crystal microbalance are used to monitor the deposition of polyelectrolytes onto an interface modified with a monolayer of cysteine. When using an anionic redox probe, Fe(CN)(6)(-4), the impedance of the cysteine modified electrode is a function of the solution pH; the charge-transfer resistance being higher at basic pH, and smaller under acidic conditions relative to the value found when the solution is buffered near the pI for cysteine. This behavior is consistent with the electrostatic interaction between the anionic redox probe and the net charge of the interface. After exposure of the cysteine-modified interface to 0.10 mol L(-1) HCl solutions containing polystyrene sulfonate, the impedance of the modified interface increases. This behavior is consistent with the interface having a net negative charge, and suggests that the polyanion is confined to the interface. Quartz crystal microbalance measurements also show that 700+/-20 ng of the PSS is deposited under the acidic conditions. After exposure to 0.10 mol L(-1) NaOH solutions containing poly(diallyldimethyl)ammonium chloride, the impedance of the modified interface decreases, consistent with the electrostatic assembly of the polycation to the cysteine monolayer under these conditions. Quartz crystal microbalance measurements indicate that 770+/-40 ng of the poly(diallyldimethylammonium chloride) are deposited under the basic conditions.

Potential driven deposition of poly(diallyldimethylammonium chloride) onto the surface of 3-mercaptopropionic acid monolayers assembled on gold.

Electrochemical impedance spectroscopy (EIS) and quartz crystal microbalance (QCM) measurements are used to examine the ability of applied potential to drive the ionic self-assembly of poly(diallyldimethylammonium) chloride (PDDA) onto a substrate modified with a monolayer of 3-mercaptopropionic acid (3-MPA). The potential of zero charge (PZC) of the gold electrode modified with a monolayer of 3-MPA was found by differential capacitance measurements to be -0.12 (+/-0.01) V versus Ag-AgCl. Changing the substrate potential to values positive (-0.01 V vs Ag-AgCl) of the PZC induces interfacial conditions that are favorable for the electrostatic deposition of cationic polymers onto the surface of 3-MPA monolayers. This result is also consistent with experimental observations obtained when the 3-MPA-modified substrate is exposed to 0.10 mol L (-1) NaOH solutions. When potentials equal or negative to the PZC are applied to the substrate, no significant accumulation of the PDDA is found by either QCM or EIS measurement. This result is consistent with results obtained when the 3-MPA modified substrate is exposed to 0.10 mol L (-1) HCl solutions where no PDDA adsorption is expected because the monolayer is neutral under these conditions. Changes in the impedance and quartz crystal frequency obtained after potential is applied to the substrate are interpreted in terms of the applied potential creating interfacial conditions that are favorable for the deprotonation of the terminal carboxylic acid groups and the subsequent electrostatic assembly of the polycation onto the negatively charged monolayer.

Characterization of carboxylic acid-terminated self-assembled monolayers by electrochemical impedance spectroscopy and scanning electrochemical microscopy.

Electrochemical impedance spectroscopy (EIS) and scanning electrochemical microscopy (SECM) are used to monitor changes in the ionization of monolayers of 11-mercaptoundecanoic acid. When using an anionic redox probe, Fe(CN)6(-4), the charge-transfer resistance of the 11-mercaptoundecanoic acid monolayer-modified interface increases in a sigmoidal fashion as the solution is made basic. The opposite effect is observed when using a cationic redox probe. The inflection points of these two titration curves, however, differ when using the different redox probes. This result is taken as being characteristic of the influence that applied potential has on the ionization of the monolayer. The role of substrate potential on the ionization of the monolayer is further investigated by SECM. The SECM measurement monitors the concentration of Ru(NH3)6(+3) as the potential of the substrate is varied about the potential of zero charge. For monolayers of 11-mercaptoundecanoic acid in solutions buffered near the pKa of the terminal carboxylic acid, potential excursions positive of the PZC cause an increase in the concentration of Ru(NH3)6(+3) local to the interface, and potential excursions negative of the PZC cause a decrease in the local concentration of Ru(NH3)6(+3). Similar experiments conducted with an interface modified with 11-undecanethiol had no impact on the local concentration of Ru(NH3)6(+3). These results are interpreted in terms of the influence that applied potential has on the pH of the solution local to the interface and the impact that this has on the ionization of the monolayer.

Metastases from renal cell carcinoma presenting as gastrointestinal bleeding: two case reports and a review of the literature.

BACKGROUND: Bleeding from small bowel neoplasms account for 1-4% of cases of upper gastrointestinal haemorrhage. Renal cell carcinoma constitutes 3% of all adult malignancies and often presents insidiously. Consequently 25-30% of patients have metastases at the time of diagnosis. Gastrointestinal bleeding from renal cell carcinoma metastases is an uncommon and under-recognised manifestation of this disease. CASE REPORT: In this report we describe two cases of gastrointestinal bleeding from renal cell carcinoma metastases - in one patient bleeding heralded the primary manifestation of disease and in the other signified recurrence of disease following nephrectomy. CONCLUSION: These cases highlight the importance endoscopic vigilance in cases of undiagnosed upper gastrointestinal haemorrhage, especially in patients with a past history of renal cell carcinoma.

Laboratory calibration of the Extreme-Ultraviolet Imaging Spectrometer for the Solar-B satellite.

The laboratory end-to-end testing of the Extreme-Ultraviolet Imaging Spectrometer (EIS) for the Solar-B satellite is reported. A short overview of the EIS, which observes in two bands in the extreme-ultraviolet wavelength range, is given. The calibration apparatus is described, including details of the light sources used. The data reduction and analysis procedure are outlined. The wavelength calibration using a Penning source to illuminate the aperture fully is presented. We discuss the aperture determination using a radiometrically calibrated hollow-cathode-based source. We then give an account of the predicted and measured efficiencies from consideration of the efficiencies of individual optical elements in first order, an account of efficiencies out of band when radiation incident in one band is detected in the other, and efficiencies in multiple orders. The efficiencies measured in first order for in band and out of band are compared with the predictions and the sensitivity, and its uncertainties are derived. Application of the radiometric calibration is discussed.

Met receptor signaling: a key effector in esophageal adenocarcinoma.

PURPOSE: The incidence of esophageal adenocarcinoma is rising, and survival rates remain poor. The hepatocyte growth factor (HGF) receptor Met has been detected in esophageal cancer. The perturbation of cadherin/catenin complexes has also been shown. We sought to investigate a link among Met expression, cadherin/catenin biology, and cell growth. We assessed the prognostic significance of Met expression in esophageal adenocarcinoma. EXPERIMENTAL DESIGN: Met and HGF expression in esophageal tissues were assessed using immunohistochemistry and ELISA. Met-positive cell lines (OE33 and SEG1) and a Met-negative cell line (TE7) were incubated with HGF. Real-time reverse transcription-PCR and Western blotting were used to assess levels of E-cadherin expression. Nuclear TCF/beta-catenin signaling was assessed following reporter construct transfection. Agar colony formation was used to assess anchorage-independent growth. A panel of 72 resected esophageal adenocarcinomas were assessed for Met expression by immunohistochemistry and correlated to survival data. RESULTS: An increased expression of Met was seen along the metaplasia- adenocarcinoma sequence. Met-positive cells showed reductions in E-cadherin mRNA (37% and 69%) and protein expression following stimulation with HGF (P < 0.01). OE33 and SEG-1 showed up to a 2-fold increase in the levels of beta-catenin nuclear signaling (P < 0.01). TE7 only responded when transfected to express Met; E-cadherin expression decreased by 64% (P < 0.01). HGF stimulation led to increased agar colony formation (P < 0.01). Patients with Met-positive tumors showed lower 6-month survival rates after surgical resection than those with Met-negative tumors (P < 0.05). CONCLUSIONS: Met activation induces changes consistent with early invasion, such as down-regulation of E-cadherin, increased nuclear TCF/beta-catenin signaling, and anchorage-independent growth. This is supported by ex vivo data associating Met with reduced short-term survival. Inhibitors of Met may be effective treatment for esophageal adenocarcinoma.