The Tissue Systems Pathology Test Outperforms Pathology Review in Risk Stratifying Patients With Low-Grade Dysplasia.

BACKGROUND & AIMS: Low-grade dysplasia (LGD) is associated with an increased risk of progression in Barrett's esophagus (BE); however, the diagnosis of LGD is limited by substantial interobserver variability. Multiple studies have shown that an objective tissue systems pathology test (TissueCypher Barrett's Esophagus Test, TSP-9), can effectively predict neoplastic progression in patients with BE. This study aimed to compare the risk stratification performance of the TSP-9 test vs benchmarks of generalist and expert pathology. METHODS: A blinded cohort study was conducted in the screening cohort of a randomized controlled trial of patients with BE with community-based LGD. Biopsies from the first endoscopy with LGD were assessed by the TSP-9 test and independently reviewed by 30 pathologists from 5 countries per standard practice. The accuracy of the test and the diagnoses in predicting high-grade dysplasia (HGD) and esophageal adenocarcinoma (EAC) were compared. RESULTS: A total of 154 patients with BE (122 men), mean age 60.9 ± 9.8 years were studied. Twenty-four patients progressed to HGD/EAC within 5 years (median time of 1.7 years) and 130 did not progress to HGD/EAC within 5 years (median 7.8 years follow-up). The TSP-9 test demonstrated higher sensitivity (71% vs mean 63%, range 33%-88% across 30 pathologists), than the pathology review in detecting patients who progressed (P = .01186). CONCLUSIONS: The TSP-9 test outperformed the pathologists in risk stratifying patients with BE with LGD. Care guided by the test can provide an effective solution to variable pathology review of LGD, improving health outcomes by upstaging care to therapeutic intervention for patients at high risk for progression, while reducing unnecessary interventions in low-risk patients.

The Tissue Systems Pathology Test Objectively Risk-Stratifies Patients With Barrett's Esophagus: Results From a Multicenter US Clinical Experience Study.

BACKGROUND: Barrett's esophagus (BE) is a diagnosis of esophageal intestinal metaplasia, which can progress to esophageal adenocarcinoma (EAC), and guidelines recommend endoscopic surveillance for early detection and treatment of EAC. However, current practices have limited effectiveness in risk-stratifying patients with BE. AIM: This study aimed to evaluate use of the TSP-9 test in risk-stratifying clinically relevant subsets of patients with BE in clinical practice. METHODS: TSP-9 results for tests ordered by 891 physicians for 8080 patients with BE with clinicopathologic data were evaluated. Orders were from nonacademic (94.3%) and academic (5.7%) settings for nondysplastic BE (NDBE; n=7586; 93.9%), indefinite for dysplasia (IND, n=312, 3.9%), and low-grade dysplasia (LGD, n=182, 2.3%). RESULTS: The TSP-9 test scored 83.2% of patients with low risk, 10.6% intermediate risk, and 6.2% high risk, respectively, for progression to HGD/EAC within 5 years. TSP-9 provided significant risk-stratification independently of clinicopathologic features, within NDBE, IND, and LGD subsets, male and female, and short- and long-segment subsets of patients. TSP-9 identified 15.3% of patients with NDBE as intermediate/high-risk for progression, which was 6.4 times more than patients with a pathology diagnosis of LGD. Patients with NDBE who scored intermediate or high risk had a predicted 5-year progression risk of 8.1% and 15.3%, respectively, which are similar to and higher than published progression rates in patients with BE with confirmed LGD. CONCLUSIONS: The TSP-9 test identified a high-risk subset of patients with NDBE who were predicted to progress at a higher rate than confirmed LGD, enabling early detection of patients requiring management escalation to reduce the incidence of EAC. TSP-9 scored the majority of patients with NDBE as low risk, providing support to adhere to 3- to 5-year surveillance per guidelines.

An Automated Tissue Systems Pathology Test Can Standardize the Management and Improve Health Outcomes for Patients With Barrett's Esophagus.

INTRODUCTION: Low-grade dysplasia (LGD) in Barrett's esophagus (BE) is associated with an increased risk of progression to high-grade dysplasia or esophageal adenocarcinoma. However, because of substantial interobserver variability in the diagnosis of LGD, a patient's management plan and health outcome depend largely on which pathologist reviews their case. This study evaluated the ability of a tissue systems pathology test that objectively risk stratifies patients with BE (TissueCypher, TSP-9) to standardize management in a manner consistent with improved health outcomes for patients with BE. METHODS: A total of 154 patients with BE with community-based LGD from the prospectively followed screening cohort of the SURF trial were studied. Management decisions were simulated 500 times with varying generalist (n = 16) and expert (n = 14) pathology reviewers to determine the most likely care plan with or without use of the TSP-9 test for guidance. The percentage of patients receiving appropriate management based on the known progression/nonprogression outcomes was calculated. RESULTS: The percentage of patients with 100% of simulations resulting in appropriate management significantly increased from 9.1% for pathology alone, to 58.4% when TSP-9 results were used with pathology, and further increased to 77.3% of patients receiving appropriate management when only TSP-9 results were used. Use of the test results also significantly increased the consistency of management decisions for patients when their slides were reviewed by different pathologists ( P < 0.0001). DISCUSSION: Management guided by the TSP-9 test can standardize care plans by increasing the early detection of progressors who can receive therapeutic interventions, while also increasing the percentage of nonprogressors who can avoid unnecessary therapy and be managed by surveillance alone.

The Marri Gudjaga project: a study protocol for a randomised control trial using Aboriginal peer support workers to promote breastfeeding of Aboriginal babies.

BACKGROUND: Breastfeeding protects against a range of conditions in the infant, including sudden infant death syndrome (SIDS), diarrhoea, respiratory infections and middle ear infections [1, 2]. The World Health Organization (WHO) recommends exclusive breastfeeding until six months of age, with continued breastfeeding recommended for at least two years and other complementary nutritious foods [3]. The 2017-18 National Health Survey (NHS) and 2018-19 National Aboriginal and Torres Strait Islander Health Survey (NATSIHS) reported that the proportion of breastfeeding in Aboriginal and Torres Strait Islander infants (0-2 years) were less than half that of non-Indigenous infants (21.2% vs. 45%, respectively)[4]. There is a lack of research on interventions supporting Aboriginal women to breastfeed, identifying an evaluation gap related to peer support interventions to encourage exclusive breastfeeding in Aboriginal women. METHODS: We will evaluate the effect of scheduled breastfeeding peer support for and by Aboriginal women, on breastfeeding initiation and the prevalence of exclusive breastfeeding. This MRFF (Medical Research Future Fund) funded project is designed as a single-blinded cluster randomised controlled trial recruiting six sites across New South Wales, Australia, with three sites being randomised to employ a peer support worker or undertaking standard care. Forty pregnant women will be recruited each year from each of the six sites and will be surveyed during pregnancy, at six weeks, four and six months postnatally with a single text message at 12 months to ascertain breastfeeding rates. In-depth interviews via an Indigenous style of conversation and storytelling called 'Yarning' will be completed at pre- and post-intervention with five randomly recruited community members and five health professionals at each site" [5]. Yarns will be audio recorded, transcribed, coded and thematic analysis undertaken. Health economic analysis will be completed to assess the health system incremental cost and effects of the breastfeeding intervention relative to usual care. DISCUSSION: Evidence will be given on the effectiveness of Aboriginal peer support workers to promote the initiation and continuation of breastfeeding of Aboriginal babies. The findings of this study will provide evidence of effectiveness and cost-effectiveness of including peer support workers in postnatal care to promote breastfeeding practices. TRIAL REGISTRATION: ACTRN12622001208796 The impact of breastfeeding peer support on nutrition of Aboriginal infants.

Tissue Systems Pathology Test Objectively Risk Stratifies Barrett's Esophagus Patients With Low-Grade Dysplasia.

INTRODUCTION: Low-grade dysplasia (LGD) is the best predictor of neoplastic progression in Barrett's esophagus (BE). Most LGD cases are downstaged to nondysplastic (ND) BE on expert pathologist review, which is prone to interobserver variation and not widely available. Recent studies indicate that a risk prediction assay (TissueCypher) risk stratifies patients with NDBE for neoplastic progression. We aimed to investigate whether this risk prediction assay predicts neoplastic progression in BE patients with LGD. METHODS: A blinded, retrospective cohort study was derived from the screening cohort of a randomized controlled trial of SURveillance vs RadioFrequency ablation for BE patients with LGD. Hematoxylin and eosin and p53 immunohistochemistry slides from the first endoscopy with LGD were independently reviewed by 3 expert pathologists and tested by the risk prediction assay. Revision diagnoses of NDBE were considered low risk, although indefinite for dysplasia, and LGD were considered high risk for progression. RESULTS: A total of 155 BE patients (123 men), mean age 61 ± 10 years, were analyzed. Thirty-four patients (22%) progressed to high-grade dysplasia/esophageal adenocarcinoma (median time 2.4 years) and 121 did not progress (median high-grade dysplasia/esophageal adenocarcinoma-free surveillance 7.9 years). The risk prediction assay sensitivity was 68% vs 76% for the 3 pathologists, and specificity was 79% vs 64%-77.0% for the pathologists. The assay detected 50%-56% of progressors that were downstaged to NDBE by the pathologists. DISCUSSION: The risk prediction assay provided significant risk stratification in BE patients with LGD and identified progressors that the experts downstaged to NDBE. This objective assay provides an effective solution to the lack of standardization of expert pathology review of LGD.

Independent Blinded Validation of a Tissue Systems Pathology Test to Predict Progression in Patients With Barrett's Esophagus.

INTRODUCTION: A risk prediction test was previously validated to predict progression to high-grade dysplasia (HGD) and esophageal adenocarcinoma (EAC) in patients with Barrett's esophagus (BE). The aim of our study was to independently validate this test to predict the risk of progression to HGD/EAC in BE patients with nondysplastic (ND), indefinite for dysplasia and low-grade dysplasia (LGD). METHODS: A single-blinded, case-control study was conducted to stratify patients with BE as low, intermediate, or high risk for progression to HGD/EAC within 5 years using a previously described risk prediction test. Patients with BE who progressed to HGD/EAC after at least 1 year (n = 58) were matched to patients undergoing surveillance without progression (n = 210, median surveillance 7 years). Baseline biopsies with subspecialist diagnoses of ND, indefinite for dysplasia, or LGD were tested in a blinded manner, and the predictive performance of the test was assessed. RESULTS: This risk prediction test stratified patients with BE based on progression risk with the high-risk group at 4.7-fold increased risk for HGD/EAC compared with the low-risk group (95% confidence interval 2.5-8.8, P < 0.0001). Prevalence-adjusted positive predictive value at 5 years was 23%. The high-risk class and male sex provided predictive power that was independent of pathologic diagnosis, age, segment length, and hiatal hernia. Patients with ND BE who scored high risk progressed at a higher rate (26%) than patients with subspecialist-confirmed LGD (21.8%) at 5 years. DISCUSSION: A risk prediction test identifies patients with ND BE who are at high risk for progression to HGD/EAC and may benefit from early endoscopic therapy or increased surveillance.

Clinical comparison of the hybrid dynamic compression plate and the castless plate for pancarpal arthrodesis in 219 dogs.

OBJECTIVE: To describe and compare a large population of dogs that had pancarpal arthrodesis (PCA) using either a hybrid dynamic compression plate (HDCP) or a CastLess Plate (CLP). STUDY DESIGN: Multicenter, retrospective, cohort study. ANIMALS: Dogs (n = 240; 261 PCA). METHODS: Medical records (2000-2012) from 12 UK orthopedic centers were reviewed for dogs that had PCA to document signalment, diagnosis, arthrodesis method, and complication rates. Follow-up data were used to compare outcome (lameness evaluation and radiographic healing) after use of HDCP and CLP plates. RESULTS: PCA was performed with HDCP in 125 cases, CLP in 105, and by other techniques in 31. Carpal hyperextension injury was the most common diagnosis in HDCP and CLP groups. Surgical site infection (18.3%) was the most common postoperative complication. There was no difference in intra- (11% HDCP, 21% CLP) or postoperative (34% HDCP, 41% CLP) complication rates. Use of external coaptation did not affect postoperative complication rates or outcome. External coaptation related complications occurred in 32% HDCP and 18% CLP (P = .02). At median follow-up, most dogs were classified as having no or mild lameness (73% HDCP, 83% CLP) and there was radiographic healing in 40% HDCP and 46% CLP (P = .8) cases. CONCLUSIONS: CLP and HDCP may both be used successfully to achieve pancarpal arthrodesis. Adjunctive external coaptation does not appear to have a measurable clinical benefit but is associated with morbidity.

Trapping of redox-mediators at the surface of Chlorella vulgaris leads to error in measurements of cell reducing power.

The reduction of the redox mediator ferricyanide, [Fe(CN)6](3-), by a range of algal and bacterial species, is frequently measured to probe plasma membrane ferrireductase activity or to quantify the reducing power of algal/bacterial biofilms and suspensions. In this study we have used rotating disk electrochemistry (RDE) to investigate the reduction of ferricyanide by the model organism Chlorella vulgaris. Importantly, we have seen that the diffusion limited current due to the oxidation of ferrocyanide, [Fe(CN)6](4-), at the electrode decreased linearly as C. vulgaris was added to the solution, even though in a pure ferrocyanide solution the algae are not able to reduce the mediator further and are simply spectator 'particles'. We attribute this effect to trapping of ferrocyanide at the cell surface, with up to 14% of the ferrocyanide missing from the solution at the highest cell concentration. The result has important implications for all techniques that use electrochemistry and other concentration dependent assays (e.g. fluorescence and colourimetry) to monitor ferrocyanide concentrations in the presence of both biofilms and cell suspensions. Analyte trapping could lead to a substantial underestimation of the concentration of reduced product.

Technical and cost analysis of zero-emission high-speed ferries: Retrofitting from diesel to green hydrogen.

This paper proposes a technical and cost analysis model to assess the change in costs of a zero-emission high-speed ferry when retrofitting from diesel to green hydrogen. Both compressed gas and liquid hydrogen are examined. Different scenarios explore energy demand, energy losses, fuel consumption, and cost-effectiveness. The methodology explores how variation in the ferry's total weight and equipment efficiency across scenarios impact results. Applied to an existing diesel high-speed ferry on one of Norway's longest routes, the study, under certain assumptions, identifies compressed hydrogen gas as the current most economical option, despite its higher energy consumption. Although the energy consumption of the compressed hydrogen ferry is slightly more than the liquid hydrogen counterpart, its operating expenses are considerably lower and comparable to the existing diesel ferry on the route. However, constructing large hydrogen liquefaction plants could reduce liquid hydrogen's cost and make it competitive with both diesel and compressed hydrogen gas. Moreover, liquid hydrogen allows the use of a superconducting motor to enhance efficiency. Operating the ferry with liquid hydrogen and a superconducting motor, besides its technical advantages, offers promising economic viability in the future, comparable to diesel and compressed hydrogen gas options. Reducing the ferry's speed and optimizing equipment improves fuel efficiency and economic viability. This research provides valuable insights into sustainable, zero-emission high-speed ferries powered by green hydrogen.

A Randomized Controlled Study on Clinical Adherence to Evidence-Based Guidelines in the Management of Simulated Patients With Barrett's Esophagus and the Clinical Utility of a Tissue Systems Pathology Test: Results From Q-TAB.

INTRODUCTION: Barrett's esophagus (BE) is a precursor to esophageal adenocarcinoma. Physicians infrequently adhere to guidelines for managing BE, leading to either reduced detection of dysplasia or inappropriate re-evaluation. METHODS: We conducted a three-arm randomized controlled trial with 2 intervention arms to determine the impact of a tissue systems pathology (TSP-9) test on the adherence to evidence-based guidelines for simulated patients with BE. Intervention 1 received TSP-9 results, and intervention 2 had the option to order TSP-9 results. We collected data from 259 practicing gastroenterologists and gastrointestinal surgeons who evaluated and made management decisions for 3 types of simulated patients with BE: nondysplastic BE, indefinite for dysplasia, and low-grade dysplasia. RESULTS: Intervention 1 was significantly more likely to correctly assess risk of progression to high-grade dysplasia/esophageal adenocarcinoma and offer treatment in accordance with US society guidelines compared with the control group (+6.9%, 95% confidence interval +1.4% to +12.3%). There was no significant difference in ordering guideline-recommended endoscopic eradication therapy. However, for cases requiring annual endoscopic surveillance, we found significant improvement in adherence for intervention 1, with a difference-in-difference of +18.5% ( P = 0.019). Intervention 2 ordered the TSP-9 test in 21.9% of their cases. Those who ordered the test performed similarly to intervention 1; those who did not, performed similarly to the control group. DISCUSSION: The TSP-9 test optimized adherence to clinical guidelines for surveillance and treatment of both patients with BE at high and low risk of disease progression. Use of the TSP-9 test can enable physicians to make risk-aligned management decisions, leading to improved patient health outcomes.

RBM39 degrader invigorates natural killer cells to eradicate neuroblastoma despite cancer cell plasticity.

The cellular plasticity of neuroblastoma is defined by a mixture of two major cell states, adrenergic (ADRN) and mesenchymal (MES), which may contribute to therapy resistance. However, how neuroblastoma cells switch cellular states during therapy remains largely unknown and how to eradicate neuroblastoma regardless of their cell states is a clinical challenge. To better understand the lineage switch of neuroblastoma in chemoresistance, we comprehensively defined the transcriptomic and epigenetic map of ADRN and MES types of neuroblastomas using human and murine models treated with indisulam, a selective RBM39 degrader. We showed that cancer cells not only undergo a bidirectional switch between ADRN and MES states, but also acquire additional cellular states, reminiscent of the developmental pliancy of neural crest cells. The lineage alterations are coupled with epigenetic reprogramming and dependency switch of lineage-specific transcription factors, epigenetic modifiers and targetable kinases. Through targeting RNA splicing, indisulam induces an inflammatory tumor microenvironment and enhances anticancer activity of natural killer cells. The combination of indisulam with anti-GD2 immunotherapy results in a durable, complete response in high-risk transgenic neuroblastoma models, providing an innovative, rational therapeutic approach to eradicate tumor cells regardless of their potential to switch cell states.

Foods, nutrients or whole diets: effects of targeting fish and LCn3PUFA consumption in a 12mo weight loss trial.

BACKGROUND: There is some evidence in the literature that emphasising fish consumption may assist with weight loss. The aim was to assess the effects of advice to consume 2 fish meals per week in a weight loss diet. METHODS: A parallel randomised placebo-controlled trial was conducted in 118 obese Australian adults (mean BMI ± SD 31.3 ± 3.5 kg/m2; mean age ± SD 45 ± 10 y; 28% male). Participants received low calorie dietary advice+placebo (1 g olive oil; CONTROL), low calorie dietary advice emphasising fish+placebo (Fish), or low calorie dietary advice emphasising fish diet + LCn3PUFA supplements (Fish+S). Individualised advice targeted 2 MJ energy deficit (30%E fat, 45%E carbohydrate and 25%E protein) with or without two servings (180 g) fatty fish/wk. RESULTS: All groups lost weight at 12 months (CONTROL -4.5 kg vs. Fish -4.3 kg vs. Fish+S -3.3 kg; p<0.001) and percentage body fat ( CONTROL: -1.5% vs. Fish: -1.4% vs. Fish+S: -0.7%; p<0.001) but there were no significant differences between groups. Cardiovascular disease risk factors changed as expected from weight loss. CONCLUSIONS: Advice to consume 2 fish meals per week did not enhance the effects on weight loss of a healthy low calorie diet. TRIAL REGISTRATION: ACTRN12608000425392.

A Systematic Review of Patient Race, Ethnicity, Socioeconomic Status, and Educational Attainment in Prostate Cancer Treatment Randomised Trials-Is the Evidence Base Applicable to the General Patient Population?

Context: Prostate cancer (PC) disproportionately affects men of Black race, and lower educational and socioeconomic status. Guidelines are based on randomised controlled trials (RCTs); however, the representation of different races, educations, and socioeconomic backgrounds in these trials is unclear. Objective: To assess reporting of equality, diversity, and inclusion characteristics (Equality, Diversity and Inclusion [EDI]) and differences in treatment effects between different races, and educational or socioeconomic status. Evidence acquisition: We conducted a systematic review of CENTRAL, MEDLINE, and Embase in April 2020 examining RCTs investigating treatments for PC. Outcomes collected were race/ethnicity, educational attainment, and socioeconomic status. RCTs investigating PC treatment in any population or setting were included. Data extraction of characteristics was performed independently by pairs of reviewers and checked by a senior author. The Cochrane risk of bias tool assessed the quality of included papers. Evidence synthesis: A total of 265 trials were included, and 138 of these were available as full-text articles. Fifty-four trials including 19 039 participants reported any EDI data. All 54 trials reported race, 11 reported ethnicity, three reported educational attainment, and one reported socioeconomic status. Patients of White race were the majority of the recruited population (82.6%), while the minority prevalence was as follows: Black 9.8% and Asian 5.7%. Three studies reported mortality outcomes depending on the participant's race. All three studies investigated different treatments, so a meta-analysis was not performed. No studies reported outcomes stratified by the educational or socioeconomic status of participants. Conclusions: There is poor reporting of patient race, ethnicity, socioeconomic background, and educational attainment in RCTs for PC treatments between 2010 and 2020. Addressing this for future studies will help explain differences in the incidence of and mortality from PC and improve the generalisability of results. Patient summary: In this study, we reviewed prostate cancer treatment trials to see whether these reported race, education, and socioeconomic backgrounds of their patient populations. We conclude that reporting of these characteristics is poor. This needs to be improved in future to improve outcomes for patients with prostate cancer of all ethnical, racial, and socioeconomic groups.

A Tissue Systems Pathology Test Outperforms the Standard-of-Care Variables in Predicting Progression in Patients With Barrett's Esophagus.

INTRODUCTION: Objective risk stratification is needed for patients with Barrett's esophagus (BE) to enable risk-aligned management to improve health outcomes. This study evaluated the predictive performance of a tissue systems pathology [TSP-9] test (TissueCypher) vs current clinicopathologic variables in a multicenter cohort of patients with BE. METHODS: Data from 699 patients with BE from 5 published studies on the TSP-9 test were evaluated. Five hundred nine patients did not progress during surveillance, 40 were diagnosed with high-grade dysplasia/esophageal adenocarcinoma (HGD/EAC) within 12 months, and 150 progressed to HGD/EAC after 12 months. Age, sex, segment length, hiatal hernia, original and expert pathology review diagnoses, and TSP-9 risk classes were collected. The predictive performance of clinicopathologic variables and the TSP-9 test was compared, and the TSP-9 test was evaluated in clinically relevant patient subsets. RESULTS: The sensitivity of the TSP-9 test in detecting progressors was 62.3% compared with 28.3% for expert-confirmed low-grade dysplasia (LGD), while the original diagnosis abstracted from medical records did not provide any significant risk stratification. The TSP-9 test identified 57% of progressors with nondysplastic Barrett's esophagus (NDBE) ( P < 0.0001). Patients with NDBE who scored TSP-9 high risk progressed at a similar rate (3.2%/yr) to patients with expert-confirmed LGD (3.7%/yr). The TSP-9 test provided significant risk stratification in clinically low-risk patients (NDBE, female, short-segment BE) and clinically high-risk patients (IND/LGD, male, long-segment BE) ( P < 0.0001 for comparison of high-risk classes vs low-risk classes). DISCUSSION: The TSP-9 test predicts risk of progression to HGD/EAC independently of current clinicopathologic variables in patients with BE. The test provides objective risk stratification results that may guide management decisions to improve health outcomes for patients with BE.

Effect of 6 weeks' consumption of ß-glucan-rich oat products on cholesterol levels in mildly hypercholesterolaemic overweight adults.

Several regulatory bodies have approved a health claim on the cholesterol-lowering effects of oat ß-glucan at levels of 3·0 g/d. The present study aimed to test whether 1·5 g/d ß-glucan provided as ready-to-eat oat flakes was as effective in lowering cholesterol as 3·0 g/d from oats porridge. A 6-week randomised controlled trial was conducted in eighty-seven mildly hypercholesterolaemic ( ≥ 5 mmol/l and < 7·5 mmol/l) men and women assigned to one of three diet arms (25 % energy (E%) protein; 45 E% carbohydrate; 30 E% fat, at energy requirements for weight maintenance): (1) minimal ß-glucan (control); (2) low-dose oat ß-glucan (1·5 g ß-glucan; oats low - OL) or (3) higher dose oat ß-glucan (3·0 g ß-glucan; oats high - OH). Changes in total cholesterol and LDL-cholesterol (LDL-C) from baseline were assessed using a linear mixed model and repeated-measures ANOVA, adjusted for weight change. Total cholesterol reduced significantly in all groups ( - 7·8 (sd 13·8) %, - 7·2 (sd 12·4) % and - 5·5 (sd 9·3) % in the OH, OL and control groups), as did LDL-C ( - 8·4 (sd 18·5) %, - 8·5 (sd 18·5) % and - 5·5 (sd 12·4) % in the OH, OL and control groups), but between-group differences were not significant. In responders only (n 60), ß-glucan groups had higher reductions in LDL-C ( - 18·3 (sd 11·1) % and - 18·1 (sd 9·2) % in the OH and OL groups) compared with controls ( - 11·7 (sd 7·9) %; P = 0·044). Intakes of oat ß-glucan were as effective at doses of 1·5 g/d compared with 3 g/d when provided in different food formats that delivered similar amounts of soluble ß-glucan.

Surface morphology and surface energy of anode materials influence power outputs in a multi-channel mediatorless bio-photovoltaic (BPV) system.

Bio-photovoltaic cells (BPVs) are a new photo-bio-electrochemical technology for harnessing solar energy using the photosynthetic activity of autotrophic organisms. Currently power outputs from BPVs are generally low and suffer from low efficiencies. However, a better understanding of the electrochemical interactions between the microbes and conductive materials will be likely to lead to increased power yields. In the current study, the fresh-water, filamentous cyanobacterium Pseudanabaena limnetica (also known as Oscillatoria limnetica) was investigated for exoelectrogenic activity. Biofilms of P. limnetica showed a significant photo response during light-dark cycling in BPVs under mediatorless conditions. A multi-channel BPV device was developed to compare quantitatively the performance of photosynthetic biofilms of this species using a variety of different anodic conductive materials: indium tin oxide-coated polyethylene terephthalate (ITO), stainless steel (SS), glass coated with a conductive polymer (PANI), and carbon paper (CP). Although biofilm growth rates were generally comparable on all materials tested, the amplitude of the photo response and achievable maximum power outputs were significantly different. ITO and SS demonstrated the largest photo responses, whereas CP showed the lowest power outputs under both light and dark conditions. Furthermore, differences in the ratios of light : dark power outputs indicated that the electrochemical interactions between photosynthetic microbes and the anode may differ under light and dark conditions depending on the anodic material used. Comparisons between BPV performances and material characteristics revealed that surface roughness and surface energy, particularly the ratio of non-polar to polar interactions (the CQ ratio), may be more important than available surface area in determining biocompatibility and maximum power outputs in microbial electrochemical systems. Notably, CP was readily outperformed by all other conductive materials tested, indicating that carbon may not be an optimal substrate for microbial fuel cell operation.

Impaired interferon signaling is a common immune defect in human cancer.

Immune dysfunction develops in patients with many cancer types and may contribute to tumor progression and failure of immunotherapy. Mechanisms underlying cancer-associated immune dysfunction are not fully understood. Efficient IFN signaling is critical to lymphocyte function; animals rendered deficient in IFN signaling develop cancer at higher rates. We hypothesized that altered IFN signaling may be a key mechanism of immune dysfunction common to cancer. To address this, we assessed the functional responses to IFN in peripheral blood lymphocytes from patients with 3 major cancers: breast cancer, melanoma, and gastrointestinal cancer. Type-I IFN (IFN-alpha)-induced signaling was reduced in T cells and B cells from all 3 cancer-patient groups compared to healthy controls. Type-II IFN (IFN-gamma)-induced signaling was reduced in B cells from all 3 cancer patient groups, but not in T cells or natural killer cells. Impaired-IFN signaling was equally evident in stage II, III, and IV breast cancer patients, and downstream functional defects in T cell activation were identified. Taken together, these findings indicate that defects in lymphocyte IFN signaling arise in patients with breast cancer, melanoma, and gastrointestinal cancer, and these defects may represent a common cancer-associated mechanism of immune dysfunction.

Clinical variation in surveillance and management of Barrett's esophagus: A cross-sectional study of gastroenterologists and gastrointestinal surgeons.

Appropriate surveillance and treatment of Barrett's esophagus (BE) is vital to prevent disease progression and decrease esophageal adenocarcinoma (EAC)-related mortality. We sought to determine the variation in BE care and identify improvement opportunities. 275 physicians (113 general gastroenterologists, 128 interventional gastroenterologists, 34 gastrointestinal surgeons) cared for 3 simulated patients, one each from 3 BE clinical scenarios: non-dysplastic BE (NDBE), BE indefinite for dysplasia (IND), and BE with low grade dysplasia (LGD), and care scores were measured against societal guidelines. Overall quality-of-care scores ranged from 17% to 85% with mean of 47.9% ± 11.8% for NDBE, 50.8% ± 11.7% for IND, and 52.7% ± 12.2% for LGD. Participants appropriately determined risk of progression 20.3% of the time: 14.4% for NDBE cases, 19.9% for LGD cases, and 26.8% for IND cases (P = .001). Treatment and follow-up care scores averaged 12.9% ± 17.5% overall. For the LGD cases, guideline-recommended twice-daily PPI treatment was ordered only 24.7% of the time. Guideline-based follow-up endoscopic surveillance was done in only 27.7% of NDBE cases and 32.7% of IND cases. For the LGD cases, 45.4% ordered endoscopic eradication therapy while 25.1% chose annual endoscopic surveillance. Finally, participants provided counseling on lifestyle modifications in just 20% of cases. Overall care of patients diagnosed with BE varied widely and showed room for improvement. Specific opportunities for improvement were adherence to guideline recommended surveillance intervals, patient counseling, and treatment selection for LGD. Physicians would potentially benefit from additional BE education, endoscopic advances, and better methods for risk stratification.