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Ann Colosia,1 Annete Njue,2 Zahid Bajwa,3 Erika Dragon,4 Rebecca L Robinson,5 Kristin M Sheffield,5 Sheena Thakkar,6 Steven H Richiemer7 1Department of Market Access and Outcomes Strategy, RTI Health Solutions, Research Triangle Park, NC, USA; 2Department of Market Access and Outcomes Strategy, RTI Health Solutions, Manchester, UK; 3Medical Affairs, Eli Lilly and Company, Indianapolis, IN, USA; 4Medical Affairs, Pfizer, Ltd, Budapest, Hungary; 5Value, Evidence, and Outcomes, Eli Lilly and Company, Indianapolis, IN, USA; 6Patient Health & Impact, Pfizer Inc, New York, NY, USA; 7Division of Pain Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USACorrespondence: Rebecca L Robinson, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, 46285, USA, Tel +1 3174331323, Fax +1 3172777444, Email rlrobinson@lilly.comAbstract: Bone pain is one of the most common forms of pain reported by cancer patients with metastatic disease. We conducted a review of oncology literature to further understand the epidemiology of and treatment approaches for metastatic cancer–induced bone pain and the effect of treatment of painful bone metastases on the patient’s quality of life. Two-thirds of patients with advanced, metastatic, or terminal cancer worldwide experience pain. Cancer pain due to bone metastases is the most common form of pain in patients with advanced disease and has been shown to significantly reduce patients’ quality of life. Treatment options for cancer pain due to bone metastases include nonsteroidal anti-inflammatory drugs, palliative radiation, bisphosphonates, denosumab, and opioids. Therapies including palliative radiation and opioids have strong evidence supporting their efficacy treating cancer pain due to bone metastases; other therapies, like bisphosphonates and denosumab, do not. There is sufficient evidence that patients who experience pain relief after radiation therapy have improved quality of life; however, a substantial proportion are nonresponders. For those still requiring pain management, even with available analgesics, many patients are undertreated for cancer pain due to bone metastases, indicating an unmet need. The studies in this review were not designed to determine why cancer pain due to bone metastases was undertreated. Studies specifically addressing cancer pain due to bone metastases, rather than general cancer pain, are limited. Additional research is needed to determine patient preferences and physician attitudes regarding choice of analgesic for moderate to severe cancer pain due to bone metastases.Keywords: cancer, pain, bone, metastasis, quality of life, cancer patients

Michael D Brown1,3, Deborah L Feairheller1, Sunny Thakkar1, Praveen Veerabhadrappa1, Joon-Young Park21Hypertension, Molecular and Applied Physiology Laboratory, 2Cardiovascular Genomics Laboratory, Department of Kinesiology, 3Cardiovascular Research Center, School of Medicine, Temple University, Philadelphia, PA, USAAbstract: African Americans (AA) tend to have heightened systemic inflammation and endothelial dysfunction. Endothelial microparticles (EMP) are released from activated/apoptotic endothelial cells (EC) when stimulated by inflammation. The purpose of our study was to assess EMP responses to inflammatory cytokine (TNF-α) and antioxidant (superoxide dismutase, SOD) conditions in human umbilical vein ECs (HUVECs) obtained from AA and Caucasians. EMPs were measured under four conditions: control (basal), TNF-α, SOD, and TNF-α + SOD. Culture supernatant was collected for EMP analysis by flow cytometry and IL-6 assay by ELISA. IL-6 protein expression was assessed by Western blot. AA HUVECs had greater EMP levels under the TNF- α condition compared to the Caucasian HUVECs (6.8 ± 1.1 vs 4.7% ± 0.4%, P = 0.04). The EMP level increased by 89% from basal levels in the AA HUVECs under the TNF-α condition (P = 0.01) compared to an 8% increase in the Caucasian HUVECs (P = 0.70). Compared to the EMP level under the TNF-α condition, the EMP level in the AA HUVECs was lower under the SOD only condition (2.9% ± 0.3%, P = 0.005) and under the TNF-α + SOD condition (2.1% ± 0.4%, P = 0.001). Basal IL-6 concentrations were 56.1 ± 8.8 pg/mL/µg in the AA and 30.9 ± 14.9 pg/mL/µg in the Caucasian HUVECs (P = 0.17), while basal IL-6 protein expression was significantly greater (P < 0.05) in the AA HUVECs. These preliminary observational results suggest that AA HUVECs may be more susceptible to the injurious effects of the proinflammatory cytokine, TNF-α.Keywords: endothelium, inflammation, endothelial microparticles, African Americans

To prevent graft rejection, we modified the EBVST with a chimeric antigen receptor (CAR) targeting CD30, an antigen that is upregulated on allo-activated T-cells, which will consequently become targets for CD30.CAR EBVST. OFF-THE-SHELF CD30.CAR-MODIFIED EPSTEIN-BARR VIRUS-SPECIFIC T CELLS (CD30.CAR EBVSTS) PROVIDE A SAFE AND EFFECTIVE THERAPY FOR PATIENTS WITH HODGKIN LYMPHOMA (HL) Off-the-shelf allogeneic T-cell therapies face the major challenges of graft-versus-host disease (GVHD) and graft rejection mediated by host and recipient alloreactive T cells, respectively. [Extracted from the article]

This article presents the results of a large-scale international survey conducted by the World Endoscopy Organization (WEO) AI committee on patient perceptions of artificial intelligence (AI) in endoscopy. The survey included 1,237 patients from all six continents, who responded to 13 statements about the use of AI in endoscopy. The majority of patients believed that AI and humans can complement each other and supported the use of AI in endoscopy. However, fewer patients believed that AI could be better than experienced endoscopists, and they felt that endoscopists should remain responsible for decision making. Additionally, most patients believed that endoscopists or hospitals should be liable for any medical malpractice caused by the use of AI. Overall, the survey revealed that patients appreciate the benefits of AI in endoscopy but also recognize the importance of human expertise and accountability. [Extracted from the article]

This article presents the results of an international survey conducted by the World Endoscopy Organization AI committee on endoscopists' opinions regarding the use of artificial intelligence (AI) in endoscopy. The survey included 465 endoscopists from 83 countries, with a range of backgrounds and experience levels. The majority of participants believed that AI would improve endoscopy quality, efficiency, and patient outcomes. However, there were concerns about financial reimbursement, medical liability, potential de-skilling, and the possibility of unnecessary resections and increased procedure times. Overall, most endoscopists expressed a willingness to use AI when available. [Extracted from the article]

Chloride ingress in concrete leads to deterioration of reinforcement and subsequent distress in concrete. The focus of the present study was to determine the amount of chloride ingress in concrete with and without supplementary cementitious materials (SCM) using Rapid Chloride Penetration Test (RCPT) and Rapid Chloride Migration Test (RCMT). A comparison of chloride ingress was made of Control concrete with six other mixtures having varying percentages of fly ash (20% & 30%), ground granulated blast furnace slag (GGBFS) (30% & 40%), silica fume (5%) as replacement of cement. Compressive strength, RCPT and RCMT tests were evaluated for all the mixtures after 28 and 90 days respectively. A correlation between RCPT and RCMT tests was established. Mixtures containing fly ash as SCM had lesser initial compressive strength compared to mixtures with GGBFS and silica fume. Chloride permeability of concrete mixture with silica fume as SCM has a significant decrease in chloride permeability in both RCPT and RCMT tests at both ages compared to concrete without SCM. Estimation of service life was carried out using Life-365TM software. It was observed that the service life of concrete without SCM was estimated to be 14.8 years while in the concrete with 5% silica fume expected service life was 24.9 years. Thus, the incorporation of supplementary cementitious material in concrete enhances the service life and is a boon to the construction industry.

Objective:. The objective of this study is to analyze oncological outcomes of patients with peritoneal metastases (PM) of colorectal origin treated with Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC). Background:. PIPAC has been demonstrated to be a feasible and safe novel treatment for patients with PM of various origins. Only small series reports on survival after PIPAC by disease entity. Methods:. International retrospective cohort study of consecutive patients with PM of colorectal origin. Outcome measures were overall survival (OS), radiological response according to Response Evaluation Criteria in Solid Tumors (RECIST), histological response (peritoneal regression grading score [PRGS]: complete response: 1–4: no response), change of peritoneal cancer index (PCI), and symptom control. Results:. Seventeen eligible centers compiled 256 non-selected patients (mean age 61 [50.6–69.2], 43% female) and 606 procedures. Sixty-three percent were treated after 2 lines of chemotherapy, median PCI at PIPAC1 was 18 (interquartile range [IQR] = 10–27). Median OS was 19.00 months (IQR = 12.9–29.8) from diagnosis and 9.4 months (IQR = 4.5–16.8) from PIPAC1. One hundred and four of 256 patients (40.6%) had ≥3 procedures (per protocol [pp]) with the following outcomes at PIPAC3: RECIST: 59.3% partial response/stable, 40.7% progression; mean PRGS: 2.1 ± 0.9. Median PCI was 21 (IQR = 15–29) at baseline and 20 (IQR = 12–27) at PIPAC3 (P = 0.02). Fifty-six (54%) and 48 (46%) patients were symptomatic at baseline and PIPAC3, respectively (P = 0.267). Median OS for the pp cohort was 11.9 months (IQR = 10.7–15.0) from PIPAC1. Independent predictors for survival were radiological response (HR = 3.0; 95% CI = 1.6–5.7) and no symptoms (HR = 4.5, 95% CI = 2.2–9.1) at PIPAC3. Conclusions:. Objective treatment response and encouraging survival were demonstrated after PIPAC for colorectal PM. Prospective registry data and comparative studies are now needed in to confirm these data.

One of the sustainable alternatives to Portland cement is geopolymer concrete consisting of industrial waste. Practical application of geopolymer concrete is restricted as it requires the use of high temperature to develop compressive strength. This study aims to develop a mixture design for geopolymer prestressed concrete specifically designed to take prestressing force using ambient curing technique and compare its performance with the same grade of Portland cement concrete mix. As ambient curing technique is used for geopolymer concrete hence a combination of blast furnace slag and fly ash is taken as source materials and due to ease of availability and economy, sodium hydroxide and silicate are chosen as activators. After several trial mixtures, M 40 grade of geopolymer concrete is developed using an equal proportion of fly ash and ground granulated blast furnace slag (GGBFS) as source material. GGBFS provides early strength at ambient curing in geopolymer concrete and hence was incorporated with fly ash. 3 ply of 3 mm diameter bars were used as pre-tensioning wire. Load v/s deflection graph for non-prestressed geopolymer concrete beams and beams with same grade Portland cement concrete show that the load-carrying capacity of both beams was at par. It was also observed that prestressed geopolymer concrete beams which were cured under ambient curing developed sufficient strength and were equally capable of carrying the load as compared to Portland cement concrete beams. Load carrying capacity increased in prestressed Portland cement concrete beams increased by 78% while in prestressed geopolymer concrete beams the increase was 83% and also the deflection of both prestressed beams was more compared to non-prestressed beams. This indicates that sustainable material can be effectively utilized in prestressing work without comprising on strength.

When pain or disability occurs after rotator cuff surgery, post-operative imaging is frequently performed. Post-operative complications and expected post-operative imaging findings in the shoulder are presented, with a focus on MRI MR arthrography (MRA) and CT arthrography. MR and CT techniques are available to reduce image degradation secondary to surgical distortions of native anatomy and implant-related artefacts and to define complications after rotator cuff surgery. A useful approach to image the shoulder after surgery is the standard radiography, followed by MRI/MRA for patients with low "metal presence" and CT for patients who have a higher metal presence. However, for the assessment of patients who have undergone surgery for rotator cuff injuries, imaging findings should always be correlated with the clinical presentation because post-operative imaging abnormalities do not necessarily correlate with symptoms. [ABSTRACT FROM AUTHOR]

Modal parameters of an instrumented multi-storied reinforced concrete building (G +9) have been studied using strong motion records of Bhuj Earthquake, 2001. The Ambient Vibration Testing (AVT) is also conducted to measure the modal parameters of the same building under ambient environmental forces. Frequency Domain Decomposition (FDD) or Peak Picking (PP) in frequency domain and Stochastic Subspace Identification (SSI) technique in time domain is used for extracting the modal parameters. The observed natural frequencies during strong motion are smaller than the ambient vibration testing. The difference in the frequencies may be caused by interaction between structure and soil due to high level of strain during strong motion earthquake. The modal pattern of first five modes obtained from strong motion records and ambient vibration records are identical. [ABSTRACT FROM PUBLISHER]

An experimental study on half-scale brick-masonry models with different strengthening and retrofitting measures has been studied under cyclic loading in a quasi-static test facility. The strengthening measures undertaken for the studies are the horizontal bond beam at the lintel and sill level with a combination of vertical reinforcement at corners and openings. The retrofitting measures studied are grouting with epoxy-sand-mortar and cement-grout-injection with welded wire mesh in the cracked region. The tests reveal that the horizontal bond beam at lintel level with vertical reinforcement is effective in reducing the cracking above the lintel level. The insertion of an additional sill-band significantly reduces the cracking in walls. The epoxy-sand-mortar techniques for retrofitting of cracked regions prove to be effective enough to restore the initial strength, stiffness and deformation capacity. Although specimen retrofitted with cement-grout-injection with welded wire mesh is effective to regain the ultimate strength yet the brittle failure is observed as the specimen is stressed beyond the elastic limit. [ABSTRACT FROM AUTHOR]

Volumetric laser endomicroscopy (VLE) uses optical coherence tomography (OCT) for real-time, microscopic cross-sectional imaging. A US-based multi-center registry was constructed to prospectively collect data on patients undergoing upper endoscopy during which a VLE scan was performed. The objective of this registry was to determine usage patterns of VLE in clinical practice and to estimate quantitative and qualitative performance metrics as they are applied to Barrett's esophagus (BE) management. All procedures utilized the NvisionVLE Imaging System (NinePoint Medical, Bedford, MA) which was used by investigators to identify the tissue types present, along with focal areas of concern. Following the VLE procedure, investigators were asked to answer six key questions regarding how VLE impacted each case. Statistical analyses including neoplasia diagnostic yield improvement using VLE was performed. One thousand patients were enrolled across 18 US trial sites from August 2014 through April 2016. In patients with previously diagnosed or suspected BE (894/1000), investigators used VLE and identified areas of concern not seen on white light endoscopy (WLE) in 59% of the procedures. VLE imaging also guided tissue acquisition and treatment in 71% and 54% of procedures, respectively. VLE as an adjunct modality improved the neoplasia diagnostic yield by 55% beyond the standard of care practice. In patients with no prior history of therapy, and without visual findings from other technologies, VLE-guided tissue acquisition increased neoplasia detection over random biopsies by 700%. Registry investigators reported that VLE improved the BE management process when used as an adjunct tissue acquisition and treatment guidance tool. The ability of VLE to image large segments of the esophagus with microscopic cross-sectional detail may provide additional benefits including higher yield biopsies and more efficient tissue acquisition. Clinicaltrials.gov NCT02215291 [ABSTRACT FROM AUTHOR]

Androgenetic alopecia (AGA) is one of the most common causes of hair loss in genetically predisposed men and women. We studied the therapeutic efficacy and safety of oral finasteride in male patients with AGA. A total of 40 male AGA patients, 18-35 years of age, wad enrolled in the study for a period of 9 months. Oral finasteride, 1mg/day, was started and the drug efficacy was assessed on the basis of pre- and post-treatment clinical photographs, trichogram, hair pull test and self assessment of hair re-growth by the investigators. Routine hematological and bio-chemical investigations and a questionnaire related to sexual disturbances were carried out to assess the safety profile of the drug at each follow-up visit every three months. Improvement in hair growth was observed by comparing the paired pre- and post-treatment global photographs (p

Abstract Background Recent advances in the management of Barrett’s Esophagus (BE) have placed greater emphasis on accurate diagnosis of BE as well as better prediction of risk for progression to esophageal adenocarcinoma (EAC). Histological evaluation of BE is particularly challenging with significant inter-observer variability. We explored the presence and extent of genomic instability in BE biopsy specimens as a means to add supplementary information to the histological classification and clinical decision-making related to early disease. Methods We reviewed histology slides from 271 patients known to have BE. Using histological features as a guide, we microdissected target cell populations with various histological classifications of BE (intestinal metaplasia, “indefinite for dysplasia”, low grade dysplasia, or high grade dysplasia). DNA was extracted from microdissected targets and analyzed for loss of heterozygosity (LOH) using a panel of 16 LOH mutational markers associated with tumor suppressor genes at chromosomal loci 1p, 3p, 5q, 9p, 10q, 17p, 17q, 18q, 21q, 22q. The presence or absence of mutations and the clonality of each mutation were determined for each marker. Results The presence and clonal expansion of LOH mutations was formulated into mutational load (ML) for each microdissected target analyzed. ML correlated with the histological classification of microdissected targets, with increasingly severe histology having higher ML. Three levels of mutation load (no ML, low ML, and high ML) were defined based on the population of microdissected targets histologically classified as intestinal metaplasia. All microdissected targets with dysplasia had mutations, with a high ML consistently present in high grade dysplasia targets. Microdissected targets histologically classified as intestinal metaplasia or “indefinite for dysplasia” spanned a range of no, low, and high ML. Conclusions The results of this study reinforce the association of genomic instability with disease progression in BE. The presence and extent (clonality) of genomic instability, as assessed by mutational load, may assist histology in defining early stages of BE that are potentially at greater risk for disease progression. Assessment of mutational load using our panel of LOH mutational markers may be a useful adjunct to microscopic inspection of biopsy specimens, and thereby, improve patient management.