tbuckley/cabot-search huggingface dataset:
Smartphone-Based Visual Acuity Measurement for Screening and Clinical Assessment
Authors: Christopher J. Brady, Allen O. Eghrari, Alain B. Labrique
Journal: JAMA (2015)

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Noninvasive vascular ultrasound An asset in vascular medicine
Authors: R Reneman
Journal: Cardiovascular Research (2000)

### 1.1 Introduction

There are always moments in life, inviting to look back on the past. Entering the next millennium is certainly such an occasion, because it happens generally only once in a life-time. Therefore, we very much liked the idea of the Editors to publish a special issue of Cardiovascular Research on the occasion of this event and to explore the impact of the articles in the journal most frequently cited over the years on further developments in the field. We gladly accepted their invitation to evaluate in this respect the article by Levenson et al. published in Cardiovascular Research in 1981 [1].

### 1.2 Content of the article

In this article the authors described an ultrasound system to assess diameter, blood flow velocity and volume flow in the brachial artery in man. The apparatus consisted of an adjustable range-gated pulsed Doppler system, emitter frequency 8 MHz, combined with a double transducer system to accurately determine the angle between ultrasound beam and vessel axis. The latter is a prerequisite for accurate determination of both the velocity in and the diameter of the artery and, hence, for proper calculation of volume flow. The length of the sample volume could be adjusted by varying the length of the reception duration. A small sample volume was used to measure velocity locally in the artery and to determine the diameter of the vessel accurately and a large one to estimate the average velocity over the cross-sectional area of the vessel. A static high-pass filter with a lower cut-off frequency of 250 Hz was used to reduce interference of high amplitude low frequency signals reflected by the arterial walls. The validity of the system was tested in an in vitro set-up and the results showed that the diameter as assessed with the system compared favorably with the diameter of the tubing in …
CA184-095: A randomized, double-blind, phase III trial to compare the efficacy of ipilimumab (Ipi) versus placebo in asymptomatic or minimally symptomatic patients (pts) with metastatic chemotherapy-naive castration-resistant prostate cancer (CRPC).
Authors: Tomasz M. Beer, Christopher Logothetis, Padmanee Sharma, Yohann Loriot, Karim Fizazi, Alberto Bossi, Eugene D. Kwon, Brent McHenry, Paul Gagnier, Winald R. Gerritsen
Journal: Journal of Clinical Oncology (2013)

TPS5093 Background: Globally, docetaxel remains the standard of care for metastatic CRPC; however, its use may be delayed until pts develop symptoms. The presence of infiltrating leukocytes in CRPC tumors suggests a natural antitumor immune response is occurring. This is supported by an overall survival (OS) benefit reported in men with asymptomatic or minimally symptomatic metastatic CRPC who received sipuleucel-T. Ipi, a monoclonal antibody that binds CTLA-4, augments antitumoral activity of cytotoxic immune cells. Ipi demonstrated OS benefit in two phase III trials for advanced melanoma, with side effects that were managed using product-specific treatment guidelines. In phase I/II trials in metastatic CRPC, Ipi has shown clinical activity (as measured by prostate-specific antigen [PSA] declines and RECIST response) with a similar toxicity profile to that observed in melanoma. This global (149 sites in 24 countries) phase III study (ClinicalTrials.gov identifier: NCT01057810) evaluates Ipi vs placebo in chemotherapy-naïve pts with asymptomatic or minimally symptomatic CRPC without visceral metastases. Methods: The primary endpoint is OS; secondary endpoints include progression-free survival, time to pain progression, time to non-hormonal systemic therapy and safety characterization. The study is designed to detect a 9.3-month median difference (HR=0.7) in OS with 90% power and 0.05 two-sided significance. Pts are randomized at a 2:1 ratio to receive Ipi 10 mg/kg every 3 weeks for up to 4 doses or placebo as induction therapy. Eligible pts will receive maintenance therapy of blinded study drug every 12 weeks. The accrual goal is 600 pts randomized. Clinical trial information: NCT01057810. [Table: see text] [Table: see text]
Patterns of first recurrence following adjuvant intraperitoneal chemotherapy for advanced ovarian cancer.
Authors: E. J. Tanner, F. Dao, O. Zivanovic, S. M. Kehoe, D. R. Black, J. A. Konner, R. R. Barakat, S. M. Lichtman, D. A. Levine
Journal: Journal of Clinical Oncology (2010)

5109 Background: Postsurgical intraperitoneal (IP) platinum-based chemotherapy should be strongly considered for patients (pts) with optimally debulked advanced epithelial ovarian cancer (EOC) due to a demonstrate survival advantage. However, anecdotal experience indicated unexpected sites of recurrence after IP chemotherapy. We hypothesize that the distribution of first recurrences will differ between pts receiving adjuvant IP chemotherapy and IV chemotherapy. Methods: Pts with stage IIIC optimally debulked EOC diagnosed between 1/03 and 6/08 were divided into two groups based on type of adjuvant chemotherapy: IV or 4+ cycles IP. Clinical data including the site of first recurrence was collected from medical records. Recurrences were defined as pelvic, lower abdominal, upper abdominal, abdominal lymph nodes (LN), extra- abdominal LNs, and distant. The distribution of recurrences was compared between IV and IP groups using standard two-sided statistical tests. Results: Sixty of 104 pts (57.7%) in the IV group and 44 of 111 pts (39.6%) in the IP group met inclusion criteria and have recurred. In both groups, 60% of pts first recurred in multiple locations. More pts in the IV group had a first recurrence in the lower abdomen/pelvis than the IP group, but more pts in the IP group had a first recurrence in the upper abdomen and extra-abdominal LNs (see Table). Conclusions: The data suggest that pts receiving IP chemotherapy more often recur in both the upper abdomen and at sites outside of the abdominal cavity, while less likely to recur exclusively in the lower abdomen/pelvis. These findings may reflect the effectiveness of IP chemotherapy dwelling within the anatomic areas of peritoneal distribution. Sites of first recurrence in patients receiving IV versus IP chemotherapy for ovarian cancer Sites of first recurrence IP group N = 44 (%) IV group N = 60 (%) P Lower abdomen/pelvis 18 (40.9) 39 (65.0) 0.015 Upper abdomen 28 (63.6) 24 (40.0) 0.017 Abdominal LNs 15 (34.1) 24 (40.0) 0.54 Extra-abdominal LNs 15 (34.1) 7 (11.7) 0.006 Distant metastasis 10 (34.1) 7 (11.7) 0.13 Only lower abdomen/pelvis 6 (13.6) 22 (32.8) 0.009 Only extra-abdominal LNs or distant metastasis 4 (9.1) 1 (1.5) 0.080 No significant financial relationships to disclose.
Limited thymic recovery after extracorporeal photopheresis in a low-body-weight patient with acute graft-versus-host disease of the skin
Authors: Benjamin Beattie, David Cole, Lindsay Nicholson, Suzy Leech, Aileen Taylor, Holly Robson, Julie Guest, Xiao Nong Wang, Andrew R. Gennery
Journal: Journal of Allergy and Clinical Immunology (2015)
Corrigendum to ‘Nanopore-Based Fourth-Generation DNA Sequencing Technology’ [GPB 144 (2015) – GPB 13/1 (4–16)]
Authors: Yanxiao Feng, Yuechuan Zhang, Cuifeng Ying, Deqiang Wang, Chunlei Du
Journal: Genomics Proteomics & Bioinformatics (2015)

[This corrects the article DOI: 10.1016/j.gpb.2015.01.009.].
Abstract 9138: QT Interval Duration and Incident Mortality in the Framingham Heart Study
Authors: Peter A Noseworthy, Gina M Peloso, Shih-Jen Hwang, Martin G Larson, Daniel Levy, Christopher J O'Donnell, Christopher Newton-Cheh
Journal: Circulation (2011)

Background: The association between QT interval and mortality has been demonstrated in multiple large, prospective population-based studies using Bazett's heart rate correction, but the strength of the association varies considerably among studies. We examined this relationship in the Framingham Heart Study. Methods and Results: Participants in the first (original cohort, n = 2,415) and second generation (offspring cohort, n = 4,478) cohorts examined in the early 1970s were included in this study. Using Cox proportional hazards regression adjusting for age and sex, a 20 msec increase in QTc (using Bazett's correction; QT/RR 1/2 interval) was associated with increased risk of all-cause mortality (HR 1.15, 95% CI 1.12-1.19, p = 7.6x10 -17 ), CHD mortality (HR 1.18, 95% CI 1.08-1.30, p = 0.0003), and sudden cardiac death (HR 1.20, 95% CI 1.04-1.39, p = 0.01). However, additional adjustment for heart rate, either by additional adjustment of the QTc for RR interval, or use of linear regression of QT on RR interval, attenuated the associations with all-cause mortality (HR 1.10, 95% CI 1.06-1.15, p= 3.6x10 -6 , Figure), CHD mortality (HR 1.11, 95% CI 0.99-1.24, p= 0.07) and SCD (HR 1.16, 95% CI 0.97-1.40, p= 0.11). Conclusion: In the FHS (mean follow up 27.35 years), there is evidence for a graded relationship between QTc and all-cause mortality, CHD death, and SCD, however, this effect is considerably attenuated by additional adjustment for RR interval. These findings demonstrate that residual confounding by heart rate overestimates the effect on mortality when using Bazett's heart rate correction.
A randomized phase II placebo-controlled trial using maintenance therapy to evaluate the vascular targeting agent BIBF 1120 following treatment of relapsed ovarian cancer (OC)
Authors: J. A. Ledermann, G. J. Rustin, A. Hackshaw, S. B. Kaye, G. Jayson, H. Gabra, L. E. James, S. Bell, G. Temple
Journal: Journal of Clinical Oncology (2009)

5501 Background: BIBF 1120 is a new targeted therapeutic agent for maintenance therapy in OC. It is a unique triple angiokinase inhibitor, targeting 3 receptor classes involved in the formation of blood vessels (VEGFR, PDGFR, and FGFR). Methods: Continuous BIBF 1120 (250 mg, oral, twice daily) for up to 9 months (mo) was compared with placebo in a novel application of a randomized double-blind trial in pts who responded to their last (at least second line) chemotherapy. The primary endpoint, progression-free survival at 36 weeks, was confirmed by CT assessment, performed at 12-week intervals. Results: 84 pts were randomized (44 BIBF 1120; 40 placebo), mean age 60y (range 27–76). All had responded according to GCIG criteria. Treatment-free interval before prior chemotherapy was &lt;6 mo for 41% and 6–12 mo for 59% of pts. Median treatment duration was 116 days (d), range, 2–281d (BIBF 1120) and 101 d, 2–239d (placebo). Five BIBF 1120 pts completed 9 mo of treatment vs 0 placebo pts. The 36-wk PFS rates (95% confidence interval [CI]) were 15.6% (3.8, 27.3) for BIBF 1120 and 2.9% (0.0, 8.4) for placebo. Although the trial was not powered for a direct comparison, the PFS hazard ratio was 0.68 (95% CI: 0.42, 1.09). Median time to RECIST progression (mo) was 4.8 for BIBF 1120, and 2.8 for placebo. There were no deaths during treatment. Grade 3 and 4 adverse events (AE) were seen in 54 and 7% (BIBF 1120) and 25 and 3% (placebo) of pts. Expected gastrointestinal toxicities occurred slightly more frequently in the BIBF 1120 arm (16 vs 10%, all gd 3; no gd 4 events). Elevated liver enzymes occurred in 43% (BIBF 1120) vs. 6.3% (placebo). Conclusions: Our trial suggests that maintenance BIBF 1120 could delay disease progression in OC pts who had previously responded to chemotherapy. A large phase III trial is needed to confirm the efficacy of this drug. [Table: see text]
Paid for by the NHS, treated privately
Authors: J. Appleby
Journal: BMJ (2015)

John Appleby looks at how much non-NHS providers contribute to NHS care

Central to the 1990 reforms of the NHS was the idea that by separating purchasers of care from providers, with the purchasers holding the money (but no services) and the providers services (but no money), the transactions that would need to take place would drive up quality and efficiency.1 Health authorities would be active purchasers of care on behalf of their resident populations. And in this “internal market” there would be freedom to shop around for the best deals from any organisation willing to supply, whether state owned or independent sector.

There have been several reboots of the original idea since then. Internal market 2.0 from the 2002 Labour administration emphasised patient choice and encouraged more private …
Trends in Insulin Use and Diabetes Control in the U.S.: 1988–1994 and 1999–2012
Authors: Elizabeth Selvin, Christina M. Parrinello, Natalie Daya, Richard M. Bergenstal
Journal: Diabetes Care (2015)

Over the past two decades, many new treatment options have been introduced for type 2 diabetes. Increasingly, there is debate regarding the effectiveness of insulin as the last-line therapy. While diabetes control has improved over the past two decades (1–3), a substantial portion of patients is still not meeting the clinical targets. To examine national trends in glycemic control by insulin and oral diabetes medication use, we conducted a cross-sectional study of 4,947 adult participants with diagnosed diabetes (all types) in the National Health and Nutrition Examination Survey (NHANES) in the 1988–1994 and 1999–2012 cycles. The NHANES surveys are cross-sectional, complex probability samples of the U.S. civilian noninstitutionalized population. All NHANES protocols were approved by an institutional review board, and informed consent was obtained from participants. Hemoglobin A1c (HbA1c …
Phase I clinical trial of BromoHydrin PyroPhosphate, BrHPP (Phosphostim), a Vγ9Vδ2 T lymphocytes agonist in combination with low dose Interleukin-2 in patients with solid tumors
Authors: J. Bennouna, J. Medioni, F. Rolland, J. L. Misset, M. Campone, H. Sicard, J. Tiollier, F. Romagne, J. Y. Douillard, F. Calvo
Journal: Journal of Clinical Oncology (2005)

2536 Background: Vγ9Vδ2 (γδ) T lymphocytes, a critical peripheral blood lymphocyte (PBL) subset, are directly cytotoxic against several tumor types, including renal carcinoma cells (RCC). (γδ) lymphocytes can be selectively expanded in vivo with BrHPP (Phosphostim) and IL-2. We conducted a phase I trial, to define the dose limiting toxicities (DLT), characterize PK and PD, and recommend a dose for phase II studies. Methods: Patients (pts), with advanced solid tumors and no organ dysfunction and PS of 0–1 were included. A single, one hour intravenous infusion of BrHPP was administered alone at cycle 1, combined with low dose of SC IL-2 (1 MIU/M2 d1 to d7) in the subsequent cycles (day 1 every 3 weeks). BrHPP dosage was escalated in cohorts of 3 pts extended to 6 if 1/3 patients on a dose level had a DLT. Results: 18 pts (10 mRCC, 1 colon, 2 breast, 1 ovarian, 1 gastric, 3 oesophageal cancer) have been enrolled to date at 4 dose levels: 4 pts 200 mg/m2, 3 pts 600 mg/m2, 6 pts 1200 mg/m2, 5 pts 1800 mg/m2. At 1800 mg/m2 (first cycle): 2 out of 5 pts presented a completely reversible serious adverse event fulfilling a DLT criteria: one Gr3 hypotension (1 pt) and one Gr3 (1 pt) hyperthermia suggesting cytokine release syndrome immediately following first infusion. At lower doses the treatment was well tolerated, the most frequent adverse events being mild fever, chills, abdominal pain, without exacerbation in the IL-2 combined cycles. BrHPP alone did not induce significant γδ lymphocytes expansion whereas the addition of SC- IL-2 demonstrated an increase of γδ in all tested doses (from 5 to 50 fold expansion rate). Complete results of pharmacokinetics, pharmacodynamics, tolerance and tumour response evaluation at all dose levels will be presented at the meeting. Conclusion: BrHPP in combination with SC low dose IL 2 is safe, well tolerated, and allows to induce a potent γδ T lymphocytes expansion in pts. Clinical activity will be evaluated in phase II clinical trials. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Innate Innate Innate
Detection of flow limitation in COPD patients using two different forced oscillation devices
Authors: K. De Soomer, A.-M. Vints, R. Heyndrickx, L. Claus, W. De Backer, E. Oostveen
Journal: European Respiratory Journal (2014)

Introduction: Dellaca et al. (Eur Respir J, 2004, 23: 232) demonstrated that expiratory flow limitation (EFL) can be detected by determining the within-breath variation of reactance at 5 Hz. The aim of our study was to compare the performance of two forced oscillation (FOT) devices in the detection of EFL in COPD patients.  Methods: Respiratory impedance was measured during quiet breathing in 43 adult patients with a clinical diagnosis of COPD prior to entry to our study (GOLD severity II/III/IV (n=21/19/3), 22M/21F, age: 69 (8) yrs, FEV1: 49 (14) %pred). In all participants, two FOT results with two different devices were obtained (Resmon Pro Full, Restech s.r.l., Italy and IOS, Jaeger, Wurzburg, Germany), with random order of the devices. Each FOT result consisted of 3 to 5 acceptable FOT recordings which lasted either 5 breaths with the Resmon Pro Full or 20 seconds using an IOS device.  Results: In 35 out of 43 COPD patients the FOT devices revealed concordant results: EFL in 11 patients, NON-EFL in 22 patients, in 2 patients in some recordings of both devices FL, in some NON-EFL. However, in 8 patients disconcordant results were obtained: EFL or NON-EFL with one device but undetermined with the other device (n=6) or contradictory results (n=2). See figure.  Conclusion: Concordant results in the detection of flow limitation with two different forced oscillation devices are obtained in the majority of COPD patients.
Abstract P087: Body Mass Index and Change in Obesity Status over 25 Years: The Relationship within Spouse Pairs in the Atherosclerosis Risk in Communities Study
Authors: Laura K Cobb, Mara McAdams-DeMarco, Cheryl A Anderson, Ellen W Demerath, Mark Woodward, Elizabeth Selvin, Josef Coresh
Journal: Circulation (2014)

Introduction: Environmental causes have been a focus of efforts to address the US obesity epidemic. Spouses share a similar environment and should therefore experience similar changes in body mass index (BMI) and obesity status over time. Existing longitudinal studies of spouses have not examined whether associations of BMI change within pairs are similar by gender. Methods: We analyzed spouse pairs from the community-based ARIC cohort, recruited from 1986 to 1989 at ages 45-64. We used linear mixed models to assess the association of changes in spousal BMI with changes in individual BMI assessed at 5 clinic visits during 25 years of follow-up. We used survival models accounting for interval censoring to evaluate the association between one spouse becoming obese (BMI&gt;30 kg/m2) and the other becoming obese. Analyses controlled for time-varying demographic, lifestyle, and clinical factors, pre-existing illness, and spousal CVD risk factors and illness. We assessed similarity of the results by gender. Results: We included 4,003 spouse pairs with information on BMI at more than one visit. Mean BMI in men at baseline was 27.5 kg/m2, increasing to 28.6 in 2011-13. For women, baseline BMI was 27.1 kg/m2, increasing to 28.1 in 2011-13. Baseline BMI correlation within spouses was 0.18 (p &lt;0.001). Among women, mean annual BMI change increased by 0.17 kg/m2 per unit increase in spousal annual BMI change (95% CI: 0.14 - 0.19); this association was lower in men: 0.11 kg/m2 (0.09 - 0.13) (Figure). Non-obese women whose husbands became obese were more likely to become obese themselves compared to women whose husbands stayed non-obese (HR 1.52, 1.09- 2.11). Results for men were similar (HR 1.59, 1.14-2.21). Conclusions: Our results suggest that changes in BMI and obesity status in spouse pairs are related, with change in men’s BMI having a somewhat stronger influence on their wives’ BMI. This finding was robust to adjustment for individual and spousal characteristics and suggests weight control strategies might benefit from addressing both spouses.
Co-expression of cathepsin B and its inhibitor Stefin A in breast cancer metastasis to lung and bone
Authors: Belinda Parker, Bradley Bidwell, John Slavin, Rohan Steel, Bedrich Eckhardt, Michael Henderson, Robin Anderson
Journal: Cancer Research (2007)

3095   Metastatic breast cancer is a life threatening disease with limited treatment options. Given the lack of molecular targets for tailored therapy, we analysed changes in gene expression associated with metastatic progression in breast cancer using a clinically relevant murine model of spontaneous metastasis to lung and bone. From microarray expression profiling of immunopurified tumor cells derived from primary tumors and matched metastases, we identified the cysteine cathepsin inhibitor Stefin A. Stefin A expression was increased in neoplastic epithelial cells isolated from metastatic primary tumors and further increased in their matched spontaneous metastases in lung and bone in the mouse model. Expression was not detected in tumor cells in culture, indicating induction within the tumor microenvironment. To establish a link with the clinical disease we investigated Stefin A expression in human breast cancer tissues. Breast cancer patients (n=24) lacking primary tumor expression of Stefin A had improved disease free survival (p=0.017). In patients who had recurrent disease, Stefin A was enhanced in lung and bone metastases. Stefin A may be a marker of enhanced cathepsin activity, since cathepsin B activity was increased in highly metastatic primary tumors. Additionally, Stefin A and cathepsin B were co-expressed in primary tumors and lung and bone metastases, both in the murine model and in human tissues. We conclude that  Stefin A is expressed in metastatic breast tumors and in distant metastases, acting as a marker of activated cysteine cathepsins, which are potential therapeutic targets for metastatic disease.
RAS-MAPK dependence underlies a rational polytherapy strategy in EML4-ALK–positive lung cancer
Authors: Gorjan Hrustanovic, Victor Olivas, Evangelos Pazarentzos, Asmin Tulpule, Saurabh Asthana, Collin M Blakely, Ross A Okimoto, Luping Lin, Dana S Neel, Amit Sabnis, Jennifer Flanagan, Elton Chan, Marileila Varella-Garcia, Dara L Aisner, Aria Vaishnavi, Sai-Hong I Ou, Eric A Collisson, Eiki Ichihara, Philip C Mack, Christine M Lovly, Niki Karachaliou, Rafael Rosell, Jonathan W Riess, Robert C Doebele, Trever G Bivona
Journal: Nature Medicine (2015)
The Cost-effectiveness of Adopting Risk-scoring Systems for Population-Based Colorectal Cancer Screening
Authors: Martin C.S. Wong, Jessica Y.L. Ching, Sunny H. Wong, Siew C. Ng, Jeffrey P. Shum, Victor C.W. Chan, Thomas Y.T. Lam, Arthur K.C. Luk, Simon S.M. Ng, Justin C.Y. Wu, Francis K.L. Chan, Joseph J.Y. Sung
Journal: Clinical Gastroenterology and Hepatology (2015)