bluuebunny/crossref_metadata_2025 huggingface dataset:
Dementia-friendly prisons: a mixed-methods evaluation of the application of dementia-friendly community principles to two prisons in England
Authors: Treacy Samantha , Haggith Anna , Wickramasinghe Nuwan Darshana , Van Bortel Tine
Published: August 2019

Objectives

To apply and evaluate dementia-friendly community (DFC) principles in prisons.

Design

A pilot study and process evaluation using mixed methods, with a 1-year follow-up evaluation period.

Setting

Two male prisons: a category C sex offender prison (prison A) and a local prison (prison B).

Participants

68 participants—50 prisoners, 18 staff.

Intervention

The delivery of dementia information sessions, and the formulation and implementation of dementia-friendly prison action plans.

Measures

Study-specific questionnaires; Alzheimer’s Society DFC criteria; semi-structured interview and focus group schedules.

Results

Both prisons hosted dementia information sessions which resulted in statistically significant (p>0.05) increases in attendees’ dementia knowledge, sustained across the follow-up period. Only prison A formulated and implemented a dementia action plan, although a prison B prisoner dedicated the prisoner magazine to dementia, post-information session. Prison A participants reported some progress on awareness raising, environmental change and support to prisoners with dementia in maintaining independence. The meeting of other dementia-friendly aims was less apparent. Numbers of older prisoners, and those diagnosed with dementia, appeared to have the greatest impact on engagement with DFC principles, as did the existence of specialist wings for older prisoners or those with additional care needs. Other barriers and facilitators included aspects of the prison institution and environment, staff teams, prisoners, prison culture and external factors.

Conclusions

DFC principles appear to be acceptable to prisons with some promising progress and results found. However, a lack of government funding and strategy to focus action around the escalating numbers of older prisoners and those living with dementia appears to contribute to a context where interventions targeted at this highly vulnerable group can be deprioritised. A more robust evaluation of this intervention on a larger scale over a longer period of time would be useful to assess its utility further.
Coronary heart disease, hypertension and use of biomass fuel among women: comparative cross-sectional study
Authors: Fatmi Zafar , Ntani Georgia , Coggon David
Published: August 2019

Objectives

To explore the associations of hypertension and coronary heart disease (CHD) with use of biomass fuel for cooking.

Design

Comparative cross-sectional study.

Setting

Rural villages in Sindh, Pakistan.

Participants

Women aged ≥40 years who had used biomass fuel for cooking for at least the last year (n=436), and a comparison group (n=414) who had cooked only with non-biomass fuel during the last year were recruited through door-to-door visits. None of those who were invited to take part declined.

Primary and secondary outcome measures

Hypertension was determined from blood pressure measurements and use of medication. CHD was assessed by three measures: history of angina (Rose angina questionnaire), previous history of ‘heart attack’, and definite or probable changes of CHD on ECG. Potentially confounding risk factors were ascertained by questionnaire and anthropometry. Associations of hypertension and CHD with use of biomass and other risk factors were assessed by logistic regression, and summarised by ORs with 95% CIs.

Results

After adjustment for potential confounders, there was no association of hypertension (OR: 1.0, 95% CI 0.8 to 1.4) angina (OR: 1.0, 95% CI 0.8 to 1.4), heart attack (OR: 1.2, 95% 0.7 to 2.2) or ECG changes of CHD (OR: 0.8, 95% CI 0.6 to 1.2) with current use of biomass for cooking. Nor were any associations apparent when analyses were restricted to long-term (≥10 years) users and non-users of biomass fuel.

Conclusions

A linked air monitoring study indicated substantially higher airborne concentrations of fine particulate matter in kitchens where biomass was used for cooking. It is possible that associations with CHD and hypertension were missed because most of the comparison group had used biomass for cooking at some time in the past, and risk remains elevated for many years after last exposure.
Medical error in the care of the unrepresented: disclosure and apology for a vulnerable patient population
Authors: Byju Arjun S , Mayo Kajsa
Published: August 2019

Defined as patients who ‘lack decision-making capacity and a surrogate decision-maker’, the unrepresented (sometimes referred to as the ‘unbefriended’, ‘isolated patients’ and/or ‘patients without surrogates’) present a major quandary to clinicians and ethicists, especially in handling errors made in their care. A novel concern presented in the care of the unrepresented is how to address an error when there is seemingly no one to whom it can be disclosed. Given that the number of unrepresented Americans is expected to rise in the coming decades, and some fraction of them will experience a medical error, creating protocols that answer this troubling question is of the utmost importance. This paper attempts to begin that conversation, first arguing that the precarious position of unrepresented patients, particularly in regards to errors made in their care, demands their recognition as a vulnerable patient population. Next, it asserts that the ethical obligation to disclose error still exists for the unrepresented because the moral status of error does not change with the presence or absence of surrogate decision-makers. Finally, this paper concludes that in outwardly acknowledging wrongdoing, a clinician or team leader can alleviate significant moral distress, satisfy the standards of a genuine apology, and validate the inherent and equivalent moral worth of the unrepresented patient.
Cone penetration test (CPT)-based subsurface soil classification and zonation in two-dimensional vertical cross section using Bayesian compressive sampling
Authors: Wang Yu , Hu Yue , Zhao Tengyuan
Published: August 2019

A novel method is developed in this study for soil classification and zonation in a two-dimensional (2D) vertical cross section using cone penetration tests (CPTs). A CPT is usually performed vertically and the number of CPT soundings in a site is often limited in geotechnical engineering practice. It is, therefore, difficult to properly interpret CPT results along the horizontal direction or accurately estimate the horizontal correlation length of CPT data. The method proposed in this study bypasses the difficulty in estimating horizontal correlation length and provides proper identification of subsurface soil stratification (i.e., soil layer number is constant along horizontal direction) and zonation (i.e., soil layer number varies along horizontal direction) in a 2D vertical cross section directly from a limited number of CPT soundings. The proposed method consists of three key elements: 2D interpolation of CPT data using 2D Bayesian compressive sampling; determination of soil behavior type (SBT) using a SBT chart at every location in the 2D section, including locations with measurements and unsampled locations; and soil layer or zone delineation using an edge detection method. Both simulated and real data examples are used to illustrate the proposed method. Results show that the method performs well even when only five sets of CPT soundings are available.
miRNA transcriptome comparison between muscle and adipose tissues indicates potential miRNAs associated with intramuscular fat in Chinese swamp buffalo
Authors: Huang Jieping , Wang Shuzhe , Feng Xue , Liu Xiaoyan , Zhao Jinhui , Zheng Qiuzhi , Wei Xuefeng , Ma Yun
Published: August 2019

The amount of intramuscular fat (IMF) affects the tenderness and juiciness of beef and is an important indicator of beef quality. A few miRNAs involved in IMF deposition have been identified in other livestock. However, in the buffalo, the association between miRNA and IMF has not been reported and the miRNA expression profile remains poorly understood. In this study, small RNA sequencing was performed to characterize the miRNA expression pattern in muscle and adipose tissues using the Illumina platform. A total of 108 differentially expressed (DE) miRNAs were identified, including 98 known miRNAs and 10 novel miRNAs. A qRT-PCR experiment confirmed the quality of the DE analysis. Eight DE miRNAs showed high expression in adipose tissue and a considerable expression level in muscle tissue. Functional enrichment indicated that bta-miR-148a, bta-miR-143, bta-miR-10b, bta-let-7i, bta-let-7f, bta-let-7b, bta-miR-30a-5p, and bta-miR-100 were significantly associated with adipogenesis, suggesting these as candidate regulators for IMF deposition in buffalo. However, further functional validation is required. This is the first characterization of the miRNA expression profile in the muscle and adipose tissues of buffalo. These results provide information for the identification of miRNAs with potential effects on IMF deposition in buffalo.
Exploring Social Recommendations with Visual Diversity-Promoting Interfaces
Authors: Tsai Chun-Hua , Brusilovsky Peter
Published: August 2019

The beyond-relevance objectives of recommender systems have been drawing more and more attention. For example, a diversity-enhanced interface has been shown to associate positively with overall levels of user satisfaction. However, little is known about how users adopt diversity-enhanced interfaces to accomplish various real-world tasks. In this article, we present two attempts at creating a visual diversity-enhanced interface that presents recommendations beyond a simple ranked list. Our goal was to design a recommender system interface to help users explore the different relevance prospects of recommended items in parallel and to stress their diversity. Two within-subject user studies in the context of social recommendation at academic conferences were conducted to compare our visual interfaces. Results from our user study show that the visual interfaces significantly reduced the exploration efforts required for given tasks and helped users to perceive the recommendation diversity. We show that the users examined a diverse set of recommended items while experiencing an improvement in overall user satisfaction. Also, the users’ subjective evaluations show significant improvement in many user-centric metrics. Experiences are discussed that shed light on avenues for future interface designs.
AnchorViz
Authors: Suh Jina , Ghorashi Soroush , Ramos Gonzalo , Chen Nan-Chen , Drucker Steven , Verwey Johan , Simard Patrice
Published: August 2019

When building a classifier in interactive machine learning (iML), human knowledge about the target class can be a powerful reference to make the classifier robust to unseen items. The main challenge lies in finding unlabeled items that can either help discover or refine concepts for which the current classifier has no corresponding features (i.e., it has
feature blindness
). Yet it is unrealistic to ask humans to come up with an exhaustive list of items, especially for rare concepts that are hard to recall. This article presents
AnchorViz
, an interactive visualization that facilitates the discovery of prediction errors and previously unseen concepts through human-driven semantic data exploration. By creating example-based or dictionary-based anchors representing concepts, users create a topology that (a) spreads data based on their similarity to the concepts and (b) surfaces the prediction and label inconsistencies between data points that are semantically related. Once such inconsistencies and errors are discovered, users can encode the new information as labels or features and interact with the retrained classifier to validate their actions in an iterative loop. We evaluated AnchorViz through two user studies. Our results show that AnchorViz helps users discover more prediction errors than stratified random and uncertainty sampling methods. Furthermore, during the beginning stages of a training task, an iML tool with AnchorViz can help users build classifiers comparable to the ones built with the same tool with uncertainty sampling and keyword search, but with fewer labels and more generalizable features. We discuss exploration strategies observed during the two studies and how AnchorViz supports discovering, labeling, and refining of concepts through a sensemaking loop.
A Visual Analytics Approach for Interactive Document Clustering
Authors: Sherkat Ehsan , Milios Evangelos E. , Minghim Rosane
Published: August 2019

Document clustering is a necessary step in various analytical and automated activities. When guided by the user, algorithms are tailored to imprint a perspective on the clustering process that reflects the user’s understanding of the dataset. More than just allow for customized adjustment of the clusters, a visual analytics approach will provide tools for the user to draw new insights on the collection. While contributing his or her perspective, the user will also acquire a deeper understanding of the data set. To that effect, we propose a novel visual analytics system for interactive document clustering. We built our system on top of clustering algorithms that can adapt to user’s feedback. In the proposed system, initial clustering is created based on the user-defined number of clusters and the selected clustering algorithm. A set of coordinated visualizations allow the examination of the dataset and the results of the clustering. The visualization provides the user with the highlights of individual documents and understanding of the evolution of documents over the time period to which they relate. The users then interact with the process by means of changing key-terms that drive the process according to their knowledge of the documents domain. In key-term-based interaction, the user assigns a set of key-terms to each target cluster to guide the clustering algorithm. We have improved that process with a novel algorithm for choosing proper seeds for the clustering. Results demonstrate that not only the system has improved considerably its precision, but also its effectiveness in the document-based decision making. A set of quantitative experiments and a user study have been conducted to show the advantages of the approach for document analytics based on clustering. We performed and reported on the use of the framework in a real decision-making scenario that relates users discussion by email to decision making in improving patient care. Results show that the framework is useful even for more complex data sets such as email conversations.
User Evaluations on Sentiment-based Recommendation Explanations
Authors: Chen Li , Yan Dongning , Wang Feng
Published: August 2019

The explanation interface has been recognized as important in recommender systems because it can allow users to better judge the relevance of recommendations to their preferences and, hence, make more informed decisions. In different product domains, the specific purpose of explanation can be different. For high-investment products (e.g., digital cameras, laptops), how to educate the typical type of new buyers about product knowledge and, consequently, improve their preference certainty and decision quality is essentially crucial. With this objective, we have developed a novel tradeoff-oriented explanation interface that particularly takes into account sentiment features as extracted from product reviews to generate recommendations and explanations in a category structure. In this manuscript, we first reported the results of an earlier user study (in both before-after and counter-balancing setups) that compared our prototype system with the traditional one that purely considers static specifications for explanations. This experiment revealed that adding sentiment-based explanations can significantly increase users’ product knowledge, preference certainty, perceived information usefulness, perceived recommendation transparency and quality, and purchase intention. In order to further identify the reason behind users’ perception improvements on the sentiment-based explanation interface, we performed a follow-up lab controlled eye-tracking experiment that investigated how users viewed information and compared products on the interface. This study shows that incorporating sentiment features into the tradeoff-oriented explanations can significantly affect users’ eye-gaze pattern. They were stimulated to not only notice bottom categories of products, but also, more frequently, to compare products across categories. The results also disclose users’ inherent information needs for sentiment-based explanations, as they allow users to better understand the recommended products and gain more knowledge about static specifications.
Resilient Clock Synchronization Using Power Grid Voltage
Authors: Rabadi Dima , Tan Rui , Yau David K. Y. , Viswanathan Sreejaya , Zheng Hao , Cheng Peng
Published: August 2019

Many clock synchronization protocols based on message passing, e.g., the Network Time Protocol (NTP), assume symmetric network delays to estimate the one-way packet transmission time as half of the round-trip time. As a result, asymmetric network delays caused by either network congestion or malicious packet delays can cause significant synchronization errors. This article exploits sinusoidal voltage signals of an alternating current (AC) power grid to limit the impact of the asymmetric network delays on these clock synchronization protocols. Our extensive measurements show that the voltage signals at geographically distributed locations in a city are highly synchronized. Leveraging calibrated voltage phases, we develop a new clock synchronization protocol that we call Grid Time Protocol (GTP), which allows direct measurement of one-way packet transmission times between its slave and master nodes, subject to an analytic condition that can be easily verified in practice. The direct measurements render GTP resilient against asymmetric network delays under this condition. A prototype implementation of GTP maintains sub-millisecond synchronization accuracy for two nodes tens of kilometers apart in the presence of malicious packet delays. The result has been demonstrated for both Singapore and Hangzhou, China. Simulations driven by real network delay measurements between Singapore and Hangzhou under both normal and congested network conditions also show the synchronization accuracy improvement by GTP. We believe that GTP is suitable for grid-connected distributed systems that are currently served by NTP but desire higher resilience against unfavorable network dynamics and packet delay attacks.
Right ventricular oxygen delivery as a determinant of right ventricular functional reserve during exercise in juvenile swine with chronic pulmonary hypertension
Authors: Cai Zongye , van Duin Richard W. B. , Stam Kelly , Uitterdijk André , van der Velden Jolanda , Vonk Noordegraaf Anton , Duncker Dirk J. , Merkus Daphne
Published: August 2019

Assessing right ventricular (RV) functional reserve is important for determining clinical status and prognosis in patients with pulmonary hypertension (PH). In this study, we aimed to establish RV oxygen (O2) delivery as a determinant for RV functional reserve during exercise in swine with chronic PH. Chronic PH was induced by pulmonary vein banding (PVB), with sham operation serving as control. RV function and RV O2 delivery were measured over time in chronically instrumented swine, up to 12 wk after PVB at rest and during exercise. At rest, RV afterload (pulmonary artery pressure and arterial elastance) and contractility ( Ees and dP/d tmax) were higher in PH compared with control with preserved cardiac index and RV O2 delivery. However, RV functional reserve, as measured by the exercise-induced relative change (Δ) in cardiac index, dP/d tmax, and end-systolic elastance ( Ees), was decreased in PH, and RV pulmonary arterial coupling was lower both at rest and during exercise in PH. Furthermore, the increase in RV O2 delivery was attenuated in PH during exercise principally due to a lower systolic coronary blood flow in combination with an attenuated increase in aorta pressure while arterial O2 content was not significantly altered in PH. Moreover, RV O2 delivery reserve correlated with RV functional reserve, Δcardiac index ( r2 = 0.85), ΔdP/d tmax ( r2 = 0.49), and Δ Ees ( r2 = 0.70), all P < 0.05. The inability to sufficiently increase RV O2 supply to meet the increased O2 demand during exercise is principally due to the reduced RV perfusion relative to healthy control values and likely contributes to impaired RV contractile function and thereby to the limited exercise capacity that is commonly observed in patients with PH.

NEW & NOTEWORTHY Impaired right ventricular (RV) O2 delivery reserve is associated with reduced RV functional reserve during exercise in a swine model of pulmonary hypertension (PH) induced by pulmonary vein banding. Our data suggest that RV function and exercise capacity might be improved by improving RV O2 delivery.
Detrimental effects of chemotherapy on human coronary microvascular function
Authors: Hader Shelby N. , Zinkevich Natalya , Norwood Toro Laura E. , Kriegel Alison J. , Kong Amanda , Freed Julie K. , Gutterman David D. , Beyer Andreas M.
Published: August 2019

Chemotherapy (CT) is a necessary treatment to prevent the growth and survival of cancer cells. However, CT has a well-established adverse impact on the cardiovascular (CV) system, even years after cessation of treatment. The effects of CT drugs on tumor vasculature have been the focus of much research, but little evidence exists showing the effects on the host microcirculation. Microvascular (MV) dysfunction is an early indicator of numerous CV disease phenotypes, including heart failure. The goal of this study was to evaluate the direct effect of doxorubicin (Dox) on human coronary MV function. To study the effect of CT on the cardiac MV function, flow-mediated dilation (FMD), pharmacologically-induced endothelial dependent dilation to acetylcholine (ACh), and smooth muscle-dependent dilation to papaverine were investigated. Vessels were freshly isolated from atrial appendages of adult patients undergoing cardiopulmonary bypass surgery or from cardiac tissue of pediatric patients, collected at the time of surgery to repair congenital heart defects. Isolated vessels were incubated in endothelial culture medium containing vehicle or Dox (100 nm, 15–20 h) and used to measure dilator function by video microscopy. Ex vivo treatment of adult human coronary microvessels with Dox significantly impaired flow-mediated dilation (FMD). Conversely, in pediatric coronary microvessels, Dox-induced impairment of FMD was significantly reduced in comparison with adult subjects. In both adult and pediatric coronary microvessels, ACh-induced constriction was reversed into dilation in the presence of Dox. Smooth muscle-dependent dilation remained unchanged in all groups tested. In vessels from adult subjects, acute treatment with Dox in clinically relevant doses caused significant impairment of coronary arteriolar function, whereas vessels from pediatric subjects showed only marginal impairment to the same stressor. This interesting finding might explain the delayed onset of future adverse CV events in children compared with adults after anthracycline therapy.

NEW & NOTEWORTHY We have characterized, for the first time, human microvascular responses to acute ex vivo exposure to doxorubicin in coronary vessels from patients without cancer. Our data show an augmented impairment of endothelial function in vessels from adult subjects compared with pediatric samples.
Hyperphosphatemia is required for initiation but not propagation of kidney failure-induced calcific aortic valve disease
Authors: Shuvy Mony , Abedat Suzan , Eliaz Ran , Abu-Rmeileh Israa , Abu-Snieneh Asmahan , Ben-Dov Iddo Z. , Meir Karen , Pereg David , Beeri Ronen , Lotan Chaim
Published: August 2019

High serum levels of phosphate are associated with uremia-induced calcific aortic valve disease (CAVD). However, it is not clear whether hyperphosphatemia is required in all phases of the process. Our aim was to determine the effects of phosphate and phosphate depletion at different phases of valve disease. The experimental design consisted of administering a uremia-inducing diet, with or without phosphate enrichment, to rats for 7 wk. Forty-two rats were fed with a phosphate-enriched uremic regimen that caused renal insufficiency and hyperphosphatemia. Another 42 rats were fed with a phosphate-depleted uremic regimen, which induces similar severity of renal insufficiency, but without its related mineral disorder. Aortic valves were evaluated at several points during the time of diet administration. In the second part, additional 54 rats were fed a phosphate-enriched diet for various time periods and were then switched to a phosphate-depleted diet to complete 7 wk of uremic diet. Osteoblast-like phenotype, inflammation, and eventually valve calcification were observed only in rats that were fed with a phosphate-enriched regimen. Significant valve calcification was observed only in rats that were fed a phosphate-enriched diet for at least 4 wk. Valve calcification was observed only when the switch to a phosphate-depleted regimen occurred after osteoblast markers and activation of Akt and ERK intracellular signaling pathways had already been found in the valve. Phosphate is essential for the initiation of the calcification process. However, when osteoblast markers are already expressed in valve tissue, phosphate depletion will not halt the disease.

NEW & NOTEWORTHY High serum levels of phosphate are associated with uremia-induced calcific aortic valve disease. However, it is not clear whether hyperphosphatemia is required in all phases of the process. Our aim was to determine the effects of phosphate and phosphate depletion at different phases of valve disease. Our findings indicated that phosphate is essential for the initiation of the process that includes macrophage accumulation and osteoblast phenotype. Furthermore, hyperphosphatemia is dispensable beyond a certain phase of the process, a point of “no return” after which phosphate depletion does not prevent calcification. This point is relatively early in the course of calcification, when no calcification is apparent, but the inflammation, osteoblast markers, and activation of ERK and Akt pathways have already been identified. Our findings emphasize the complexity of the calcification process and suggest that different mediators might be required during different phases and that the role of phosphate precedes the actual calcification.
Epigenomic mechanisms of alcohol-induced impaired differentiation of skeletal muscle stem cells; role of Class IIA histone deacetylases
Authors: Adler Katherine , Molina Patricia E. , Simon Liz
Published: August 2019

Loss of functional metabolic muscle mass remains a strong and consistent predictor of mortality among people living with human immunodeficiency virus (PLWH). PLWH have a higher incidence of alcohol use disorder (AUD), and myopathy is a significant clinical comorbidity due to AUD. One mechanism of skeletal muscle (SKM) mass maintenance and repair is by differentiation and fusion of satellite cells (SCs) to existing myofibers. Previous studies demonstrated that chronic binge alcohol (CBA) administration decreases SC differentiation potential, myogenic gene expression, and miR-206 expression in simian immunodeficiency virus (SIV)-infected male rhesus macaques and that miR-206 targets the Class IIA histone deacetylase, HDAC4. The aim of this study was to determine whether alcohol-induced increases in Class IIA HDACs mediate the observed decrease in differentiation potential of SCs. Data show that CBA dysregulated HDAC gene expression in SKM and myoblasts of SIV-infected macaques. CBA and antiretroviral therapy increased HDAC activity in SKM and this was positively correlated with HDAC4 gene expression. In vitro ethanol (ETOH) treatment increased HDAC expression during differentiation and decreased differentiation potential of myoblasts. HDAC expression was negatively correlated with fusion index and myotube formation, indicators of differentiation potential. Treatment with a Class II HDAC inhibitor, TMP195, restored differentiation in ETOH-treated myoblasts. MEF2C expression at day 3 of differentiation was positively correlated with fusion index and myotube formation. These findings suggest that an alcohol-mediated increase in Class IIA HDAC expression contributes to decreased myoblast differentiation by downregulating MEF2C, a transcription factor critical for myogenesis.
Association between Alcohol Consumption and Survival in Colorectal Cancer: A Meta-analysis
Authors: Kim Youngyo , Je Youjin , Giovannucci Edward L.
Published: August 2019

Background:

Although an association between alcohol consumption and risk of colorectal cancer is well established, little is known about the association between alcohol consumption and colorectal cancer survival. We conducted a meta-analysis of prospective cohort studies to quantitatively assess this association.

Methods:

Data searches were performed using PubMed and ISI Web of Science databases through December 2018. We estimated pooled RRs with 95% confidence intervals (CI) using random-effects models.

Results:

Twelve studies with 32,846 patients with colorectal cancer were included in the meta-analysis. Compared with no alcohol consumption, light (RR = 0.87; 95% CI, 0.81–0.94) and moderate (RR = 0.92; 95% CI, 0.85–1.00) prediagnostic alcohol consumption were associated with lower risk of all-cause mortality. Light prediagnostic alcohol consumption was associated with lower risk of colorectal cancer–specific mortality (RR = 0.87; 95% CI, 0.78–0.98). However, heavy prediagnostic alcohol consumption was not significantly associated with colorectal cancer survival. In a dose–response analysis, a nonlinear association between prediagnostic alcohol consumption and all-cause mortality was observed (Pnonlinearity = 0.0025), showing the reduction in RR at <30 g/day of alcohol consumption. By type of alcohol, wine consumption was associated with lower risk of mortality from all-causes and colorectal cancer, but a positive association was observed between moderate liquor consumption and all-cause mortality. There was no association between postdiagnostic alcohol consumption and colorectal cancer survival.

Conclusions:

Light and moderate prediagnostic alcohol consumption were associated with better survival in colorectal cancer.

Impact:

Our findings suggest that light and moderate alcohol consumption may be associated with better survival in colorectal cancer, but further studies are warranted.
Calcium Channel Blockers and Risk of Lymphedema among Breast Cancer Patients: Nested Case–Control Study
Authors: Stolarz Amanda J. , Lakkad Mrinmayee , Klimberg V. Suzanne , Painter Jacob T.
Published: August 2019

Background:

To assess the risk of lymphedema associated with the use of calcium channel blockers (CCB) among breast cancer patients.

Methods:

A nested case–control study of adult female breast cancer patients receiving an antihypertensive agent was conducted using administrative claims data between 2007 and 2015. Cases were patients with lymphedema who were matched to 5 controls based on nest entry date (±180 days), age (±5 years), number of hypertensive drug classes, Charlson Comorbidity Index (CCI), thiazide exposure, and insurance type. Exposure to CCBs and covariates was identified in the 180-day period prior to event date. Conditional logistic regression was used to assess the impact of exposure among cases and controls.

Results:

A total of 717 cases and 1,681 matched controls were identified. After matching on baseline characteristics, mastectomy (7.8% vs. 4.8%; P = 0.0039), exposure to radiotherapy (27.1% vs. 21.7%; P = 0.0046), taxane-based chemotherapy (11.7% vs. 7.4%; P = 0.0007), anthracycline-based chemotherapy (6.0% vs. 3.6%; P = 0.0073), CCB use (28.3% vs. 23.3%; P = 0.0087), and CCI (19.8% vs. 12.7%; P < 0.0001; score of 4 or above) were all higher in cases during the 180 days prior to the event date. In the adjusted analysis, CCB exposure was significantly associated with increased risk of lymphedema (OR = 1.320; 95% confidence interval, 1.003–1.737).

Conclusions:

CCB use was significantly associated with the development of lymphedema in breast cancer patients.

Impact:

CCBs should be avoided or used with caution in breast cancer patients to reduce the risk for developing lymphedema.
The Genomic Landscape of Merkel Cell Carcinoma and Clinicogenomic Biomarkers of Response to Immune Checkpoint Inhibitor Therapy
Authors: Knepper Todd C. , Montesion Meagan , Russell Jeffery S. , Sokol Ethan S. , Frampton Garrett M. , Miller Vincent A. , Albacker Lee A. , McLeod Howard L. , Eroglu Zeynep , Khushalani Nikhil I. , Sondak Vernon K. , Messina Jane L. , Schell Michael J. , DeCaprio James A. , Tsai Kenneth Y. , Brohl Andrew S.
Published: August 2019

Purpose:

Merkel cell carcinoma (MCC) is a rare, aggressive cutaneous malignancy, which has demonstrated sensitivity to immune checkpoint inhibitor therapy. Here, we perform the largest genomics study in MCC to date to characterize the molecular landscape and evaluate for clinical and molecular correlates to immune checkpoint inhibitor response.

Experimental Design:

Comprehensive molecular profiling was performed on 317 tumors from patients with MCC, including the evaluation of oncogenic mutations, tumor mutational burden (TMB), mutational signatures, and the Merkel cell polyomavirus (MCPyV). For a subset of 57 patients, a retrospective analysis was conducted to evaluate for clinical and molecular correlates to immune checkpoint inhibitor response and disease survival.

Results:

Genomic analyses revealed a bimodal distribution in TMB, with 2 molecularly distinct subgroups. Ninety-four percent (n = 110) of TMB-high specimens exhibited an ultraviolet light (UV) mutational signature. MCPyV genomic DNA sequences were not identified in any TMB-high cases (0/117), but were in 63% (110/175) of TMB-low cases. For 36 evaluable patients treated with checkpoint inhibitors, the overall response rate was 44% and response correlated with survival at time of review (100% vs. 20%, P < 0.001). Response rate was 50% in TMB-high/UV-driven and 41% in TMB-low/MCPyV-positive tumors (P = 0.63). Response rate was significantly correlated with line of therapy: 75% in first-line, 39% in second-line, and 18% in third-line or beyond (P = 0.0066). PD-1, but not PD-L1, expression was associated with immunotherapy response (77% vs. 21%, P = 0.00598, for PD-1 positive and negative, respectively).

Conclusions:

We provide a comprehensive genomic landscape of MCC and demonstrate clinicogenomic associates of immunotherapy response.
Scented Candles as an Unrecognized Factor that Increases the Risk of Bladder Cancer; Is There Enough Evidence to Raise a Red Flag?
Authors: Adamowicz Jan , Juszczak Kajetan , Poletajew Slawomir , Van Breda Shane Vontelin , Pokrywczynska Marta , Drewa Tomasz
Published: August 2019

The causes of bladder cancer are not yet fully uncovered, however the research has identified a number of factors that may increase the risk of developing this cancer. The chemical carcinogenesis of bladder cancer due to chronic exposure to aromatic hydrocarbons has been well-established. The identification of this correlation led to an improvement of safety measures in chemical industry and a gradual decrease of bladder cancer cases among workers. Nevertheless, in the majority of bladder cancer cases, the specific cause of the disease still can't be specified. It makes the question of unrecognized factors associated with bladder cancer development even more relevant. Taking under consideration known chemical carcinogenesis of bladder cancer, this minireview takes under investigation the possible link between using scented candles and a risk of bladder cancer development. Burning scented candles contain many of the substances that are associated with a bladder cancer. Furthermore the scented candles are not only very popular but also widely available on the market, with limited quality regulations and unspecified raw materials determining a spectrum of potentially dangerous substances emitted during burning.
De portas abertas para o consumo
Authors: Mozdzenski Leonardo , Silva Bruno Anselmo da
Published: August 2019

O consumo de alimentos ligados à saudabilidade e sustentabilidade vem conquistando notoriedade midiática e valoração social e marcária positiva. Partindo desta constatação, propomos discutir este fenômeno alicerçando-nos nos preceitos da análise do discurso de linha francesa, com o objetivo de observar como as redes de restaurante fast-food buscam se reinventar neste novo cenário. Em particular, investigamos de que modo se dá a construção retórico-discursiva do ethos e do pathos na campanha publicitária McDonald’s Portas Abertas e quais efeitos de sentidos são aí evocados para persuadir o consumidor sobre a qualidade dos produtos da rede.
Ripple-AT Study
Authors: Luther Vishal , Agarwal Sharad , Chow Anthony , Koa-Wing Michael , Cortez-Dias Nuno , Carpinteiro Luís , de Sousa João , Balasubramaniam Richard , Farwell David , Jamil-Copley Shahnaz , Srinivasan Neil , Abbas Hakam , Mason James , Jones Nikki , Katritsis George , Lim Phang Boon , Peters Nicholas S. , Qureshi Norman , Whinnett Zachary , Linton Nick W.F. , Kanagaratnam Prapa
Published: August 2019

Background:

Ripple mapping (RM) is an alternative approach to activation mapping of atrial tachycardia (AT) that avoids electrogram annotation. We tested whether RM is superior to conventional annotation based local activation time (LAT) mapping for AT diagnosis in a randomized and multicenter study.

Methods:

Patients with AT were randomized to either RM or LAT mapping using the CARTO3v4 CONFIDENSE system. Operators determined the diagnosis using the assigned 3D mapping arm alone, before being permitted a single confirmatory entrainment manuever if needed. A planned ablation lesion set was defined. The primary end point was AT termination with delivery of the planned ablation lesion set. The inability to terminate AT with this first lesion set, the use of more than one entrainment manuever, or the need to crossover to the other mapping arm was defined as failure to achieve the primary end point.

Results:

One hundred five patients from 7 centers were recruited with 22 patients excluded due to premature AT termination, noninducibility or left atrial appendage thrombus. Eighty-three patients (pts; RM=42, LAT=41) completed mapping and ablation within the 2 groups of similar characteristics (RM versus LAT: prior ablation or cardiac surgery n=35 [83%] versus n=35 [85%],
P
=0.80). The primary end point occurred in 38/42 pts (90%) in the RM group and 29/41pts (71%) in the LAT group (
P
=0.045). This was achieved without any entrainment in 31/42 pts (74%) with RM and 18/41 pts (44%) with LAT (
P
=0.01). Of those patients who failed to achieve the primary end point, AT termination was achieved in 9/12 pts (75%) in the LAT group following crossover to RM with entrainment, but 0/4 pts (0%) in the RM group crossing over to LAT mapping with entrainment (
P
=0.04).

Conclusions:

RM is superior to LAT mapping on the CARTO3v4 CONFIDENSE system in guiding ablation to terminate AT with the first lesion set and with reduced entrainment to assist diagnosis.

Clinical Trials Registration:

https://www.clinicaltrials.gov
. Unique identifier: NCT02451995.
Low‐Cost Fetal Magnetocardiography: A Comparison of Superconducting Quantum Interference Device and Optically Pumped Magnetometers
Authors: Strand Sarah , Lutter William , Strasburger Janette F. , Shah Vishal , Baffa Oswaldo , Wakai Ronald T.
Published: August 2019

Background

Fetal magnetocardiography (
fMCG
) is a highly effective technique for evaluation of fetuses with life‐threatening arrhythmia, but its dissemination has been constrained by the high cost and complexity of Superconducting Quantum Interference Device (SQUID) instrumentation. Optically pumped magnetometers (
OPM
s) are a promising new technology that can replace
SQUID
s for many applications. This study compares the performance of an
fMCG
system, utilizing
OPM
s operating in a person‐sized magnetic shield, to that of a conventional
fMCG
system, utilizing
SQUID
magnetometers operating in a magnetically shielded room.

Methods and Results

fMCG
recordings were made in 24 subjects using the
SQUID
system with the mother lying supine in a magnetically shielded room and the
OPM
system with the mother lying prone in a person‐sized, cylindrical shield. Signal‐to‐noise ratios of the
OPM
and
SQUID
recordings were not statistically different and were adequate for diagnostic purposes with both technologies. Although the environmental noise was higher using the small open‐ended shield, this was offset by the higher signal amplitude achieved with prone positioning, which reduced the distance between the fetus and sensors and improved patient comfort. In several subjects,
fMCG
provided a differential diagnosis that was more precise and/or definitive than was possible with echocardiography alone.

Conclusions

The
OPM
‐based system was portable, improved patient comfort, and performed as well as the
SQUID
‐based system at a small fraction of the cost. Electrophysiological assessment of fetal rhythm is now practical and will have a major impact on management of fetuses with long
QT
syndrome and other life‐threatening arrhythmias.
Circulating DNAs, a Marker of Neutrophil Extracellular Traposis and Cancer-Related Stroke
Authors: Bang Oh Young , Chung Jong-Won , Cho Yeon Hee , Oh Mi Jeong , Seo Woo-Keun , Kim Gyeong-Moon , Ahn Myung-Ju
Published: August 2019

Background and Purpose—

The role of circulating neutrophil extracellular traps (NETs) in cancer-related stroke is unknown.

Methods—

We conducted a prospective cohort study to test whether NETs are increased in cancer-related stroke and whether elevated NETs levels are associated with coagulopathy, assessed using D-dimer levels (≥2 μg/mL). Plasma DNA and nucleosome were assessed as NET-specific biomarkers.

Results—

In total, 138 patients were recruited; 38 patients had cancer-related stroke (active cancer and acute cryptogenic embolic stroke), 33 patients were healthy-controls, 27 patients were cancer-controls (active cancer but no stroke), and 40 patients were stroke-controls (acute ischemic stroke but no cancer). Plasma DNA and nucleosome levels were significantly elevated in cancer-related stroke patients than in healthy-controls (
P
<0.05). These levels were correlated with the D-dimer levels (
P
<0.01). In multiple regression analyses, increased plasma DNA levels were associated with cancer-related stroke (odds ratio=11.65 for highest quartile; 95% CI, 3.199–42.46) and D-dimer levels of ≥2 μg/mL (odds ratio=19.09 for highest quartile; 95% CI, 4.143–87.95) after adjusting for possible confounders.

Conclusions—

Increased circulating DNA levels were associated with cancer-related stroke, suggesting that NETosis is one of the molecular mechanisms of cancer-related stroke. Further long-term follow-up studies in large cohorts are needed to confirm the role of NET-specific biomarkers.
Why Open-Endedness Matters
Authors: Stanley Kenneth O.
Published: August 2019

Rather than acting as a review or analysis of the field, this essay focuses squarely on the motivations for investigating open-endedness and the opportunities it opens up. It begins by contemplating the awesome accomplishments of evolution in nature and the profound implications if such a process could be ignited on a computer. Some of the milestones in our understanding so far are then discussed, finally closing by highlighting the grand challenge of formalizing open-endedness as a computational process that can be encoded as an algorithm. The main contribution is to articulate why open-endedness deserves a place alongside artificial intelligence as one of the great computational challenges, and opportunities, of our time.
Individual Differences in the Neural Dynamics of Response Inhibition
Authors: Molloy M. Fiona , Bahg Giwon , Lu Zhong-Lin , Turner Brandon M.
Published: August 2019

Response inhibition is a widely studied aspect of cognitive control that is particularly interesting because of its applications to clinical populations. Although individual differences are integral to cognitive control, so too is our ability to aggregate information across a group of individuals, so that we can powerfully generalize and characterize the group's behavior. Hence, an examination of response inhibition would ideally involve an accurate estimation of both group- and individual-level effects. Hierarchical Bayesian analyses account for individual differences by simultaneously estimating group and individual factors and compensate for sparse data by pooling information across participants. Hierarchical Bayesian models are thus an ideal tool for studying response inhibition, especially when analyzing neural data. We construct hierarchical Bayesian models of the fMRI neural time series, models assuming hierarchies across conditions, participants, and ROIs. Here, we demonstrate the advantages of our models over a conventional generalized linear model in accurately separating signal from noise. We then apply our models to go/no-go and stop signal data from 11 participants. We find strong evidence for individual differences in neural responses to going, not going, and stopping and in functional connectivity across the two tasks and demonstrate how hierarchical Bayesian models can effectively compensate for these individual differences while providing group-level summarizations. Finally, we validated the reliability of our findings using a larger go/no-go data set consisting of 179 participants. In conclusion, hierarchical Bayesian models not only account for individual differences but allow us to better understand the cognitive dynamics of response inhibition.
Missing Elsewhere: Domain Extension in Contextual Allomorphy
Authors: Ganenkov Dmitry
Published: August 2019

Much work in Distributed Morphology ( Embick 2010 , 2015 , Bobaljik 2012 , Harley, Tubino, and Haugen 2017 , Bobaljik and Harley to appear ) holds that morphosyntactically conditioned contextual allomorphy, including suppletion, can only work in a very local fashion: two morphemes must be linearly or structurally adjacent for one to determine the morphological exponence of the other. Recently, however, the existence of nonlocal patterns has come into focus, with growing evidence that nonlocal allomorphy is an attested empirical option. 1 In this squib, I discuss the allomorphy of verb stems in the Nakh-Daghestanian language Aqusha Dargwa and argue that the choice between allomorphs in morphological causatives in that language is determined nonlocally by tense-aspect-mood (TAM), proposing that Vocabulary Insertion (VI) can be exempt from locality requirements under certain conditions.