bluuebunny/crossref_metadata_2025 huggingface dataset:
Is Benzodiazepine Use Associated With the Risk of Dementia and Cognitive Impairment–Not Dementia in Older Persons? The Canadian Study of Health and Aging
Authors: Nafti Mohamed , Sirois Caroline , Kröger Edeltraut , Carmichael Pierre-Hugues , Laurin Danielle
Published: October 2019

Background: The use of benzodiazepines in relation to cognitive decline remains an area of controversy in aging populations. Objective: This study aims to evaluate the risk of cognitive impairment–not dementia (CIND), Alzheimer disease (AD), and all-cause dementia with benzodiazepine use. The effect modification by sex was also investigated. Methods: Data come from the Canadian Study of Health and Aging, a 10-year multicentric study involving 10 263 participants randomly selected, 65 years and older, living in the community and in institutions. Current exposure to benzodiazepines was assessed in a face-to-face interview or self-reported in a questionnaire. Cox proportional hazard regression models, using age as time scale, were conducted to estimate hazard ratios, with adjustment for sex, education, smoking, alcohol intake, depression, physical activity, nonsteroidal anti-inflammatory drug use, and vascular comorbidities. Results: Data sets included 5281 participants for dementia as the outcome, 5015 for AD, and 4187 for CIND. Compared with nonusers, current use of benzodiazepines was associated with an increased risk of CIND (hazard ratio = 1.36; 95% CI = 1.08-1.72) in the simplest model. Results remained similar in the fully adjusted model (hazard ratio = 1.32; 95% CI = 1.04-1.68). There was no association between benzodiazepine use and the risk of dementia or AD. All these effects were similar between men and women. Conclusion and Relevance: Benzodiazepine use in older people from the general population is related to subsequent occurrence of cognitive dysfunction but not implicated in the pathogenesis of dementia or AD. Caution should be exercised when prescribing benzodiazepines to preserve global cognitive function.
Antiwhaling Groups in Japan: Their Historical Lack of Development and Relationship With National Identity
Authors: Nomura Ko
Published: October 2019

This article reviews the history of antiwhaling groups in Japan from a politicocultural perspective, examining how the connection between whaling and national identity has significantly constrained their development. It is interesting to note that this connection, or “framing,” in terms of social movement theory, was not an invention of the prowhaling camp. It was rather induced and facilitated by Western activists’ protests, which have been unwelcome in Japanese political culture, making the antiwhaling cause come across as “foreign.” In fact, Japanese antiwhaling groups have attempted to counter-frame this by distinguishing themselves from Western activists, emphasizing moderate strategies, limiting their opposition to large-scale modern whaling, and allowing small-scale coastal whaling with a view to detaching the issue from national claims. However, they have not been successful due to prominent foreign protests. This study also suggests the key role of national identity in the success or failure of environmental activism.
Temporizing External Fixation vs Splinting Following Ankle Fracture Dislocation
Authors: Wawrose Richard A. , Grossman Leonid S. , Tagliaferro Matthew , Siska Peter A. , Moloney Gele B. , Tarkin Ivan S.
Published: October 2019

Background:

Closed reduction and splinting followed by outpatient management is standard of care for temporizing most ankle fractures. However, ankle fracture-dislocation potentially warrants a different approach based on the propensity for loss of reduction. The purpose of this study was to determine the rate of complications associated with closed reduction and splinting of unstable ankle fracture-dislocations. Further, we sought to determine the efficacy of immediate external fixation as an alternative to splinting in cases too swollen for acute operation.

Methods:

This retrospective chart review analyzed all ankle-fracture dislocations that came through a large health care system from 2008 to 2018. Patients managed with acute open reduction internal fixation (ORIF) and open fractures were excluded. In patients managed late, the cohorts were divided into those temporized with closed reduction/splinting vs external fixation. Reduction quality and splint technique were additionally assessed in splinted patients. A total of 354 closed ankle fracture-dislocations were identified: 298 patients (84%) underwent ORIF within 48 hours and were excluded; 28 (15 female/13 male, average age 46.8 years) were placed in an external fixator and 28 (22 female/6 male, average age 57.2 years) were reduced, splinted, and discharged.

Results:

At follow-up, 14 of the patients (50%) in the splint group developed loss of reduction and 5 of these patients (17.6%) developed anteromedial skin necrosis from skin tenting. None of the patients in the ex-fix group developed loss of reduction or skin necrosis. The rate of redislocation and the rate of development of skin necrosis was statistically higher in cases temporized with a splint versus an external fixator ( P < .01 and P = .05, respectively).

Conclusion:

We found that in ankle fracture-dislocations not treated with acute ORIF, splint immobilization was associated with an increased risk of complications, including redislocation and skin necrosis, when compared to a temporizing external fixator.

Level of Evidence:

Level III, retrospective comparative study.
Evaluation of the use of non-formulary oncology medications restricted to outpatient use in hospitalized patients after implementation of a criteria-for-use algorithm
Authors: Randle Hope , Smith Leticia V , Padilla-Tolentino Eimeira , Goodgame Boone W
Published: October 2019

Objective

To decrease the number of orders and total hospital spend for inpatient use of antineoplastic drugs of interest, while evaluating each case for urgent or emergent need for administration.

Methodology

This study is a multicenter, retrospective, cost-evaluation, cohort study performed in five Ascension Seton hospitals in the Austin, Texas area between 1 January 2013 and 31 December 2018. Patients were identified via a dispense analysis report for the antineoplastic drugs of interest.

Results

An overall reduction of 56% was seen in orders processed with a 62% decrease in annual hospital spending after implementation of the criteria-for-use algorithm. When results were evaluated without including rituximab orders, a reduction of 17% was seen in orders processed with a 21% decrease in annual hospital spending.

Discussion and conclusion

The decreases in our primary outcomes were primarily driven by a reduction in the use of one drug, rituximab. Overall, implementation of a criteria-for-use algorithm was effective in reducing both overall number of orders and hospital spending for restricted antineoplastic agents.
Durable response after interruption of nivolumab in patients with metastatic renal cell carcinoma: Is renal toxicity a marker to predict the benefit of nivolumab?
Authors: Kus Tulay , Aktas Gokmen
Published: October 2019

Introduction

Nivolumab is a human IgG4 programmed death-1 immune checkpoint inhibitor antibody. Immune-related toxicity may be associated with higher response even after interruption of nivolumab.

Case report

We reported a case diagnosed with metastatic clear cell renal cell carcinoma and treated with nivolumab as fourth-line therapy. Although nivolumab treatment was stopped after two cycles due to grade 3 renal toxicity, progression-free survival rates of 11 months, that is quite a long time for fourth-line treatment of renal cell carcinoma was observed.

Management and outcome

Therefore, we speculate that when renal toxicity develops, response may continue even after interruption of nivolumab in renal cell carcinoma.

Discussion

Nivolumab was approved to be used for second-line treatment of renal cell carcinoma with 4.6 months of median progression-free survival benefit. Higher immune-related toxicity can produce higher efficacy for some instances such as malignant melanoma, lung cancer, and renal cell carcinoma. Renal disturbance during nivolumab treatment is extremely rare, and there are no data on survival after interruption due to renal toxicity of nivolumab without further treatment in renal cell carcinoma. In the present case, we obtained long duration of stable disease, with two cycles of nivolumab after the development of nephrotoxicity. Close follow-up without any treatment until progression may be a treatment choice, because nephrotoxicity can be a sign of benefit and durable response to nivolumab.
How do they measure up? Differences in stakeholder perceptions of quality measures used in English community nursing
Authors: Pollard Katherine , Horrocks Sue , Duncan Lorna , Petsoulas Christina , Allen Pauline , Cameron Ailsa , Cook Jane , Gibbard Emma , Harland Lizanne , Husband Pete , Loydon Geoff , McDonald Ruth , Wye Lesley , Salisbury Chris
Published: October 2019

Objectives

To establish how quality indicators used in English community nursing are selected and applied, and their perceived usefulness to service users, commissioners and service providers.

Methods

A qualitative multi-site case study was conducted with five commissioning organizations and their service providers. Participants included commissioners, provider organization managers, nurses and service users.

Results

Indicator selection and application often entail complex processes influenced by wider health system and cross-organizational factors. All participants felt that current indicators, while useful for accountability and management purposes, fail to reflect the true quality of community nursing care and may sometimes indirectly compromise care.

Conclusions

Valuable resources may be better used for comprehensive system redesign, to ensure that patient, carer and nurse priorities are given equivalence with those of other stakeholders.
De-individualising the ‘NEET problem’: An ecological systems analysis
Authors: Lőrinc Magdolna , Ryan Louise , D’Angelo Alessio , Kaye Neil
Published: October 2019

Periods of being NEET (not in education, employment or training) can have long-term consequences for individuals’ future job opportunities, earnings, psycho-social well-being and health, all with high societal costs. Therefore, policy-makers across Europe seek interventions that successfully reduce NEET numbers. Drawing on a longitudinal qualitative study in London, this paper explores the processes and mechanisms that contribute to young people becoming NEET after leaving education.

Through analysis of 53 young NEETs’ accounts of their school and transition experiences, we draw upon Bronfenbrenner’s ecological systems theory to explore the multitude of factors and structures of disadvantage that might have contributed to these young people’s marginalisation in education and employment. We discuss how unfulfilled support needs, a lack of career advice and socio-economic disadvantage can lead to educational disengagement, dropping out and, ultimately, becoming NEET. While many of these issues were presented as personal difficulties, in this article we reject the individualisation of the ‘NEET problem’. Instead, we argue that negative school experiences need to be understood in the context of structural conditions, including funding cuts in education and support services, transformations in the labour market and socio-economic deprivation.
Findings From a Pilot Study Examining the Positive and Negative Achievement Emotions Associated With Undergraduates’ First-Year Experience
Authors: Allaire Franklin S.
Published: October 2019

Research shows that undergraduate students’ achievement emotions are critical in determining motivation and success in higher education. This article reports on the results of a pilot study using the Achievement Emotions Questionnaire involving 10 ( n = 10) mostly ethnic minority undergraduates at an urban 4-year university. In general, findings reveal increases in feelings of hope, hopelessness, and boredom as well as decreases in enjoyment throughout students’ first-year experience. Students’ positive and negative emotions impact their perceptions of both their classes and instructors and affect their motivation, on-task behavior, and academic success. These results also compare and show significant differences in the emotions associated with the first-year experiences of immigrants, Hispanic, and first-generation students as compared with their citizen, non-Hispanic, and nonfirst-generation peers, respectively. These findings paint an intimate portrait of the narrators’ experiences and the impact that emotions had on their motivation and achievement during their first year in college.
The Effects of Dosage-Controlled Cannabis Capsules on Cancer-Related Cachexia and Anorexia Syndrome in Advanced Cancer Patients: Pilot Study
Authors: Bar-Sela Gil , Zalman Daniela , Semenysty Valerya , Ballan Eyal
Published: October 2019

Background: Cancer-related cachexia and anorexia syndrome (CACS) is a common phenomenon in cancer patients. Cannabis has been suggested to stimulate appetite but research on this issue has yielded mixed results. The current study aimed to evaluate the effect of dosage-controlled cannabis capsules on CACS in advanced cancer patients. Methods: The cannabis capsules used in this study contained two fractions of oil-based compounds. The planned treatment was 2 × 10 mg per 24 hours for six months of tetrahydrocannabinol (THC) 9.5 mg and cannabidiol (CBD) 0.5 mg. If patients suffered from side effects, dosage was reduced to 5 mg × 2 per day (THC 4.75 mg, CBD 0.25 mg). Participants were weighed on every physician visit. The primary objective of the study was a weight gain of ≥10% from baseline. Results: Of 24 patients who signed the consent form, 17 started the cannabis capsules treatment, but only 11 received the capsules for more than two weeks. Three of six patients who completed the study period met the primary end-point. The remaining three patients had stable weights. In quality of life quaternaries, patients reported less appetite loss after the cannabis treatment ( p=0.05). Tumor necrosis factor-α (TNF-α) levels decreased after the cannabis treatment but without statistical significance. According to patients’ self-reports, improvement in appetite and mood as well as a reduction in pain and fatigue was demonstrated. Conclusions: Despite various limitations, this preliminary study demonstrated a weight increase of ≥10% in 3/17 (17.6%) patients with doses of 5mgx1 or 5mgx2 capsules daily, without significant side effects. The results justify a larger study with dosage-controlled cannabis capsules in CACS.
Optimization of LMBP high-speed railway wheel size prediction algorithm based on improved adaptive differential evolution algorithm
Authors: Zhang Yu , Zhang Jiawen , Luo Lin , Gao Xiaorong
Published: October 2019

It is beneficial for maintenance department to make maintenance strategy and reduce maintenance cost to forecast the hidden danger index value. Based on the analysis of the research status of wheel-to-life prediction at home and abroad and the repair of wheel-set wear and tear, this article designs and implements an adaptive differential evolution algorithm Levenberg–Marquardt back propagation wheel-set size prediction model. Aiming at the shortcomings of back propagation neural network, it is easy to fall into local extreme value. The back propagation algorithm is improved by Levenberg–Marquardt numerical optimization algorithm. Aiming at the shortcomings of back propagation neural network algorithm for randomly initializing connection weights and thresholds to fall into local extreme value, the differential evolution algorithm is used to optimize the initial connection weights and thresholds between the layers of the neural network. In order to speed up the search of the optimal initial weights and thresholds of the differential evolution algorithm Levenberg–Marquardt back propagation neural network, the initial values are further optimized, and an adaptive differential evolution algorithm Levenberg–Marquardt back propagation wheel-set size prediction model is designed and implemented. Compared with the proposed combine adaptive differential evolution algorithm with LMBP optimization (ADE-LMBP) is effective and significantly improves the prediction accuracy.
A method for predicting the blasting pressure of balloons using the surface strain in low pressure
Authors: Shen Yong-Zheng , Lin Guo-Chang , Tan Hui-Feng
Published: October 2019

Balloons made by cut fabric pieces are widely used in space research. To predict the blasting pressure of a balloon, we propose a novel method based on the non-contact test strain at a low internal pressure. The three-dimensional digital image correlation technique is introduced to measure the surface strain of the balloon. Representative regions of the balloon are selected as the test regions. A correction factor is proposed that accounts for the relationship between the internal pressure and the surface strain for the actual and the ideal balloon. By combining the maximum surface strain at a given internal pressure and the correction factor, we can predict the blasting pressure of the balloon. A blasting test is carried out to verify the feasibility of the predictive method. When the value of the ratio of the maximum test strain to the limiting strain reaches about a reference value, the absolute value of the deviation percentage between the predicted blasting pressure and the actual blasting pressure is less than 10%. The blasting pressure for balloon can be predicted accurately. This method does not require the balloon to be inflated to a high internal pressure, which improves the practicality of the prediction.
Perceived goal setting practices across a competitive season
Authors: Forsblom Kim , Konttinen Niilo , Weinberg Robert , Matilainen Pertti , Lintunen Taru
Published: October 2019

Goal setting is an effective and frequently used tool for performance enhancement in sports. However, in the previous studies, the focus has been on goal effectiveness among individual male athletes and at one point in time. Therefore, the purpose of this longitudinal study was to examine goal setting practices in women’s sport teams across a competitive season from players’ individual and team perspectives. A total of 146 female players representing 24 teams in ice hockey, ringette, or floorball completed three online surveys. Surveys focused on setting outcome, process, and performance goals, as well as evaluating the follow-through of setting goals and actually reaching these goals across the season. The results indicated that teams set collective outcome goals, and several process, and performance goals at the outset of the season. One-third of the participants reported that these goals were recorded. Furthermore, results revealed that after the season, the achievement of the outcome goal was evaluated, whereas the attainment of process and performance goals was evaluated only occasionally. It is argued that the lack of follow-through in evaluating process and performance goals may be attributed to setting too many goals and not writing them down. It appeared that one-third of the teams did consistently follow the goal setting principles, and although this resulted in increased goal evaluation, it did not result in increased goal attainment. A number of future directions for research are offered and it is recommended that coaches should be made more aware of these guidelines and the importance of following them to achieve maximum benefits of a goal setting program.
Producing Antipetismo: Media activism and the rise of the radical, nationalist right in contemporary Brazil
Authors: Davis Stuart , Straubhaar Joe
Published: October 2019

When examining the decline of the leftist Partido dos Trabalhadores and the ascension of the right-wing extremist Jair Bolsanaro of the far-right Partido Liberal Social to the 2018 presidency, political scientists David Samuels and Cesar Zucco have argued that this shift is best understood not through positive characteristics of Bolsonaro’s candidacy but through antipetismo [‘anti-PT-ism’], an intensely personal resentment of the Partido dos Trabalhadores. We assert that popular right-wing Facebook groups and networks formed around the communication network WhatsApp-fueled antipetismo by channeling anger originating in the 2013 nationwide protests away from a variety of social, political, and issues and toward a villainous depiction of Partido dos Trabalhadores leaders and valorization of anti-Partido dos Trabalhadores activists like Bolsanaro, as well as some focus on his own conservative, nationalist agenda.

To interrogate this assertion, we propose two specific lines of research. The first is a qualitative textual analysis of the social media accounts of two of the most active anti-Partido dos Trabalhadores groups: Vem Pra Rua and O Movimento Brasil Livre. Through close reading of the materials distributed on these sites, we will illustrate how they channeled general unrest into a specifically partisan attack. The next line of research and case will be an examination of the role of mainstream news networks (namely TV Record) and WhatsApp by those campaigning for recently elected president Bolsonaro for a continued negative campaign against left candidates, specifically the Partido dos Trabalhadores, using fake news items like the supposed ‘gay kit’ that was being circulated in schools by the Partido dos Trabalhadores and others on the left to persuade children to become gay. When possible, we will analyze examples of the materials that were circulated that have emerged in the press coverage and will examine the processes that were used to target and persuade people to forward the materials created for the campaign.
The duration of acupuncture effects and its associated factors in chronic severe functional constipation: secondary analysis of a randomized controlled trial
Authors: Wang Yang , Liu Yan , Zhou Kehua , Bauer Brent A. , Liu Baoyan , Su Tongsheng , Mo Qian , Liu Zhishun
Published: October 2019

Background:

Electroacupuncture (EA) has been shown to improve complete spontaneous bowel movements (CSBMs), but the duration of its effects remains unknown. The objective of this study was to explore the duration of acupuncture effects after treatment and its associated factors for chronic severe functional constipation (CSFC).

Methods:

This was a secondary analysis of a multicenter, randomized, sham-acupuncture (SA) controlled trial that included 1075 participants with CSFC. The primary outcome, the duration of acupuncture effects after treatment, was the number of weeks during the 12-week follow-up period that participants were to meet the weekly CSBM responder criteria. A weekly CSBM responder was defined as a participant who had at least three CSBMs for a given week and an increase from baseline of at least one CSBM for that same week. We performed a retrospective multivariate analysis to explore potential factors associated with sustained acupuncture effects.

Results:

The duration of acupuncture effects in the EA group (5.5 weeks) was significantly higher than the duration of SA effects in the SA group (2.2 weeks) with a between-group difference of 3.2 weeks (95% CI, 2.77–3.78; p < 0.001). A younger age and higher baseline CSBMs per week [regression coefficient (RC) –0.06, 95% confidence interval (CI) (−0.06 to −0.04); RC 2.43, 95% CI 1.78–3.60; respectively] were associated with longer durations of acupuncture effects.

Conclusions:

EA had sustained post-treatment effects for CFSC. A significant association among a younger age, higher baseline CSBMs and sustained acupuncture effects was observed. Further research is needed to confirm the association.

Trial registration:

ClinicalTrials.gov (NCT01726504). Registered on 26 August 2012.
Prediction of Diabetic Foot Ulceration: The Value of Using Microclimate Sensor Arrays
Authors: Jones Petra , Bibb Richard , Davies Melanie , Khunti Kamlesh , McCarthy Matthew , Webb David , Zaccardi Francesco
Published: October 2019

Background:

Accurately predicting the risk of diabetic foot ulceration (DFU) could dramatically reduce the enormous burden of chronic wound management and amputation. Yet, the current prognostic models are unable to precisely predict DFU events. Typically, efforts have focused on individual factors like temperature, pressure, or shear rather than the overall foot microclimate.

Methods:

A systematic review was conducted by searching PubMed reports with no restrictions on start date covering the literature published until February 20, 2019 using relevant keywords, including temperature, pressure, shear, and relative humidity. We review the use of these variables as predictors of DFU, highlighting gaps in our current understanding and suggesting which specific features should be combined to develop a real-time microclimate prognostic model.

Results:

The current prognostic models rely either solely on contralateral temperature, pressure, or shear measurement; these parameters, however, rarely reach 50% specificity in relation to DFU. There is also considerable variation in methodological investigation, anatomical sensor configuration, and resting time prior to temperature measurements (5-20 minutes). Few studies have considered relative humidity and mean skin resistance.

Conclusion:

Very limited evidence supports the use of single clinical parameters in predicting the risk of DFU. We suggest that the microclimate as a whole should be considered to predict DFU more effectively and suggest nine specific features which appear to be implicated for further investigation. Technology supports real-time in-shoe data collection and wireless transmission, providing a potentially rich source of data to better predict the risk of DFU.
Adaptive Control of an Artificial Pancreas Using Model Identification, Adaptive Postprandial Insulin Delivery, and Heart Rate and Accelerometry as Control Inputs
Authors: Resalat Navid , Hilts Wade , Youssef Joseph El , Tyler Nichole , Castle Jessica R. , Jacobs Peter G.
Published: October 2019

Background:

People with type 1 diabetes (T1D) have varying sensitivities to insulin and also varying responses to meals and exercise. We introduce a new adaptive run-to-run model predictive control (MPC) algorithm that can be used to help people with T1D better manage their glucose levels using an artificial pancreas (AP). The algorithm adapts to individuals’ different insulin sensitivities, glycemic response to meals, and adjustment during exercise as a continuous input during free-living conditions.

Methods:

A new insulin sensitivity adaptation (ISA) algorithm is presented that updates each patient’s insulin sensitivity during nonmeal periods to reduce the error between the actual glucose levels and the process model. We further demonstrate how an adaptive learning postprandial hypoglycemia prevention algorithm (ALPHA) presented in the previous work can complement the ISA algorithm, and the algorithm can adapt in several days. We further show that if physical activity is incorporated as a continuous input (heart rate and accelerometry), performance is improved. The contribution of this work is the description of the ISA algorithm and the evaluation of how ISA, ALPHA, and incorporation of exercise metrics as a continuous input can impact glycemic control.

Results:

Incorporating ALPHA, ISA, and physical activity into the MPC improved glycemic outcome measures. The adaptive learning postprandial hypoglycemia prevention algorithm combined with ISA significantly reduced time spent in hypoglycemia by 71.7% and the total number of rescue carbs by 67.8% to 0.37% events/day/patient. Insulin sensitivity adaptation significantly reduced model-actual mismatch by 12.2% compared to an AP without ISA. Incorporating physical activity as a continuous input modestly improved time in the range 70 to 180 mg/dL during high physical activity days from 84.4% to 84.9% and reduced the percentage time in hypoglycemia by 23.8% from 2.1% to 1.6%.

Conclusion:

Adapting postprandial insulin delivery, insulin sensitivity, and adapting to physical exercise in an MPC-based AP systems can improve glycemic outcomes.
Patient-Reported Outcome Measures and Provocative Testing in the Workup of Empty Nose Syndrome—Advances in Diagnosis: A Systematic Review
Authors: Gill Amarbir S. , Said Mena , Tollefson Travis T. , Strong E. Bradley , Nayak Jayakar V. , Steele Toby O.
Published: October 2019

Background

The last 5 years have seen a surge of both clinical and scientific interest in empty nose syndrome (ENS). Although ENS is still considered a controversial diagnosis plagued by a lack of standardized diagnostic criteria, ENS is increasingly becoming recognized as a legitimate, physiologic disease entity. As such, it is important for clinicians to understand the most up-to-date diagnostic tools to assess ENS, confirm the diagnosis, and create a more standardized means to counsel these complex patients.

Objective

Contemporary literature review to discuss diagnostic modalities in the evaluation of ENS, in order to introduce evidence-based diagnostic criteria.

Methods

A systematic review was conducted in PubMed and Embase (2013–2019) using the search term “empty nose syndrome” to identify peer-reviewed articles on the topic of ENS. Articles advancing contemporary methods of ENS diagnosis and testing were included. A quality assessment was conducted using The Rational Clinical Examination Levels of Evidence.

Results

The novel development of the Empty Nose Syndrome 6 Questionnaire (ENS6Q) offers the clinician a validated patient-reported outcome measure to supplement history and physical examination. The in-office cotton test, performed by placing an endoscopically directed cotton plug in the site of tissue loss, may help to identify patients who may benefit from turbinate augmentation. Tools such as the sinus computed tomography scan, computational fluid dynamics, and intranasal trigeminal nerve function testing currently have insufficient evidence to support routine use in the workup of ENS. Up to 66% of ENS patients present with comorbid anxiety or depression.

Conclusion

The ENS6Q and cotton test assist in creating a standardized approach to the evaluation of patients suspected of ENS. These instruments should be used as an adjunct, rather than the sole criteria, on which to ascertain the presumptive diagnosis. Patients suspected of ENS should be screened for comorbid psychological dysfunction.
Endoscopic measurement of gastric pH is associated with persistent acid reflux in patients treated with proton pump inhibitors for gastroesophageal reflux disease
Authors: Januszewicz Wladyslaw , Hartley James , Waldock William , Roberts Geoffrey , Alias Bincy , Hobson Anthony , Wernisch Lorenz , di Pietro Massimiliano
Published: October 2019

Background

Although proton pump inhibitors are the mainstay of gastroesophageal reflux disease treatment, up to 30% of patients have a poor symptomatic response. Ambulatory pH impedance monitoring is the gold standard to assess whether this is due to persistent acid reflux. We aimed to characterize clinical predictors of persistent esophageal acid reflux on proton pump inhibitors including gastric pH measured during endoscopy.

Methods

We prospectively recruited patients with gastroesophageal reflux disease and/or Barrett esophagus on proton pump inhibitors. All patients completed a symptom questionnaire and underwent gastroscopy with gastric pH analysis, immediately followed by ambulatory 24‐hour pH impedance. We used a modified cutoff of 1.3% for pathological esophageal acid exposure time. A multiple linear regression model was used to analyze the correlation between acid exposure time and predictive variables.

Results

We recruited 122 patients, of whom 92 (75.4%) were included in the final analysis (44 male (47.8%), median age 53 years (interquartile range (IQR): 43–66)). Forty‐four patients (47.8%) had persistent acid reflux with a median total acid exposure time of 2.2% (IQR: 1.2–5.0), compared with 0.1% (IQR: 0.0–0.2) in patients without persistent reflux (n = 48; p < .001). There was no difference in age, sex, body mass index, proton pump inhibitor regimen, diagnosis of hiatus hernia or Barrett esophagus, and severity of symptoms between patients with normal and abnormal acid exposure time. Median gastric pH was significantly lower in patients with persistent acid reflux (5.8 vs 6.6, p = .032) and it correlated with the total acid exposure time (p = .045; R2 = 12.0%). With a pH cutoff of 5.05, single‐point endoscopic gastric pH analysis had an area under the receiver operating characteristic curve of 63.0% (95% confidence interval: 51.3–74.7) for prediction of persistent acid reflux.

Conclusions

Symptoms and clinical characteristics are not useful to predict persistent acid reflux in patients on proton pump inhibitors. One‐point gastric pH correlates with 24‐hour esophageal acid exposure time and could guide clinicians to assess treatment response; however, its utility needs validation in larger studies.
The significance of communication and care in one’s mother tongue: Patients’ views
Authors: Hemberg Jessica , Sved Emelie
Published: October 2019

Language barriers in the healthcare sector, for example as a result of failure to use a patient’s mother tongue, can lead to misunderstandings and/or care errors, especially when circumstances require that nursing staff or patients speak a language other than their own mother tongue. The aim of this study was to explore the importance of patients receiving care in their mother tongue. A hermeneutic approach was used and the method was inspired by content analysis. The data material was collected through semi-structured interviews with nine adult patients. One main theme and four subthemes were seen. The main theme was that care in a patient’s mother tongue can enhance quality of care. To reduce suffering in care caused by language barriers, nurses’ language skills should be supported and encouraged. Further research should focus on nurses’ perspectives on the significance of minority-language patients using their mother tongue in a nursing context.
Mamlakhtiyut from Across the Ocean: Ben-Gurion and the American-Jewish Community
Authors: Sherzer Adi
Published: October 2019

The concept of Mamlakhtiyut, defined by Bareli and Kedar as the Israeli version of republicanism, has shaped Israeli political system and civil culture from the 1950s onward. This article examines how this inter-Israeli concept affected David Ben-Gurion’s inter-Jewish policy toward the Jews of the Diaspora during the constructive era of the first year of statehood. The discussion focuses on the journey of Ben-Gurion to the USA during the spring of 1951 and the launching of the Bonds campaign as an alternative Israeli fundraising tool. The study of the journey’s context and a deep analysis of Ben-Gurion’s speeches during the journey demonstrate the importance of the Mamlakhti approach in the setting of Israel–Diaspora relations. I argue that the Mamlakhti-republican discourse was needed by both sides to deepen the relationship during the 1950s, point its deep influence on both policy and discourse, and suggest that today too it may foster the discourse and reframe some of the fundamental subjects that divide Israel from the Diaspora.
Diagnostic Accuracy of Transvaginal Sonography in the Detection of Endometrial Polyps
Authors: Poliakova Yevheniia , Lutsenko Nataliia
Published: October 2019

Background:

Transvaginal sonography (TVS) is considered a simple and generally accepted method for detecting uterine anomalies. With TVS, the uterus can be clearly visualized, but so far, the diagnostic accuracy of TVS varies across different studies. This retrospective study was devised to evaluate the accuracy of a sonographic diagnosis of endometrial polyps in a Ukrainian hospital.

Methods:

This was a single-center retrospective study of woman who underwent TVS and had hysteroscopy or dilation and curettage for endometrial pathology. A cohort of 156 women were included in this yearlong study. A comparative analysis was based on the preoperative diagnosis, according to TVS, compared with the postoperative histopathology results.

Results:

The overall sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of TVS in diagnosing endometrial polyps were 69%, 51%, 73%, 46%, and 63%, respectively.

Conclusion:

This retrospective study provided data on the lack of accuracy for a sonographic diagnosis of endometrial polyps. This was based on 26% of women whose diagnosis was not confirmed by histology. A false-negative result occurred for 54% of women who had polyps that were not detected at the preoperative stage. These data raise the question of the feasibility of further invasive procedures based on a single TVS study.
Crystal chemistry and nomenclature of rhodonite-group minerals
Authors: Shchipalkina Nadezhda V. , Pekov Igor V. , Chukanov Nikita V. , Biagioni Cristian , Pasero Marco
Published: October 2019

This paper presents the nomenclature of the rhodonite group accepted by the Commission on New Minerals, Nomenclature and Classification of the International Mineralogical Association (IMA). An overview of the previous studies of triclinic (space group P$\bar{1}$) pyroxenoids belonging to the rhodonite structure type, with a focus on their crystal chemistry, is given. These minerals have the general structural formula VIIM(5)VIM(1)VIM(2)VIM(3)VIM(4)[Si5O15]. The following dominant cations at the M sites are known at present: M(5) = Ca or Mn2+, M(1–3) = Mn2+; and M(4) = Mn2+ or Fe2+. In accordance with the nomenclature, the rhodonite group consists of three IMA-approved mineral species having the following the general chemical formulae: M(5)AM(1–3)B3M(4)C[Si5O15], where A = Ca or Mn2+; B = Mn2+; and C = Mn2+ or Fe2+. The end-member formulae of approved rhodonite-group minerals are as follows: rhodonite CaMn3Mn[Si5O15]; ferrorhodonite CaMn3Fe[Si5O15]; and vittinkiite MnMn3Mn[Si5O15].
Adult T Cell Leukemia/Lymphoma Development in HTLV-1-Infected Humanized SCID Mice.
Authors: Banerjee Prabal , Lairmore Michael D , Ramos Juan Carlos , Harrington William J , Beilke Mark A , Feuer Gerold
Published: October 2019

Abstract 1425

Poster Board I-448

Human T-lymphotropic virus type-1 (HTLV-1) is the first human retrovirus linked to cancer and is the etiologic agent of adult T-cell leukemia/lymphoma (ATLL), an aggressive CD4+ T cell malignancy. The molecular and genetic factors induced by HTLV-1 that initiate ATLL remain unclear, in part, due to the lack of an animal model which recapitulates leukemogenic events. In particular, early target cell infection and transformation events have not been identified or defined. Herein, we have created humanized NOD/SCID (HU-NOD/SCID) mice by inoculation of NOD/SCID mice with CD34+ hematopoietic progenitor and stem cells (CD34+ HP/HSCs) infected ex vivo with HTLV-1. HTLV-1-HU-NOD/SCID mice consistently developed CD4+ T cell lymphomas with characteristics similar to ATLL. Elevated proliferation of infected human stem cells (CD34+CD38−) in the bone marrow was observed in mice developing malignancies. Furthermore, examination of CD34+ HP/HSCs from HTLV-1-infected patients revealed proviral integrations suggesting a role of human bone marrow-derived stem cells in leukemogenesis. NOD/SCID mice reconstituted with CD34+ HP/HSCs transduced with a lentivirus vector (LV) expressing the HTLV-1 oncoprotein (Tax1) also developed CD4+ lymphomas. The recapitulation of a CD4+ T cell lymphoma in HTLV-1- and Tax1-HU-NOD/SCID mice suggest that hematopoietic stem cells serve as a viral reservoir in vivo and provide a cellular target for cell transformation in humans. This animal model of HTLV-1 induced ATLL will provide an important tool for the identification of molecular and cellular events that control the initiation and progression of the lymphoma and potential therapeutic targets to block tumor development.

Disclosures:

No relevant conflicts of interest to declare.
Treatment with Bortezomib Overcomes Resistance to Imatinib in Ph-Leukemia Quiescent Cells.
Authors: Kuwatsuka Yachiyo , Minami Yosuke , Tanizaki Ryohei , Minami Miho , Abe Akihiro , Nomura Yuka , Kiyoi Hitoshi , Naoe Tomoki
Published: October 2019

Abstract 1426

Poster Board I-449

Recent studies suggest that leukemia stem cells (LSCs) are responsible for relapse of leukemia following conventional or targeted agents and that eradication of LSCs might be necessary to cure the disease. In order to examine mechanisms of drug resistance in LSCs and to seek strategies to overcome the resistance, we used Ph-positive acute lymphoblastic leukemia patient cells serially xenotransplanted into immunodeficient NOD/SCID/IL2rγnull (NOG) mice. Engrafted bone marrow and spleen cells were almost identical to the original leukemia cells as to phenotypes including karyotypes and distribution of primitive populations. Recently several publications have suggested that proteasome inhibitors can induce selective cell death in LSCs. Spleen cells derived from leukemic NOG mice were treated ex vivo with imatinib and the proteasome inhibitor, bortezomib and cell viablility (PI-/Annexin-V-) was compared between treated and non-treated cells. After treatment with imatinib, significantly more residual cells were observed in the CD34+CD38- population compared to the CD34+CD38+ or CD34-CD38+ populations. With nM level of bortezomib, substantial cell death was induced in all populations with up-regulation of phospho-p53 (Ser15). Phosphorylation of BCR-ABL and CrkL was completely inhibited in all populations with imatinib treatment, but not with bortezomib treatment. Regarding cell cycle states, a higher percentage of Hoechst-33342low/Pyronin-Ylow cells was observed in the CD34+CD38- population relative to the other populations, suggesting more cells in the G0 state among the CD34+CD38- population. In co-culturing with S17 stromal cells, quiescent (Hoechst-33342low/Pyronin-Ylow) CD34+ cells were insensitive to imatinib, while substantial cell death including CD34+ population was induced with nM level of bortezomib. We are also investigating more detailed biomarkers in the cell death and effects of these drugs both on the primitive leukemia cells and normal hematopoietic cells using the in vivo leukemic NOG mice systems. These results imply that resistance to imatinib in Ph-positive leukemia quiescent cells is independent of BCR-ABL phosphorylation and that treatment with bortezomib can overcome the resistance of Ph-positive LSCs.

Disclosures

Kiyoi: Kyowa Hakko Kirin: Consultancy. Naoe: Kyowa Hakko Kirin, Wyeth and Chugai: Research Funding.
An Expanded Set of Direct BLIMP-1 Targets Identifies Novel Links in Differentiation, Immune Response and Lymphoma.
Authors: Tooze Reuben M , Care Matthew A , Westhead David R , Doody Gina M
Published: October 2019

Abstract 1466

Poster Board I-489

B-lymphocyte induced maturation protein 1 (BLIMP-1) has been defined as a key driver of the genetic reprogramming during differentiation of B-cells to plasma cells. Frequent inactivation of PRDM1, the BLIMP-1 gene, in diffuse large B-cell lymphoma (DLBCL) indicates that loss of function is an important event in lymphomagenesis. Only a limited set of direct BLIMP-1 target genes have been defined. In order to better understand the function of human BLIMP-1 in differentiation and malignancy we have established a more comprehensive set of occupied promoters. These data provide an extended view of the regulatory network controlled by BLIMP-1, and identify novel sets of targets involved in transcription and immune response. The composition of occupied promoters identifies complexity in BLIMP-1 binding motif selection, and substantial overlap between BLIMP-1 sites and Interferon regulatory factor (IRF) elements. Consistent with active competition between BLIMP-1 and IRFs, target genes associated with such overlapping motifs are found to be preferentially induced in response to BLIMP-1 knockdown. Finally BLIMP-1 targets are found to include key components of DLBCL gene expression signatures. This map of BLIMP-1 occupied promoters thus illuminates key aspects of function in normal and malignant cell biology.

Disclosures:

No relevant conflicts of interest to declare.
C6-Deficient Mice Are Protected From the Pathogenic Effects of Antiphospholipid Antibodies.
Authors: Carrera-Marin Ana Laura , Romay-Penabad Zurina , Aguilar-Valenzuela Renan , Martinez-Martinez Laura Aline , Papalardo Elizabeth , Pierangeli Silvia S
Published: October 2019

Abstract 147

Background:

The pathogenic mechanisms mediated by antiphospholipid (aPL) antibodies are only partially understood. Tissue factor (TF) upregulation has been shown to play an important role and recent studies have demonstrated that mice deficient in complement C3, C5 or C5a receptor (R) are resistant to the thrombogenic effects of aPL antibodies. The complement membrane attack (C5b-9 MAC) complex has been shown to bind specific receptors, to induce TF expression and to exert procoagulant effect in various cell types (i.e. endothelial cells). However whether C5b-9 MAC plays a role in the pathogenesis of thrombosis in Antiphospholipid Syndrome (APS) is unknown. Here we addressed that question by studying the effects of human aPL antibodies on thrombosis and TF upregulation in C6 deficient (−/−) mice.

Methods:

C6 deficient (−/−) mice and the corresponding wild-type (WT) mice C3H/HeJ (C6+/+) were injected twice with 500γg/ml IgG isolated from a patient with APS (IgG-APS) or with the corresponding control IgG-NHS. Seventy-two h after the first injection the size of induced thrombi in the femoral vein, IgG anticardiolipin (ACL) activity in the sera were determined. TF activity was determined in homogenates of carotid arteries and in peritoneal macrophages using a chromogenic assay.

Results:

Thrombus sizes were significantly larger in WT mice C6 (+/+) treated with IgG-APS when compared with C6 (+/+) mice treated with IgG-NHS (p= <0.001) The sizes of thrombi were significantly smaller in the C6 (−/−) mice injected with IgG-APS compared to their WT C6 (+/+) counterparts (p= <0.001) showing an important abrogation of thrombus formation in mice lacking C6. Thrombus sizes in C6 (−/−) mice injected with IgG-NHS were not different when compared to C6 (+/+) mice treated with IgG-NHS (p= 0.786), Similarly, upregulation of TF activity in carotid arteries homogenates and in peritoneal macrophages in C6 (+/+) mice treated with IgG-APS were significantly diminished in C6 (−/−) mice (p=0.036 and p=0.041, respectively). All mice injected with IgG-APS had medium-high titers of aCL in their serum (see Table)

Conclusions:

These data indicate that the C6 component of the complement system mediates aPL-thrombogenic effects and not only underscore the importance of complement activation by aPL antibodies, but also propose its inhibition as a possibly novel therapeutic target for thrombosis in APS .

Disclosures:

No relevant conflicts of interest to declare.