bluuebunny/crossref_metadata_2025 huggingface dataset:
Beliefs and knowledge of cardiovascular-related disease among uninsured primary care patients: A cross-sectional study
Authors: Kamimura Akiko , Nourian Maziar M. , Chernenko Alla , Rathi Naveen , Oslund Michael-Ann , Ashby Jeanie
Published: December 2017

Objective

The purpose of this study was to examine cardiovascular disease-related health beliefs and how they are influenced by knowledge and a sense of community among uninsured primary care patients.

Method

This study was a cross-sectional study using a self-administered paper survey (January to April 2016). The study population included medically uninsured US-born English speakers, non-US-born English speakers, and Spanish speakers.

Results

Medically uninsured adults utilizing a free clinic (N = 374) participated in the survey. Increasing knowledge about major risk factors for developing cardiovascular disease helped enhance levels of perceived severity of cardiovascular disease and benefits of healthy diet and physical activity. Spanish speakers reported higher levels of perceived severity of cardiovascular disease but lower levels of knowledge compared to US-born or non-US-born English speakers.

Conclusion

Spanish speakers may need different approaches to promote cardiovascular disease prevention due to their higher levels of perceived severity of cardiovascular disease but lower levels of cardiovascular disease-related knowledge compared to English speakers. Developing a healthy “community” in a clinic setting may be effective to promote cardiovascular disease-related health for underserved populations.
Mediated pathways, negotiated identities: a critical phenomenological analysis of the experience of sexuality in the context of intellectual disability
Authors: Pariseau-Legault Pierre , Holmes Dave
Published: December 2017

Questions of sexuality and intellectual disability have now moved beyond the institutional era, and contemporary sexual health interventions have gradually been reconfigured in terms of social participation, partnership and normalising approaches. That being said, they also appear to be part of a complex negotiation process between support systems for individuals identified as having an intellectual disability. The aim of this study was to provide a better understanding of the experience of affective (sentimental and emotional) and sexual (identity and value-mediated) expression in the context of intellectual disability, as well as related factors of influence. Inspired by a critical theoretical framework and a phenomenological methodology, this research shows that these experiences are part of a negotiation process that is simultaneously systemic and intimate. It is systemic because it responds to knowledge systems specific to intellectual disability and sexuality, thus authorising a variety of interventions focused on normalising the individual. It is also intimate because these practices involve every axis of affective existence, from inhabiting restrictive spaces to reconfiguring people’s intimate relationships with themselves and others. Through these findings, nursing’s ability to recognise and advocate for this group’s sexual needs and rights is called into question.
An availability-based warranty policy considering preventive maintenance and learning effects
Authors: Su Chun , Cheng Longfei
Published: December 2017

By considering learning effects during the process of maintenance, this article investigates an availability-based warranty policy from the manufacturer’s perspective. Imperfect preventive maintenance activities are implemented to reduce the number of equipment failures so as to meet the product’s availability requirement and minimize warranty servicing cost during the warranty period. Hybrid hazard rate model is used to describe imperfect preventive maintenance actions; maintenance plan and warranty servicing cost are optimized by considering learning effects. Preventive maintenance schedule within a warranty period is optimized cycle by cycle, and the warranty cost rate is minimized under the requirement of availability within each cycle. Numerical example of a wind turbine gearbox is provided to verify the effectiveness of the proposed availability-based warranty policy. Sensitivity analysis shows that by considering learning effects on maintenance, the gearbox can maintain a higher availability level with a lower warranty cost than the case without consideration of learning effects.
‘The BP is a great British company’: The discursive transformation of an environmental disaster into a national economic problem
Authors: Cramer Rahel
Published: December 2017

In the contemporary globalized economy, multinational companies have come to hold considerable power that may previously have rested with nation states. However, state structures remain relevant. With Brexit, the year 2016 featured an exemplary case in which the ongoing importance of nation states came to the fore. Preceding the British referendum to exit the European Union (EU), discourses of national identity were deployed to promote a vote for the anti-globalization campaign. It is against this background that this research investigates how the relationship between multinational corporations and nation states is constructed in news discourse. The underlying assumption is that news actively construct rather than merely reflects the nature of this relationship. Drawing on Social Actor Analysis and Transitivity as a theoretical framework, this study examines news coverage of the BP oil spill that occurred in the United States in 2010 but was caused by a multinational company headquartered in the United Kingdom. The main research question is ‘How does the media establish a link between multinational corporations and nation states?’. To address this central question, this study investigates how (1) corporate responsibility is assigned, (2) the role of the nation state is portrayed and (3) victim status is allocated in the news. Findings show that the nature of the problem is constructed differently according to diverging national interests or priorities of the two nations represented by the media sources analyzed. The study indicates that the discourse around British nationality emphasized in the political struggle around Brexit was already mobilized extensively in the years leading up to the referendum.
Micro air vehicle local pose estimation with a two-dimensional laser scanner: A case study for electric tower inspection
Authors: Viña Carlos , Morin Pascal
Published: December 2017

Automation of inspection tasks is crucial for the development of the power industry, where micro air vehicles have shown a great potential. Self-localization in this context remains a key issue and is the main subject of this work. This article presents a methodology to obtain complete three-dimensional local pose estimates in electric tower inspection tasks with micro air vehicles, using an on-board sensor set-up consisting of a two-dimensional light detection and ranging, a barometer sensor and an inertial measurement unit. First, we present a method to track the tower’s cross-sections in the laser scans and give insights on how this can be used to model electric towers. Then, we show how the popular iterative closest point algorithm, that is typically limited to indoor navigation, can be adapted to this scenario and propose two different implementations to retrieve pose information. This is complemented with attitude estimates from the inertial measurement unit measurements, based on a gain-scheduled non-linear observer formulation. An altitude observer to compensate for barometer drift is also presented. Finally, we address velocity estimation with views to feedback position control. Validations based on simulations and experimental data are presented.
Computational fluid dynamics investigation of thermal-hydraulic characteristics in a simplified pebbled bed modular reactor core using different arrangements of fuel elements
Authors: Bai Yuyu , Gui Nan , Yang Xingtuan , Tu Jiyuan , Jiang Shengyao
Published: December 2017

High-temperature gas-cooled reactor is a kind of advanced nuclear reactor in which the core is packed with spherical fuel elements. In high-temperature gas-cooled reactors, the operating temperature is higher than that in ordinary light water reactors. In an attempt to analyze the flow pattern and heat transfer situation to provide reference for the safe operation of the pebble bed reactors, a segment of simplified high-temperature gas-cooled reactor core is simulated with computational fluid dynamics method. Four kinds of arrangement, including simple cubic, body-centered cubic, face-centered cubic, and a combination structure of body-centered cubic and face-centered cubic, are studied, respectively. Based on the simulation results, higher heat transfer capability and lower pebble temperature are obtained in the case with the most compact arrangement. The drag coefficient ( Cd) for four arrangements with different inlet Reynolds number (Re) is obtained and relationship between Re and Cd is analyzed. In addition, a simulation with a broken fuel element in the body-centered cubic fluid domain has been performed. The results show that the presence of broken fuel may result in uneven flow, which will change the heat transfer condition. So it is better to avoid broken fuel element in a high-temperature gas-cooled reactor.
Risk of Hypoglycemia During Insulin Infusion Directed by Paper Protocol Versus Electronic Glycemic Management System in Critically Ill Patients at a Large Academic Medical Center
Authors: Rabinovich Marina , Grahl Jessica , Durr Emily , Gayed Rita , Chester Katleen , McFarland Raymie , McLean Barbara
Published: December 2017

Background:

Insulin infusions are commonly utilized to control hyperglycemia in critically ill patients and decrease hyperglycemia associated complications. Safety concerns have been raised in trials evaluating methods of glycemic control regarding the incidence of hypoglycemia and its relationship to increased mortality. Electronic glycemic management systems (eGMS) may result in less variable blood glucose (BG) control and less hypoglycemia. This study aimed to compare BG control, time in target BG range, and the rate of hypoglycemia when critically ill patients were managed with an insulin infusion guided by paper-based protocol (PBP) versus eGMS.

Methods:

This retrospective review compared critically ill patients ≥ 18 years old that received insulin infusion from March to May 2015 (PBP group) and October to January 2017 (eGMS group). The primary outcome was the incidence of hypoglycemia. Secondary outcomes included frequency and severity of hypoglycemia, duration in glycemic target, length of insulin therapy, as well as ICU and hospital length of stay.

Results:

Fifty-four patients were evaluated, 27 in each group. Percentage of days with BG <70 mg/dL was significantly reduced after eGMS implementation (21.5% v 1.3%, P < .0001) including the frequency of severe hypoglycemia (BG < 40 mg/dL) (5.4% v 0.01%, P < .0001). Patients in the eGMS group spent a greater amount of time in target BG range (31.5% v 63.7%, P < .0001).

Conclusions:

An eGMS has the potential to address many of the unmet needs of an optimal glycemic control strategy, minimizing hypoglycemia, and glycemic variability in a heterogeneous critically ill population.
The future cooperation between OLAF and the European Public Prosecutor’s Office
Authors: Weyembergh Anne , Brière Chloé
Published: December 2017

Establishing the European Public Prosecutor’s Office (EPPO) will represent an important step for cross-border cooperation in criminal matters within the European Union, and more particularly for the protection of the Union’s financial interests. The EPPO’s work will complement the work carried out by the European Anti-Fraud Office. This article, based on a briefing paper commissioned by the European Parliament’s Policy Department for Budgetary Affairs, at the request of the Committee on Budgetary Control, analyses future cooperation between these two bodies, OLAF and the EPPO. Three main dimensions of their cooperation are analysed as well as the elements of complexity that may influence it. The article highlights elements essential for their close cooperation and complementarity, especially with regard to a potential revision of OLAF’s legal framework.
The transpulmonary ratio of endothelin 1 is elevated in patients with preserved left ventricular ejection fraction and combined pre‐ and post‐capillary pulmonary hypertension
Authors: Meoli David F. , Su Yan Ru , Brittain Evan L. , Robbins Ivan M. , Hemnes Anna R. , Monahan Ken
Published: December 2017

Pulmonary hypertension complicating left heart disease (PH‐LHD) is associated with increased morbidity and mortality, especially in patients who develop combined pre‐ and post‐capillary PH (Cpc‐PH). Mechanisms underlying PH‐LHD are incompletely understood, particularly for individuals with preserved left ventricular ejection fraction (LVEF). We hypothesized that transpulmonary concentrations of biomarkers representing signaling pathways with known effects on the pulmonary circulation could provide insight into the molecular etiology of PH‐LHD in patients with preserved LVEF. Blood samples were collected from the pulmonary artery (PA) and wedge positions of outpatients with normal LVEF referred for right heart catheterization. Hemodynamic tracings were reviewed to classify patients as “no PH” (n = 23) or “PH‐LHD” (n = 22). A biomarker’s transpulmonary ratio (TPR) was calculated as the quotient of wedge and PA concentrations. The TPR of endothelin 1 (ET‐1) was elevated in Cpc‐PH (n = 10) compared to no PH or isolated post‐capillary PH (Ipc‐PH, n = 12); cAMP and cGMP TPRs were not different among groups. Higher ET‐1 TPR in Cpc‐PH was due to increased wedge ET‐1 concentration. Pulmonary vascular resistance (PVR) strongly correlated with wedge ET‐1 exclusively in Cpc‐PH patients. In patients with normal LVEF and Cpc‐PH, ET‐1 TPR is higher, due to elevated wedge ET‐1, compared to those without PH or with Ipc‐PH. Strong correlation between PVR and wedge ET‐1, observed only in the Cpc‐PH group, may suggest increased pulmonary vascular responsiveness to ET‐1 in these patients. These findings implicate elevated pulmonary ET‐1 as a marker of, and a potential contributor to, development of Cpc‐PH in this population.
The impact of ambrisentan and tadalafil upfront combination therapy on cardiac function in scleroderma associated pulmonary arterial hypertension patients: cardiac magnetic resonance feature tracking study
Authors: Sato Takahiro , Ambale‐Venkatesh Bharath , Lima Joao A.C. , Zimmerman Stefan L. , Tedford Ryan J. , Fujii Tomoki , Hulme Olivia L. , Pullins Erica H. , Corona‐Villalobos Celia P. , Zamanian Roham T. , Minai Omar A. , Girgis Reda E. , Chin Kelly , Khair Rubina , Damico Rachel L. , Kolb Todd M. , Mathai Stephen C. , Hassoun Paul M.
Published: December 2017

The aim of this study was to evaluate the effect of upfront combination therapy with ambrisentan and tadalafil on left ventricular (LV) and right ventricular (RV) function in patients with systemic sclerosis‐associated pulmonary arterial hypertension (SSc‐PAH). LV and RV peak longitudinal and circumferential strain and strain rate (SR), which consisted of peak systolic SR (SRs), peak early diastolic SR (SRe), and peak atrial‐diastolic SR (SRa) were analyzed using cardiac magnetic resonance imaging (CMRI) data from the recently published ATPAHSS‐O trial (ambrisentan and tadalafil upfront combination therapy in SSc‐PAH). Twenty‐one patients completed the study protocol. Measures of RV systolic function (RV free wall [RVFW] peak longitudinal strain [pLS], RVFW peak longitudinal SRs [pLSRs]) and RV diastolic function (RVFW peak longitudinal SRa [pLSRa], RVFW peak circumferential SRe) were improved after treatment. LV systolic function (LV peak global longitudinal strain [pGLS]) and diastolic function (LV peak global longitudinal SRe [pGLSRe]) were also significantly improved at follow‐up. Increased 6‐min walk distance was significantly correlated with RVFW pLS and pLSRs, while the decrease in N‐terminal pro‐brain natriuretic peptide was correlated with LV pGLS. Increased cardiac index was associated with improved LV pGLSRe, and reduction in mean right atrial pressure was correlated with improved RVFW pLS and pLSRa. Combination therapy was associated with a significant improvement in both RV and LV function as assessed by CMR‐derived strain and SR. Importantly, the improvement in RV and LV strain and SR correlated with improvements in known prognostic markers of PAH. (Approved by clinicaltrials.gov [NCT01042158] before patient recruitment.)
Acute and chronic dissection of pulmonary artery: new challenges in pulmonary arterial hypertension?
Authors: Florczyk Michał , Wieteska Maria , Kurzyna Marcin , Gościniak Piotr , Pepke‐Żaba Joanna , Biederman Andrzej , Torbicki Adam
Published: December 2017

Right ventricular failure is a leading cause of mortality in patients with pulmonary arterial hypertension (PAH). However, up to 25% of such patients die unexpectedly, without warning signs of hemodynamical decompensation. We previously documented that pulmonary artery (PA) dilatation significantly increases the risk of those deaths. Some of them may be due to dissection of PA resulting in cardiac tamponade. However, direct confirmation of this mechanism is difficult as most of such deaths occur outside hospitals. We present 4 patients with severe PAH and PA dilatation in whom PA dissection has been confirmed. Three patients had IPAH, one had PAH associated with congenital heart disease. All patients had mean pulmonary artery pressure (PAP) > 50 mmHg at diagnosis and dissection occurred late in the course of apparently well controlled disease (6 to 14 years). Several clinical elements were common to our patients ‐ high systolic PAP, long lasting PH, progressive dilatation of PA to more than 50 mm with chest pain prior to dissection. However, clinical course followed three different patterns: sudden death due to cardiac tamponade, hemopericarditis caused by blood leaking from dissected aneurysm with imminent but not immediate cardiac tamponade, or chronic asymptomatic PA dissection. Indeed, two of our patients are alive and on lung transplantation waiting list for more than 2 years now. Further research is needed to suggest optimal management strategies for patients with stable PAH but significantly dilated proximal pulmonary arteries or confirmed PA dissection depending on the clinical presentation and expected outcome.
Young adults’ knowledge and understanding of personal finance in Germany: Interviews with experts and test-takers
Authors: Happ Roland , Förster Manuel , Rüspeler Ann-Katrin , Rothweiler Jasmin
Published: December 2017

In recent years, the financial education of young adults has gained importance in Germany; however, very few valid test instruments to assess the knowledge and understanding of personal finance are suitable for use in Germany. In this article, we describe results of a survey in which experts in Germany in areas related to personal finance judged the relevance of the items of the American Council of Economic Education’s Test of Financial Literacy for use in Germany. Overall, they found the German version of the Test of Financial Literacy to be a valid instrument for assessing the knowledge and understanding of personal finance of young adults in Germany. Also, we conducted cognitive interviews with young adults in Germany to identify the sources of their knowledge of personal finance. Most of the participants claimed they gained a significant amount but not the majority of their knowledge and understanding of personal finance through formal school education. We conclude that personal finance should be addressed more thoroughly at secondary schools in Germany
Successful febuxostat desensitization in a patient with febuxostat hypersensitivity: A Malaysian experience
Authors: Sulaiman Narisa , Othman Ahmad Zaidi , Shahril Nor Shuhaila , Abdul Rashid Anna Misyail , Md Noh Mohamad Syafeeq Faeez
Published: December 2017

Over the years, allopurinol has been widely used as the preferred choice of urate lowering therapy in patients with gout. However, its role in patients with renal impairment is limited; and adverse reactions are well documented. Febuxostat, a newer oral non-purine xanthine oxidase inhibitor has been proven in several trials to be more effective and tolerable compared to allopurinol and may be used in patients with renal impairment. Here, we describe a case of successful febuxostat desensitization in a patient with a history of allopurinol- and febuxostat-induced adverse cutaneous reaction, as well as the protocol utilized.
HIV and the menopause: A review
Authors: Bull Lauren , Tittle Victoria , Rashid Taslima , Nwokolo Nneka
Published: December 2017

Effective antiretroviral therapy has resulted in a close to normal life expectancy for people living with HIV. This has led to a shift in the age distribution of women living with HIV in the UK, with one in three attending for HIV care estimated to be aged 45–56 years in 2014. The lack of experience of many HIV physicians in managing menopause, and the perceived complexity of managing menopause in women living with HIV by general practitioners means that many women are unable to access appropriate care and support. This is aggravated by the relative paucity of data on menopause in women living with HIV and conflicting results in this field, for example with regard to age of onset of menopause and symptomatology experienced. Furthermore, women living with HIV have unique considerations such as potential interactions between antiretroviral therapy and menopause hormone therapy (previously called hormone replacement therapy) and other physiological concerns such as a multifactorial propensity towards decreased bone mineral density and potentially increased cardiovascular risk. On the whole, menopause hormone therapy is probably underutilised in this group of women due to perceived concerns around drug–drug interactions, as well as fears shared with women in the general population about menopause hormone therapy. Menopausal women should be given adequate information on symptomatology, lifestyle modification and treatment options including menopause hormone therapy. Furthermore, a holistic approach which considers the increased burden of poor mental health in this population is essential.
Family functioning and trait emotional intelligence among youth
Authors: Alavi Masoumeh , Mehrinezhad Seyed Abolghasem , Amini Mansour , Parthaman Singh Minder Kaur a/p
Published: December 2017

This study explored the relationship between family functioning and trait emotional intelligence among 547 respondents, between the age of 16 and 24 years from Malaysia, Iran, China, Sudan, Somalia, Morocco, the United Kingdom, Germany and the Netherlands. The questionnaires were Family Adaptability and Cohesion Evaluation Scale III and Trait Emotional Intelligence Questionnaire Short Form. Pearson correlation analysis revealed a significant relationship between family functioning and trait emotional intelligence. The higher the family functioning, the higher the trait emotional intelligence among youths. The findings provide a deeper understanding in the field of family functioning and trait emotional intelligence and have implications for parents, administrators and child relationships dealing with trait emotional intelligence.
Could chronic mechanical irritation facilitate entry of human papillomavirus (HPV) facilitating oral HPV infection?
Authors: Gilligan Gerardo M , Galindez Costa María F Fernanda , Moine Lorena , Panico René L , Piemonte Eduardo D
Published: December 2017

There are similarities between the clinical conditions associated with genital and oral mucosal human papillomavirus (HPV). The role of HPV infection in oral carcinogenesis is currently controversial. Also, factors underlying this infection are still unclear. The frequent location of HPV lesions in areas of trauma indicates the role of mechanical irritation as a necessary event for the penetration and/or reactivation of the virus into the epithelium. Oral mucosa is frequently exposed to mechanical irritation, as it is in constant and intimate association with hard tissues. During the oral HPV infection, favorable conditions must be generated for the infection to be successful. Some of them, associated with proliferation of basal keratinocytes, are related to the presence of external stimuli, such as chronic mechanical irritation (CMI). The objective of this work is to demonstrate, through the presentation of three clinical cases, the possible role of CMI in the pathophysiology of HPV lesions of the oral mucosa.
Advancing Research on Traditional Whole Systems Medicine Approaches
Authors: Mills Paul J. , Patel Sheila , Barsotti Tiffany , Peterson Christine Tara , Chopra Deepak
Published: December 2017

While the intention of Integrative Medicine (IM) is whole person medicine, it has for the most part remained driven by individual modalities. Like the practice of IM itself, IM research too has been driven primarily by studies on individual modalities. There are significant challenges to moving research on whole systems medicine forward, with funding being at the top of the list. Historically, NIH has not been receptive to supporting research on whole systems, preferring instead to support studies that are more individual modality driven so that mechanisms can be identified. Purely mechanistic research, however, assumes unidirectional causality and linear responses yet clinical responses to whole systems approaches are more often multidirectional and dynamically unpredictable. The concept of emergence is applicable here. Whole systems approaches suggest that by incorporating therapies into holistic treatment programs we not only treat symptoms but accomplish more by activating the body's inherent self-organizing healing mechanisms and treat the root cause of illnesses as well as associated symptoms. Given that interest in integrative therapies with the general public and medical community is steadily increasing, there is need for more research that explores intact whole systems approaches to elucidate the relevant system-wide effects and dynamic interactions related to these practices.
Climate Change Scepticism: Reconsidering How to Respond to Core Criticisms of Climate Science and Policy
Authors: Van Rensburg Willem , Head Brian W.
Published: December 2017

The contextual drivers of climate change scepticism are well described and explained in the literature. A key assumption underlying most of the scholarly constructions of the sceptical phenomenon is that the key objections raised by sceptics to climate science and climate policy proposals represent some form of submerged deception or self-delusion on their part. This article refocuses attention on sceptics’ central criticisms, and argues that direct responses to these criticisms should not be neglected in favor of a primary focus on sceptics’ possible inner motivations. The article investigates the core objections raised by sceptics, with particular attention to the views of one prominent Australian sceptic, Andrew Bolt. We argue that some of these objections should be treated as legitimate forms of dissent, and that ongoing constructive responses to such criticisms are necessary to counter the impact of climate change scepticism.
Injury Incidence and Patterns Among Dutch CrossFit Athletes
Authors: Mehrab Mirwais , de Vos Robert-Jan , Kraan Gerald A. , Mathijssen Nina M.C.
Published: December 2017

Background:

CrossFit is a strength and conditioning program that has gained widespread recognition, with 11,000 affiliated gyms worldwide. The incidence of injuries during CrossFit training is poorly analyzed.

Purpose:

To investigate the incidence of injuries for persons participating in CrossFit. Risk factors for injury and injury mechanisms were also explored through athlete demographics and characteristics.

Study Design:

Descriptive epidemiology study.

Methods:

A questionnaire that focused on injury incidence in CrossFit in the past year and included data on athlete demographics and characteristics was distributed to all 130 CrossFit gyms in the Netherlands and was also available online in active Facebook groups. Data were collected from July 2015 to January 2016. Inclusion criteria consisted of age ≥18 years and training at a registered CrossFit gym in the Netherlands. A total of 553 participants completed the survey. Univariable and multivariable generalized linear mixed models were used to identify potential risk factors for injury.

Results:

A total of 449 participants met the inclusion criteria. Of all respondents, 252 athletes (56.1%) sustained an injury in the preceding 12 months. The most injured body parts were the shoulder (n = 87, 28.7%), lower back (n = 48, 15.8%), and knee (n = 25, 8.3%). The duration of participation in CrossFit significantly affected the injury incidence rates (≥24 months vs <6 months; odds ratio, 3.687 [95% CI, 2.091-6.502]; P < .001). The majority of injuries were caused by overuse (n = 148, 58.7%).

Conclusion:

The injury incidence for athletes participating in CrossFit was 56.1%. The most frequent injury locations were the shoulder, lower back, and knee. A longer duration of participation (≥24 months) was significantly associated with an increased risk for injury.
The Strategic Alliance Game: Bringing Alliances to Life
Authors: Bell Geoffrey G. , Liang Xin , Lü Li
Published: December 2017

Strategic alliances—voluntary interfirm arrangements involving resource sharing—are critical to firm success. To help strategic management students better understand alliance negotiation and formation, we developed a simple game that places them in a real alliance negotiation situation, involving simultaneous cooperation and competition (i.e., co-opetition), in which they negotiate and potentially build alliances. Teams receive either production or knowledge resources and cooperate and/or compete with each other to build a product. In the process, they understand that partners have different objectives, they analyze available resources, and they evaluate whom to trust. In this article, we describe the game and provide debriefing suggestions.
Phytochemical Analysis, Antioxidant and Antibacterial Properties of Spilanthes mauritiana Used Traditionally in Limpopo Province, South Africa
Authors: Masoko Peter
Published: December 2017

Spilanthes mauritiana belonging to the family Asteraceae, was screened for biological activity against bacterial pathogen. Antibacterial activity of the plant was investigated using microbroth dilution assay and bioautography. Total phenols and tannins of the extract were 52.47 ± 2.29 and 23.9 ± 1.18 as mg of gallic acid equivalents, respectively. Total flavonoid content was 25.1 ± 0.79 as mg of quercetin equivalents. Free radical scavenging activity of constituents in all the extract, against 2,2-diphenyl-1-picrylhydrazyl showed minimal activity. All extracts contained compounds with antibacterial activity against tested pathogens. Hexane extract had an average minimum inhibitory concentration value of 2.50 mg/mL, followed by methanol extract (1.72 mg/mL), acetone and dichloromethane extracts (1.96 mg/mL). The present study revealed the presence of compounds in S mauritiana with potent antibacterial activity against tested pathogens that are exhibiting the observed activity independent of other constituents contained in the extracts.
How I treat CLL patients with ibrutinib
Authors: Brown Jennifer R.
Published: December 2017

Ibrutinib is a transformative therapy for high-risk and relapsed refractory chronic lymphocytic leukemia (CLL) patients. In clinical trials in relatively healthy younger patients, ibrutinib has been well tolerated. As its use has become more widespread in the community, however, its full adverse event profile has emerged and proven more challenging than was initially anticipated. Reports of community-based use have estimated discontinuation rates as high as 40% in the first year of therapy. This article therefore reviews my approach to the evaluation and management of a CLL patient starting on ibrutinib, with the goal of minimizing and managing toxicity to maintain patients on ibrutinib. Key topics discussed include bleeding risk; cardiac complications, particularly atrial fibrillation; drug interactions; and infections.
Loss of NRF2 function exacerbates the pathophysiology of sickle cell disease in a transgenic mouse model
Authors: Zhu Xingguo , Xi Caixia , Thomas Bobby , Pace Betty S.
Published: December 2017

Key Points

NRF2 knockout inhibits fetal hemoglobin expression during gestational erythropoiesis in SCD mice. Loss of the cellular antioxidant response mediated by NRF2 exacerbates spleen damage, inflammation, and oxidative stress in SCD mice.
T-cell prolymphocytic leukemia in an adolescent with ataxia-telangiectasia: novel approach with a JAK3 inhibitor (tofacitinib)
Authors: Li Geling , Waite Emily , Wolfson Julie
Published: December 2017

Key Points

A 19-year-old ataxia-telangiectasia patient with T-cell prolymphocytic leukemia harbored 2 JAK3-activating hotspot mutations. The patient suffered toxicities with chemotherapy, but demonstrated a clinical response to novel use of a JAK3 inhibitor (tofacitinib).
Complete genome sequence of lytic bacteriophage RG-2014 that infects the multidrug resistant bacterium Delftia tsuruhatensis ARB-1
Authors: Bhattacharjee Ananda Shankar , Motlagh Amir Mohaghegh , Gilcrease Eddie B. , Islam Md Imdadul , Casjens Sherwood R. , Goel Ramesh
Published: December 2017

A lytic bacteriophage RG-2014 infecting a biofilm forming multidrug resistant bacterium Delftia tsuruhatensis strain ARB-1 as its host was isolated from a full-scale municipal wastewater treatment plant. Lytic phage RG-2014 was isolated for developing phage based therapeutic approaches against Delftia tsuruhatensis strain ARB-1. The strain ARB-1 belongs to the Comamonadaceae family of the Betaproteobacteria class. RG-2014 was characterized for its type, burst size, latent and eclipse time periods of 150 ± 9 PFU/cell, 10-min, <5-min, respectively. The phage was found to be a dsDNA virus belonging to the Podoviridae family. It has an isometric icosahedrally shaped capsid with a diameter of 85 nm. The complete genome of the isolated phage was sequenced and determined to be 73.8 kbp in length with a G + C content of 59.9%. Significant similarities in gene homology and order were observed between Delftia phage RG-2014 and the E. coli phage N4 indicating that it is a member of the N4-like phage group.
Draft genome sequences of three fungal-interactive Paraburkholderia terrae strains, BS007, BS110 and BS437
Authors: Pratama Akbar Adjie , Haq Irshad Ul , Nazir Rashid , Chaib De Mares Maryam , van Elsas Jan Dirk
Published: December 2017

Here, we report the draft genome sequences of three fungal-interactive
Paraburkholderia terrae
strains, denoted BS110, BS007 and BS437. Phylogenetic analyses showed that the three strains belong to clade II of the genus
Burkholderia
, which was recently renamed
Paraburkholderia
. This novel genus primarily contains environmental species, encompassing non-pathogenic plant- as well as fungal-interactive species. The genome of strain BS007 consists of 11,025,273 bp, whereas those of strains BS110 and BS437 have 11,178,081 and 11,303,071 bp, respectively. Analyses of the three annotated genomes revealed the presence of (1) a large suite of substrate capture systems, and (2) a suite of genetic systems required for adaptation to microenvironments in soil and the mycosphere. Thus, genes encoding traits that potentially  confer fungal interactivity were found, such as type 4 pili, type 1, 2, 3, 4 and 6 secretion systems, and biofilm formation (PGA, alginate and pel) and glycerol uptake systems. Furthermore, the three genomes also revealed the presence of a highly conserved five-gene cluster that had previously been shown to be upregulated upon contact with fungal hyphae. Moreover, a considerable number of prophage-like and CRISPR spacer sequences was found, next to genetic systems responsible for secondary metabolite production. Overall, the three
P. terrae
strains possess the genetic repertoire necessary for adaptation to diverse soil niches, including those influenced by soil fungi.
Study of transient electromagnetic method measurements using a superconducting quantum interference device as B sensor receiver in polarizable survey area
Authors: Du Shangyu , Zhang Yi , Pei Yifeng , Jiang Kun , Rong Liangliang , Yin Changchun , Ji Yanju , Xie Xiaoming
Published: December 2017

Time-domain transient electromagnetic method (TEM) measurements sometimes exhibit a sign reversal in the secondary field during the off-time, which is usually attributed to the induced-polarization (IP) effect. In contrast with the conventional IP method, which uses a current source, TEM with an ungrounded transmitting loop operates using a pure voltage source, which is induced by the primary field switching on and off. We performed TEM measurements in a resistive survey area showing an IP effect, and we used a low-temperature superconducting quantum interference device (LT-SQUID) with sensitivity of [Formula: see text] as a magnetic field sensor. A sign reversal in all of our measurements was observed; furthermore, the negative amplitude reached [Formula: see text]. In-depth analysis with an extended version of a wire-filament circuit reveals that the large negative signal may be due to discharging of in-ground capacitance, an IP effect. The conduction response of the ground can be restored by subtracting the fitted discharging response (negative valued) from the observed data. To verify this operation, we compared TEM measurements with and without wire-loop targets, which can induce a conduction field with a known decay time constant during the off-time. The extracted conduction responses of the wire-loop targets match the expected ones well. This research reveals that the primary field switch-off must always be included when interpreting TEM data with sign reversal and an LT-SQUID may be a good alternative sensor for studying the IP effect in TEM.
Phase I Study of ATR Inhibitor M6620 in Combination With Topotecan in Patients With Advanced Solid Tumors
Authors: Thomas Anish , Redon Christophe E. , Sciuto Linda , Padiernos Emerson , Ji Jiuping , Lee Min-Jung , Yuno Akira , Lee Sunmin , Zhang Yiping , Tran Lan , Yutzy William , Rajan Arun , Guha Udayan , Chen Haobin , Hassan Raffit , Alewine Christine C. , Szabo Eva , Bates Susan E. , Kinders Robert J. , Steinberg Seth M. , Doroshow James H. , Aladjem Mirit I. , Trepel Jane B. , Pommier Yves
Published: December 2017

Purpose

Our preclinical work identified depletion of ATR as a top candidate for topoisomerase 1 (TOP1) inhibitor synthetic lethality and showed that ATR inhibition sensitizes tumors to TOP1 inhibitors. We hypothesized that a combination of selective ATR inhibitor M6620 (previously VX-970) and topotecan, a selective TOP1 inhibitor, would be tolerable and active, particularly in tumors with high replicative stress.

Patients and Methods

This phase I study tested the combination of M6620 and topotecan in 3-week cycles using 3 + 3 dose escalation. The primary end point was the identification of the maximum tolerated dose of the combination. Efficacy and pharmacodynamics were secondary end points.

Results

Between September 2016 and February 2017, 21 patients enrolled. The combination was well tolerated, which allowed for dose escalation to the highest planned dose level (topotecan 1.25 mg/m2, days 1 to 5; M6620 210 mg/m2, days 2 and 5). One of six patients at this dose level experienced grade 4 thrombocytopenia that required transfusion, a dose-limiting toxicity. Most common treatment-related grade 3 or 4 toxicities were anemia, leukopenia, and neutropenia (19% each); lymphopenia (14%); and thrombocytopenia (10%). Two partial responses (≥ 18 months, ≥ 7 months) and seven stable disease responses ≥ 3 months (median, 9 months; range, 3 to 12 months) were seen. Three of five patients with small-cell lung cancer, all of whom had platinum-refractory disease, had a partial response or prolonged stable disease (10, ≥ 6, and ≥ 7 months). Pharmacodynamic studies showed preliminary evidence of ATR inhibition and enhanced DNA double-stranded breaks in response to the combination.

Conclusion

To our knowledge, this report is the first of an ATR inhibitor-chemotherapy combination. The maximum dose of topotecan plus M6620 is tolerable. The combination seems particularly active in platinum-refractory small-cell lung cancer, which tends not to respond to topotecan alone. Phase II studies with biomarker evaluation are ongoing.
FGF receptors control alveolar elastogenesis
Authors: Li Rongbo , Herriges John C. , Chen Lin , Mecham Robert P. , Sun Xin
Published: December 2017

Alveologenesis, the final step of lung development, is characterized by the formation of millions of alveolar septa that constitute the vast gas-exchange surface area. The genetic network driving alveologenesis is poorly understood compared with earlier steps in lung development. FGF signaling through receptors Fgfr3 and Fgfr4 is crucial for alveologenesis, but the mechanisms through which they mediate this process remain unclear. Here we show that in Fgfr3;Fgfr4 (Fgfr3;4) global mutant mice, alveolar simplification is first observed at the onset of alveologenesis at postnatal day 3. This is preceded by disorganization of elastin, indicating defects in the extracellular matrix (ECM). Although Fgfr3 and Fgfr4 are expressed in the mesenchyme and epithelium, inactivation in the mesenchyme, but not the epithelium, recapitulated the defects. Expression analysis of components of the elastogenesis machinery revealed that Mfap5 (also known as Magp2), which encodes an elastin-microfibril bridging factor, is upregulated in Fgfr3;4 mutants. Mfap5 mutation in the Fgfr3;4 mutant background partially attenuated the alveologenesis defects. These data demonstrate that, during normal lung maturation, FGF signaling restricts expression of the elastogenic machinery in the lung mesenchyme to control orderly formation of the elastin ECM, thereby driving alveolar septa formation to increase the gas-exchange surface.
Drosophila β-Tubulin 97EF is upregulated at low temperature and stabilizes microtubules
Authors: Myachina Faina , Bosshardt Fritz , Bischof Johannes , Kirschmann Moritz , Lehner Christian F.
Published: December 2017

Cells in ectotherms function normally within an often wide temperature range. As temperature dependence is not uniform across all the distinct biological processes, acclimation presumably requires complex regulation. The molecular mechanisms that cope with the disruptive effects of temperature variation are still poorly understood. Interestingly, one of five different β-tubulin paralogs, βTub97EF, was among the genes upregulated at low temperature in cultured Drosophila cells. As microtubules are known to be cold sensitive, we analyzed whether βTub97EF protects microtubules at low temperatures. During development at the optimal temperature (25°C), βTub97EF was expressed in a tissue-specific pattern primarily in the gut. There, as well as in hemocytes, expression was increased at low temperature (14°C). Although βTub97EF mutants were viable and fertile at 25°C, their sensitivity within the well-tolerated range was slightly enhanced during embryogenesis specifically at low temperatures. Changing β-tubulin isoform ratios in hemocytes demonstrated that β-Tubulin 97EF has a pronounced microtubule stabilizing effect. Moreover, βTub97EF is required for normal microtubule stability in the gut. These results suggest that βTub97EF upregulation at low temperature contributes to acclimation by stabilizing microtubules.
Mechanisms of gene regulation in human embryos and pluripotent stem cells
Authors: Theunissen Thorold W. , Jaenisch Rudolf
Published: December 2017

Pluripotent stem cells have broad utility in biomedical research and their molecular regulation has thus garnered substantial interest. While the principles that establish and regulate pluripotency have been well defined in the mouse, it has been difficult to extrapolate these insights to the human system due to species-specific differences and the distinct developmental identities of mouse versus human embryonic stem cells. In this Review, we examine genome-wide approaches to elucidate the regulatory principles of pluripotency in human embryos and stem cells, and highlight where differences exist in the regulation of pluripotency in mice and humans. We review recent insights into the nature of human pluripotent cells in vivo, obtained by the deep sequencing of pre-implantation embryos. We also present an integrated overview of the principal layers of global gene regulation in human pluripotent stem cells. Finally, we discuss the transcriptional and epigenomic remodeling events associated with cell fate transitions into and out of human pluripotency.
An interview with Claudio Stern
Authors: Grewal Seema
Published: December 2017

Claudio Stern is the J. Z. Young Professor of Anatomy at University College London (UCL), UK. His lab studies the processes that regulate patterning and cell diversity in the early embryos of vertebrates, mostly in chick. Claudio, an elected fellow of the Royal Society, the UK Academy of Medical Sciences, and the Latin-American Academy of Medical Sciences, was awarded the 2006 Waddington Medal by the British Society of Developmental Biology, and he also served as President of the International Society for Developmental Biology (ISDB) from 2010-2013. At the 18th Congress of the ISDB (Singapore, June 2017), Claudio was awarded the ISDB's Ross Harrison Prize, which recognises an individual's outstanding contributions to developmental biology. We met with Claudio to ask him more about his career, his thoughts on the field, and his advice for early career researchers.
Solid-State Esterification via Ionic-to-Covalent Bond Transformation in Ionic Molecular Crystals Consisting of Disubstituted Anthracene Anion-Cation Combinations
Authors: Suzuki Masato , Fujii Takahiro , Naito Yoko , Yamoto Kazuhisa , Matsuoka Shin-ichi , Takagi Koji , Sugiyama Haruki , Uekusa Hidehiro
Published: December 2017

Thermal solid-state reactions involving ionic-to-covalent bond transformation were achieved in the ionic molecular crystals of 1,8-bis[(pyridin-1-ium-1-yl)methyl]anthracene anthracene-1,8-dicarboxylate to produce the cyclic diester. The crystal structure given by X-ray diffraction analysis showed that the electrostatic interaction between the benzyl pyridinium cation and the carboxylate anion successfully works to locate these reaction sites close to each other and that there are channels for crystalline solvents and the liberated pyridine to escape. Thereby, the cyclic diester was selectively formed by the crystal-to-crystal reaction, which was proven by powder XRD profiles and optical microscopic and SEM images of the crystals before and after the reaction. This is the first thermal crystal-to-crystal condensation reaction. Another ionic molecular crystal of 1,8-bis[(pyridin-1-ium-1-yl)methyl]anthracene anthraquinone-1,8-dicarboxylate was also studied. Therein, the corresponding cyclic diester was also obtained, but the crystals were transformed to amorphous solid by the reaction.
Social sustainability in supply chains: A framework and a Latin America illustrative case
Authors: Morais Dafne Oliveira Carlos de
Published: December 2017

Social issues are under-represented in sustainability, considering historical predominance of economic and environmental issues. This also applies to Sustainable Supply Chain Management. Even with its definition clarified regarding Triple Bottom Line, research still advances disproportionately in environmental and economic dimensions, facing the social dimension. This research aims to analyze how social sustainability is addressed in focal firms and managed into its supply chain. The study explores the concepts of social issues and governance mechanisms, presenting elements discussed in the literature. A framework for managing social sustainability in supply chains is presented, followed by a case to illustrate the discussed concepts in a Latin American context.