bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring failure of antimicrobial prophylaxis and pre-emptive therapy for transplant recipients: a systematic review
Authors: Märtson Anne-Grete , Bakker Martijn , Blokzijl Hans , Verschuuren Erik A M , Berger Stefan P , Span Lambert F R , van der Werf Tjip S , Alffenaar Jan-Willem C
Published: January 2020

Objectives

Infections remain a threat for solid organ and stem cell transplant recipients. Antimicrobial prophylaxis and pre-emptive therapy have improved survival of these patients; however, the failure rates of prophylaxis are not negligible. The aim of this systematic review is to explore the reasons behind failure of antimicrobial prophylaxis and pre-emptive therapy.

Setting

This systematic review included prospective randomised controlled trials and prospective single-arm studies.

Participants

The studies included were on prophylaxis and pre-emptive therapy of opportunistic infections in transplant recipients. Studies were included from databases MEDLINE, CENTRAL and Embase published until October first 2018.

Primary and secondary outcome measures

Primary outcome measures were breakthrough infections, adverse events leading to stopping of treatment, switching medication or dose reduction. Secondary outcome measures were acquired resistance to antimicrobials, antifungals or antivirals and death.

Results

From 3317 identified records, 30 records from 24 studies with 2851 patients were included in the systematic review. Seventeen focused on prophylactic and pre-emptive treatment of cytomegalovirus and seven studies on invasive fungal infection. The main reasons for failure of prophylaxis and pre-emptive therapy were adverse events and breakthrough infections, which were described in 54% (13 studies) and 38% (9 studies) of the included studies, respectively. In 25%, six of the studies, a detailed description of patients who experienced failure of prophylaxis or pre-emptive therapy was unclear or lacking.

Conclusions

Our results show that although failure is reported in the studies, the level of detail prohibits a detailed analysis of failure of prophylaxis and pre-emptive therapy. Clearly reporting on patients with a negative outcome should be improved. We have provided guidance on how to detect failure early in a clinical setting in accordance to the results from this systematic review.

PROSPERO registration number

CRD42017077606.
Improving preoperative haemoglobin using a quality improvement approach to treat iron deficiency anaemia
Authors: Sinclair Rhona CF , Duffield Kate E , de Pennington Jane H
Published: January 2020

Optimising preoperative haemoglobin (Hb) before elective surgery is recommended by the National Institute of Clinical Excellence. We have used a quality improvement (QI) approach to treat iron deficiency anaemia in patients presenting to the preoperative assessment clinic (PAC) before major elective oesophagogastric surgery. Through a series of three QI cycles, we have treated iron deficiency, improved preoperative haemoglobin (Hb) and reduced the rate of postoperative blood transfusion. Our methods have included the early diagnosis of iron deficiency at the PAC attendance, the development and implementation of a new clinical guideline on the treatment of preoperative anaemia and the introduction of a one-stop clinic facilitating same-day treatment with intravenous iron, where appropriate, in conjunction with comprehensive preoperative assessment. The incidence of severe preoperative anaemia (Hb<100 g/L) has fallen from 10% in 2014 to 1.6% in 2018. The overall incidence of preoperative anaemia (defined as Hb<130 g/L by international consensus statement) has reduced from 57.9% in 2014 to 43.9% in 2018. Blood transfusion rate has declined from 16% to 6.5% of patients between 2014 and 2018. In 2018, none of the patients who required a postoperative blood transfusion presented to theatre with preoperative anaemia, a significant change from prior to the interventions. There has been a reduction of 63% in the number of units transfused. The project has successfully optimised these patients, leading to improved preoperative Hb and reduced use of blood transfusion.
Improving timely analgesia administration for musculoskeletal pain in the emergency department
Authors: Woolner Victoria , Ahluwalia Reena , Lum Hilary , Beane Kevin , Avelino Jackie , Chartier Lucas B
Published: January 2020

Delays to adequate analgesia result in worse patient care, decreased patient and provider satisfaction and increased patient complaints. The leading presenting symptom to emergency departments (EDs) is pain, with approximately 34 000 such patients per year in our academic hospital ED and 3300 visits specific for musculoskeletal (MSK) injuries. Our aim was to reduce the time-to-analgesia (TTA; time from patient triage to receipt of analgesia) for patients with MSK pain in our ED by 55% (to under 60 min) in 9 months’ time (May 2018). Our outcome measures included mean TTA and ED length of stay (LOS). Process measures included rates of analgesia administration and of use of medical directives. We obtained weekly data capture for Statistical Process Control (SPC) charts, as well as Mann-Whitney U tests for before-and-after evaluation. We performed wide stakeholder engagement, root cause analyses and created a Pareto Diagram to inform Plan–Do–Study–Act (PDSA) cycles, which included: (1) nurse-initiated analgesia at triage; (2) a new triage documentation aid for medication administration; (3) a quick reference medical directive badge for nurses; and (4) weekly targeted feedback of the project’s progress at clinical team huddle. TTA decreased from 129 min (n=153) to 100 min (22.5%; n=87, p<0.05). Special cause variation was identified on the ED LOS SPC chart with nine values below the midline after the first PDSA. The number of patients that received any analgesia increased from 42% (n=372) to 47% (n=192; p=0.13) and those that received them via medical directives increased from 22% (n=154) to 44% (n=87; p<0.001). We achieved a significant reduction of TTA and an increased use of medical directives through front-line focused improvements.
Concerns about disclosing a high-risk cervical human papillomavirus (HPV) infection to a sexual partner: a systematic review and thematic synthesis
Authors: Bennett Kirsty F , Waller Jo , Ryan Mairead , Bailey Julia V , Marlow Laura A V
Published: January 2020

Background

Human papillomavirus (HPV)-based cervical screening is now replacing cytology-based screening in several countries and many women in screening programmes will consequently receive HPV-positive results. Because of the sexually transmitted nature of HPV, receiving an HPV-positive result may raise questions about disclosing the infection to a sexual partner.

Objective

To review the quantitative and qualitative literature exploring women’s concerns about disclosing a high-risk cervical HPV infection to a sexual partner.

Methods

We searched MEDLINE, PsycINFO, CINAHL Plus, Web of Science and EMBASE for studies reporting at least one disclosure-related outcome among women with high-risk HPV. We also searched the grey literature and carried out forward/backward citation searches. A narrative synthesis for quantitative studies and a thematic synthesis for qualitative studies were conducted.

Results

Thirteen articles met the inclusion criteria (12 qualitative, 1 quantitative). In the quantitative study, 60% of HPV-positive women felt disclosing an HPV result was ‘risky’. Concerns about disclosing HPV to a sexual partner were influenced by the stigma that is associated with having an STI and uncertainty about how their partner would respond. Women questioned how, when and to whom they should disclose their HPV-positive status.

Conclusions

The studies included in this review provide rich information about the range of concerns women have, the reasons for these concerns, and the questions women have about disclosing HPV to sexual partners. As studies were predominantly qualitative, the prevalence of concerns is unclear.
Seven-day vonoprazan and low-dose amoxicillin dual therapy as first-lineHelicobacter pyloritreatment: a multicentre randomised trial in Japan
Authors: Suzuki Sho , Gotoda Takuji , Kusano Chika , Ikehara Hisatomo , Ichijima Ryoji , Ohyauchi Motoki , Ito Hirotaka , Kawamura Masashi , Ogata Yohei , Ohtaka Masahiko , Nakahara Moriyasu , Kawabe Koichi
Published: January 2020

Objective

To date, no randomised trials have compared the efficacy of vonoprazan and amoxicillin dual therapy with other standard regimens forHelicobacter pyloritreatment. This study aimed to investigate the efficacy of the 7-day vonoprazan and low-dose amoxicillin dual therapy as a first-lineH. pyloritreatment, and compared this with vonoprazan-based triple therapy.

Design

This prospective, randomised clinical trial was performed at seven Japanese institutions. Patients withH. pylori–positive culture test and naive to treatment were randomly assigned in a 1:1 ratio to either VA-dual therapy (vonoprazan 20 mg+amoxicillin 750 mg twice/day) or VAC-triple therapy (vonoprazan 20 mg+amoxicillin 750 mg+clarithromycin 200 mg twice/day) for 7 days, with stratification by age, sex,H. pyloriantimicrobial resistance and institution. Eradication success was evaluated by13C-urea breath test at least 4 weeks after treatment.

Results

Between October 2018 and June 2019, 629 subjects were screened and 335 were randomised. The eradication rates of VA-dual and VAC-triple therapies were 84.5% and 89.2% (p=0.203) by intention-to-treat analysis, respectively, and 87.1% and 90.2% (p=0.372) by per-protocol analysis, respectively. VA-dual was non-inferior to VAC-triple in the per-protocol analysis. The eradication rates in strains resistant to clarithromycin for VA-dual were significantly higher than those for VAC-triple (92.3% vs 76.2%; p=0.048). The incidence of adverse events was equal between groups.

Conclusion

The 7-day vonoprazan and low-dose amoxicillin dual therapy provided acceptableH. pylorieradication rates and a similar effect to vonoprazan-based triple therapy in regions with high clarithromycin resistance.

Trial registration number

UMIN000034140.
Association of designated open water swim area regulations and open water drowning rates
Authors: Quan Linda , Mills Brianna , Chau Suet Sen , Bennett Elizabeth , Bolt Kaylin , Gomez Anthony
Published: January 2020

Background

Although most persons over 5 years of age drown in open water, few laws have sought to regulate open water swim sites. We examined the association between regulations for designated open water swim sites and open water drowning death rates by state.

Methods

Using International Classification of Disease (ICD)-10 codes in the CDC Web-based Injury Statistics Query and Reporting System (WISQARS), we identified and calculated open water drowning deaths involving all ages from 2012 to 2017 for 50 states and calculated open water drowning death rates. We then identified and categorised types of state regulations (lifeguards, water quality, rescue equipment, tracking/planning/reporting and signage) for open water swim sites in place in 2017 for a sample of 30 states (20 high-drowning, 10 low-drowning). Analyses evaluated associations between open water drowning rates in three groups (overall, youth and non-white) and the total number and types of state regulations.

Results

Swim site regulations and open water drowning death rates for 10 839 victims were associated in all regression models. States with more types of regulations had lower open water drowning death rates in a dose-response relationship. States lacking regulations compared with states with all five types of regulations had open water drowning death rates 3.02 times higher among youth (95% CI 1.82 to 4.99) and 4.16 times higher among non-white residents (95% CI 2.46 to 7.05). Lifeguard and tracking/planning/reporting regulations were associated with a 33% and 45% reduction in open water drowning rates overall and among those aged 0–17 years.

Conclusion

States’ open water swim area regulations, especially addressing tracking/planning/reporting and lifeguards, were associated with lower open water drowning death rates.
Institutional conflict of interest: attempting to crack the deferiprone mystery
Authors: Schafer Arthur
Published: January 2020

A recent study by Olivieri et al, published in PLOS ONE, reports that between 2009 and 2015 a third of patients with thalassaemia in Canada’s largest hospital were switched from first-line licensed drugs to regimens of deferiprone, an unlicensed drug of unproven safety and efficacy. Based on retrospective data from patient records, the PLOS Study reports that patients treated with deferiprone, either as monotherapy or in combination with first-line drugs, suffered serious (and often irreversible) adverse effects. The data reported by Olivieri et al give rise to a number of ethical issues. These ethical issues are identified, placed in historical context and analysed. For purposes of this analysis, reliance is placed on two core principles of research ethics, harm minimisation and informed consent, and also on the hospital’s mission statement. Then a mystery is explored: How and why did it happen that Toronto’s University Health Network treated large numbers of patients with an unlicensed drug over a period of many years? ‘Institutional conflict of interest’ is considered as a possible explanatory hypothesis.
Fatigue numeric rating scale validity, discrimination and responder definition in patients with psoriatic arthritis
Authors: Gladman Dafna , Nash Peter , Goto Hitoshi , Birt Julie A , Lin Chen-Yen , Orbai Ana-Maria , Kvien Tore K
Published: January 2020

Objectives

This study assessed the psychometric properties of the fatigue numeric rating scale (NRS) and sought to establish values for clinically meaningful change (responder definition).

Methods

Using disease-specific clinician-reported and patient-reported data from two randomised clinical trials of patients with psoriatic arthritis (PsA), the fatigue NRS was evaluated for test–retest reliability, construct validity and responsiveness. A responder definition was also explored using anchor-based and distribution-based methods.

Results

Test–retest reliability analyses supported the reproducibility of the fatigue NRS in patients with PsA (intraclass correlation coefficient=0.829). Mean (SD) values at baseline and week 2 were 5.7 (2.2) and 5.7 (2.4), respectively. Supporting construct validity of the fatigue NRS, moderate-to-large correlations with other assessments measuring similar concepts as measured by Sackett’s conventions were demonstrated. Fatigue severity was reduced when the underlying disease activity was improved and reductions remained consistent at week 12 and 24. A 3-point improvement was identified as being optimal for demonstrating a level of clinically meaningful improvement in fatigue NRS after 12–24 weeks of treatment.

Conclusions

Fatigue NRS is a valid and responsive patient-reported outcome instrument for use in patients with PsA. The established psychometric properties from this study support the use of fatigue NRS in clinical trials and in routine clinical practice. Robust validation of reliability for use in routine clinical practice in treating patients with active PsA in less active disease states and other more diverse ethnic groups is needed.
Pathogenesis of ischaemic and non-ischaemic heart diseases in rheumatoid arthritis
Authors: Błyszczuk Przemysław , Szekanecz Zoltan
Published: January 2020

Rheumatoid arthritis (RA) is characterised by a chronic inflammatory condition of the joints, but the comorbidities of RA predominantly contribute to the reduced lifespan associated with this disease. Clinical data indicate that cardiovascular disease is the major comorbidity associated with mortality in RA. In this review, we aimed to describe the pathogenesis of heart failure in RA. First, we emphasised the fundamental differences between ischaemic and non-ischaemic heart diseases and referred to their relevance in excessive cardiovascular-dependent mortality in RA. Second, we highlighted aspects of asymptomatic changes in cardiac tissue and in coronary blood vessels that are commonly found in patients with diagnosed RA. Third, we focused on high-grade systemic inflammation as a key trigger of ischaemic and non-ischaemic heart diseases in RA, and described the implication of conventional and biologic antirheumatic medications on the development and progression of heart disease. In particular, we discussed the roles of tumour necrosis factor-alpha (TNF-α) and anti-TNF-α therapies on the development and progression of ischaemic and non-ischaemic heart diseases in RA.
Olfactory EEG Signal Classification Using a Trapezoid Difference-Based Electrode Sequence Hashing Approach
Authors: Hou Huirang , Zhang Xiaonei , Meng Qinghao
Published: January 2020

Olfactory-induced electroencephalogram (EEG) signal classification is of great significance in a variety of fields, such as disorder treatment, neuroscience research, multimedia applications and brain–computer interface. In this paper, a trapezoid difference-based electrode sequence hashing method is proposed for olfactory EEG signal classification. First, an [Formula: see text]-layer trapezoid feature set whose size ratio of the top, bottom and height is 1:2:1 is constructed for each frequency band of each EEG sample. This construction is based on [Formula: see text] optimized power-spectral-density features extracted from [Formula: see text] real electrodes and [Formula: see text] nonreal electrode’s features. Subsequently, the [Formula: see text] real electrodes’ sequence (ES) codes of each layer of the constructed trapezoid feature set are obtained by arranging the feature values in ascending order. Finally, the nearest neighbor classification is used to find a class whose ES codes are the most similar to those of the testing sample. Thirteen-class olfactory EEG signals collected from 11 subjects are used to compare the classification performance of the proposed method with six traditional classification methods. The comparison shows that the proposed method gives average accuracy of 94.3%, Cohen’s kappa value of 0.94, precision of 95.0%, and F1-measure of 94.6%, which are higher than those of the existing methods.
Charged gravastars with cylindrical spacetime
Authors: Bhatti M. Z.
Published: January 2020

The objective of this work is to construct a gravastar model using thin-shell formalism and discuss its realistically accepted properties with the background of cylindrical metric. In this scenario, we matched the interior cylindrical geometry with exterior metric via Israel matching conditions. The stability of the constructed model under the influence of electric charge is then examined using linear perturbations around the equilibrium condition. We explored some stable regimes near the equilibrium condition with different values of charge as well as involved parameters.
A Universal Method for Designing Multi-Digit Ternary to Binary Converter Using CNTFET
Authors: Shahangian Maryam , Hosseini Seied Ali , Mirzaee Reza Faghih
Published: January 2020

Ternary logic can reduce the number of interconnections, chip area and power dissipation. In addition, one of the important features of carbon nanotube field effect transistors (CNTFETs) is the capability of adjusting threshold voltage. As a result, the design complexity of ternary circuits can be decreased. The structure of a mixed radix system which is based on multi-valued and binary logic is more appropriate compared to only multiple-valued logic (MVL). Therefore, ternary-to-binary and binary-to-ternary converters are the essential components for the ternary signaling on the bus and the binary logic processing circuits. It is also important for the creation of compatibility between the binary and ternary logic. This study is about a multi-digit binary-to-ternary converter by using CNTFET. At first, the algorithm used for the multi-digit conversion from ternary to binary logic is addressed in this paper. Then, the paper proposes a block diagram suitable for designing the multi-digit ternary-to-binary converter. Some new gates including One-Active Gate and Two-Active Gate, as well as two types of binary half-and full-adders, are designed for the purpose of implementing the proposed block diagram. This is done by adjusting the proper threshold voltage for CNTFETs. The proposed algorithm can also be applied to any desired number of bits. The proper operation and high efficiency of the proposed converter are confirmed by HSPICE simulation results and 32[Formula: see text]nm CNTFET technology from the Stanford University.
About this title - Folding and Fracturing of Rocks: 50 Years of Research since the Seminal Text Book of J. G. Ramsay
Authors: Bond Clare E. , Lebit Hermann D.
Published: January 2020

This Special Publication is a celebration of research into the
Folding and Fracturing of Rocks
to mark the 50th anniversary of the publication of the seminal textbook by J. G. Ramsay.
Folding and Fracturing of Rocks
summarised the key structural geology concepts of the time. Through his numerical and geometric focus John pioneered and provided solutions to understanding the processes leading to the folding and fracturing of rocks. His strong belief that numerical and geometric solutions, to understanding crustal processes, should be tested against field examples added weight and clarity to his work. The basic ideas and solutions presented in the text are as relevant now as they were 50 years ago, and this collection of papers celebrates John's contribution to structural geology. The papers explore the lasting impact of John and his work, they present case studies and a modern understanding of the process documented in the
Folding and Fracturing of Rocks
.
Morphological signature of gully development by rapid slide retrogression in a layered coarse-grained delta foreslope
Authors: Locat Jacques , Azizian Ali , Stronach Jim , Hospital Aurélien , Young Chris , Turmel Dominique , Bevan Andrew
Published: January 2020

Coarse-grained deltas are often characterized by steep foreslopes (often more than 10°) that are traversed by delta-front channels. The channels thus erode into relatively steeply inclined bedding. In this context, the slopes flanking the channels can be steeper than the friction angle since they include a component of dip related to the delta-front slope as well as the channel-related erosion slope. In this study, part of the Busu River delta (Papua New Guinea) was imaged using a high-resolution multibeam bathymetry survey over an area where the angle of the slopes flanking the channels locally reaches 50°. A detailed analysis of the delta slope morphology has revealed an additional source of instability due to erosion within the main channels. In some places, erosion cuts into the channel flank forming a local knickpoint inclined in a direction approaching that of the bed dip. The cut can then initiate breaching or static liquefaction failure from that point up to the crest of the interfluve resulting in a V-shaped gully.
The influence of clay content on submarine slope failure: insights from laboratory experiments and numerical models
Authors: Silver M. M. W. , Dugan B.
Published: January 2020

Submarine slope failures pose risks to coastlines because they can damage infrastructure and generate tsunamis. Passive margin slope failures represent the largest mass failures on Earth, yet we know little about their dynamics. While numerous studies characterize the lithology, structure, seismic attributes and geometry of failure deposits, we lack direct observations of failure evolution. Thus, we lack insight into the relationships between initial conditions, slope failure initiation and evolution, and final deposits. To investigate submarine slope failure dynamics in relation to initial conditions and to observe failure processes we performed physical experiments in a benchtop flume and produced numerical models. Submarine slope failures were induced under controlled pore pressure within sand–clay mixtures (0–5 wt% clay). Increased clay content corresponded to increased cohesion and pore pressure required for failure. Subsurface fractures and tensile cracks were only generated in experiments containing clay. Falling head tests showed a log-linear relation between hydraulic conductivity and clay content, which we used in our numerical models. Models of our experiments effectively simulate overpressure (pressure in excess of hydrostatic) and failure potential for (non)cohesive sediment mixtures. Overall our work shows the importance of clay in reducing permeability and increasing cohesion to create different failure modes due to overpressure.
Revisiting the tsunamigenic volcanic flank collapse of Fogo Island in the Cape Verdes, offshore West Africa
Authors: Barrett Rachel , Lebas Elodie , Ramalho Ricardo , Klaucke Ingo , Kutterolf Steffen , Klügel Andreas , Lindhorst Katja , Gross Felix , Krastel Sebastian
Published: January 2020

Volcanic archipelagos are a source of numerous on- and offshore geohazards, including explosive eruptions and potentially tsunamigenic large-scale flank collapses. Fogo Island in the southern Cape Verdes is one of the most active volcanoes in the world, making it both prone to collapse (as evidenced by the
c.
73 ka Monte Amarelo volcanic flank collapse), and a source of widely distributed tephra and volcanic material. The offshore distribution of the Monte Amarelo debris avalanche deposits and the surrounding volcaniclastic apron were previously mapped using only medium-resolution bathymetric data. Here, using recently acquired, higher-resolution acoustic data, we revisit Fogo's flank collapse and find evidence suggesting that the deposition of hummocky volcanic debris originating from the failed eastern flank most likely triggered the contemporaneous, multi-phase failure of pre-existing seafloor sediments. Additionally, we identify, for the first time, multiple mass-transport deposits in the southern part of the volcaniclastic apron of Fogo and Santiago based on the presence of acoustically chaotic deposits in parametric echo sounder data and volcaniclastic turbiditic sands in recovered cores. These preliminary findings indicate a long and complex history of instability on the southern slopes of Fogo and suggest that Fogo may have experienced multiple flank collapses.
Principles and Applications of Biological Membrane Organization
Authors: Zeno Wade F. , Day Kasey J. , Gordon Vernita D. , Stachowiak Jeanne C.
Published: January 2020

Many critical biological events, including biochemical signaling, membrane traffic, and cell motility, originate at membrane surfaces. Each such event requires that members of a specific group of proteins and lipids rapidly assemble together at a specific site on the membrane surface. Understanding the biophysical mechanisms that stabilize these assemblies is critical to decoding and controlling cellular functions. In this article, we review progress toward a quantitative biophysical understanding of the mechanisms that drive membrane heterogeneity and organization. We begin from a physical perspective, reviewing the fundamental principles and key experimental evidence behind each proposed mechanism. We then shift to a biological perspective, presenting key examples of the role of heterogeneity in biology and asking which physical mechanisms may be responsible. We close with an applied perspective, noting that membrane heterogeneity provides a novel therapeutic target that is being exploited by a growing number of studies at the interface of biology, physics, and engineering.
Slow Slip Events in New Zealand
Authors: Wallace Laura M.
Published: January 2020

Continuously operating global positioning system sites in the North Island of New Zealand have revealed a diverse range of slow motion earthquakes on the Hikurangi subduction zone. These slow slip events (SSEs) exhibit diverse characteristics, from shallow (<15 km), short (<1 month), frequent (every 1–2 years) events in the northern part of the subduction zone to deep (>30 km), long (>1 year), less frequent (approximately every 5 years) SSEs in the southern part of the subduction zone. Hikurangi SSEs show intriguing relationships to interseismic coupling, seismicity, and tectonic tremor, and they exhibit a diversity of interactions with large, regional earthquakes. Due to the marked along-strike variations in Hikurangi SSE characteristics, which coincide with changes in physical characteristics of the subduction margin, the Hikurangi subduction zone presents a globally unique natural laboratory to resolve outstanding questions regarding the origin of episodic, slow fault slip behavior. ▪  New Zealand's Hikurangi subduction zone hosts slow slip events with a diverse range of depth, size, duration, and recurrence characteristics. ▪  Hikurangi slow slip events show intriguing relationships with seismicity ranging from small earthquakes and tremor to larger earthquakes. ▪  Slow slip events play a major role in the accommodation of plate motion at the Hikurangi subduction zone. ▪  Many aspects of the Hikurangi subduction zone make it an ideal natural laboratory to resolve the physical processes controlling slow slip.
The Changing Cleavage Politics of Western Europe
Authors: Ford Robert , Jennings Will
Published: January 2020

How are the contours of Western European politics shifting? To what extent do these shifts reflect changes in the underlying social and economic structure of European polities? In this article, we reflect on insights from the classic literature on how cleavages structure party systems and consider how the emergence and persistence of new parties and new ideological conflicts are leading to both shifts of dividing lines of party competition and the fragmentation of party systems. While increasing attention has been given to the so-called second dimension of European electoral politics, we highlight the relatively limited focus on structural changes that are helping to drive this transformation. We identify some socio-demographic developments that are potentially generating new cleavages in Western European democracies: the expansion of higher education; mass migration and the growing ethnic diversity of electorates; the aging of societies and sharpening of generational divides; and increased geographical segregation of populations between prospering, globalized major cities and declining hinterlands.
Mental Health of Refugee Children and Youth: Epidemiology, Interventions, and Future Directions
Authors: Frounfelker Rochelle L. , Miconi Diana , Farrar Jordan , Brooks Mohamad Adam , Rousseau Cécile , Betancourt Theresa S.
Published: January 2020

The number of refugee youth worldwide receives international attention and is a top priority in both academic and political agendas. This article adopts a critical eye in summarizing current epidemiological knowledge of refugee youth mental health as well as interventions aimed to prevent or reduce mental health problems among children and adolescents in both high- and low-to-middle-income countries. We highlight current challenges and limitations of extant literature and present potential opportunities and recommendations in refugee child psychiatric epidemiology and mental health services research for moving forward. In light of the mounting xenophobic sentiments we are presently witnessing across societies, we argue that, as a first step, all epidemiological and intervention research should advocate for social justice to guarantee the safety of and respect for the basic human rights of all refugee populations during their journey and resettlement. A constructive dialogue between scholars and policy makers is warranted.
High-mobility group box-1 increases epithelial sodium channel activity and inflammation via the receptor for advanced glycation end products
Authors: Grant Garett J. , Liou Theodore G. , Paine Robert , Helms My N.
Published: January 2020

Cystic fibrosis (CF) lung disease persists and remains life-limiting for many patients. Elevated high-mobility group box-1 protein (HMGB-1) levels and epithelial sodium channel hyperactivity (ENaC) are hallmark features of the CF lung. The objective of this study was to better understand the pathogenic role of HMGB-1 signaling and ENaC in CF airway cells. We hypothesize that HMGB-1 links airway inflammation [via signaling to the receptor for advanced glycation end products (RAGE)] and airway surface liquid dehydration (via upregulation of ENaC) in the CF lung. We calculated equivalent short-current ( Isc) and single-channel ENaC open probability ( Po) in normal and CF human small airway epithelial cells (SAEC) in the presence and absence of human HMGB-1 peptide (0.5 μg/mL). In normal SAECs, HMGB-1 increased amiloride-sensitive Isc and elevated ENaC Po from 0.15 ± 0.03 to 0.28 ± 0.04 ( P < 0.01). In CF SAECs, ENaC Po increased from 0.45 ± 0.06 to 0.73 ± 0.04 ( P < 0.01). Pretreatment with 1 μM FPS-ZM1 (a RAGE inhibitor) attenuated all HMGB-1 effects on ENaC current in normal and CF SAECs. Confocal analysis of SAECs indicates that nuclear size and HMBG-1 localization can be impacted by ENaC dysfunction. Masson’s trichrome labeling of mouse lung showed that intraperitoneally injected HMGB-1 significantly increased pulmonary fibrosis. Bronchoalveolar lavage fluid from HMGB-1-treated mice showed significant increases in IL-1β, IL-10, IL-6, IL-27, IL-17A, IFN-β, and granulocyte-macrophage colony-stimulating factor compared with vehicle-injected mice ( P < 0.05). These studies put forth a new model in which HMGB-1 signaling to RAGE plays an important role in perpetuating ENaC dysfunction and inflammation in the CF lung.
The CC and CXC chemokines: major regulators of tumor progression and the tumor microenvironment
Authors: Bikfalvi Andreas , Billottet Clotilde
Published: January 2020

Chemokines are a family of soluble cytokines that act as chemoattractants to guide the migration of cells, in particular of immune cells. However, chemokines are also involved in cell proliferation, differentiation, and survival. Chemokines are associated with a variety of human diseases including chronic inflammation, immune dysfunction, cancer, and metastasis. This review discusses the expression of CC and CXC chemokines in the tumor microenvironment and their supportive and inhibitory roles in tumor progression, angiogenesis, metastasis, and tumor immunity. We also specially focus on the diverse roles of CXC chemokines (CXCL9–11, CXCL4 and its variant CXCL4L1) and their two chemokine receptor CXCR3 isoforms, CXCR3-A and CXCR3-B. These two distinct isoforms have divergent roles in tumors, either promoting (CXCR3-A) or inhibiting (CXCR3-B) tumor progression. Their effects are mediated not only directly in tumor cells but also indirectly via the regulation of angiogenesis and tumor immunity. A full comprehension of their mechanisms of action is critical to further validate these chemokines and their receptors as biomarkers or therapeutic targets in cancer.
The septate junction protein Mesh is required for epithelial morphogenesis, ion transport, and paracellular permeability in the Drosophila Malpighian tubule
Authors: Jonusaite Sima , Beyenbach Klaus W. , Meyer Heiko , Paululat Achim , Izumi Yasushi , Furuse Mikio , Rodan Aylin R.
Published: January 2020

Septate junctions (SJs) are occluding cell-cell junctions that have roles in paracellular permeability and barrier function in the epithelia of invertebrates. Arthropods have two types of SJs, pleated SJs and smooth SJs (sSJs). In Drosophila melanogaster, sSJs are found in the midgut and Malpighian tubules, but the functions of sSJs and their protein components in the tubule epithelium are unknown. Here we examined the role of the previously identified integral sSJ component, Mesh, in the Malpighian tubule. We genetically manipulated mesh specifically in the principal cells of the tubule at different life stages. Tubules of flies with developmental mesh knockdown revealed defects in epithelial architecture, sSJ molecular and structural organization, and lack of urine production in basal and kinin-stimulated conditions, resulting in edema and early adult lethality. Knockdown of mesh during adulthood did not disrupt tubule epithelial and sSJ integrity but decreased the transepithelial potential, diminished transepithelial fluid and ion transport, and decreased paracellular permeability to 4-kDa dextran. Drosophila kinin decreased transepithelial potential and increased chloride permeability, and it stimulated fluid secretion in both control and adult mesh knockdown tubules but had no effect on 4-kDa dextran flux. Together, these data indicate roles for Mesh in the developmental maturation of the Drosophila Malpighian tubule and in ion and macromolecular transport in the adult tubule.
Prolonged nonobstructive urinary retention induced by tibial nerve stimulation in cats
Authors: Li Shun , Browning Jeffery , Theisen Katherine , Yecies Todd , Shen Bing , Wang Jicheng , Roppolo James R. , de Groat William C. , Tai Changfeng
Published: January 2020

Nonobstructive urinary retention (NOUR) is a medical condition without an effective drug treatment, but few basic science studies have focused on this condition. In α-chloralose-anesthetized cats, the bladder was cannulated via the dome and infused with saline to induce voiding that could occur without urethral outlet obstruction. A nerve cuff electrode was implanted for tibial nerve stimulation (TNS). The threshold (T) intensity for TNS to induce toe twitch was determined initially. Repeated (6 times) application of 30-min TNS (5 Hz, 0.2 ms, 4–6T) significantly ( P < 0.05) increased bladder capacity to 180% of control and reduced the duration of the micturition contraction to 30% of control with a small decrease in contraction amplitude (80% of control), which resulted in urinary retention with a low-voiding efficiency of 30% and a large amount of residual volume equivalent to 130% of control bladder capacity. This NOUR condition persisted for >2 h after the end of repeated TNS. However, lower frequency TNS (1 Hz, 0.2 ms, 4T) applied during voiding partially reversed the NOUR by significantly ( P < 0.05) increasing voiding efficiency to 60% and reducing residual volume to 70% of control bladder capacity without changing bladder capacity. These results revealed that tibial nerve afferent input can activate either an excitatory or an inhibitory central nervous system mechanism depending on afferent firing frequencies (1 vs. 5 Hz). This study established the first NOUR animal model that will be useful for basic science research aimed at developing new treatments for NOUR.
Electrophysiological responses to sugars and amino acids in the nucleus of the solitary tract of type 1 taste receptor double-knockout mice
Authors: Kalyanasundar B. , Blonde Ginger D. , Spector Alan C. , Travers Susan P.
Published: January 2020

Strong evidence supports a major role for heterodimers of the type 1 taste receptor (T1R) family in the taste transduction of sugars (T1R2+T1R3) and amino acids (T1R1+T1R3), but there are also neural and behavioral data supporting T1R-independent mechanisms. Most neural evidence for alternate mechanisms comes from whole nerve recordings in mice with deletion of a single T1R family member, limiting conclusions about the functional significance and T1R independence of the remaining responses. To clarify these issues, we recorded single-unit taste responses from the nucleus of the solitary tract in T1R double-knockout (double-KO) mice lacking functional T1R1+T1R3 [KO1+3] or T1R2+T1R3 [KO2+3] receptors and their wild-type background strains [WT; C57BL/6J (B6), 129X1/SvJ (S129)]. In both double-KO strains, responses to sugars and a moderate concentration of an monosodium glutamate + amiloride + inosine 5′-monophosphate cocktail (0.1 M, i.e., umami) were profoundly depressed, whereas a panel of 0.6 M amino acids were mostly unaffected. Strikingly, in contrast to WT mice, no double-KO neurons responded selectively to sugars and umami, precluding segregation of this group of stimuli from those representing other taste qualities in a multidimensional scaling analysis. Nevertheless, residual sugar responses, mainly elicited by monosaccharides, persisted as small “sideband” responses in double-KOs. Thus other receptors may convey limited information about sugars to the central nervous system, but T1Rs appear critical for coding the distinct perceptual features of sugar and umami stimuli. The persistence of amino acid responses supports previous proposals of alternate receptors, but because these stimuli affected multiple neuron types, further investigations are necessary.

NEW & NOTEWORTHY The type 1 taste receptor (T1R) family is crucial for transducing sugars and amino acids, but there is evidence for T1R-independent mechanisms. In this study, single-unit recordings from the nucleus of the solitary tract in T1R double-knockout mice lacking T1R1+T1R3 or T1R2+T1R3 receptors revealed greatly reduced umami synergism and sugar responses. Nevertheless, residual sugar responses persisted, mainly elicited by monosaccharides and evident as “sidebands” in neurons activated more vigorously by other qualities.
Phonotactic steering and representation of directional information in the ascending auditory pathway of a cricket
Authors: Lv M. , Zhang X. , Hedwig B.
Published: January 2020

Directional hearing is crucial for animals depending on acoustic signals to locate a mate. We focused on crickets to explore the reliability of directional information forwarded to the brain by the ascending auditory interneuron AN1, which is crucial for phonotactic behavior. We presented calling song from −45° to +45° in steps of 3° and compared the phonotactic steering of females walking on a trackball with the directional responses of AN1. Forty percent of females showed good steering behavior and changed their walking direction when the speaker passed the body’s longitudinal axis. The bilateral latency difference between right and left AN1 responses was small and may not be reliable for auditory steering. In respect to spike count, all AN1 recordings presented significant bilateral differences for angles larger than ±18°, yet 35% showed a mean significant difference of 1–3 action potentials per chirp when the frontal stimulus deviated by 3° from their length axis. For small angles, some females had a very similar AN1 activity forwarded to the brain, but the accuracy of their steering behavior was substantially different. Our results indicate a correlation between directional steering and the response strength of AN1, especially for large angles. The reliable steering of animals at small angles would have to be based on small bilateral differences of AN1 activity, if AN1 is the only source providing directional information. We discuss whether such bilateral response difference at small angles can provide a reliable measure to generate auditory steering commands descending from the brain, as pattern recognition is intensity independent.

NEW & NOTEWORTHY The ascending auditory interneuron AN1 has been implicated in cricket auditory steering, but at small acoustic stimulation angles, it does not provide reliable directional information. We conclude that either the small bilateral auditory activity differences of the AN1 neurons are enhanced to generate reliable descending steering commands or, more likely, directional auditory steering is mediated via a thoracic pathway, as indicated by the reactive steering hypothesis.
Dunaliella salina Attenuates Diabetic Neuropathy Induced by STZ in Rats: Involvement of Thioredoxin
Authors: El-Baz Farouk K. , Salama Abeer , Salama Rania A. A.
Published: January 2020

Diabetic neuropathy (DN) is a widespread disabling disorder including peripheral nerves’ damage. The aim of the current study was to estimate the potential ameliorative effect of Dunaliella salina (D. salina) on DN and the involvement of the thioredoxin. Diabetes was induced by streptozotocin (STZ; 50 mg/kg; i.p). Glimepiride (0.5 mg/kg) or D. salina powder (100 or 200 mg/kg) were given orally, after 2 days of STZ injection for 4 weeks. Glucose, total antioxidant capacity (TAC), superoxide dismutase (SOD), and catalase (CAT) serum levels as well as brain contents of thioredoxin (Trx), tumor necrosis factor‐alpha (TNF‐α), and interleukin‐6 (IL‐6) were measured with the histopathological study. STZ‐induced DN resulted in a significant (P < 0.05) rise in glucose blood level and brain contents of TNF‐α and IL‐6 and produced a reduction in serum TAC, SOD, CAT, and brain Trx levels with irregular islets of Langerhans cells and loss of brain Purkinje cells. Treatment with glimepiride or both doses of D. salina alleviated these biochemical and histological parameters as compared to the STZ group. D. salina has a neurotherapeutic effect against DN via its inhibitory effect on inflammatory mediators and oxidative stress molecules with its upregulation of Trx activity.
Comparative Study on Beneficial Effects of Hydroxytyrosol‐ and Oleuropein‐Rich Olive Leaf Extracts on High‐Fat Diet‐Induced Lipid Metabolism Disturbance and Liver Injury in Rats
Authors: Fki Ines , Sayadi Sami , Mahmoudi Asma , Daoued Ines , Marrekchi Rim , Ghorbel Hela
Published: January 2020

Oleuropein and hydroxytyrosol, as major compounds of olive leaves, have been reported to exert numerous pharmacological properties, including anticancer, antidiabetic, and anti‐inflammatory activities. The purpose of this study is to evaluate and compare the protective effect of oleuropein‐ and hydroxytyrosol‐rich extracts, derived from olive leaves, on high‐fat diet‐induced lipid metabolism disturbance and liver injury in rats. In this respect, four groups of male rats (8 per group) were used: control group (Control), group treated with high‐fat diet (HFD), group treated with HFD and oleuropein (HFD + OLE), and group treated with HFD and hydroxytyrosol (HFD + HYD). The current research showed that the treatment with the HFD increased the body weight and adipose tissue mass in male rats. Moreover, the plasma levels of triglycerides, total cholesterol, LDL‐cholesterol, AST, ALT, LDH, and TNF‐α were also raised. The hepatic immunohistochemical analysis revealed a significant increase in the expression of inflammatory genes (COX‐2, NF‐κB, and TNF‐α). Equally, it showed a rise of the apoptotic markers (a decrease in the expression of the Bcl‐2 and an increase of the P53). In addition, the oral administration of oleuropein‐ and hydroxytyrosol‐rich olive leaf extracts at 16 mg/kg similarly reduced the body weight and adipose tissue mass and improved the lipid profile. Moreover, these extracts, mainly the hydroxytyrosol‐rich extract, reduced the elevated liver enzymes, enhanced the antioxidant status, and attenuated the liver inflammation and apoptosis. These findings suggest that the oleuropein‐ and hydroxytyrosol‐rich olive leaf extracts possessed hypolipidemic and hepatoprotective effects against the HFD‐induced metabolic disorders by enhancing the antioxidative defense system and blocking the expression of the proteins involved in inflammation and liver damage.