bluuebunny/crossref_metadata_2025 huggingface dataset:
Transient “rest” induces functional reinvigoration and epigenetic remodeling in exhausted CAR-T cells
Authors: Weber Evan W. , Lynn Rachel C. , Parker Kevin R. , Anbunathan Hima , Lattin John , Sotillo Elena , Good Zinaida , Malipatlolla Meena , Xu Peng , Vandris Panos , Majzner Robbie G. , Qi Yanyan , Chen Ling-Chun , Gentles Andrew J. , Wandless Thomas J. , Satpathy Ansuman T. , Chang Howard Y. , Mackall Crystal L.
Published: January 2020

T cell exhaustion limits immune responses against cancer and is a major cause of resistance to CAR-T cell therapeutics. Using a model wherein tonic CAR signaling induces hallmark features of exhaustion, we employed a drug-regulatable CAR to test the impact of transient cessation of receptor signaling (i.e. “rest”) on the development and maintenance of exhaustion. Induction of rest in exhausting or already-exhausted CAR-T cells resulted in acquisition of a memory-like phenotype, improved anti-tumor functionality, and wholescale transcriptional and epigenetic reprogramming. Similar results were achieved with the Src kinase inhibitor dasatinib, which reversibly suppresses CAR signaling. The degree of functional reinvigoration was proportional to the duration of rest and was associated with expression of transcription factors TCF1 and LEF1. This work demonstrates that transient cessation of CAR-T cell signaling can enhance anti-tumor potency by preventing or reversing exhaustion and challenges the paradigm that exhaustion is an epigenetically fixed state.
Transcriptional regulator PAX4 links Receptor Tyrosine Kinases (RTKs) and cytoskeleton stability in Alzheimer’s disease and type 2 diabetes
Authors: Majumder Piyali , Chanda Kaushik , Das Debajyoti , Singh Brijesh Kumar , Chakrabarti Partha , Jana Nihar Ranjan , Mukhopadhyay Debashis
Published: January 2020

Alzheimer’s Disease (AD) and Type 2 Diabetes (T2D) share a common hallmark of insulin resistance. Besides Insulin Receptor (IR), two non-canonical RTKs, ALK and RYK, exhibit significant and consistent functional downregulation inpost-mortemAD and T2D tissues. Incidentally, both have Grb2 as a common downstream adapter and NOX4 as a common ROS producing factor. Here we show that Grb2 and NOX4 play critical roles in reducing the severity of both the diseases. The study demonstrates that the abundance of Grb2 in degenerative conditions, in conjunction with NOX4, reverse cytoskeletal degradation by counterbalancing the network of small GTPases. PAX4, a transcription factor for both Grb2 and NOX4, emerges as the key link between the common pathways of AD and T2D. Both ALK and RYK downregulation elevate the PAX4 level by reducing its suppressor ARX via Wnt/β-Catenin signaling pathway. For the first time, this study brings together RTKs other than Insulin Receptor (IR), their common transcription factor PAX4 and both AD and T2D pathologies on a common regulatory platform.
Structure analysis of supported disordered molybdenum oxides using pair distribution function analysis and automated cluster modelling
Authors: Lindahl Christiansen Troels , Kjær Emil T. S. , Kovyakh Anton , Röderen Morten L. , Høj Martin , Vosch Tom , Jensen Kirsten M. Ø.
Published: January 2020

Molybdenum oxides and sulfides on various low-cost high-surface-area supports are excellent catalysts for several industrially relevant reactions. The surface layer structure of these materials is, however, difficult to characterize due to small and disordered MoO
x
domains. Here, it is shown how X-ray total scattering can be applied to gain insights into the structure through differential pair distribution function (d-PDF) analysis, where the scattering signal from the support material is subtracted to obtain structural information on the supported structure. MoO
x
catalysts supported on alumina nanoparticles and on zeolites are investigated, and it is shown that the structure of the hydrated molybdenum oxide layer is closely related to that of disordered and polydisperse polyoxometalates. By analysing the PDFs with a large number of automatically generated cluster structures, which are constructed in an iterative manner from known polyoxometalate clusters, information is derived on the structural motifs in supported MoO
x
.
Multi-wavelength Bragg coherent X-ray diffraction imaging of Au particles
Authors: Lauraux F. , Cornelius T. W. , Labat S. , Richard M.-I. , Leake S. J. , Zhou T. , Kovalenko O. , Rabkin E. , Schülli T. U. , Thomas O.
Published: January 2020

Multi-wavelength (mw) Bragg coherent X-ray diffraction imaging (BCDI) is demonstrated on a single Au particle. The multi-wavelength Bragg diffraction patterns are inverted using conventional phase-retrieval algorithms where the dilation of the effective pixel size of a pixelated 2D detector caused by the variation of the X-ray beam energy is mitigated by interpolating the raw data. The reconstructed Bragg electron density and phase field are in excellent agreement with the results obtained from conventional rocking scans of the same particle. Voxel sizes of about 63 nm3 are obtained for reconstructions from both approaches. Phase shifts as small as 0.41 rad, which correspond to displacements of 14 pm and translate into strain resolution better than 10−4 in the Au particle, are resolved. The displacement field changes shape during the experiment, which is well reproduced by finite element method simulations considering an inhomogeneous strained carbon layer deposited on the Au particle over the course of the measurements. These experiments thus demonstrate the very high sensitivity of BCDI and mw-BCDI to strain induced by contaminations. Furthermore, mw-BCDI offers new opportunities for in situ and operando 3D strain imaging in complex sample environments.
crystalAligner: a computer program to align crystal directions in a scanning electron microscope by global optimization
Authors: Niessen Frank
Published: January 2020

Alignment of a crystal with the coordinate system of a scanning electron microscope (SEM) is essential for obtaining controlled diffraction conditions or investigating anisotropic material properties. The computer program crystalAligner was developed to enable the weighted constrained alignment of one or two crystal directions in crystals of arbitrary orientation and structure with the coordinate system of a SEM. For a given set of crystal directions, alignment objectives and rotational constraints, the algorithm simulates the rotation of the crystal on any constrained SEM stage and minimizes the misalignment of the crystal directions with prescribed coordinate axes of the SEM. The possibility of applying crystal symmetry and the use of a genetic algorithm for optimization ensure the determination of the global optimal alignment even in severely constrained conditions. In cases where ideal alignment is not obtainable, weighting factors can be applied to conflicting alignment objectives. Two application examples, the alignment of two crystal directions for a lamella lift out for nano-mechanical testing and the rotation of an orientation-related dual-phase microstructure into a standard projection, demonstrate the functionality and workflow of the freely available open-source program crystalAligner.
Room-temperature X-ray response of cadmium–zinc–telluride pixel detectors grown by the vertical Bridgman technique
Authors: Abbene Leonardo , Principato Fabio , Gerardi Gaetano , Buttacavoli Antonino , Cascio Donato , Bettelli Manuele , Amadè Nicola Sarzi , Seller Paul , Veale Matthew C. , Fox Oliver , Sawhney Kawal , Zanettini Silvia , Tomarchio Elio , Zappettini Andrea
Published: January 2020

In this work, the spectroscopic performances of new cadmium–zinc–telluride (CZT) pixel detectors recently developed at IMEM-CNR of Parma (Italy) are presented. Sub-millimetre arrays with pixel pitch less than 500 µm, based on boron oxide encapsulated vertical Bridgman grown CZT crystals, were fabricated. Excellent room-temperature performance characterizes the detectors even at high-bias-voltage operation (9000 V cm−1), with energy resolutions (FWHM) of 4% (0.9 keV), 1.7% (1 keV) and 1.3% (1.6 keV) at 22.1, 59.5 and 122.1 keV, respectively. Charge-sharing investigations were performed with both uncollimated and collimated synchrotron X-ray beams with particular attention to the mitigation of the charge losses at the inter-pixel gap region. High-rate measurements demonstrated the absence of high-flux radiation-induced polarization phenomena up to 2 × 106 photons mm−2 s−1. These activities are in the framework of an international collaboration on the development of energy-resolved photon-counting systems for high-flux energy-resolved X-ray imaging.
The effect of service innovation on customer behavioral intention in the Taiwanese insurance sector: the role of word of mouth and corporate social responsibility
Authors: Chang Jui-I , Lee Chen-Ying
Published: January 2020

Purpose

Service innovation has been one of the essential elements to meet the customers’ requirements, but few studies discuss service innovation regarding behavioral intention in the insurance industry. This paper aims to investigate the effects of service innovation on customer behavioral intention and examines the role of word-of-mouth (WOM) and corporate social responsibility (CSR).

Design/methodology/approach

This paper used a survey to assess consumer behavioral intention regarding service innovation activities from life insurance. Questionnaires were administered to consumers who have purchased life insurance in Taiwan and the survey questions were tested through factor analysis. An analysis of multiple and hierarchical regression was performed to test the hypotheses.

Findings

The empirical results demonstrate that life insurance service innovation has a significantly positive influence on WOM and behavioral intention. Additionally, WOM has a partially mediating effect between service innovation and behavioral intention. Furthermore, the study indicates that CSR has a moderating effect on the relationship between service innovation and behavioral intentions.

Originality/value

Considering the uniqueness of this study in the context of Taiwan, the research draws on signaling theory as the framework to explore service innovation and the impact of social responsibility on consumer behavioral intentions in the Taiwanese insurance industry. Additionally, the results can be considered a service marketing strategy and are applicable to the financial service industry in some developing Asian countries
The determinants of bank insolvency risk: evidence from Finland
Authors: Huhtilainen Matias
Published: January 2020

Purpose

This paper aims to contribute to the literature on the determinants of bank-specific insolvency risk.

Design/methodology/approach

By applying a dynamic two-step System GMM estimator on a novel, representative panel of 339 Finnish unlisted cooperative and savings banks over the period 2002-2018.

Findings

This study contributes to the literature on the determinants of bank-specific insolvency risk by applying a dynamic two-step System GMM estimator on a novel, representative panel of 339 Finnish unlisted cooperative and savings banks over the period 2002-2018. The key findings suggest that Finnish banks have become less fragile under the renewed EU banking regulation. In particular, the CRD IV has affected banks’ equity levels. This study also captures the detrimental effect of cost inefficiency as well as a positive relationship between the income diversification and insolvency risk. A negative relationship between the GDP growth rate and the insolvency risk is also reported although results suggest that the effect is not immediate.

Originality/value

This result is discussed together with other macroeconomic factors. The consequent conclusion underlines the fundamental significance of overall macroeconomic dynamics. From the perspective of regulatory harmonization, more research is needed to address the level of homogeneity of macroeconomic dynamics between different geographical and cultural regions.
What’s done in the dark will be brought to the light: effects of influencer transparency on product efficacy and purchase intentions
Authors: Woodroof Parker J. , Howie Katharine M. , Syrdal Holly A. , VanMeter Rebecca
Published: January 2020

Purpose

The purpose of this paper is to examine the impact of the type of disclosure used by social media influencers on consumer evaluations of influencer transparency, product performance expectations and how those factors ultimately influence purchase intentions.

Design/methodology/approach

An experiment was conducted with 321 participants recruited from MTurk to test a moderated serial-mediation model.

Findings

The results indicate that when consumers become cognizant that an influencer’s branded promotional post may have been motivated by an underlying financial relationship, they evaluate the influencer as significantly less transparent if a more ambiguous disclosure is used relative to a clearer disclosure. Transparency perceptions of the influencer impact consumers’ perceptions of product efficacy as well as purchase intentions.

Originality/value

Social media influencers are rapidly emerging as a popular marketing tool for brand managers, but consumer response to this form of promotion is not well understood. To the best of the authors’ knowledge, this is the first study to investigate how the type of endorsement disclosure used by a social media influencer impacts consumer perception of influencer transparency, product efficacy and purchase intentions. Further, this research demonstrates the applicability of the persuasion knowledge model in the domain of influencer marketing.
Red cabbage anthocyanins content as a natural colorant for obtaining different color on wool fibers
Authors: Barani Hossein , Maleki Homa
Published: January 2020

Purpose

Finding blue colorants from natural sources is extremely difficult and, usually, the anthocyanin compounds are used for producing the blue color. This study aims to apply the Red Cabbage as a natural colorant to obtain different colors on wool yarn, as well as specify the optimum dyeing condition by response surface methodology for obtaining a blue color.

Design/methodology/approach

The effect of dyeing process parameters such as mordant concentration, dyeing time, pH of dyeing bath and dyeing temperature examined in the color characteristics of the dyed wool samples.

Findings

The obtained results indicated that the diverse colors achieve by varying the dyeing process parameters, which is in the range of 26° up to 271°. The non-mordanted dyed wool samples showed a red and red brownish color (Hue angle = 26° up to 70°), and the mordanted dyed wool samples showed a blue and blue-greenish color (Hue angle = 230° up to 271°). The obtained blue color with the optimized dyeing condition presented a considerable good wash and lightfastness.

Originality/value

This study provides a promising application of Red Cabbage as a natural colorant for obtaining different colors by varying the dyeing process parameters such as pH and stannous ion concentrations. The stannous ions yielded a co-pigmentation and presented a blue color on wool fibers, which is extremely difficult to obtain with natural colorant.
Single bath dyeing of modified nylon/cotton blended fabrics using direct/acid dyes
Authors: Iqbal Kashif , Javid Amjed , Rehman Abdur , Rehman Aisha , Ashraf Munir , Abid Hafiz Affan
Published: January 2020

Purpose

This study aims to deal with the dyeing of nylon-/cotton-blended fabric in one bath using direct and acid dyes.

Design/methodology/approach

The cellulose in cotton/nylon-blended fabric was chemically modified using 3-chloro-2-hydroxypropyl tri-methyl ammonium chloride (CHPTAC) as cationizing agent to impart positive charge on the cellulose. The modified and unmodified blended fabrics were dyed in a single bath with direct and acid dyes under various concentrations of 0.5, 1, 2, 4 and 6 per cent on the weight of fabric by exhaust method. The dyeing of modified and unmodified fabrics was characterized through the properties such as K/S and colorfastness to washing, rubbing and light.

Findings

The modified fabric exhibited higher color yield, comparable rubbing fastness and good washing fastness.

Originality/value

The dye uptake was maximum in a single-bath dyeing process of nylon-/cotton-blended fabrics without electrolyte addition, which minimizes the impact of dyes on environment.
Substrate quality and not dominant plant community determines the vertical distribution and C assimilation of enchytraeids in peatlands
Authors: Briones María Jesús Iglesias , Carrera Noela , Huang Jinhua , Barreal Maria Esther , Schmelz Rüdiger Maria , Garnett Mark H.
Published: January 2020

Peatlands are important carbon (C) stores as a result of acidity, waterlogging conditions and low temperatures slowing decomposition rates. However, climate change is predicted to bring not only changes in abiotic conditions but also the replacement of peat‐forming vegetation, such asSphagnummosses, with vascular plants. In these systems, enchytraeid worms represent the dominant mesofaunal group, and previous climate change manipulations have shown that their abundances and vertical distribution are strongly influenced by temperature and moisture gradients, with important implications for C cycling. Therefore, determining their behavioural responses to changes in both abiotic and biotic factors is crucial to quantify their contribution to decomposition processes.

We investigated the importance of vertical edaphic gradients (soil moisture and labile C) on enchytraeids total numbers, vertical distribution and feeding activities by inverting intact soil cores and hence, reversing both substrate quality but leaving the microclimatic gradients intact. This manipulative experiment was set up in two different peatland areas, one dominated by heather (Erica mackaiana) and another by mosses (Sphagnumsp.) to determine the influence of different plant functional growth forms on these responses.

Our results showed that most enchytraeid species were ‘stayers’ (i.e. in the ‘Upturned cores’, they remained in the same layer where they are ‘Normally’ located), and hence, their vertical distribution was more dependent on substrate quality than a change in microclimate. This response was more evident under drier conditions (i.e. the highest locations of the height gradient at the heather site) than at the wettest locations (i.e. the bottom of the slope and under mosses) due to more pronounced vertical gradients in substrate quality. Furthermore, radiocarbon measurements on enchytraeid tissues showed that to avoid competition among the growing populations for the limited labile resources present in the top layers, enchytraeids selected older C sources.

These findings indicate that future climate change scenarios will not only bring important changes in the abiotic conditions (temperature and moisture) and biotic properties of peatlands (both vegetation composition and below‐ground soil biota community structure and vertical distribution) but also alterations in the feeding preferences of key decomposers that could result in the mobilization of previously unavailable C pools.

A freePlain Language Summarycan be found within the Supporting Information of this article.
Measuring Firms’ Market Orientation Using Textual Analysis of 10‐K Filings
Authors: Andreou Panayiotis C. , Harris Terry , Philip Dennis
Published: January 2020

Market‐oriented firms are committed to understanding their customers’ evolving expectations and meeting their needs, while outwitting competitors, to achieve a sustainable competitive advantage and improve performance. This paper develops a measure for market orientation based on textual analysis of 10‐K filings. It utilizes a bag‐of‐words method to identify relevant information from the management's disclosure that underpins the corporate traits measured by the MKTOR scale, a renowned survey instrument for measuring market orientation. Unlike previous studies that rely extensively on small‐scale survey data to estimate market orientation, this novel method leverages instead on the use of big public archival data. We empirically establish strong construct validity for the measures of market orientation and its components, namely customer orientation and competitor orientation. Furthermore, our analyses demonstrate that firms’ performance is positively affected by market orientation and that this relationship is more pronounced in competitive environments. We contribute to the literature by developing an elegant measure of market orientation, which allows for conducting large‐scale longitudinal analyses of its antecedents and consequences.
Child outcomes after amnioinfusion compared with no intervention in women with second‐trimester rupture of membranes: a long‐term follow‐up study of the PROMEXIL‐III trial
Authors: de Ruigh AA , Simons NE , van 't Hooft J , van Teeffelen AS , Duijnhoven RG , van Wassenaer‐Leemhuis AG , Aarnoudse‐Moens C , van de Beek C , Oepkes D , Haak MC , Woiski M , Porath MM , Derks JB , van Kempen LEM , Roseboom TJ , Mol BW , Pajkrt E
Published: January 2020

Objective

To assess the effect of transabdominal amnioinfusion or no intervention on long‐term outcomes in children born after second‐trimester prelabour rupture of the membranes (PROM between 16+0/7–24+0/7 weeks) and oligohydramnios.

Population

Follow up of infants of women who participated in the randomised controlled trial: PPROMEXIL‐III (NTR3492).

Methods

Surviving infants were invited for neurodevelopmental assessment up to 5 years of corrected age using a Bayley Scales of Infant and Toddler Development or a Wechsler Preschool and Primary Scale of Intelligence. Parents were asked to complete several questionnaires.

Main outcome measures

Neurodevelopmental outcomes were measured. Mild delay was defined as −1 standard deviation (SD), severe delay as −2 SD. Healthy long‐term survival was defined as survival without neurodevelopmental delay or respiratory problems.

Results

In the amnioinfusion group, 18/28 children (64%) died versus 21/28 (75%) in the no intervention group (relative risk 0.86; 95% confidence interval [CI] 0.60–1.22). Follow‐up data were obtained from 14/17 (82%) children (10 amnioinfusion, 4 no intervention). In both groups, 2/28 (7.1%) had a mild neurodevelopmental delay. No severe delay was seen. Healthy long‐term survival occurred in 5/28 children (17.9%) after amnioinfusion versus 2/28 (7.1%) after no intervention (odds ratio 2.50; 95% CI 0.53–11.83). When analysing data for all assessed survivors, 10/14 (71.4%) survived without mild neurodevelopmental delay and 7/14 (50%) were classified healthy long‐term survivor.

Conclusions

In this small sample of women suffering second‐trimester PROM and oligohydramnios, amnioinfusion did not improve long‐term outcomes. Overall, 71% of survivors had no neurodevelopmental delay.

Tweetable abstract

Healthy long‐term survival was comparable for children born after second‐trimester PROM and treatment with amnioinfusion or no intervention.
In‐group solidarity or out‐group hostility in response to terrorism in France? Evidence from a regression discontinuity design
Authors: VAN HAUWAERT STEVEN M. , HUBER ROBERT A.
Published: January 2020

Conventional wisdom holds that terrorism has a wide‐ranging impact on a polity. At the same time, a complementary, yet less extensive body of research discusses the impact of terrorism on the crux of representative democracy, namely its citizens. In contribution to that literature, and to further explore how external shocks affect public opinions, we propose a two‐dimensional analytical framework to examine the effects of the November 2015 terrorist events in Paris and Saint Denis. Drawing from extant scholarship, we argue that we can expect both in‐group solidarity and out‐group hostility to increase in direct response to these events. This study relies on a regression discontinuity design to analyse a representative survey (DREES) that was in the field at the time of the events. Findings are two‐fold. First, and perhaps surprisingly, we find no conclusive evidence of increasing out‐group hostilities as a direct consequence of the terrorist events. Second, we find a definite strengthening of in‐group solidarity indicators following the events. This not only confirms that citizens adjust their opinions in response to environmental stimuli, but also highlights the democratic resilience of citizens, particularly when faced with a collective threat. Altogether, these findings add to our understanding of why and how individual behaviour changes in light of exogenous shocks.
The Downward Spiral: Socioeconomic Causes and Consequences of Alcohol Dependence among Men in Late Young Adulthood, and Relations to Racial/Ethnic Disparities
Authors: Zemore Sarah E. , Lui Camillia , Mulia Nina
Published: January 2020

Background

While young adults are generally at highest risk for alcohol problems, not all age out of problem drinking. Evidence suggests that Blacks and Latinos age out more slowly than Whites, particularly among men. Targeting men, we investigated whether differences in lifecourse SES might explain racial/ethnic disparities in alcohol dependence in late young adulthood, along with how experiencing alcohol dependence at that life stage relates to subsequent SES.

Methods

We used longitudinal, national data to (i) describe racial/ethnic disparities in late young adult alcohol dependence criteria (LYADC), (ii) examine whether income trajectory in early young adulthood contributes to these racial/ethnic disparities, and (iii) test whether LYADC reciprocally predicts income trajectory in early midlife. Data were from the 1979 National Longitudinal Survey of Youth (N = 3,993), which measured LYADC in 1994 (mean age = 33). Income trajectory classes were derived for early young adulthood (mean ages = 21 to 31) and, separately, early midlife (mean ages = 35 to 45). Analyses included negative binomial regressions and multinomial regressions.

Results

Both Black and US‐born Latino men reported more LYADC than White men. Further, membership in the persistently low and slow increase (vs. stable middle) early young adult income trajectory classes was associated with more LYADC. Multivariate analyses suggested that Black–White disparities in LYADC were explained by early young adult income trajectories, whereas Latino–White disparities in the same were explained by both early young adult income trajectories and early education. In controlled models, more LYADC predicted a higher likelihood of membership in the persistently low (vs. stable middle) income trajectory class in early midlife.

Conclusions

This study found that poorer SES in early adulthood contributes to alcohol dependence, which reciprocally contributes to poorer SES in early midlife. This cycle appears particularly likely to affect Black and US‐born Latino men. Results underline the need to address socioeconomic factors in addressing racial/ethnic disparities in alcohol problems.
Brief interventions targeting long‐term benzodiazepine and Z‐drug use in primary care: a systematic review and meta‐analysis
Authors: Lynch Tom , Ryan Cristín , Hughes Carmel M. , Presseau Justin , van Allen Zachary M. , Bradley Colin P. , Cadogan Cathal A.
Published: January 2020

Aims

To assess the effectiveness of brief interventions in primary care aimed at reducing or discontinuing long‐term benzodiazepine/Z‐drug (BZRA) use.

Method

Systematic review of randomized controlled trials of brief interventions in primary care settings aimed at reducing or discontinuing long‐term BZRA use in adults taking BZRAs for ≥ 3 months. Four electronic databases were searched: PubMed, EMBASE, PsycINFO and CENTRAL. The primary outcome was BZRA use, classified as discontinuation or reduction by ≥ 25%. The Theoretical Domains Framework (TDF) was used to retrospectively code behavioural determinants targeted by the interventions. The Behaviour Change Technique (BCT) Taxonomy was used to identify the interventions’ active components. Study‐specific estimates were pooled, where appropriate, to yield summary risk ratios (RRs) and 95% confidence intervals (CIs). Pearson's correlations were used to determine the relationship between intervention effect size and the results of both the TDF and BCT coding.

Results

Eight studies were included (n = 2071 patients). Compared with usual care, intervention patients were more likely to have discontinued BZRA use at 6 months (eight studies, RR = 2.73, 95% CI = 1.84–4.06) and 12 months post‐intervention (two studies, RR = 3.41, 95% CI = 2.22–5.25). TDF domains ‘knowledge’, ‘memory, attention and decision processes’, ‘environmental context and resources’ and ‘social influences’ were identified as having been included in every intervention. Commonly identified BCTs included ‘information about health consequences’, ‘credible source’ and ‘adding objects to the environment’. There was no detectable relationship between effect size and the results of either the TDF or BCT coding.

Conclusion

Brief interventions delivered in primary care are more effective than usual care in reducing and discontinuing long‐term benzodiazepine/Z‐drug use.
The influence of irrigation solutions in the inorganic and organic radicular dentine composition
Authors: Barón Marta , Morales Victoria , Fuentes Mª Victoria , Linares María , Escribano Nuria , Ceballos Laura
Published: January 2020

The aim of this study was to analyse changes in radicular dentine composition after different irrigation regimes using attenuated total reflectance Fourier‐transform infrared spectroscopy (ATR‐FTIR). Dentine slices from human single‐root teeth were immersed in: (i) 5.25% sodium hypochlorite (NaOCl) for 1, 5 and 20 min; (ii) 17% EDTA for 1 min; and (iii) 5.25% NaOCl for 20 min, and 17% EDTA and 5.25% NaOCl, both for 1 min. Carbonate/mineral, Amide I/mineral and Amide III/CH2 ratios were determined using ATR‐FTIR before and after immersion in the irrigation solutions tested. Results showed that 5.25% NaOCl significantly decreased carbonate/mineral, Amide I/mineral and Amide III/CH2 ratios (P < 0.05). Application of 17% EDTA produced no change in carbonate/mineral ratio (P = 0.120), while an increase in Amide I/mineral in apical third (P = 0.002) and Amide III/CH2 (P < 0.001) was observed. The combination of NaOCl, EDTA and NaOCl increased carbonate/mineral ratio in coronal third (P = 0.037), and Amide I/mineral (P = 0.003) and Amide III/CH2 (P = 0.001) ratios. In conclusion, irrigation solutions tested significantly affected radicular dentine composition.
Vulvar quality of life index (VQLI) – A simple tool to measure quality of life in patients with vulvar disease
Authors: Saunderson Rebecca Bronwyn , Harris Victoria , Yeh Rudy , Mallitt Kylie‐Ann , Fischer Gayle
Published: January 2020

Background/Objectives

Vulvar disease leads to significant disease burden and reduced quality of life (QOL). However, vulvar disease‐specific instruments to measure QOL are lacking. We developed the Vulvar Quality of Life Index (VQLI) to comprehensively and reproducibly assess symptomatic, psychosexual and physical aspects of vulvar disease.

Methods

The VQLI was inferred from a review of the literature regarding QOL of vulvar disease, and responses from a cohort of patients attending specialist clinics. Seven domains and a 15‐item questionnaire were developed. This was tested and optimised prior to validation on 248 women, using a control group as a baseline. The VQLI was further tested on 157 women, and the total VQLI score was compared to a self‐determined Likert global score on how vulvar disease had impacted their overall health.

Results

The VQLI had excellent internal consistency (Cronbach’s alpha, 0.93), and test–retest reliability showed that 9/15 questions had a substantial weighted kappa value of 0.5 or above, with good intraclass correlation coefficient (0.88; CI 0.8–0.93). Spearman correlations were consistently positive. Further testing on 157 women demonstrated a significant relationship between the total VQLI score and the effect of vulvar disease on overall health, with high levels of the impact of vulvar disease on overall health associated with high total VQLI score (P < 0.001).

Conclusions

The VQLI is a validated, fast and reliable tool to measure the global impact of vulvar disease on QOL and can be used to monitor response to treatment or in a research setting.
Hemidiaphragmatic paralysis following ultrasound‐guided anterior vs. posterior suprascapular nerve block: a double‐blind, randomised control trial
Authors: Ferré F. , Pommier M. , Laumonerie P. , Ferrier A. , Menut R. , Bosch L. , Balech V. , Bonnevialle N. , Minville V.
Published: January 2020

Interscalene brachial plexus block provides analgesia for shoulder surgery but is associated with hemidiaphragmatic paralysis. Before considering a combined suprascapular and axillary nerve block as an alternative to interscalene brachial plexus block, evaluation of the incidence of diaphragmatic dysfunction according to the approach to the suprascapular nerve is necessary. We randomly allocated 84 patients undergoing arthroscopic shoulder surgery to an anterior or a posterior approach to the suprascapular nerve block combined with an axillary nerve block using 10 ml ropivacaine 0.375% for each nerve. The primary outcome was the incidence of hemidiaphragmatic paralysis diagnosed by ultrasound. Secondary outcomes included: characterisation of the hemidiaphragmatic paralysis over time; numeric rating scale pain scores; oral morphine equivalent consumption; and patient satisfaction. The incidence of hemidiaphragmatic paralysis was 40% (n = 17) vs. 2% (n = 1) in the anterior and posterior groups, respectively (p < 0.001). In one third of patients with hemidiaphragmatic paralysis, it persisted beyond the eighth hour. The median (interquartile range [range]) oral morphine equivalent consumption was significantly higher in the posterior approach when compared with the anterior approach, whether in the recovery area (20 [5–31 (0–60)] mg vs. 7.5 [0–14 (0–52)] mg, respectively; p = 0.004) or during the first 24 h (82 [61–127 (12–360) mg] vs. 58 [30–86 (0–160)] mg, respectively; p = 0.01). Patient satisfaction was comparable between groups (p = 0.6). Compared with the anterior approach, diaphragmatic function is best preserved with the posterior needle approach to the suprascapular nerve block.
T‐Wave Alternans in Nonpathological Preterm Infants
Authors: Marcantoni Ilaria , Sbrollini Agnese , Agostinelli Gloria , Surace Francesca Chiara , Colaneri Massimo , Morettini Micaela , Pozzi Marco , Burattini Laura
Published: January 2020

Background

Sudden infant death syndrome is more frequent in preterm infants (PTI) than term infants and may be due to cardiac repolarization instability, which may manifest as T‐wave alternans (TWA) on the electrocardiogram (ECG). Therefore, the aim of the present work was to analyze TWA in nonpathological PTI and to open an issue on its physiological interpretation.

Methods

Clinical population consisted of ten nonpathological PTI (gestational age ranging from 29 to 34 weeks; birth weight ranging from 0.84 to 2.10 kg) from whom ECG recordings were obtained (“Preterm infant cardio‐respiratory signals database” by Physionet). TWA was identified through the heart‐rate adapting match filter method and characterized in terms of mean amplitude values (TWAA). TWA correlation with several other clinical and ECG features, among which gestational age–birth weight ratio, RR interval, heart‐rate variability, and QT interval, was also performed.

Results

TWA was variable among infants (TWAA = 26 ± 11 µV). Significant correlations were found between TWAA versus birth weight (ρ = −0.72, p = .02), TWAA versus gestational age–birth weight ratio (ρ = 0.76, p = .02) and TWAA versus heart‐rate variability (ρ = −0.71, p = .02).

Conclusions

Our preliminary retrospective study suggests that nonpathological PTI show TWA of few tens of µV, the interpretation of which is still an open issue but could indicate a condition of cardiac risk possibly related to the low development status of the infant. Further investigations are needed to solve this issue.
Nutritional physiology of the Santa Ana sucker (Catostomus santaanae): A threatened freshwater fish endemic to Southern California
Authors: Nguyen‐Phuc Bao‐Quang , Demetropoulos Carl , Stewart Sam , Saffarinia Parsa , Bastian Salgado José , Hawkins Elin , Frederick Alyssa R. , German Donovan P.
Published: January 2020

The herbivorous fish Catostomus santaanae is a federally “threatened” freshwater fish species endemic to southern California and is the centre of legal battles over water use. Because little is known about the nutritional ecology of this species, we investigated the nutritional physiology of C. santaanae to better understand their dietary and energetic needs with the goal of generating data useful in conservation efforts. Individuals of C. santaanae were raised for six weeks on an algal diet in the laboratory. They digested approximately 45%, 55% and 80% of protein, soluble carbohydrate and lipid, respectively, from the algal diet. Their metabolic rate (~0.0024 mg O2 min−1 g−1) suggested they would need to eat more than their body mass per day of an algal diet to thrive. Digestive enzyme activities of the laboratory‐reared and wild‐caught fish showed patterns typical of a “plug‐flow reactor” gut with high intake and rapid gut transit. However, lipase activities remained elevated throughout the gut, and this result, coupled with the lipid digestibility data, and evidence of feeding selectivity on specific diatom taxa in nature, suggests that C. santaanae targets diatoms as it grazes and that diatom lipid may be crucial to their survival. Our data set provides parameters that can be used in conservation modelling efforts towards habitat restoration.
The clinical and pathological panoply of systemic mastocytosis
Authors: Radia Deepti H. , Green Anna , Oni Clare , Moonim Mufaddal
Published: January 2020

Mastocytosis is a rare disease with varied presentation, myriad symptomatology and variable prognosis. Most patients present with cutaneous disease and mediator‐related symptomatology with a small subset having systemic disease (systemic mastocytosis, SM). A subset of the latter develops synchronous or metachronous haematologic neoplasms (SM‐AHN), most commonly chronic myelomonocytic leukaemia (CMML). Advanced systemic mastocytosis (ASM) is seen in a relatively small number of patients and is usually associated with organ dysfunction, and may present with hepatosplenomegaly, lymphadenopathy and ascites with progression to leukaemic transformation (mast cell leukaemia/acute myeloid leukaemia) occurring in a few patients. This paper discusses the clinical and pathologic features of the entire spectrum of SM in adults.
Use of ixazomib, lenalidomide and dexamethasone in patients with relapsed amyloid light‐chain amyloidosis
Authors: Cohen Oliver C. , Sharpley Faye , Gillmore Julian D. , Lachmann Helen J. , Sachchithanantham Sajitha , Mahmood Shameem , Fontana Marianna , Whelan Carol J. , Martinez‐Naharro Ana , Kyriakou Charalampia , Rabin Neil , Popat Rakesh , Yong Kwee , Cheesman Simon , Shah Raakhee , Hawkins Philip N. , Wechalekar Ashutosh D.
Published: January 2020

With improving outcomes in amyloid light‐chain (AL) amyloidosis, there is a need to study novel agents in this setting. We report outcomes of 40 patients with relapsed AL amyloidosis treated with ixazomib + lenalidomide + dexamethasone (IRd). Haematological responses were assessed on an intention‐to‐treat basis at three months: complete response (CR) – 8 (20·5%), very good partial response (VGPR) – 8 (20·5%), partial response (PR) – 7 (17·9%) and no response (NR) – 16 (41·0%). One patient had missing data. Six patients subsequently improved response. Best responses were: CR – 10 (25·6%), VGPR – 8 (20·5%), PR – 7 (17·9%), NR – 14 (35·9%). Cardiac and renal organ responses occurred in 5·6% and 13·3% respectively. Median progession‐free survival (PFS) was 17·0 months (95% CI 7·3–20·7 months), improving to 28·8 months (95% CI 20·6–37·0 months) in those achieving CR/VGPR. Median overall survival was 29·1 months (95% CI 24–33 months). Serious adverse events were seen in 14 (35·0%) patients inclusive of 15 admissions due to: infection (6/15, 40·0%), fluid overload (5/15, 33·3%), cardiac arrhythmia (2/15, 13·3%), renal dysfunction (1/15, 6·6%) and anaemia (1/15, 6·6%). In summary, IRd is an oral treatment option with a manageable toxicity profile leading to deep responses in 47% of patients with relapsed AL amyloidosis.
Urothelial cancer harbours EGFR and HER2 amplifications and exon 20 insertions
Authors: Madison Russell W. , Gupta Sumati V. , Elamin Yasir Y. , Lin Douglas I. , Pal Sumanta K. , Necchi Andrea , Miller Vincent A. , Ross Jeffrey S. , Chung Jon H. , Alexander Brian M. , Schrock Alexa B. , Heymach John V. , Reddy Prasanth , Ali Siraj M.
Published: January 2020

Objective

To review the genomic landscape of advanced urothelial carcinoma (UC) to assess the frequencies of EGFR and ERBB2 (HER2) alterations.

Materials and Methods

Tumour specimens from 3753 patients with advanced UC were assayed with hybrid capture‐based comprehensive genomic profiling of 180–395 genes. Tumour mutational burden (TMB) was assessed on 0.8 or 1.1 Mb of DNA, and is reported as mutations per megabase.

Results

In 3753 cases of UC, EGFR alterations were detected in 4.1% (154) and were most commonly amplifications (64%; 99/154), while exon 20 insertions (EGFRexon20ins) were the second most common alteration (18%; 27/154). Alterations in ERBB2 were observed in 15% (552/3753) of cases and, similarly, ERBB2 amplification was the most commonly observed alteration (278/552; 50%); ERBB2exon20ins occurred in 3.6% (20/552) of cases. EGFRexon20ins and ERBB2exon20ins occurred in younger patients (median age 62 vs 69 years, P = 2.6E‐2 and 60 vs 68 years, P = 7.8E‐4), and these cases had significantly lower TMB (median 3.6 vs 7.2, P = 2.7E‐4 and 2.5 vs 10, P = 1.2E‐7) and less frequent TP53 alterations (3.7% vs 83%, P = 4.3E‐14 and 20% vs 68%, P = 9.8E‐4) compared to cases with other EGFR or ERBB2 alterations.

Conclusion

EGFR and ERBB2 alterations occur in 4% and 15% of UC, respectively. EGFRexon20ins and ERBB2exon20ins were present in 0.7% and 0.5% of UC overall and collectively define a small, but distinct, subset of UC with infrequent co‐occurrence of other drivers and low TMB. Given recent promising clinical studies of inhibitors with activity against exon 20 insertions in non‐small cell lung cancer, consideration should be given to developing a trial inclusive of patients with UC harbouring these alterations.
Does greater income inequality cause increased work hours? New evidence from high income economies
Authors: Alexiou Constantinos , Kartiyasa Adimulya
Published: January 2020

We explore the extent to which individual's allocation of time between labour and leisure is affected by the consumption standards of the rich. Utilizing a panel data methodology and panel Granger causality tests we investigate the relationship between income inequality and work hours for a cluster of 24 high‐income OECD countries over the period 1990–2015. Four alternative measures of income inequality are considered. We find that greater income inequality is associated with longer work hours indicating stronger concern for conspicuous consumption rather than conspicuous leisure. Even though the resulting estimates lend support to the theoretical framework on consumption emulation, the generated evidence also appears to be in line with a Duesenberry's and Frank's expenditure cascading approach. The ambiguity however arising from the Granger Causality tests appears to lead – to a certain extent – to different conclusions about the direction of causality or whether a causal relationship does even exist. It is therefore imperative that caution should be exercised when interpreting the direction of the causal dimension.
Age and provenance of upland gravels in Missouri, USA, and their relationship to Early Pleistocene glaciation
Authors: Rovey Charles W. , Spoering Grant
Published: January 2020

The age and origin of the Grover Gravel, which is preserved on stable uplands in St. Louis County, Missouri, USA, and similar gravels along the Mississippi River bluffs farther south, have been controversial for over a century. These gravels have some features consistent with a glacial origin but lack obvious erratics such as igneous rock fragments. New observations, however, show that the earliest tills within the Mississippi basin nearly lack such constituents as well, and that the Grover Gravel is a Pleistocene deposit derived from such a till. A Mississippi River terrace deposit in St. Louis County also includes typical clasts of this till and formed between 2.0–1.8 Ma, based on various dating methods. This deposit may correspond to a pulse of glacial meltwater recorded within sediment near the mouth of the Mississippi River and represent outwash from a previously unrecognized glaciation within the US midcontinent. The Mounds Gravel (or Upland Complex) is present farther south around the perimeter of the Mississippi Embayment and contains the same distinct clasts as the gravels in St. Louis County. Given that the age of the Mounds is <~3 Ma based on cosmogenic‐nuclide ratios, the southern gravel could be the same age as the gravel terrace in St. Louis County. If so, these gravels could mark a geomorphic transition to glacial‐dominated sedimentation farther south in and around the Gulf of Mexico. Regardless, all the upland gravels have insignificant amounts of zircon from provinces west of Hudson Bay. Therefore, detrital zircon provenance does not support a recent hypothesis that the Mounds (Upland Complex) was deposited by a giant Mississippi River with a drainage basin extending across broad areas west of Hudson Bay.
3D structure of the transporter ABCG2—What's new?
Authors: Eckenstaler Robert , Benndorf Ralf A.
Published: January 2020

ABCG2 belongs to the ABC transporter superfamily and functions as a poly‐specific efflux pump. As it can transport a broad spectrum of substrates out of cells, ABCG2 is thought to alter the pharmacokinetics of drugs applied to treat certain diseases. Especially, its potential to induce resistance to chemotherapy is currently the object of intense research. To foster understanding of mechanisms relevant for substrate recognition and selection of ABCG2 substrates and to finally develop selective therapeutic modulators (e.g. inhibitors) of ABCG2 transport activity, it is important to further explore the precise 3D structure of the transporter. While efforts to elucidate the three‐dimensional structure of ABCG2 using X‐ray crystal structure analysis have not been successful so far, high‐resolution cryo‐electron microscopy‐based investigations have revealed exciting new insights into the structure and function of the transporter. In this review, we will focus on these seminal publications to summarize the current understanding of tertiary and quaternary structure, homodimerization or oligomerization, and functions of the ABCG2 transporter protein.