bluuebunny/crossref_metadata_2025 huggingface dataset:
“F*ck off Google”: protest against Google Campus Berlin
Authors: Fritze Martin Paul , Gänser-Stickler Gertraud Maria , Türk Sarah , Zhao Yingshuai
Published: October 2019

Theoretical basis

This case applies a stakeholder analysis to examine the trade-offs between the firm’s strategy and the interests of different stakeholder groups. A PESTEL analysis supports an evaluation of the firm’s situation. Consumer behavior theories on psychological ownership and territoriality offer a framework for analyzing the conflicts that arise from the inhabitants’ protests.

Research methodology

This case relies on secondary sources, including news reports, social media sites and company websites. This case has been classroom tested with undergraduate students in a strategic management course in January 2019 at the University of Cologne, Germany.

Case overview/synopsis

In November 2016, Google announced its intentions to rent a building in the Kreuzberg district of Berlin to open a Google Campus, a business incubator for tech start-ups that would offer entrepreneurs support, workshops and access to networks. Following the announcement, dissatisfied local communities organized protests, in which leaders complained that “It is extremely violent and arrogant of this mega-corporation, whose business model is based on mass surveillance and which speculates like crazy, to set up shop here” (Business Times, 2018). Berlin’s Government supported the Google Campus plan; inhabitants rejected it with fierce and persistent protests. In face of this challenge, was it still possible for Google to continue its plans in Berlin?

Complexity academic level

This case qualifies for use in strategic management classes at undergraduate and MBA levels. Its focus aligns well with stakeholder analyses, PESTEL analyses and business strategy. In addition, for courses on organizational communications or public relations, this case provides a way to explore the relationship between Google and its stakeholders, especially protesters, in detail. Moreover, this case is well suited for consumer research and public policy courses (e.g., transformative consumer research) centered on discussions of territoriality.
The older person as a client, customer or service user?
Authors: Corlin Tinna Elfstrand , Kazemi Ali
Published: October 2019

Purpose

The purpose of this paper is to describe three different approaches to work in elderly care (i.e. professional, market-oriented and person-centred) and examine whether these theoretically derived approaches can be confirmed empirically. Additional aims were to examine the endorsement of these approaches and whether there were differences in the endorsement of these approaches in nursing home vs home care and municipality vs privately run care units.

Design/methodology/approach

Data were collected using a cross-sectional survey study of frontline care staff (n=1,342). Exploratory factor analysis was used to investigate the empirical validity of the proposed approaches to work in elderly care. A series of paired and independent samples t-tests were conducted to analyse mean differences between the proposed approaches to work.

Findings

A principal axis factoring analysis yielded three theoretically meaningful factors as proposed. These results indicated that the respondents were able to differentiate between three distinct but related approaches to work with older persons. The results also showed that the professional care approach was the highest endorsed and the market-oriented the lowest endorsed approach. No notable differences in approaches to work were observed in nursing home vs home care and municipality vs privately run care units.

Originality/value

This is the first study to examine multiple approaches to work in elderly care as previous research studies mainly have investigated the person-centred care approach. Current findings indicate that these approaches to work often coexist in various combinations and that the care staff adopts all these approaches but to varying degrees. The approaches differ in several important respects (e.g. legitimacy and view of the older person) and most likely affect the way care staff treats the older person and how the older person perceives their relationship with the care staff. Knowledge about these differences facilitates management of the care staff’s work situation and helps to improve the quality of care.
Low‐rank seismic denoising with optimal rank selection for hankel matrices
Authors: Wang Chong , Zhu Zhihui , Gu Hanming
Published: October 2019

Based on the fact that the Hankel matrix representing clean seismic data is low rank, low‐rank approximation methods have been widely utilized for removing noise from seismic data. A common strategy for real seismic data is to perform the low‐rank approximations for small local windows where the events can be approximately viewed as linear. This raises a fundamental question of selecting an optimal rank that best captures the number of events for each local window. Gavish and Donoho proposed a method to select the rank when the noise is independent and identically distributed. Gaussian matrix by analysing the statistical performance of the singular values of the Gaussian matrices. However, such statistical performance is not available for noisy Hankel matrices. In this paper, we adopt the same strategy and propose a rule that computes the number of singular values exceed the median singular value by a multiplicative factor. We suggest a multiplicative factor of 3 based on simulations which mimic the theories underlying Gavish and Donoho in the independent and identically distributed Gaussian setting. The proposed optimal rank selection rule can be incorporated into the classical low‐rank approximation method and many other recently developed methods such as those by shrinking the singular values. The low‐rank approximation methods with optimally selected rank rule can automatically suppress most of the noise while preserving the main features of the seismic data in each window. Experiments on both synthetic and field seismic data demonstrate the superior performance of the proposed rank selection rule for seismic data denoising.
Assessing restoration success by predicting time to recovery—But by which metric?
Authors: Rydgren Knut , Auestad Inger , Halvorsen Rune , Hamre Liv Norunn , Jongejans Eelke , Töpper Joachim P. , Sulavik Jan
Published: October 2019

Restoration of degraded ecosystems may take decades or even centuries. Accordingly, information about the current direction and speed of recovery provided by methods for predicting time to recovery may give important feedback to restoration schemes. While predictions of time to recovery have so far been based mostly upon change in species richness and other univariate predictors, the novel ordination‐regression based approach (ORBA) affords a multivariate approach based upon species compositional change.

We used species composition data from four alpine spoil heaps in western Norway, recorded at three time points, to predict time to recovery using ORBA. This approach uses distances between restored plots and reference plots along a successional gradient, represented by a vector in ordination space, to model linear or asymptotic relationships of compositional change as a function of time. Results from ORBA were compared with results from models of more generic univariate attributes, that is total cover, species richness and properties of the physical environment as functions of time.

ORBA predictions of time to species compositional recovery varied from less than 60 years with linear models to 115–212 years with asymptotic models. The long estimated time to recovery suggests that the restoration schemes adopted for these spoil heaps are likely to be suboptimal.

Much shorter time to recovery was predicted from some of the more generic univariate attributes, that is species richness and total cover, than from species composition. Given the current rates of recovery, most spoil heaps will reach reference levels for total cover and species richness within 50 years, whereas predictions indicate that 67–111 years are needed to restore levels of soil organic matter and pH.

Synthesis and applications. Species composition and soil conditions provide information of generally higher relevance for evaluation of ecosystem recovery processes than the most commonly used metric to assess restoration success, species richness. Species richness is decoupled from species compositional recovery, and likely to be a generally poor measure of restoration success. We therefore encourage further improvement of methods like the ordination‐regression based approach that use species compositional data to predict time to recovery.
Those Glass Chains that Bind You: How British Muslim Women Professionals Experience Career, Faith and Family
Authors: Arifeen Shehla R. , Gatrell Caroline
Published: October 2019

This paper contributes to gender and diversity research through proposing a new theoretical construct: glass chains. We develop ‘glass chains’ as a metaphor to illuminate how highly educated British Pakistani Muslim women professionals in the UK negotiate a fine balance between faith, family and personal ambition. Using a qualitative approach, we highlight tensions between religious and familial guidance within Islam, and workplace practices. Drawing upon the construct of ‘glass chains’, we articulate how 37 British Pakistani Muslim career women felt bound, by invisible glass chains, to the tenets of their faith. We show how the pull of glass chains obliged these women to resist certain career‐advancing opportunities. In so doing, we borrow from French philosopher Michel Foucault ideas about self‐oriented moral codes, engaging with his arguments that individuals may prioritize, over other obligations, the ties (or glass chains) which bind them to personal value sets in order that they may become ‘ethical selves’. While previous glass metaphors highlight barriers to female progression from external and structural angles, ‘glass chains’ are, by contrast, concerned with the potential for internal and personal constraints on women's ambitions. The metaphor ‘glass chains’ may be extended to enhance understanding of career constraints among other workers.
Healing architecture and psychiatric practice: (re)ordering work and space in an in‐patient ward in Denmark
Authors: Simonsen Thorben P. , Duff Cameron
Published: October 2019

Healing architecture is a defining feature of contemporary hospital design in many parts of the world, with psychiatric in‐patient facilities in Denmark at the forefront of this innovation. The approach rests on the contention that designed clinical spaces and the particular dispositions they express may promote patient recovery. Although the idea that health may be spatially mediated is well‐established, the means of this mediation are far from settled. This article contributes to this debate by analysing medical encounters in the context of a new purpose‐built psychiatric hospital opened in Slagelse, Denmark in late 2015 as an example of healing architecture for the region. Grounded in qualitative research conducted in two wards between 2016 and 2017, we explore the key material and social effects of the hospital's healing architecture, and the spaces and practices it enacts. Following the work of Michael Lynch, we consider both the designed ‘spatial order’ of the in‐patient wards and the ‘spatial orderings’ unfolding therein with a particular interest in how order is accomplished in psychiatric work. With much of the existing discussion of healing architectures focusing on their impacts on patient wellbeing, we consider how healing architectures may also be transforming psychiatric work.
The role of plan choice in health care utilization of high‐deductible plan enrollees
Authors: Abdus Salam
Published: October 2019

Objective

To study whether the negative association between enrollment in high‐deductible plans and health care utilization is driven by reverse moral hazard or favorable selection, by examining adults with and without a choice of plans.

Data Source

2011‐2016 Medical Expenditure Panel Survey Household Component data on nonelderly adults enrolled in employer‐sponsored insurance.

Study Design

Four types of plans were examined: high‐deductible health plans (HDHPs), consumer‐directed health plans (CDHPs), low‐deductible health plans (LDHPs), and no‐deductible health plans (NDHPs). Multivariate logistic regressions of various measures of health care utilization were conducted to estimate the differences in utilization across plan types among those who had a choice of plans and those who did not.

Principal Findings

Among adults with a choice of plans, HDHP enrollees had lower levels of utilization compared with those of the NDHP enrollees for any ambulatory visit, any specialist visit, and most preventive services. Among adults without any choice of plans, the differences between HDHP enrollees and NDHP enrollees were not statistically significant.

Conclusions

The differences between those with and without choice of plans in the relationship between HDHP enrollment and health care utilization might possibly be explained by favorable selection.
Discrimination in the United States: Experiences of Native Americans
Authors: Findling Mary G. , Casey Logan S. , Fryberg Stephanie A. , Hafner Steven , Blendon Robert J. , Benson John M. , Sayde Justin M. , Miller Carolyn
Published: October 2019

Objective

To examine reported racial discrimination and harassment against Native Americans, which broadly contribute to poor health outcomes.

Data Source and Study Design

Data come from a nationally representative, probability‐based telephone survey including 342 Native American and 902 white US adults, conducted January‐April 2017.

Methods

We calculated the percent of Native Americans reporting discrimination in several domains, including health care. We used logistic regression to compare the Native American‐white difference in odds of discrimination and conducted exploratory analyses among Native Americans only to examine variation by socioeconomic and geographic/neighborhood characteristics.

Principal Findings

More than one in five Native Americans (23 percent) reported experiencing discrimination in clinical encounters, while 15 percent avoided seeking health care for themselves or family members due to anticipated discrimination. A notable share of Native Americans also reported they or family members have experienced violence (38 percent) or have been threatened or harassed (34 percent). In adjusted models, Native Americans had higher odds than whites of reporting discrimination across several domains, including health care and interactions with the police/courts. In exploratory analyses, the association between geographic/neighborhood characteristics and discrimination among Native Americans was mixed.

Conclusions

Discrimination and harassment are widely reported by Native Americans across multiple domains of their lives, regardless of geographic or neighborhood context. Native Americans report major disparities compared to whites in fair treatment by institutions, particularly with health care and police/courts. Results suggest modern forms of discrimination and harassment against Native Americans are systemic and untreated problems.
Discrimination in the United States: Experiences of Asian Americans
Authors: McMurtry Caitlin L. , Findling Mary G. , Casey Logan S. , Blendon Robert J. , Benson John M. , Sayde Justin M. , Miller Carolyn
Published: October 2019

Objective

To examine experiences of racial discrimination among Asian Americans, which broadly contribute to poor health outcomes.

Data Source and Study Design

Data come from a nationally representative, probability‐based telephone survey, including 500 Asian and a comparison group of 902 white US adults, conducted January to April 2017.

Methods

We calculated the percent of Asian Americans reporting discrimination in several domains, including health care. We used logistic regression to compare the Asian‐white difference in odds of discrimination, and among Asians only to examine variation by geographic heritage group (South Asian versus East Asian) and gender.

Principal Findings

13 percent of Asians reported discrimination in healthcare encounters. At least one in four adults reported experiencing discrimination in employment (27 percent job applications, 25 percent equal pay/promotions); housing (25 percent); and interpersonal interactions (35 percent microaggressions, 32 percent racial slurs). In unadjusted models, East and South Asians were more likely than whites to report experiences of institutional discrimination, and South Asians were more likely than whites to report microaggressions. In adjusted models, Asians had higher odds than whites of reporting avoiding health care due to discrimination concerns and also when obtaining housing.

Conclusions

Asians in the United States experience discrimination interpersonally and across many institutional settings, including housing and health care. South Asians may be especially vulnerable to forms of institutional discrimination and microaggressions. These results illustrate a need for greater investigation into the unique experiences of Asian subgroups and greater protections for groups at higher risk of discrimination, within health care and beyond.
Methodology of the Discrimination in the United States survey
Authors: Benson John M. , Ben‐Porath Eran N. , Casey Logan S.
Published: October 2019

Objective

To describe survey methods used to examine reported experiences of discrimination against African Americans, Latinos, Asian Americans, Native Americans, women, and LGBTQ (lesbian, gay, bisexual, transgender, and queer) adults.

Data Source and Study Design

Data came from a nationally representative, probability‐based telephone survey of 3453 US adults, conducted January‐April 2017.

Methods

We examined the survey instrument, sampling design, and weighting of the survey, and present selected survey findings.

Principal Findings

Examining reported discrimination experienced by multiple groups in a telephone survey requires attention to details of sampling and weighting. In health care settings, 32 percent of African Americans reported discrimination, as did 23 percent of Native Americans, 20 percent of Latinos, 18 percent of women, 16 percent of LGBTQ adults, and 13 percent of Asian Americans. Also, 51 percent of LGBTQ adults, 42 percent of African Americans, and 38 percent of Native Americans reported identity‐based violence against themselves or family members; 57 percent of African Americans and 41 percent of women reported discrimination in pay or promotions; 50 percent of African Americans, 29 percent of Native Americans, and 27 percent of Latinos reported being discriminated against in interactions with police.

Conclusions

Even the small selection of results presented in this article as examples of survey measures show a pattern of substantial reported discrimination against all six groups studied.
A relict habitat became an isolated habitat in the Luoshan Nature Reserve from 1977 to 2017: Natural or man‐made disaster?
Authors: Ma Chao , Wang Xiabing , Zhang Wenhao
Published: October 2019

Understanding the ecological trends of the relict habitats in the Luoshan Nature Reserve (LNR) has an important role in the persistence of endangered species and the socio‐economic sustainability in the Ningxia section of the arid desertification belt in North China. Based on data from the Landsat Multispectral Scanner (MSS)/Thematic Mapper (TM)/Enhanced Thematic Mapper Plus (ETM+)/Operational Land Imager (OLI) sensors (from 1977 to 2017), the MODIS normalized difference vegetation index (NDVI) and net primary productivity (NPP) (from 2000 to 2017), the Shuttle Radar Topography Mission (SRTM) digital elevation model (DEM), annual average air temperature and precipitation (from 1977 to 2017), typical anthropogenic factors (population size, cultivated land and residential area) and natural ecological elements (MSS/TM/ETM+/OLI/MODIS NDVI and NPP) were quantitatively contrasted and analyzed for potential correlations. Some indicators of human activities, ecological processes and landscape geography have changed in the LNR. The proportion of residential area increased 3.09‐fold from 1977 to 2017. The population increased 34.30‐fold due to ecological immigration policy implementation in the Hongsipu immigration district. Before immigration, cultivated land increased, but after immigration, this land decreased quickly. Most of the dry‐cultivated land was converted through afforestation and a small part of the land was converted to irrigate cultivation land. We conclude that natural evolution led to the ecological relics, the isolated management to the LNR has objectively created an ecological island that will accelerate inbreeding depression and reduce biodiversity.
Rationale‐based selection of optimal operating strategies and gene dosage impact on recombinant protein production in Komagataella phaffii (Pichia pastoris)
Authors: Nieto‐Taype Miguel Angel , Garrigós‐Martínez Javier , Sánchez‐Farrando Marc , Valero Francisco , Garcia‐Ortega Xavier , Montesinos‐Seguí José Luis
Published: October 2019

Its features as a microbial and eukaryotic organism have turned Komagataella phaffii (Pichia pastoris) into an emerging cell factory for recombinant protein production (RPP). As a key step of the bioprocess development, this work aimed to demonstrate the importance of tailor designing the cultivation strategy according to the production kinetics of the cell factory. For this purpose, K. phaffii clones constitutively expressing (PGAP) Candida rugosa lipase 1 (Crl1) with different gene dosage were used as models in continuous and fed‐batch cultures. Production parameters were much greater with a multicopy clone (MCC) than with the single‐copy clone (SCC). Regarding production kinetics, the specific product generation rate (qP) increased linearly with increasing specific growth rate (µ) in SCC; by contrast, qP exhibited saturation in MCC. A transcriptional analysis in chemostat cultures suggested the presence of eventual post‐transcriptional bottlenecks in MCC. After the strain characterization, in order to fulfil overall development of the bioprocess, the performance of both clones was also evaluated in fed‐batch mode. Strikingly, different optimal strategies were determined for both models due to the different production kinetic patterns observed as a trade‐off for product titre, yields and productivity. The combined effect of gene dosage and adequate µ enables rational process development with a view to optimize K. phaffii RPP bioprocesses.
When are populations not connected like a circuit? Identifying biases in gene flow from coalescent times
Authors: Thomaz Andréa T. , He Qixin
Published: October 2019

Connectivity and movement patterns of populations are influenced by past and present environmental and biotic factors, which are reflected in genetic relatedness among populations. Methods that estimate the “commute time” between populations based on electrical resistance (i.e., isolation‐by‐resistance [IBR]) have been widely applied to either infer movement patterns directly from environmental factors or detect possible barriers to gene flow given empirical genetic relatedness. Yet, the commute time is only equivalent to the coalescence time between populations under symmetric migration with isotropic landscapes. Asymmetric gene flow is relatively common when populations are expanding, retreating, or with source‐sink dynamics. In a From the Cover paper in this issue of Molecular Ecology Resources, Lundgren and Ralph (Molecular Ecology Resources, 19, 2019) describe a Bayesian method to infer bidirectional gene flow rates and population sizes without the assumption of symmetry. The method shows great accuracy in connectivity estimations under symmetric, as well as asymmetric gene flow scenarios where resistance methods fail. However, computational complexity limits the method to a few populations, preventing its application to finescale environmental maps. Also, as a discrete‐deme static model, the inferred differences in gene flow rates are sensitive to population discretization and cannot be directly used to differentiate among processes (e.g., past expansion vs. current barrier). Here, we discuss scenarios where the new method can best be utilized and provide potential directions to identify the underlying processes causing deviations in gene flow patterns.
Chronic Alcohol Consumption Enhances Skeletal Muscle Wasting in Mice Bearing Cachectic Cancers: The Role of TNFα/Myostatin Axis
Authors: Li Yuanfei , Zhang Faya , Modrak Samantha , Little Alex , Zhang Hui
Published: October 2019

Background

Chronic alcohol consumption enhances cancer‐associated cachexia, which is one of the major causes of decreased survival. The precise molecular mechanism of how alcohol consumption enhances cancer‐associated cachexia, especially skeletal muscle loss, remains to be elucidated.

Methods

We used a mouse model of chronic alcohol consumption, in which 20% (w/v) alcohol was provided as sole drinking fluid, and Lewis lung carcinoma to study the underlying mechanisms.

Results

We found that alcohol consumption up‐regulated the expression of MAFbx, MuRF‐1, and LC3 in skeletal muscle, suggesting that alcohol enhanced ubiquitin‐mediated proteolysis and LC3‐mediated autophagy. Alcohol consumption enhanced phosphorylation of Smad2/3, p38, and ERK and decreased the phosphorylation of FOXO1. These are the signaling molecules governing protein degradation pathways. Moreover, alcohol consumption slightly up‐regulated the expression of insulin receptor substrate‐1, did not affect phosphatidylinositol‐3 kinase, but decreased the phosphorylation of Akt and mammalian target of rapamycin (mTOR), and down‐regulated the expression of Raptor and p70 ribosomal kinase S6 kinase, suggesting that alcohol impaired protein synthesis signaling pathway in skeletal muscle of tumor‐bearing mice. Alcohol consumption enhanced the expression of myostatin in skeletal muscle, plasma, and tumor, but did not affect the expression of myostatin in non–tumor‐bearing mice. In TNFα knockout mice, the effects of alcohol‐enhanced expression of myostatin and protein degradation‐related signaling molecules, and decreased protein synthesis signaling in skeletal muscle were abolished. Consequently, alcohol consumption neither affected cancer‐associated cachexia nor decreased the survival of TNFα KO mice bearing cachectic cancer.

Conclusions

Chronic alcohol consumption enhances cancer‐associated skeletal muscle loss through suppressing Akt/mTOR‐mediated protein synthesis pathway and enhancing protein degradation pathways. This process is initiated by TNFα and mediated by myostatin.
Survival and cardiac toxicity in patients with HER2‐positive, metastatic breast cancer treated with trastuzumab in routine clinical practice
Authors: Vasista Anuradha , Ryan Luke , Naher Sayeda , Moylan Eugene , Stockler Martin R , Wilcken Nicholas , Kiely Belinda E
Published: October 2019

Aims

We sought to describe survival outcomes and toxicities of trastuzumab in real‐world patients with HER2‐positive, metastatic breast cancer (MBC) and compare these to a recent systematic review of clinical trials.

Methods

We searched the medical records of three Sydney cancer centers for patients with HER2‐positive, MBC starting trastuzumab from January 2001 to March 2017. We recorded patient, tumor, and treatment characteristics; survival times from start of palliative trastuzumab; and rates of cardiac toxicity. Survival distribution was summarized using the following percentiles (represented scenario): 90th (worst‐case), 75th (lower‐typical), 25th (upper‐typical), and 10th (best‐case). Survival times were compared to recent review of HER2‐positive MBC randomized trials. Factors associated with survival were assessed with Cox models.

Results

Characteristics of the 126 patients were: median age 53 years, ER positive cancer (50%), de‐novo metastatic disease (23%), prior adjuvant trastuzumab (15%), liver metastases (37%), and brain metastases (23%). The median duration of first‐line trastuzumab was 11 months (interquartile range, (IQR) 5–27). Survival times in months (vs the systematic review) were: 90th percentile 8 (9); 75th percentile 16 (19); and median 34 (33). Follow‐up duration was insufficient to estimate the 25th and 10th percentiles, similar to the systematic review. Liver metastases were associated with shorter survival (HR = 1.74, 95% CI, 1.1‐2.76, P = .02). Seventy percent of patients had a baseline cardiac assessment. Five patients (3.9%) developed symptomatic cardiac toxicity, similar to clinical trials.

Conclusion

Survival and cardiac toxicity rates for women starting trastuzumab in routine practice were comparable to clinical trials. Oncologists can use clinical trial data as a reference point when explaining survival outcomes to women with HER2‐positive MBC.
Impact of sequential lines of palliative chemotherapy in patients with recurrent/metastatic esophageal squamous cell carcinoma: A retrospective analysis of 107 patients at a single center
Authors: Kim Eo Jin , Kim Jong Hoon , Song Ho June , Park Sook Ryun , Kim Yong‐Hee , Kim Hyeong Ryul , Kim Sung‐Bae
Published: October 2019

Aim

This study was conducted to evaluate the efficacy of palliative chemotherapy by the lines of chemotherapy in recurrent/metastatic esophageal squamous cell carcinoma (ESCC) and to compare the efficacy between the patients with initially metastatic ESCC and those with recurrent/progressed ESCC after curative treatment.

Materials and Methods

All 107 patients who began palliative chemotherapy for recurrent/metastatic ESCC from March 2015 to October 2017 were included, and grouped according to previous treatment: Groups A (previous chemoradiation alone, n = 30), B (previous surgery alone, n = 11), C (previous chemoradiation and surgery, n = 30), and D (initially metastatic or de novo stage IV, n = 36). Groups A, B, and C (pretreated group) and Group D (treatment‐naïve group) were reorganized according to treatment history. Overall response rate (ORR) and survival data were retrospectively evaluated for each group, lines of chemotherapy, and chemotherapeutic regimen.

Results

ORR was 25.2%, 7.3%, and 3.4% in first‐, second‐, and third‐line chemotherapy, respectively. The median progression‐free survival (PFS) was 4.7, 2.0, and 2.2 months in first‐, second‐, third‐line chemotherapy, respectively. The median overall survival (OS) after first‐line palliative chemotherapy was 10.1 months, and it was not significantly different between pretreated and treatment‐naive groups. Previous surgery, good performance, ≥3 lines of chemotherapy, and low C‐reactive protein level were linked to a significantly longer OS in multivariate analysis.

Conclusion

Because PFS rapidly declines with advancement of line of chemotherapy, incorporation of effective treatment modalities in early line treatments is crucial in the management of recurrent/metastatic ESCC. If tolerable, continuing advanced lines of chemotherapy may prolong survival.
A Comparison of New Factor Models in the Korean Stock Market
Authors: Kang Hankil , Kang Jangkoo , Kim Wooyeon
Published: October 2019

We compare the empirical performance of the Fama and French (2015) five‐factor model, the Hou et al. (2015) q‐factor model, and their variations in the Korean stock market. Among the models considered, we demonstrate that the adjusted five‐factor model, which includes the quarterly‐ rather than the yearly‐based profitability factor, best explains the size‐, value‐, investment‐, and profitability‐sorted portfolio returns. We also document supporting evidence that high‐minus‐low (HML) may not be a redundant factor in the existence of q‐factors. The adjusted five‐factor model outperforms the other factor models in digesting various anomalies in the Korean market.
The identification of key indicators to drive quality improvement in obstetric anaesthesia: results of the Obstetric Anaesthetists’ Association/National Perinatal Epidemiology Unit collaborative Delphi project
Authors: Bamber J. H. , Lucas D. N. , Plaat F. , Allin B. , Knight M. ,   collaborators for the Obstetric Anaesthetists’ Association Quality and Outcomes Working Group
Published: October 2019

A three‐stage Delphi survey process was undertaken to identify the quality indicators considered the most relevant to obstetric anaesthesia. The initial quality indicators assessed were derived from national peer‐reviewed publications and were divided into service provision, service quality and clinical outcomes. A range of stakeholders were invited to participate and divided into three panels: obstetric anaesthetists; other maternity care health professionals; and women who had used maternity services. In total, 133 stakeholders registered to participate with 80% completing all three phases of the survey process. Participants ranked indicators for their relative importance using the grading of recommendations assessment, development and evaluation scale. From an initial list of 31 quality indicators, 11 indicators were rated as extremely important by > 90% of participants in at least two panels. These 11 indicators were presented to stakeholders; they were asked to vote for the five indicators they considered most relevant and useful for assessing and benchmarking the quality of obstetric anaesthesia provided. The indicators chosen were: the percentage of women who had an epidural/combined spinal‐epidural for labour analgesia with accidental dural puncture; the presence of guidelines for the referral of patients to an anaesthetist for antenatal review; whether there are dedicated elective caesarean section lists; the availability of point‐of‐care testing for estimation of haemoglobin concentration; and the percentage of epidurals for labour analgesia that provided adequate pain relief within 45 min of the start of epidural insertion. These indicators may be used for quality improvement and national benchmarking to support the implementation of quality standards in obstetric anaesthesia.
Pharmacokinetics of intravenous and inhaled salbutamol and tobramycin: An exploratory study to investigate the potential of exhaled breath condensate as a matrix for pharmacokinetic analysis
Authors: Kruizinga Matthijs D. , Birkhoff Willem A.J. , van Esdonk Michiel J. , Klarenbeek Naomi B. , Cholewinski Tomasz , Nelemans Tessa , Dröge Melloney J. , Cohen Adam F. , Zuiker Rob G.J.A.
Published: October 2019

Concentrations of drugs acting in the lungs are difficult to measure, resulting in relatively unknown local pharmacokinetics. The aim of this study is to assess the potential of exhaled breath condensate (EBC) as a matrix for pharmacokinetic analysis of inhaled and intravenous medication. A 4‐way crossover study was conducted in 12 volunteers with tobramycin and salbutamol intravenously and via inhalation. EBC and plasma samples were collected postdose and analysed for drug concentrations. Sample dilution, calculated using urea concentrations, was used to estimate the epithelial lining fluid concentration. Salbutamol and tobramycin were largely undetectable in EBC after intravenous administration and were detectable after inhaled administration in all subjects in 50.8 and 51.5% of EBC samples, respectively. Correction of EBC concentrations for sample dilution did not explain the high variability. This high variability of EBC drug concentrations seems to preclude EBC as a matrix for pharmacokinetic analysis of tobramycin and salbutamol.
Clinical trial simulations of the interaction between cannabidiol and clobazam and effect on drop‐seizure frequency
Authors: Bergmann Kirsten Riber , Broekhuizen Karen , Groeneveld Geert Jan
Published: October 2019

With this study, we aim to test the hypothesis that the effect of cannabidiol on drop‐seizure frequency in patients with Lennox–Gastaut syndrome and Dravet syndrome could be attributed to a drug–drug interaction with clobazam. We performed clinical trial simulations for the effect of 20 mg/kg/day cannabidiol on drop‐seizure frequency in patients with Lennox–Gastaut syndrome. We assumed that patients taking 10 or 20 mg clobazam would have a 2‐ to 7‐fold increase in N‐desmethylclobazam exposure, whereas patients not taking clobazam would have a median reduction in drop‐seizure frequency and a variability in the percent reduction similar to the placebo group. The results show that the effect of cannabidiol on the median reduction in drop‐seizure frequency in patients with Lennox–Gastaut syndrome may be explained by a drug–drug interaction with clobazam. This may have important implications for the use of cannabidiol and its Food and Drug Administration registration.
Carbonic anhydrase II does not regulate nitrite‐dependent nitric oxide formation and vasodilation
Authors: Wang Ling , Sparacino‐Watkins Courtney E. , Wang Jun , Wajih Nadeem , Varano Paul , Xu Qinzi , Cecco Eric , Tejero Jesús , Soleimani Manoocher , Kim‐Shapiro Daniel B. , Gladwin Mark T.
Published: October 2019

Background and purpose

Although it has been reported that bovine carbonic anhydrase CAII is capable of generating NO from nitrite, the function and mechanism of CAII in nitrite‐dependent NO formation and vascular responses remain controversial. We tested the hypothesis that CAII catalyses NO formation from nitrite and contributes to nitrite‐dependent inhibition of platelet activation and vasodilation.

Experiment approach

The role of CAII in enzymatic NO generation was investigated by measuring NO formation from the reaction of isolated human and bovine CAII with nitrite using NO photolysis‐chemiluminescence. A CAII‐deficient mouse model was used to determine the role of CAII in red blood cell mediated nitrite reduction and vasodilation.

Key results

We found that the commercially available purified bovine CAII exhibited limited and non‐enzymatic NO‐generating reactivity in the presence of nitrite with or without addition of the CA inhibitor dorzolamide; the NO formation was eliminated with purification of the enzyme. There was no significant detectable NO production from the reaction of nitrite with recombinant human CAII. Using a CAII‐deficient mouse model, there were no measurable changes in nitrite‐dependent vasodilation in isolated aorta rings and in vivo in CAII−/−, CAII+/−, and wild‐type mice. Moreover, deletion of the CAII gene in mice did not block nitrite reduction by red blood cells and the nitrite‐NO‐dependent inhibition of platelet activation.

Conclusion and implications

These studies suggest that human, bovine and mouse CAII are not responsible for nitrite‐dependent NO formation in red blood cells, aorta, or the systemic circulation.
Angiotensin‐(1‐7) mitigated angiotensin II‐induced abdominal aortic aneurysms in apolipoprotein E‐knockout mice
Authors: Xue Fei , Yang Jianmin , Cheng Jing , Sui Wenhai , Cheng Cheng , Li Hongxuan , Zhang Meng , Zhang Jie , Xu Xingli , Ma Jing , Lu Lin , Xu Jinfeng , Zhang Meng , Zhang Yun , Zhang Cheng
Published: October 2019

Background and Purpose

To test the hypothesis that angiotensin‐(1‐7) [Ang‐(1‐7)] may attenuate abdominal aortic aneurysm (AAA) via inhibiting vascular inflammation, extracellular matrix degradation, and smooth muscle cell (SMC) apoptosis, an animal model of AAA was established by angiotensin II (Ang II) infusion to apolipoprotein E‐knockout (ApoE‐/‐) mice.

Experimental Approach

All mice and cultured SMCs or macrophages were divided into control, Ang II‐treated, Ang II + Ang‐(1‐7)‐treated, Ang II + Ang‐(1‐7) + A779‐treated and Ang II + Ang‐(1‐7) + PD123319‐treated groups respectively. In vivo, aortic mechanics and serum lipids were assessed. Ex vivo, AAA were examined by histology, immunohistochemistry and zymography. Cultured cells were analysed by RT‐PCR, western blots and TUNEL assays.

Key Results

In vivo, Ang‐(1‐7) reduced the incidence and severity of AAA induced by Ang II infusion, by inhibiting macrophage infiltration, attenuating expression of IL‐6, TNF‐α, CCL2 and MMP2, and decreasing SMC apoptosis in abdominal aortic tissues. Addition of A779 or PD123319 reversed Ang‐(1‐7)‐mediated beneficial effects on AAA. In vitro, Ang‐(1‐7) decreased expression of mRNA for IL‐6, TNF‐α, and CCL2 induced by Ang II in macrophages. In addition, Ang‐(1‐7) suppressed apoptosis and MMP2 expression and activity in Ang II‐treated SMCs. These effects were accompanied by inhibition of the ERK1/2 signalling pathways via Ang‐(1‐7) stimulation of Mas and AT2 receptors.

Conclusion and Implications

Ang‐(1‐7) treatment attenuated Ang II‐induced AAA via inhibiting vascular inflammation, extracellular matrix degradation, and SMC apoptosis. Ang‐(1‐7) may provide a novel and promising approach to the prevention and treatment of AAA.
Number Representations Drive Number‐Line Estimates
Authors: Yuan Lei , Prather Richard , Mix Kelly S. , Smith Linda B.
Published: October 2019

The number‐line task has been extensively used to study the mental representation of numbers in children. However, studies suggest that proportional reasoning provides a better account of children’s performance. Ninety 4‐ to 6‐year‐olds were given a number‐line task with symbolic numbers, with clustered dot arrays that resembled a perceptual scaling task, or with spread‐out dot arrays that involved numerical estimation. Children performed well with clustered dot arrays, but poorly with symbolic numbers and spread‐out dot arrays. Performances with symbolic numbers and spread‐out dot arrays were highly correlated and were related to counting skill; neither was true for clustered dot arrays. Overall, results provide evidence for the role of mental representation of numbers in the symbolic number‐line task.
Lateralized Neural Responses to Letters and Digits in First Graders
Authors: Lochy Aliette , Schiltz Christine
Published: October 2019

The emergence of visual cortex specialization for culturally acquired characters like letters and digits, both arbitrary shapes related to specific cognitive domains, is yet unclear. Here, 20 young children (6.12 years old) were tested with a frequency‐tagging paradigm coupled with electroencephalogram recordings to assess discrimination responses of letters from digits and vice‐versa. One category of stimuli (e.g., letters) was periodically inserted (1/5) in streams of the other category (e.g., digits) presented at a fast rate (6 Hz). Results show clear right‐lateralized discrimination responses at 6 Hz/5 for digits within letters, and a trend for left‐lateralization for letters. These results support an early developmental emergence of ventral occipito‐temporal cortex specialization for visual recognition of digits and letters, potentially in relation with relevant coactivated brain networks.
High‐definition transcranial direct current stimulation—An open‐label pilot intervention in alleviating depressive symptoms and cognitive deficits in late‐life depression
Authors: Wong Hau‐lam , Chan Wai Chi , Wong Yiu‐lung , Wong Sze‐nga , Yung Hui‐yan , Wong Sau‐man Corine , Cheng Pak‐wing Calvin
Published: October 2019

The efficacy of high‐definition transcranial direct current stimulation (HD‐tDCS) in late‐life depression (LLD) remains unknown due to limited research on its therapeutic effects on the hallmarks of LLD—the depressive and cognitive symptoms. The present open‐label pilot study aimed to examine the effectiveness of HD‐tDCS as an augmentation therapy with antidepressants in improving the depressive and cognitive symptoms for LLD. Significant improvements were hypothesized in the depressive, cognitive, and daily functioning outcomes over time. A total of 15 subjects with LLD (13 females, mean age = 73.27 ± 6.25) received five consecutive daily sessions of 20‐minute active HD‐tDCS interventions weekly for 2 weeks, with a 2 mA anodal stimulation over F3 and cathodal stimulation over FC1, AF3, F7, and FC5. Depressive symptoms and cognitive and daily functioning were assessed across five assessment timepoints. The results revealed that the HD‐tDCS was effective in reducing the depressive severity and the remission rates, with a sustained effect at both the 1‐month and 3‐month follow‐up. Pre‐post improvements were seen in the overall cognitive functioning and in verbal fluency, but not in executive functioning. Our pilot study provides a preliminary result of HD‐tDCS in LLD, which was a safe and effective treatment in alleviating depressive symptoms, with mild cognitive improvements observed. Further larger scale randomized controlled trials are needed to confirm this result.
Isothiazolinones in cleaning products: Analysis with liquid chromatography tandem mass spectrometry of samples from sensitized patients and market
Authors: Marrero‐Alemán Gabriel , Borrego Leopoldo , Antuña Ana González , Macías Montes Ana , Pérez Luzardo Octavio
Published: October 2019

Background

Methylchloroisothiazolinone (MCI) and methylisothiazolinone (MI) contact dermatitis is a severe problem. The high concentrations of these substances and other isothiazolinones such as benzisothiazolinone (BIT) and octylisothiazolinone (OIT) contained in cleaning products may cause allergic contact dermatitis in sensitized patients.

Objectives

To evaluate the exposure to isothiazolinones contained in cleaning products on the market and from sensitized patients, and to verify the accuracy of labeling.

Methods

A total of 34 cleaning products were collected (17 supplied by sensitized patients and 17 bought randomly). Analysis was made of the concentrations of MI, MCI, BIT, and OIT using liquid chromatography tandem mass spectrometry (LC‐MS/MS).

Results

MI and BIT were the components most frequently detected. Of all the products analyzed, 76.5% contained at least one isothiazolinone. Twelve products had an MI concentration above the permitted level for rinse‐off cosmetics. Most of them were coming into direct contact with the skin in daily use. Mislabeling occurred in eight products.

Conclusions

Some cleaning products with high concentrations of isothiazolinones may cause cutaneous symptoms in sensitized patients, especially in spray form. The labeling should be correct, also regarding the use of each article.
Primary cutaneous Epstein‐Barr virus‐positive diffuse large B‐cell lymphoma, not otherwise specified, in a nonimmunocompromised young man: A case report
Authors: Mo Xiang‐lan , Zhou Min‐yan , Ye Qiu‐rong
Published: October 2019

Primary cutaneous EBV (Epstein‐Barr virus)‐positive diffuse large B‐cell lymphoma, not otherwise specified (DLBCL, NOS), is an extremely rare disease. The clinical and pathological features of DLBCL, NOS have not been clearly illustrated. We report a case of primary cutaneous EBV‐positive DLBCL, NOS in a 35‐year‐old Chinese male with multiple ulcerated and nodular lesions on his trunk and arms for 6 months. No other organs, except the skin, were involved. The lesions were localized in the dermis with focal necrosis. The tumor cells were immunoblastic‐ or centroblastic‐like cells and diffusely distributed. There were numerous inflammatory cells in the background. The tumor cells were positive for CD20, PAX‐5, MUM1, LMP1, CD30, and Epstein‐Barr virus encodedsmall RNA, but negative for EBNA2. Polymerase chain reaction showed a monoclonal IG gene rearrangement. The patient received 6 cycles of CHOP (cyclophosphamide, hydroxydaunorubicin, Oncovin®, prednisone) chemotherapy and went into complete remission. There was no evidence of relapse after 35 months of follow‐up.