bluuebunny/crossref_metadata_2025 huggingface dataset:
Higher order assembly of Sorting Nexin 16 controls tubulation and distribution of neuronal endosomes
Authors: Wang ShiYu , Zhao Zechuan , Rodal Avital A.
Published: November 2018

The activities of neuronal signaling receptors depend on the maturation state of the endosomal compartments in which they reside. However, it remains unclear how the distribution of these compartments within the uniquely complex morphology of neurons is regulated, and how this distribution itself affects signaling. Here we identified mechanisms by which Sorting Nexin 16 (SNX16) controls neuronal endosomal maturation and distribution. We found that higher-order assembly of SNX16 via its coiled-coil domain drives membrane tubulation in vitro and endosome association in cells. In Drosophila motor neurons, activation of Rab5 and coiled-coil-dependent self-association of SNX16 lead to its endosomal enrichment, concomitant with depletion of SNX16-positive endosomes from the synapse, and their accumulation as Rab5- and Rab7-positive tubulated compartments at the cell body. This leads to higher levels of synaptic growth-promoting BMP receptors at the cell body, and correlates with increased synaptic growth. Our results indicate that Rab regulation of SNX16 assembly controls the endosomal distribution and signaling activities of neuronal receptors.
From Space to Sequence and Back Again: Iterative DNA Proximity Ligation and its Applications to DNA-Based Imaging
Authors: Boulgakov Alexander A. , Xiong Erhu , Bhadra Sanchita , Ellington Andrew D. , Marcotte Edward M.
Published: November 2018

We extend the concept of DNA proximity ligation from a single readout per oligonucleotide pair to multiple reversible, iterative ligations re-using the same oligonucleotide molecules. Using iterative proximity ligation (IPL), we can in principle capture multiple ligation events between each oligonucleotide and its various neighbors and thus recover a far richer knowledge about their relative positions than single, irreversible ligation events. IPL would thus act to sample and record local molecular neighborhoods. By integrating a unique DNA barcode into each participating oligonucleotide, we can catalog the individual ligation events and thus capture the positional information contained therein in a high throughput manner using next-generation DNA sequencing. We propose that by interpreting IPL sequencing results in the context of graph theory and by applying spring layout algorithms, we can recover geometric patterns of objects labeled by DNA. Using simulations, we demonstrate that we can in principle recover letter patterns photolithographed onto slide surfaces using only IPL sequencing data, illustrating how our technique maps complex spatial configurations into DNA sequences and then – using only this sequence information – recovers them. We complement our theoretical work with an experimental proof-of-concept of iterative proximity ligation on an oligonucleotide population.
How motivations and satisfaction influence wine tourists’ loyalty? An analysis of the Italian case
Authors: Brandano Maria Giovanna , Osti Linda , Pulina Manuela
Published: November 2018

Purpose

The purpose of this paper is to assess the “motivation-satisfaction-loyalty” framework. Through a structural equation model (SEM), it is possible to disentangle attitudinal and behavioral loyalty as a multifaceted latent variable.

Design/methodology/approach

The empirical analysis is based on data collected in wineries located in two important wine destinations: Trentino and South Tyrol (Italy). Notably, the motivation–satisfaction relationship is confirmed, and the SEM has also assessed the importance of winery services in affecting loyalty, expressed in terms of “visit other cellars,” “repeat a wine vacation” and “recommend wine routes.”

Findings

Destination managers should consider the wine-related “relaxation” as the main push motivation, while the interactions experience are important pull motivations to drive wine tourists’ satisfaction. Nevertheless, the findings reveal that more proactive policies are needed to enhance local wines loyalty.

Originality/value

The novelty of this study is to explore loyalty. In this respect, a multifaceted latent variable is expressed as follows: “buy local wines,” “visit other cellars,” “repeat a wine vacation” as behavioral attitudinal stated loyalty and “recommend wine routes” as attitudinal stated loyalty.
Servitization intent as a factor in the servitization process
Authors: Crowley Edward , Burton Jamie , Zolkiewski Judith
Published: November 2018

Purpose

This paper aims to investigate the role of servitization intent in the servitization process, and specifically the role dissonance (at an organizational level) in servitization intent can play in creating barriers to the servitization effort. Servitization intent is defined as the desire to achieve a future state of increased servitization.

Design/methodology/approach

The research uses elite interviews and secondary data to explore servitization intent and its role during the servitization process. It examines the resistance to change resulting from a misalignment of the executive intent to servitize, and the organizational intent to retain the existing manufacturing business model. By encompassing data from companies representing a significant portion of the total industry (as measured by revenue), the study provides an industry level perspective of servitization intent and alignment.

Findings

Servitization intent and three key managerial challenges related to servitization intent that act as barriers to servitization were identified: lack of servitization intent, overcoming the manufacturing mindset associated with the organizational intent and the constraints resulting from managerial experience. Servitization intent and its associated managerial challenges were present at an industry level with consistent findings being shown across the major firms in the industry studied. A number of managerial strategies for overcoming these barriers were identified.

Research limitations/implications

The research focuses on a single industry; the findings, potentially, have application across a broad range of industries.

Practical implications

A key management implication from these findings is the need for a clear understanding of the organizational intent in relation to servitization in addition to the need to bring this organizational intent in alignment with the executives’ servitization intent.

Originality/value

This research makes a contribution by identifying the misalignment between servitization intent in different levels of the organization during the servitization process and the mechanisms that can improve alignment and help effect servitization.
Back to the future: returning to silver-backed money in Sri Lanka
Authors: Sinna Lebbe Suhail , Mohamad Azhar , Mohammad Sifat Imtiaz
Published: November 2018

Purpose

The purpose of this paper is to investigate the drivers of the behaviour intention to use the Silver-Backed Mobile Payment System (SBMPS) among the residents of Kattankudy, Sri Lanka.

Design/methodology/approach

Based on technology adoption model theory, a conceptual framework was devised, which was later tested via structural equation modelling (SEM) using valid responses from a survey questionnaire.

Findings

The results indicated that perceived usefulness and subjective norms have positive relationships and perceived risk a negative relationship with people’s behavioural intention to adopt SBMPS. In addition, the respondents were primarily motivated by faith (Islam) and also by economic advantages to adopt SBMPS.

Research limitations/implications

Religion, culture, gender, income level, age and educational level could be used as moderating factors for better understanding of people’s behaviour intentions. A Multi-cultural demographic may shed further light.

Social implications

This paper not only makes awareness of the importance of real (commodity) money but also provides the understanding of people’s willingness and the underlying motivations to practically implement the system without threatening the legal tender.

Originality/value

Extant research has mainly focused on the validity and the conceptual ideas to return to gold and silver money. This paper has been an extension to practically implement real money without threatening the legal tender by investigating the determinants of people’s willingness to return to silver money and understanding their motivations underlying those decisions
Does online service failure matter to offline customer loyalty in the integrated multi-channel context? The moderating effect of brand strength
Authors: Wang Xuhui , Zhang Qilin
Published: November 2018

Purpose

The purpose of this paper is to investigate the effect of online service failure on online customer satisfaction and offline customer loyalty, and the moderating role of brand strength is also examined. While extant research on brick and click service mode recognizes the positive spillover effect from offline stores to online stores, this study analyzes the negative spillover effect from online stores to offline stores.

Design/methodology/approach

This paper tests the hypotheses by two studies. Study 1 is based on a 2 (failure severity: mild vs severe) × 2 (brand strength: strong vs weak) between-subjects experimental design using scenarios in a brick and click retailer context, while study 2 is based on data collected from a scenario-based questionnaire survey and analyzed through the structural equation modeling.

Findings

The results indicate that participants exposed to severe online service failure show lower online satisfaction as compared to their counterparts exposed to mild online service failure, but they show the similar level of offline loyalty in both degrees of online service failure. Nevertheless, these results are not moderated by brand strength significantly.

Research limitations/implications

An experimental design and a scenario-based questionnaire survey are used to test the framework. However, the generalizability of the research findings is still limited to a specific study setting. Future research in a different setting is needed to further validate the presented findings.

Practical implications

The findings suggest that physical service providers should adopt aggressive online expansion strategy to seize the market and pay more attention to online service quality rather than online marketing only.

Originality/value

This is one of few studies to explore the risk of brick and click service mode, and provide a clear understanding of the likely occurrence of online service failure and its impact on online customer satisfaction and offline customer loyalty. It extends prior research by exploring non-existence of negative perceptual effect from online service failure to offline customer loyalty in the short run and weakening brand effect, which contributes to cross-channel spillover effect in the integrated multi-channel context and brand building in the internet era.
Strategic partnerships enhance resources for care of rural-dwelling older adults
Authors: Holley Lyn M. , Kelly Christopher M. , Deichert Jerome , Juanes Silvester , Wolf Loretta
Published: November 2018

Purpose

The purpose of this paper is to disseminate a new model that addresses the urgent social challenge of providing adequate long-term care in rural circumstances through innovative use of existing resources, and to suggest future research.

Design/methodology/approach

This paper is exploratory in and is based upon the analysis of qualitative observations (interviews and site visits) framed in the financial and operational records of the facility studied, macro- and micro-level demographics, and the scholarly and practice literatures.

Findings

Significant cost savings upon implementation, improvements in quality of care and both worker and client satisfaction were observed.

Research limitations/implications

The model has been in operation only one year; the trend has been positive, however, more research is needed to identify its stability and develop a more refined description of its components: while essential features of this innovative model can be applied in any residential long-term care situation, replicating its success is obviously linked with the skill and authority of the director. Evaluation research is currently in progress.

Practical implications

The paper suggests budget-neutral solutions to persistent challenges of caring for older adults in rural circumstances.

Social implications

Quality and financing of long-term residential care for elders is insufficient and worsening. This model addresses problems central to financing and quality of care by connecting existing resources in new ways. It does not require additional funding or changes in qualifications required for jobs.

Originality/value

The model is the original creation of a residential long-term care facility director working with a network of partnerships that he discovered and developed: partnerships include a broad range of organizations in the public and non-profit sectors, and the state university.
Forensic Performance Analysis of Load‐Limiting Devices in Automotive Seat Belt Retractors
Authors: D'Aulerio Louis , Whitman Gary , Sicher Larry , Cantor Alan , Markushewski Mike
Published: November 2018

The introduction of frontal airbags and seatbelt pretensioners for front seat occupants provided an opportunity to address injuries caused by seatbelt loading by introducing load‐limiters, which were intended to reduce belt loading while maintaining proper restraint. Investigation and forensic analysis of real‐world crashes identified that the implementation of these devices, in some circumstances, increased the potential of injury. This paper focuses on the trade‐offs of load‐limiters, that is, the reduction loading to the occupant versus the corresponding increase in seatbelt webbing and occupant movement. If the additional webbing introduced is not controlled, the risk of injury to the occupant is increased and could result in more frequent and severe injuries rather than a reduction. This paper quantifies the webbing introduced by load‐limiter activation through forensic analysis of the seatbelt involved in real‐world crashes and testing and assesses its effect on the injuries sustained by the occupant.
ACEM involvement in a successful African emergency medicine programme
Authors: Cox Megan
Published: November 2018

In the past 5 years Botswana graduated its first home‐grown doctors and emergency medicine specialists for the country. The postgraduate emergency medicine specialist training arrangement between Botswana and South Africa was challenging in development, implementation and maintenance. Numerous varied supports from ACEM and its International Emergency Medicine Network were integral to these successes. This article encourages further investment of ACEM grants and scholarships in Africa by describing how ACEM supported significant advances in Botswana emergency medicine.
Extracting individual trees from lidar point clouds using treeseg
Authors: Burt Andrew , Disney Mathias , Calders Kim
Published: November 2018

Recent studies have demonstrated the potential of lidar‐derived methods in plant ecology and forestry. One limitation to these methods is accessing the information content of point clouds, from which tree‐scale metrics can be retrieved. This is currently undertaken through laborious and time‐consuming manual segmentation of tree‐level point clouds from larger‐area point clouds, an effort that is impracticable across thousands of stems.

Here, we present treeseg, an open‐source software to automate this task. This method utilises generic point cloud processing techniques including Euclidean clustering, principal component analysis, region‐based segmentation, shape fitting and connectivity testing. This data‐driven approach uses few a priori assumptions of tree architecture, and transferability across lidar instruments is constrained only by data quality requirements.

We demonstrate the treeseg algorithm here on data acquired from both a structurally simple open forest and a complex tropical forest. Across these data, we successfully automatically extract 96% and 70% of trees, respectively, with the remainder requiring some straightforward manual segmentation.

treeseg allows ready and quick access to tree‐scale information contained in lidar point clouds. treeseg should help contribute to more wide‐scale uptake of lidar‐derived methods to applications ranging from the estimation of carbon stocks through to descriptions of plant form and function.
Prospective Validation of a Checklist to Predict Short‐term Death in Older Patients After Emergency Department Admission in Australia and Ireland
Authors: Cardona Magnolia , O'Sullivan Michael , Lewis Ebony T. , Turner Robin M. , Garden Frances , Alkhouri Hatem , Asha Stephen , Mackenzie John , Perkins Margaret , Suri Sam , Holdgate Anna , Winoto Luis , Chang David C. W. , Gallego‐Luxan Blanca , McCarthy Sally , Hillman Ken , Breen Dorothy
Published: November 2018

Background

Emergency departments (EDs) are pressured environment where patients with supportive and palliative care needs may not be identified. We aimed to test the predictive ability of the CriSTAL (Criteria for Screening and Triaging to Appropriate aLternative care) checklist to flag patients at risk of death within 3 months who may benefit from timely end‐of‐life discussions.

Methods

Prospective cohorts of >65‐year‐old patients admitted for at least one night via EDs in five Australian hospitals and one Irish hospital. Purpose‐trained nurses and medical students screened for frailty using two instruments concurrently and completed the other risk factors on the CriSTAL tool at admission. Postdischarge telephone follow‐up was used to determine survival status. Logistic regression and bootstrapping techniques were used to test the predictive accuracy of CriSTAL for death within 90 days of admission as primary outcome. Predictability of in‐hospital death was the secondary outcome.

Results

A total of 1,182 patients, with median age 76 to 80 years (IRE‐AUS), were included. The deceased had significantly higher mean CriSTAL with Australian mean of 8.1 (95% confidence interval [CI] = 7.7–8.6) versus 5.7 (95% CI = 5.1–6.2) and Irish mean of 7.7 (95% CI = 6.9–8.5) versus 5.7 (95% CI = 5.1–6.2). The model with Fried frailty score was optimal for the derivation (Australian) cohort but prediction with the Clinical Frailty Scale (CFS) was also good (areas under the receiver‐operating characteristic [AUROC] = 0.825 and 0.81, respectively). Values for the validation (Irish) cohort were AUROC = 0.70 with Fried and 0.77 using CFS. A minimum of five of 29 variables were sufficient for accurate prediction, and a cut point of 7+ or 6+ depending on the cohort was strongly indicative of risk of death. The most significant independent predictor of short‐term death in both cohorts was frailty, carrying a twofold risk of death. CriSTAL's accuracy for in‐hospital death prediction was also good (AUROC = 0.795 and 0.81 in Australia and Ireland, respectively), with high specificity and negative predictive values.

Conclusions

The modified CriSTAL tool (with CFS instead of Fried's frailty instrument) had good discriminant power to improve certainty of short‐term mortality prediction in both health systems. The predictive ability of models is anticipated to help clinicians gain confidence in initiating earlier end‐of‐life discussions. The practicalities of embedding screening for risk of death in routine practice warrant further investigation.
Identifying the optimal regional predictor of right ventricular global function: a high‐resolution three‐dimensional cardiac magnetic resonance study
Authors: Dawes T. J. W. , de Marvao A. , Shi W. , Rueckert D. , Cook S. A. , O'Regan D. P.
Published: November 2018

Right ventricular (RV) function has prognostic value in acute, chronic and peri‐operative disease, although the complex RV contractile pattern makes rapid assessment difficult. Several two‐dimensional (2D) regional measures estimate RV function, however the optimal measure is not known. High‐resolution three‐dimensional (3D) cardiac magnetic resonance cine imaging was acquired in 300 healthy volunteers and a computational model of RV motion created. Points where regional function was significantly associated with global function were identified and a 2D, optimised single‐point marker (SPM‐O) of global function developed. This marker was prospectively compared with tricuspid annular plane systolic excursion (TAPSE), septum‐freewall displacement (SFD) and their fractional change (TAPSE‐F, SFD‐F) in a test cohort of 300 patients in the prediction of RV ejection fraction. RV ejection fraction was significantly associated with systolic function in a contiguous 7.3 cm2 patch of the basal RV freewall combining transverse (38%), longitudinal (35%) and circumferential (27%) contraction and coinciding with the four‐chamber view. In the test cohort, all single‐point surrogates correlated with RV ejection fraction (p < 0.010), but correlation (R) was higher for SPM‐O (R = 0.44, p < 0.001) than TAPSE (R = 0.24, p < 0.001) and SFD (R = 0.22, p < 0.001), and non‐significantly higher than TAPSE‐F (R = 0.40, p < 0.001) and SFD‐F (R = 0.43, p < 0.001). SPM‐O explained more of the observed variance in RV ejection fraction (19%) and predicted it more accurately than any other 2D marker (median error 2.8 ml vs 3.6 ml, p < 0.001). We conclude that systolic motion of the basal RV freewall predicts global function more accurately than other 2D estimators. However, no markers summarise 3D contractile patterns, limiting their predictive accuracy.
The early repolarization pattern: Echocardiographic characteristics in elite athletes
Authors: Reinhard Wibke , Trenkwalder Teresa , Haller Bernhard , Meindl Christine , Schoenfeld Julia , Kaess Bernhard M , Hengstenberg Christian , Schunkert Heribert , Pressler Axel , Halle Martin , Scherr Johannes
Published: November 2018

Background

The electrocardiographic early repolarization (ER) pattern is associated with idiopathic ventricular fibrillation and increased long‐term cardiovascular mortality. Whether structural cardiac aberrations influence the phenotype is unclear. Since ER is particularly common in athletes, we evaluated its prevalence and investigated predisposing echocardiographic characteristics and cardiopulmonary exercise capacity in a cohort of elite athletes.

Methods

A total of 623 elite athletes (age 21 ± 5 years) were examined during annual preparticipation screening from 2006 until 2012 including electrocardiography, echocardiography, and exercise testing. ECGs were analyzed with focus on ER. All athletes participated in a clinical follow‐up.

Results

The prevalence of ER was 17% (108/623). ER‐positive athletes were predominantly male (71%, 77/108), showed a lower heart rate (57.1 ± 9.3 bpm versus 60.0 ± 11.2 bpm; p = 0.015) and a higher lean body mass compared to ER‐negative participants (88.1% ± 5.6% versus 86.5% ± 6.3%; p = 0.015). Echocardiographic measurements and cardiopulmonary exercise capacity in male and female athletes with and without ER largely showed similar results. Only the notching ER subtype (n = 15) was associated with an increased left atrial diameter (OR 7.01, 95%CI 1.65–29.83; p = 0.008), a higher left ventricular mass (OR 1.02, 95%CI 1.00–1.03; p = 0.038) and larger relative heart volume (OR 1.01, 95%CI 1.00–1.01; p = 0.01). During a follow‐up of 7.4 ± 1.5 years, no severe cardiovascular event occurred in the study sample.

Conclusions

In elite athletes presence of ER is not associated with distinct alterations in echocardiography and cardiopulmonary exercise. Athletes presenting with ER are rather male, lean with a low heart rate.
“He came back a changed man”: The popularity and influence of policy tourism
Authors: Baker Tom , McGuirk Pauline
Published: November 2018

Why does policy tourism remain a popular and influential method of policy learning and mobility in an age of information abundance? Framed by a case study of homelessness policy tourism to New York City, this paper suggests that policy tourism remains popular because it allows for: (1) thinking outside the everyday strictures of the bureaucratic workplace; (2) the development of associational bonds between policy tourists, and between tourists and hosts; (3) the verification of information; and (4) the legitimation of decisions/positions. Noting the powerful influence that tourist encounters have on policy tourists, the paper then discusses the production of authenticity. The paper calls for greater attention to the active and affective production of authenticity as a means to better understand policy tourism and its significant effect on policy learning and mobility.
Complete intracorporeal defect closure using unidirectional barbed suture in laparoscopic incisional hernia repair: Preliminary experience with short‐term follow‐up
Authors: Tsujinaka Shingo , Kakizawa Nao , Fukuda Rintaro , Kikugawa Rina , Toyama Nobuyuki , Rikiyama Toshiki
Published: November 2018

Introduction

Surgical techniques to close defects in laparoscopic incisional hernia repair vary across the literature. We herein demonstrate our original and standardized surgical technique for laparoscopic incisional hernia repair with complete intracorporeal defect closure using barbed suture.

Materials and Surgical Technique

Complete intracorporeal defect closures were indicated for defects less than or equal to 6 cm in transverse diameter. We performed a defect closure with a running suture using barbed suture in a caudal to cranial direction, with tissue bites and inter‐suture spacing of 1 cm each. The hernial sac was incorporated into the suturing to reduce possible dead space. After the procedure, intraperitoneal onlay mesh was placed. Seven patients underwent this procedure. The median total operative time was 188 min, and the median time specifically for defect closure was 25 min. There was no seroma, mesh bulge, persisting pain, or hernia recurrence at follow‐up.

Discussion

Our proposed technique is simple and can be safely performed with good short‐term outcomes.
Physiologically‐based pharmacokinetic modelling to predict oprozomib CYP3A drug–drug interaction potential in patients with advanced malignancies
Authors: Ou Ying , Xu Yang , Gore Lia , Harvey R. Donald , Mita Alain , Papadopoulos Kyriakos P. , Wang Zhengping , Cutler Richard E. , Pinchasik Dawn E. , Tsimberidou Apostolia M.
Published: November 2018

Aims

Oprozomib is an oral, second‐generation, irreversible proteasome inhibitor currently in clinical development for haematologic malignancies, including multiple myeloma and other malignancies. Oprozomib is a rare example of a small molecule drug that demonstrates cytochrome P450 (CYP) mRNA suppression. This unusual property elicits uncertainty regarding the optimal approach for predicting its drug–drug interaction (DDI) risk. The current study aims to understand DDI potential during early clinical development of oprozomib.

Methods

To support early development of oprozomib (e.g. inclusion/exclusion criteria, combination study design), we used human hepatocyte data and physiologically‐based pharmacokinetic (PBPK) modelling to predict its CYP3A4‐mediated DDI potential. Subsequently, a clinical DDI study using midazolam as the substrate was conducted in patients with advanced malignancies.

Results

The clinical DDI study enrolled a total of 21 patients, 18 with advanced solid tumours. No patient discontinued oprozomib due to a treatment‐related adverse event. The PBPK model prospectively predicted oprozomib 300 mg would not cause a clinically relevant change in exposure to CYP3A4 substrates (≤30%), which was confirmed by the results of this clinical DDI study.

Conclusions

These results indicate oprozomib has a low potential to inhibit the metabolism of CYP3A4 substrates in humans. The study shows that cultured human hepatocytes are a more reliable system for DDI prediction than human liver microsomes for studying this class of compounds. Developing a PBPK model prior to a clinical DDI study has been valuable in supporting clinical development of oprozomib.
Ex vivo culture of cells derived from circulating tumour cell xenograft to support small cell lung cancer research and experimental therapeutics
Authors: Lallo Alice , Gulati Sakshi , Schenk Maximilian W , Khandelwal Garima , Berglund Ulrika Warpman , Pateras Ioannis S , Chester Christopher P E , Pham Therese M , Kalderen Christina , Frese Kristopher K , Gorgoulis Vassilis G , Miller Crispin , Blackhall Fiona , Helleday Thomas , Dive Caroline
Published: November 2018

Background and Purpose

Small cell lung cancer (SCLC) is an aggressive disease with median survival of <2 years. Tumour biopsies for research are scarce, especially from extensive‐stage patients, with repeat sampling at disease progression rarely performed. We overcame this limitation for relevant preclinical models by developing SCLC circulating tumour cell derived explants (CDX), which mimic the donor tumour pathology and chemotherapy response. To facilitate compound screening and identification of clinically relevant biomarkers, we developed short‐term ex vivo cultures of CDX tumour cells.

Experimental Approach

CDX tumours were disaggregated, and the human tumour cells derived were cultured for a maximum of 5 weeks. Phenotypic, transcriptomic and pharmacological characterization of these cells was performed.

Key Results

CDX cultures maintained a neuroendocrine phenotype, and most changes in the expression of protein‐coding genes observed in cultures, for up to 4 weeks, were reversible when the cells were re‐implanted in vivo. Moreover, the CDX cultures exhibited a similar sensitivity to chemotherapy compared to the corresponding CDX tumour in vivo and were able to predict in vivo responses to therapeutic candidates.

Conclusions and Implications

Short‐term cultures of CDX provide a tractable platform to screen new treatments, identify predictive and pharmacodynamic biomarkers and investigate mechanisms of resistance to better understand the progression of this recalcitrant tumour.
Science in support of Amazonian conservation in the 21st century: the case of Brazil
Authors: Simmons Cynthia S. , Famolare Lisa , Macedo Marcia N. , Walker Robert T. , Coe Michael T. , Scheffers Brett , Arima Eugenio , Munoz‐Carpena Rafael , Valle Denis , Fraisse Clyde , Moorcroft Paul , Diniz Marcelo , Diniz Marcia , Szlafsztein Claudio , Pereira Ritaumaria , Ruiz Cesar , Rocha Gilberto , Juhn Daniel , Otávio do Canto Lopes Luis , Waylen Michael , Antunes Aghane , Galvan Yankuic M
Published: November 2018

This article presents a 21st Century agenda for Amazonian conservation. The agenda calls for developing a system of refugia and a scientific methodology for predicting impacts of the infrastructure development vision for the region. It also calls for a collaborative approach to conservation planning, in the interest of fruitful engagement with decision‐makers and stakeholders. The ideas explored here emerged from the collaboration of peers over a decade, which culminated in a panel presentation, Scientific Analysis, and Simulation Models to Support Conservation and Development Decision‐Making, at the Tools and Strategies Workshop held at the University of Florida in October, 2017.
Methylchloroisothiazolinone and/or methylisothiazolinone in cosmetic products—A market survey
Authors: Sukakul Thanisorn , Kanchanapenkul Dollaporn , Bunyavaree Monthathip , Limphoka Pichaya , Kumpangsin Titinun , Boonchai Waranya
Published: November 2018

Background

There was a global epidemic of methylchloroisothiazolinone (MCI) and/or methylisothiazolinone (MI) contact allergy from 2009 to 2015. In response, the Thai Ministry of Public Health regulated the use of MCI/MI in cosmetics.

Objective

To survey the presence of MCI/MI and MI alone, as labelled on cosmetics sold on the Thai market, before and after the ministerial directive.

Methods

The presence of MCI and/or MI in leave‐on and rinse‐off cosmetics sold on the market, based on the labelling of ingredients in 3445 products, was analysed.

Results

Before the implementation date, most leave‐on products contained MCI/MI. After the regulations came into force, the only leave‐on cosmetic subcategories that complied with the law were facial skin‐care, sunscreen and make‐up products. MCI/MI and MI alone were found on the labels of both leave‐on and rinse‐off products, the presence of each varying between product subcategories.

Conclusions

Despite the ministerial regulations restricting their use, MCI and/or MI are still found in cosmetics sold on the Thai market. Dermatologists should be aware of this situation, and counsel patients to avoid products containing MCI and/or MI.
Does Cancellation of Preferential Tax Policy Reduce Foreign Direct Investment Inflows?
Authors: Luo Zhi , Wang Chen , Zhang Xun
Published: November 2018

In light of recent tax cuts by the US, should China reintroduce a preferential tax policy to attract foreign direct investment? This paper investigates whether China's 2008 tax policy change affected inward foreign direct investment. In contrast to previous studies, we break foreign investment down into suspect and real foreign investment using firm‐level data from 1998 to 2008 and conduct a difference‐in‐difference estimation to determine the effect of the tax policy change on both types of foreign investment and compare these to the effect on domestic investment. The results show that the 2008 tax policy change reduced the amount of suspect foreign investment and its effect on real foreign investment was insignificant, indicating that foreign firms in China are more concerned with the investment environment and economic stability than taxes. Therefore, China should create a regulated business environment instead of readopting supernational treatment for foreign enterprises.
Prevention of esophageal stricture after endoscopic resection
Authors: Ishihara Ryu
Published: November 2018

Stricture formation after esophageal endoscopic resection has a negative impact on patients’ quality of life because it causes dysphagia and requires multiple endoscopic dilations. Various methods by which to prevent stricture have recently been developed and reported. Among these methods, local steroid injection is the most commonly used and is currently considered the standard method for noncircumferential resection. However, local steroid injection has a limited effect on circumferential resection. Thus, oral steroid administration is used for such cases because it may have a stronger effect than local injection. Steroid treatment, both by local injection and oral administration, is effective and low‐cost; however, it may cause fragility of the esophageal wall, resulting in adverse events such as perforation during balloon dilatation. Many innovative approaches have been developed, such as tissue‐shielding methods with polyglycolic acid, tissue engineering approaches with autologous oral mucosal epithelial cell sheet transplantation, and stent insertion. These methods may be promising, but they are limited by a scarcity of data. Further investigations are needed to confirm the efficacy of these methods.
Gender, autonomy and return migration: negotiating street harassment in Lima, Peru
Authors: ALCALDE M. CRISTINA
Published: November 2018

In this article, I approach street harassment broadly as a phenomenon to which women relate globally and as one that affects multiple aspects of their lives, or more specifically their experiences of return migration to Lima, Peru. I propose that street sexual harassment contributes to a restricted sense of autonomy among women return migrants in Lima. I emphasize that, given its pervasiveness, a consideration of street sexual harassment in relation to return migration contributes to a richer, gender‐conscious understanding of women's everyday experiences as return migrants. In examining a little studied yet significant form of everyday violence against women in the context of return migration, this article contributes to the growing literature on the intersections of gender, autonomy, and migration. More specifically, I draw on the experiences of middle‐ and upper‐class Peruvians to examine these intersections.
Basic Considerations for the Use of Monoclonal Antibodies in Migraine
Authors: Levin Morris , Silberstein Stephen D. , Gilbert Robert , Lucas Sylvia , Munsie Leanne , Garrelts Alyssa , Kennedy Kate , Everman Nicole , Pearlman Eric
Published: November 2018

Background

Migraine impacts more than 36 million people in the United States and 1 billion people worldwide. Despite the increasing availability of acute and preventive therapies, there is still tremendous unmet need. Potential treatments in development include monoclonal antibodies (mAbs). Appropriate use of these “biologic” treatments will necessitate an understanding of the aspects that distinguish them from traditional medications.

Aim

Many drug classes are prescribed for migraine treatment, but all have limitations. Recently, calcitonin gene‐related peptide (CGRP) activity has shown a significant promise as a target for preventive therapy. In this review, we provide an overview of the potential role of CGRP mAbs in migraine, with a focus on their design, pharmacokinetics, safety, and immunogenicity.

Conclusions

The CGRP mAbs are an innovative new therapy for migraine and address the need for effective and tolerable preventive options. MAbs, including those that target CGRP or its receptor, bind to a target with high specificity and affinity and lead to few off‐target adverse effects, although mechanism‐based adverse reactions may occur. Unlike other therapeutic antibodies used to treat neurologic disease, CGRP mAbs do not have a target within the immune system and have been designed to avoid altering the immune system. The safety and efficacy of mAbs against CGRP or its receptors are being investigated in clinical development programs, and the first of these therapies has received regulatory approval in the United States.
Circulating tumor cells detected using fluid‐assisted separation technique in esophageal squamous cell carcinoma
Authors: Choi Mun Ki , Kim Gwang Ha , I Hoseok , Park Su Jin , Lee Moon Won , Lee Bong Eun , Park Do Youn , Cho Yoon‐Kyoung
Published: November 2018

Background and Aim

Esophageal squamous cell carcinoma (ESCC) is one of the aggressive gastrointestinal tract cancers. Detection of circulating tumor cells (CTCs) in peripheral blood from patients with various malignancies has been reported to have diagnostic, prognostic, and therapeutic implications. We aimed to evaluate CTCs in patients with ESCC and assess the clinical significance of CTCs in the early diagnosis of ESCC.

Methods

Peripheral blood samples for CTCs analyses were prospectively obtained from 73 patients with ESCC prior to treatment between March 2015 and June 2018. CTCs were detected using a centrifugal microfluidic system with a new fluid‐assisted separation technique. Blood samples from 31 healthy volunteers were used as controls.

Results

After creating a receiver operating characteristic curve to determine the optimal CTC threshold to differentiate patients with ESCC from healthy controls, sensitivity and specificity were most optimized at a CTC threshold of two per 7.5 mL of blood. Among 66 subjects with ≥ 2 CTCs per 7.5 mL of blood, 63 (95.5%) had ESCC. Among 38 subjects with < 2 CTCs per 7.5 mL of blood, 28 (73.7%) were healthy controls. When using this threshold, the sensitivity and specificity for differentiating patients with ESCC from healthy controls were 86.3% and 90.3%, respectively. CTC count was associated with tumor–node–metastasis stage, especially lymph node metastasis, but there was no correlation with any other relevant clinicopathologic variable.

Conclusions

Our results suggest that CTCs detected using fluid‐assisted separation technique could be helpful for early diagnosis of ESCC. Further large‐scale prospective studies are warranted to validate our findings.
Estimated Pulmonary Artery Systolic Pressure and Mortality in Older‐Elderly Heart Failure Patients
Authors: Matsushita Kenichi , Sakata Konomi , Satoh Toru , Yoshino Hideaki
Published: November 2018

OBJECTIVES

To evaluate the association between high estimated pulmonary artery systolic pressure (ePASP) obtained by echocardiography and 1‐year mortality in patients with acute heart failure (HF), comparing findings in individuals aged 80 and older with those of individuals younger than 80.

DESIGN

Retrospective cohort study.

SETTING

Kyorin University Hospital.

PARTICIPANTS

Individuals with acute decompensated HF (N = 335).

MEASUREMENTS

High ePASP was defined as a tricuspid regurgitation pressure gradient greater than 47 mmHg (ePASP >50 mmHg). Potential risk factors for 1‐year mortality were selected using univariate analysis followed by multivariate Cox regression analysis with backward stepwise selection of variables with P < .10 on univariate analysis to identify significant factors.

RESULTS

In individuals aged 80 and older, high ePASP (hazard ratio (HR)=3.07; 95% confidence interval (CI)=1.21–7.80), discharge medications without diuretics (HR=4.18, 95% CI=1.66–10.54), and discharge medications without renin–angiotensin–aldosterone system inhibitors (HR=3.38, 95% CI=1.29–8.81) were independent risk factors for 1‐year mortality. In contrast, low systolic blood pressure at admission was the sole independent risk factor for 1‐year mortality (HR=0.94, 95% CI=0.89–0.99) in those younger than 80.

CONCLUSION

High ePASP is a significant predictor of 1‐year mortality in individuals aged 80 and older with acute HF but not in those younger than 80. Elucidation of the pathophysiological mechanisms behind these findings should facilitate the development of more effective individualized therapies for older adults with acute HF. J Am Geriatr Soc 67:323–328, 2019.
Comparison of vaccination coverage of four childhood vaccines in New Zealand and New York State
Authors: Baumann Katherine E , Paynter Janine , Petousis‐Harris Helen , Prymula Roman , Yang Y Tony , Shaw Jana
Published: November 2018

Aim

To ensure that children are vaccinated, different national governments use diverse strategies. We compared childhood vaccination coverage rates between New York State (NYS) and New Zealand (NZ) as the vaccination strategies are different.

Methods

We used vaccination records from the NYS Immunisation Information System and the National Immunisation Register of NZ to measure (i) vaccination coverage by school entry and by age six; (ii) coverage of different socio‐demographic groups; and (iii) trend in vaccination coverage between 2011 and 2015.

Results

We analysed the records of 583 767 NYS children and 269 800 NZ children 7 years of age. NZ children were 3.3–21.5% more likely than NYS children to receive each of the vaccines. Compared to NYS, NZ children were 39.6% more likely to be up‐to‐date by the start of school and 28.1% more likely to be up‐to‐date by age 6 years. Both NYS and NZ had statistically significant increases in the proportion of children who were up to date on each vaccine and all vaccines by the start of school and by 6 years of age (P < 0.001).

Conclusions

We identified under‐vaccinated groups and examined the point in the vaccine series where children were most vulnerable to being under‐vaccinated. This information is useful in targeting future investigations and interventions aimed at mitigating disparities in vaccine coverage. This comparison of regions with different vaccination programmes and policies is important when considering whether the particular vaccination coverage strategies of one region could be adapted and applied for the benefit of another.
Ambiguity aversion in the all‐pay auction and war of attrition
Authors: Stong Steven
Published: November 2018

Ambiguity aversion is introduced to a class of commonly applied games including the war of attrition and all‐pay auction. In contrast to subjective expected utility, the all‐pay auction is shown to generate less expected expenditure than the first‐price auction. The war of attrition generates less expected expenditure than the all‐pay auction and second‐price auction. In the all‐pay auction, increasing ambiguity causes low types to bid lower and high types to bid higher. In the war of attrition, ambiguity can decrease the bids for all types.
Burden and determinants of undernutrition among young pregnant women in Ethiopia
Authors: Workicho Abdulhalik , Belachew Tefera , Ghosh Shibani , Kershaw Meghan , Lachat Carl , Kolsteren Patrick
Published: November 2018

Undernutrition is a major public health concern due to its association with the mortality and disease burden of women and children. This study aimed at identifying the extent and determinants of undernutrition among young pregnant women in Ethiopia. A multivariable regression analysis was fitted to identify determinants of undernutrition and anaemia in a sample of 1,393 pregnant women. Risk ratios (RRs) with 95% confidence interval (CI) were estimated. All the analyses were performed using STATA version 14 and adjusted for clustering. The study revealed that 38% of the women were undernourished and 22% were anaemic. Improved maternal education, RR = 0.94, 95% CI [0.89, 0.98]; higher wealth status, RR = 0.72, 95% CI [0.47, 0.95]; higher minimum dietary diversity for women, RR = 0.87, 95% CI [0.77, 0.98]; increased maternal height, RR = 0.96, 95% CI [0.94, 0.98]; and protected water source, RR = 0.93, 95% CI [0.86, 0.96], have decreased the risk of undernutrition while using unimproved toilet, RR = 1.31, 95% CI [1.06, 1.63], and depression, RR = 1.33, 95% CI [1.14, 1.55], increased the risk of anaemia. Animal source food consumption decreased both the risk of undernutrition, RR = 0.85, 95% CI [0.77, 0.94], and anaemia, RR = 0.91, 95% CI [0.85, 0.95]. The burden of undernutrition is still high. Although improved socio‐economic status and dietary practices decreased the risk of undernutrition, poor health and environmental conditions were still significant risk factors. These findings suggest the need to target this set of important determinants to significantly decrease the burden of undernutrition among young pregnant women.
Seeds in motion: Genetic assignment and hydrodynamic models demonstrate concordant patterns of seagrass dispersal
Authors: Sinclair Elizabeth A. , Ruiz‐Montoya Leonardo , Krauss Siegfried L. , Anthony Janet M. , Hovey Renae K. , Lowe Ryan J. , Kendrick Gary A.
Published: November 2018

Movement is fundamental to the ecology and evolutionary dynamics within species. Understanding movement through seed dispersal in the marine environment can be difficult due to the high spatial and temporal variability of ocean currents. We employed a mutually enriching approach of population genetic assignment procedures and dispersal predictions from a hydrodynamic model to overcome this difficulty and quantify the movement of dispersing floating fruit of the temperate seagrass Posidonia australis Hook.f. across coastal waters in south‐western Australia. Dispersing fruit cohorts were collected from the water surface over two consecutive years, and seeds were genotyped using microsatellite DNA markers. Likelihood‐based genetic assignment tests were used to infer the meadow of origin for seed cohorts and individuals. A three‐dimensional hydrodynamic model was coupled with a particle transport model to simulate the movement of fruit at the water surface. Floating fruit cohorts were mainly assigned genetically to the nearest meadow, but significant genetic differentiation between cohort and most likely meadow of origin suggested a mixed origin. This was confirmed by genetic assignment of individual seeds from the same cohort to multiple meadows. The hydrodynamic model predicted 60% of fruit dispersed within 20 km, but that fruit was physically capable of dispersing beyond the study region. Concordance between these two independent measures of dispersal provides insight into the role of physical transport for long distance dispersal of fruit and the consequences for spatial genetic structuring of seagrass meadows.