bluuebunny/crossref_metadata_2025 huggingface dataset:
R&D and non-R&D in the innovation process among firms in ASEAN countries
Authors: Tsuji Masatsugu , Ueki Yasushi , Shigeno Hidenori , Idota Hiroki , Bunno Teruyuki
Published: April 2018

Purpose

The purpose of this paper is to identify factors promoting innovation in the framework of R&D based on surveys conducted on firms in five ASEAN countries, Indonesia, Laos, Thailand, the Philippines, and Vietnam.

Design/methodology/approach

The analytical method divided sample firms into two categories, namely, “the R&D group” and “non-R&D group.” The analysis attempts to identify which of the internal capabilities, consisting of technology, human factors and organization factors, promote innovation. Ordered probit analysis is employed.

Findings

Findings from the estimations indicate that the two groups pursue product innovation differently. The R&D group promotes innovation by cross-functional teams of production, engineering, and marketing and IT use, whereas the non-R&D group promote product innovation by HRD programs for workers, group awards for suggestions or QC, and ISO9000 series.

Research limitations/implications

The number of samples related to the non-R&D group is too small to conduct statistical analysis. External linkages played an important role in the authors’ previous studies. The introduction of external linkages into the model may yield different results, though the analysis would become more complex.

Practical implications

The results of this paper provide the solid basis of policy to promote innovation and upgrading SMEs in the region.

Social implications

Many ASEAN SMEs successfully achieve innovation without owning specified in-house departments or sections to conduct R&D.

Originality/value

The features of this paper lie in the original firm-level survey data and rigorous estimation method using ordered probit analysis, which are new to this literature.
Project and processes: a convenient but simplistic dichotomy
Authors: Harvey Jean , Aubry Monique
Published: April 2018

Purpose

The purpose of this paper is to explore commonalities and differences between projects and processes, and between project management (PjM) and process management (PcM), with a view to challenge this dichotomic typology, clarify the gray areas in between and propose better ways to classify and manage different endeavors.

Design/methodology/approach

The research compares different tools and techniques used in both fields, explores the respective literatures and uses various examples to bring out similarities and differences.

Findings

The current paradigms engender a number of organizational endeavors, which are actually complex processes being managed as projects, using the PjM body of knowledge. Because each instantiation takes a somewhat different form, it is treated as a one-of-a-kind undertaking; whereby many of the opportunities for learning and continuous improvement associated with PcM are lost. A reframing and typology is proposed to clarify the central notions involved.

Research limitations/implications

The proposed model has not been tested empirically and the authors could not agree on all aspects of the paper, though existing differences are more about degrees, nuances and wording than about the basic findings of the paper.

Practical implications

The research makes the case that two research and practice communities that are evolving independently have much to gain by adopting a unified model and integrating their respective bodies of knowledge. Practitioners would thus access resources that are better adapted to the management challenges they are facing and gain a sustainable source of strategic advantage.

Originality/value

The paper challenges long-established paradigms between two distinct research streams. A new typology and classification criteria are proposed.
Enhancing information impact: how do we make the most of our information senses?
Authors: Smedley Jo
Published: April 2018

Purpose

This paper discusses the importance of effectively using senses in sharing information and managing the opportunities they individually and collaboratively offer.

Design/methodology/approach

The paper considers how information is best portrayed by each sense, individually and collaboratively.

Findings

How information takes account of senses to ensure that information engagement is maximised through its entertainment and education value.

Research limitations/implications

As the value and importance of information continues to grow, so will the urgency of information engagement and ensuring that its portrayal is appropriate, effective and efficient through a variety of sensory approaches – whether individual or collaborative.

Practical implications

One sensory size does not fit all. It is important that the dimensions and flexibility of information are reflected to ensure that it can adapt to suit various audiences. These flexible approaches will ensure that learner engagement is maximised.

Social implications

All information methods are of equal value. By ensuring that learners are able to access the information method that is most appropriate to them, then learning potential can be maximised. There is a growing urgency to move away from a status quo information approach and thereby enhance variety and enable potential.

Originality/value

Information is power. Each person is unique. How they learn combines these two qualities. A flexible approach to information engagement will encourage and enable information and learning sharing to maximise achievement and contribute to ongoing information entrepreneurship, resilience and sustainability.
Technical and economic modelling and evaluation of a water distribution system equipped with an autoclave for industrial production applications
Authors: Faccio Maurizio , Gamberi Mauro , Nedaei Mojtaba , Pilati Francesco
Published: April 2018

Purpose

The purpose of this paper is to investigate the autoclave-pump pressured water distribution system. Pressured water is used in many manufacturing processes, as a raw material or as a service fluid for different applications.

Design/methodology/approach

The performances and the total installation costs of such systems are strongly related to its design and to its decision variables definition. The authors first identify the independent variables (i.e. the decision variables) and the dependent variables of the system and, second, propose a techno-economic mathematical method able to determine its minimum installation cost with an integrated approach.

Findings

The trade-off between the autoclave installation costs versus the pump installation costs is demonstrated. A sensitive analysis of the cost of the system as function of its decision variables has been performed to propose a practical graphical analysis tools to proper design the integrated pump-autoclave pressured water distribution system.

Originality/value

Many previous researches focus only on the pump system optimization or in the tank system optimization without an integrated approach. The wide utilization in industry of the autoclave-pump pressured water distribution system together with the lack of similar contributions in this area enforces the value of this research.
Criminal Justice Statistics—An Evolution
Authors: Wormeli Paul
Published: April 2018

The origins of the Bureau of Justice Statistics and criminal justice statistics in general go back 150 years, but the U.S. President's Commission on Law Enforcement and Administration of Justice in 1967, along with subsequent panels and commissions, added urgency and specificity to the work to be done to improve our understanding of the operation of the criminal justice system and of crime. Criminal justice statistics have the potential to be used to shape and evaluate specific policies and programs when the statistics are timely, accurate, and relevant to the decisions being made for policy formulation or evaluation. The full development of effective criminal justice statistics on crime and the administration of the justice system can provide for informed decision making and more insightful resource allocation. In this article, I summarize the historical progressions and evolution of criminal justice statistics in light of the changes affecting the justice environment and propose future work.
Challenges and Opportunities for Creating Intelligent Hazard Alerts: The “FloodHippo” Prototype
Authors: Johnson J. Michael , Coll Jim M. , Ruess Paul J. , Hastings Jordan T.
Published: April 2018

Disasters evolving from hazards are a persistent and deadly occurrence in the United States. Despite this, hazard alerts have remained spatially vague, temporally imprecise, and lack actionable information. These deficiencies indicate a divide between the status quo and what is possible given modern environmental models, geographic information systems (GIS), and smartphone capabilities. This work describes an alternative, prototype system, “FloodHippo,” which integrates operational model outputs, cloud‐based GIS, and expanded communication channels to provide personal and interactive disaster alerts for floods. The precepts and methods underpinning FloodHippo apply equally to other disasters that evolve over space and time, presenting the opportunity for a more intelligent disaster response system. The development of such a system would not only minimize current shortcomings in disaster alerts but also improve resilience through individual action, along with community, academic, and federal cooperation.
Nrf2 and Keap1 abnormalities in esophageal squamous cell carcinoma and association with the effect of chemoradiotherapy
Authors: Zhang Jingze , Jiao Qinghua , Kong Li , Yu Jing , Fang Aiju , Li Minghuan , Yu Jinming
Published: April 2018

Background

The Keap1‐Nrf2 pathway is a key antioxidant and redox signaling cascade. Pathway abnormalities enhance the reactive oxygen species scavenging ability of cancer cells; thus the pathway is involved in carcinogenesis and resistance to chemoradiotherapy (CRT). This retrospective study was conducted to examine the status of the Keap1‐Nrf2 pathway in locally advanced esophageal squamous cell carcinoma (ESCC) and to analyze its prognostic value in patients receiving CRT.

Methods

Nrf2 and Keap1 expression were immunohistochemically examined in 152 ESCC and 31 normal esophageal mucosae. All ESCC specimens were obtained from patients with locally advanced ESCC who underwent CRT.

Results

Strong staining of nuclear and cytoplasmic Nrf2 and limited or absent Keap1 expression was uncommon in normal tissues, but frequently observed in ESCC. Interaction between Nrf2 and Keap1 in normal mucosae is negatively correlated, while in tumors there is no negative correlation, indicating that there is little to no interaction between Nrf2 and Keap1 in ESCC. Positive Nrf2 expression in the nucleus was of diagnostic value for predicting ESCC from normal esophageal mucosae, and was significantly associated with poorer clinical response and poor progression‐free survival after CRT. The value of Keap1 expression for diagnosis and predicting CRT outcomes was marginal. These different influences of Keap1 and Nrf2 on ESCC indicated that the signaling of this pathway was disturbed and displayed a Keap1‐independent pattern.

Conclusion

Aberrant signaling via the Keap1‐Nrf2 pathway was common in ESCC and was associated with response and survival after CRT.
Pulmonary pleomorphic carcinoma: A case harboring EGFR mutation treated with EGFR‐TKIs
Authors: Masuda Ken , Tokito Takaaki , Azuma Koichi , Yanagida Eriko , Nakamura Masayuki , Naito Yoshiko , Matsuo Norikazu , Ishii Hidenobu , Yamada Kazuhiko , Akiba Jun , Hoshino Tomoaki
Published: April 2018

Pulmonary pleomorphic carcinoma (PPC) is a very rare type of primary lung cancer with an aggressive clinical course. Few reports have documented therapeutic options for PPC with EGFR mutations. Herein, we report a case of PPC with EGFR mutation treated with EGFR‐tyrosine kinase inhibitors (TKIs). A 65‐year‐old Japanese woman was diagnosed with stage IV lung adenocarcinoma with L858R point mutation in exon 21. Despite treatment with erlotinib, the patient died after two weeks as a result of rapid disease progression. Postmortem examination indicated that the thoracic tumors consisted primarily of spindle/sarcomatous components, while expression of the mutated EGFR protein was only observed in adenocarcinoma components. We speculate that the tumor was not driven by EGFR mutation. Clinicians should bear in mind the possibility of pleomorphic carcinoma if EGFR‐TKI treatment fails to achieve a clinical response for adenocarcinoma harboring an activating EGFR mutation diagnosed on the basis of small biopsy specimens.
Nerve entrapment syndromes in dermatology: Review and practical approach to treatment
Authors: Zagarella Samuel
Published: April 2018

A good understanding of cutaneous nerve entrapment syndromes is important for physicians to provide early and accurate diagnosis and treatment. These syndromes have traditionally been managed with analgesics, antidepressants or antiepileptic medication but this approach is often inadequate and causes frequent adverse medication effects. With early diagnosis and treatment, many nerve entrapment syndromes can be successfully managed with physical, non‐pharmacological approaches including stretches, exercises and physiotherapy.
Use of fragmented QRS in prognosticating clinical deterioration and mortality in pulmonary embolism: A meta‐analysis
Authors: Qaddoura Amro , Digby Geneviève C. , Kabali Conrad , Kukla Piotr , Tse Gary , Glover Benedict , Baranchuk Adrian M.
Published: April 2018

Background

Fragmented QRS (fQRS) on electrocardiography is potentially valuable in prognosticating acute pulmonary embolism (PE). ECG is one of the first tests performed in the emergency department, quickly interpretable, noninvasive, inexpensive, and available in remote areas. We aimed to review fQRS's role in PE prognostication.

Methods

We searched MEDLINE, EMBASE, Google Scholar, Web of Science, abstracts, conference proceedings, and reference lists until October 2017. Eligible studies used fQRS to prognosticate patients for the main outcomes of death and clinical deterioration or escalation of therapy. Two authors independently selected studies, with disagreement resolved by consensus. Ad hoc piloted forms were used to extract data and assess risk of bias. We used a random‐effects model to pool relevant data in meta‐analysis with odds ratios (OR) and 95% confidence intervals (CI), while all other data were synthesized qualitatively. Statistical heterogeneity was assessed using the I2 index.

Results

We included five studies (1,165 patients). There was complete agreement in study selection. fQRS significantly predicted in‐hospital mortality (OR [95% CI], 2.92 [1.73–4.91]; p < .001), cardiogenic shock (OR [95% CI], 4.71 [1.61–13.70]; p = .005), and total mortality at 2‐year follow‐up (OR [95% CI], 4.42 [2.57–7.60]; p < .001). Adjusted analyses were generally consistent with these results.

Conclusion

Although few studies have explored the current study's question, they showed that fQRS is potentially valuable in PE prognostication. fQRS should be considered as an entry, along with other clinical and ECG findings, in a PE risk score.
Co‐production in peer support group research with disabled people
Authors: Purcal Christiane , Fisher Karen R. , Robinson Sally , Meltzer Ariella , Bevan Ngila
Published: April 2018

Peer support action research is a co‐production method used by groups of people with a shared experience, in order to generate knowledge and mutual assistance. This paper analyses co‐production experiences from a recent Australian research project, which formed peer support groups to explore how disabled people were managing their transition to self‐directed support. Using the project as a case study and applying a community participation framework derived from social geography, this paper addresses questions about which collaborative mechanisms strengthen peer support research so that the research process and outputs benefit each of the participants involved. The project used a mixed‐method, co‐production approach. University researchers formed research partnerships with disability community organisations to support the research activity in each Australian state. The community organisations formed peer support groups, facilitated the groups and communicated group processes and findings to the university researchers. The group members and facilitators decided what they wanted to do in the group and how to do it. The academics provided research support, training, a topic guide and resources for group activities. All participants reflected on challenges and lessons learnt and modified the project as it progressed. Both the methods and findings have implications for peer support as co‐productive research. The process enhanced the research capacity of the participants, disability community and academics, and strengthened peer support, advocacy and confidence about self‐directed support. The findings from the peer support groups about their transition to self‐directed support demonstrated their preference for, and trust in, peers as information sources. The regular collective reflections with the facilitators produced an additional level of data collection and analysis that enhanced the quality of the co‐production, enabling greater participant control over design and knowledge generation.
Exploring the Role of Blame in Couple Relationships within the Triangular Setting of Couple Psychotherapy
Authors: Sehgal Amita
Published: April 2018

This paper describes the process of couple therapy with two couples that used blame as the currency of exchange in their relationship. Both couples struggled with managing three‐person relationships. The triangular setting of couple psychotherapy provoked and triggered primitive anxieties around exclusion, rejection and abandonment in both cases. I draw upon clinical work with two such couples to illustrate how one repeatedly collapsed the triangular space whereas the other gradually became more able to bear it. I refer to scientific evidence of the brain's ability to continue to change in response to new learning by forming fresh neural connections throughout life. I suggest that the repetitive occurrence of new experiences within couple psychotherapy can generate new neural pathways thereby biologically influencing new ways of how partners might respond to each other. I conclude by highlighting the therapeutic potential of the framework within which couple psychotherapy takes place, a triangular configuration which offers a developmental opportunity for navigating primitive anxieties related to triangular relationships.
Senescent cells re‐engineered to express soluble programmed death receptor‐1 for inhibiting programmed death receptor‐1/programmed death ligand‐1 as a vaccination approach against breast cancer
Authors: Chen Zehong , Hu Kang , Feng Lieting , Su Ruxiong , Lai Nan , Yang Zike , Kang Shijun
Published: April 2018

Various types of vaccines have been proposed as approaches for prevention or delay of the onset of cancer by boosting the endogenous immune system. We previously developed a senescent‐cell‐based vaccine, induced by radiation and veliparib, as a preventive and therapeutic tool against triple‐negative breast cancer. However, the programmed death receptor‐1/programmed death ligand‐1 (PD‐1/PD‐L1) pathway was found to play an important role in vaccine failure. Hence, we further developed soluble programmed death receptor‐1 (sPD1)‐expressing senescent cells to overcome PD‐L1/PD‐1‐mediated immune suppression while vaccinating to promote dendritic cell (DC) maturity, thereby amplifying T‐cell activation. In the present study, sPD1‐expressing senescent cells showed a particularly active status characterized by growth arrest and modified immunostimulatory cytokine secretion in vitro. As expected, sPD1‐expressing senescent tumor cell vaccine (STCV/sPD‐1) treatment attracted more mature DC and fewer exhausted‐PD1+ T cells in vivo. During the course of the vaccine studies, we observed greater safety and efficacy for STCV/sPD‐1 than for control treatments. STCV/sPD‐1 pre‐injections provided complete protection from 4T1 tumor challenge in mice. Additionally, the in vivo therapeutic study of mice with s.c. 4T1 tumor showed that STCV/sPD‐1 vaccination delayed tumorigenesis and suppressed tumor progression at early stages. These results showed that STCV/sPD‐1 effectively induced a strong antitumor immune response against cancer and suggested that it might be a potential strategy for TNBC prevention.
Efficacy of extracting indices from large‐scale acoustic recordings to monitor biodiversity
Authors: Buxton Rachel T. , McKenna Megan F. , Clapp Mary , Meyer Erik , Stabenau Erik , Angeloni Lisa M , Crooks Kevin , Wittemyer George
Published: April 2018

Passive acoustic monitoring could be a powerful way to assess biodiversity across large spatial and temporal scales. However, extracting meaningful information from recordings can be prohibitively time consuming. Acoustic indices (i.e., a mathematical summary of acoustic energy) offer a relatively rapid method for processing acoustic data and are increasingly used to characterize biological communities. We examined the relationship between acoustic indices and the diversity and abundance of biological sounds in recordings. We reviewed the acoustic‐index literature and found that over 60 indices have been applied to a range of objectives with varying success. We used 36 of the most indicative indices to develop a predictive model of the diversity of animal sounds in recordings. Acoustic data were collected at 43 sites in temperate terrestrial and tropical marine habitats across the continental United States. For terrestrial recordings, random‐forest models with a suite of acoustic indices as covariates predicted Shannon diversity, richness, and total number of biological sounds with high accuracy (R2 ≥ 0.94, mean squared error [MSE] ≤170.2). Among the indices assessed, roughness, acoustic activity, and acoustic richness contributed most to the predictive ability of models. Performance of index models was negatively affected by insect, weather, and anthropogenic sounds. For marine recordings, random‐forest models poorly predicted Shannon diversity, richness, and total number of biological sounds (R2 ≤ 0.40, MSE ≥ 195). Our results suggest that using a combination of relevant acoustic indices in a flexible model can accurately predict the diversity of biological sounds in temperate terrestrial acoustic recordings. Thus, acoustic approaches could be an important contribution to biodiversity monitoring in some habitats.
Wage Regulation and the Quality of Police Applicants
Authors: Crawford Rowena , Disney Richard
Published: April 2018

Pay structures may not reflect differences in individual productivity and effort; in particular, public pay regulation can distort labour markets. We analyse the impact of nationally regulated pay on the quality of applicants to be police officers across England and Wales, exploiting a unique dataset of individual test scores from the national assessment required of all police applicants, and combining this with data on local labour markets and policing conditions. National wage setting impacts on the quality of police applicants through two channels: first, through spatial variations in the relative wage of policing compared to other occupations, and second, because national wages cannot compensate for local variations in the disamenity of policing. We also provide preliminary evidence on whether police recruit quality is associated with police force performance.
Asp 58 modulates lens αA‐crystallin oligomer formation and chaperone function
Authors: Takata Takumi , Nakamura‐Hirota Tooru , Inoue Rintaro , Morishima Ken , Sato Nobuhiro , Sugiyama Masaaki , Fujii Noriko
Published: April 2018

Senile cataract onset is caused by insolubilization of lens proteins. The lens crystallin protein family correctly orders the formation of homo‐ or hetero‐oligomers in lens fiber cells. Because lens fiber cells do not divide, covalent post‐translational modifications, such as isomerization of aspartate residues, accumulate with aging. Although many isomerization sites of αA‐crystallin have been reported, their structural and functional contributions have never been identified. In this study, αA‐crystallin was extracted from aged human lens and separated into each oligomeric state by size exclusion chromatography and electrophoresis. The novel combination methodology of in‐solution/gel tryptic digestion with liquid chromatography equipped with mass spectrometry (LC‐MS/MS) was used to evaluate the isomerization of Asp 58. The contributions of isomerization to assembly, solubility, and chaperone functions of αA‐crystallin were estimated using a series of mutations of Asp 58 in αA‐crystallin. The results indicated that the isomerization of Asp 58 depended on the oligomer size and age of the lens. The substitution of Asp 58 for hydrophobic residues increased αA‐crystallin oligomer size and decreased solubility. All substitutions decreased the chaperone function of αA‐crystallin for aggregates of bovine βL‐crystallin and alcohol dehydrogenase. The data indicated that Asp 58 in αA‐crystallin was critical for intermolecular interactions in the lens. Our results also suggested that LC‐MS/MS‐based isomerization analyses of in‐gel‐digested products could be useful for investigating the isomerization of Asp residues in oligomeric states. This method could also be used to analyze d/l ratios of amino acid residues in soluble protein aggregates.
What Are Boards For? Evidence from Closely Held Firms in Colombia
Authors: Villalonga Belén , Trujillo María‐Andrea , Guzmán Alexander , Cáceres Neila
Published: April 2018

Using a large survey database on the corporate governance practices of privately held Colombian firms, we investigate why firms have boards, and how that choice and the balance of power among the board, controlling shareholders, and minority shareholders affect the trade‐offs between control, liquidity, and growth and, ultimately, firm performance. We find that the probability of having a board increases with the number of shareholders and in family firms. When the preferences of controlling and minority shareholders diverge, as with respect to capital structure and dividend policy, boards support controlling shareholders’ decisions, thereby exacerbating the agency conflict between the two groups of shareholders.
Normative properties of multidimensional inequality indices with data‐driven dimensional weights: The case of a Gini index
Authors: Banerjee Asis Kumar
Published: April 2018

A central problem in constructing multidimensional inequality indices is that of devising weights on the dimensions. There are two different approaches to the problem: the normative and the data‐driven. Indices derived from data‐driven weights have the limitation that they may violate normatively desired properties. This paper asks whether it is possible to obtain normatively acceptable inequality indices from a data‐driven approach. A multidimensional Gini index is derived from an endogenous weighting scheme and is shown to possess a number of desired properties. The existing literature does not seem to contain a Gini index that satisfies all of these properties.
Characterization of a novel allelic variant in HLA‐B*40 lineage, HLA‐B*40:298:02, by cloning and sequencing
Authors: Tian W. , Zhu F. M. , Wang W. Y. , Li L. X. , Cai J. H.
Published: April 2018

A novel allelic variant in HLA‐B*40 lineage, HLA‐B*40:298:02, has been identified in an individual of Han ethnicity afflicted with nasopharyngeal carcinoma in Hunan province, southern China. Following polymerase chain reaction–Sanger sequence‐based typing (PCR–SBT), this new variant was further confirmed by two distinct strategies of cloning and sequencing. HLA‐B*40:298:02 differs from HLA‐B*40:298:01 by a single synonymous cytosine substitution at nucleotide position 26 (T→C) in exon 3, which corresponds to codon 99 of the mature HLA‐B mRNA molecule. This new allele has an estimated frequency of 0.0002, in about 2,500 sequence‐based typed subjects from the same population.
Self‐Selection in Migration Between Developing Countries: The Role of Unobservable Skills of Gauteng's Migrant Population
Authors: Nontenja Nwabisa , Kollamparambil Umakrishnan
Published: April 2018

The present study investigates the presence of self‐selection among internal and international migrants in Gauteng, South Africa and further disentangles the effects of observed and unobserved characteristics in the self‐selection of migrants by conducting Oaxaca‐Blinder decomposition on overall employment and self‐employment outcome variables. Our analysis, based on system‐GMM analysis of pseudo‐panel data, indicates that international migrants experienced markedly higher levels of employment than both locals and internal migrants driven by higher rates of informal and self‐employment. International migrants were also found to outperform their South African‐born counterparts on various variables indicative of well‐being like total household income, per capita household income, higher life satisfaction, and lower debt levels. Even though international migrants did not have higher levels of education, the Oaxaca‐Blinder decomposition provided evidence of the positive selection of international migrants to Gauteng, based on unobservable characteristics, to achieve higher levels of employment and self‐employment.
Husbandry and breeding of Greater green leafbird Chloropsis sonnerati at Jurong Bird Park, Singapore
Authors: Kumar M. , Lee J. , Cabana F.
Published: April 2018

The only chloropseids known that are alive today, are the leafbirds. The Greater green leafbird Chloropsis sonnerati is a small‐sized, South East Asian passerine that is being threatened by the songbird trade. At Jurong Bird Park, Singapore, C. sonnerati bred for the first time in January 2017. This article will describe the methods utilized to breed this species successfully, including using a bamboo‐fibre canary nest. Initial observations of nesting Greater green leafbirds in a mixed aviary showed that C. sonnerati were consistently disturbed by the pair of Red crested turaco Tauraco erythrolophus. The turacos were removed from the aviary and this allowed the Greater green leafbirds to build a nest and lay two eggs. Chloropsis sonnerati incubated the eggs for 14 days and the first egg hatched on 1 January 2017. Parents were observed taking good care of the chicks for the first 6 days but one chick was found dead on the ground on day 7. The remaining chick was transferred to the Breeding & Research Centre (BRC) to be hand reared. The C. sonnerati juvenile was observed perching on the nest basket on day 16 and it fledged on day 34. We attribute this successful leafbird breeding to the type of nest, nesting materials, diet and hand‐rearing diet, and the detailed observations and care by the keepers.
Electronic health record reviews to measure diagnostic uncertainty in primary care
Authors: Bhise Viraj , Rajan Suja S. , Sittig Dean F. , Vaghani Viralkumar , Morgan Robert O. , Khanna Arushi , Singh Hardeep
Published: April 2018

Rationale, aims and objectives

Diagnostic uncertainty is common in primary care. Because it is challenging to measure, there is inadequate scientific understanding of diagnostic decision‐making during uncertainty. Our objective was to understand how diagnostic uncertainty was documented in the electronic health record (EHR) and explore a strategy to retrospectively identify it using clinician documentation.

Methods

We reviewed the literature to identify documentation language that could identify both direct expression and indirect inference of diagnostic uncertainty and designed an instrument to facilitate record review. Direct expression included clinician's use of question marks, differential diagnoses, symptoms as diagnosis, or vocabulary such as “probably, maybe, likely, unclear or unknown,” while describing the diagnosis. Indirect inference included absence of documented diagnosis at the end of the visit, ordering of multiple consultations or diagnostic tests to resolve diagnostic uncertainty, and use of suspended judgement, test of treatment, and risk‐averse disposition. Two physician‐reviewers independently reviewed notes on a sample of outpatient visits to identify diagnostic uncertainty at the end of the visit. Documented Ninth Revision of the International Classification of Diseases (ICD‐9) diagnosis codes and note quality were assessed.

Results

Of 389 patient records reviewed, 218 had evidence of diagnostic activity and were included. In 156 visits (71.6%), reviewers identified clinicians who experienced diagnostic uncertainty with moderate inter‐reviewer agreement (81.7%; Cohen's kappa: 0.609). Most cases (125, 80.1%) showed evidence of both direct expression and indirect inference. Uncertainty was directly expressed in 139 (89.1%) cases, most commonly by using symptoms as diagnosis (98, 62.8%), and inferred in 144 (92.3%). In more than 1/3 of visits (58, 37.2%), diagnostic uncertainty was recorded inappropriately using ICD‐9 codes.

Conclusions

While current diagnosis coding mechanisms (ICD‐9 and ICD‐10) are unable to capture uncertainty, our study finds that review of EHR documentation can help identify diagnostic uncertainty with moderate reliability. Better measurement and understanding of diagnostic uncertainty could help inform strategies to improve the safety and efficiency of diagnosis.
Application of a reflective microscope objective for multiphoton microscopy
Authors: KABIR MOHAMMAD M. , CHOUBAL AAKASH M. , TOUSSAINT KIMANI C
Published: April 2018

Reflective objectives (ROs) mitigate chromatic aberration across a broad wavelength range. Yet, a systematic performance characterisation of ROs has not been done. In this paper, we compare the performance of a 0.5 numerical‐aperture (NA) reflective objective (RO) with a 0.55 NA standard glass objective (SO), using two‐photon fluorescence (TPF) and second‐harmonic generation (SHG). For experiments spanning ∼1 octave in the visible and NIR wavelengths, the SO leads to defocusing errors of 25–40% for TPF images of subdiffraction fluorescent beads and 10–12% for SHG images of collagen fibres. The corresponding error for the RO is ∼4% for both imaging modalities. This work emphasises the potential utility of ROs for multimodal multiphoton microscopy applications.
Identification and quantification of blood–brain barrier transporters in isolated rat brain microvessels
Authors: Al Feteisi Hajar , Al‐Majdoub Zubida M. , Achour Brahim , Couto Narciso , Rostami‐Hodjegan Amin , Barber Jill
Published: April 2018

The blood–brain barrier (BBB) maintains brain homeostasis by tightly regulating the exchange of molecules with systemic circulation. It consists primarily of microvascular endothelial cells surrounded by astrocytic endfeet, pericytes, and microglia. Understanding the make‐up of transporters in rat BBB is essential to the translation of pharmacological and toxicological observations into humans. In this study, experimental workflows are presented in which the optimization of (a) isolation of rat brain microvessels (b) enrichment of endothelial cells, and (c) extraction and digestion of proteins were evaluated, followed by identification and quantification of BBB proteins. Optimization of microvessel isolation was indicated by 15‐fold enrichment of endothelial cell marker Glut1 mRNA, whereas markers for other cell types were not enriched. Filter‐aided sample preparation was shown to be superior to in‐solution sample preparation (10251 peptides vs. 7533 peptides). Label‐free proteomics was used to identify nearly 2000 proteins and quantify 1276 proteins in isolated microvessels. A combination of targeted and global proteomics was adopted to measure protein abundance of 6 ATP‐binding cassette and 27 solute carrier transporters. Data analysis using proprietary Progenesis and open access MaxQuant software showed overall agreement; however, Abcb9 and Slc22a8 were quantified only by MaxQuant, whereas Abcc9 and Abcd3 were quantified only by Progenesis. Agreement between targeted and untargeted quantification was demonstrated for Abcb1 (19.7 ± 1.4 vs. 17.8 ± 2.3) and Abcc4 (2.2 ± 0.7 vs. 2.1 ± 0.4), respectively. Rigorous quantification of BBB proteins, as reported in this study, should assist with translational modeling efforts involving brain disposition of xenobiotics.

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High‐mobility group box 1 in Parkinson's disease: from pathogenesis to therapeutic approaches
Authors: Angelopoulou Efthalia , Piperi Christina , Papavassiliou Athanasios G.
Published: April 2018

Parkinson's disease (PD) presents the second most common neurodegenerative disorder with largely unknown pathogenesis and inefficient therapeutic management. Accumulating data indicate that neuroinflammation, autophagy impairment, α‐synuclein aggregation, and mitochondrial dysfunction may contribute to PD onset; however, the molecular mechanisms underlying these pathophysiological processes are still under elucidation. Interestingly, recent evidence has indicated that High‐mobility group box 1 (HMGB1), a DNA‐binding protein that can be actively secreted by inflammatory cells and passively released by necrotic cells may play a key role in PD pathogenesis. HMGB1 has been shown to participate in neuroinflammation, modulate autophagy and apoptosis as well as regulate gene transcription. Furthermore, therapeutic targeting of HMGB1 with either anti‐HMGB1 antibodies or selective inhibitors, such as glycyrrhizin, has been shown to inhibit neurodegeneration in animal models. This review provides an update of recent data on the emerging role of HMGB1 in PD pathogenesis and discusses potential therapeutic approaches.

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Selective Inversion Recovery Quantitative Magnetization Transfer Brain MRI at 7T: Clinical and Postmortem Validation in Multiple Sclerosis
Authors: Bagnato Francesca , Hametner Simon , Franco Giulia , Pawate Siddharama , Sriram Subramaniam , Lassmann Hans , Gore John , Smith Seth E. , Dortch Richard
Published: April 2018

BACKGROUND AND PURPOSE

An imaging biomarker of myelin integrity is an unmet need in multiple sclerosis (MS). Selective inversion recovery (SIR) quantitative magnetization transfer imaging (qMT) provides assays of myelin content in the human brain. We previously translated the SIR method to 7T and incorporated a rapid turbo field echo (TFE) readout for whole‐brain imaging within clinically acceptable scan times. We herein provide histological validation and test in vivo feasibility and applicability of the SIR‐TFE protocol in MS.

METHODS

Clinical (T1‐ and T2‐weighted) and SIR‐TFE MRI scans were performed at 7T in a postmortem MS brain and MRI data were acquired in 10 MS patients and 14 heathy volunteers in vivo. The following parameters were estimated from SIR data: the macromolecular‐to‐free water pool‐size‐ratio (PSR), the spin‐lattice relaxation rate of water (R1f), and the MT exchange rate (kmf). Differences in SIR parameters across tissue types, eg, white matter lesions (WM‐Ls) and normal appearing WM (NAWM) in patients, and normal white matter (NWM) in heathy volunteers were evaluated. Associations between SIR parameters and disability scores were assessed.

RESULTS

For postmortem scans, correspondence was observed between WM‐Ls and NAWM from histology and PSR/R1f values. In vivo differences were detected for PSR, R1f, and kmf between WM‐Ls and NWM (P ≤ .041). Associations were seen between WM‐Ls/ NAWM PSR and disability scores (r ≤ –.671, P ≤ .048).

CONCLUSIONS

SIR‐qMT at 7T provides sensitive, quantitative measures of myelin integrity for clinical and research applications.
Perception and Expressing Habits of Smiling and Angry Expressions Modulated by Facial Physical Attractiveness in Asian Female Persons
Authors: Song Miao , Shinomori Keizo , Qian Qian
Published: April 2018

In this study, we investigated the effects of facial physical attractiveness on perception and expressing habit of smiling and angry expressions. In experiment 1, 20 participants rated 60 photo subjects’ smiling and angry expressions of uncontrolled physical expression configuration. The results showed that for the angry faces, the perceived expression intensity and the expression naturalness in the attractive group were significantly stronger than those in the unattractive group; for the smiling faces, this attractiveness bias was not observed. In experiment 2, using artificial expressions made by an identical expression template, interestingly, the perceived expression intensity and the expression naturalness of the smiling faces in the attractive group were stronger than those in the unattractive group, while the impression strength of anger between the two groups was approximately the same. A comparison of the two observations suggests that facial physical attractiveness can enhance the perceived intensity of a smiling expression but not an angry expression, and that the inconsistencies between the two experiments are due to the difference of expressing habits between unattractive and attractive persons. These results have implications as regards the effect of facial attractiveness on the expressing habits of expression senders and the person’s development of social skills.
Reading Swift's poetry, 1967–2017
Authors: Cook Daniel
Published: April 2018

This essay surveys major scholarship on Jonathan Swift's poetry published after 1967, the 300th anniversary of his birth up to the 350th, in 2017. What is the current status of Swift as a poet, as distinct from Swift the prose satirist or even Swift the Hibernian Patriot? Is he best placed in separate Irish or English traditions or in both? Was he a mere man of rhymes or an ambitious poet? How have scholars approached his verse? Which works have received the most attention? Which deserve more?
Acute liver failure caused by hepatitis E virus genotype 3 and 4: A systematic review and pooled analysis
Authors: Haffar Samir , Shalimar  , Kaur Ravinder J. , Wang Zhen , Prokop Larry J. , Murad Mohammad H. , Bazerbachi Fateh
Published: April 2018

Background & Aims

Acute liver failure caused by hepatitis E virus genotype 3 and 4 has been rarely described. Because of the presence of a short golden therapeutic window in patients with viral acute liver failure from other causes, it is possible that early recognition and treatment might reduce the morbidity and mortality. We performed a systematic review and pooled analysis of acute liver failure caused by hepatitis E virus genotype 3 and 4.

Methods

Two reviewers appraised studies after searching multiple databases on June 12th, 2017. Appropriate tests were used to compare hepatitis E virus genotype 3 vs 4, suspected vs confirmed genotypes, hepatitis E virus‐RNA positive vs negative, and to discern important mortality risk factors.

Results

We identified 65 patients, with median age 58 years (range: 3‐79), and a male to female ratio of 1.2:1. The median bilirubin, ALT, AST and alkaline phosphatase (expressed by multiplication of the upper limit of normal) levels were 14.8, 45.3, 34.8 and 1.63 respectively. Antihepatitis E virus IgG, antihepatitis E virus IgM and hepatitis E virus‐RNA were positive in 84%, 91% and 86% of patients respectively. The median interval from symptoms onset to acute liver failure was 23 days, and 16 patients underwent liver transplantation. Final outcome was reported in 58 patients and mortality was 46%. Age was a predictor of poor prognosis in multivariate analysis. No important differences were found between patients infected with genotype 3 vs 4, patients with confirmed vs suspected genotypes, or patients with positive vs negative RNA.

Conclusion

Acute liver failure caused by hepatitis E virus genotype 3 and 4 is rare, similar between genotypes, occurs commonly in middle‐aged/elderly patients and has a very high mortality. Age is predictive of poor prognosis in multivariate analysis.
Hydrocarbons mediate seed dispersal: a new mechanism of vespicochory
Authors: Chen Gao , Wang Zheng‐Wei , Wen Ping , Wei Wei , Chen Ya , Ai Hui , Sun Wei‐Bang
Published: April 2018

Vespicochory, seed dispersal by hornets, is an uncommon seed dispersal pattern in angiosperms. To date, this phenomenon has been recorded in only four families. Because of its rarity, the causes and consequences of vespicochory remain unclear. Hence, this seed dispersal syndrome is often regarded as anecdotal.

Through field investigations, chemical analyses, electrophysiological tests, identification of chemosensory proteins from the antennae of hornets, and behavioral assays, we investigated whether olfactory and/or visual cues of the diaspores of Stemona tuberosa mediate the behavior of the social hornets and maintain their mutualism.

This study demonstrated that the elaiosome of S. tuberosa emits hydrocarbons, which are attractive to hornets. However, these compounds, which induce responses in the antennae of naive hornets, are ubiquitous substances on insect cuticle surfaces. Innate preference and experienced foraging behavior of hornets can increase their seed dispersal efficiency.

This is the first example in which hydrocarbons have been identified as a diaspore odour involved in the attraction of hornets. Given that the ubiquity of hornets, and the communication function of hydrocarbons in insects, we predict that this rare seed dispersal mechanism may be an overlooked mechanism of insect–plant mutualism.
Epigenetically Enhanced PDT Induces Significantly Higher Levels of Multiple Extrinsic Pathway Apoptotic Factors than Standard PDT, Resulting in Greater Extrinsic and Overall Apoptosis of Cutaneous T‐cell Lymphoma
Authors: Salva Katrin A. , Kim Youn H. , Rahbar Ziba , Wood Gary S.
Published: April 2018

Aminolevulinate‐based photodynamic therapy (ALA‐PDT) selectively eliminates diseased tissues primarily through the induction of intrinsic apoptotic pathway. ALA‐PDT is a first‐line therapy for actinic keratosis, however, it is less effective for cutaneous T‐cell lymphoma (CTCL). We have previously demonstrated that the resistance of CTCL to apoptosis correlates with decreased expression of death receptors such as FAS, and that methotrexate functions as an epigenetic regulator that reestablishes the susceptibility of CTCL to extrinsic pathway apoptosis. We showed previously that MTX augments the effectiveness of PDT by sensitizing cells to apoptosis by induction of apoptotic factors, a process we call “epigenetically enhanced” PDT (ePDT). Here, in CTCL cell lines, leukemic CTCL cells, and normal blood T cells, we analyzed multiple components of the FAS, TRAIL, and TNF families using multispectral imaging of immunostained cytopreparations, a quantitative technique with five‐fold greater sensitivity than standard immunocytology. ePDT induced significantly greater FAS, FASL, TRAIL‐R1 & ‐R2, and TNFα levels than standard PDT. This correlated with significantly greater induction of extrinsic pathway apoptosis and/or overall apoptosis in all CTCL samples. There was no appreciable effect on normal T cells. These data set the stage for clinical trials of ePDT as a novel localized treatment of CTCL.