bluuebunny/crossref_metadata_2025 huggingface dataset:
Suspected neurological conditions: when to refer
Authors: Chaplin Steve
Published: November 2019

Earlier this year, NICE published a new guideline on the recognition and referral of patients with suspected neurological conditions (NG127), to help non‐specialist healthcare professionals identify people who should be offered further specialist investigation. This article provides a brief summary of the guidance.
Ertugliflozin: a new SGLT2 inhibitor for type 2 diabetes
Authors: Chaplin Steve
Published: November 2019

Ertugliflozin (Steglatro) is a new sodiumglucose co‐transporter‐2 (SGLT2) inhibitor for the treatment of adults with type 2 diabetes. This article examines its place in therapy, clinical trial efficacy and adverse effects.
Antibiotic side‐effects: from the anticipated to the bizarre
Authors: Wade Sue , Williams Martin
Published: November 2019

In light of the recent MHRA restrictions on the use of fluoroquinolone antibiotics, this article provides an overview of the adverse reactions associated with all classes of antibiotic ‐ from the most common side‐effects such as gastrointestinal disturbance to rare, idiosyncratic reactions.
Tackling antimicrobial resistance: the progress so far
Authors: Ogden Joy
Published: November 2019

In January, the UK government published its second five‐year national action plan for tackling antimicrobial resistance (AMR), as well as its vision for effectively containing and controlling AMR by 2040. But how much progress has been made so far, what more needs to be done, and is the government's vision a realistic one?
Fexofenadine ‐ why is it still not available OTC in the UK?
Authors: Thompson Angus
Published: November 2019

The non‐sedating antihistamine fexofenadine superseded its parent drug terfenadine back in the 1990s, and is now available OTC in many countries, including Australia, New Zealand, the USA and some European countries. So why does it remain prescription‐only in the UK, ponders Angus Thompson.
α‐Hederin induces the apoptosis of gastric cancer cells accompanied by glutathione decrement and reactive oxygen species generation via activating mitochondrial dependent pathway
Authors: Wang Jing , Deng Huanying , Zhang Jixiang , Wu Dandan , Li Jiao , Ma Jingjing , Dong Weiguo
Published: November 2019

α‐Hederin, a monodesmosidic triterpenoid saponin, exhibited promising antitumor potential against a variety of human cancer cell lines. However, few related studies about effects of α‐hederin on gastric cancer are available. Herein, our results showed that α‐hederin significantly inhibited the proliferation of gastric cancer cells and arrested the cell cycle in G1 phase in vitro (p < .05). Further research of the potential mechanism reflected that α‐hederin could induce intracellular glutathione decrement, adenosine triphosphate level, and mitochondrial membrane potential variation via inducing reactive oxygen species accumulation during the apoptosis of gastric cancer cells. Moreover, the detection of mitochondrial and cytosol proteins with apoptosis‐inducing factor, apoptosis protease activating factor‐1, and cytochrome C showed an increase in the cytosol, followed by a decrease of Bcl‐2 levels and increases of caspase‐3, caspase‐8, caspase‐9, and Bax, which revealed that α‐hederin induced apoptosis via triggering activation of the mitochondrial pathway. Furthermore, the above changes were amplified when pretreated with buthionine sulfoximine, whereas attenuated in the group pretreated with NAC than α‐hederin alone (p < .05). In addition, α‐hederin significantly inhibited the growth of xenografted gastric tumors with favorable safety. In conclusion, α‐hederin could inhibit the proliferation and induce apoptosis of gastric cancer accompanied by glutathione decrement and reactive oxygen species generation via activating mitochondrial dependent pathway.
Combination therapy with antioxidants improves total motile sperm counts: A Preliminary Study
Authors: Terai Kazutaka , Horie Shigeo , Fukuhara Shinichiro , Miyagawa Yasushi , Kobayashi Kazuhiro , Tsujimura Akira
Published: November 2019

Purpose

Optimal strategies to treat idiopathic male infertility have remained unclear. The aim of this study was to evaluate the effectiveness of combination antioxidant therapy with several vitamins and supplements on semen parameters.

Methods

Thirty‐one men with oligozoospermia and/or asthenozoospermia evaluated by a Makler counting chamber were randomly assigned to two treatment groups: a combination of antioxidant supplements (L‐carnitine, zinc, astaxanthin, coenzyme Q10, vitamin C, vitamin B12, and vitamin E) and a Chinese herbal medicine, hochu‐ekki‐to (HE). Serum endocrinological profiles and semen parameters, especially total motile sperm count, were compared between before and after 12 weeks of treatment in both groups.

Results

In the supplement group, endocrinological findings were not significantly improved. The semen parameters of semen volume, sperm concentration, and sperm motility were not statistically significantly improved, whereas total motile sperm count was significantly improved. In contrast, none of the endocrinological factors or semen findings were significantly improved by the Chinese herbal medicine although semen concentration, semen motility, and total motile sperm count showed a tendency to increase.

Conclusion

Because combination antioxidant therapy could improve sperm motility significantly for patients with idiopathic oligoasthenozoospermia, our supplement could be one treatment option for idiopathic male infertility.
Robust output tracking of constrained perturbed linear systems via model predictive sliding mode control
Authors: Steinberger M. , Castillo I. , Horn M. , Fridman L.
Published: November 2019

A robustifying strategy for constrained linear multivariable systems is proposed. A combination of tracking model predictive control with output integral sliding mode techniques is used to completely reject bounded matched perturbations. It can be guaranteed that all constraints on inputs, states, and outputs are satisfied although only output information is used. Finally, real‐world experiments with an unstable plant are presented in order to demonstrate the validity and the effectiveness of the proposed approach.
The effects of hedonic, gain, and normative motives on sustainable consumption: Multiple mediating evidence from China
Authors: Tang Yanmei , Chen Shuangzhou , Yuan Zongjin
Published: November 2019

This study used goal‐framing theory to test the impacts of hedonic, gain, and normative goals on green consumer behavior (GCB). Moreover, we explored the potential multiple mediation effects of perceived risk and lifestyle between goal frames and GCB. The participants were 2,340 Jiangsu residents in China. Structure equation modeling was used to examine the hypothesized association between the variables. The results revealed that hedonic and normative goals had significant impacts on GCB, whereas gain goal had no significant influence on GCB. Perceived risk had a significant negative effect on GCB. Lifestyle had a significant positive impact on GCB. In addition, perceived risk and lifestyle mediated the relationship between hedonic goal and GCB and normative goal and GCB, respectively. The current research helps gain a better understanding of the relationship and multiple mediating mechanisms between hedonic goal, gain goal, normative goal, perceived risk, lifestyle, and GCB in the field of sustainable development. Implications and recommendations for future research are discussed.
The Confinement Effect of Angstrom‐Sized Pores in Asymmetrical Membrane Constructed by Zeolitic Imidazolate Frameworks: Partially Dehydrated Ion Transport Performance
Authors: Li Ruirui , Lu Bingxin , Xie Zhiqiang , Zhai Jin
Published: November 2019

The confinement effect in asymmetrical biological ion channels makes the state of molecules and ions differs from that in the external environment, and the mass transfer confined in the biological ion channels is in a single strand form. Herein, an asymmetrical membrane with angstrom‐sized pores is constructed by growth of ZIF‐90 membrane on the porous anodic aluminum oxide film. Due to the confinement effect of angstrom‐sized pores of ZIF‐90, ions transport through the pores of ZIF‐90 suffer from multiple dehydration‐hydration‐dehydration process in the form of a single ionic chain. Molecular dynamics simulations imply that ions inside the pores of ZIF‐90 are partially dehydrated. In alkaline condition, high rectification ratios of 237, 295, and 357 can be achieved in 10 × 10−3 m KCl, NaCl, and LiCl electrolyte, respectively. Besides, the strong electrostatic interaction between ions and the confined ZIF‐90 pores makes the ions transport through the asymmetrical membrane suffer from an energy barrier, and the energy barrier is different with different ion species. This work helps to understand the ions transfer mechanism through angstrom‐sized pores, which can provide guidance for the design of asymmetrical membrane and boost their applications.
An exploration of effective fuzzing for side‐channel cache leakage
Authors: Basu Tiyash , Aggarwal Kartik , Wang Chundong , Chattopadhyay Sudipta
Published: November 2019

Adversaries can compute the secret information of a program, such as the key for encryption routines, from side channels in the light of timing‐based and access‐based CPU cache behaviours. As a result, it is crucial to understand whether a program is vulnerable to side‐channel cache leakage or not. Yet how we can find out such a vulnerability in a program remains a problem. In this paper, we revisit this problem and contemplate a test‐generation methodology, which, in both timing‐based and access‐based dimensions, systematically discovers the cache side‐channel leakage of an arbitrary software program. At the core of our test‐generation framework is an algorithm that explores the program's input space and adapts at runtime according to observed cache performance in the executed tests. We have implemented our test generator for timing‐based and access‐based attack tests and evaluated it with open‐source subject programs, including ones from OPENSSL and Linux GDK libraries. Our extensive evaluation effectively discloses the vulnerabilities of these real‐world software to both timing‐based and access‐based cache attacks. We also empirically show that our test generator achieves higher and comparable effectiveness, respectively, in simulations and real hardware platforms with regard to revealing cache side‐channel leakage than do state‐of‐the‐art fuzz testing tools.
Research on transmission line model based on phase‐mode transformation in HVDC system
Authors: Li Xiaodong , Xu Zheng , Lai Qiuju , Zhang Zheren
Published: November 2019

For a high‐voltage DC (HVDC) transmission system, this paper describes an improved algorithm for the coupled multi‐phase transmission line model and complete procedures for the calculation of the DC‐side harmonic currents. First, based on the phase‐mode transformation, an improved coupled multi‐phase transmission line model is proposed. In other words, the transmission line is represented as a nodal admittance matrix form, considering computational accuracy and efficiency. In addition, when calculating the DC‐side harmonic currents, the line‐commutated converters at the rectifier side and the inverter side are equivalent to the three‐pulse harmonic voltage source models. Second, based on the DC‐side equivalent models mentioned previously and the nodal voltage analysis method, an analytical method and complete procedures for the calculation of the DC‐side harmonic currents in the HVDC systems, namely, the equivalent disturbing current, are described. Finally, a case study is carried out on a 4000 MW/±800 kV HVDC system. In the same condition, the analytical results are basically consistent with the simulation results of PSCAD/EMTDC, thus proving the accuracy of the proposed model. © 2019 Institute of Electrical Engineers of Japan. Published by John Wiley & Sons, Inc.
Present state and future prospect of autonomous control technology for industrial drones
Authors: Nonami Kenzo
Published: November 2019

This article includes of a technical and general discussion about a future prospective of flying robot. Drones or unmanned aerial vehicles (UAVs) should be evolving to real and bio‐inspired flying robots. The concept of guidance, navigation and control is first explained and defined. Next, the autonomy (safety) class of drones, future roadmaps, and a correlation diagram between the flight level of drone and autonomy (safety) will be described, and a fault‐tolerant control system is introduced. Finally, the ideal state of autonomous control in the near future and realization of autonomy, as well as top‐level autonomy as Class A by a supervisor (guidance system), will be defined. © 2019 Institute of Electrical Engineers of Japan. Published by John Wiley & Sons, Inc.
Introduction
Authors: Pineda Victor Santiago
Published: November 2019

Cities around the world are failing people with disabilities, who represent 15–20% of the world’s population. These failures exist across every sector of life. Historically, people with disabilities have been treated as objects of charity in need of custodial care. However, urban planners who are well positioned to help usher in a new wave of urban reforms and cities around the world like Dubai are experimenting with more inclusive and equitable policies. These new approaches are fundamentally restructuring urban planning and design. The Convention on the Rights of Persons with Disabilities and UAE Federal Law No. 29 challenge normative approaches to spatial justice and policy. This chapter explores how these innovations seek to remove obstacles for people with disabilities. The case of the United Arab Emirates may at first glance appear to be an atypical case of disability-related development, but its unique position illustrates broader structural challenges and tensions inherent to the process of broad-based, cross-sectoral reforms. Building upon an original innovative framework, this book assesses the transformation of disability rights in Dubai and adds an urban dimension to the Capability Model of Disability by addressing the theoretical gaps that impede social inclusion of people with disabilities in cities.
Exploring Functionings and Freedoms in Dubai
Authors: Pineda Victor Santiago
Published: November 2019

The period from 2006 to 2013 in Dubai was an era of hyper-urbanization and rapid growth. Disability policies, programs, and engagement with people with disabilities were occurring in tandem with the rapid modernization of the city-state. How did these changing physical, social, and institutional contexts impact the lives of people with disabilities across the two separate but interconnected domains, basic functionings and basic freedoms? This time period was also notable for the lack of a comprehensive approach to disability policy and accessibility reforms. Interview respondents indicated that approaches were fragmented and there was a clear gap between what the public sector agencies said they were doing and the type of services and opportunities people with disabilities and their families actually received. This highlighted the importance of advocating for specific actions and policies to ensure the provisions outlined in Federal Law No. 29 and the UN Convention on the Rights of Persons with Disabilities were being achieved.
Charting Access and Inclusion in Future Cities
Authors: Pineda Victor Santiago
Published: November 2019

How can access and inclusion become an integral part of the cities of the future? Initiatives such as Smart Dubai hold the answers to making infrastructure investments that deliver economic and social advantage to all of a city’s people. This chapter looks at the concept of the “Smart City,” namely cities that use decision making, planning, and infrastructure to achieve vastly improved connectivity, efficiency, and access to city services. However, the Smart City also needs to be an accessible city. The Dubai Disability Strategy created a framework for shared governance and measurable progress toward ensuring that Dubai would become an inclusive, rights-based, barrier-free city for people with disabilities. By integrating accessibility standards into the procurement process and standardizing national platforms in line with global access requirements, the government of Dubai can leverage technology to bridge the divide between people with disabilities and those without. The success of the Dubai Strategic Plan and the Dubai Disability Strategy have created a blueprint for inclusive public policy and spurred new initiatives at the federal level. Dubai’s local law and strategy is reforming federal institutions. The scaling up of local practices promises to be a catalyst for an even greater commitment to building accessible and inclusive cities across the region.
Plant cell wall integrity maintenance in model plants and crop species-relevant cell wall components and underlying guiding principles
Authors: Gigli-Bisceglia Nora , Engelsdorf Timo , Hamann Thorsten
Published: November 2019

The walls surrounding the cells of all land-based plants provide mechanical support essential for growth and development as well as protection from adverse environmental conditions like biotic and abiotic stress. Composition and structure of plant cell walls can differ markedly between cell types, developmental stages and species. This implies that wall composition and structure are actively modified during biological processes and in response to specific functional requirements. Despite extensive research in the area, our understanding of the regulatory processes controlling active and adaptive modifications of cell wall composition and structure is still limited. One of these regulatory processes is the cell wall integrity maintenance mechanism, which monitors and maintains the functional integrity of the plant cell wall during development and interaction with environment. It is an important element in plant pathogen interaction and cell wall plasticity, which seems at least partially responsible for the limited success that targeted manipulation of cell wall metabolism has achieved so far. Here, we provide an overview of the cell wall polysaccharides forming the bulk of plant cell walls in both monocotyledonous and dicotyledonous plants and the effects their impairment can have. We summarize our current knowledge regarding the cell wall integrity maintenance mechanism and discuss that it could be responsible for several of the mutant phenotypes observed.
Stability Within $$T^2$$-Symmetric Expanding Spacetimes
Authors: Berger Beverly K. , Isenberg James , Layne Adam
Published: November 2019

We prove a nonpolarised analogue of the asymptotic characterisation of $$T^2$$T2-symmetric Einstein flow solutions completed recently by LeFloch and Smulevici. In this work, we impose a condition weaker than polarisation and so our result applies to a larger class. We obtain similar rates of decay for the normalised energy and associated quantities for this class. We describe numerical simulations which indicate that there is a locally attractive set for $$T^2$$T2-symmetric solutions not covered by our main theorem. This local attractor is distinct from the local attractor in our main theorem, thereby indicating that the polarised asymptotics are unstable.
Selectively reduced contrast sensitivity in high schizotypy
Authors: Harper Lauren , Spencer Emily , Davidson Colin , Hutchinson Claire V.
Published: November 2019

Deficits in the ability to encode small differences in contrast between adjacent parts of an image (contrast sensitivity) are well documented in schizophrenic patients. In the present study, we sought to determine whether contrast sensitivity deficits reported in schizophrenic patients are also evident in those who exhibit high schizotypy scores in a typical (i.e., non-schizophrenic) population. Using the O-Life Questionnaire, we determined the effects of schizotypy on spatial (0.5, 2 and 8 c/deg) and spatiotemporal (0.5 and 8 c/deg at 0.5 and 8 Hz) contrast sensitivity in 73 young (18–26 years), majority female (n = 68) participants. We found differences in contrast sensitivity that were spatial, spatiotemporal and O-Life subscale specific. Spatial contrast sensitivity was significantly lower in high, compared to low schizotypes at low spatial frequencies (0.5 c/deg) in those who scored highly on the Unusual Experiences and Cognitive Disorganisation O-Life subscales. For moving stimuli, individuals with high scores on the Unusual Experiences subscale exhibited lower spatiotemporal contrast sensitivity for 0.5 and 8 c/deg patterns drifting at 8 Hz. Although the effects reported here were relatively small, this is the first report of reduced contrast sensitivity in schizotypy.
Clinical outcome of standardized 177Lu-PSMA-617 therapy in metastatic prostate cancer patients receiving 7400 MBq every 4 weeks
Authors: Rasul Sazan , Hacker Marcus , Kretschmer-Chott Elisabeth , Leisser Asha , Grubmüller Bernhard , Kramer Gero , Shariat Shahrokh , Wadsak Wolfgang , Mitterhauser Markus , Hartenbach Markus , Haug Alexander R.
Published: November 2019

Purpose

[177Lu]Lu-PSMA-617 radio-ligand therapy (PSMA-RLT) is emerging in patients with an advanced metastatic castration-resistant prostate cancer (mCRPC). Here, we aimed to estimate the results of PSMA-RLT in terms of response, progression-free survival (PFS), and overall survival (OS) in patients receiving a highly standardized treatment regimen due to mCRPC. The toxicity of PSMA-RLT has also been evaluated.

Patients and methods

Fifty-four patients (mean age 72 ± 7 years, median PSA at time of initial therapy 66 [range 1.0–4890 μg/L]), receiving three PSMA-RLT cycles (mean 7315 ± 573 MBq) at four weekly intervals, were included in this retrospective analysis. Hematological and biochemical parameters were regularly determined in every patient. Kaplan-Meier estimates were used to assess PFS and OS and a Cox proportional hazard model was used to analyze significant associations. Treatment response was based on PSA measurements 4 weeks after the 3rd treatment.

Results

The majority of patients were previously treated with abiraterone/enzalutamide (69%) and docetaxel/cabazitaxel (67%). In total, 79% of the patients showed a decrease in PSA (median PSA decrease from 66 to 19.8, range 0.7–4563 μg/L, P < 0.001) 1 month after the 3rd therapy cycle. Among them, 58% and 35% demonstrated a PSA-decline of > 50% and > 80%, respectively. Median OS was 119 weeks; median PFS was 25 weeks. Patients presenting with a PSA decline had significantly longer PFS (27 vs. 15 weeks, P < 0.0001) and OS (median survival not reached vs. 52 weeks, P < 0.001) than patients with no PSA reduction. Moreover, patients with reduction in PSA levels ≥ 50% (median survival not reached vs. 52 weeks, P < 0.0001) and ≥ 80% (median survival not reached vs. 87 weeks, P = 0.008) lived significantly longer. While hemoglobin did not change during treatment, levels of platelets (236 ± 71 g/L vs. 193 ± 67 g/L) and leucocytes (6.5, range 2.9–13.7 g/L vs. 4.8, range 1.5–12.3 g/L) decreased significantly, both P < 0.001. Two grade 3 leukocytopenia and one grade 3 anemia were observed.

Conclusion

Intense PSMA-RLT regime with four weekly intervals between the cycles is well-tolerated and offers favorable response rates, PFS, and survival rates for patients with mCRPC.
Correction to: Longitudinal multi-modal muscle-based biomarker assessment in motor neuron disease
Authors: Jenkins Thomas M. , Alix James J. P. , Fingret Jacob , Esmail Taniya , Hoggard Nigel , Baster Kathleen , McDermott Christopher J. , Wilkinson Iain D. , Shaw Pamela J.
Published: November 2019

The original version of this article unfortunately contained a mistake. The numbers in the Table 5 appear to have been reproduced wrongly as dates, rather than percentages.
New stories for a more conscious, sustainable society: claiming authorship of the climate story
Authors: Hendersson Heidi , Wamsler Christine
Published: November 2019

Sustainability philosophers claim that we are at an impasse of stories, finding ourselves in a blank chapter between the old and the new. The old story, characterized by separation, technological dominance and human superiority over nature, is unfolding in an ecological crisis giving space for a new narrative defined by inter-being, cooperation and balance. It has been put forward that this crisis is climate change, a phenomenon that epitomizes the old, while holding the potential to act as a bridge to the new. Our study shows the benefits of framing climate change as a problem of story and how the dominant story we have told about climate change can be changed. Based on an approach called “Rising strong”, we address the question of how sustainability students relate to the story on climate change, how they conceptualize and situate it within a bigger narrative, and identify barriers and catalysts for authorship. The results show a clear lack of personal authorship, a feeling of disconnection to the climate story and a disbelief in any revolutionary endings, yet still a slight belief in co-authorship. Catalysts that can help to claim back authorship were identified to be positive emotions (e.g., empathy and hope), integral thinking, creation of space for creativity and co-creation. Barriers were scientific rationality and complexity alongside perceived negative emotions, such as shame and self-doubt. One of the most crucial findings was the re-occurring theme of joint engagement for story-transitioning. This point to the urgent need for both increased co-creation as well as the creation of conditions needed to enable people to engage in such processes.
Infill Asymptotics and Bandwidth Selection for Kernel Estimators of Spatial Intensity Functions
Authors: van Lieshout M. N. M.
Published: November 2019

We investigate the asymptotic mean squared error of kernel estimators of the intensity function of a spatial point process. We derive expansions for the bias and variance in the scenario thatnindependent copies of a point process in$\mathbb {R}^{d}$ℝdare superposed. When the same bandwidth is used in allddimensions, we show that an optimal bandwidth exists and is of the ordern− 1/(d+ 4)under appropriate smoothness conditions on the true intensity function.
Spillovers from high growth firms: evidence from Hungary
Authors: de Nicola Francesca , Muraközy Balázs , Tan Shawn W.
Published: November 2019

How do high-growth firms (HGFs) affect the rest of the economy? We explore this question using Hungarian administrative microdata. Relying on the Birch definition of HGFs, we find evidence for stronger productivity growth for firms operating in industries with more HGFs and for firms supplying industries with more HGFs. Knowledge spillovers or the surge of HGFs’ demand for intermediate inputs could explain these positive associations. Firms with intermediate productivity levels seem most likely to benefit from this effect, while we find no differences by age or export status. The results hold irrespective of the level of spatial aggregation and are robust to alternative definitions of HGFs as well as different measures of productivity or spillover.
Sexist Slurs: Reinforcing Feminine Stereotypes Online
Authors: Felmlee Diane , Inara Rodis Paulina , Zhang Amy
Published: November 2019

Social media platforms are accused repeatedly of creating environments in which women are bullied and harassed. We argue that online aggression toward women aims to reinforce traditional feminine norms and stereotypes. In a mixed methods study, we find that this type of aggression on Twitter is common and extensive and that it can spread far beyond the original target. We locate over 2.9 million tweets in one week that contain instances of gendered insults (e.g., “bitch,” “cunt,” “slut,” or “whore”)—averaging 419,000 sexist slurs per day. The vast majority of these tweets are negative in sentiment. We analyze the social networks of the conversations that ensue in several cases and demonstrate how the use of “replies,” “retweets,” and “likes” can further victimize a target. Additionally, we develop a sentiment classifier that we use in a regression analysis to compare the negativity of sexist messages. We find that words in a message that reinforce feminine stereotypes inflate the negative sentiment of tweets to a significant and sizeable degree. These terms include those insulting someone’s appearance (e.g., “ugly”), intellect (e.g., “stupid”), sexual experience (e.g., “promiscuous”), mental stability (e.g., “crazy”), and age (“old”). Messages enforcing beauty norms tend to be particularly negative. In sum, hostile, sexist tweets are strategic in nature. They aim to promote traditional, cultural beliefs about femininity, such as beauty ideals, and they shame victims by accusing them of falling short of these standards.
Meeting technical challenges for protein characterization and surrogate equivalence studies that resulted from insecticidal protein co-expression in maize event MZIR098
Authors: Walters Frederick S. , Young Scott , Graser Gerson
Published: November 2019

Safety assessment of genetically modified plants includes protein characterization to confirm the intended trait protein expression. In addition, to conduct safety tests, the large amount of purified protein needed is usually met through the use of a surrogate, microbially produced protein source. Characterization of the eCry3.1Ab and mCry3A proteins as derived from Event MZIR098 maize was challenging because of the difficulty in purifying/isolating these proteins that are of similar molecular weight and have considerable shared sequence and immunogenicity. This also applies to establishing the biochemical equivalence to the microbially produced surrogate proteins, as highly-purified plant protein is required. While use of crude plant extracts facilitated functional equivalence testing with the surrogate proteins, a separate technical challenge had to be met. The eCry3.1Ab and mCry3A proteins display differentiated modes of action toward CRW pests, however, with the same overall target pest spectrum, no differential test organism existed to allow equivalence testing for one insecticidal protein in the presence of the other. To establish that the microbially produced proteins are suitable surrogates for the plant-produced proteins, the challenges in the protein purification and bioactivity testing had to be addressed. This article describes technical solutions to assess and characterize the insecticidal proteins in this new event and thereby confirm equivalence/suitability of the microbially produced protein surrogates.
Embedded carbon fiber-reinforced polymer rod in reinforced concrete frame and ultra-high-performance concrete frame joints
Authors: Basim Shahnaz , Hejazi Farzad , Rashid Raizal Saifulnaz Bin Muhammad
Published: November 2019

Beam–column joints play an important role in providing lateral stiffness and integrity of frames during dynamic loading such as earthquake. In the high humidity areas, during functioning of the building cracks occur, which leads to the corrosion of the reinforcement due to the environmental exposures. Therefore, one of the main failures mechanism of building during an earthquake is caused by easily yielding of corroded steel reinforcement, which leads to reduce functionality of the frame joints in transferring the loads. This study proposed a new design to reinforce the beam-column joints with embedded carbon fiber-reinforced polymer (CFRP) rods, due to their extremely high strength and stiffness, along with the fact that they will not rust or corrode and very light weight. CFRP rods are used in reinforced concrete (RC) frame and ultra-high-performance concrete (UHPC) frame subjected to dynamic load. The prototype of the proposed design is constructed as frame with conventional concrete and frame with UHPC material to conduct experiments Test as well as numerical analysis to evaluate the performance of the proposed joints under dynamic loads. The results showed improvement in the performance of the frames reinforced with embedded CFRP in joints in terms of lateral load resistance capacity, ductility behaviour, overall stiffness, and failure mechanism.
Photovoltaic–thermal (PV/T) technology: a comprehensive review on applications and its advancement
Authors: Diwania Sourav , Agrawal Sanjay , Siddiqui Anwar S. , Singh Sonveer
Published: November 2019

Over the most recent couple of decades, tremendous consideration is drawn towards photovoltaic–thermal systems because of their advantages over the solar thermal and PV applications. This paper intends to show different electrical and thermal aspects of photovoltaic–thermal systems and the researches in absorber design modification, development, and applications. From the previous review articles, it has been concluded that the heat energy exhausted from the PV module can be further utilized in different ways and helps in achieving better efficiency. Furthermore, the types of photovoltaic–thermal systems such as air collector, water collector, and combi system, coupling with heat pump and their application to buildings are also stated. This paper also discussed certain design aspects like modifications in the flow channel by adding fins, thin metallic sheets, roll-bond absorber, and porous media and the effect of these modifications on the hybrid system’s efficiency. Furthermore, the use of the latest technologies such as nanofluids, thermoelectric generators, and phase-change materials improves the overall system performance. The role of soft-computing techniques is forecasting the impact of various parameters on the photovoltaic–thermal system is also discussed.
Regional Climate Impacts of Future Changes in the Mid–Latitude Atmospheric Circulation: a Storyline View
Authors: Zappa Giuseppe
Published: November 2019

Purpose of Review

Atmospheric circulation exerts a strong control on regional climate and extremes. However, projections of future circulation change remain uncertain, thus affecting the assessment of regional climate change. The purpose of this review is to describe some key cases where regional precipitation and windiness strongly depend on the mid-latitude atmospheric circulation response to warming, and summarise this into alternative plausible storylines of regional climate change.

Recent Findings

Recent research has enabled to better quantify the importance of dynamical aspects of climate change in shaping regional climate. The cold season precipitation response in Mediterranean-like regions is identified as one of the most susceptible impact-relevant aspects of regional climate driven by mid-latitude circulation changes. A circulation-forced drying might already be emerging in the actual Mediterranean, Chile and southwestern Australia. Increasing evidence indicates that distinct regional changes in atmospheric circulation and European windiness might unfold depending on the interplay of different climate drivers, such as surface warming patterns, sea ice loss and stratospheric changes.

The multi-model mean circulation response to warming tends to show washed-out signals due to the lack of robustness in the model projections, with implications for regional changes. To better communicate the information contained within these projections, it is useful to discuss regional climate change conditionally on alternative plausible storylines of atmospheric circulation change. As progress continues in understanding the factors driving the response of circulation to global warming, developing such storylines will provide end–to–end and physically self-consistent descriptions of plausible future unfoldings of regional climate change.
A Scoping Review on the Characteristics of Human Exposome Studies
Authors: Haddad Nadine , Andrianou Xanthi D. , Makris Konstantinos C.
Published: November 2019

Embraced as a breaking through methodological framework, the exposome is accompanied by novel exposure assessment methods and data processing tools or models. However, systematic mapping of the landscape of exposome studies, including their characteristics, components, tools and language has not been done so far. We conducted a scoping review to answer the question: “Which main domains of the human exposome have been included in the literature and which metrics of exposure(s)/outcome(s) have been used?” We performed a comprehensive search of human studies containing the word “exposom*” and published up to March 8, 2019. We screened 1133 records and 82 studies were included in the analysis. Most studies took place in Europe. Data analysis showed the non-systematic use of the exposome term. Most studies had a longitudinal design (n = 30, 37%), were conducted on adults (n = 40, 51%), and had a clearly defined health outcome in methodology (n = 48, 61%). Omics tools, such as metabolomics were used in 38 studies (49%), while environment-wide association analysis was used in 9 studies (11%). Thirty-seven (48%) studies included all three exposome domains (general external, specific external and internal) while 33 (42%) studies included two. Despite the large number of environmental components that comprise each of the exposome domains, only a subset has been currently studied. An optimized consideration of the components from all exposome domains, as well as the standardization of the exposure and outcome assessment methods is warranted to advance the utility of the human exposome concept.
Interdisziplinäres Management immunmediierter Erkrankungen – eine österreichische Perspektive
Authors: Högenauer Christoph , Häusler Daniela , Pieringer Herwig , Richter Leo , Funk Marion , Müllegger Robert , Langner-Wegscheider Beate , Moschen Alexander , Redlich Kurt , Vogelsang Harald , Weger Wolfgang , Dejaco Christian
Published: November 2019

Immunmediierte inflammatorische Erkrankungen (IMID) sind eine klinisch heterogene Gruppe von Erkrankungen, die genetische, ätiologische und auch klinische Überschneidungen aufweisen. Nach dem heutigen Stand der Forschung liegen den sog. primären IMID gemeinsame pathogene Mechanismen und zytokinassoziierte Signaltransduktionswege zugrunde. Zu den primären IMID zählen unter anderem chronisch-entzündliche Darm‑, Haut- und Augenerkrankungen sowie rheumatische Erkrankungen. Patienten, die an einer primären IMID erkrankt sind, weisen ein erhöhtes Risiko für die Entwicklung einer sekundären IMID auf. Die vorliegende Arbeit skizziert die Abgrenzung zwischen primären und sekundären IMID unter Berücksichtigung von Komplikationen und Komorbiditäten. Ausgehend von den Fächern Gastroenterologie, Dermatologie, Rheumatologie und Ophthalmologie wird ein möglicher optimaler interdisziplinärer Umgang mit IMID-Patienten diskutiert. Im speziellen werden Leitsymptome, die auf eine IMID hinweisen, und diagnostische Maßnahmen beschrieben, die vor Überweisung eines Patienten zum entsprechenden Spezialisten durchgeführt werden sollten. Da einzelne Patienten, die unter mehreren IMID leiden, eine therapeutische Herausforderung darstellen, können hierfür interdisziplinäre Sprechstunden bzw. sog. Immunoboards in der klinischen Praxis hilfreich sein.
Prioritizing Democracy: A Commentary on Smith’s Presidential Address to the Society for Business Ethics
Authors: Singer Abraham , Ron Amit
Published: November 2019

In his 2018 presidential address to the Society of Business Ethics, Jeffery Smith claimed that political approaches to business ethics must be attentive to both the distinctive nature of commercial activity and, at the same time, the degree to which such commercial activity is structured by political decisions and choices. In what we take to be a friendly extension of the argument, we claim that Smith does not go far enough with this insight. Smith’s political approach to business ethics focuses solely on the outcomes of political choices. But if we think of politics in terms of processes—as in, ongoing disagreement and contest—and not merely a series of legal, administrative, or institutional outcomes, a different view of business ethics emerges. In particular, we argue that such an emphasis points us toward seeing business actors as having a normative duty to preserve the integrity and functioning of democracy.
Bringing party organization back in: a comparative analysis of party representation in Europe
Authors: Giger Nathalie , Schumacher Gijs
Published: November 2019

In this study we focus on party organizational characteristics as key determinants of party congruence. We examine how the horizontal and vertical integration of parties is linked to representation in comparative perspective. We further focus on how congruence is achieved by detailing our expectation regarding effects on the uncertainty versus bias in the estimates of party constituents' opinion. Exploiting a comparative database on political parties and data from Comparative Studies of Electoral Systems, we show that having a complex organizational structure and being leadership dominated makes parties less representative of their constituencies. These findings carry important implications for the study of political representation but also for the literature on political parties in crisis.
Modulation of growth hormone receptor-insulin-like growth factor 1 axis by dietary protein in young ruminants
Authors: Firmenich Caroline S. , Schnepel Nadine , Hansen Kathrin , Schmicke Marion , Muscher-Banse Alexandra S.
Published: November 2019

A reduced protein intake causes a decrease in insulin-like growth factor 1 (IGF1) concentrations and modulates Ca homoeostasis in young goats. IGF1 is synthesised by the liver in response to stimulation by growth hormone (GH). Due to rumino-hepatic circulation of urea, ruminants are suitable for investigating the effects of protein reduction despite sufficient energy intake. The present study aimed to investigate the impact of a protein-reduced diet on the expression of components of the somatotropic axis. Male young goats were divided into two feeding groups receiving either a control diet (20 % crude protein (CP)) or a reduced-protein diet (9 % CP). Blood concentrations of IGF1 and GH were measured, and a 24-h GH secretion profile was compiled. Moreover, ionised Ca and insulin concentrations as well as mRNA and protein expression levels of hepatic proteins involved in GH signalling were quantified. Due to the protein-reduced diet, concentrations of ionised Ca, insulin and IGF1 decreased significantly, whereas GH concentrations remained unchanged. Expression levels of the hepatic GH receptor (GHR) decreased during protein reduction. GHR expression was down-regulated due to diminished insulin concentrations as both parameters were positively correlated. Insulin itself might be reduced due to reduced blood Ca levels that are involved in insulin release. The protein-reduced diet had an impact on the expression of components of the somatotropic axis as a disruption of the GH–IGF1 axis brought about by diminished GHR expression was shown in response to a protein-reduced diet.
Is information theory, or the assumptions that surround it, holding back neuroscience?
Authors: de-Wit Lee , Ekroll Vebjørn , Schwarzkopf Dietrich Samuel , Wagemans Johan
Published: November 2019

The challenges raised in this article are not with information theory per se, but the assumptions surrounding it. Neuroscience isn't sufficiently critical about the appropriate ‘receiver’ or ‘channel’, focuses on decoding ‘parts’, and often relies on a flawed ‘veridicality’ assumption. If these problematic assumptions were questioned, information theory could be better directed to help us understand how the brain works.
Codes are for messages, not for neurons
Authors: Merker Bjorn
Published: November 2019

My commentary draws on extensive arguments against “coding in the brain” developed by my neuroscience mentor, the late Eugene Sachs, who summarized them as follows: “[T]he energy in the signal is the only code there is for information…. The code is the same for each cell, but each cell's location is different, and location is the only basis for significance” (p. 13).
Plasticity of the neural coding metaphor: An unnoticed rhetoric in scientific discourse
Authors: Frezza Giulia , Zoccolotti Pierluigi
Published: November 2019

The convincing argument that Brette makes for the neural coding metaphor as imposing one view of brain behavior can be further explained through discourse analysis. Instead of a unified view, we argue, the coding metaphor's plasticity, versatility, and robustness throughout time explain its success and conventionalization to the point that its rhetoric became overlooked.
Modest and immodest neural codes: Can there be modest codes?
Authors: Cao Rosa , Rathkopf Charles
Published: November 2019

We argue that Brette's arguments, or some variation on them, work only against the immodest codes imputed by neuroscientists to the signals they study; they do not tell against “modest” codes, which may be learned by neurons themselves. Still, caution is warranted: modest neural codes likely lead to only modest explanatory gains.
Quantifying the role of neurons for behavior is a mediation question
Authors: Jones Ilenna Simone , Kording Konrad Paul
Published: November 2019

Many systems neuroscientists want to understand neurons in terms of mediation; we want to understand how neurons are involved in the causal chain from stimulus to behavior. Unfortunately, most tools are inappropriate for that while our language takes mediation for granted. Here we discuss the contrast between our conceptual drive toward mediation and the difficulty of obtaining meaningful evidence.
Implementing health technology assessment in Ghana to support universal health coverage: building relationships that focus on people, policy, and process
Authors: Hollingworth Samantha , Gyansa-Lutterodt Martha , Dsane-Selby Lydia , Nonvignon Justice , Lopert Ruth , Gad Mohamed , Ruiz Francis , Tunis Sean , Chalkidou Kalipso
Published: November 2019

Ghana is one of the few African countries to enact legislation and earmark significant funding to establish universal health coverage (UHC) through the National Health Insurance Scheme, although donor funds have declined recently. Given a disproportionate level of spending on medicines, health technology assessment (HTA) can support resource allocation decisions in the face of highly constrained budgets, as commonly found in low-resource settings. The Ghanaian Ministry of Health, supported by the International Decision Support Initiative (iDSI), initiated a HTA study in 2016 to examine the cost-effectiveness of antihypertensive medicines. We aimed to summarize key insights from this work that highlights success factors beyond producing purely technical outputs. These include the need for capacity building, academic collaboration, and ongoing partnerships with a broad range of experts and stakeholders. By building on this HTA study, and with ongoing interactions with iDSI, HTAi, WHO, and others, Ghana will be well positioned to institutionalize HTA in resource allocation decisions and support progress toward UHC.
The ‘Top 10’ Challenges for Health Technology Assessment: INAHTA Viewpoint
Authors: O'Rourke Brian , Werkö Sophie Söderholm , Merlin Tracy , Huang Li Ying , Schuller Tara
Published: November 2019

The International Network of Agencies for Health Technology Assessment (INAHTA) spans the globe as a network of 50 publicly-funded health technology assessment (HTA) agencies supporting health system decision making for 1.4 billion people in thirty countries. Agency members are non-profit HTA organizations that are part of, or directly support, regional or national governments. Recently, INAHTA surveyed its members to gather perspectives from agency leadership on the most important issues in HTA today. This paper describes the top 10 challenges identified by INAHTA members. Addressing these challenges requires a call for action from INAHTA member agencies and the many other actors involved in the HTA ecosystem. In opening this call for action, INAHTA will lead the way; however, a comprehensive undertaking from all players is needed to effectively address these challenges and to continue to evolve HTA in its role as a strong and effective contributor to health systems.