bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of processing parameters on forming defects during selective laser melting of AlSi10Mg powder
Authors: Wu Haihua , Li Junfeng , Wei Zhengying , Wei Pei
Published: January 2020

Purpose

To fabricate a selective laser melting (SLM)-processed AlSi10Mg part with almost full density and free of any apparent pores, this study aims to investigate the effect of ambient argon pressure and laser scanning speed on the particles splash during the AlSi10Mg powder bed laser melting.

Design/methodology/approach

Based on the discrete element method (DEM), a 3D model of random distribution of powder particles was established, and the 3D free surface of SLM forming process was dynamically tracked by the volume of fluid, where a Gaussian laser beam acts as the energy source melting the powder bed. Through the numerical simulation and process experimental research, the effect of the applied laser power and scanning speed on the operating laser melting temperature was studied.

Findings

The process stability has a fundamental role in the porosity formation, which is process-dependent. The effect of the processing conditions on the process stability and the resultant forming defects were clarified.

Research limitations/implications

The results shows that the pores were the main defects present in the SLM-processed AlSi10Mg sample, which decreases the densification level of the sample.

Practical implications

The optimal processing parameters (argon pressure of 1,000 Pa, laser power of 180 W, scan speed of 1,000 mm/s, powder layer thickness of 35 µm and hatch spacing of 50 µm ) applied during laser melting can improve the quality of selective laser melting of AlSi10Mg,

Social implications

It can provide a technological support for 3D printing.

Originality/value

Based on the analysis of the pore and balling formation mechanisms, the optimal processing parameters have been obtained, which were argon pressure of 1,000 Pa, laser power of 180 W, scan speed of 1,000 mm/s, powder layer thickness of 35 µm and hatch spacing of 50 µm. Then, a near-fully dense sample free of any apparent pores on the cross-sectional microstructure was produced by SLM, wherein the relative density of the as-built samples is larger than 97.5%.
A review on advancements in applications of fused deposition modelling process
Authors: T. Sathies , P. Senthil , M.S. Anoop
Published: January 2020

Purpose

Fabrication of customized products in low volume through conventional manufacturing incurs a high cost, longer processing time and huge material waste. Hence, the concept of additive manufacturing (AM) comes into existence and fused deposition modelling (FDM), is at the forefront of researches related to polymer-based additive manufacturing. The purpose of this paper is to summarize the research works carried on the applications of FDM.

Design/methodology/approach

In the present paper, an extensive review has been performed related to major application areas (such as a sensor, shielding, scaffolding, drug delivery devices, microfluidic devices, rapid tooling, four-dimensional printing, automotive and aerospace, prosthetics and orthosis, fashion and architecture) where FDM has been tested. Finally, a roadmap for future research work in the FDM application has been discussed. As an example for future research scope, a case study on the usage of FDM printed ABS-carbon black composite for solvent sensing is demonstrated.

Findings

The printability of composite filament through FDM enhanced its application range. Sensors developed using FDM incurs a low cost and produces a result comparable to those conventional techniques. EMI shielding manufactured by FDM is light and non-oxidative. Biodegradable and biocompatible scaffolds of complex shapes are possible to manufacture by FDM. Further, FDM enables the fabrication of on-demand and customized prosthetics and orthosis. Tooling time and cost involved in the manufacturing of low volume customized products are reduced by FDM based rapid tooling technique. Results of the solvent sensing case study indicate that three-dimensional printed conductive polymer composites can sense different solvents. The sensors with a lower thickness (0.6 mm) exhibit better sensitivity.

Originality/value

This paper outlines the capabilities of FDM and provides information to the user about the different applications possible with FDM.
Local extinction risk under climate change in a neotropical asymmetrically dispersed epiphyte
Authors: Acevedo Miguel A. , Beaudrot Lydia , Meléndez‐Ackerman Elvia J. , Tremblay Raymond L.
Published: January 2020

The long‐term fate of populations experiencing disequilibrium conditions with their environment will ultimately depend on how local colonization and extinction dynamics respond to abiotic conditions (e.g. temperature and rainfall), dispersal limitation and biotic interactions (e.g. competition, facilitation or interactions with natural enemies). Understanding how these factors influence distributional dynamics under climate change is a major knowledge gap, particularly for small ranged and dispersal‐limited plant species, which are at higher risk of extinction. Epiphytes are hypothesized to be particularly vulnerable to climate change and we know little about what drives their distribution and how they will respond to climate change. To address this issue, we leveraged a 10‐year dataset on the occupancy dynamics of the endemic orchid Lepanthes rupestris to identify the drivers of local colonization and extinction dynamics and assess the long‐term fate of this population under multiple climate change scenarios.

We compared 290 dynamic occupancy models in their ability to predict the colonization and extinction dynamics of a L. rupestris metapopulation. The model set predicted colonization–extinction dynamics as a function of asymmetric patch connectivity, moss area, elevation, temperature (minimum, maximum and variability) and/or rainfall.

The best model predicted that local colonization increases with increasing asymmetric patch connectivity but decreases as minimum temperature and maximum temperature variability increase. The best model also predicted that local extinction increases with increasing variability in maximum temperature. Negative effects were more severe in smaller patches.

Synthesis. Overall, our results demonstrate the role of asymmetric connectivity, climate and interactions with moss area as drivers of colonization and extinction dynamics. Moreover, our results suggest that asymmetrically dispersed epiphytes may struggle to persist under climate change because their limited connectivity may not be enough to counterbalance the negative effects of increasing mean or variability in temperature.
The effect of rural hospital closures on emergency medical service response and transport times
Authors: Miller Katherine E. M. , James Hailey J. , Holmes George Mark , Van Houtven Courtney H.
Published: January 2020

Objective

To examine the effect of rural hospital closures on EMS response time (minutes between dispatch notifying unit and arriving at scene); transport time (minutes between unit leaving the scene and arriving at destination); and total activation time (minutes between 9‐1‐1 call to responding unit returning to service), as longer EMS times are associated with worse patient outcomes.

Data Sources/Study Setting

We use secondary data from the National EMS Information System, Area Health Resource, and Center for Medicare & Medicaid Provider of Service files (2010‐2016).

Study Design

We examined the effects of rural hospital closures on EMS transport times for emergent 9‐1‐1 calls in rural areas using a pre‐post, retrospective cohort study with the matched comparison group using difference‐in‐difference and quantile regression models.

Principal Findings

Closures increased mean EMS transport times by 2.6 minutes (P = .09) and total activation time by 7.2 minutes (P = .02), but had no effect on mean response times. We also found closures had heterogeneous effects across the distribution of EMS times, with shorter response times, longer transport times, and median total activation times experiencing larger effects.

Conclusions

Rural hospital closures increased mean transport and total activation times with varying effects across the distribution of EMS response, transport, and total times. These findings illuminate potential barriers to accessing timely emergency services due to closures.
Supporting Real‐Time Contextual Inquiry through Sensor Data
Authors: GORKOVENKO KATERINA , BURNETT DAN , MURRAY‐RUST DAVE , THORP JAMES , RICHARDS DANIEL
Published: January 2020

A key challenge in carrying out product design research is obtaining rich contextual information about use in the wild. We present a method that algorithmically mediates between participants, researchers, and objects in order to enable real‐time collaborative sensemaking. It facilitates contextual inquiry, revealing behaviours and motivations that frame product use in the wild. In particular, we are interested in developing a practice of use driven design, where products become research tools that generate design insights grounded in user experiences. The value of this method was explored through the deployment of a collection of Bluetooth speakers that capture and stream live data to remote but co‐present researchers about their movement and operation. Researchers monitored a visualisation of the real‐time data to build up a picture of how the speakers were being used, responding to moments of activity within the data, initiating text conversations and prompting participants to capture photos and video. Based on the findings of this explorative study, we discuss the value of this method, how it compares to contemporary research practices, and the potential of machine learning to scale it up for use within industrial contexts. As greater agency is given to both objects and algorithms, we explore ways to empower ethnographers and participants to actively collaborate within remote real‐time research.
Mitochondrial function in skeletal myofibers is controlled by a TRF2‐SIRT3 axis over lifetime
Authors: Robin Jérôme D. , Jacome Burbano Maria‐Sol , Peng Han , Croce Olivier , Thomas Jean Luc , Laberthonniere Camille , Renault Valerie , Lototska Liudmyla , Pousse Mélanie , Tessier Florent , Bauwens Serge , Leong Waiian , Sacconi Sabrina , Schaeffer Laurent , Magdinier Frédérique , Ye Jing , Gilson Eric
Published: January 2020

Telomere shortening follows a developmentally regulated process that leads to replicative senescence of dividing cells. However, whether telomere changes are involved in postmitotic cell function and aging remains elusive. In this study, we discovered that the level of the TRF2 protein, a key telomere‐capping protein, declines in human skeletal muscle over lifetime. In cultured human myotubes, TRF2 downregulation did not trigger telomere dysfunction, but suppressed expression of the mitochondrial Sirtuin 3 gene (SIRT3) leading to mitochondrial respiration dysfunction and increased levels of reactive oxygen species. Importantly, restoring the Sirt3 level in TRF2‐compromised myotubes fully rescued mitochondrial functions. Finally, targeted ablation of the Terf2 gene in mouse skeletal muscle leads to mitochondrial dysfunction and sirt3 downregulation similarly to those of TRF2‐compromised human myotubes. Altogether, these results reveal a TRF2‐SIRT3 axis controlling muscle mitochondrial function. We propose that this axis connects developmentally regulated telomere changes to muscle redox metabolism.
A parent‐reported standardised checklist is not sensitive to screen for motor problems at school age following neonatal critical illness
Authors: Toussaint‐Duyster Leontien C. C. , van der Cammen‐van Zijp Monique H. M. , Tibboel Dick , Gischler Saskia , van Rosmalen Joost , IJsselstijn Hanneke
Published: January 2020

Aim

As nowadays more children survive neonatal critical illness, evaluation of long‐term morbidities becomes more important. We determined whether the parent‐reported Movement Assessment Battery for Children‐Second Edition (MABC‐2) Checklist is a proper tool to screen for motor problems in school‐aged children born with severe anatomical anomalies and/or treated with neonatal extracorporeal membrane oxygenation.

Methods

We analysed data of 190/253 children (60.0% male) participating in our multidisciplinary follow‐up programme who were routinely assessed at the ages of five, eight and/or 12 years. Parents completed the Checklist prior to assessment of the child's actual motor performance by a physical therapist using the MABC‐2 Test. The sensitivity and specificity of the Checklist with a cut‐off point of the 16th percentile were determined.

Results

The sensitivity of the MABC‐2 Checklist was 57.1%, which implies that 42.9% of the children at risk for motor problems were not identified. The specificity was 79.1%.

Conclusion

The low sensitivity of the MABC‐2 Checklist suggests that this instrument does not suffice to screen for motor problems in children who survived neonatal critical illness. Yet, it may help to gain insight in parental perceptions of the child's motor performance and to provide tailored advice on lifestyle.
Merkel cell polyomavirus and non‐Merkel cell carcinomas: guilty or circumstantial evidence?
Authors: Csoboz Balint , Rasheed Kashif , Sveinbjørnsson Baldur , Moens Ugo
Published: January 2020

Merkel cell polyomavirus (MCPyV) is the major causative factor of the rare but aggressive cancer, Merkel cell carcinoma (MCC). Two characteristics of MCPyV‐positive MCCs are integration of the viral genome and expression of a truncated version of one of its oncogenic proteins, namely large T antigen. The strong association of MCPyV with MCC development has incited researchers to further investigate a possible role of this virus in other cancers. However, many of the examples displaying the presence of the virus in the various non‐MCC cancers are not able to clearly demonstrate a direct connection between cellular transformation and the presence of the virus. The prevalence of the virus is significantly lower in non‐MCC cancers compared to MCCs, with a lower level of viral load and sparse viral protein expression. Moreover, the state of the viral genome, and whether a truncated large T antigen is expressed, has rarely been investigated. Nonetheless, considering the strong oncogenic potential of MCPyV proteins in MCC, the plausible contribution of MCPyV to transformation and cancer growth in non‐MCC tumors cannot be ruled out. Furthermore, the absence of MCPyV in cancers does not exclude a hit‐and‐run mechanism, or the oncoproteins of MCPyV may potentiate the neoplastic process mediated by co‐infecting oncoviruses such as high‐risk human papillomaviruses and Epstein–Barr virus. The current review is focusing on the available data describing the presence of MCPyV in non‐MCC tumors, with an aim to provide a comprehensive overview of the corresponding literature and to discuss the potential contribution of MCPyV to non‐MCC cancer in light of this.
Beyond the frame, beyond critique: Reframing place through more‐than visual participant‐photography
Authors: Kelly David
Published: January 2020

There is an abundance of critique in tourism studies, human geography, and the social sciences that takes tourism‐driven depictions of place as its object. Indeed, the problematics of touristic imaginaries tend to fix, obscure, and exclude object‐subjects that more‐or‐less sit familiarly within/out frames of representation. Beyond the frame, beyond critique, there are practices that are less observed – practices that radically challenge the potency of ubiquitous “good life” narratives. This paper draws on visual ethnographic research methods in a frequently photographed but narrowly experienced place. Broome, in the remote Kimberley region of Australia, is an idyllic small urban town with a large tourism economy and operates as a service hub for extractive resource industries inland and offshore. Through the use of picture postcards and participant‐driven photography, this paper presents a narrative of “the beach” that demonstrates the fragility of normative “good life” tropes. By amplifying practices of inhabiting the beach that exceed representational critique and stimulate other ways of authoring place, this paper looks for an activism that resists settling on colonial ways of knowing place.
Tectono‐sedimentary evolution of transverse extensional faults in a foreland basin: Response to changes in tectonic plate processes
Authors: Carrillo Emilio , Guinea Ander , Casas Albert , Rivero Lluis , Cox Nicole , Vázquez‐Taset Yaniel Misael
Published: January 2020

Late Paleocene to Middle Eocene strata in the easternmost part of the Southern Pyrenees, up to 4 km thick, provide information on tectono‐sedimentary evolution of faults transversal to the Pyrenean chain. To know how changes in tectonic plate processes control the structural evolution of transverse faults and the synchronous thickness and lithological distribution of sedimentary strata in a foreland basin, field observations, interpretation of 2D seismic lines tied to lithostratigraphic data of exploration wells and gravity modelling constrains were carried out. This resulted in the following two tectono‐sedimentary phases in a foreland basin: first phase, dominated by transverse extensional faulting, synchronous with deposition of marine carbonates (ca. 57 to 51 Ma); and second phase, characterized by transverse contractional faulting, coeval to accumulation of marine and transitional siliciclastics (51 to 44 Ma). During the first phase, Iberia and Adria were moving to the east and west respectively. Therefore, lithospheric flexure in the easternmost part of the Iberian plate was developed due to that Sardinia was over‐thrusting Iberia. Consequently, activation of E‐dipping normal faults was generated giving rise to thick‐deep and thin‐shallow carbonate platform deposits across the hanging walls and footwalls of the transverse structures. During the second phase, a shearing interaction between Iberia and Sardinia prevailed re‐activating the transverse faults as contractional structures generating thin‐shelf and thick‐submarine fan deposits across the hanging walls and footwalls of the transverse structures. In the transition between the first and second phases, evaporitic conditions dominated in the basin suggesting a tectonic control on basin marine restriction. The results of our study demonstrate how thickness and lithology distribution, controlled by transverse faulting in a compressional regimen, are influenced by phases related to processes affecting motions and interactions between tectonic plates and continental blocks.
Treaty of Paris vs. Treaty of Niagara: Rethinking Canadian economic history in the 21st century
Authors: Redish Angela
Published: January 2020

In this paper, I argue that in focussing on the role of natural resource exports (“staples”) as drivers of the extent and characteristics of economic growth, Canadian economic history has overlooked questions of resource ownership. Equally it has focused on the development of the settler economy rather than on that of Indigenous nations, with little acknowledgement of the relationship between the two. I review some milestones in the evolution of legal recognition of Indigenous land and resource rights, an evolution that has a direct impact on today's Canadian economy. I then survey some recent papers to demonstrate that the theoretical and empirical tools of economists can combine to provide important new insights into, and a more holistic picture of, the development of the Canadian economy.
Novel mutation in MKKS/BBS6 linked with arRP and polydactyly in a family of North Indian origin
Authors: Goyal Shiwali , Singh Indu R. , Vanita Vanita
Published: January 2020

Background

To identify the underlying genetic defect in a fourth‐generation autosomal recessive retinitis pigmentosa (arRP) family. Detailed family history and clinical data were collected from nine members, including three affected, from an arRP family.

Methods

Whole‐exome sequencing (WES) was performed on DNA sample of an affected individual IV: 2. Variants obtained by WES were annotated using Ion Reporter Software (ver. 5.2). Potential pathogenic variants detected in an affected member were validated in other affected and unaffected family members by Sanger sequencing. Further 150 ethnically‐matched controls were tested for the variant that co‐segregated completely with disease in the family, so as to exclude it as a polymorphism. Various web‐based bioinformatics tools were also applied to access pathogenic potential of the observed variant.

Results

All the three patients had RP with polydactyly of both hands and feet, however, they did not show other symptoms of Bardet‐Biedl syndrome (BBS) or McKusick‐Kaufmann Syndrome (MKKS). A novel missense mutation, that is, c.518A>C (p.His173Pro) was identified in MKKS/BBS6 that co‐segregated completely with the disease phenotype in all the three affected members and was not observed in six unaffected members of the family. Also the c.518A>C change was not observed in 150 ethnically matched controls (300 chromosomes), hence excluding it as a polymorphism.

Conclusions

Present study is the second report of identifying a novel mutation in MKKS/BBS6 that is linked with arRP in association with polydactyly, however, with no other signs of BBS or MKKS. These findings further expand the mutation spectrum of MKKS/BBS6 for arRP with polydactyly.
The uses and implications of avian vocalizations for conservation planning
Authors: Lewis Rebecca N. , Williams Leah J. , Gilman R. Tucker
Published: January 2020

There is a growing recognition that animal behavior can affect wildlife conservation, but there have been few direct studies of animal behavior in conservation programs. However, a great deal of existing behavioral research can be applied in the context of conservation. Research on avian vocalizations provides an excellent example. The conspicuous nature of the vocal behavior of birds makes it a useful tool for monitoring populations and measuring biodiversity, but the importance of vocalizations in conservation goes beyond monitoring. Geographic song variants with population‐specific signatures, or dialects, can affect territory formation and mate choice. Dialects are influenced by cultural evolution and natural selection and changes can accumulate even during the timescale of conservation interventions, such as translocations, reintroductions, and ex situ breeding. Information from existing research into avian vocalizations can be used to improve conservation planning and increase the success of interventions. Vocalizations can confer a number of benefits for conservation practitioners through monitoring, providing baseline data on populations and individuals. However, the influence of cultural variation on territory formation, mate choice, and gene flow should be taken into account because cultural differences could create obstacles for conservation programs that bring birds from multiple populations together and so reduce the success of interventions.
Giant cell tumour‐like features of myositis ossificans in cytology—a case report
Authors: Ravi Soundarya , Gochhait Debasis , Stephen Norton , Umamahesweran Sandyya , Srinivas Bheemanathi Hanuman , Penumadu Prasanth
Published: January 2020

The diagnosis of myositis ossificans onfine needle aspiration cytology is a challenge due to variation in clinical, radiological and pathological findings in its three stages. A case is described with particular attention to the cytological features and diferential diagnosis.
The cost of prevalent and incident cardiovascular disease in people with type 2 diabetes in Scotland: data from the Scottish Care Information–Diabetes Collaboration
Authors: McMeekin P. , Geue C. , Mocevic E. , Hoxer C. S. , Ochs A. , McGurnaghan S. , Colhoun H. M. , Wild S. H. , Wu O. ,   the Scottish Diabetes Research Network Epidemiology Subgroup
Published: January 2020

Aim

To compare costs for three groups of people with type 2 diabetes, those at high risk of future cardiovascular disease, those without cardiovascular disease and those with established cardiovascular disease, and to also compare costs incurred by people with type 2 diabetes with an incident cardiovascular disease event with those who remain incident event‐free over a 3‐year period.

Methods

Data about people with type 2 diabetes in Scotland were obtained from the Scottish Care Information Diabetes registry. Data linkage was used to retrieve information on healthcare utilization, care home use and deaths. Productivity effects were estimated for those of non‐pensionable age. We estimated costs over 12 months (prevalent cardiovascular disease) and 3 years from incident cardiovascular disease event.

Results

Mean annual cost per person with established cardiovascular disease was £6900, £3300 for a person at high risk of future cardiovascular disease, and £2500 for a person without cardiovascular disease and not at high risk. In year 1, the cost of an incident cardiovascular disease event was £16 700 compared with £2100 for people without an incident event. Over 2 years, the cumulative costs were £21 500 and £4200, and by year 3, £25 000 and £5900, respectively.

Conclusions

Cardiovascular disease in people with type 2 diabetes places a significant financial burden on healthcare and the wider economy. Our results emphasize the financial consequences of cardiovascular disease prevention strategies.
The contribution of Parkin, PINK1 and DJ‐1 genes to selective neuronal degeneration in Parkinson's disease
Authors: van der Vlag Marc , Havekes Robbert , Heckman Pim R. A.
Published: January 2020

Parkinson's disease (PD) is characterised by selective and severe degeneration of the substantia nigra pars compacta and the locus coeruleus (LC), which underlies the most prominent symptoms. Although α‐synuclein accumulation has long been established to play a causal role in the disease, it alone cannot explain the selective degenerative pattern. Recent evidence shows that the selective vulnerability could arise due to the large presence of cytosolic catecholamines and Ca2+ ions in the substantia nigra pars compacta and LC specifically that can be aberrantly affected by α‐synuclein accumulation. Moreover, each has its own toxic potential, and disturbance of one can exacerbate the toxic effects of the others. This presents a mechanism unique to these areas that can lead to a vicious degenerative cycle. Interestingly, in familial variants of PD, the exact same brain areas are affected, implying the underlying process is likely the same. However, the exact disease mechanisms of many of these genetic variants remain unclear. Here, we review the effects of the PD‐related genes Parkin, PINK1 and DJ‐1. We establish that these mutant varieties can set in motion the same degenerative process involving α‐synuclein, cytosolic catecholamines and Ca2+. Additionally, we show indications that model organisms might not accurately represent all components of this central mechanism, explaining why Parkin, PINK1 and DJ‐1 model organisms often lack a convincing PD‐like phenotype.
Metabolic rate is negatively linked to adult survival but does not explain latitudinal differences in songbirds
Authors: Boyce Andy J. , Mouton James C. , Lloyd Penn , Wolf Blair O. , Martin Thomas E.
Published: January 2020

Survival rates vary dramatically among species and predictably across latitudes, but causes of this variation are unclear. The rate‐of‐living hypothesis posits that physiological damage from metabolism causes species with faster metabolic rates to exhibit lower survival rates. However, whether increased survival commonly observed in tropical and south temperate latitudes is associated with slower metabolic rate remains unclear. We compared metabolic rates and annual survival rates that we measured across 46 species, and from literature data across 147 species of birds in northern, southern and tropical latitudes. High metabolic rates were associated with lower survival but survival varied substantially among latitudinal regions independent of metabolism. The inability of metabolic rate to explain latitudinal variation in survival suggests (1) species may evolve physiological mechanisms that mitigate physiological damage from cellular metabolism and (2) extrinsic rather than intrinsic sources of mortality are the primary causes of latitudinal differences in survival.
Effects of long‐term straw return on soil organic carbon storage and sequestration rate in North China upland crops: A meta‐analysis
Authors: Berhane Medhn , Xu Miao , Liang Zhiying , Shi Jianglan , Wei Gehong , Tian Xiaohong
Published: January 2020

Soil organic carbon (SOC) is essential for soil fertility and climate change mitigation, and carbon can be sequestered in soil through proper soil management, including straw return. However, results of studies of long‐term straw return on SOC are contradictory and increasing SOC stocks in upland soils is challenging. This study of North China upland agricultural fields quantified the effects of several fertilizer and straw return treatments on SOC storage changes and crop yields, considering different cropping duration periods, soil types, and cropping systems to establish the relationships of SOC sequestration rates with initial SOC stocks and annual straw C inputs. Our meta‐analysis using long‐term field experiments showed that SOC stock responses to straw return were greater than that of mineral fertilizers alone. Black soils with higher initial SOC stocks also had lower SOC stock increases than did soils with lower initial SOC stocks (fluvo‐aquic and loessial soils) following applications of nitrogen‐phosphorous‐potassium (NPK) fertilizer and NPK+S (straw). Soil C stocks under the NPK and NPK+S treatments increased in the more‐than‐20‐year duration period, while significant SOC stock increases in the NP and NP+S treatment groups were limited to the 11‐ to 20‐year period. Annual crop productivity was higher in double‐cropped wheat and maize under all fertilization treatments, including control (no fertilization), than in the single‐crop systems (wheat or maize). Also, the annual soil sequestration rates and annual straw C inputs of the treatments with straw return (NP+S and NPK+S) were significantly positively related. Moreover, initial SOC stocks and SOC sequestration rates of those treatments were highly negatively correlated. Thus, long‐term straw return integrated with mineral fertilization in upland wheat and maize croplands leads to increased crop yields and SOC stocks. However, those effects of straw return are highly dependent on fertilizer management, cropping system, soil type, duration period, and the initial SOC content.
Screening for vulnerable older people: Is the Probability of Repeated Admission scale an accurate tool?
Authors: Perez Mariangela , Moreira Virgílio G , Lourenço Roberto A
Published: January 2020

Aim

To evaluate the Probability of Repeated Admission (Pra) scale performance in predicting healthcare utilization and death in a community sample of Rio de Janeiro city, Brazil.

Methods

This was a prospective longitudinal study. The sample was composed of community‐dwelling older people who participated in the research network Frailty in Brazilian Older People Study, Rio de Janeiro section. It analyzed data from the baseline and the follow up. At the baseline, 764 older adults were stratified by the Pra, and, 3 years later, data on health services utilization and survival status were collected. The Pra accuracy, obtained by the area under the curve, the sensitivity and the specificity to predict hospitalization in 3 years; visits to the emergency department; and death were determined. Cox regression estimated the survival curves, according to the risk strata.

Results

The accuracy, the sensitivity and the specificity of Pra were 62% (95% CI 57–68%), 8.8% and 95.4% for hospitalization in 3 years; 59% (95% CI 53–64%), 8.3% and 94.8% for emergency room visits; 66% (95% CI 59–74%) and 68% (95% CI 63–73%), 15.0% and 96.0% for death. Survival curves showed that high‐risk individuals were more likely to die compared with the low‐risk individuals, adjusted to covariables (P < 0.001).

Conclusions

The Pra presented low accuracy, low sensitivity and high specificity for all outcomes observed, indicating a poor performance to screen vulnerable older adults in Brazil. Therefore, this tool should not be used alone, as a case‐finding instrument. Geriatr Gerontol Int 2020; 20: 360–365.
Lagrangian bounds for large‐scale multicommodity network design: a comparison between Volume and Bundle methods
Authors: Shibasaki Rui S. , Baiou Mourad , Barahona Francisco , Mahey Philippe , de Souza Mauricio C.
Published: January 2020

The Bundle Method and the Volume Algorithm are among the most efficient techniques to obtain accurate Lagrangian dual bounds for hard combinatorial optimization problems. We propose here to compare their performance on very large scale Fixed‐Charge Multicommodity Capacitated Network Design problems. The motivation is not only the quality of the approximation of these bounds as a function of the computational time but also the ability to produce feasible primal solutions and thus to reduce the gap for very large instances for which optimal solutions are out of reach. Feasible solutions are obtained through the use of Lagrangian information in constructive and improving heuristic schemes. We show in particular that, if the Bundle implementation has provided great quality bounds in fewer iterations, the Volume Algorithm is able to reduce the gaps of the largest instances, taking profit of the low computational cost per iteration compared to the Bundle Method.
Heuristic approaches for the family traveling salesman problem
Authors: Bernardino Raquel , Paias Ana
Published: January 2020

In this article, we address the family traveling salesman problem (FTSP), an NP‐hard problem that may be seen as a generalization of the traveling salesman problem. In the FTSP, the set of cities is partitioned into several families and one wants to find the minimum cost route that visits a given number of cities in each family. We propose two metaheuristics, a population‐based method and a local search method, and a hybrid algorithm, which combines a branch‐and‐cut algorithm with a local search procedure. All the proposed methods improve the best known upper bounds from the literature. The local search method and the hybrid algorithm improve the best known upper bounds for all the benchmark instances with unknown optimal value, while the population‐based method improves the best known upper bounds for all instances, except two. Furthermore, we developed an instance generator to create additional test instances with different visit patterns. These newly generated instances were considered in the computational experiment and, thus, we provide optimal values or upper bounds for each instance. Additionally, we created a website dedicated to the FTSP, where this information is made available to the scientific community (http://familytsp.rd.ciencias.ulisboa.pt/).
Microstructural evolution of 3YSZ flash‐sintered with current ramp control
Authors: R. Lavagnini Isabela , Campos João V. , Ferreira Julieta A. , A. Pallone Eliria M. J.
Published: January 2020

The effect of a controlled current ramp during flash sintering (FS) on the densification and microstructural evolution of 3 mol% yttria‐stabilized zirconia was investigated. The samples were flash sintered using a current ramp control with six different current ramp rates and compared with samples sintered by FS without current ramp control. In both cases, maximum electric current densities of 100 and 200 mA mm−2 were used. The microstructure of cylindrical samples was observed, showing grain size heterogeneity between the curved surface and the core for the flash‐sintered (FSed) samples regardless of the maximum current density used. By contrast, the current ramp FSed samples exhibited a homogeneous grain size when the electric current density of 100 mA mm−2 was applied. Thus, controlling a current ramp during FS can be an alternative for avoiding grain size heterogeneity on ceramics sintered by this technique.
Dihydrotestosterone potentiates insulin to up‐regulate prokineticin‐1 in decidualizing human endometrial stromal cells
Authors: Ujvari Dorina , Graells Brugalla Carlota , Hirschberg Angelica Lindén
Published: January 2020

Prokineticin 1 (PROK1) is a key regulator of embryo implantation and placentation, and its dysregulation is associated with pregnancy complications, such as pre‐eclampsia and foetal growth restriction. We have previously shown that insulin strongly enhances the expression of PROK1 in human decidualizing stromal cells. Here, we demonstrate that dihydrotestosterone (DHT), but not testosterone, potentiates insulin to up‐regulate PROK1 in these cells. However, the androgens alone do not influence the expression of PROK1. Our findings suggest that insulin and androgens both are involved in the regulation of PROK1 that could have implications for normal and pathological pregnancies.
Pre‐treatment systemic immune‐inflammation index is a useful prognostic indicator in patients with breast cancer undergoing neoadjuvant chemotherapy
Authors: Chen Li , Kong Xiangyi , Wang Zhongzhao , Wang Xiangyu , Fang Yi , Wang Jing
Published: January 2020

The systemic immune‐inflammation index (SII = N × P/L) based on neutrophil (N), platelet (P) and lymphocyte (L) counts is used to predict the survival of patients with malignant tumours and can fully reflect the balance between host inflammatory and immune status. This study is conducted to explore the potential prognostic significance of SII in patients with breast cancer undergoing neoadjuvant chemotherapy (NACT). A total of 262 patients with breast cancer received NACT were enrolled in this study. According to the receiver operating characteristic curve, the optimal cut‐off value of SII was divided into two groups: low SII group (<602 × 109/L) and high SII group (≥602 × 109/L). The associations between breast cancer and clinicopathological variables by SII were determined by chi‐squared test or Fisher's exact test. The Kaplan‐Meier plots and log‐rank test were used to determine clinical outcomes of disease‐free survival (DFS) and overall survival (OS). The prognostic value of SII was analysed by univariate and multivariate Cox proportional hazards regression models. The toxicity of NACT was accessed by National Cancer Institute Common Toxicity Criteria (NCICTC). According to univariate and multivariate Cox regression survival analyses, the results showed that the value of SII had prognostic significance for DFS and OS. The patients with low SII value had longer DFS and OS than those with high SII value (31.11 vs 40.76 months, HR: 1.075, 95% CI: 0.718‐1.610, P = .006; 44.47 vs 53.68 months, HR: 1.051, 95% CI: 0.707‐1.564, P = .005, respectively). The incidence of DFS and OS in breast cancer patients with low SII value was higher than that in those patients with high SII value in 3‐, 5‐ and 10‐year rates. The common toxicities after NACT were haematological and gastrointestinal reaction, and there were no differences by SII for the assessment of side effects of neoadjuvant chemotherapy. Meanwhile, the results also proved that breast cancer patients with low SII value and high Miller and Payne grade (MPG) survived longer than those breast cancer with high SII value and low MPG grade. In patients without lymph vessel invasion, these breast cancer patients with low SII value had better prognosis and lower recurrence rates than those with high SII value. Pre‐treatment SII with the advantage of reproducible, convenient and non‐invasive was a useful prognostic indicator for breast cancer patients undergoing neoadjuvant chemotherapy and is a promising biomarker for breast cancer on treatment strategy decisions.
Lobetyolin induces apoptosis of colon cancer cells by inhibiting glutamine metabolism
Authors: He Wei , Tao Weiwei , Zhang Feng , Jie Qian , He Yun , Zhu Wei , Tan Jiani , Shen Weixing , Li Liu , Yang Ye , Cheng Haibo , Sun Dongdong
Published: January 2020

The purpose of the present study was to evaluate the anti‐cancer property of Lobetyolin on colorectal cancer and explore its potential mechanism. Lobetyolin was incubated with HCT‐116 cells in the absence or presence of ASCT2 inhibitor Benser or p53 inhibitor Pifithrin‐α. The levels of glutamine, glutamic acid, α‐ketoglutarate, ATP and GSH were determined to measure the glutamine metabolism. Annexin V‐FITC/PI staining and TUNEL assay were applied to estimate the apoptotic condition. The levels of ASCT2 were examined by RT‐qPCR, Western blot and immunofluorescence staining. The expressions of cleaved‐caspase‐3, caspase‐3, cleaved‐caspase‐7, caspase‐7, cleaved‐PARP, PARP, p53, p21, bax and survivin were detected using Western blot analysis. As a result, the treatment with Lobetyolin effectively induced apoptosis and glutamine metabolism in HCT‐116 cells through ASCT2 signalling. The inhibition of ASCT2 reduced the glutamine‐related biomarkers and augmented the apoptotic process. We further found that the effect of Lobetyolin on HCT‐116 was related to the expressions of p21 and bax, and transportation of p53 to nucleus. The inhibition of p53 by Pifithrin‐α promoted the inhibitory effect of Lobetyolin on ASCT2‐mediated apoptosis. Lobetyolin also exerted anti‐cancer property in nude mice. In conclusion, the present work suggested that Lobetyolin could induce the apoptosis via the inhibition of ASCT2‐mediated glutamine metabolism, which was possibly governed by p53.
Adrenomedullin has a cytoprotective role against endoplasmic reticulum stress for pancreatic β‐cells in autocrine and paracrine manners
Authors: Suetomi Risa , Ohta Yasuharu , Akiyama Masaru , Matsumura Takuro , Taguchi Akihiko , Yamamoto Kaoru , Kamatani Takashi , Tanizawa Yukio
Published: January 2020

Aims/Introduction

Pancreatic β‐cells are sensitive to endoplasmic reticulum (ER) stress, which has a major role in the context of β‐cell death. Adrenomedullin (ADM) has been shown to exert a cytoprotective effect under various pathophysiological conditions. Several studies have suggested that thiazolidinediones have protective effects on β‐cells. During the course to elucidate the molecular mechanisms by which pioglitazone prevents β‐cell death, ADM emerged as a candidate. Here, we studied the regulation of ADM expression, including the effects of pioglitazone, and its role in pancreatic islets.

Materials and Methods

We analyzed ADM expression in islet cell lines treated with pioglitazone. The effects of ER stress on ADM and ADM receptor expressions were investigated by analyzing thapsigargin‐treated MIN6 cells and islets isolated from Wfs1−/− and db/db mice. To study the anti‐apoptotic effect of ADM, ER stress‐exposed MIN6 cells were treated with ADM peptides or transfected with ADM expression plasmid.

Results

Pioglitazone increased the production and secretion of ADM in islets through peroxisome‐proliferator activated receptor‐γ‐dependent mechanisms. Thapsigargin treatment increased expressions of both ADM and ADM receptor, composed of Ramp2, Ramp3 and Crlr, in MIN6 cells. ADM and ADM receptor expressions were also increased in isolated islets from Wfs1−/− and db/db mice. ADM peptides and ADM overexpression protected MIN6 cells from thapsigargin‐induced apoptosis.

Conclusions

ER stress stimulates ADM production and secretion in islets. ADM signaling might protect β‐cells from ER stress‐induced apoptosis, and might be one of the self‐protective mechanisms. β‐Cell protection by pioglitazone is partly through induction of ADM. ADM‐based therapy could be a novel strategy for treating diabetes.
Clinical characteristics including cardiovascular and metabolic risk factors in adolescents with psoriasis
Authors: Blegvad C. , Nybo Andersen A.‐M. , Groot J. , Zachariae C. , Barker J. , Skov L.
Published: January 2020

Background

Clinical studies on psoriasis in adolescents have mainly been performed in patients with severe psoriasis. Population‐based studies of clinical characteristics and risk factors for later cardiovascular and metabolic disease in children and adolescents are lacking.

Objectives

To examine the clinical characteristics of adolescents with psoriasis nested in a general population cohort. Furthermore, to investigate cardiovascular and metabolic risk factors in the adolescents with psoriasis compared to parentally predisposed and non‐predisposed adolescents without psoriasis from the same birth cohort.

Methods

We identified adolescents with and without psoriasis using a nationwide general population birth cohort in Denmark. A clinical examination included skin inspection and scoring of psoriasis severity, completion of a questionnaire on psoriasis and comorbidities, physical measurements, and blood sampling. Participants also completed self‐administered questionnaires on quality of life and mental health.

Results

We included 81 adolescents with psoriasis and 234 controls (110 with genetic predisposition for psoriasis and 124 without predisposition). Median age was 15.6 (13.5–18.5) years, and in those with active psoriasis, median Psoriasis Area and Severity Index score was 1.2 (0.1–11.4). The scalp was the most common site of psoriasis, both at debut and at time of examination. Diaper rash in infancy was more frequent in the psoriasis group. No significant differences regarding quality of life, anxiety and depression were found. More adolescents with psoriasis were obese (8.6% vs. 1.7%, P = 0.008), and physical measures of abdominal obesity were also significantly higher. HbA1c was significantly higher (31.55 vs. 30.81 mmol/mol, P = 0.048), while no differences were found for blood pressure, lipids or high‐sensitivity C‐reactive protein. In a subgroup analysis, this was evident in the non‐predisposed psoriasis‐free controls only.

Conclusions

Overall, adolescents with psoriasis from this general population had mild disease. Still, early markers of cardiovascular and metabolic disease were elevated.
Sonidegib and vismodegib in the treatment of patients with locally advanced basal cell carcinoma: a joint expert opinion
Authors: Dummer R. , Ascierto P.A. , Basset‐Seguin N. , Dréno B. , Garbe C. , Gutzmer R. , Hauschild A. , Krattinger R. , Lear J.T. , Malvehy J. , Schadendorf D. , Grob J.J.
Published: January 2020

Sonidegib and vismodegib are hedgehog pathway inhibitors (HhIs) approved for the treatment of advanced basal cell carcinoma (BCC). Until recently, vismodegib was the only targeted treatment available for patients with locally advanced BCC (laBCC) in cases where surgery and radiotherapy are inappropriate. Sonidegib has recently been approved and now presents an alternative treatment option. The clinical differences between the two HhIs in patients with laBCC are unclear, as no head‐to‐head randomized controlled trials are or will be initiated. Moreover, there were important differences in the designs of their pivotal studies, BOLT (sonidegib) and ERIVANCE (vismodegib), and these differences complicate evidence‐based analysis of their relative efficacy and safety profiles. In this paper, a group of clinical experts in the management of laBCC summarizes the clinical and pharmacological profiles of sonidegib and vismodegib based on published data and their own clinical experience. One key difference between the two pivotal studies was the criteria used to assess BCC severity. ERIVANCE (a single‐arm phase II trial) used the conventional Response Evaluation Criteria in Solid Tumors (RECIST), while the more recent double‐blind randomized BOLT trial used the stringent modified RECIST. A preplanned analysis adjusted the outcomes from BOLT with RECIST‐like criteria, and this enabled the experts to discuss relative efficacy outcomes for the two treatments. Centrally reviewed objective response rate (ORR) for vismodegib was 47.6% (95% CI: 35.5–60.6) at 21‐month follow‐up using RECIST. After adjusting with RECIST‐like criteria, the ORR for sonidegib according to central review at 18‐month follow‐up was 60.6% (95% CI: 47.8–72.4). Both treatments were associated with similar patterns of adverse events. Sonidegib and vismodegib share the same efficacy and tolerability profiles, but their pharmacokinetic profiles show several differences, such as volume of distribution and half‐life. Further studies are needed to understand how these differences may impact clinical practice.