bluuebunny/crossref_metadata_2025 huggingface dataset:
Water hydraulic axial piston motor cavitation characteristics based on CFD technology
Authors: Yang Lijie , Yin Shuai , Niu Qingna
Published: March 2017

Purpose

The purpose of this paper is to analyze the cavitation characteristics of a water hydraulic axial piston motor (WHAPM) to improve the water motor performance, to reduce the vibration and noise and to prolong the service life of the motor.

Design/methodology/approach

The computational fluid dynamics (CFD) software PumpLinx is chosen to do cavitation analysis of the WHAPM. In this case, first, cavitation mechanism of the water piston motor is analyzed in depth. Then, considering the effects of bubble dynamics, the rate of phase transition, turbulence effects and non-condensable gas, the full cavitation model is selected, the dynamic CFD numerical model of internal flow field on the water hydraulic piston motor is established based on PumpLinx software and the fluid cavitation inside is numerically studied. Finally, the influence of the valve plate and pistons on motor cavitation is analyzed.

Findings

Research results show that there are two serious cavitation regions: one is the pressure transition region of the valve plate that is near the top dead center, and the other is the low-pressure region of the piston that is near the low-pressure transition area. Moreover, the more serious cavitation area is on the valve plate region.

Originality/value

The simulation results show that the proposed algorithm is able to detect the cavitation characteristics of the water piston motor. Besides, it is deduced that valve-plate structure optimization is more important than pistons to reduce cavitation influence.
Review paper: Virtual sources and their responses, Part II: data‐driven single‐sided focusing
Authors: Wapenaar Kees , Thorbecke Jan , van der Neut Joost , Slob Evert , Snieder Roel
Published: March 2017

In Part I of this paper, we defined a focusing wave field as the time reversal of an observed point‐source response. We showed that emitting a time‐reversed field from a closed boundary yields a focal spot that acts as an isotropic virtual source. However, when emitting the field from an open boundary, the virtual source is highly directional and significant artefacts occur related to multiple scattering. The aim of this paper is to discuss a focusing wave field, which, when emitted into the medium from an open boundary, yields an isotropic virtual source and does not give rise to artefacts. We start the discussion from a horizontally layered medium and introduce the single‐sided focusing wave field in an intuitive way as an inverse filter. Next, we discuss single‐sided focusing in two‐dimensional and three‐dimensional inhomogeneous media and support the discussion with mathematical derivations. The focusing functions needed for single‐sided focusing can be retrieved from the single‐sided reflection response and an estimate of the direct arrivals between the focal point and the accessible boundary. The focal spot, obtained with this single‐sided data‐driven focusing method, acts as an isotropic virtual source, similar to that obtained by emitting a time‐reversed point‐source response from a closed boundary.
Research Note: Near‐surface layer replacement for sparse data: is interpolation needed?
Authors: Sun Yimin , Verschuur Eric , Luo Yi
Published: March 2017

Near‐surface problem is a common challenge faced by land seismic data processing, where often, due to near‐surface anomalies, events of interest are obscured. One method to handle this challenge is near‐surface layer replacement, which is a wavefield reconstruction process based on downward wavefield extrapolation with the near‐surface velocity model and upward wavefield extrapolation with a replacement velocity model. This requires, in theory, that the original wavefield should be densely sampled. In reality, data acquisition is always sparse due to economic reasons, and as a result in the near‐surface layer replacement data interpolation should be resorted to. For datasets with near‐surface challenges, because of the complex event behaviour, a suitable interpolation scheme by itself is a challenging problem, and this, in turn, makes it difficult to carry out the near‐surface layer replacement. In this research note, we first point out that the final objective of the near‐surface layer replacement is not to obtain a newly reconstructed wavefield but to obtain a better final image. Next, based upon this finding, we propose a new thinking, interpolation‐free near‐surface layer replacement, which can handle complex datasets without any interpolation. Data volume expansion is the key idea, and with its help, the interpolation‐free near‐surface layer replacement is capable of preserving the valuable information of areas of interest in the original dataset. Two datasets, i.e., a two‐dimensional synthetic dataset and a three‐dimensional field dataset, are used to demonstrate this idea. One conclusion that can be drawn is that an attempt to interpolate data before layer replacement may deteriorate the final image after layer replacement, whereas interpolation‐free near‐surface layer replacement preserves all image details in the subsurface.
Seismic facies analysis through musical attributes
Authors: Amendola A. , Gabbriellini G. , Dell'Aversana P. , Marini A. J.
Published: March 2017

Seismic facies analysis is a well‐established technique in the workflow followed by seismic interpreters. Typically, huge volumes of seismic data are scanned to derive maps of interesting features and find particular patterns, correlating them with the subsurface lithology and the lateral changes in the reservoir. In this paper, we show how seismic facies analysis can be accomplished in an effective and complementary way to the usual one. Our idea is to translate the seismic data in the musical domain through a process called sonification, mainly based on a very accurate time–frequency analysis of the original seismic signals. From these sonified seismic data, we extract several original musical attributes for seismic facies analysis, and we show that they can capture and explain underlying stratigraphic and structural features. Moreover, we introduce a complete workflow for seismic facies analysis starting exclusively from musical attributes, based on state‐of‐the‐art machine learning computational techniques applied to the classification of the aforementioned musical attributes. We apply this workflow to two case studies: a sub‐salt two‐dimensional seismic section and a three‐dimensional seismic cube. Seismic facies analysis through musical attributes proves to be very useful in enhancing the interpretation of complicated structural features and in anticipating the presence of hydrocarbon‐bearing layers.
An alternative approach in establishing relation between vertical and horizontal gradients of 2D potential field
Authors: Roy Indrajit G.
Published: March 2017

The relation in which the vertical and horizontal gradients of potential field data measured along a profile across a two‐dimensional source are a Hilbert transform pair is re‐established using complex domain mathematics. In addition, a relation between the measured field and its vertical gradient in terms of a closed‐form formula is also established. The formula is based on hypersingular or Hadamard's finite‐part integral. To estimate the vertical gradient directly from the field data, Linz's algorithm of computing Hadamard's finite‐part integral is implemented. Numerical experiments are conducted on synthetically generated total magnetic intensity data with a mild level of noise contamination. A model of a magnetically polarised vertical thin sheet buried at a finite depth within a non‐magnetic half‐space was considered in generating the synthetic response. The results from numerical experiments on the mildly noise‐contaminated synthetic response are compared with those from using classical Fourier and robust regularised Hilbert transform‐based techniques.
Urban development, land sharing and land sparing: the importance of considering restoration
Authors: Collas Lydia , Green Rhys E. , Ross Alexander , Wastell Josie H. , Balmford Andrew
Published: March 2017

At present, there is limited knowledge of how best to reconcile urban development with biodiversity conservation, and in particular whether populations of wild species would be greater under low‐density housing (with larger gardens), or high‐density housing (allowing more area to be left as undeveloped green spaces). The land sharing/sparing framework – originally developed in the context of farming – can be applied to address this question.

We sampled the abundance of trees in the city of Cambridge, UK, along a gradient of human density. We designed different scenarios of urban growth to accommodate the human population predicted in 2031. For each scenario, we projected the future city‐wide tree population size and quantified its carbon sequestration potential. We also considered, for the first time in an urban sharing‐sparing context, the implications of habitat restoration on degraded urban green space.

We found that the density of most native and non‐native tree species is presently highest in areas of low human density, compared to both higher density areas and green space (which is largely maintained with few trees). However, restoring woodland in green spaces would lead to far greater densities of native trees than on any existing land use. Hence, provided >2% of green space is restored, native tree population sizes would be larger if urban growth followed a land‐sparing approach. Likewise, carbon sequestration would be maximised under land sparing coupled with restoration, but even so only a maximum of 2·5% of the city's annual greenhouse gas emissions could be offset.

Although both tree populations and carbon storage thus appear to benefit from land‐sparing development, the risk that this might widen the existing disconnect between people and nature must also be addressed – perhaps through a combination of adding housing in low‐density areas while ensuring these are in close proximity to high‐quality green space.

Synthesis and applications. In regions which have already been cleared of intact habitat, a combination of land‐sparing urban development with the restoration of green space could accommodate urban population growth whilst dramatically improving the existing status of local tree populations. Where cities are expanding into intact habitat, the merits of urban development by land sparing may be even more pronounced. Studies in such regions are urgently needed.
Phenological responsiveness to climate differs among four species of Quercus in North America
Authors: Gerst Katharine L. , Rossington Natalie L. , Mazer Susan J.
Published: March 2017

The timing of the seasonal activity of organisms is a tractable indicator of climate change. Many studies in North America have investigated the role of temperature on the onset date of phenological transitions in temperate deciduous trees and found that the onset of leafing and flowering in numerous species has occurred earlier in recent years, apparently in response to higher temperatures in winter and spring.

Few studies have examined the climatic and biogeographic drivers of phenological responses in water‐limited ecosystems or explored interspecific variation in responses of phenological metrics other than the timing of onset, such as the periodicity or duration of phenological activity.

This study used phenological observations of four species of Quercus contributed to the USA National Phenology Network database from 2009 to 2014 to investigate how responses to climate (temperature and precipitation) and geographic location (latitude, longitude and elevation) varied among two western North American species (Q. agrifolia and Q. lobata) and two eastern and central North American species (Q. alba and Q. rubra).

Within years, in species in the western, water‐limited ecosystems, the phenological phases observed here (bud break, flowers or flower buds) tend to occur intermittently throughout the growing season, and each event is of longer duration than the same phenophases of the temperate‐zone species, rendering a single onset date an incomplete metric with which to track responsiveness or to compare species. By contrast, the eastern/central U.S. species were phenologically more responsive than the western species to spatial and temporal variation in winter, spring, and fall precipitation and maximum temperature.

Synthesis. Within and between regions these congeners exhibited a diversity of responses to seasonal temperature and precipitation. This indicates that for predictive model development it is critical to understand how each underlying driver influences species that are adapted to different climatic regimes. These results underscore the value of studying a range of phenological metrics and species from a variety of ecosystems to better predict phenological responses to short‐term variation and to long‐term change in climate.
Where knowledge meets: heritage expertise at the intersection of people, perspective, and place
Authors: Yarrow Thomas
Published: March 2017

Drawing on ethnographic research with heritage professionals in Scotland, the essay explores meetings as organizational devices for differentiating and relating various forms of epistemic, social, and material context. The account describes how the bureaucratic ideal of institutional consistency is achieved through staged encounters between the perspectives of the various people who meet, and the buildings that are the objects of their meeting. These ethnographic examples are used to develop two linked points. Firstly, it is suggested that the lens of ‘meeting’ complicates the relatively monolithic characterizations of heritage expertise evident in widely influential deconstructive critiques of heritage practice. Secondly, it is argued that heritage practitioners’ own accounts of these negotiations highlight material and spatial dimensions of bureaucratic conduct that have that have received relatively little ethnographic attention in prevalent textually orientated accounts.
Unbroken: RADseq remains a powerful tool for understanding the genetics of adaptation in natural populations
Authors: Catchen Julian M. , Hohenlohe Paul A. , Bernatchez Louis , Funk W. Chris , Andrews Kimberly R. , Allendorf Fred W.
Published: March 2017

Recently, Lowry et al. addressed the ability of RADseq approaches to detect loci under selection in genome scans. While the authors raise important considerations, such as accounting for the extent of linkage disequilibrium in a study system, we strongly disagree with their overall view of the ability of RADseq to inform our understanding of the genetic basis of adaptation. The family of RADseq protocols has radically improved the field of population genomics, expanding by several orders of magnitude the number of markers available while substantially reducing the cost per marker. Researchers whose goal is to identify regions of the genome under selection must consider the LD of the experimental system; however, there is no magical LD cutoff below which researchers should refuse to use RADseq. Lowry et al. further made two major arguments: a theoretical argument that modeled the likelihood of detecting selective sweeps with RAD markers, and gross summaries based on an anecdotal collection of RAD studies. Unfortunately, their simulations were off by two orders of magnitude in the worst case, while their anecdotes merely showed that it is possible to get widely divergent densities of RAD tags for any particular experiment, either by design or due to experimental efficacy. We strongly argue that RADseq remains a powerful and efficient approach that provides sufficient marker density for studying selection in many natural populations. Given limited resources, we argue that researchers should consider a wide range of trade‐offs among genomic techniques, in light of their study question and the power of different techniques to answer it.
Flap endonuclease‐1 rs174538 G>A polymorphisms are associated with the risk of esophageal cancer in a Chinese population
Authors: Sang Yonghua , Bo Lin , Gu Haiyong , Yang Wengtao , Chen Yongbing
Published: March 2017

Background

Esophageal cancer has a high mortality rate, particularly in Asia, and there are obvious racial differences in regard to incidence. The purpose of our study was to assess the genetic susceptibility of functional single nucleotide polymorphisms in flap endonuclease‐1 (FEN1) in esophageal squamous cell carcinoma ESCC.

Methods

Clinical blood samples of 629 ESCC cases and 686 control samples were collected. The ligation detection reaction method was used to determine FEN
1 rs174538 G>A genotypes.

Results

A significantly decreased risk of ESCC was associated with FEN1 rs174538 GA genotypes among patients under 63 years old.

Conclusions

Our results suggest that functional polymorphism FEN1 rs174538 G>A might affect personal susceptibility to ESCC. This result provides a solid theoretical foundation for further clinical study using larger sample sizes.
Evaluating helicopter emergency medical missions: a reliability study of the HEMS benefit and NACA scores
Authors: Raatiniemi L. , Liisanantti J. , Tommila M. , Moilanen S. , Ohtonen P. , Martikainen M. , Voipio V. , Reitala J. , Iirola T.
Published: March 2017

Background

The benefits of the Helicopter Emergency Medical Service (HEMS) and dispatch accuracy are continuously debated, and a widely accepted score to measure the benefits of the mission is lacking. The HEMS Benefit Score (HBS) has been used in Finnish helicopter emergency medical services, but studies are lacking. The National Advisory Committee for Aeronautics (NACA) score is widely used to measure the severity of illness or injury in the pre‐hospital setting, but it has many critics due to its subjectivity. We investigated the inter‐rater and rater‐against‐reference reliability of these scores.

Methods

Twenty‐five fictional HEMS missions were created by an expert panel. A total of 22 pre‐hospital physicians were recruited to participate in the study from two different HEMS bases. The participants received written instructions on the use of the scores. Intraclass correlation coefficients (ICCs) and mean differences between rater‐against‐reference values were calculated.

Results

A total of 17 physicians participated in the study. The ICC was 0.70 (95% CI 0.57–0.83) for the HBS and 0.65 (95% CI 0.51–0.79) for the NACA score. Mean differences between references and raters were −0.09 (SD 0.72) for the HBS and 0.28 (SD 0.61) for the NACA score, indicating that raters scored some lower NACA values than reference values formed by an expert panel.

Conclusion

The HBS and NACA score had substantial inter‐rater reliability. In addition, the rater‐against‐reference values were acceptable, though large differences were observed between individual raters and references in some clinical cases.
Co‐creating a Peer Education program to improve skin health in older people from diverse communities: An innovation in health promotion
Authors: Ogrin Rajna , Brasher Kathleen , Occleston Jessica , Byrne Jennifer
Published: March 2017

Objective

Chronic wounds, debilitating and costly to manage, are more common in older people. Prevention is possible through improving skin health. We developed, implemented and evaluated an innovative health promotion program to improve skin health of older adults.

Methods

A one‐hour, peer education program was co‐created and delivered to culturally diverse community‐dwelling older people. A mixed‐methods evaluation approach comprised objective measures of skin health and barrier function at commencement and six weeks posteducation, and focus groups posteducation.

Results

Seventy‐three participants participated in the study (mean age 74.38 ± 11.80 years). Hydration significantly improved at follow‐up for English speaking participants (t(27) = −2.90, P = 0.007). The majority of participants reported the education to be informative and useful in supporting behaviour changes.

Conclusion

The peer education program improved skin hydration in older English speaking individuals. Peer education may effectively deliver health promotion information in some groups.
Exploratory study of Australian aged care staff knowledge and attitudes of later life sexuality
Authors: Chen Yung‐Hui , Jones Cindy , Osborne Debora
Published: March 2017

Objective

To explore aged care staff knowledge and attitudes towards later life sexuality and attitudes about intimacy in people with dementia.

Methods

Fifty‐two care staff working in two aged care facilities with secure dementia care units were recruited. Knowledge and attitudes on later life sexuality and attitudes towards later life sexuality in people with dementia were surveyed using the Aging Sexual Knowledge and Attitudes Scale and the selected eight items of the Staff Attitudes about Intimacy and Dementia, respectively.

Results

The results indicated that aged care staff knowledge of later life sexuality is inadequate, but attitudes towards later life sexuality and about intimacy and dementia were relatively permissive.

Conclusion

Improving aged care staff knowledge of later life sexuality is needed. Continuing education and training should provide to support the expression of later life sexuality including those with dementia.
Occupational respiratory allergy in peach crop workers
Authors: Pérez‐Calderón R. , Gonzalo‐Garijo M. Á. , Rodríguez‐Velasco F. J. , Sánchez‐Vega S. , Bartolomé‐Zavala B.
Published: March 2017

Background

Occupational respiratory diseases in workers of peach tree crops have been reported punctually and have been associated with sensitization to proteins present in both pollen and leaf tree. We report the study of 37 workers with respiratory symptoms related to occupational exposure to peach trees.

Methods

Prick tests and specific IgE determinations were performed with extracts from leaves and branches of peach tree. Immunodetection in leaf extract was realized by sodium dodecyl sulfate–polyacrylamide gel electrophoresis SDS‐PAGE‐immunoblotting with patient sera and rabbit serum anti‐Pru p 3. Immunodetection inhibition was performed with rPru p 3 and pollen profilins. The clinical relevance of sensitization was demonstrated by specific bronchial challenge test (SBCT) with peach leaf extract.

Results

Most patients suffered symptoms when peach trees had leaves, specifically during thinning and harvesting fruit (rhinoconjunctivitis: 100% and asthma: 67.5%). Sensitization to leaf extract was demonstrated in 86% of patients. IgE‐immunoblotting with peach leaf extract revealed in six patient sera a pair of bands of 10 and 16 kDa, and in nine a 16‐kDa band. Those bands could be two isoforms of peach leaf lipid transfer proteins( LTP), so the recognition frequency of some LTP isoform by our patient sera was 42%. 33% of the sera recognized a doubled band of about 14.5 kDa and this recognition was inhibited by nPho d 2. The SBCT with peach leaf extract was positive in the asthmatic sensitized patients tested.

Conclusions

Sensitization to peach leaves was the cause of occupational respiratory symptoms in our patients. Some patient sera revealed IgE‐binding proteins matching LTP and/or profilin.
Histopathological tumour viability after neoadjuvant chemotherapy influences survival in resected pancreatic cancer: analysis of early outcome data
Authors: Townend Phil , de Reuver Phil R. , Chua Terence C. , Mittal Anubhav , Clark Stephen J. , Pavlakis Nick , Gill Anthony J. , Samra Jaswinder S.
Published: March 2017

Background

Neoadjuvant therapy is increasingly recognized as an effective strategy prior to pancreatoduodenectomy. We investigate the role of neoadjuvant chemotherapy (NAC) followed by surgery and the predictive role of viable residual tumour cells histopathologically on outcomes.

Methods

The study population comprised of 195 consecutive patients with pancreatic adenocarcinoma who were treated with either NAC or a surgery‐first (SF) strategy. Histopathological viable tumour cells were examined in the NAC patients and clinicopathological factors were correlated with overall survival.

Results

Forty‐two patients (22%) were treated with NAC and 153 patients (78%) underwent SF. NAC was associated with higher estimated blood loss during surgery (928 mL versus 615 mL; P = 0.004), fewer (<15) excised lymph nodes (37% versus 17%; P = 0.015) and lower rates of lymphovascular invasion (65% versus 45%; P = 0.044) when compared with SF. Two‐year survival of patients undergoing NAC was 63% and 51% in patients undergoing SF (P = 0.048). The 2‐year survival of patients who had >65% residual tumour cells was 45% and 90% in patients who had <65% residual tumour cells (P = 0.022). Favourable responders (<65% viable tumour cells) were observed to have shorter operation time (<420 min) (55% versus 13%; P = 0.038), trend towards negative lymph node status (38% versus 10%; P = 0.067) and greater lymph node harvest in node positive patients (≥4 positive lymph nodes) (77% versus 37%; P = 0.045).

Conclusion

The improved survival of patients undergoing NAC indicates effective management of micrometastatic disease and is an effective option requiring further investigation. Histopathological viable tumour cells after NAC was a surrogate marker for survival.
Paediatric vertebral artery aneurysms: a literature review
Authors: Phan Kevin , Schultz Konrad , Lu Victor M. , Campbell Ryan J. , Wang Nelson , Rao Prashanth J.
Published: March 2017

Vertebral artery (VA) aneurysms in the paediatric population are a rare but a serious condition. However, the epidemiology of paediatric VA aneurysms is poorly understood and there is little consensus on what constitutes the appropriate treatment. Although multiple treatment options are available, including surgery, endovascular approaches, coil embolization and parent artery occlusion, there is limited clinical evidence regarding which approach is most optimal. This review outlines the current literature and evidence outlining the epidemiology, presentation, pathogenesis and treatment of paediatric VA aneurysms.
Diabetes and an inescapable (auto)ethnography
Authors: Lucherini Mark
Published: March 2017

This paper reports on personal reflections from a recent research project on the geographies of living with diabetes. Drawing from research participants’ written and oral accounts alongside the researcher's own everyday experiences, this project aimed to provide a detailed account of life with diabetes. However, issues of the researcher's own diagnosis with diabetes confounded the project so that completing the research soon became a potentially overwhelming task. The paper questions to what extent an autoethnographical approach can be mediated in a project in which the researcher's own involvement is complex. Three different types of fieldwork encounter are discussed in the paper: an anxiety‐inducing encounter; supportive encounters; and disciplinary encounters. Each of these encounters involved a different form of personal engagement and degree of vulnerability on the part of the researcher in order to complete the research. Autoethnography was inescapable in this research project, hence the bracketing of the ‘auto’ to indicate the researcher's desire for less personal involvement but still acknowledging that this aim can be difficult to achieve. This paper offers a personal account of how autoethnography can be managed in the interests of the researcher's preferred approach, and for the completion of the research.
Social risks and public pension in South Korea
Authors: Kim Soo‐Wan
Published: March 2017

This study investigated how traditional and new social risks have emerged in South Korea and how policies have coped with them, focusing on the public pension program. Using national statistics data and publicly published government reports, factors such as marital status, economic activity, and the insurance trend of the public pension by age and gender for the last decade were examined. Main results are as follows. Women's labor force participation has slightly increased; however, career discontinuity remains and new family risks have increased. Second, women's public pension coverage as a percentage of the employment rate has substantially increased, implying that old labor market risks have largely been reduced for female workers. Third, the public pension insured rate among male workers has decreased to a small degree, which implies that new labor market risks are increasing for male workers. Consequently, the gender gap in risk has been reduced; however, policies established to deal with new risks have introduced some gender effects
Defamilization/familization measures and women's pension income—The case of Taiwan
Authors: Chau Ruby C. M. , Foster Liam , Yu Sam W. K. , Yu Yuk Pun
Published: March 2017

This paper examines how defamilization and familization measures can affect women's capacity to accumulate pension income and their subsequent standard of living after retirement. Firstly, it highlights the concepts of defamilization and familization and discusses the potential of these measures in assisting women to save pension income through the “commodification” and “decommodification” of labor. Secondly, it examines the major pension policies and examples of defamilization and familization measures in Taiwan. It shows how the current limited provision of such measures could create “double jeopardy” for women, affecting access to paid employment or resources to enable women who wish to undertake caring responsibilities to do so, ultimately impacting their capacity to accumulate pension income. Thirdly, it suggests ways to strengthen defamilization and familization measures in order to enable women to accumulate sufficient retirement income on the basis of three preconditions: policy attention to the reciprocal relationship between familization/defamilization measures and pension schemes for women; a recognition of differences between women in their preferred strategies to accumulate pension income; and an emphasis on a life course perspective to understand the double jeopardies faced by women in saving for retirement.
SERPINC1 gene mutations in antithrombin deficiency
Authors: Mulder René , Croles F. Nanne , Mulder André B. , Huntington James A. , Meijer Karina , Lukens Michaël V.
Published: March 2017

Existing evidence suggests that in most cases antithrombin deficiency can be explained by mutations in its gene, SERPINC1. We investigated the molecular background of antithrombin deficiency in a single centre family cohort study. We included a total of 21 families comprising 15 original probands and sixty‐six relatives, 6 of who were surrogate probands for the genetic analysis. Antithrombin activity and antigen levels were measured. The heparin‐antithrombin binding ratio assay was used to distinguish between the different subtypes of type II antithrombin deficiency. SERPINC1 mutations were detected by direct sequencing of all 7 exons and regulatory regions, and multiplex ligation‐dependent probe amplification. Eighty‐six per cent of the families had a detrimental SERPINC1 gene mutation that segregated in the family. We detected 13 different SERPINC1 gene mutations of which 5 were novel. Among all these mutations, 44% was associated with type I deficiency, whereas the remainder was associated with type II heparin binding site (11%), type II pleiotropic effect (33%), type II reactive site (6%) or had the antithrombin Cambridge II mutation (6%). The current study reports several novel SERPINC1 mutations, thereby adding to our knowledge of the molecular background of antithrombin deficiency. Finally, our results point out the importance of future research outside the conventional SERPINC1 gene approach.
Future of robotic surgery in urology
Authors: Rassweiler Jens J. , Autorino Riccardo , Klein Jan , Mottrie Alex , Goezen Ali Serdar , Stolzenburg Jens‐Uwe , Rha Koon H. , Schurr Marc , Kaouk Jihad , Patel Vipul , Dasgupta Prokar , Liatsikos Evangelos
Published: March 2017

Objectives

To provide a comprehensive overview of the current status of the field of robotic systems for urological surgery and discuss future perspectives.

Materials and Methods

A non‐systematic literature review was performed using PubMed/Medline search electronic engines. Existing patents for robotic devices were researched using the Google search engine. Findings were also critically analysed taking into account the personal experience of the authors.

Results

The relevant patents for the first generation of the da Vinci platform will expire in 2019. New robotic systems are coming onto the stage. These can be classified according to type of console, arrangement of robotic arms, handles and instruments, and other specific features (haptic feedback, eye‐tracking). The Telelap ALF‐X robot uses an open console with eye‐tracking, laparoscopy‐like handles with haptic feedback, and arms mounted on separate carts; first clinical trials with this system were reported in 2016. The Medtronic robot provides an open console using three‐dimensional high‐definition video technology and three arms. The Avatera robot features a closed console with microscope‐like oculars, four arms arranged on one cart, and 5‐mm instruments with six degrees of freedom. The REVO‐I consists of an open console and a four‐arm arrangement on one cart; the first experiments with this system were published in 2016. Medicaroid uses a semi‐open console and three robot arms attached to the operating table. Clinical trials of the SP 1098‐platform using the da Vinci Xi for console‐based single‐port surgery were reported in 2015. The SPORT robot has been tested in animal experiments for single‐port surgery. The SurgiBot represents a bedside solution for single‐port surgery providing flexible tube‐guided instruments. The Avicenna Roboflex has been developed for robotic flexible ureteroscopy, with promising early clinical results.

Conclusions

Several console‐based robots for laparoscopic multi‐ and single‐port surgery are expected to come to market within the next 5 years. Future developments in the field of robotic surgery are likely to focus on the specific features of robotic arms, instruments, console, and video technology. The high technical standards of four da Vinci generations have set a high bar for upcoming devices. Ultimately, the implementation of these upcoming systems will depend on their clinical applicability and costs. How these technical developments will facilitate surgery and whether their use will translate into better outcomes for our patients remains to be determined.
Starch contamination landscapes in field archaeology: Olduvai Gorge, Tanzania
Authors: Mercader Julio , Abtosway Matthew , Baquedano Enrique , Bird Robert W. , Díez‐Martín Fernando , Domínguez‐Rodrigo Manuel , Favreau Julien , Itambu Makarius , Lee Patrick , Mabulla Audax , Patalano Robert , Pérez‐González Alfredo , Santonja Manuel , Tucker Laura , Walde Dale
Published: March 2017

No agreement on what constitutes a safe and reproducible anticontamination protocol exists for ancient starch research. Protocols applied to laboratory work may represent ‘symptomatic treatment’ only, as contamination of archaeological materials in the field may be more extensive than realized. This paper is the first systematic study on the impact that modern starches from surface and buried soils, windborne dispersal, human motion, excavation techniques and toolkits, and field attire has on archaeological sample quality. The study area is Olduvai Gorge, Tanzania. We identify seven starch types (discrete granules, n = 788) that embody the starch contamination landscape for the region. This study also demonstrates the various diagenetic changes that buried starch granules undergo in a short time, such as cavitation, fissuring, disruption and gelatinization. There are significant differences in morphotype class representation between the topsoil starches and those collected deeper below ground at excavated sites. Diagenetically transformed granules from underground storage organs dominate in soils, while native starches from cereal endosperm (Panicoideae and Triticeae) abound above ground in airborne samples. Furthermore, we illustrate how lithic samples excavated under standard field conditions can be contaminated, and that when a sample is compromised during excavation, it may be impossible to distinguish between target and introduced starches, especially when granules are identical or morphologically similar. The paper provides field recommendations to control false positives.
Dexpramipexole improves bioenergetics and outcome in experimental stroke
Authors: Muzzi Mirko , Gerace Elisabetta , Buonvicino Daniela , Coppi Elisabetta , Resta Francesco , Formentini Laura , Zecchi Riccardo , Tigli Laura , Guasti Daniele , Ferri Martina , Camaioni Emidio , Masi Alessio , Pellegrini‐Giampietro Domenico E , Mannaioni Guido , Bani Daniele , Pugliese Anna M , Chiarugi Alberto
Published: March 2017

Background and Purpose

Dexpramipexole, a drug recently tested in patients with amyotrophic lateral sclerosis (ALS,) is able to bind F1Fo ATP synthase and increase mitochondrial ATP production. Here, we have investigated its effects on experimental ischaemic brain injury.

Experimental Approach

The effects of dexpramipexole on bioenergetics, Ca2+ fluxes, electrophysiological functions and death were evaluated in primary neural cultures and hippocampal slices exposed to oxygen‐glucose deprivation (OGD). Effects on infarct volumes and neurological functions were also evaluated in mice following proximal or distal middle cerebral artery occlusion (MCAo). Distribution of dexpramipexole within the ischaemic brain was evaluated by means of mass spectrometry imaging.

Key Results

Dexpramipexole increased mitochondrial ATP production in cultured neurons or glia and reduces energy failure, prevents intracellular Ca2+ overload and affords cytoprotection when cultures are exposed to OGD. This compound also counteracted ATP depletion, mitochondrial swelling, anoxic depolarization, loss of synaptic activity and neuronal death in hippocampal slices subjected to OGD. Post‐ischaemic treatment with dexpramipexole, at doses consistent with those already used in ALS patients, reduced brain infarct size and ameliorated neuroscore in mice subjected to transient or permanent MCAo. Notably, the concentrations of dexpramipexole reached within the ischaemic penumbra equalled those found neuroprotective in vitro.

Conclusion and Implications

Dexpramipexole, a compound able to increase mitochondrial F1Fo ATP‐synthase activity reduced ischaemic brain injury. These findings, together with the excellent brain penetration and favourable safety profile in humans, make dexpramipexole a drug with realistic translational potential for the treatment of stroke.

Linked Articles

This article is part of a themed section on Inventing New Therapies Without Reinventing the Wheel: The Power of Drug Repurposing. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.2/issuetoc
Documenting the urbanistic policy bias in rural early childhood services: Toward a functional definition of rurality
Authors: Vilches Silvia L. , Pighini Maria J. , Stewart Mary , Goelman Hillel
Published: March 2017

Key Messages

Current per capita funding models have an urbanistic policy bias.

The concept of rurality is undertheorized for social planning purposes.

Four key characteristics define rural service barriers: travel time, travel modalities, jurisdictional divides, and per capita funding models.
Cancer with low cathepsin D levels is susceptible to vacuolar (H+)‐ATPase inhibition
Authors: Kitazawa Satoshi , Nishizawa Satoru , Nakagawa Hideyuki , Funata Masaaki , Nishimura Kazuho , Soga Tomoyoshi , Hara Takahito
Published: March 2017

Vacuolar (H+)‐ATPases (V‐ATPases) have important roles in the supply of nutrients to tumors by mediating autophagy and the endocytic uptake of extracellular fluids. Accordingly, V‐ATPases are attractive therapeutic targets for cancer. However, the clinical use of V‐ATPase inhibitors as anticancer drugs has not been realized, possibly owing to their high toxicity in humans. Inhibition of V‐ATPase may be an appropriate strategy in highly susceptible cancers. In this study, we explored markers of V‐ATPase inhibitor sensitivity. V‐ATPase inhibitors led to pH impairment in acidic intracellular compartments, suppression of macropinocytosis, and decreased intracellular amino acid levels. The sensitivity of cells to V‐ATPase inhibitors was correlated with low cathepsin D expression, and cancer cells showed increased sensitivity to V‐ATPase inhibitors after pretreatment with a cathepsin D inhibitor and siRNA targeting the cathepsin D gene (CTSD). In addition, V‐ATPase inhibitor treatment led to the induction of the amino acid starvation response, upregulation of endoplasmic reticulum stress markers, and suppression of mammalian target of rapamycin (mTOR) signaling in cells expressing low levels of cathepsin D. Some colorectal cancer patients showed the downregulation of cathepsin D in tumor tissues compared with matched normal tissues. These findings indicate that V‐ATPase inhibitors are promising therapeutic options for cancers with downregulated cathepsin D.
Cockroach allergen serine proteinases: Isolation, sequencing and signalling via proteinase‐activated receptor‐2
Authors: Polley D. J. , Mihara K. , Ramachandran R. , Vliagoftis H. , Renaux B. , Saifeddine M. , Daines M. O. , Boitano S. , Hollenberg M. D.
Published: March 2017

Background

Allergy to the German cockroach (Blattella germanica) is a significant asthma risk factor for inner‐city communities. Cockroach, like other allergens, contains trypsin‐like enzyme activity that contributes to allergenicity and airway inflammation by activating proteinase‐activated receptors (PARs). To date, the enzymes responsible for the proteolytic activity of German cockroach allergen have not been characterized.

Objectives

We aimed to identify, isolate and characterize the trypsin‐like proteinases in German cockroach allergen extracts used for clinical skin tests. For each enzyme, we sought to determine (1) its substrate and inhibitor enzyme kinetics (Km and IC50), (2) its amino acid sequence and (3) its ability to activate calcium signalling and/or ERK1/2 phosphorylation via PAR2.

Methods

Using a trypsin‐specific activity‐based probe, we detected three distinct enzymes that were isolated using ion‐exchange chromatography. Each enzyme was sequenced by mass spectometery (deconvoluted with an expressed sequence tag library), evaluated kinetically for its substrate/inhibitor profile and assessed for its ability to activate PAR2 signalling.

Findings

Each of the three serine proteinase activity‐based probe‐labelled enzymes isolated was biochemically distinct, with different enzyme kinetic profiles and primary amino acid sequences. The three enzymes showed a 57%‐71% sequence identity with a proteinase previously cloned from the American cockroach (Per a 10). Each enzyme was found to activate both Ca++ and MAPK signalling via PAR2.

Conclusions and Relevance

We have identified three different serine proteinases from the German cockroach that may, via PAR2 activation, play different roles for allergen sensitization in vivo and may represent attractive therapeutic targets for asthma.
CXCL4 is a novel nickel‐binding protein and augments nickel allergy
Authors: Kuroishi T. , Bando K. , Tanaka Y. , Shishido K. , Kinbara M. , Ogawa T. , Muramoto K. , Endo Y. , Sugawara S.
Published: March 2017

Background

Nickel (Ni) is the most frequent metal allergen and induces a TH1‐dependent type‐IV allergy. Although Ni2+ is considered to bind to endogenous proteins, it currently remains unclear whether these Ni‐binding proteins are involved in Ni allergy in vivo. We previously reported the adjuvant effects of lipopolysaccharide (LPS) in a Ni allergy mouse model. As LPS induces a number of inflammatory mediators, we hypothesized that Ni‐binding protein(s) are also induced by LPS.

Objective

The objective of this study was to purify and identify Ni‐binding protein(s) from serum taken from LPS‐injected mice (referred as LPS serum) and examined the augmenting effects of these Ni‐binding protein(s) on Ni allergy in an in vivo model.

Methods

BALB/cA mice were sensitized with an i.p. injection of NiCl2 and LPS. Ten days after sensitization, mice were challenged with NiCl2 by an i.d. injection into ear pinnae. Ni‐binding protein(s) were purified by Ni‐affinity column chromatography and gel filtration.

Results

Lipopolysaccharide serum, but not serum taken from saline‐injected mice, augmented ear swelling induced by Ni‐allergic inflammation. Ni‐binding, but not non‐binding fraction, purified from LPS serum augmented Ni‐allergic inflammation. Mass spectrometry and Western blotting detected CXCL4 in the active fraction. A batch analysis with Ni‐sepharose and a surface plasmon resonance analysis revealed direct binding between CXCL4 and Ni2+. Recombinant CXCL4 augmented Ni‐allergic inflammation and exerted adjuvant effects at the sensitization phase.

Conclusions

These results indicate that CXCL4 is a novel Ni‐binding protein that augments Ni allergy at the elicitation and sensitization phases. This is the first study to demonstrate that the Ni‐binding protein augments Ni allergy in vivo.
Plasma levels of MASP-1, MASP-3 and MAp44 in patients with type 2 diabetes: influence of glycaemic control, body composition and polymorphisms in the MASP1 gene
Authors: Krogh S S , Holt C B , Steffensen R , Funck K L , Høyem P , Laugesen E , Poulsen P L , Thiel S , Hansen T K
Published: March 2017

Mounting evidence indicates that adverse activation of the complement system plays a role in the development of diabetic vascular complications. Plasma levels of the complement proteins mannan-binding lectin (MBL) and its associated serine proteases (MASP-1 and MASP-2) are elevated in diabetes. We hypothesized that single nucleotide polymorphisms (SNPs) in the MASP1 gene may contribute to altered plasma levels of the belonging gene products; MASP-1, MASP-3 and mannan-binding lectin-associated protein of 44 kDa (MAp44) in patients with type 2 diabetes. To investigate this, we compared plasma levels of MASP-1, MASP-3 and MAp44 in 100 patients with type 2 diabetes and 100 sex- and age-matched controls. Ten carefully selected SNPs were analysed using TaqMan® genotyping assay. Additionally, we included a streptozotocin-induced diabetes mouse model to directly examine the effect of inducing diabetes on MASP-1 levels. MASP-1 levels were significantly higher among patients with type 2 diabetes compared with healthy controls (P = 0·017). Five SNPs (rs874603, rs72549254, rs3774275, rs67143992, rs850312) in the MASP1 gene were associated with plasma levels of MASP-1, MASP-3 and MAp44. In the diabetes mouse model, diabetic mice had significantly higher MASP-1 levels than control mice (P = 0·003). In conclusion, MASP-1 levels were higher among patients with type 2 diabetes and diabetic mice. The mechanism behind this increase remains elusive.
The neuroprotective effects of caffeine in neurodegenerative diseases
Authors: Kolahdouzan Mahshad , Hamadeh Mazen J.
Published: March 2017

Caffeine is the most widely used psychostimulant in Western countries, with antioxidant, anti‐inflammatory and anti‐apoptotic properties. In Alzheimer's disease (AD), caffeine is beneficial in both men and women, in humans and animals. Similar effects of caffeine were observed in men with Parkinson's disease (PD); however, the effect of caffeine in female PD patients is controversial due to caffeine's competition with estrogen for the estrogen‐metabolizing enzyme, CYP1A2. Studies conducted in animal models of amyotrophic lateral sclerosis (ALS) showed protective effects of A2AR antagonism. A study found caffeine to be associated with earlier age of onset of Huntington's disease (HD) at intakes >190 mg/d, but studies in animal models have found equivocal results. Caffeine is protective in AD and PD at dosages equivalent to 3‐5 mg/kg. However, further research is needed to investigate the effects of caffeine on PD in women. As well, the effects of caffeine in ALS, HD and Machado‐Joseph disease need to be further investigated. Caffeine's most salient mechanisms of action relevant to neurodegenerative diseases need to be further explored.