bluuebunny/crossref_metadata_2025 huggingface dataset:
Extracting meaning from biological imaging data
Authors: Cohen Andrew R.
Published: November 2014

Biological imaging continues to improve, capturing continually longer-term, richer, and more complex data, penetrating deeper into live tissue. How do we gain insight into the dynamic processes of disease and development from terabytes of multidimensional image data? Here I describe a collaborative approach to extracting meaning from biological imaging data. The collaboration consists of teams of biologists and engineers working together. Custom computational tools are built to best exploit application-specific knowledge in order to visualize and analyze large and complex data sets. The image data are summarized, extracting and modeling the features that capture the objects and relationships in the data. The summarization is validated, the results visualized, and errors corrected as needed. Finally, the customized analysis and visualization tools together with the image data and the summarization results are shared. This Perspective provides a brief guide to the mathematical ideas that rigorously quantify the notion of extracting meaning from biological image, and to the practical approaches that have been used to apply these ideas to a wide range of applications in cell and tissue optical imaging.
Teaching quantitative biology: goals, assessments, and resources
Authors: Aikens Melissa L. , Dolan Erin L.
Published: November 2014

More than a decade has passed since the publication of BIO2010, calling for an increased emphasis on quantitative skills in the undergraduate biology curriculum. In that time, relatively few papers have been published that describe educational innovations in quantitative biology or provide evidence of their effects on students. Using a “backward design” framework, we lay out quantitative skill and attitude goals, assessment strategies, and teaching resources to help biologists teach more quantitatively. Collaborations between quantitative biologists and education researchers are necessary to develop a broader and more appropriate suite of assessment tools, and to provide much-needed evidence on how particular teaching strategies affect biology students' quantitative skill development and attitudes toward quantitative work.
NF1 regulation of RAS/ERK signaling is required for appropriate granule neuron progenitor expansion and migration in cerebellar development
Authors: Sanchez-Ortiz Efrain , Cho Woosung , Nazarenko Inga , Mo Wei , Chen Jian , Parada Luis F.
Published: November 2014

Cerebellar development is regulated by a coordinated spatiotemporal interplay between granule neuron progenitors (GNPs), Purkinje neurons, and glia. Abnormal development can trigger motor deficits, and more recent data indicate important roles in aspects of memory, behavior, and autism spectrum disorders (ASDs). Germline mutation in the NF1 tumor suppressor gene underlies Neurofibromatosis type 1, a complex disease that enhances susceptibility to certain cancers and neurological disorders, including intellectual deficits and ASD. The NF1 gene encodes for neurofibromin, a RAS GTPase-activating protein, and thus negatively regulates the RAS signaling pathway. Here, using mouse models to direct conditional NF1 ablation in either embryonic cerebellar progenitors or neonatal GNPs, we show that neurofibromin is required for appropriate development of cerebellar folia layering and structure. Remarkably, neonatal administration of inhibitors of the ERK pathway reversed the morphological defects. Thus, our findings establish a critical cell-autonomous role for the NF1–RAS–ERK pathway in the appropriate regulation of cerebellar development and provide a basis for using neonatal ERK inhibitor-based therapies to treat NF1-induced cerebellar disorders.
Pericellular proteolysis in cancer
Authors: Sevenich Lisa , Joyce Johanna A.
Published: November 2014

Pericellular proteases have long been associated with cancer invasion and metastasis due to their ability to degrade extracellular matrix components. Recent studies demonstrate that proteases also modulate tumor progression and metastasis through highly regulated and complex processes involving cleavage, processing, or shedding of cell adhesion molecules, growth factors, cytokines, and kinases. In this review, we address how cancer cells, together with their surrounding microenvironment, regulate pericellular proteolysis. We dissect the multitude of mechanisms by which pericellular proteases contribute to cancer progression and discuss how this knowledge can be integrated into therapeutic opportunities.
ATP-dependent chromatin remodeling shapes the long noncoding RNA landscape
Authors: Alcid Eric A. , Tsukiyama Toshio
Published: November 2014

Long noncoding RNAs (lncRNAs) are pervasively transcribed across eukaryotic genomes, but functions of only a very small subset of them have been demonstrated. This has led to active debate about whether many of them have any biological functions. In addition, very few regulators of lncRNAs have been identified. We developed a novel genetic screen using reconstituted RNAi in Saccharomyces cerevisiae and systematically identified a large number of putative lncRNA repressors. Among them, we found that four highly conserved chromatin remodeling factors are global lncRNA repressors that play major roles in shaping the eukaryotic lncRNA transcriptome. Importantly, we identified >250 antisense lncRNAs (CRRATs [chromatin remodeling-repressed antisense transcripts]) whose repression by these chromatin remodeling factors is required for the maintenance of normal levels of overlapping mRNA transcripts. Our results strongly suggest that regulation of mRNA through repression of antisense lncRNAs is far more broadly used than previously appreciated.
Real time 3D localization and mapping for USAR robotic application
Authors: Będkowski Janusz , Masłowski Andrzej , De Cubber Geert
Published: November 2014

Purpose

The purpose of this paper is to demonstrate a real time 3D localization and mapping approach for the USAR (Urban Search and Rescue) robotic application, focusing on the performance and the accuracy of the General‐purpose computing on graphics processing units (GPGPU)‐based iterative closest point (ICP) 3D data registration implemented using modern GPGPU with FERMI architecture.

Design/methodology/approach

The authors put all the ICP computation into GPU, and performed the experiments with registration up to 106 data points. The main goal of the research was to provide a method for real‐time data registration performed by a mobile robot equipped with commercially available laser measurement system 3D. The main contribution of the paper is a new GPGPU based ICP implementation with regular grid decomposition. It guarantees high accuracy as equivalent CPU based ICP implementation with better performance.

Findings

The authors have shown an empirical analysis of the tuning of GPUICP parameters for obtaining much better performance (acceptable level of the variance of the computing time) with minimal lost of accuracy. Loop closing method is added and demonstrates satisfactory results of 3D localization and mapping in urban environments. This work can help in building the USAR mobile robotic applications that process 3D cloud of points in real time.

Practical implications

This work can help in developing real time mapping for USAR robotic applications.

Originality/value

The paper proposes a new method for nearest neighbor search that guarantees better performance with minimal loss of accuracy. The variance of computational time is much less than SoA.
Vision‐based isolated translations and rotations estimation for inverted robot approaching a target
Authors: Jan Ibrar , Khan Umer , Iqbal Naeem
Published: November 2014

Purpose

Vision‐based inverted robot control exhibits a complex and a multi‐parameter estimation task. Compromises over speed and accuracy must be made to reduce the cost of the system, if high profile techniques are not utilized. The purpose of this paper is to present such a technique where many parameter estimation problems admit partitioning process. The process eliminates the complexity by dividing such a high dimension task into several reduced dimension problems. The partition procedure is defined by human understanding of the task. Here a mechanical setup is designed that handles the pose parameters estimations as a set of sub‐problems. The estimated pose parameters are applied to an inverted robot approaching a target on the floor.

Design/methodology/approach

A novel technique that helps the inverted robot to approach its target is detailed here. The new methodology is based upon the modified versions of existing and proven techniques of pure translations and rotations estimations. Providing valid conditions, the parameters of the two vectors of the camera's pose are isolated. In the first pass, the roll angle is adjusted. A subsequent pass uses modified 2‐point algorithm to estimate partial translational vector. Introducing 4‐point algorithm; an extension of pure rotational vector estimation technique, to estimate partial rotational vector. Lastly, visual depth is estimated to complete the task. For simplicity, the robot dynamics are not detailed here. It is assumed that the robot can possibly achieve any position if the desired pose parameters are known.

Findings

It is found that the isolated vectors estimation process reduces the complexity of the system and so reduces the computational cost and processing time. The proposed technique is applied to a prototype inverted Cartesian robot having 3D rotary wrist. Through analysis, it is observed that the estimated parameters are very close to the actual pose parameters.

Practical implications

The proposed technique can aid CNC vertical milling machines to countercheck the exact position and orientation of the tool w.r.t. the job. Similar systems in practice are DECKEL MAHO, DMU 60/80/100, 5‐axis package and DMC 35 V series.

Originality/value

The dynamic nature of the method proposed in the paper makes it more efficacious for mechanical/robotic systems with vertically downward tool under gravity effect.
The application of future‐oriented technology analysis (FTA) to law: the cases of legal research, legislative drafting and law enforcement
Authors: Nuno Gomes de Andrade Norberto
Published: November 2014

Purpose

This paper seeks to propose the application of future‐oriented technology analysis (FTA) to law. As law traditionally reacts after events and is resistant to change and transformation, the article argues for equipping legal activities with a set of tools, methods and approaches that enables them to acknowledge and anticipate the various possible futures that will guide society.

Design/methodology/approach

The paper describes a series of real world examples and case studies – pilot projects, research consortia and academic programmes – that are already employing FTA methodological approaches to pursue their objectives.

Findings

Based on these examples, the article explains the various benefits that the application of specific FTA methodological approaches (such as scenario‐planning, modelling techniques and backcasting) may bring to three specific legal fields: legal research, legislative drafting and law enforcement. The article also examines the prospective perils that systematically applying FTA to law may bring about. While the introduction of FTA tools and techniques to law is deemed extremely important and useful, the paper also draws attention to the problems and challenges that this entails, indicating paths for future research.

Originality/value

Future‐oriented legal studies are rare and, what is worse, the ones that exist lack proper methodology, failing to encompass the use of forecasting methods or foresight tools in the development of their studies. This paper attempts to fill the gap produced by this notorious lack of methodology in the legal analysis of the future, and presents a new methodological approach to law. It proposes the application of future‐oriented analysis (FTA) – as a common umbrella term that encompasses foresight, forecasting and technology assessment methods and tools – to the legal sphere.
Supply chain resilience: a state-of-the-art review and research directions
Authors: Mandal Santanu
Published: November 2014

Purpose

– The purpose of this paper is to report a comprehensive review of supply chain resilience and identify several research issues.

Design/methodology/approach

– The articles which have been published in international journals in the period 1980-2012 were collected by using databases like ISI Web of Knowledge, ScienceDirect and EBSCO. The articles were scrutinized based on relevance to context and value addition. The articles contributing significantly in the domain of supply chain resilience were selected for final review and various issues were identified.

Findings

– The paper argues that though several conceptual to few empirical works been done on supply chain resilience in recent years, there is large scope for research to address the issues in risk management, supply chain design, sourcing strategies, green practices, sustainable competitive advantage, supply chain security, supply chain performance and supply chain resilience.

Research limitations/implications

– The insights deduced in the paper are primarily based on 45 articles selected for critical review and analysis in the domain of supply chain resilience and hence should be interpreted only as key concerns in the area.

Originality/value

– The paper reports an evaluation of 45 key articles reported in the domain of supply chain resilience and indicates the research opportunities in the area.
A qualitative comparative analysis of neighborhood recovery following Hurricane Katrina
Authors: Jordan Elizabeth , Javernick-Will Amy , Amadei Bernard
Published: November 2014

Purpose

– The purpose of this research is to examine why communities facing the same disaster recover differentially and determine pathways to successful disaster recovery in the research setting of New Orleans neighborhoods affected by Hurricane Katrina. While previous studies suggest that there are a variety of pathways to recovery, a broader cross-case comparison is necessary to generalize these pathways into a recovery framework. Specifically, this study seeks to determine what pre-disaster and post-disaster causal factors, alone or in combination, were important to recovery following Hurricane Katrina.

Design/methodology/approach

– This paper presents a cross-case comparative study of neighborhood-level recovery. Based on prior work, which used the Delphi method to determine hypothesized causal factors and indicators of recovery, data was collected through publically available sources, including the US Census, the Greater New Orleans Community Data Center and previously completed studies for 18 damaged neighborhoods. Fuzzy-set qualitative comparative analysis was used due to its ability to analyze both quantitative and qualitative data for smaller case studies.

Findings

– The results show that there are multiple pathways combining pre-disaster community factors and post-disaster actions that led to recovery, as measured by population return. For example, economic capacity is nearly sufficient for recovery, but a combination of low social vulnerability, post-disaster community participation, a high proportion of pre-World War II housing stock and high amounts of post-disaster funds also led to recovery.

Originality/value

– This research uses a novel method to link pre-disaster measures of resilience and vulnerability to recovery outcomes and, through cross-case comparison, generates results that will enable researchers to develop a theory of sustainable community recovery.
Exploring the drivers of service quality perceptions in the tertiary education sector
Authors: Chavan Meena , Bowden-Everson Jana , Lundmark Erik , Zwar Jan
Published: November 2014

Purpose

– The purpose of this paper was to identify similarities and differences between domestic and international student’s expectations of their tertiary experience, as well as the way in which they evaluate the quality of the service that they receive from their tertiary provider. The paper develops an augmented model of service quality which is adapted to suit the tertiary education context.

Design/methodology/approach

– The study adopted a qualitative research approach. A total of six focus groups were conducted with a total of 36 International students and domestic students. All students were enrolled in the third year of an undergraduate degree at one large metropolitan university in Australia. The data were analyzed using qualitative analytic techniques and coded using NVIVO.

Findings

– First, the study found that there are significant challenges with regard to the use of student expectations as the foundation for assessing students’ service quality evaluations. This is because students were found to have vague expectations, and limited prior experience of the service from which to shape their expectations. In addition students were found to form their expectations as they consumed the service, throughout their degree program which often spanned three to four years. Second, the study found that traditional dimensions of service quality were not sufficient to capture the depth of international and domestic students’ service evaluations. The study proposed the inclusion of an additional two service quality constructs, namely, social benefits and co-creation/participation.

Originality/value

– Two new dimensions of service quality emerged from this study, “Social benefits” and “Co-creation/Participation”. The study therefore suggests that the tertiary experience should be enhanced through the provision of additional opportunities for student to staff and student to student interactions. In addition, tertiary institutions should also enhance opportunities for engagement within both the academic and industry environment.
Professional medical leadership: a relational training model
Authors: MacCarrick Geraldine R.
Published: November 2014

Purpose

– This paper aims to describe the educational philosophy and practice underpinning the Royal Australasian College of Medical Administrators (RACMA) program and how it is aligned with the needs of the Australian and New Zealand health care systems. Preparing future doctors as medical leaders requires keeping pace with developments in medical education and increased sophistication on the part of teaching and supervising faculty.

Design/methodology/approach

– This paper is a descriptive case study. The data are complemented by workforce data and excerpts from the RACMA Management and Leadership Curriculum.

Findings

– The RACMA has developed a program informed by current best practices in medical education. The educational underpinnings and instructional practices of the RACMA emphasize leadership as a collaborative social process and the importance of relational leadership in successful modern day practice. The ongoing development of the program has a focus on setting of clear learning objectives, regular and continuous feedback to trainees and reflective practice facilitated by the close relationship between trainees and their preceptor.

Research limitations/implications

– Although a site-specific case study, the application of relational models of teaching can be applied in other settings.

Practical implications

– The application of relational models of teaching can be applied in other settings.

Social implications

– This paper fulfils a social need to describe successful competency models used for medical leadership development.

Originality/value

– This paper fulfils an identified need to define competency models used as a foundation for medical leadership development.
Developing junior doctors as leaders of service improvement
Authors: Micallef Jason , Straw Brodene
Published: November 2014

Purpose

– This paper aims to provide an overview of the design and initial outcomes of a leadership and service improvement program for junior medical staff.

Design/methodology/approach

– This paper describes the rationale, initial set-up, structure, program outcomes and future directions of the Medical Service Improvement Program for junior doctors. This program is a recent initiative of the Western Australian public healthcare system.

Findings

– The Medical Service Improvement Program illustrates a successful approach to developing junior doctors to lead improvements in health service delivery. The program has resulted in tangible personal outcomes for participants, in addition to important organisational outcomes.

Practical implications

– This paper provides an evidence-based structured approach to developing the leadership abilities of junior medical staff. It provides practical information on the design of the leadership program that aligns the participant learning outcomes to postgraduate medical competencies. The program has demonstrated clear service outcomes, confirming that junior medical staff is both capable and committed to leading service improvement and reform.

Originality/value

– This paper provides clear evidence for the benefits of providing dedicated non-clinical time for junior medical staff to lead quality and improvement initiatives. This case study will assist hospital administrators, postgraduate education units and those involved in designing and administering clinical leadership development programs.
Impact of Regional Road Infrastructure Improvement on Intra‐Regional Trade in ECOWAS
Authors: Akpan Uduak
Published: November 2014

This study employs the gravity model of trade to examine the impact of improving the quality of a regional road infrastructure in the ECOWAS sub‐region, from its current level to the level of roads in South Africa, on intra‐regional trade. The study augments the traditional gravity model to include variables for language, common border and road quality. The positive difference in per capita GDP of trading partners is also included to test the Linder hypothesis. The parameters in the model are estimated using the random‐effect model and the result shows that such improvement will lead to a US$356.06 million (4.97 per cent) increase in intra‐regional trade relative to the 2012 level, ceteris paribus. Moreover, the ancillary benefits of improvement in road quality in terms of increased movement of factors of production will foster further intra‐regional trade in the medium and long terms. To enhance the benefits of the improvement in the road quality, ECOWAS governments needs to put in place other ‘soft’ infrastructures to fast‐track the achievement of the objectives of the ECOWAS trade liberalization scheme. However, increasing the quality of roads demands huge financial investment, thus a cost‐benefit trade‐off must be carefully considered.
Performance of Intra‐COMESA Trade Integration: A Comparative Study with ASEAN's Trade Integration
Authors: Ebaidalla Ebaidalla M. , Yahia Abdelrahim M.
Published: November 2014

This paper aims at assessing the performance of intra‐COMESA trade integration on the basis of success of ASEAN integration, using an out‐of‐sample approach. The analysis employed a gravity approach to estimate the coefficients of the ASEAN model which are used as a benchmark to project the potential trade for eight COMESA members. The success of COMESA is estimated by the ratio of potential to actual trade. The results pointed out that all countries of the selected sample are far from their potential trade level, implying unfavorable performance of the regional trade integration among COMESA members. The results also indicate that the gap between potential and actual trade has decreased in the last decade, suggesting a convergence toward the potential trade level over time. Finally, the paper ends with some policy recommendations regarding promoting regional cooperation among COMESA members.
Governance as a Global Development Goal? Setting, Measuring and Monitoring the Post‐2015 Development Agenda
Authors: Hulme David , Savoia Antonio , Sen Kunal
Published: November 2014

The increasing realisation that governance quality is a fundamental element of long‐run development has led to its consideration as a desirable development goal in its own right. To contribute to such a process, this article provides a framework to set, measure and monitor governance goals in the post‐2015 development agenda. First, we assess whether existing cross‐national measures on governance quality can be exploited to measure and monitor aspects of legal, bureaucratic and administrative quality. Such a ‘quick fix’ approach to measuring governance quality is fraught with challenges. The current practice of measurement is still subject to the short country coverage of most available measures, issues of comparability and legitimacy, as well as methodological shortcomings. Second, we argue that, in the long run, measuring and monitoring governance quality may require reconceptualising ‘good governance’ and designing internationally shared measures that are routinely provided by national statistical offices (but, international groups should also continue to make their independent measures). Finally, we consider the different approaches to setting governance goals, arguing in favour of a combination of national target setting and minimum standard with continuous improvement.
Thirteen‐year outcomes in the Anatomique Benoist Girard II hip prosthesis
Authors: Catanach Michael J. M. , Sorial Rami M. , Eslick Guy D.
Published: November 2014

Background

The Stryker Anatomique Benoist Girard (ABG) hip implant system was a commonly used cementless prosthesis in the early 2000s, which fell from favour after several studies emerged implicating the prosthesis in high rates of revision. This retrospective, single‐surgeon clinical study examines the fracture rate, revision rate and reasons for revision in 500 consecutive ABG II primary total conventional hip replacements.

Methods

Follow‐up was conducted by audit of patient notes, patient mailout survey, patient phone contact and audit of the Australian National Joint Replacement Registry (NJRR) database to find instances of fracture and revision. End points were periprosthetic fracture and revision for any reason.

Results

Follow‐up was 1.2–13.8 years with a mean of 6.58 years. Of the 500 hips, 17 (3.4%) had undergone a revision. Of these, 13 were due to periprosthetic fracture. Four further fractures occurred that were not revised. Eight of these periprosthetic fractures occurred within 1 year post‐operatively. There were four revisions for recurrent dislocations. Kaplan–Meier survival curve demonstrates a 93.7% survivorship at 6.58 years for revision for any reason. Multivariate analysis showed the only statistically significant factor for increased risk of revision was smaller stem size.

Conclusion

Our results were consistent with the literature in that the ABG II system has good medium‐term results but is prone to periprosthetic fractures, especially in the early post‐operative period. When used as a primary total hip arthroplasty, the ABG II system has an 8‐year revision rate of 5.6% compared with the 4.9% of all primary total hip arthroplasties.
Serial changes in the bleb wall after glaucoma drainage implant surgery: characteristics during the hypertensive phase
Authors: Jung Kyoung In , Park Hana , Jung Younhea , Park Chan Kee
Published: November 2014

Purpose

To investigate serial changes in the bleb wall using anterior segment optical coherence tomography (AS‐OCT) in patients who had undergone Ahmed glaucoma valve (AGV) implantation.

Methods

A total of 52 patients who had undergone AGV implantation were enrolled. Reflectivity and mean thickness of the bleb wall were examined using AS‐OCT at 1 day, 1 week, 1 month, 3 months and 6 months postoperatively. Intra‐ocular pressure (IOP) and the number of glaucoma medications were evaluated. The hypertensive phase was defined as IOP >21 mmHg during the first 3 months after surgery. Patients were divided into two groups: hypertensive and non‐hypertensive groups.

Results

Following AGV implantation, IOP decreased at each time‐point during postoperative follow‐up (p value < 0.001, all) with a peak in the first month. Mean bleb wall thickness showed a U‐shaped curve postoperatively, being thinnest 1 month after the operation. Reflectivity showed an inverted U‐shaped curve postoperatively, being brightest 1 month after the operation. A hypertensive phase was observed in 44 patients (84.6%). The bleb wall was significantly more reflective (130.67 ± 27.00 versus 106.57 ± 10.35; p = 0.044) in the hypertensive group than in non‐hypertensive group 1 month postoperatively.

Conclusions

Hypertensive phase peaked at 1 month after aqueous shunt surgery. At that time, the bleb wall had the highest reflectivity. The unique IOP pattern after tube surgery is related to fibrosis of the bleb wall qualitatively. Specific modulation of wound healing may be the target for attempts to decrease the development of hypertensive phase.
Clinico‐biological characteristics and treatment of type I monoclonal cryoglobulinaemia: a study of 64 cases
Authors: Harel Stephanie , Mohr Melanie , Jahn Isabelle , Aucouturier Francoise , Galicier Lionel , Asli Bouchra , Malphettes Marion , Szalat Raphael , Brouet Jean‐Claude , Lipsker Dan , Fermand Jean‐Paul
Published: November 2014

This retrospective analysis was conducted in 64 patients diagnosed with type I cryoglobulinaemia (CG) followed at two French centres. Median follow‐up was 6·75 years. CG was IgG in 60% and IgM in 40% of all cases and was asymptomatic in 16 patients (25%). Cold‐triggered ischaemic skin manifestations were observed in 33 patients (51%). Neurological manifestations were observed in 15 patients and renal manifestations in 13. Most of the patients with necrotic purpura (14/16, P = 0·009) and renal manifestations (11/13, P = 0·057) had IgG CG. IgG CG was associated with monoclonal gammopathy of undetermined significance (MGUS), myeloma, chronic lymphocytic leukaemia and lymphoplasmocytic lymphoma in 18, 13, 5 and 2 patients, respectively. IgM CG was associated with MGUS and Waldenström macroglobulinaemia in 8 and 18 cases, respectively. One third of patients did not receive any specific treatment. Various treatments, including rituximab, were administered to 25/31 patients with IgG CG and 6/25 patients with IgM CG due to CG‐related symptoms. Rituximab was ineffective in all cases associated with a predominantly plasmacytic proliferation. To conclude, type I CG has specific clinico‐biological characteristics compared to type II CG. Furthermore, there are differences in terms of related manifestations between type I IgG and type I IgM CG.
NFKB1 −94ins/delATTG polymorphism is a novel prognostic marker in first line‐treated multiple myeloma
Authors: Varga Gergely , Mikala Gábor , Andrikovics Hajnalka , Koszarska Magdalena , Balassa Katalin , Ádám Emma , Kozma András , Tordai Attila , Masszi Tamás
Published: November 2014

Nuclear factor kappa B (NFKB) plays an important role in multiple myeloma (MM), and bortezomib affects this pathway. We retrospectively analysed the effect of the NFKB1 −94ins/delATTG polymorphism on the survival of 295 MM patients treated at a single centre. The median progression‐free survival (PFS) was 790 (659–921) d in patients with NFKB1 homozygous insertion genotype (I/I, n = 99) and 624 (515–733) d in deletion‐carriers (I/D&D/D, n = 196, P = 0·013). In multivariate analysis, I/I carriers showed a favourable PFS compared to I/D&D/D with a hazard ratio of 0·622 (0·457–0·847), P = 0·003, in addition to international staging system (ISS) score, fluorescence in situ hybridization (FISH) risk score, age and bortezomib treatment. I/I patients benefited more from bortezomib treatment [PFS 902 (703–1101) and 580 (343–817), P = 0·008] than I/D&D/D patients [PFS 659 (487–831) and 488 (323–653), P = 0·531]; in addition the beneficial effect of low ISS score was not observed in the I/D&D/D group [PFS 639 (454–824) and 650 (458–842), P = 0·226], while it was clear in I/I patients [PFS 1140 (803–1477) and 580 (408–752), P < 0·001]. We conclude that homozygous carriers of the insertion allele of the NFKB1 −94ins/delATTG polymorphism have a better prognosis and probably benefit more from bortezomib treatment than MM patients carrying the deletion allele.
Noble gases as cardioprotectants – translatability and mechanism
Authors: Smit Kirsten F , Weber Nina C , Hollmann Markus W , Preckel Benedikt
Published: November 2014

Several noble gases, although classified as inert substances, exert a tissue‐protective effect in different experimental models when applied before organ ischaemia as an early or late preconditioning stimulus, after ischaemia as a post‐conditioning stimulus or when given in combination before, during and/or after ischaemia. A wide range of organs can be protected by these inert substances, in particular cardiac and neuronal tissue. In this review we summarize the data on noble gas‐induced cardioprotection, focusing on the underlying protective mechanisms. We will also look at translatability of experimental data to the clinical situation.

Linked Articles

This article is part of a themed section on Conditioning the Heart – Pathways to Translation. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue‐8
Differential activation of human constitutive androstane receptor and its SV23 and SV24 splice variants by rilpivirine and etravirine
Authors: Sharma Devinder , Lau Aik Jiang , Sherman Matthew A , Chang Thomas K H
Published: November 2014

Background and Purpose

Rilpivirine and etravirine are second‐generation non‐nucleoside reverse transcriptase inhibitors (NNRTIs) indicated for the treatment of HIV/AIDS. The constitutive androstane receptor (CAR) regulates the expression of genes involved in various biological processes, including the transport and biotransformation of drugs. We investigated the effect of rilpivirine and etravirine on the activity of the wild‐type human CAR (hCAR‐WT) and its hCAR‐SV23 and hCAR‐SV24 splice variants, and compared it with first‐generation NNRTIs (efavirenz, nevirapine, and delavirdine).

Experimental Approach

Receptor activation, ligand‐binding domain (LBD) transactivation, and co‐activator recruitment were investigated in transiently transfected, NNRTI‐treated HepG2 cells. Nuclear translocation of green fluorescent protein‐tagged hCAR‐WT and CYP2B6 gene expression were assessed in NNRTI‐treated human hepatocytes.

Key Results

Rilpivirine and etravirine activated hCAR‐WT, but not hCAR‐SV23 or hCAR‐SV24, and without transactivating the LBD or recruiting steroid receptor coactivators SRC‐1, SRC‐2, or SRC‐3. Among the first‐generation NNRTIs investigated, only efavirenz activated hCAR‐WT, hCAR‐SV23, and hCAR‐SV24, but none of them transactivated the LBD of these receptors or substantively recruited SRC‐1, SRC‐2, or SRC‐3. Rilpivirine, etravirine, and efavirenz triggered nuclear translocation of hCAR‐WT and increased hCAR target gene (CYP2B6) expression.

Conclusion and Implications

NNRTIs activate hCAR‐WT, hCAR‐SV23, and hCAR‐SV24 in a drug‐specific and isoform‐selective manner. The activation occurs by a mechanism that does not appear to involve binding to the LBD or recruitment of SRC‐1, SRC‐2, or SRC‐3.
Ultrasound assessment of hamstring muscle size using posterior thigh muscle thickness
Authors: Abe Takashi , Loenneke Jeremy P. , Thiebaud Robert S.
Published: November 2014

Several studies have investigated the relationship between ultrasound‐measured muscle thickness (MT) and individual muscle cross‐sectional area (CSA) and muscle volume (MV) in extremity and trunk muscles; however, the hamstring muscle has not been studied. The purpose of this study was to examine the relationship between posterior thigh MT by ultrasound and the muscle CSA and MV of the hamstring obtained by magnetic resonance imaging (MRI). Ten young women aged 20–31 had MT measured by ultrasound at three sites on the medial anterior (50% of thigh length; TL) and posterior (50% and 70% of TL) aspects of the thigh. On the same day, a series of continuous muscle CSA along the thigh was measured by MRI. In each slice, the anatomical CSA of the hamstring (biceps femoris, semitendinosus and semimembranosus) and quadriceps muscle was analysed, and the CSAs at 50% and 70% of TL and maximal CSA of the hamstring (CSAmax) were determined. MV was calculated by multiplying CSA by slice thickness. A significant correlation was observed between posterior 50% MT and 50% hamstring CSA (r = 0·848, P = 0·002) and between posterior 70% MT and 70% hamstring CSA (r = 0·679, P = 0·031). Posterior 50% MT (r = 0·732, P = 0·016) and 50% MTxTL (r = 0·873, P = 0·001) were also correlated to hamstring MV. Anterior:posterior 50% thigh MT ratio was correlated to MV ratio of quadriceps and hamstring muscles (r = 0·803, P = 0·005). Our results suggest that posterior thigh MT reflects hamstring muscle CSA and MV. The anterior:posterior MT ratio may serve as a surrogate for MV ratio of quadriceps and hamstring.
Locally adapted traits maintained in the face of high gene flow
Authors: Fitzpatrick S. W. , Gerberich J. C. , Kronenberger J. A. , Angeloni L. M. , Funk W. C.
Published: November 2014

Gene flow between phenotypically divergent populations can disrupt local adaptation or, alternatively, may stimulate adaptive evolution by increasing genetic variation. We capitalised on historical Trinidadian guppy transplant experiments to test the phenotypic effects of increased gene flow caused by replicated introductions of adaptively divergent guppies, which were translocated from high‐ to low‐predation environments. We sampled two native populations prior to the onset of gene flow, six historic introduction sites, introduction sources and multiple downstream points in each basin. Extensive gene flow from introductions occurred in all streams, yet adaptive phenotypic divergence across a gradient in predation level was maintained. Descendants of guppies from a high‐predation source site showed high phenotypic similarity with native low‐predation guppies in as few as ~12 generations after gene flow, likely through a combination of adaptive evolution and phenotypic plasticity. Our results demonstrate that locally adapted phenotypes can be maintained despite extensive gene flow from divergent populations.
7T MRI features in control human hippocampus and hippocampal sclerosis: An ex vivo study with histologic correlations
Authors: Coras Roland , Milesi Gloria , Zucca Ileana , Mastropietro Alfonso , Scotti Alessandro , Figini Matteo , Mühlebner Angelika , Hess Andreas , Graf Wolfgang , Tringali Giovanni , Blümcke Ingmar , Villani Flavio , Didato Giuseppe , Frassoni Carolina , Spreafico Roberto , Garbelli Rita
Published: November 2014

Objective

Hippocampal sclerosis (HS) is the major structural brain lesion in patients with temporal lobe epilepsy (TLE). However, its internal anatomic structure remains difficult to recognize at 1.5 or 3 Tesla (T) magnetic resonance imaging (MRI), which allows neither identification of specific pathology patterns nor their proposed value to predict postsurgical outcome, cognitive impairment, or underlying etiologies. We aimed to identify specific HS subtypes in resected surgical TLE samples on 7T MRI by juxtaposition with corresponding histologic sections.

Methods

Fifteen nonsclerotic and 18 sclerotic hippocampi were studied ex vivo using an experimental 7T MRI scanner. T2‐weighted images (T2wi) and diffusion tensor imaging (DTI) data were acquired and validated using a systematic histologic analysis of same specimens along the anterior‐posterior axis of the hippocampus.

Results

In nonsclerotic hippocampi, differences in MR intensity could be assigned to seven clearly recognizable layers and anatomic boundaries as confirmed by histology. All hippocampal subfields could be visualized also in the hippocampal head with three‐dimensional imaging and angulated coronal planes. Only four discernible layers were identified in specimens with histopathologically confirmed HS. All sclerotic hippocampi showed a significant atrophy and increased signal intensity along the pyramidal cell layer. Changes in DTI parameters such as an increased mean diffusivity, allowed to distinguish International League Against Epilepsy (ILAE) HS type 1 from type 2. Whereas the increase in T2wi signal intensities could not be attributed to a distinct specific histopathologic substrate, that is, decreased neuronal or increased glial cell densities, intrahippocampal projections and fiber tracts were distorted in HS specimens suggesting a complex disorganization of the cellular composition, fiber networks, as well as its extracellular matrix.

Significance

Our data further advocate high‐resolution MRI as a helpful and promising diagnostic tool for the investigation of hippocampal pathology along the anterior‐posterior extent in TLE, as well as in other neurologic and neurodegenerative disorders.
Incidence of spinal injuries in migratory Yellowstone cutthroat trout captured at electric and waterfall‐velocity weirs
Authors: Larson E. I. , Meyer K. A. , High B.
Published: November 2014

The South Fork Snake River (Idaho, USA) supports a native Yellowstone cutthroat trout (YCT) population Oncorhynchus clarkii bouvieri (Richardson) threatened by non‐native rainbow trout O. mykiss (Walbaum). Electric weirs prevent rainbow trout passage into YCT spawning tributaries but may cause spinal injuries. YCT captured at electric weirs on Palisades and Pine Creeks and a control waterfall‐velocity weir on Burns Creek were X‐rayed in 2012 and 2013 to estimate spinal injury rates. Electrical pulse frequency was increased from 2012 to 2013 at the Palisades (from 11.5 to 20 Hz) and Pine weirs (13–20 Hz), and spinal injury rates were found to increase from 11.3 to 21.3% at Palisades and from 6.5 to 14.7% at Pine, while Burns injury rates remained constant (4.5% in 2012 and 6.0% in 2013), suggesting the electric weirs caused spinal injuries in YCT. Lower pulse frequencies may minimise YCT spinal injury but still prevent rainbow trout from accessing YCT spawning tributaries.
Trade‐offs between land and water requirements for large‐scale bioenergy production
Authors: Bonsch Markus , Humpenöder Florian , Popp Alexander , Bodirsky Benjamin , Dietrich Jan Philipp , Rolinski Susanne , Biewald Anne , Lotze‐Campen Hermann , Weindl Isabelle , Gerten Dieter , Stevanovic Miodrag
Published: November 2014

Bioenergy is expected to play an important role in the future energy mix as it can substitute fossil fuels and contribute to climate change mitigation. However, large‐scale bioenergy cultivation may put substantial pressure on land and water resources. While irrigated bioenergy production can reduce the pressure on land due to higher yields, associated irrigation water requirements may lead to degradation of freshwater ecosystems and to conflicts with other potential users. In this article, we investigate the trade‐offs between land and water requirements of large‐scale bioenergy production. To this end, we adopt an exogenous demand trajectory for bioenergy from dedicated energy crops, targeted at limiting greenhouse gas emissions in the energy sector to 1100 Gt carbon dioxide equivalent until 2095. We then use the spatially explicit global land‐ and water‐use allocation model MAgPIE to project the implications of this bioenergy target for global land and water resources. We find that producing 300 EJ yr−1 of bioenergy in 2095 from dedicated bioenergy crops is likely to double agricultural water withdrawals if no explicit water protection policies are implemented. Since current human water withdrawals are dominated by agriculture and already lead to ecosystem degradation and biodiversity loss, such a doubling will pose a severe threat to freshwater ecosystems. If irrigated bioenergy production is prohibited to prevent negative impacts of bioenergy cultivation on water resources, bioenergy land requirements for meeting a 300 EJ yr−1 bioenergy target increase substantially (+ 41%) – mainly at the expense of pasture areas and tropical forests. Thus, avoiding negative environmental impacts of large‐scale bioenergy production will require policies that balance associated water and land requirements.
Does ongoing general practitioner care in elderly patients help reduce the risk of unplanned hospitalization related to Beers potentially inappropriate medications?
Authors: Price Sylvie D , Holman C D'Arcy J , Sanfilippo Frank M , Emery Jon D
Published: November 2014

Aim

To compare estimates of unplanned hospitalizations associated with exposure to Beers potentially inappropriate medications (PIM) in elderly people receiving different levels of ongoing general practitioner (GP) care.

Methods

Using the pharmaceutical claims and other linked health data of 245 436 Western Australians aged ≥65 years with one or more claims for a medication from a PIM‐related drug class (1993–2005), we applied an enhanced case–time–control design to obtain odds ratios (OR) for unplanned hospitalization, from which attributable fractions, numbers, proportions and rates of admissions related to PIM exposure were derived.

Results

Overall, 383 150 unplanned hospitalizations (“index subjects”) were identified. PIM exposure was associated with a similar relative risk of unplanned hospitalization in elderly people receiving the lowest and highest levels of ongoing GP care, but with a decreasing risk in the three highest tiers; adjusted OR (95% CI; attributable fractions) were 1.15 (1.09–1.21; 12.9%), 1.36 (1.27–1.46; 26.6%), 1.20 (1.15–1.26; 16.9%) and 1.13 (1.09–1.17; 11.4%) for groups from the lowest to highest levels. However, those with higher GP coverage had higher rates of PIM‐related hospitalization. Similar patterns were shown for commonly used high‐risk PIM (temazepam, diazepam, oxazepam, naproxen and digoxin).

Conclusions

Increased requirement for ongoing GP contact in less healthy elderly people appears to help minimize their risk of unplanned hospitalization due to PIM‐related harm. GPs should continue to avoid Beers medications in older patients where possible, given their greater predisposition to medication exposure (including PIM) and adverse drug events. Nevertheless, close monitoring of elderly patients who need to use PIM should prove beneficial. Geriatr Gerontol Int 2015; 15: 1031–1039.
Literacy disparities in patient access and health‐related use of Internet and mobile technologies
Authors: Bailey Stacy C. , O'Conor Rachel , Bojarski Elizabeth A. , Mullen Rebecca , Patzer Rachel E. , Vicencio Daniel , Jacobson Kara L. , Parker Ruth M. , Wolf Michael S.
Published: November 2014

Background

Age and race‐related disparities in technology use have been well documented, but less is known about how health literacy influences technology access and use.

Objective

To assess the association between patients’ literacy skills and mobile phone ownership, use of text messaging, Internet access, and use of the Internet for health‐related purposes.

Methods

A secondary analysis utilizing data from 1077 primary care patients enrolled in two, multisite studies from 2011–2013. Patients were administered an in‐person, structured interview.

Results

Patients with adequate health literacy were more likely to own a mobile phone or smartphone in comparison with patients having marginal or low literacy (mobile phone ownership: 96.8 vs. 95.2 vs. 90.1%, respectively, P < 0.001; smartphone ownership: 70.6 vs. 62.5 vs. 40.1%, P < 0.001) and to report text messaging (78.6 vs. 75.2 vs. 53.1%, P < 0.001). They were also more likely to have access to the Internet from their home (92.1 vs. 74.7 vs. 44.9%, P < 0.001) and to report using the Internet for email (93.0 vs. 75.7 vs. 38.5%, P < 0.001), browsing the web (93.9 vs. 80.2 vs. 44.5%, P < 0.001), accessing health information (86.3 vs. 75.5 vs. 40.8%, P < 0.001), and communicating with providers (54.2 vs. 29.8 vs. 13.0%, P < 0.001). Relationships remained significant in multivariable analyses controlling for relevant covariates.

Conclusions

Results reveal that literacy‐related disparities in technology access and use are widespread, with lower literate patients being less likely to own smartphones or to access and use the Internet, particularly for health reasons. Future interventions should consider these disparities and ensure that health promotion activities do not further exacerbate disparities.