bluuebunny/crossref_metadata_2025 huggingface dataset:
Real-time predictions of reservoir size and rebound time during antiretroviral therapy interruption trials for HIV
Authors: Hill Alison L. , Rosenbloom Daniel I.S. , Goldstein Edward , Hanhauser Emily , Kuritzkes Daniel R. , Siliciano Robert F. , Henrich Timothy J.
Published: January 2016

Monitoring the efficacy of novel reservoir-reducing treatments for HIV is challenging. The limited ability to sample and quantify latent infection means that supervised antiretroviral therapy (ART) interruption studies are generally required. Here we introduce a set of mathematical and statistical modeling tools to aid in the design and interpretation of ART-interruption trials. We show how the likely size of the remaining reservoir can be updated in real-time as patients continue off treatment, by combining the output of laboratory assays with insights from models of reservoir dynamics and rebound. We design an optimal schedule for viral load sampling during interruption, whereby the frequency of follow-up can be decreased as patients continue off ART without rebound. While this scheme can minimize costs when the chance of rebound between visits is low, we find that the reservoir will be almost completely reseeded before rebound is detected unless sampling occurs at least every two weeks and the most sensitive viral load assays are used. We use simulated data to predict the clinical trial size needed to estimate treatment effects in the face of highly variable patient outcomes and imperfect reservoir assays. Our findings suggest that large numbers of patients – between 40 and 150 – will be necessary to reliably estimate the reservoir-reducing potential of a new therapy and to compare this across interventions. As an example, we apply these methods to the two “Boston patients”, recipients of allogeneic hematopoietic stem cell transplants who experienced large reductions in latent infection and underwent ART-interruption. We argue that the timing of viral rebound was not particularly surprising given the information available before treatment cessation. Additionally, we show how other clinical data can be used to estimate the relative contribution that remaining HIV+ cells in the recipient versus newly infected cells from the donor made to the residual reservoir that eventually caused rebound. Together, these tools will aid HIV researchers in the evaluating new potentially-curative strategies that target the latent reservoir.
Micro-Magellan: A flexible, open source acquisition software for high throughput biological light microscopy
Authors: Pinkard Henry , Stuurman Nico , Corbin Kaitlin , Vale Ronald , Krummel Matthew F.
Published: January 2016

We demonstrate the capabilities of μMagellan: a flexible, open source microscopy software for reproducible high throughput imaging of biological samples across heterogeneous scales of space and time. μMagellan provides a simple user interface for exploration and automated imaging of non-cuboidal regions. By utilizing the hardware abstraction layer of μMagellan, μMagellan provides a powerful and extensible platform for imaging heterogeneous biological samples on a wide range of existing microscopes.
Plastid degeneration inTillandsia(Bromeliaceae) provides evidence about the origin of multilamellar bodies in plants
Authors: van Doorn Wouter G. , Papini Alessio
Published: January 2016

Vesicle-like structures containing several to numerous concentric membranes, called multilamellar bodies (MLBs), are present both in animal and plant cells. The origin of MLBs in animal cells has been elucidated partially, while that of plant MLBs is unknown. MLBs in plant cells are present in the cytoplasm, at the interface of cytoplasm and vacuole, and inside vacuoles. This suggests that they become transported from the cytoplasm to the vacuole. The function of plant MLBs thus seems transfer of cellular membranes to the vacuole. Although it is often impossible to discern whether they have a single or a double outer membrane, in some examples a double outer membrane is present. This might suggest autophagic/mitochondrial/plastidial origin. Membrane structures similar to those in MLBs have not been described, apparently, in mitochondria. By contrast, structures similar to MLBs are found in autophagous structures and in degenerating chloroplasts and other plastids. The data might suggest the hypothesis that plant MLBs derive from autophagous structures and/or from plastids.
A gain-of-function senescence bypass screen identifies the homeobox transcription factor DLX2 as a regulator of ATM–p53 signaling
Authors: Wang Yifan , Xu Qikai , Sack Laura , Kang Chanhee , Elledge Stephen J.
Published: February 2016

Senescence stimuli activate multiple tumor suppressor pathways to initiate cycle arrest and a differentiation program characteristic of senescent cells. We performed a two-stage, gain-of-function screen to select for the genes whose enhanced expression can bypass replicative senescence. We uncovered multiple genes known to be involved in p53 and Rb regulation and ATM regulation, two components of the CST (CTC1–STN1–TEN1) complex involved in preventing telomere erosion, and genes such asRESTandFOXO4that have been implicated in aging. Among the new genes now implicated in senescence, we identified DLX2, a homeobox transcription factor that has been shown to be required for tumor growth and metastasis and is associated with poor cancer prognosis. Growth analysis showed that DLX2 expression led to increased cellular replicative life span. Our data suggest that DLX2 expression reduces the protein components of the TTI1/TTI2/TEL2 complex, a key complex required for the proper folding and stabilization of ATM and other members of the PIKK (phosphatidylinositol 3-kinase-related kinase) family kinase, leading to reduced ATM–p53 signaling and senescence bypass. We also found that the overexpression of DLX2 exhibited a mutually exclusive relationship with p53 alterations in cancer patients. Our functional screen identified novel players that may promote tumorigenesis by regulating the ATM–p53 pathway and senescence.
Structural basis for human PRDM9 action at recombination hot spots
Authors: Patel Anamika , Horton John R. , Wilson Geoffrey G. , Zhang Xing , Cheng Xiaodong
Published: February 2016

The multidomain zinc finger (ZnF) protein PRDM9 (PRD1–BF1–RIZ1 homologous domain-containing 9) is thought to influence the locations of recombination hot spots during meiosis by sequence-specific DNA binding and trimethylation of histone H3 Lys4. The most common variant of human PRDM9, allele A (hPRDM9A), recognizes the consensus sequence 5′-NCCNCCNTNNCCNCN-3′. We cocrystallized ZnF8–12 of hPRDM9Awith an oligonucleotide representing a known hot spot sequence and report the structure here. ZnF12 was not visible, but ZnF8–11, like other ZnF arrays, follows the right-handed twist of the DNA, with the α helices occupying the major groove. Each α helix makes hydrogen-bond (H-bond) contacts with up to four adjacent bases, most of which are purines of the complementary DNA strand. The consensus C:G base pairs H-bond with conserved His or Arg residues in ZnF8, ZnF9, and ZnF11, and the consensus T:A base pair H-bonds with an Asn that replaces His in ZnF10. Most of the variable base pairs (N) also engage in H bonds with the protein. These interactions appear to compensate to some extent for changes from the consensus sequence, implying an adaptability of PRDM9 to sequence variations. We investigated the binding of various alleles of hPRDM9 to different hot spot sequences. Allele C was found to bind a C-specific hot spot with higher affinity than allele A bound A-specific hot spots, perhaps explaining why the former is dominant in A/C heterozygotes. Allele L13 displayed higher affinity for several A-specific sequences, allele L9/L24 displayed lower affinity, and allele L20 displayed an altered sequence preference. These differences can be rationalized structurally and might contribute to the variation observed in the locations and activities of meiotic recombination hot spots.
Charge density of the biologically active molecule (2-oxo-1,3-benzoxazol-3(2H)-yl)acetic acid
Authors: Wang Ai , Ashurov Jamshid , Ibragimov Aziz , Wang Ruimin , Mouhib Halima , Mukhamedov Nasir , Englert Ulli
Published: January 2016

(2-Oxo-1,3-benzoxazol-3(2H)-yl)acetic acid is a member of a biologically active class of compounds. Its molecular structure in the crystal has been determined by X-ray diffraction, and its gas phase structure was obtained by quantum chemical calculations at the B3LYP/6-311++G(d,p) level of theory. In order to understand the dynamics of the molecule, two presumably soft degrees of freedom associated with the relative orientation of the planar benzoxazolone system and its substituent at the N atom were varied systematically. Five conformers have been identified as local minima on the resulting two-dimensional potential energy surface within an energy window of 27 kJ mol−1. The energetically most favourable minimum closely matches the conformation observed in the crystal. Based on high-resolution diffraction data collected at low temperature, the experimental electron density of the compound was determined. Comparison with the electron density established by theory for the isolated molecule allowed the effect of intermolecular interactions to be addressed, in particular a moderately strong O—H...O hydrogen bond with a donor...acceptor distance of 2.6177 (9) Å: the oxygen acceptor is clearly polarized in the extended solid. The hydrogen bond connects consecutive molecules to chains, and the pronounced charge separation leads to stacking between neighburs with antiparallel dipole moments perpendicular to the chain direction.
Polarization inRMnO3multiferroics
Authors: Pirogov A. N.
Published: January 2016

Some comments on the review by Simet al.[(2016).Acta Cryst.B72, 3–19] are given. The review is devoted to hexagonal multiferroicsRMnO3, in which there are ferroelectric and magnetic orders. Strong interaction between these orders causes a series of interesting properties of multiferroics.
Crystal structure of (1S,2R)-6,6-dimethyl-4,8-dioxo-2-phenylspiro[2.5]octane-1-carbaldehyde
Authors: Chelli Saloua , Troshin Konstantin , Lakhdar Sami , Mayr Herbert , Mayer Peter
Published: January 2016

In the title compound, C17H18O3, the two non-spiro C atoms of the cyclopropane ring bear a formyl and a phenyl substituent which aretrans-oriented. In the crystal, molecules are linked by weak C—H...O and C—H...π contacts resulting in a three-dimensional supramolecular structure.
An interactive virtual lighting maintenance environment for human factors evaluation
Authors: He Qichang , Qiu Shiguang , Fan Xiumin , Liu Keyan
Published: January 2016

Purpose

– The paper aims to establish a virtual lighting maintenance environment (VLME), and to analyze the visibility-related human factors (HFs) during maintenance operations through interactive simulations.

Design/methodology/approach

– First, an accurate task lighting modeling method was developed, which includes lighting information modeling and illuminant parameters calibration. Then, the real-time interaction between the task lighting and three-dimensional virtual human was modeled. After that, the attenuation coefficient of visibility was determined. Also, the HFs’ analysis process in VLME was described in detail.

Findings

– A case study of power supply module replacement of radar equipment was performed in VLME. The HFs’ analysis demonstrated that the task lighting significantly affects the visibility, which causes indirect impact on posture comfort and operation safety.

Practical implications

– Through evaluating maintenance operation processing in lighting environment, engineers can better analyze and validate the maintainability design for complex equipment, and some potential ergonomics and safety issues can be found and dealt earlier.

Originality/value

– An VLME was built for interactive “human-in-loop” maintenance operation simulation, which can support HFs’ evaluation in lighting environment accurately and effectively.
Whither the accounting profession, accountants and accounting researchers? Commentary and projections
Authors: Guthrie James , Parker Lee D.
Published: February 2016

Purpose

– This commentary reflects on possible disruptions for the accounting profession, accountants and academics in the next 25 years. The traditional and highly valued role of the accounting professional, accountants and academic scholarship is rapidly changing in an intensely networked and interdisciplinary world. The purpose of this paper is to provide a summary of AAAJ activities for 2015 and in the next few years, it also delivers a call to action to interdisciplinary accounting researchers to undertake innovative research that reflects on what these turbulent times mean for society, nations, organisations and individual accountants, practitioners and educators.

Design/methodology/approach

– The paper employs a literature-based analysis and critique to provide a critical reflection on current and future developments in academic accounting research.

Findings

– In highlighting disruption to traditional accounting practice and research the authors provide a foundation from which researchers should contemplate their motivation, informing theories and values to ensure that their academic endeavours make a contribution to practice, policy and a wider societal good.

Practical implications

– It is hoped the practical and research issues explored in this commentary will invoke more interdisciplinary perspectives on accounting and the accounting profession, and assist scholars to reflect on the challenges they face.

Originality/value

– Providing a forward looking vision on the important role of academic researchers, the authors urge colleagues not to limit their vision to the narrowness that is an increasing feature of North American economics-based accounting research and to not simply observe, but rather construct an enabling accounting that can benefit society more widely.
Critical success factors of adapting heritage buildings: an exploratory study
Authors: Dyson Kristy , Matthews Jane , Love Peter E.D.
Published: January 2016

Purpose

– The loss of heritage buildings should be avoided as they provide a tangible example of a period of life that is now gone. Adaptive re-use enables buildings to be given a second life, enabling them to live on when they may have been previously underutilized. Changing the capacity, function or performance of underutilized buildings for a different purpose, or to suit new conditions, or making use of pre-existing structural elements has become necessary to preserve heritage buildings. The purpose of this paper is to identify the critical success factors (CSF) for the adaptive re-use of heritage buildings.

Design/methodology/approach

– Identification of CSF for adaptive re-use can provide asset owners, developers and key stakeholders with the knowledge needed to ensure a project is delivered successfully. Due to a lack of research in the area of CSF for heritage buildings, an exploratory approach was undertaken. Semi-structured interviews were undertaken with stakeholders to solicit their views as to CSFs that lead to the successful adaption of all heritage buildings that had been subjected to re-use program in Perth, Western Australia, were examined.

Findings

– Four CSFs were identified: research; matching function; function; and design and minimal change. It is proffered that by addressing the CSFs issues associated with latent conditions, building layout and commercial risk and uncertainty can be addressed. Yet, the Building Code of Australia will continue to be the most significant issue for owners/developers and project teams who embrace an adaptive re-use project.

Originality/value

– To date there has been limited research undertaken with regard to determining the CSF for heritage buildings that have been subjected to adaptive re-use. The work presented in this paper identifies the key CSFs that emerged from the stock of heritage building’s in Perth, WA. Further research is required to determine the validity of the CSFs, however, those identified provide a benchmark for further studies in this fertile area.
Revisiting the cataloging of free Internet resources at the University of Denver
Authors: Brown Christopher C. , Elzi Erin
Published: January 2016

Purpose

– This paper aims to present updated statistics demonstrating the value of cataloging free Internet resources and the challenges of batch loading, vendor records, electronic resource modules and discovery tools, as an update to the 2008 paper in this journal

Design/methodology/approach

– Updates the statistics from the URL redirection system for tracking user access to freely available Web publications.

Findings

– With more projects and bibliographic records included within the scope of the project, users still find and use the links to outbound content. New technologies and management methods support the cataloging of free Web content, even if, at times, cataloging standards are compromised.

Originality/value

– Several studies have focused on US federal document clickthroughs from the library catalog, but this is the only study to exclusively track clickthroughs to freely available Web content.
Reference Services Review: content analysis, 2012-2014
Authors: Clark Katherine W.
Published: February 2016

Purpose

– The purpose of this paper is to present a retrospective analysis of content published in Reference Services Review between 2012 and 2014.

Design/methodology/approach

– This analysis utilizes the methods and format outlined by Katy Mahraj, author of Reference Services Review: content analysis, 2006-2011 (2012). The author manually reviewed the content of all journal issues from 2012 through 2014 using both print and online copies of the journal, accessed through the Emerald Group Publishing web site. Information reviewed included total number of articles per issue, author affiliations, article format and article content focus. The type, size and location of author institutions were confirmed using institutions’ official web sites as necessary. The results of this analysis are compared to Mahraj’s results to identify changing trends.

Findings

– Reference Services Review has published an average of 38 articles per year between 2012 and 2014. Articles have focused most commonly on information literacy and instruction and emerging technologies. Reference services, outreach and library management have also received regular coverage. All authors during this time period have been affiliated with academic institutions, primarily large academic institutions with 5,000 or more students.

Originality value

– This analysis continues the work of Katy Mahraj to consolidate data on the volume, focus and authorship of Reference Services Review. These data continue to provide an overview of trends in the field’s professional and scholarly literature, with implications for broader trends in academic librarianship.
HIV RNA and proviral HIV DNA can be detected in semen after 6 months of antiretroviral therapy although HIV RNA is undetectable in blood
Authors: Du Peiwei , Liu An , Jiao Yanmei , Liu Cuie , Jiang Taiyi , Zhu Weijun , Zhu Yunxia , Wu Hao , Sun Lijun
Published: February 2016

The risk of sexual transmission of HIV is strongly correlated with amounts of genital HIV RNA. Few studies have reported amounts of HIV RNA and HIV DNA in semen in HIV‐infected Chinese patients undergoing antiviral treatment (ART). In this observational study, the amounts of HIV RNA and HIV DNA in semen were assessed after six months of ART in HIV‐infected Chinese individuals, when HIV RNA was undetectable in blood . This study included 19 HIV‐infected Chinese men undergoing ART for six months. Amounts of HIV in paired semen and blood samples were assessed using real‐time PCR. The C2‐V5 region of the HIV envelope (env) genes was cloned and sequenced and genotype and co‐receptor usage predicted based on the sequence. It was found that HIV RNA was undetectable in the plasma of most patients (17/19), whereas HIV RNA could be detected in the semen of most patients (16/19). HIV DNA could be detected in both semen and blood. Genetic diversity of HIV between the seminal and blood compartments was identified. Thus, amounts of HIV RNA and HIV DNA remain high in semen of HIV‐infected Chinese patients after six months of ART treatment, even when HIV RNA was undetectable in blood.
The rules for symbiont community assembly change along a mutualism–parasitism continuum
Authors: Skelton James , Doak Sam , Leonard Meredith , Creed Robert P. , Brown Bryan L.
Published: February 2016

Symbiont community assembly is driven by host–symbiont and symbiont–symbiont interactions. The effects that symbionts exert on their hosts are often context‐dependent, and existing theoretical frameworks of symbiont community assembly do not consider the implications of variable outcomes to assembly processes.

We hypothesized that symbiont–symbiont interactions become increasingly important along a parasitism/mutualism continuum because; (i) negative outcomes favour host resistance which in turn reduces symbiont colonization and subsequently reduce symbiont–symbiont interactions, whereas (ii) positive host outcomes favour tolerance and consequently higher symbiont colonization rates, leading to stronger interactions among symbionts. We found support for this hypothesis in the cleaning symbiosis between crayfish and ectosymbiotic branchiobdellidan worms.

The symbiosis between crayfish and their worms can shift from parasitism/commensalism to mutualism as crayfish age. Here, field surveys identified changes in worm density, diversity and composition that were concomitant to changing symbiosis outcomes. We conducted several laboratory experiments and behavioural assays to relate patterns from the field to their likely causal processes.

Young crayfish typically hosted only two relatively small worm species. Older crayfish hosted two additional larger species. In laboratory experiments, young crayfish exhibited a directed grooming response to all worm species, but were unable to remove small species. Conversely, adult crayfish did not exhibit grooming responses to any worm species. Relaxed grooming allowed the colonization of large worm species and initiated symbiont–symbiont intraguild predation that reduced the abundance and altered the behaviour of small worm species. Thus, the dominant processes of symbiont community assembly shifted from host resistance to symbiont–symbiont interactions through host ontogeny and a concomitant transition towards mutualism.

This work shows that host resistance can have a prevailing influence over symbiont community assembly when symbiosis is disadvantageous to the host. However, when symbiosis is advantageous and resistance is relaxed, symbiont colonization rate and consequently abundance and diversity increases and interactions among symbionts become increasingly important to symbiont community assembly.
The role of water and fire in driving tree dynamics in Australian savannas
Authors: Strickland Christopher , Liedloff Adam C. , Cook Garry D. , Dangelmayr Gerhard , Shipman Patrick D.
Published: February 2016

Ecologists rely on models to explore tree compositional changes especially when occurring over decades or centuries. In this article, we construct a theoretical, mathematical model to investigate the long‐term relationships between savanna stand structure, water resource availability and fire disturbance.

We show how dry season length, rather than mean annual precipitation, leads to savanna stability, and how the soil properties and variation in annual rainfall distribution determines a climatic equilibrium for woody total basal area, with fire disturbance acting as a perturbation away from this state. This leads to our premise that rainfall and tree population dynamics drives the savanna state leading to grasses and fire, rather than grasses promoting fire to drive the savannas.

The model predicts that savanna tree stands undergo cyclic variation in tree populations as a result of long‐term population cycles and germination events. This outcome is true regardless of the presence of fire, however, fire does introduce a more heterogeneous stand size structure.

Synthesis. Using a mathematically transparent model for water resource availability and stand structure in savannas, we demonstrate how seasonal rainfall distribution, specifically seasonal drought, acts as the primary determinant for stand structure through stand water dynamics, with frequent fire disturbance able to reduce the populations from the climatically induced state.
Uncertainty in biological monitoring: a framework for data collection and analysis to account for multiple sources of sampling bias
Authors: Ruiz‐Gutierrez Viviana , Hooten Mevin B. , Campbell Grant Evan H.
Published: February 2016

Biological monitoring programmes are increasingly relying upon large volumes of citizen‐science data to improve the scope and spatial coverage of information, challenging the scientific community to develop design and model‐based approaches to improve inference.

Recent statistical models in ecology have been developed to accommodate false‐negative errors, although current work points to false‐positive errors as equally important sources of bias. This is of particular concern for the success of any monitoring programme given that rates as small as 3% could lead to the overestimation of the occurrence of rare events by as much as 50%, and even small false‐positive rates can severely bias estimates of occurrence dynamics.

We present an integrated, computationally efficient Bayesian hierarchical model to correct for false‐positive and false‐negative errors in detection/non‐detection data. Our model combines independent, auxiliary data sources with field observations to improve the estimation of false‐positive rates, when a subset of field observations cannot be validated a posteriori or assumed as perfect. We evaluated the performance of the model across a range of occurrence rates, false‐positive and false‐negative errors, and quantity of auxiliary data.

The model performed well under all simulated scenarios, and we were able to identify critical auxiliary data characteristics which resulted in improved inference. We applied our false‐positive model to a large‐scale, citizen‐science monitoring programme for anurans in the north‐eastern United States, using auxiliary data from an experiment designed to estimate false‐positive error rates. Not correcting for false‐positive rates resulted in biased estimates of occupancy in 4 of the 10 anuran species we analysed, leading to an overestimation of the average number of occupied survey routes by as much as 70%.

The framework we present for data collection and analysis is able to efficiently provide reliable inference for occurrence patterns using data from a citizen‐science monitoring programme. However, our approach is applicable to data generated by any type of research and monitoring programme, independent of skill level or scale, when effort is placed on obtaining auxiliary information on false‐positive rates.
Behavioral Pain Scale – translation, reliability, and validity in a Swedish context
Authors: Hylén M. , Akerman E. , Alm‐Roijer C. , Idvall E.
Published: February 2016

Background

Assessing pain in the intensive care unit (ICU) is challenging. Due to intubation and sedation, communication can be limited. International guidelines recommend assessing pain with instruments based on behavioral parameters when critically ill patients are unable to self‐report their pain level. One of the recommended instruments, the Behavioral Pain Scale (BPS), has shown good validity and reliability in international studies. The aim of this study was to translate and adapt the BPS for critically ill intubated and non‐intubated patients in a Swedish ICU context and to assess inter‐rater reliability and discriminant validity.

Methods

The BPS (both for intubated and non‐intubated patients) was translated and adapted into Swedish using a translation method consisting of ten steps. The Swedish version was then tested for inter‐rater reliability and discriminant validity on 20 critically ill patients (10 intubated and 10 non‐intubated) before and directly after a potentially painful procedure (repositioning).

Results

The Swedish version of the BPS showed inter‐rater reliability with a percentage agreement of 85% when tested on a sample of critically ill patients. The instrument also showed discriminant validity between assessments at rest and after repositioning.

Conclusion

Results of the Swedish version of the BPS support its use in critically ill patients who cannot self‐report their pain level. Still, additional studies are needed to further explore its reliability and validity in the Swedish ICU context.
Characterization of white matter integrity deficits in cocaine‐dependent individuals with substance‐induced psychosis compared with non‐psychotic cocaine users
Authors: Willi Taylor S. , Barr Alasdair M. , Gicas Kristina , Lang Donna J. , Vila‐Rodriguez Fidel , Su Wayne , Thornton Allen E. , Leonova Olga , Giesbrecht Chantelle J. , Procyshyn Ric M. , Rauscher Alexander , MacEwan William G. , Honer William G. , Panenka William J.
Published: February 2016

With sufficient drug exposure, some individuals develop transient psychotic symptoms referred to as ‘substance‐induced psychosis’ (SIP), which closely resemble the symptoms observed in schizophrenia spectrum disorders. The comparability in psychotic presentation between SIP and the schizophrenias suggests that similar underlying neural deficits may contribute to the emergence of psychosis across these disorders. Only a small number of studies have investigated structural alterations in SIP, and all have been limited to volumetric imaging methods, with none controlling for the effects of chronic drug exposure. To investigate white matter abnormalities associated with SIP, diffusion tensor imaging was employed in a group of individuals with cocaine‐associated psychosis (CAP; n = 24) and a cocaine‐dependent non‐psychotic (CDN) group (n = 43). Tract‐based spatial statistics was used to investigate group differences in white matter diffusion parameters. The CAP group showed significantly lower fractional anisotropy values than the CDN group (p < 0.05) in voxels within white matter tracts of fronto‐temporal, fronto‐thalamic and interhemispheric pathways. The greatest differences in white matter integrity were present in the corpus callosum, corona radiata, bilateral superior longitudinal fasciculi and bilateral inferior longitudinal fasciculi. Additionally, the CAP group had voxels of significantly higher radial diffusivity in a subset of the previously mentioned pathways. These results are the first description of white matter integrity abnormalities in a SIP sample and indicate that differences in these pathways may be a shared factor in the expression of different forms of psychosis.
Should Deceased Donation be Morally Preferred in Uterine Transplantation Trials?
Authors: Williams Nicola
Published: February 2016

In recent years much research has been undertaken regarding the feasibility of the human uterine transplant (UTx) as a treatment for absolute uterine factor infertility (AUFI). Should it reach clinical application this procedure would allow such individuals what is often a much‐desired opportunity to become not only social mothers (via adoption or traditional surrogacy arrangements), or genetic and social mothers (through gestational surrogacy) but mothers in a social, genetic and gestational sense. Like many experimental transplantation procedures such as face, hand, corneal and larynx transplants, UTx as a therapeutic option falls firmly into the camp of the quality of life (QOL) transplant, undertaken with the aim, not to save a life, but to enrich one. However, unlike most of these novel procedures – where one would be unlikely to find a willing living donor or an ethics committee that would sanction such a donation – the organs to be transplanted in UTx are potentially available from both living and deceased donors.

In this article, in the light of the recent nine‐case research trial in Sweden which used uteri obtained from living donors, and the assertions on the part of a number of other research teams currently preparing trials that they will only be using deceased donors, I explore the question of whether, in the case of UTx, there exist compelling moral reasons to prefer the use of deceased donors despite the benefits that may be associated with the use of organs obtained from the living.
Mechanisms of late Quaternary fault throw‐rate variability along the north central Gulf of Mexico coast: implications for coastal subsidence
Authors: Shen Zhixiong , Dawers Nancye H. , Törnqvist Torbjörn E. , Gasparini Nicole M. , Hijma Marc P. , Mauz Barbara
Published: January 2016

Quaternary sea‐level cycles have caused dramatic depocentre shifts near the mouths of major rivers. The effects of these shifts on fault activity in passive margin settings is poorly known, as no studies have constrained passive margin fault throw‐rate variability over 103 to 105 year time scales. Here we present 11 mean throw rates for the Tepetate–Baton Rouge fault zone along the northern Gulf of Mexico coast in southern Louisiana. These data were obtained by optically stimulated luminescence dating over time scales spanning the last interglacial to the late Holocene. The mean throw rate is ca. 0.22 mm year−1 during the late Holocene, ca. 0.03 mm year−1 during the last glacial and at least 0.07 mm year−1 during the last interglacial. Throw rates averaged over the late Pleistocene to present are spatially uniform within our study area. The temporal variability in throw rates suggests that shifts of the Mississippi River depocentre relative to this fault zone, driven by Quaternary sea‐level cycles, may have imposed a significant control on fault activity. The late Holocene throw rate is at least in the order of magnitude smaller than the rates of land‐surface subsidence in the Mississippi Delta, indicating that this fault zone is not a dominant contributor to subsidence in this region.
The Importance of Ficus (Moraceae) Trees for Tropical Forest Restoration
Authors: Cottee‐Jones H. Eden W. , Bajpai Omesh , Chaudhary Lal B. , Whittaker Robert J.
Published: February 2016

Forest restoration is an increasingly important tool to offset and indeed reverse global deforestation rates. One low cost strategy to accelerate forest recovery is conserving scattered native trees that persist across disturbed landscapes and which may act as seedling recruitment foci. Ficus trees, which are considered to be critically important components of tropical ecosystems, may be particularly attractive to seed dispersers in that they produce large and nutritionally rewarding fruit crops. Here, we evaluate the effectiveness of remnant Ficus trees in inducing forest recovery compared to other common trees. We studied the sapling communities growing under 207 scattered trees, and collected data on seed rain for 55 trees in a modified landscape in Assam, India. We found that Ficus trees have more sapling species around them (species richness = 140.1 ± 9.9) than non‐Ficus trees (79.5 ± 12.9), and significantly more saplings of shrub and large tree species. Sapling densities were twice as high under Ficus trees (median = 0.06/m2) compared to non‐Ficus (0.03/m2), and seed rain densities of non‐parent trees were significantly higher under Ficus trees (mean = 12.73 ± 3/m2/wk) than other fruit or non‐zoochorous trees (2.19 ± 0.97/m2/wk). However, our regression model found that canopy area, used as a proxy for tree size, was the primary predictor of sapling density, followed by remnant tree type. These results suggest that large trees, and in particular large Ficus trees, may be more effective forest restoration agents than other remnant trees in disturbed landscapes, and therefore the conservation of these trees should be prioritized.
Inflammation in gastric cancer: Interplay of the COX‐2/prostaglandin E2 and Toll‐like receptor/MyD88 pathways
Authors: Echizen Kanae , Hirose Osamu , Maeda Yusuke , Oshima Masanobu
Published: February 2016

Cyclooxygenase‐2 (COX‐2) and its downstream product prostaglandin E2 (PGE2) play a key role in generation of the inflammatory microenvironment in tumor tissues. Gastric cancer is closely associated with Helicobacter pylori infection, which stimulates innate immune responses through Toll‐like receptors (TLRs), inducing COX‐2/PGE2 pathway through nuclear factor‐κB activation. A pathway analysis of human gastric cancer shows that both the COX‐2 pathway and Wnt/β‐catenin signaling are significantly activated in tubular‐type gastric cancer, and basal levels of these pathways are also increased in other types of gastric cancer. Expression of interleukin‐11, chemokine (C‐X‐C motif) ligand 1 (CXCL1), CXCL2, and CXCL5, which play tumor‐promoting roles through a variety of mechanisms, is induced in a COX‐2/PGE2 pathway‐dependent manner in both human and mouse gastric tumors. Moreover, the COX‐2/PGE2 pathway plays an important role in the maintenance of stemness with expression of stem cell markers, including CD44, Prom1, and Sox9, which are induced in both gastritis and gastric tumors through a COX‐2/PGE2‐dependent mechanism. In contrast, disruption of Myd88 results in suppression of the inflammatory microenvironment in gastric tumors even when the COX‐2/PGE2 pathway is activated, indicating that the interplay of the COX‐2/PGE2 and TLR/MyD88 pathways is needed for inflammatory response in tumor tissues. Furthermore, TLR2/MyD88 signaling plays a role in maintenance of stemness in normal stem cells as well as gastric tumor cells. Accordingly, these results suggest that targeting the COX‐2/PGE2 pathway together with TLR/MyD88 signaling, which would suppress the inflammatory microenvironment and maintenance of stemness, could be an effective preventive or therapeutic strategy for gastric cancer.
The Contributions of Maternal Sensitivity and Maternal Depressive Symptoms to Epigenetic Processes and Neuroendocrine Functioning
Authors: Conradt Elisabeth , Hawes Katheleen , Guerin Dylan , Armstrong David A. , Marsit Carmen J. , Tronick Edward , Lester Barry M.
Published: January 2016

This study tested whether maternal responsiveness may buffer the child to the effects of maternal depressive symptoms on DNA methylation of NR3C1, 11β‐HSD2, and neuroendocrine functioning. DNA was derived from buccal epithelial cells and prestress cortisol was obtained from the saliva of 128 infants. Mothers with depressive symptoms who were more responsive and who engaged in more appropriate touch during face‐to‐face play had infants with less DNA methylation of NR3C1 and 11β‐HSD2 compared to mothers with depressive symptoms who were also insensitive. The combination of exposure to maternal depressive symptoms and maternal sensitivity was related to the highest prestress cortisol levels, whereas exposure to maternal depressive symptoms and maternal insensitivity was related to the lowest prestress cortisol levels.
Oxytocin Receptor Genetic and Epigenetic Variations: Association With Child Abuse and Adult Psychiatric Symptoms
Authors: Smearman Erica L. , Almli Lynn M. , Conneely Karen N. , Brody Gene H. , Sales Jessica M. , Bradley Bekh , Ressler Kerry J. , Smith Alicia K.
Published: January 2016

Childhood abuse can alter biological systems and increase risk for adult psychopathology. Epigenetic mechanisms, alterations in DNA structure that regulate the gene expression, are a potential mechanism underlying this risk. While abuse associates with methylation of certain genes, particularly those in the stress response system, no study to date has evaluated abuse and methylation of the oxytocin receptor (OXTR). However, studies support a role for OXTR in the link between abuse and adverse adult outcomes, showing that abuse can confer greater risk for psychiatric symptoms in those with specific OXTR genotypes. This study therefore sought to (a) assess the role of epigenetics in the link between abuse and psychopathology and (b) begin to integrate the genetic and epigenetic literature by exploring associations between OXTR genotypes and DNA CpG methylation. Data on 18 OXTR CpG sites, 44 single nucleotide polymorphisms, childhood abuse, and adult depression and anxiety symptoms were assessed in 393 African American adults (age = 41 ± 12.8 years). Overall, 68% of genotypes were associated with methylation of nearby CpG sites, with a subset surviving multiple test correction. Child abuse associated with higher methylation of two CpG sites yet did not survive correction or serve as a mediator of psychopathology. However, abuse interacted with CpG methylation to predict psychopathology. These findings suggest a role for OXTR in understanding the influence of early environments on adult psychiatric symptoms.
Diagnosis of Autism Spectrum Disorders Using Temporally Distinct Resting‐State Functional Connectivity Networks
Authors: Wee Chong‐Yaw , Yap Pew‐Thian , Shen Dinggang
Published: January 2016

Introduction

Resting‐state functional magnetic resonance imaging (R‐fMRI) is dynamic in nature as neural activities constantly change over the time and are dominated by repeating brief activations and deactivations involving many brain regions. Each region participates in multiple brain functions and is part of various functionally distinct but spatially overlapping networks. Functional connectivity computed as correlations over the entire time series always overlooks interregion interactions that often occur repeatedly and dynamically in time, limiting its application to disease diagnosis.

Aims

We develop a novel framework that uses short‐time activation patterns of brain connectivity to better detect subtle disease‐induced disruptions of brain connectivity. A clustering algorithm is first used to temporally decompose R‐fMRItime series into distinct clusters with similar spatial distribution of neural activity based on the assumption that functionally distinct networks should be largely temporally distinct as brain states do not simultaneously coexist in general. A Pearson correlation‐based functional connectivity network is then constructed for each cluster to allow for better exploration of spatiotemporal dynamics of individual neural activity. To reduce significant intersubject variability and to remove possible spurious connections, we use a group‐constrained sparse regression model to construct a backbone sparse network for each cluster and use it to weight the corresponding Pearson correlation network.

Results

The proposed method outperforms the conventional static, temporally dependent fully connected correlation‐based networks by at least 7% on a publicly available autism dataset. We were able to reproduce similar results using data from other centers.

Conclusions

By combining the advantages of temporal independence and group‐constrained sparse regression, our method improves autism diagnosis.
Simultaneous Assessment of Myocardial Perfusion, Wall Motion, and Deformation during Myocardial Contrast Echocardiography: A Feasibility Study
Authors: Zoppellaro Giacomo , Venneri Lucia , Khattar Rajdeep S. , Li Wei , Senior Roxy
Published: February 2016

Aims

Ultrasound contrast agents may be used for the assessment of regional wall motion and myocardial perfusion, but are generally considered not suitable for deformation analysis. The aim of our study was to assess the feasibility of deformation imaging on contrast‐enhanced images using a novel methodology.

Methods and Results

We prospectively enrolled 40 patients who underwent stress echocardiography with continuous intravenous infusion of SonoVue for the assessment of myocardial perfusion imaging with flash replenishment technique. We compared longitudinal strain (Lε) values, assessed with a vendor‐independent software (2D CPA), on 68 resting contrast‐enhanced and 68 resting noncontrast recordings. Strain analysis on contrast recordings was evaluated in the first cardiac cycles after the flash. Tracking of contrast images was deemed feasible in all subjects and in all views. Contrast administration improved image quality and increased the number of segments used for deformation analysis. Lε of noncontrast and contrast‐enhanced images were statistically different (−18.8 ± 4.5% and −22.8 ± 5.4%, respectively; P < 0.001), but their correlation was good (ICC 0.65, 95%CI 0.42–0.78). Patients with resting wall‐motion abnormalities showed lower Lε values on contrast recordings (−18.6 ± 6.0% vs. −24.2 ± 5.5%, respectively; P < 0.01). Intra‐operator and inter‐operator reproducibility was good for both noncontrast and contrast images with no statistical differences.

Conclusions

Our study shows that deformation analysis on postflash contrast‐enhanced images is feasible and reproducible. Therefore, it would be possible to perform a simultaneous evaluation of wall‐motion abnormalities, volumes, ejection fraction, perfusion defects, and cardiac deformation on the same contrast recording.
Intraventricular Isovolumic Relaxation Flow Patterns Studied by Using Vector Flow Mapping
Authors: Zhang Haibin , Ren Xiaofeng , Song Jin , Cao Xinyu , Wang Benna , Liu Ying , Li Zhiguo , Ma Na
Published: February 2016

Aims

The purpose of this study was to characterize isovolumic relaxation flow (IRF) in the left ventricle (LV) in patients with a wide spectrum of LV dysfunction.

Methods

Color Doppler flow imaging was performed in 61 patients with coronary artery disease, 29 patients with dilated cardiomyopathy, and 41 healthy controls. Vector flow mapping was used to analyze the Doppler data.

Results

IRF patterns were divided into three types: pattern A, an apically directed flow; pattern B, a bidirectional flow with small scattered vortices; and pattern C, a large vortex persisting throughout the entire isovolumic relaxation (IVR) period. All controls demonstrated an IRF corresponding to pattern A. Of the 90 patients, 42 demonstrated IRF as pattern A, 26 as pattern B, and 22 as pattern C. There were significant differences among the subgroups of patients with different IRF patterns and the control group in LV‐ejection fraction, size, wall‐motion score index, apical wall‐motion score index, systolic and diastolic mitral annular velocities, ratio of the mitral inflow E velocity to early diastolic mitral annular velocity (E/e′), and left atrial diameter (all P < 0.05). In the patient group, a higher wall‐motion score index independently predicted the IRF pattern. In patients with severe LV dysfunction, a higher E/e′ ratio was the independent predictor of the persistence of a large vortex during the IVR period.

Conclusions

The IRF pattern is associated with LV function. A large intraventricular vortex persisting during the IVR period should be indicative of increasingly depressed LV function.
Portosystemic shunts: A diagnostic challenge
Authors: Gold J. R.
Published: February 2016

The case report in this issue by Woodfordet al. (2017) describes the surgical management of an extrahepatic portosystemic shunt in a 5‐week old miniature foal. Only a handful of reports exist in the literature describing surgical procedures for repair of these congenital abnormalities in foals. One of the important aspects of the accompanying case report was the multidisciplinary approach taken in handling, imaging and surgical repair of the extrahepatic shunt. Small animal internal medicine specialists and surgeons diagnose portosystemic shunts much more frequently than equine veterinarians, regardless of whether they are general practitioners or specialists. It is therefore important to work as a team with small and large animal practitioners. The case described by Woodfordet al. (2017) had a positive outcome.