bluuebunny/crossref_metadata_2025 huggingface dataset:
Extensive tonotopic mapping across auditory cortex is recapitulated by spectrally-directed attention, and systematically related to cortical myeloarchitecture
Authors: Dick Frederic K. , Lehet Matt I. , Callaghan Martina F. , Keller Tim A. , Sereno Martin I. , Holt Lori L.
Published: May 2017

Auditory selective attention is vital in natural soundscapes. But, it is unclear how attentional focus on the primary dimension of auditory representation - acoustic frequency - might modulate basic auditory functional topography during active listening. In contrast to visual selective attention, which is supported by motor-mediated optimization of input across saccades and pupil dilation, the primate auditory system has fewer means of differentially sampling the world. This makes spectrally-directed endogenous attention a particularly crucial aspect of auditory attention. Using a novel functional paradigm combined with quantitative MRI, we establish that human frequency-band-selective attention drives activation in both myeloarchitectonically-estimated auditory core, and across the majority of tonotopically-mapped non-primary auditory cortex. The attentionally-driven best-frequency maps show strong concordance with sensory-driven maps in the same subjects across much of the temporal plane, with poor concordance in non-auditory areas. There is significantly greater activation across most of auditory cortex when best frequency is attended, versus ignored. Moreover, the single frequency bands that evoke the least activation and the frequency bands that elicit the least activation when attention is directed to them also correspond closely. Finally, the results demonstrate that there is spatial correspondence between the degree of myelination and the strength of the tonotopic signal across a number of regions in auditory cortex. Strong frequency preferences across tonotopically-mapped auditory cortex spatially correlate with R1-estimated myeloarchitecture, indicating shared functional and anatomical organization that may underlie intrinsic auditory regionalization.

Significance

Perception is an active process especially sensitive to attentional state. Listeners direct auditory attention to track a violin’s melody within an ensemble performance, or to follow a voice in a crowded cafe. Although diverse pathologies reduce quality of life by impacting such spectrally-directed auditory attention, its neurobiological bases are unclear. We demonstrate that human primary and non-primary auditory cortical activation is modulated by spectrally-directed attention in a manner that recapitulates its tonotopic sensory organization. Further, the graded activation profiles evoked by single frequency bands are correlated with attentionally-driven activation when these bands are presented in complex soundscapes. Finally, we observe a strong concordance in the degree of cortical myelination and the strength of tonotopic activation across several auditory cortical regions.
A multi-stage representation of cell proliferation as a Markov process
Authors: Yates Christian A. , Ford Matthew J. , Mort Richard L.
Published: May 2017

The stochastic simulation algorithm commonly known as Gillespie’s algorithm (originally derived for modelling well-mixed systems of chemical reactions) is now used ubiquitously in the modelling of biological processes in which stochastic effects play an important role. In well mixed scenarios at the sub-cellular level it is often reasonable to assume that times between successive reaction/interaction events are exponentially distributed and can be appropriately modelled as a Markov process and hence simulated by the Gillespie algorithm. However, Gillespie’s algorithm is routinely applied to model biological systems for which it was never intended. In particular, processes in which cell proliferation is important (e.g. embryonic development, cancer formation) should not be simulated naively using the Gillespie algorithm since the history-dependent nature of the cell cycle breaks the Markov process. The variance in experimentally measured cell cycle times is far less than in an exponential cell cycle time distribution with the same mean.

Here we suggest a method of modelling the cell cycle that restores the memoryless property to the system and is therefore consistent with simulation via the Gillespie algorithm. By breaking the cell cycle into a number of independent exponentially distributed stages we can restore the Markov property at the same time as more accurately approximating the appropriate cell cycle time distributions. The consequences of our revised mathematical model are explored analytically as far as possible. We demonstrate the importance of employing the correct cell cycle time distribution by recapitulating the results from two models incorporating cellular proliferation (one spatial and one non-spatial) and demonstrating that changing the cell cycle time distribution makes quantitative and qualitative differences to the outcome of the models. Our adaptation will allow modellers and experimentalists alike to appropriately represent cellular proliferation - vital to the accurate modelling of many biological processes - whilst still being able to take advantage of the power and efficiency of the popular Gillespie algorithm.
HIV disrupts CD34+progenitors involved in T-cell differentiation
Authors: Tsukamoto Tetsuo
Published: May 2017

HIV-1 causes the loss of CD4+T cells via depletion or impairment of their production. The latter involves infection of thymocytes, but the involvement of other cells including haematopoietic CD34+cells remains unclear even though HIV-positive patients frequently manifest myelosuppression. This study utilised the OP9-DL1 coculture system, which supports in vitro T-lineage differentiation of human haematopoietic stem/progenitor cells. Cord-derived CD34+cells were infected with CXCR4-tropic HIV-1NL4-3and cocultured. HIV-infected cocultures exhibited sustained viral replication for 5 weeks, as well as reduced CD4+T-cell growth at weeks 3–5. It was further revealed that CD34+CD7+CXCR4+cells can be quickly depleted as early as in 1 week after infection of the subset, and this was accompanied by the emergence of CD34+CD7+CD4+cells. These results indicate that CXCR4-tropic HIV-1 strains may disrupt CD34+CD7+lymphoid progenitor cell pools, presumably leading to impaired T-cell production potential.
Marginal Returns and Levels of Research Grant Support among Scientists Supported by the National Institutes of Health
Authors: Lauer Michael , Roychowdhury Deepshikha , Patel Katie , Walsh Rachael , Pearson Katrina
Published: May 2017

The current era of worsening hypercompetition in biomedical research has drawn attention to the possibility of decreasing marginal returns from research funding. Recent work has described decreasing marginal returns as a function of annual dollars granted to individual scientists. However, different fields of research incur varying cost structures. Therefore, we developed a Grant Support Index (GSI) that focuses on grant activity code, as opposed to field of study or cost. In a cohort of over 71,000 unique scientists funded by NIH between 1996 and 2014 we analyzed the association of grant support (as measured by annual GSI) with 3 bibliometric outcomes, maximum Relative Citation Ratio (which arguably reflects a scientist’s most influential work), median Relative Citation Ratio, and annual weighted Relative Citation Ratio (which is more dependent on publication counts). We found that for all 3 measures marginal returns decline as annual GSI increases. Thus, we confirm prior findings of decreasing marginal returns with higher levels of research funding support.
Mutations in Membrin/GOSR2reveal stringent secretory pathway demands of dendritic growth and synaptic integrity
Authors: Praschberger Roman , Lowe Simon A. , Malintan Nancy T. , Houlden Henry , Kullmann Dimitri M. , Usowicz Maria M. , Krishnakumar Shyam S. , Hodge James J.L. , Rothman James E. , Jepson James E.C.
Published: May 2017

Mutations in the Golgi SNARE protein Membrin (encoded by theGOSR2gene) cause progressive myoclonus epilepsy (PME). Membrin is a ubiquitously important protein mediating ER-to-Golgi membrane fusion, and hence it is unclear how these mutations result in a disorder restricted to the nervous system. Here we use a multi-layered strategy to elucidate the consequences of Membrin mutations from protein to neuron. We show that the pathogenic mutations cause partial reductions in SNARE-mediated membrane fusion. Importantly, these alterations were sufficient to profoundly impair dendritic growth in novelDrosophilamodels ofGOSR2-PME. We also observed axonal trafficking abnormalities in this model, as well as synaptic malformations, trans-synaptic instability and hyperactive synaptic transmission. Our study highlights how dendritic growth is vulnerable even to subtle secretory pathway deficits, uncovers a previously uncharacterized role for Membrin in synaptic function, and provides a comprehensive explanatory basis for genotype-phenotype relationships inGOSR2-PME.
A sequencer coming of age:de novogenome assembly using MinION reads
Authors: de Lannoy Carlos , de Ridder Dick , Risse Judith
Published: May 2017

Nanopore technology provides a novel approach to DNA sequencing that yields long, label-free reads of constant quality. The first commercial implementation of this approach, the MinION, has shown promise in various sequencing applications. The presented literature review gives an up-to-date overview of the MinION’s utility as ade novosequencing device. It is argued that the MinION may allow for portable and affordablede novosequencing of even complex genomes in the near future, despite the currently error-prone nature of its reads. Through continuous updates to the MinION hardware and the development of new assembly pipelines, both sequencing accuracy and assembly quality have already risen rapidly. However, this fast pace of development has also lead to a lack of oversight in the expanding landscape of analysis tools, as performance evaluations are outdated quickly. Now that the MinION is approaching a state of maturity, a thorough comparative benchmarking effort ofde novoassembly pipelines may be at place.
Wireless implantable sensor for non-invasive, longitudinal quantification of axial strain across rodent long bone defects
Authors: Klosterhoff Brett S. , Ong Keat Ghee , Krishnan Laxminarayanan , Hetzendorfer Kevin M. , Chang Young-Hui , Allen Mark G. , Guldberg Robert E. , Willett Nick J.
Published: May 2017

Bone development, maintenance, and regeneration are remarkably sensitive to mechanical cues. Consequently, mechanical stimulation has long been sought as a putative target to promote endogenous healing after fracture. Given the transient nature of bone repair, tissue-level mechanical cues evolve rapidly over time after injury and are challenging to measure non-invasively. The objective of this work was to develop and characterize an implantable strain sensor for non-invasive monitoring of axial strain across a rodent femoral defect during functional activity. Herein, we present the design, characterization, andin vivodemonstration of the device’s capabilities for quantitatively interrogating physiological dynamic strains during bone regeneration.Ex vivoexperimental characterization of the device showed that it exceeded the technical requirements for sensitivity, signal resolution, and electromechanical stability. The digital telemetry minimized power consumption, enabling long-term intermittent data collection. Devices were implanted in a rat 6 mm femoral segmental defect model and after three days, data were acquired wirelessly during ambulation and synchronized to corresponding radiographic videos, validating the ability of the sensor to non-invasively measure strain in real-time. Lastly,in vivostrain measurements were utilized in a finite element model to estimate the strain distribution within the defect region. Together, these data indicate the sensor is a promising technology to quantify local tissue mechanics in a specimen specific manner, facilitating more detailed investigations into the role of the mechanical environment in dynamic skeletal healing and remodeling.
Quantitative analysis shows that repair of Cas9-induced double-strand DNA breaks is slow and error-prone
Authors: Brinkman Eva K. , Chen Tao , Haas Marcel de , Holland Hanna A. , Akhtar Waseem , Steensel Bas van
Published: May 2017

The RNA-guided DNA endonuclease Cas9 is a powerful tool for genome editing. Little is known about the kinetics and fidelity of the double-strand break (DSB) repair process that follows a Cas9 cutting event in living cells. Here, we developed a strategy to measure the kinetics of DSB repair for single loci in human cells. Quantitative modeling of repaired DNA in time series after Cas9 activation reveals a relatively slow repair rate (~6h). Furthermore, the double strand break is predominantly repaired in an error-prone fashion (at least 70%). Both classical and microhomology-mediated end-joining pathways are active and contribute to the repair in a stochastic manner. However, the balance between these two pathways changes over time and can be altered by chemical inhibition of DNAPKcs or additional ionizing radiation. Our strategy is generally applicable to study DSB repair kinetics and fidelity in single loci, and demonstrates that Cas9-induced DSBs are repaired in an unusual manner.
Genetically engineered orange petunias on the market
Authors: Bashandy Hany , Teeri Teemu H.
Published: May 2017

Genetic engineering of petunia was shown to lead to novel flower color some twenty years ago. Here we show that petunia lines with orange flowers, generated for scientific purposes, apparently found their way to petunia breeding programmes, intentionally or unintentionally. Today they are widely available, but have not been registered for commerce.
Translation Inhibition and Resource Balance in the Cell-Free Gene Expression System
Authors: Nagaraj Vijayalakshmi H. , Greene James M. , Sengupta Anirvan M. , Sontag Eduardo D.
Published: May 2017

Quantifying the effect of vital resources on transcription and translation helps to understand the degree to which the concentration of each resource must be regulated for achieving homeostasis. Utilizing the synthetic transcription-translation (TX-TL) system, we study the impact of nucleotide triphosphates (NTPs) and magnesium (Mg2+), on gene expression. Recent observations of the counterintuitive phenomenon of suppression of gene expression at high NTP concentrations have led to the speculation that such suppression is due to the consumption of resources by transcription, hence leaving fewer resources for translation. In this work, we investigate an alternative hypothesis: direct suppression of the translation rate via stoichiometric mismatch in necessary reagents. We observe NTP-dependent suppression even in the early phase of gene expression, contradicting the resource limitation argument. To further decouple the contributions of transcription and translation, we performed gene expression experiments with purified mRNA. Simultaneously monitoring mRNA and protein abundances allowed us to extract a time-dependent translation rate. Measuring translation rates for different Mg2+and NTP concentrations, we observe a complex resource dependence. We demonstrate that translation is the rate-limiting process that is directly inhibited by high NTP concentrations. Additional Mg2+can partially reverse this inhibition. In several experiments, we observe two maxima of the translation rate viewed as a function of both Mg2+and NTP concentration, which can be explained in terms of an NTP-independent effect on the ribosome complex and an NTP-Mg2+titration effect. The non-trivial compensatory effects of abundance of different vital resources signals the presence of complex regulatory mechanisms to achieve optimal gene expression.
Strategies for Partitioning Clock Models in Phylogenomic Dating: Application to the Angiosperm Evolutionary Timescale
Authors: Foster Charles S. P. , Ho Simon Y. W.
Published: June 2017

Evolutionary timescales can be inferred from molecular sequence data using a Bayesian phylogenetic approach. In these methods, the molecular clock is often calibrated using fossil data. The uncertainty in these fossil calibrations is important because it determines the limiting posterior distribution for divergence-time estimates as the sequence length tends to infinity. Here we investigate how the accuracy and precision of Bayesian divergence-time estimates improve with the increased clock-partitioning of genome-scale data into clock-subsets. We focus on a data set comprising plastome-scale sequences of 52 angiosperm taxa. There was little difference among the Bayesian date estimates whether we chose clock-subsets based on patterns of among-lineage rate heterogeneity or relative rates across genes, or by random assignment. Increasing the degree of clock-partitioning usually led to an improvement in the precision of divergence-time estimates, but this increase was asymptotic to a limit presumably imposed by fossil calibrations. Our clock-partitioning approaches yielded highly precise age estimates for several key nodes in the angiosperm phylogeny. For example, when partitioning the data into 20 clock-subsets based on patterns of among-lineage rate heterogeneity, we inferred crown angiosperms to have arisen 198–178 Ma. This demonstrates that judicious clock-partitioning can improve the precision of molecular dating based on phylogenomic data, but the meaning of this increased precision should be considered critically.
Precise timing of sensory modulations coupled to eye movements during active vision
Authors: Devia Christ , Montefusco-Siegmund Rodrigo , Egaña José Ignacio , Maldonado Pedro E.
Published: June 2017

Perception is the result of ongoing brain activity combined with sensory stimuli. In natural vision, changes in the visual input typically occur as the result of self-initiated eye movements. Nonetheless, in most studies, stimuli are flashed, and natural eye movements are avoided or restricted. As a consequence, the neural sensory processing associated with active vision is poorly understood. Here, we show that occipital event-related potentials (ERP) to eye movements during free exploration of natural images exhibited different amplitudes, time course and motor dependency than that from the same flashed stimuli. We found that the ERP to visual fixations doubles in P1 magnitude and does not show a late component, which is classically seen with flashed stimuli1,2. In addition, we discovered that the ERP to the saccade onset was as large as the ERP to fixations onset, with an early component that preceded the visual input, suggesting that a motor modulation was associated with the saccades3. Furthermore, the use of different visual scenes revealed that both the ERP amplitude and time course were dependent on the type of image explored. Our results demonstrated that during active vision, the nervous system engages a mechanism of sensory modulation that is precisely timed to the self-initiated stimulus changes. This mechanism could help coordinate neural activity across different cortical areas and, by extension, serve as a general mechanism for the global coordination of neural networks.
Associations of prenatal and postnatal growth with insulin-like growth factor-I levels in pre-adolescence
Authors: Arathimos R , Macdonald-Wallis C , Bull CJ , Holly JMP , Oken E , Kramer MS , Gusina N , Bogdanovich N , Vilchuck K , Patel R , Martin R M , Tilling K
Published: June 2017

Background

Rapid pre - and postnatal growth have been associated with later life adverse health outcomes, which could implicate (as a mediator) circulating insulin-like-growth-factor I (IGF-I), an important regulator of growth. We investigated associations of prenatal (birth weight and length) and postnatal growth in infancy and childhood with circulating IGF-I measured at 11.5 years of age.

Methods

We analysed 11.5-year follow-up data from 17,046 Belarusian children who participated in the Promotion of Breastfeeding Intervention Trial (PROBIT) since birth.

Results

Complete data were available for 5422 boys and 4743 girls (60%). We stratified the analyses by sex, as there was evidence of interaction between growth and sex in their associations with IGF-I. Weight and length/height velocity during childhood were positively associated with IGF-I at 11.5 years; associations increased with age at growth assessment and were stronger for length/height gain than for weight gain. The change in internal run-normalized IGF-I z-score at 11.5 years was 0.038 (95% CI -0.004,0.080) per standard deviation (SD) increase in length gain at 0-3 months amongst girls and 0.025 (95% CI - 0.011,0.060) amongst boys, increasing to 0.336 (95% CI 0.281,0.391;) and 0.211 (95% CI 0.165,0.256) for girls and boys, respectively, for growth during 6.5-11.5 years.

Conclusion

Postnatal growth velocities in childhood are positively associated with levels of circulating IGF-I in pre-adolescents. Future studies should focus on assessing whether IGF-I is on the causal pathway between early growth and later health outcomes, such as cancer and diabetes.
SCENIC: Single-cell regulatory network inference and clustering
Authors: Aibar Sara , González-Blas Carmen Bravo , Moerman Thomas , Wouters Jasper , Huynh-Thu Vân Anh , Imrichova Hana , Atak Zeynep Kalender , Hulselmans Gert , Dewaele Michael , Rambow Florian , Geurts Pierre , Aerts Jan , Marine Jean-Christophe , den Oord Joost van , Aerts Stein
Published: June 2017

Single-cell RNA-seq allows building cell atlases of any given tissue and infer the dynamics of cellular state transitions during developmental or disease trajectories. Both the maintenance and transitions of cell states are encoded by regulatory programs in the genome sequence. However, this regulatory code has not yet been exploited to guide the identification of cellular states from single-cell RNA-seq data. Here we describe a computational resource, called SCENIC (Single Cell rEgulatory Network Inference and Clustering), for the simultaneous reconstruction of gene regulatory networks (GRNs) and the identification of stable cell states, using single-cell RNA-seq data. SCENIC outperforms existing approaches at the level of cell clustering and transcription factor identification. Importantly, we show that cell state identification based on GRNs is robust towards batch-effects and technical-biases. We applied SCENIC to a compendium of single-cell data from the mouse and human brain and demonstrate that the proper combinations of transcription factors, target genes, enhancers, and cell types can be identified. Moreover, we used SCENIC to map the cell state landscape in melanoma and identified a gene regulatory network underlying a proliferative melanoma state driven by MITF and STAT and a contrasting network controlling an invasive state governed by NFATC2 and NFIB. We further validated these predictions by showing that two transcription factors are predominantly expressed in early metastatic sentinel lymph nodes. In summary, SCENIC is the first method to analyze scRNA-seq data using a network-centric, rather than cell-centric approach. SCENIC is generic, easy to use, and flexible, and allows for the simultaneous tracing of genomic regulatory programs and the mapping of cellular identities emerging from these programs. Availability: SCENIC is available as an R workflow based on three new R/Bioconductor packages:GENIE3, RcisTargetandAUCell.As scalable alternative to GENIE3, we also provideGRNboost,paving the way towards the network analysis across millions of single cells.
Learning and transfer of working memory gating policies
Authors: Bhandari Apoorva , Badre David
Published: June 2017

Abstract knowledge about the tasks we encounter enables us to rapidly and flexibly adapt to novel task contexts. Previous research has focused primarily on abstract rules that leverage shared structure in stimulus-response (S-R) mappings as the basis of such task knowledge. Here we provide evidence that working memory (WM) gating policies – a type of control policy required for internal control of WM during a task – constitute a form of abstract task knowledge that can be transferred across contexts. In two experiments, we report specific evidence for the transfer of selective WM gating policies across changes of task context. We show that this transfer is not tied to shared structure in S-R mappings, but instead in the dynamic structure of the task. Collectively, our results highlight the importance of WM gating policies in particular, and control policies in general, as a key component of the task knowledge that supports flexible behavior and task generalization.
Market‐driven production of biospecimens and the role of NHS hospital‐led biobanks
Authors: Timmons Stephen , Vezyridis Paraskevas
Published: May 2017

Biobanks are vital for biospecimen production in research, despite the regulatory, recruitment and commercial difficulties they face. We conducted interviews with clinicians, researchers, volunteers who recruit biobank participants, regulators and NHS managers about the integration of a biobank into an NHS hospital. We show that medical waste collected for biomedical research acquires its socio‐ethical and economic value from the level of integration (both technologically and organisationally) of the biobank into the NHS hospital. There is extensive investment in a range of intellectual and commercial relationships and labour among stakeholders involved in the production of biospecimens. It is not only the boundaries of research, clinical care and commercialisation of biospecimens that blur but also those of volunteerism and citizenship. Hospital‐led biobanks provide an opportunity to study the intertwining of biomedical innovation and healthcare.
Effect of temporal data aggregation on the perceived structure of a quantitative plant–floral visitor network
Authors: Sajjad Asif , Saeed Shafqat , Ali Mudssar , Khan Fawad Zafar Ahmad , Kwon Yong Jung , Devoto Mariano
Published: May 2017

Seasonal turnover in plant and floral visitor communities changes the structure of the network of interactions they are involved in. Despite the dynamic nature of plant–visitor networks, a usual procedure is to pool year‐round interaction data into a single network which may result in a biased depiction of the real structure of the interaction network. The annual temporal dynamics and the effect of merging monthly data have previously been described for qualitative data (i.e. describing the occurrence of interactions) alone, while its quantitative aspect (i.e. the actual frequency with which interactions occur) remain little explored. For this, we built a set of 12 monthly networks describing year‐round plant–floral visitor interactions in a 30‐hectare planted forest and its adjacent agricultural landscape at Bahauddin Zakariya University Multan, Pakistan. A total of 80 plant and 162 insect species, which engaged in 1573 unique interactions, were recorded. Most network properties (particularly the number of plants, visitors and unique interactions) varied markedly during the year. Data aggregation showed that while animal species, plant species, unique interaction, weighted nestedness, interaction diversity and robustness increased, connectance and specialization decreased. The only metric which seemed relatively unaffected by data pooling was interaction evenness. In general, quantitative metrics were relatively less affected by temporal data aggregation than qualitative ones. Avoiding data aggregation not only gives a more realistic depiction of the dynamic nature of plant–visitor community networks, but also avoids biasing network metrics and, consequently, their expected response to disturbances such as the loss of species.
Isolation of Egg Yolk Granules as Low‐Cholesterol Emulsifying Agent in Mayonnaise
Authors: Motta‐Romero Hollman , Zhang Zhong , Tien Nguyen An , Schlegel Vicki , Zhang Yue
Published: May 2017

Egg yolk is an essential ingredient for many food products due to its excellent functional properties such as emulsification. However, the consumers’ concern of its cholesterol level has led food industry to seek solutions for its replacement. Utilization of low‐fat egg yolk granules as emulsifier can be an alternative strategy. In this study, granules with low cholesterol content were separated from egg yolk by a simple method under easily scalable centrifugal conditions. The egg yolk granules isolated within 0.17 M NaCl solution achieved a 22.5% yield that was similar to that using higher centrifugation speeds and longer time. The yield of egg yolk granules increased from 25% to 32% when the yolk:water ratio was changed from 1:1 to 1:2. Mayonnaise was prepared to evaluate the emulsifying capacity of the egg yolk granules. It was found that egg yolk granules exhibited similar emulsifying activity as that of whole egg yolk, but a better emulsion stabilizing property that is evidenced by the higher viscosity of mayonnaise prepared with the granules. In addition, the viscosities of mayonnaise prepared by spray dried yolk and granules were slightly higher than the liquid counterpart, showing a further improvement by spray drying on the emulsion stabilizing properties. The mechanical spectra of mayonnaise samples by frequency sweep also suggested that granules favored the formation of stronger 3‐dimensional arrangements of oil droplets and therefore a more stable emulsion. Results suggest that granules isolated within 0.17 M NaCl solution present best emulsifying properties and can be applied as whole yolk replacer in food emulsions.
elementr: An R package for reducing elemental data from LA‐ICPMS analysis of biological calcified structures
Authors: Sirot Charlotte , Ferraton Franck , Panfili Jacques , Childs Amber‐Robyn , Guilhaumon François , Darnaude Audrey M.
Published: May 2017

Elemental analysis of biological calcified structures (e.g. fish otoliths, mollusc shelves, coral skeletons or fish and shark bones) provides invaluable information regarding ecological processes for many aquatic species. Despite this importance, the reduction of the raw data obtained through Laser‐ablation Inductively Coupled Plasma Mass Spectrometry (LA‐ICPMS) (i.e. the conversion of the machine raw signal into elemental concentrations) remains a challenge as the tools developed so far for carrying out this task have important limitations for aquatic ecologists.

Here, we introduce the elementr R‐package which provides a handy, reliable and transparent way to reduce elemental data acquired from spot or transect LA‐ICPMS analysis of biological calcified structures. This free and open‐source software, implemented based on state‐of‐the‐art literature, handles data from both standards and samples, allowing fast and simultaneous calculations of concentration for any chemical element, correction for potential machine drift, and realignment and averaging for sample replicates when needed.

The major attributes of elementr are: (i) its user‐friendly graphical interface which provides widgets to set all the reduction settings (i.e. no programming skills are required to run it), (ii) its reactivity whereby the software continuously observes any setting change made by the user, re‐calculates and displays all updated results, allowing therefore users to visually check the validity of their settings and to tune them if needed and (iii) an object oriented underlying that facilitates subsequent handling of LA‐ICPMS data in R.

Despite the elementr design being most suited to the needs of aquatic ecologists, its use could be broadened to other research fields (i.e. geology, material engineering) due to its flexibility. Moreover, the open‐source approach used for programming this software allows its expansion in order to refine calculation procedures or to add new functionalities.
An analysis of purchase price of legal and illicit cigarettes in urban retail environments in 14 low‐ and middle‐income countries
Authors: Brown Jennifer , Welding Kevin , Cohen Joanna E. , Cherukupalli Rajeev , Washington Carmen , Ferguson Jacqueline , Clegg Smith Katherine
Published: May 2017

Background/Aims

To estimate and compare price differences between legal and illicit cigarettes in 14 low‐ and middle‐income countries (LMIC).

Design

A cross‐sectional census of all packs available on the market was purchased.

Setting

Cigarette packs were purchased in formal retail settings in three major cities in each of 14 LMIC: Bangladesh, Brazil, China, Egypt, India, Indonesia, Mexico, Pakistan, the Philippines, Russia, Thailand, Turkey, Ukraine and Vietnam.

Participants

A total of 3240 packs were purchased (range = 58 packs in Egypt to 505 in Russia). Packs were categorized as ‘legal’ or ‘illicit’ based on the presence of a health warning label from the country of purchase and existence of a tax stamp; 2468 legal and 772 illicit packs were in the analysis.

Measurements

Descriptive statistics stratified by country, city and neighborhood socio‐economic status were used to explore the association between price and legal status of cigarettes.

Findings

The number of illicit cigarettes in the sample setting was small (n < 5) in five countries (Brazil, Egypt, Indonesia, Mexico, Russia) and excluded from analysis. In the remaining nine countries, the median purchase price of legal cigarettes ranged from US$0.32 in Pakistan (n = 72) to US$3.24 in Turkey (n = 242); median purchase price of illicit cigarettes ranged from US$0.80 in Ukraine (n = 14) to US$3.08 in India (n = 41). The difference in median price between legal and illicit packs as a percentage of the price of legal packs ranged from 32% in Philippines to 455% in Bangladesh. Median purchase price of illicit cigarette packs was higher than that of legal cigarette packs in six countries (Bangladesh, India, Pakistan, Philippines, Thailand, Vietnam). Median purchase price of illicit packs was lower than that of legal packs in Turkey, Ukraine and China.

Conclusions

The median purchase price of illicit cigarettes is higher than that of legal cigarette packs in Bangladesh, India, Pakistan, Philippines, Thailand, and Vietnam, Brazil, Egypt, Indonesia, Mexico, Russia appear to have few or no illicit cigarettes for purchase from formal, urban retailers.
Association between smoking and alcohol‐related behaviours: a time–series analysis of population trends in England
Authors: Beard Emma , West Robert , Michie Susan , Brown Jamie
Published: May 2017

Aims

This paper estimates how far monthly changes in prevalence of cigarette smoking, motivation to quit and attempts to stop smoking have been associated with changes in prevalence of high‐risk drinking, and motivation and attempts to reduce alcohol consumption in England.

Design

Data were used from the Alcohol and Smoking Toolkit Studies between April 2014 and June 2016. These involve monthly household face‐to‐face surveys of representative samples of ~1700 adults in England.

Measurements

Autoregressive Integrated Moving Average with Exogeneous Input (ARIMAX) modelling was used to assess the association over time between monthly prevalence of (a) smoking and high‐risk drinking; (b) high motivation to quit smoking and high motivation to reduce alcohol consumption; and (c) attempts to quit smoking and attempts to reduce alcohol consumption.

Findings

Mean smoking prevalence over the study period was 18.6% and high‐risk drinking prevalence was 13.0%. A decrease of 1% of the series mean smoking prevalence was associated with a reduction of 0.185% of the mean prevalence of high‐risk drinking 2 months later [95% confidence interval (CI) = 0.033 to 0.337, P = 0.017]. A statistically significant association was not found between prevalence of high motivation to quit smoking and high motivation to reduce alcohol consumption (β = 0.324, 95% CI = –0.371 to 1.019, P = 0.360) or prevalence of attempts to quit smoking and attempts to reduce alcohol consumption (β = −0.026, 95% CI = –1.348 to 1.296, P = 0.969).

Conclusion

Between 2014 and 2016, monthly changes in prevalence of smoking in England were associated positively with prevalence of high‐risk drinking. There was no significant association between motivation to stop and motivation to reduce alcohol consumption, or attempts to quit smoking and attempts to reduce alcohol consumption.
Does coffee consumption impact on heaviness of smoking?
Authors: Ware Jennifer J. , Tanner Julie‐Anne , Taylor Amy E. , Bin Zhao , Haycock Philip , Bowden Jack , Rogers Peter J. , Davey Smith George , Tyndale Rachel F. , Munafò Marcus R.
Published: May 2017

Background and Aims

Coffee consumption and cigarette smoking are strongly associated, but whether this association is causal remains unclear. We sought to: (1) determine whether coffee consumption influences cigarette smoking causally, (2) estimate the magnitude of any association and (3) explore potential mechanisms.

Design

We used Mendelian randomization (MR) analyses of observational data, using publicly available summarized data from the Tobacco and Genetics (TAG) consortium, individual‐level data from the UK Biobank and in‐vitro experiments of candidate compounds.

Setting

The TAG consortium includes data from studies in several countries. The UK Biobank includes data from men and women recruited across England, Wales and Scotland.

Participants

The TAG consortium provided data on n ≤ 38 181 participants. The UK Biobank provided data on 8072 participants.

Measurements

In MR analyses, the exposure was coffee consumption (cups/day) and the outcome was heaviness of smoking (cigarettes/day). In our in‐vitro experiments we assessed the effect of caffeic acid, quercetin and p‐coumaric acid on the rate of nicotine metabolism in human liver microsomes and cDNA‐expressed human CYP2A6.

Findings

Two‐sample MR analyses of TAG consortium data indicated that heavier coffee consumption might lead to reduced heaviness of smoking [beta = −1.49, 95% confidence interval (CI) = −2.88 to −0.09]. However, in‐vitro experiments found that the compounds investigated are unlikely to inhibit significantly the rate of nicotine metabolism following coffee consumption. Further MR analyses in UK Biobank found no evidence of a causal relationship between coffee consumption and heaviness of smoking (beta = 0.20, 95% CI = –1.72 to 2.12).

Conclusions

Amount of coffee consumption is unlikely to have a major causal impact upon amount of cigarette smoking. If it does influence smoking, this is not likely to operate via effects of caffeic acid, quercetin or p‐coumaric acid on nicotine metabolism. The observational association between coffee consumption and cigarette smoking may be due to smoking impacting on coffee consumption or confounding.
Changes in the structure of Melolonthidae (Coleoptera: Scarabaeoidea) assemblages along a temporal gradient in a natural reserve in Chaco, Argentina
Authors: Ibarra Polesel Mario G , Damborsky Miryam P
Published: May 2017

Melolonthidae beetles have been proposed as bioindicators because of their important role in the ecosystem and sensitivity to disturbance processes. However, the assemblage structure of these species in Argentina is unknown. In this study, the first attempt at determining Melolonthidae diversity, we analysed the abundance and diversity of the Melolonthidae assemblage and the species richness turnover over a period of three years. We collected samples in a gallery forest relict of a small protected area in which two light traps were installed. We collected a total of 474 specimens belonging to 38 species, two of which are new records for Argentina. The assemblage was characterised by numerous rare species, and the richness and diversity as well as the distribution of species abundance varied over the three years of the study. Replacement values varied based on the similarity indices that were used. Selected environmental variables (relative humidity, temperature and rainfall) were correlated with the richness and the abundance of the beetles. Our results suggest that the community of Melolonthidae could be considered dynamic, even over relatively short periods of time. Rare species play a major role in analyses of the similarity between assemblages and could suggest exaggerated turnover values. The high richness of the study area may be due to its good state of preservation or to its small area, which allows the entry of species from surrounding environments, showing how complex and fluid the Melolonthidae community can be in small patches of forest.
Impact of postoperative positioning on the outcome of pars plana vitrectomy with gas tamponade for primary rhegmatogenous retinal detachment: comparison between supine and prone positioning
Authors: Otsuka Keiko , Imai Hisanori , Miki Akiko , Nakamura Makoto
Published: May 2017

Purpose

To compare the postoperative anatomic success rates and the frequency of complications between prone or supine postoperative positioning after transconjunctival sutureless vitrectomy (TSV) for rhegmatogenous retinal detachment (RRD).

Methods

All patients underwent primary 27‐gauge TSV for the treatment of primary RRD. Patients were divided into two groups as follows: group A was patients instructed to keep strict postoperative prone positioning for a minimum of 8 days. Group B was patients instructed to keep the prone positioning on the day of the surgery followed by supine positioning for minimum of 7 days from the day after surgery.

Result

Sixty‐two eyes were enrolled (group A: 32, group B: 30). There was no significant difference in baseline data between two groups. The initial and final anatomical success rates were 93.8% and 100% in group A and 93.3% and 100% in group B, respectively (p = 1, p = 1, respectively). Posterior synechia of the iris occurred in one eye in group A and in two eyes in group B (p = 0.61). Macular pucker and retinal fold did not occur in either group. Preoperative intraocular pressure (IOP; mmHg) was 14.5 ± 2.9 in group A and 14.5 ± 2.6 in group B (p = 0.92). Intraocular pressure (IOP) was not statistically different between the groups during the follow‐up period (p = 0.36, p = 0.07, respectively).

Conclusion

Supine positioning may be an option as a postoperative positioning after TSV and gas tamponade for the treatment of RRD.
Bullying and cyberbullying studies in the school‐aged population on the island of Ireland: A meta‐analysis
Authors: Foody Mairéad , Samara Muthanna , O'Higgins Norman James
Published: May 2017

Background

Bullying research has gained a substantial amount of interest in recent years because of the implications for child and adolescent development.

Aim and sample

We conducted a meta‐analysis of traditional and cyberbullying studies in the Republic and North of Ireland to gain an understanding of prevalence rates and associated issues (particularly psychological correlates and intervention strategies) among young people (primary and secondary school students).

Method

Four electronic databases were searched (PsychArticles, ERIC, PsychInfo and Education Research Complete) for studies of traditional bullying and cyberbullying behaviours (perpetrators, victims or both) published between January 1997 and April 2016.

Results

A final sample of 39 articles fit our selection criteria. CMA software was used to estimate a pooled prevalence rate for traditional/cyberbullying victimization and perpetration. A systematic review on the psychological impacts for all types of bullying and previously used interventions in an Irish setting is also provided.

Conclusions

The results demonstrate the influence moderating factors (e.g., assessment tools, answer scale, time frame) have on reported prevalence rates. These results are discussed in light of current studies, and points for future research are considered.
Acetylsalicylic acid in critically ill patients: a cross‐sectional and a randomized trial
Authors: Schoergenhofer Christian , Hobl Eva‐Luise , Schwameis Michael , Gelbenegger Georg , Staudinger Thomas , Heinz Gottfried , Speidl Walter S. , Zauner Christian , Reiter Birgit , Lang Irene , Jilma Bernd
Published: May 2017

Background

Despite decades of clinical use, the pharmacokinetics and the effects of acetylsalicylic acid (ASA) in critically ill patients remain ill‐defined. We aimed to investigate the pharmacokinetics and the effects of different ASA formulations during critical illness.

Design

A cross‐sectional study and a randomized, parallel‐group trial were performed. Critically ill patients under chronic oral ASA treatment (100 mg enteric‐coated) were screened for high ‘on‐treatment’ platelet reactivity (HTPR) according to arachidonic acid‐induced whole‐blood aggregometry. Thirty patients with HTPR were randomized to receive 100 mg ASA intravenously, 100 mg enteric‐coated ASA bid (bis in die) or 81 mg chewable ASA (n = 10 per group). Serum thromboxane B2 (TXB2) levels, ASA and salicylic acid levels were quantified.

Results

Of 66 patients, 85% (95% confidence intervals 74–93%) had HTPR. Compared to baseline infusion of 100 mg, ASA significantly reduced platelet aggregation after 24 h to median 80% (Quartiles: 66–84%). Intake of 81 mg chewable ASA significantly reduced platelet aggregation to 75% (54–86%) after four hours, but increased it to 117% after 24 h (81–163%). Treatment with 100 mg enteric‐coated ASA bid decreased platelet aggregation after 24 h to median 56% (52–113%). Baseline TXB2 levels were median 0·35 ng/mL (0·07–0·94). Infusion of ASA or intake of 100 mg ASA bid reduced TXB2 levels to 0·07–0·18 ng/mL after 24 h, respectively. Chewable ASA reduced TXB2 levels only transiently. Pharmacokinetic analysis revealed highly variable absorption patterns of oral ASA formulations.

Conclusion

There is a very high prevalence of HTPR in critically ill patients on peroral ASA therapy, caused by an incomplete suppression of TXB2 and/or by impaired absorption of ASA.
Outcome predictors in dilated cardiomyopathy or myocarditis
Authors: Kuethe Friedhelm , Franz Marcus , Jung Christian , Porrmann Christiane , Reinbothe Franziska , Schlattmann Peter , Egerer Renate , Mall Gerhard
Published: May 2017

Background

The objective of this study was to identify parameters of prognostic relevance in patients presenting with chronic left ventricular dysfunction who underwent endomyocardial biopsy.

Materials and methods

A total of 351 consecutive patients (age 47·7 ± 12·6 years, 281 male) with a chronic left ventricular dysfunction were enrolled. Endomyocardial biopsies were analysed by histopathology according to Dallas criteria and immunohistological WHO criteria. Virus genome was detected by polymerase chain reaction. The combined end point was time to death or heart transplantation.

Results

About 19% of patients (n = 67) showed positive Dallas criteria and 39% (n = 118) immunohistochemical signs of inflammation. Viral genome was present in 58% (n = 155). During follow‐up, 25% (n = 89; 76 death, 13 HTx) reached the end point. Dallas‐positive histopathology (hazard ratio: 0·42; 95% CI: 0·29–0·84, P = 0·031), ejection fraction (hazard ratio: 0·97; 95% CI: 0·94–0·99, P = 0·019) and β‐blocker therapy (hazard ratio: 0·41; 95% CI: 0·23–0·69, P = 0·003) were independent outcome predictors. For patients under β‐blocker therapy, Dallas‐positive histopathology (hazard ratio: 0·37; 95% CI: 0·25–0·76, P = 0·009) and NYHA class III and class IV (hazard ratio: 2·11; 95% CI: 1·04–3·12, P = 0·006) were independent predictors.

Conclusions

For patients with a chronic left ventricular dysfunction, Dallas‐positive histopathology, β‐blocker therapy and left ventricular ejection fraction are the most striking parameters for outcome prediction.