bluuebunny/crossref_metadata_2025 huggingface dataset:
Interkingdom Cross-Feeding of Ammonium from Marine Methylamine-Degrading Bacteria to the Diatom Phaeodactylum tricornutum
Authors: Suleiman Marcel , Zecher Karsten , Yücel Onur , Jagmann Nina , Philipp Bodo
Published: October 2016

Methylamines occur ubiquitously in the oceans and can serve as carbon, nitrogen, and energy sources for heterotrophic bacteria from different phylogenetic groups within the marine bacterioplankton. Diatoms, which constitute a large part of the marine phytoplankton, are believed to be incapable of using methylamines as a nitrogen source. As diatoms are typically associated with heterotrophic bacteria, the hypothesis came up that methylotrophic bacteria may provide ammonium to diatoms by degradation of methylamines. This hypothesis was investigated with the diatom
Phaeodactylum tricornutum
and monomethylamine (MMA) as the substrate. Bacteria supporting photoautotrophic growth of
P. tricornutum
with MMA as the sole nitrogen source could readily be isolated from seawater. Two strains,
Donghicola
sp. strain KarMa, which harbored genes for both monomethylamine dehydrogenase and the
N
methylglutamate pathway, and
Methylophaga
sp. strain M1, which catalyzed MMA oxidation by MMA dehydrogenase, were selected for further characterization. While strain M1 grew with MMA as the sole substrate, strain KarMa could utilize MMA as a nitrogen source only when, e.g., glucose was provided as a carbon source. With both strains, release of ammonium was detected during MMA utilization. In coculture with
P. tricornutum
, strain KarMa supported photoautotrophic growth with 2 mM MMA to the same extent as with the equimolar amount of NH
4
Cl. In coculture with strain M1, photoautotrophic growth of
P. tricornutum
was also supported, but to a much lower degree than by strain KarMa. This proof-of-principle study with a synthetic microbial community suggests that interkingdom cross-feeding of ammonium from methylamine-degrading bacteria is a contribution to phytoplankton growth which has been overlooked so far.

IMPORTANCE
Interactions between diatoms and heterotrophic bacteria are important for marine carbon cycling. In this study, a novel interaction is described. Bacteria able to degrade monomethylamine, which is a ubiquitous organic nitrogen compound in marine environments, can provide ammonium to diatoms. This interkingdom metabolite transfer enables growth under photoautotrophic conditions in coculture, which would not be possible in the respective monocultures. This proof-of-principle study calls attention to a so far overlooked contribution to phytoplankton growth.
Pendimethalin Nitroreductase Is Responsible for the Initial Pendimethalin Degradation Step in Bacillus subtilis Y3
Authors: Ni Hai-yan , Wang Fei , Li Na , Yao Li , Dai Chen , He Qin , He Jian , Hong Qing
Published: October 2016

Pendimethalin [
N
-(1-ethylpropyl)-2,6-dinitro-3,4-xylidine] is a selective preemergence dinitroaniline herbicide. Several fungi and bacteria have been reported to degrade pendimethalin, but the enzymes or genes involved in this process have not been characterized. Nitroreduction is the initial degradation and detoxification step for pendimethalin. In this study, a pendimethalin nitroreductase (PNR), responsible for the nitroreduction of pendimethalin, was purified from the pendimethalin-degrading strain
Bacillus subtilis
Y3. Based on a comparison of its mass fingerprints with all of the deduced proteins from the draft genome of strain Y3, a protein annotated as a nitroreductase was identified, and its corresponding encoding gene was termed
pnr
. PNR was a functional homodimer with a subunit molecular mass of approximately 23 kDa. PNR reduced the C-6 nitro group of the aromatic ring of pendimethalin, yielding 2-nitro-6-amino-
N
-(1-ethylpropyl)-3,4-xylidine. PNR could also catalyze the nitroreduction of three other major varieties of dinitroaniline herbicides, including butralin, oryzalin, and trifluralin. However, the number of reduced nitro groups was two instead of one, which differed from the nitroreduction of pendimethalin by PNR and which may be due to the symmetry in the chemical structures of the two nitro groups. A detoxification assay revealed that 2-nitro-6-amino-
N
-(1-ethylpropyl)-3,4-xylidine (PNR-reduced pendimethalin) showed no inhibitory effect on the growth of
Saccharomyces cerevisiae
BY4741, whereas pendimethalin showed an obvious inhibitory effect on its growth, indicating the detoxification effect of pendimethalin by PNR. Therefore, PNR has potential in pendimethalin detoxification applications. This report describes an enzyme (and corresponding gene) involved in the biodegradation of pendimethalin and dinitroaniline herbicides.

IMPORTANCE
Pendimethalin [
N
-(1-ethylpropyl)-2,6-dinitro-3,4-xylidine] is a widely used selective preemergence dinitroaniline herbicide, and its residue has been frequently detected in the environment. The U.S. Environmental Protection Agency (EPA) has classified pendimethalin as a persistent bioaccumulative toxin. To date, no enzymes or genes involved in pendimethalin biodegradation have been reported. In the present study, the gene
pnr
, which encodes the nitroreductase PNR, responsible for the nitroreduction of pendimethalin, was cloned from the pendimethalin-degrading strain
Bacillus subtilis
Y3. PNR could also catalyze the nitroreduction of three other major varieties of dinitroaniline herbicides, including butralin, oryzalin, and trifluralin. The reduction of pendimethalin by PNR might eliminate its toxicity against
Saccharomyces cerevisiae
BY4741, indicating the application potential of PNR in the detoxification of pendimethalin.
Soil Nutrient Depletion Is Associated with the Presence of Burkholderia pseudomallei
Authors: Hantrakun Viriya , Rongkard Patpong , Oyuchua Malinee , Amornchai Premjit , Lim Cherry , Wuthiekanun Vanaporn , Day Nicholas P. J. , Peacock Sharon J. , Limmathurotsakul Direk
Published: October 2016

Burkholderia pseudomallei
is a soil-dwelling bacterium and the cause of melioidosis, which kills an estimated 89,000 people per year worldwide. Agricultural workers are at high risk of infection due to repeated exposure to the bacterium. Little is known about the soil physicochemical properties associated with the presence or absence of the organism. Here, we evaluated the soil physicochemical properties and presence of
B. pseudomallei
in 6,100 soil samples collected from 61 rice fields in Thailand. The presence of
B. pseudomallei
was negatively associated with the proportion of clay, proportion of moisture, level of salinity, percentage of organic matter, presence of cadmium, and nutrient levels (phosphorus, potassium, calcium, magnesium, and iron). The presence of
B. pseudomallei
was not associated with the level of soil acidity (
P
= 0.54). In a multivariable logistic regression model, the presence of
B. pseudomallei
was negatively associated with the percentage of organic matter (odds ratio [OR], 0.06; 95% confidence interval [CI], 0.01 to 0.47;
P
= 0.007), level of salinity (OR, 0.06; 95% CI, 0.01 to 0.74;
P
= 0.03), and percentage of soil moisture (OR, 0.81; 95% CI, 0.66 to 1.00;
P
= 0.05). Our study suggests that
B. pseudomallei
thrives in rice fields that are nutrient depleted. Some agricultural practices result in a decline in soil nutrients, which may impact the presence and amount of
B. pseudomallei
bacteria in affected areas.

IMPORTANCE
Burkholderia pseudomallei
is an environmental Gram-negative bacillus and the cause of melioidosis. Humans acquire the disease following skin inoculation, inhalation, or ingestion of the bacterium in the environment. The presence of
B. pseudomallei
in soil defines geographic regions where humans and livestock are at risk of melioidosis, yet little is known about the soil properties associated with the presence of the organism. We evaluated the soil properties and presence of
B. pseudomallei
in 61 rice fields in East, Central, and Northeast Thailand. We demonstrated that the organism was more commonly found in soils with lower levels of organic matter and nutrients, including phosphorus, potassium, calcium, magnesium, and iron. We also demonstrated that crop residue burning after harvest, which can reduce soil nutrients, was not uncommon. Some agricultural practices result in a decline in soil nutrients, which may impact the presence and amount of
B. pseudomallei
bacteria in affected areas.
Interactions of Plutonium with Pseudomonas sp. Strain EPS-1W and Its Extracellular Polymeric Substances
Authors: Boggs Mark A. , Jiao Yongqin , Dai Zurong , Zavarin Mavrik , Kersting Annie B.
Published: October 2016

Safe and effective nuclear waste disposal, as well as accidental radionuclide releases, necessitates our understanding of the fate of radionuclides in the environment, including their interaction with microorganisms. We examined the sorption of Pu(IV) and Pu(V) to
Pseudomonas
sp. strain EPS-1W, an aerobic bacterium isolated from plutonium (Pu)-contaminated groundwater collected in the United States at the Nevada National Security Site (NNSS) in Nevada. We compared Pu sorption to cells with and without bound extracellular polymeric substances (EPS). Wild-type cells with intact EPS sorbed Pu(V) more effectively than cells with EPS removed. In contrast, cells with and without EPS showed the same sorption affinity for Pu(IV).
In vitro
experiments with extracted EPS revealed rapid reduction of Pu(V) to Pu(IV). Transmission electron microscopy indicated that 2- to 3-nm nanocrystalline Pu(IV)O
2
formed on cells equilibrated with high concentrations of Pu(IV) but not Pu(V). Thus, EPS, while facilitating Pu(V) reduction, inhibit the formation of nanocrystalline Pu(IV) precipitates.

IMPORTANCE
Our results indicate that EPS are an effective reductant for Pu(V) and sorbent for Pu(IV) and may impact Pu redox cycling and mobility in the environment. Additionally, the resulting Pu morphology associated with EPS will depend on the concentration and initial Pu oxidation state. While our results are not directly applicable to the Pu transport situation at the NNSS, the results suggest that, in general, stationary microorganisms and biofilms will tend to limit the migration of Pu and provide an important Pu retardation mechanism in the environment. In a broader sense, our results, along with a growing body of literature, highlight the important role of microorganisms as producers of redox-active organic ligands and therefore as modulators of radionuclide redox transformations and complexation in the subsurface.
Patient-reported outcome measure for neuromyelitis optica: pretesting of preliminary instrument and protocol for further development in accordance with international guidelines
Authors: Moore P , Jackson C , Mutch K , Methley A , Pollard C , Hamid S , Jacob A
Published: October 2016

Objective

This study outlines the development of a patient-reported outcome measure (PROM), an instrument to obtain self-reported health status for neuromyeltis optica (NMO), a disabling neurological condition.

Design

Development was conducted in accordance with international guidance for PROMs including systematic review of existing literature, item generation guided by qualitative interviews, health-related quality of life conceptual framework and clinical expert panel and cognitive interviews with NMO patients.

Setting

Participants were identified through a national NMO clinic in a tertiary NHS neurosciences service.

Participants

15 individuals with NMO participated in cognitive interviews requiring review and ranking of proposed PROM items and qualitative feedback on content, layout and response options.

Results

Participants endorsed the draft instrument as reflecting their experience of the condition and as being easy to understand. Rating and ranking of item relevance and importance reduced the draft instrument from 106 to 48 items. Participant feedback on overlapping items eliminated a further 2 items and resulted in a preliminary instrument of 46 items. As a direct result of participant feedback ordering of the 10 domains was revised, a 4 option Likert scale was employed and a 4-week recall period for impact of symptoms was selected.

Conclusions

A 46-item instrument developed in accordance with international PROM development guidelines through literature review, developed by subject matter experts and refined through pretesting examining content validity provides a preliminary measure for assessing patient-report of health status in NMO. Further evaluation is proposed including sensitivity to clinical change, and international contributions to evaluating the measure are encouraged.
Effectiveness of the ‘Back-to-Sleep’ campaigns among healthcare professionals in the past 20 years: a systematic review
Authors: de Luca Federico , Hinde Andrew
Published: October 2016

Objectives

From the late 1980s ‘Back-to-Sleep’ (BTS) campaigns were run in most developed countries to increase awareness of the supine position's protective effect against sleep-related infant deaths. Once the media awareness-raising action associated with these campaigns ended, healthcare professionals' role became crucial. The goal of this paper is to determine if healthcare professionals' knowledge and parent advice consistent with evidence-based infant sleep recommendations have changed over the past 20 years.

Setting

All studies investigating healthcare professionals' knowledge and/or advice to parents were included in a systematic review. The search was performed in PubMed and in MEDLINE, and 21 studies were identified.

Results

The correctness of healthcare professionals' knowledge and parent advice about the supine sleeping position increased over the past 20 years. However, the percentage of those aware that parents should avoid putting their babies to sleep in a prone position is decreasing over time: from about 97% in the 1990s to about 90% at the end of the 2000s.

Conclusions

The effectiveness of the BTS campaigns in publicising the benefits of the supine position is confirmed by this paper. More and more healthcare professionals know that it is the best position to reduce the risk of sleep-related deaths and they recommend it exclusively. However, the decrease in the knowledge about non-prone positions suggests that the campaigns may not have focused enough on the dangers of the prone position.
Implementing the RISE second victim support programme at the Johns Hopkins Hospital: a case study
Authors: Edrees Hanan , Connors Cheryl , Paine Lori , Norvell Matt , Taylor Henry , Wu Albert W
Published: October 2016

Background

Second victims are healthcare workers who experience emotional distress following patient adverse events. Studies indicate the need to develop organisational support programmes for these workers. The RISE (Resilience In Stressful Events) programme was developed at the Johns Hopkins Hospital to provide this support.

Objective

To describe the development of RISE and evaluate its initial feasibility and subsequent implementation. Programme phases included (1) developing the RISE programme, (2) recruiting and training peer responders, (3) pilot launch in the Department of Paediatrics and (4) hospital-wide implementation.

Methods

Mixed-methods study, including frequency counts of encounters, staff surveys and evaluations by RISE peer responders. Descriptive statistics were used to summarise demographic characteristics and proportions of responses to categorical, Likert and ordinal scales. Qualitative analysis and coding were used to analyse open-ended responses from questionnaires and focus groups.

Results

A baseline staff survey found that most staff had experienced an unanticipated adverse event, and most would prefer peer support. A total of 119 calls, involving ∼500 individuals, were received in the first 52 months. The majority of calls were from nurses, and very few were related to medical errors (4%). Peer responders reported that the encounters were successful in 88% of cases and 83.3% reported meeting the caller's needs. Low awareness of the programme was a barrier to hospital-wide expansion. However, over the 4 years, the rate of calls increased from ∼1–4 calls per month. The programme evolved to accommodate requests for group support.

Conclusions

Hospital staff identified the need for a multidisciplinary peer support programme for second victims. Peer responders reported success in responding to calls, the majority of which were for adverse events rather than for medical errors. The low initial volume of calls emphasises the importance of promoting awareness of the value of emotional support and the availability of the programme.
Effect of vitreomacular adhesion and vitreous gel on age-related reduction of macular thickness: a retrospective observational study
Authors: Kumagai Kazuyuki , Hangai Masanori , Furukawa Mariko , Suetsugu Tetsuyuki , Ogino Nobuchika
Published: October 2016

Objective

To investigate the effects of vitreomacular adhesion (VMA), vitreomacular separation (VMS) and absence of vitreous gel due to vitrectomy on macular thickness measured in the spectral domain optical coherence tomographic (SD-OCT) images.

Design

A longitudinal, retrospective, observational study.

Setting

Secondary multicentre study.

Participants

218 eyes of 218 healthy patients and 119 vitrectomised eyes of 119 patients were studied. The healthy individuals were classified into a VMA group (54 eyes) and a VMS group (164 eyes), while the vitrectomised patients were classified into an internal limiting membrane (ILM)-on group (26 eyes) and an ILM-off group (93 eyes). In all participants, 2 Cirrus HD-OCT recordings were made with an average interval of 36 months (range 24–60 months).

Primary and secondary outcome measures

The primary outcome measure was the rate of change in macular thickness in the central sector. The secondary outcomes were the rates of change in macular thickness in the inner 4 sectors.

Results

The annual rate of change in the macular thickness of the central sector was 0.76±1.8 µm/year in the VMA group, −0.58±2.3 µm/year in the VMS group, −1.57±1.9 µm/year in the ILM-on group and −0.86±3.1 µm/year in the ILM-off group. There was a significant difference between the rate of the central sector thickness change in the VMA and VMS groups (p=0.0001). The presence of VMA was a significant factor associated with an increase in the central sector thickness (p=0.0055). When the healthy and ILM-on groups were compared, the rate of decrease in the central sector thickness was faster in the ILM-on group (p=0.0043). Multiple regression analyses showed that not peeling the ILM during the vitrectomy was a significant factor associated with a decrease in the central sector thickness (p=0.044).

Conclusions

The presence of a VMA and a vitreous gel may help restrain the macular thickness reduction.
Uncoupling of mucosal gene regulation, mRNA splicing and adherent microbiota signatures in inflammatory bowel disease
Authors: Häsler Robert , Sheibani-Tezerji Raheleh , Sinha Anupam , Barann Matthias , Rehman Ateequr , Esser Daniela , Aden Konrad , Knecht Carolin , Brandt Berenice , Nikolaus Susanna , Schäuble Sascha , Kaleta Christoph , Franke Andre , Fretter Christoph , Müller Werner , Hütt Marc-Thorsten , Krawczak Michael , Schreiber Stefan , Rosenstiel Philip
Published: October 2016

Objective

An inadequate host response to the intestinal microbiota likely contributes to the manifestation and progression of human inflammatory bowel disease (IBD). However, molecular approaches to unravelling the nature of the defective crosstalk and its consequences for intestinal metabolic and immunological networks are lacking. We assessed the mucosal transcript levels, splicing architecture and mucosa-attached microbial communities of patients with IBD to obtain a comprehensive view of the underlying, hitherto poorly characterised interactions, and how these are altered in IBD.

Design

Mucosal biopsies from Crohn's disease and patients with UC, disease controls and healthy individuals (n=63) were subjected to microbiome, transcriptome and splicing analysis, employing next-generation sequencing. The three data levels were integrated by different bioinformatic approaches, including systems biology-inspired network and pathway analysis.

Results

Microbiota, host transcript levels and host splicing patterns were influenced most strongly by tissue differences, followed by the effect of inflammation. Both factors point towards a substantial disease-related alteration of metabolic processes. We also observed a strong enrichment of splicing events in inflamed tissues, accompanied by an alteration of the mucosa-attached bacterial taxa. Finally, we noted a striking uncoupling of the three molecular entities when moving from healthy individuals via disease controls to patients with IBD.

Conclusions

Our results provide strong evidence that the interplay between microbiome and host transcriptome, which normally characterises a state of intestinal homeostasis, is drastically perturbed in Crohn's disease and UC. Consequently, integrating multiple OMICs levels appears to be a promising approach to further disentangle the complexity of IBD.
Doctors in space (ships): biomedical uncertainties and medical authority in imagined futures
Authors: Henderson Lesley , Carter Simon
Published: October 2016

There has been considerable interest in images of medicine in popular science fiction and in representations of doctors in television fiction. Surprisingly little attention has been paid to doctors administering space medicine in science fiction. This article redresses this gap. We analyse the evolving figure of ‘the doctor’ in different popular science fiction television series. Building upon debates within Medical Sociology, Cultural Studies and Media Studies we argue that the figure of ‘the doctor’ is discursively deployed to act as the moral compass at the centre of the programme narrative. Our analysis highlights that the qualities, norms and ethics represented by doctors in space (ships) are intertwined with issues of gender equality, speciesism and posthuman ethics. We explore the signifying practices and political articulations that are played out through these cultural imaginaries. For example, the ways in which ‘the simple country doctor’ is deployed to help establish hegemonic formations concerning potentially destabilising technoscientific futures involving alternative sexualities, or military dystopia. Doctors mostly function to provide the ethical point of narrative stability within a world in flux, referencing a nostalgia for the traditional, attentive, humanistic family physician. The science fiction doctor facilitates the personalisation of technological change and thus becomes a useful conduit through which societal fears and anxieties concerning medicine, bioethics and morality in a ‘post 9/11’ world can be expressed and explored.
Update on cerebral small vessel disease: a dynamic whole-brain disease
Authors: Shi Yulu , Wardlaw Joanna M
Published: October 2016

Cerebral small vessel disease (CSVD) is a very common neurological disease in older people. It causes stroke and dementia, mood disturbance and gait problems. Since it is difficult to visualise CSVD pathologies in vivo, the diagnosis of CSVD has relied on imaging findings including white matter hyperintensities, lacunar ischaemic stroke, lacunes, microbleeds, visible perivascular spaces and many haemorrhagic strokes. However, variations in the use of definition and terms of these features have probably caused confusion and difficulties in interpreting results of previous studies. A standardised use of terms should be encouraged in CSVD research. These CSVD features have long been regarded as different lesions, but emerging evidence has indicated that they might share some common intrinsic microvascular pathologies and therefore, owing to its diffuse nature, CSVD should be regarded as a ‘whole-brain disease’. Single antiplatelet (for acute lacunar ischaemic stroke) and management of traditional risk factors still remain the most important therapeutic and preventive approach, due to limited understanding of pathophysiology in CSVD. Increasing evidence suggests that new studies should consider drugs that target endothelium and blood–brain barrier to prevent and treat CSVD. Epidemiology of CSVD might differ in Asian compared with Western populations (where most results and guidelines about CSVD and stroke originate), but more community-based data and clear stratification of stroke types are required to address this.
Re‐emergence of the Schmallenberg virus associated triad hydranencephaly‐micromyelia‐arthrogryposis in a newborn calf in Belgium, 2016
Authors: Bayrou Calixte , Garigliany Mutien , Cassart Dominique , Sartelet Arnaud , Desmecht Daniel JM
Published: October 2016

Schmallenberg virus (SBV) emerged in Germany in 2011, then spread rapidly across Europe, causing an epizootic outbreak of abortion, stillbirth and birth at term of lambs, kids and calves with neurological signs and/or musculoskeletal malformations. SBV‐associated disease in newborns disappeared in Belgium in 2013. Here, the authors describe a SBV genomic RNA‐positive malformed calf born in May 2016. It reveals the return of SBV circulation during the fall of 2015 in the said area.
Potential vectors of equine arboviruses in the UK
Authors: Chapman G. E. , Archer D. , Torr S. , Solomon T. , Baylis M.
Published: October 2016

There is growing concern about the increasing risk of disease outbreaks caused by arthropod‐borne viruses (arboviruses) in both human beings and animals. There are several mosquito‐borne viral diseases that cause varying levels of morbidity and mortality in horses and that can have substantial welfare and economic ramifications. While none has been recorded in the UK, vector species for some of these viruses are present, suggesting that UK equines may be at risk. The authors undertook, therefore, the first study of mosquito species on equine premises in the UK. Mosquito magnet traps and red‐box traps were used to sample adults, and larvae were collected from water sources such as tyres, buckets, ditches and pools. Several species that are known to be capable of transmitting important equine infectious arboviruses were trapped. The most abundant, with a maximum catch of 173 in 72 hours, was Ochlerotatus detritus, a competent vector of some flaviviruses; the highest densities were found near saltmarsh habitats. The most widespread species, recorded at >75 per cent of sites, was Culiseta annulata. This study demonstrates that potential mosquito vectors of arboviruses, including those known to be capable of infecting horses, are present and may be abundant on equine premises in the UK.
Toward the creation of models to predict static and dynamic fault-seal potential in carbonates
Authors: Solum J. G. , Huisman B. A. H.
Published: October 2016

In contrast to faults in clastic reservoirs, rules to predict the exploration and production timescale fault-seal potential in carbonates are lacking. This paper provides a summary of carbonate reservoirs with cross-fault column height differences that represent examples of apparent static fault seal, and a summary of observed examples of dynamic fault seal in carbonate reservoirs and aquifers. These include cross-fault differences in water table depths across carbonate–carbonate juxtapositions, cross-fault pressure differences in carbonate aquifers separated by faults, production-induced cross-fault pressure differences in carbonate hydrocarbon reservoirs, sealing behaviour of faults in carbonate reservoirs inferred from well tests, and examples of low fault transmissibilities from history-matching exercises from carbonate reservoirs. This paper also documents the range of compositions of fault rocks in carbonates and the range of permeabilities that have been reported from low-permeability fault cores in carbonate fault zones, as well as the implications of the observed range of fault permeabilities in carbonates for sealing behaviours. The purpose of this paper is not to argue that every fault in a carbonate reservoir will seal or will even be capable of sealing. There are, however, enough examples of faults in carbonates that are sealing in a dynamic sense, and in a static sense, that the topic of carbonate fault seal should warrant much more study. Creation of predictive models will ultimately require a considerable amount of subsurface data, but these models should be created.
The impact of fine-scale reservoir geometries on streamline flow patterns in submarine lobe deposits using outcrop analogues from the Karoo Basin
Authors: Hofstra M. , Pontén A. S. M. , Peakall J. , Flint S. S. , Nair K. N. , Hodgson D. M.
Published: October 2016

Improved prediction of the recovery of oil-in-place in basin-floor fan reservoirs requires accurate characterization and modelling of multiscale heterogeneities. The use of outcrop analogues is a key tool to augment this process by documenting and quantifying sedimentary architecture, hierarchy and sedimentary facies relationships. A 3D geological modelling workflow is presented that tests the impact of fine-scale heterogeneities within basin-floor lobe complexes on reservoir connectivity. Construction of geological models of a basin-floor lobe complex allows realistic depositional architecture and facies distributions to be captured. In addition, detailed models are constructed from channelized areas within a basin-floor lobe complex. Petrophysical modelling and streamline analysis are employed to test the impact on reservoir connectivity between lobe models with: (i) vertically stacked facies with coarsening- and thickening-upwards trends in all locations; and (ii) lateral facies changes with dimensions and distributions constrained from outcrop data. The findings show that differences in facies architecture and, in particular, lobe-on-lobe amalgamation have a significant impact on connectivity and macroscopic sweep efficiency, which influence the production results. Channelized lobe areas are less predictable reservoir targets owing to uncertainties associated with channel-fill heterogeneities. The use of deterministic sedimentary architecture concepts and facies relationships have proven vital in the accurate modelling of reservoir heterogeneities.
Syneresis effect on the permeability of chemically grouted sand
Authors: Mollamahmutoğlu Murat , Avcı Eyubhan
Published: October 2016

The aim of this research was to investigate the permeability of sodium silicate grouted sand specimens having various gradations and relative densities. Initially, rheological properties of sodium silicate grouts were studied. The gel time decreased as the sodium silicate content increased. Viscosities of sodium silicate grouts increased as the silicate content increased. Syneresis of sodium silicate grout gels increased with the increase of silicate content up to a point and then started decreasing sharply. The penetrability of chemical grouts with different sodium silicate contents into various graded sand specimens prepared at different relative densities was highly successful. Grouted sand samples were kept in humid conditions at a temperature of 20°C until testing time and were subjected to permeability tests at different time intervals. In general, sodium silicate grouting reduced the permeability of various graded sand specimens. The permeability of grouted sand specimens slightly increased with time as a result of syneresis.
Splicing recharge and groundwater flow models in the Environment Agency National Groundwater Modelling System
Authors: Farrell Rolf , Ververs Marcel , Davison Paul , Howlett Paul , Whiteman Mark
Published: October 2016

This paper explains the background and development of the Environment Agency National Groundwater Modelling System (NGMS) to integrate recharge functionality with the existing groundwater modelling (Modflow functionality).

The Environment Agency groundwater models were originally developed primarily as a tool for making high-level strategic decisions but their use for short-term extreme event scenarios, such as drought or flood, has been relatively limited. This functionality has been constrained by the format of the rainfall/recharge input datasets. Undertaking scenario runs based on change in climate and weather has only been possible by direct manual alteration of those input datasets, which is not always practical on a day-to-day basis.

Full implementation of recharge models into NGMS changes this, allowing the recharge models to be run in the NGMS environment and output to be generated. The fusion aspect of the process involves that output being processed in such a way that it can be used by NGMS as input into a Modflow scenario run. This process is explained using the example of a recent drought scenario in the Wessex Basin groundwater model.
The tectonomagmatic significance of Neoarchaean variably alkali-enriched gabbro and diorite intrusions of the western Karelia Province
Authors: Mikkola Perttu , Heilimo Esa , Halkoaho Tapio , Käpyaho Asko
Published: October 2016

This study describes a group of Neoarchaean alkali enriched gabbros and diorites from the western Karelia Province of the Fennoscandian Shield. We provide new field observations, petrography, whole-rock chemical data and additional whole-rock Sm–Nd and O-isotope data from these Neoarchean rocks. Compositionally, the rocks can be classified as shoshonitic with elevated rare earth element, K
2
O, Ba and Sr contents together with variable MgO, Ni and Cr contents. The MgO, Ni and Cr depletion observed especially in one of the intrusions could have been caused by fractionation of olivine and clinopyroxene from the system. Zircon O-isotope values from one of the intrusions (δ
18
O=7.34±0.10‰) indicate the involvement of material that had undergone low-temperature fractionation of oxygen in the genesis. Samarium–Nd data imply contribution from older material in the petrogenesis of these rocks. The above-mentioned characteristics can be explained with a magma source in the mantle that was heterogeneous owing to the variable degrees of metasomatism. The alkali-enriched gabbros and diorites provide additional evidence for magmatism derived from heterogeneously enriched mantle during the Neoarchaean in the Karelia Province and associated with the cratonization of the area.

Supplementary material:
Table detailing oxygen-isotope analyses from this study is available at
https://doi.org/10.6084/m9.figshare.c.3466575
Geochronology of Neoarchaean granitoids of the NW eastern Dharwar craton: implications for crust formation
Authors: Dey Sukanta , Halla Jaana , Kurhila Matti , Nandy Jinia , Heilimo Esa , Pal Sayantan
Published: October 2016

The Neoarchaean Era is characterized by large preserved record of continental crust formation. Yet the actual mechanism(s) of Neoarchaean crustal growth remains controversial. In the northwestern part of the eastern Dharwar craton (EDC) granitoid magmatism started at 2.68 Ga with gneissic granodiorites showing intermediate character between sanukitoid and tonalite–trondhjemite–granodiorite (TTG). This was followed by intrusion of transitional (large-ion lithophile element-enriched) TTGs at 2.58 Ga. Finally 2.53–2.52 Ga sanukitoid and Closepet-type magmatism and intrusion of K-rich leucogranites mark the cratonization in the area. These granitoids mostly display initial negative εNd and Mesoarchaean depleted mantle model ages, suggesting presence of older crust in the area. Available data show that most of the Neoarchaean sodic granitoids in the EDC are transitional TTGs demonstrating the importance of reworking of older crust. It is suggested that the various
c.
2.7 Ga greenstone mafic–ultramafic volcanic rocks of EDC formed in oceanic arcs and plateaus which accreted to form continental margin environment. Subsequent 2.7–2.51 Ga granitoid magmatism involved juvenile addition of crust as well as reworking of felsic crust forming transitional TTGs, sanukitoids and K-rich leucogranites. Microcratons were possibly the source of older crustal signatures and their accretion appears to be one of the important processes of Neoarchaean crustal growth globally.

Supplementary material:
Analytical techniques are available at
https://doi.org/10.6084/m9.figshare.c.3470724
Dietary nitrate supplementation attenuates the reduction in exercise tolerance following blood donation
Authors: McDonagh Sinead T. J. , Vanhatalo Anni , Fulford Jonathan , Wylie Lee J. , Bailey Stephen J. , Jones Andrew M.
Published: October 2016

We tested the hypothesis that dietary nitrate (NO3−)-rich beetroot juice (BR) supplementation could partially offset deteriorations in O2transport and utilization and exercise tolerance after blood donation. Twenty-two healthy volunteers performed moderate-intensity and ramp incremental cycle exercise tests prior to and following withdrawal of ∼450 ml of whole blood. Before donation, all subjects consumed seven 70-ml shots of NO3−-depleted BR [placebo (PL)] in the 48 h preceding the exercise tests. During the 48 h after blood donation, subjects consumed seven shots of BR (each containing 6.2 mmol of NO3−, n = 11) or PL ( n = 11) before repeating the exercise tests. Hemoglobin concentration and hematocrit were reduced by ∼8–9% following blood donation ( P < 0.05), with no difference between the BR and PL groups. Steady-state O2uptake during moderate-intensity exercise was ∼4% lower after than before donation in the BR group ( P < 0.05) but was unchanged in the PL group. The ramp test peak power decreased from predonation (341 ± 70 and 331 ± 68 W in PL and BR, respectively) to postdonation (324 ± 69 and 322 ± 66 W in PL and BR, respectively) in both groups ( P < 0.05). However, the decrement in performance was significantly less in the BR than PL group (2.7% vs. 5.0%, P < 0.05). NO3−supplementation reduced the O2cost of moderate-intensity exercise and attenuated the decline in ramp incremental exercise performance following blood donation. These results have implications for improving functional capacity following blood loss.
Carboxy-terminal deletion of the HDL receptor reduces receptor levels in liver and steroidogenic tissues, induces hypercholesterolemia, and causes fatal heart disease
Authors: Pal Rinku , Ke Qingen , Pihan German A. , Yesilaltay Ayce , Penman Marsha L. , Wang Li , Chitraju Chandramohan , Kang Peter M. , Krieger Monty , Kocher Olivier
Published: October 2016

The HDL receptor SR-BI mediates the transfer of cholesteryl esters from HDL to cells and controls HDL abundance and structure. Depending on the genetic background, loss of SR-BI causes hypercholesterolemia, anemia, reticulocytosis, splenomegaly, thrombocytopenia, female infertility, and fatal coronary heart disease (CHD). The carboxy terminus of SR-BI (505QEAKL509) must bind to the cytoplasmic adaptor PDZK1 for normal hepatic—but not steroidogenic cell—expression of SR-BI protein. To determine whether SR-BI's carboxy terminus is also required for normal protein levels in steroidogenic cells, we introduced into SR-BI's gene a507Ala/STOP mutation that produces a truncated receptor (SR-BIΔCT). As expected, the dramatic reduction of hepatic receptor protein in SR-BIΔCT mice was similar to that in PDZK1 knockout (KO) mice. Unlike SR-BI KO females, SR-BIΔCT females were fertile. The severity of SR-BIΔCT mice's hypercholesterolemia was intermediate between those of SR-BI KO and PDZK1 KO mice. Substantially reduced levels of the receptor in adrenal cortical cells, ovarian cells, and testicular Leydig cells in SR-BIΔCT mice suggested that steroidogenic cells have an adaptor(s) functionally analogous to hepatic PDZK1. When SR-BIΔCT mice were crossed with apolipoprotein E KO mice (SR-BIΔCT/apoE KO), pathologies including hypercholesterolemia, macrocytic anemia, hepatic and splenic extramedullary hematopoiesis, massive splenomegaly, reticulocytosis, thrombocytopenia, and rapid-onset and fatal occlusive coronary arterial atherosclerosis and CHD (median age of death: 9 wk) were observed. These results provide new insights into the control of SR-BI in steroidogenic cells and establish SR-BIΔCT/apoE KO mice as a new animal model for the study of CHD.
Simvastatin prevents and reverses chronic pulmonary hypertension in newborn rats via pleiotropic inhibition of RhoA signaling
Authors: Wong Mathew J. , Kantores Crystal , Ivanovska Julijana , Jain Amish , Jankov Robert P.
Published: October 2016

Chronic neonatal pulmonary hypertension (PHT) frequently results in early death. Systemically administered Rho-kinase (ROCK) inhibitors prevent and reverse chronic PHT in neonatal rats, but at the cost of severe adverse effects, including systemic hypotension and growth restriction. Simvastatin has pleiotropic inhibitory effects on isoprenoid intermediates that may limit activity of RhoA, which signals upstream of ROCK. We therefore hypothesized that statin treatment would safely limit pulmonary vascular RhoA activity and prevent and reverse experimental chronic neonatal PHT via downstream inhibitory effects on pathological ROCK activity. Sprague-Dawley rats in normoxia (room air) or moderate normobaric hypoxia (13% O2) received simvastatin (2 mg·kg−1·day−1ip) or vehicle from postnatal days 1–14 (prevention protocol) or from days 14–21 (rescue protocol). Chronic hypoxia increased RhoA and ROCK activity in lung tissue. Simvastatin reduced lung content of the isoprenoid intermediate farnesyl pyrophosphate and decreased RhoA/ROCK signaling in the hypoxia-exposed lung. Preventive or rescue treatment of chronic hypoxia-exposed animals with simvastatin decreased pulmonary vascular resistance, right ventricular hypertrophy, and pulmonary arterial remodeling. Preventive simvastatin treatment improved weight gain, did not lower systemic blood pressure, and did not cause apparent toxic effects on skeletal muscle, liver or brain. Rescue therapy with simvastatin improved exercise capacity. We conclude that simvastatin limits RhoA/ROCK activity in the chronic hypoxia-exposed lung, thus preventing or ameliorating hemodynamic and structural markers of chronic PHT and improving long-term outcome, without causing adverse effects.
Finally, An Apoptosis-Targeting Therapeutic for Cancer
Authors: Croce Carlo M. , Reed John C.
Published: October 2016

Resistance to cell death represents one of the hallmarks of cancer. Various genetic and epigenetic changes in malignant cells afford cytoprotection in the face of genomic instability, oncogene activation, microenvironment stress, chemotherapy, targeted anticancer drugs, and even immunotherapy. Central among the regulators of cell life and death are Bcl-2 family proteins, with the founding member of the family (B-cell lymphoma/leukemia-2) discovered via its involvement in chromosomal translocations in lymphomas. The quest for therapeutics that target cell survival protein Bcl-2 represents a long road traveled, with many dead-ends, disappointments, and delays. Finally, a Bcl-2–targeting medicine has gained approval as a new class of anticancer agent. Cancer Res; 76(20); 5914–20. ©2016 AACR.
Concepts in Cancer Modeling: A Brief History
Authors: Thomas Renee M. , Van Dyke Terry , Merlino Glenn , Day Chi-Ping
Published: October 2016

Modeling, an experimental approach to investigate complex biological systems, has significantly contributed to our understanding of cancer. Although extensive cancer research has been conducted utilizing animal models for elucidating mechanisms and developing therapeutics, the concepts in a good model design and its application have not been well elaborated. In this review, we discuss the theory underlying biological modeling and the process of producing a valuable and relevant animal model. Several renowned examples in the history of cancer research will be used to illustrate how modeling can be translatable to clinical applications. Finally, we will also discuss how the advances in cancer genomics and cancer modeling will influence each other going forward. Cancer Res; 76(20); 5921–5. ©2016 AACR.
The Burden of Cancer in Asian Americans: A Report of National Mortality Trends by Asian Ethnicity
Authors: Thompson Caroline A. , Gomez Scarlett Lin , Hastings Katherine G. , Kapphahn Kristopher , Yu Peter , Shariff-Marco Salma , Bhatt Ami S. , Wakelee Heather A. , Patel Manali I. , Cullen Mark R. , Palaniappan Latha P.
Published: October 2016

Background: Asian Americans (AA) are the fastest growing U.S. population, and when properly distinguished by their ethnic origins, exhibit substantial heterogeneity in socioeconomic status, health behaviors, and health outcomes. Cancer is the second leading cause of death in the United States, yet trends and current patterns in the mortality burden of cancer among AA ethnic groups have not been documented.

Methods: We report age-adjusted rates, standardized mortality ratios, and modeled trends in cancer-related mortality in the following AA ethnicities: Asian Indians, Chinese, Filipinos, Japanese, Koreans, and Vietnamese, from 2003 to 2011, with non-Hispanic whites (NHW) as the reference population.

Results: For most cancer sites, AAs had lower cancer mortality than NHWs; however, mortality patterns were heterogeneous across AA ethnicities. Stomach and liver cancer mortality was very high, particularly among Chinese, Koreans, and Vietnamese, for whom these two cancer types combined accounted for 15% to 25% of cancer deaths, but less than 5% of cancer deaths in NHWs. In AA women, lung cancer was a leading cause of death, but (unlike males and NHW females) rates did not decline over the study period.

Conclusions: Ethnicity-specific analyses are critical to understanding the national burden of cancer among the heterogeneous AA population.

Impact: Our findings highlight the need for disaggregated reporting of cancer statistics in AAs and warrant consideration of tailored screening programs for liver and gastric cancers. Cancer Epidemiol Biomarkers Prev; 25(10); 1371–82. ©2016 AACR.
Messages to Motivate Human Papillomavirus Vaccination: National Studies of Parents and Physicians
Authors: Malo Teri L. , Gilkey Melissa B. , Hall Megan E. , Shah Parth D. , Brewer Noel T.
Published: October 2016

Background: Physician communication about human papillomavirus (HPV) vaccine is a key determinant of uptake. To support physician communication, we sought to identify messages that would motivate HPV vaccination.

Methods: From 2014 to 2015, we surveyed national samples of parents of adolescents ages 11 to 17 (n = 1,504) and primary care physicians (n = 776). Parents read motivational messages, selected from nine longer messages developed by the Centers for Disease Control and Prevention and six brief messages developed by the study team. Parents indicated whether each message would persuade them to get HPV vaccine for their adolescents. Physicians read the brief messages and indicated whether they would use them to persuade parents to get HPV vaccine for 11- to 12-year-old children.

Results: The highest proportion of parents (65%) and physicians (69%) found this brief message to be persuasive: “I strongly believe in the importance of this cancer-preventing vaccine for [child's name].” Parents disinclined to vaccinate were most receptive to messages with information about HPV infection being common, cancers caused by HPV, and HPV vaccine effectiveness. Parents' endorsement did not vary by race/ethnicity, education, child age, or child sex (all P > 0.05).

Conclusions: Our national surveys of parents and physicians identified messages that could motivate HPV vaccination, even among parents disinclined to vaccinate their children. The lack of difference across demographic subgroups in parental endorsement may suggest that these messages can be used across these subgroups.

Impact: Our findings support physicians' use of these messages with parents to help motivate uptake of this important cancer-preventing vaccine. Cancer Epidemiol Biomarkers Prev; 25(10); 1383–91. ©2016 AACR.