bluuebunny/crossref_metadata_2025 huggingface dataset:
Hydrocarbon-Degrading Bacteria Exhibit a Species-Specific Response to Dispersed Oil while Moderating Ecotoxicity
Authors: Overholt Will A. , Marks Kala P. , Romero Isabel C. , Hollander David J. , Snell Terry W. , Kostka Joel E.
Published: November 2015

The Deepwater Horizon blowout in April 2010 represented the largest accidental marine oil spill and the largest release of chemical dispersants into the environment to date. While dispersant application may provide numerous benefits to oil spill response efforts, the impacts of dispersants and potential synergistic effects with crude oil on individual hydrocarbon-degrading bacteria are poorly understood. In this study, two environmentally relevant species of hydrocarbon-degrading bacteria were utilized to quantify the response to Macondo crude oil and Corexit 9500A-dispersed oil in terms of bacterial growth and oil degradation potential. In addition, specific hydrocarbon compounds were quantified in the dissolved phase of the medium and linked to ecotoxicity using a U.S. Environmental Protection Agency (EPA)-approved rotifer assay. Bacterial treatment significantly and drastically reduced the toxicity associated with dispersed oil (increasing the 50% lethal concentration [LC
50
] by 215%). The growth and crude oil degradation potential of
Acinetobacter
were inhibited by Corexit by 34% and 40%, respectively; conversely, Corexit significantly enhanced the growth of
Alcanivorax
by 10% relative to that in undispersed oil. Furthermore, both bacterial strains were shown to grow with Corexit as the sole carbon and energy source. Hydrocarbon-degrading bacterial species demonstrate a unique response to dispersed oil compared to their response to crude oil, with potentially opposing effects on toxicity. While some species have the potential to enhance the toxicity of crude oil by producing biosurfactants, the same bacteria may reduce the toxicity associated with dispersed oil through degradation or sequestration.
Divergent Evolution of the repFII Replicon of IncF Plasmids Carrying Cytotoxic Necrotizing Factor
cnf2
, Cytolethal Distending Toxin
cdtIII
, and
f17Ae
Fimbrial Variant Genes in Type 2 Necrotoxigenic Escherichia coli Isolates from Calves
Authors: Bihannic Morgan , Haenni Marisa , Oswald Eric , Madec Jean-Yves
Published: November 2015

Among the pathovars of
Escherichia coli
in cattle, necrotoxigenic
E. coli
(NTEC) is defined by the production of cytotoxic necrotizing factors (CNFs). In particular, type 2 NTEC (NTEC2) strains are frequent in diarrheic and septicemic calves and usually coproduce CNF type 2 (CNF2), cytolethal distending toxin type III (CDTIII), and fimbrial adhesins of the F17 family, whose genetic determinants have frequently been reported on the same Vir-like plasmid. In this study, we investigated the genetic environment of the
cnf2
,
f17Ae
, and
cdtIII
genes in a collection of fecal
E. coli
isolates recovered from 484 French and 58 Iranian calves. In particular, we highlighted the spread of
cnf2
,
f17Ae
, and
cdtIII
on similar 150-kb IncF plasmids harboring the newly assigned repFII replicon allele F74 in NTEC2 isolates. Interestingly, this 150-kb IncF plasmid differed from the 140-kb IncF plasmid harboring the newly assigned repFII replicon allele F75 and carrying
cnf2
alone. These results suggest two divergent lineages of
cnf2
-carrying IncF plasmids depending on the presence of the
f17Ae
and
cdtIII
genes. This partition was observed in
E. coli
strains of unrelated backgrounds, suggesting two different evolutionary paths of
cnf2
-carrying IncF plasmids rather than divergent evolutions of NTEC2 clones. The driving forces for such divergent evolutions are not known, and further studies are required to clarify the selection of plasmid subtypes spreading virulence determinants in
E. coli
, in particular, plasmids of the IncF family.
Application of the Environmental Relative Moldiness Index in Finland
Authors: Täubel Martin , Karvonen Anne M. , Reponen Tiina , Hyvärinen Anne , Vesper Stephen , Pekkanen Juha
Published: November 2015

The environmental relative moldiness index (ERMI) metric was previously developed to quantify mold contamination in U.S. homes. This study determined the applicability of the ERMI for quantifying mold and moisture damage in Finnish residences. Homes of the LUKAS2 birth cohort in Finland were visually inspected for moisture damage and mold, and vacuumed floor dust samples were collected. An ERMI analysis including 36 mold-specific quantitative PCR assays was performed on the dust samples (
n
= 144), and the ERMI metric was analyzed against inspection-based observations of moisture damage and mold. Our results show that the ERMI was significantly associated with certain observations of visible mold in Finnish homes but not with moisture damage. Several mold species occurred more frequently and at higher levels in Finnish than in U.S. homes. Modification of the ERMI toward Finnish conditions, using a subsample of LUKAS2 homes with and without moisture damage, resulted in a simplified metric based on 10 mold species. The Finnish ERMI (FERMI) performed substantially better in quantifying moisture and mold damage in Finnish homes, showing significant associations with various observations of visible mold, strongest when the damage was located in the child's main living area, as well as with mold odor and moisture damage. As shown in Finland, the ERMI as such is not equally well usable in different climates and geographic regions but may be remodeled to account for local outdoor and indoor fungal conditions as well as for moisture damage characteristics in a given country.
The Extracellular Wall-Bound β-
N
-Acetylglucosaminidase from Lactobacillus casei Is Involved in the Metabolism of the Human Milk Oligosaccharide Lacto-
N
-Triose
Authors: Bidart Gonzalo N. , Rodríguez-Díaz Jesús , Yebra María J.
Published: November 2015

Human milk oligosaccharides (HMOs) are considered to play a key role in establishing and maintaining the infant gut microbiota. Lacto-
N
-triose forms part of both type 1 and type 2 HMOs and also of the glycan moieties of glycoproteins. Upstream of the previously characterized gene cluster involved in lacto-
N
-biose and galacto-
N
-biose metabolism from
Lactobacillus casei
BL23, there are two genes,
bnaG
and
manA
, encoding a β-
N
-acetylglucosaminidase precursor and a mannose-6-phosphate isomerase, respectively. In this work, we show that
L. casei
is able to grow in the presence of lacto-
N
-triose as a carbon source. Inactivation of
bnaG
abolished the growth of
L. casei
on this oligosaccharide, demonstrating that BnaG is involved in its metabolism. Interestingly, whole cells of a
bnaG
mutant were totally devoid of β-
N
-acetylglucosaminidase activity, suggesting that BnaG is an extracellular wall-attached enzyme. In addition to hydrolyzing lacto-
N
-triose into
N
-acetylglucosamine and lactose, the purified BnaG enzyme also catalyzed the hydrolysis of 3′-
N
-acetylglucosaminyl-mannose and 3′-
N
-acetylgalactosaminyl-galactose.
L. casei
can be cultured in the presence of 3′-
N
-acetylglucosaminyl-mannose as a carbon source, but, curiously, the
bnaG
mutant strain was not impaired in its utilization. These results indicate that the assimilation of 3′-
N
-acetylglucosaminyl-mannose is independent of BnaG. Enzyme activity and growth analysis with a
manA
-knockout mutant showed that ManA is involved in the utilization of the mannose moiety of 3′-
N
-acetylglucosaminyl-mannose. Here we describe the physiological role of a β-
N
-acetylglucosaminidase in lactobacilli, and it supports the metabolic adaptation of
L. casei
to the
N
-acetylglucosaminide-rich gut niche.
Impact of Nisin-Activated Packaging on Microbiota of Beef Burgers during Storage
Authors: Ferrocino Ilario , Greppi Anna , La Storia Antonietta , Rantsiou Kalliopi , Ercolini Danilo , Cocolin Luca
Published: November 2015

Beef burgers were stored at 4°C in a vacuum in nisin-activated antimicrobial packaging. Microbial ecology analyses were performed on samples collected between days 0 and 21 of storage to discover the population diversity. Two batches were analyzed using RNA-based denaturing gradient gel electrophoresis (DGGE) and pyrosequencing. The active packaging retarded the growth of the total viable bacteria and lactic acid bacteria. Culture-independent analysis by pyrosequencing of RNA extracted directly from meat showed that
Photobacterium phosphoreum
,
Lactococcus piscium
,
Lactobacillus sakei
, and
Leuconostoc carnosum
were the major operational taxonomic units (OTUs) shared between control and treated samples. Beta diversity analysis of the 16S rRNA sequence data and RNA-DGGE showed a clear separation between two batches based on the microbiota. Control samples from batch B showed a significant high abundance of some taxa sensitive to nisin, such as
Kocuria rhizophila
,
Staphylococcus xylosus
,
Leuconostoc carnosum
, and
Carnobacterium divergens
, compared to control samples from batch A. However, only from batch B was it possible to find a significant difference between controls and treated samples during storage due to the active packaging. Predicted metagenomes confirmed differences between the two batches and indicated that the use of nisin-based antimicrobial packaging can determine a reduction in the abundance of specific metabolic pathways related to spoilage. The present study aimed to assess the viable bacterial communities in beef burgers stored in nisin-based antimicrobial packaging, and it highlights the efficacy of this strategy to prolong beef burger shelf life.
Terracidiphilus gabretensis gen. nov., sp. nov., an Abundant and Active Forest Soil Acidobacterium Important in Organic Matter Transformation
Authors: García-Fraile Paula , Benada Oldrich , Cajthaml Tomáš , Baldrian Petr , Lladó Salvador
Published: November 2015

Understanding the activity of bacteria in coniferous forests is highly important, due to the role of these environments as a global carbon sink. In a study of the microbial biodiversity of montane coniferous forest soil in the Bohemian Forest National Park (Czech Republic), we succeeded in isolating bacterial strain S55
T
, which belongs to one of the most abundant operational taxonomic units (OTUs) in active bacterial populations, according to the analysis of RNA-derived 16S rRNA amplicons. The 16S rRNA gene sequence analysis showed that the species most closely related to strain S55
T
include
Bryocella elongata
SN10
T
(95.4% identity),
Acidicapsa ligni
WH120
T
(95.2% identity), and
Telmatobacter bradus
TPB6017
T
(95.0% identity), revealing that strain S55
T
should be classified within the phylum
Acidobacteria
, subdivision 1. Strain S55
T
is a rod-like bacterium that grows at acidic pH (3 to 6). Its phylogenetic, genotypic, phenotypic, and chemotaxonomic characteristics indicate that strain S55
T
corresponds to a new genus within the phylum
Acidobacteria
; thus, we propose the name
Terracidiphilus gabretensis
gen. nov., sp. nov. (strain S55
T
= NBRC 111238
T
= CECT 8791
T
). This strain produces extracellular enzymes implicated in the degradation of plant-derived biopolymers. Moreover, analysis of the genome sequence of strain S55
T
also reveals the presence of enzymatic machinery required for organic matter decomposition. Soil metatranscriptomic analyses found 132 genes from strain S55
T
being expressed in the forest soil, especially during winter. Our results suggest an important contribution of
T. gabretensis
S55
T
in the carbon cycle in the
Picea abies
coniferous forest.
Dry Needling versus Acupuncture: The Ongoing Debate
Authors: Zhou Kehua , Ma Yan , Brogan Michael S
Published: November 2015

Although Western medical acupuncture (WMA) is commonly practised in the UK, a particular approach called dry needling (DN) is becoming increasingly popular in other countries. The legitimacy of the use of DN by conventional non-physician healthcare professionals is questioned by acupuncturists. This article describes the ongoing debate over the practice of DN between physical therapists and acupuncturists, with a particular emphasis on the USA. DN and acupuncture share many similarities but may differ in certain aspects. Currently, little information is available from the literature regarding the relationship between the two needling techniques. Through reviewing their origins, theory, and practice, we found that DN and acupuncture overlap in terms of needling technique with solid filiform needles as well as some fundamental theories. Both WMA and DN are based on modern biomedical understandings of the human body, although DN arguably represents only one subcategory of WMA. The increasing volume of research into needling therapy explains its growing popularity in the musculoskeletal field including sports medicine. To resolve the debate over DN practice, we call for the establishment of a regulatory body to accredit DN courses and a formal, comprehensive educational component and training for healthcare professionals who are not physicians or acupuncturists. Because of the close relationship between DN and acupuncture, collaboration rather than dispute between acupuncturists and other healthcare professionals should be encouraged with respect to education, research, and practice for the benefit of patients with musculoskeletal conditions who require needling therapy.
Three-decade neurological and neurocognitive follow-up of HIV-1-infected patients on best-available antiretroviral therapy in Finland
Authors: Heikinheimo T , Poutiainen E , Salonen O , Elovaara I , Ristola M
Published: November 2015

Objectives

Is it possible to live without neurocognitive or neurological symptoms after being infected with HIV for a very long time? These study patients with decades-long HIV infection in Finland were observed in this follow-up study during three time periods: 1986–1990, in 1997 and in 2013.

Setting

Patients from greater Helsinki area were selected from outpatient's unit of infectious diseases.

Participants

The study included 80 HIV patients. Patients with heavy alcohol consumption, central nervous system disorder or psychiatric disease were excluded.

Primary and secondary outcome measures

The patients underwent neurological and neuropsychological examinations, MRI of the brain and laboratory tests, including blood CD4 cells and plasma HIV-1 RNA. Neuropsychological examination included several measures: subtests of Wechsler Adult Intelligence Scale, Wechsler Memory Scale-Revised, list learning, Stroop and Trail-Making-B test. The Beck Depression Inventory and Fatigue Severity Scale were also carried out. The obtained data from the three time periods were compared with each other.

Results

Owing to high mortality among the original 80 patients, eventually, 17 participated in all three examinations performed between 1986 and 2013. The time from the HIV diagnosis was 27 (23–30) years. Blood CD4 cells at the diagnosis were 610 (29–870) cells/mm3, and the nadir CD4 168 (4–408) cells/mm3. The time on combined antiretroviral treatment was 13 (5–17) years. 9 patients suffered from fatigue, 5 had polyneuropathy and 3 had lacunar cerebral infarcts. There was a subtle increase of brain atrophy in 2 patients. Mild depressive symptoms were common. The neuropsychological follow-up showed typical age-related cognitive changes. No HIV-associated dementia features were detected.

Conclusions

Polyneuropathy, fatigue and mild depression were common, but more severe neurological abnormalities were absent. These long-term surviving HIV-seropositive patients, while on best-available treatment, showed no evidence of HIV-associated neurocognitive disorder in neuropsychological and neuroradiological evaluations.
Barriers faced by healthcare professionals when managing falls in older people in Kuala Lumpur, Malaysia: a qualitative study
Authors: Loganathan Annaletchumy , Ng Chirk Jenn , Tan Maw Pin , Low Wah Yun
Published: November 2015

Objective

To explore the barriers faced by healthcare professionals (HCPs) in managing falls among older people (aged above 60 years) who have a high risk of falling.

Research design

The study used a qualitative methodology, comprising 10 in-depth interviews and two focus group discussions. A semistructured topic guide was used to facilitate the interviews, which were audio recorded, transcribed verbatim and checked for accuracy. Data were analysed thematically using WeftQDA software.

Participants

20 HCPs who managed falls in older people.

Setting

This study was conducted at the Primary Care Clinic in the University Malaya Medical Centre (UMMC), Malaysia.

Results

Four categories of barriers emerged—these were related to perceived barriers for older people, HCPs’ barriers, lack of caregiver support and healthcare system barriers. HCPs perceived that older people normalised falls, felt stigmatised, were fatalistic, as well as in denial regarding falls-related advice. HCPs themselves trivialised falls and lacked the skills to manage falls. Rehabilitation was impeded by premature decisions to admit older people to nursing homes. Lastly, there was a lack of healthcare providers as well as a dearth of fall education and training on fall prevention for HCPs.

Conclusions

This study identified barriers that explain poor fall management in older people with a high risk of falls. The lack of structured fall prevention guidelines and insufficient training in fall management made HCPs unable to advise patients on how to prevent falls. The findings of this study warrant evidence-based structured fall prevention intervention targeted to patients as well as to HCPs.
Ranolazine for the treatment of chronic stable angina: a cost-effectiveness analysis from the UK perspective
Authors: Coleman Craig I , Freemantle Nick , Kohn Christine G
Published: November 2015

Objectives

To estimate the cost-effectiveness of ranolazine when added to standard-of-care (SoC) antianginals compared with SoC alone in patients with stable coronary disease experiencing ≥3 attacks/week.

Setting

An economic model utilising a UK health system perspective, a 1-month cycle-length and a 1-year time horizon.

Participants

Patients with stable coronary disease experiencing ≥3 attacks/week starting in 1 of 4 angina frequency health states based on Seattle Angina Questionnaire Angina Frequency (SAQAF) scores (100=no; 61–99=monthly; 31–60=weekly; 0–30=daily angina).

Intervention

Ranolazine added to SoC or SoC alone. Patients were allowed to transition between SAQAF states (first cycle only) or death (any cycle) based on probabilities derived from the randomised, controlled Efficacy of Ranolazine in Chronic Angina trial and other studies. Patients not responding to ranolazine in month 1 (not improving ≥1 SAQAF health state) discontinued ranolazine and were assumed to behave like SoC patients.

Primary and secondary outcomes measures

Costs (£2014) and quality-adjusted life-years (QALYs) for patients receiving and not receiving ranolazine.

Results

Ranolazine patients lived a mean of 0.701 QALYs at a cost of £5208. Those not receiving ranolazine lived 0.662 QALYs at a cost of £5318. The addition of ranolazine to SoC was therefore a dominant economic strategy. The incremental cost-effectiveness ratio was sensitive to ranolazine cost; exceeding £20 000/QALY when ranolazine's cost was >£203/month. Ranolazine remained a dominant strategy when indirect costs were included and mortality rates were assumed to increase with worsening severity of SAQAF health states. Monte Carlo simulation found ranolazine to be a dominant strategy in ∼71% of 10 000 iterations.

Conclusions

Although UK-specific data on ranolazine's efficacy and safety are lacking, our analysis suggest ranolazine added to SoC in patients with weekly or daily angina is likely cost-effective from a UK health system perspective.
Associations of volume and other hospital characteristics on mortality within 30 days of acute myocardial infarction in South Korea
Authors: Han Kyu-Tae , Kim Sun Jung , Kim Woorim , Jang Sung-In , Yoo Ki-Bong , Lee Seo Yoon , Park Eun-Cheol
Published: November 2015

Objective

The mortality for acute myocardial infarction (AMI) has declined worldwide. However, improvements in care for AMI in South Korea have lagged slightly behind those in other countries. Therefore, it is important to investigate how factors such as hospital volume, structural characteristics of hospital and hospital staffing level affect 30-day mortality due to AMI in South Korea.

Setting

We used health insurance claim data from 114 hospitals to analyse 30-day mortality for AMI.

Participants

These data consisted of 19 638 hospitalisations during 2010–2013.

Interventions

No interventions were made.

Outcome measure

Multilevel models were analysed to examine the association between the 30-day mortality and inpatient and hospital level variables.

Results

In the 30 days after hospitalisation, 10.5% of patients with AMI died. Hospitalisation cases at hospitals with a higher AMI volume had generally inverse associations with 30-day mortality (1st quartile=ref; 2nd quartile=OR 0.811, 95% CI 0.658 to 0.998, 3rd quartile=OR 0.648, 95% CI 0.500 to 0.840, 4th quartile=OR 0.807, 95% CI 0.573 to 1.138). In addition, hospitals with a greater proportion of specialists were associated with better outcomes (above median=OR 0.789, 95% CI 0.663 to 0.940).

Conclusions

Health policymakers need to include volume and staffing when defining the framework for treatment of AMI in South Korean hospitals. Otherwise, they must consider increasing the proportion of specialists or regulating the hiring of emergency medicine specialists. In conclusion, they must make an effort to reduce 30-day mortality following AMI based on such considerations.
Do marginal investments made by NHS healthcare commissioners in the UK produce the outcomes they hope to achieve? Observational study
Authors: O'Cathain Alicia , Sampson Fiona , Strong Mark , Pickin Mark , Goyder Elizabeth , Dixon Simon
Published: November 2015

Objective

To investigate the effect of targeted marginal annual investments by local healthcare commissioners on the outcomes they expected to achieve with these investments.

Design

Controlled before and after study.

Setting:

152 commissioning organisations (primary care trusts) in England.

Methods

National surveys of commissioning managers in 2009 and 2010 to identify: the largest marginal investments made in four key conditions/services (diabetes, coronary heart disease, chronic pulmonary airways disease and emergency and urgent care) in 2008/2009 and 2009/2010; the outcomes commissioners expected to achieve with these investments; and the processes commissioners used to develop these investments. Collation of routinely available data on outcomes commissioners expected from these investments over the period 2007/2008 to 2010/2011.

Results

51% (77/152) of commissioners agreed to participate in the survey in 2009 and 60% (91/152) in 2010. Around half reported targeted marginal investments in each condition/service each year. Routine data on many of the outcomes they expected to achieve through these investments were not available. Also, commissioners expected some outcomes to be achieved beyond the time scale of our study. Therefore, only a limited number of outcomes of investments were tested. Outcomes included directly standardised emergency admission rates for the four conditions/services, and the percentage of patients with diabetes with glycated haemoglobin <7. There was no evidence that targeted marginal investments reduced emergency admission rates. There was evidence of an improvement in blood glucose management for diabetes for commissioners investing to improve diabetes care but this was compromised by a change in how the outcome was measured in different years. This investment was unlikely to be cost-effective.

Conclusions

Commissioners made marginal investments in specific health conditions and services with the aim of improving a wide range of outcomes. There was little evidence of impact on the limited number of outcomes measured.
Protocol for a process-oriented qualitative evaluation of the Waltham Forest and East London Collaborative (WELC) integrated care pioneer programme using the Researcher-in-Residence model
Authors: Eyre Laura , George Bethan , Marshall Martin
Published: November 2015

Introduction

The integration of health and social care in England is widely accepted as the answer to fragmentation, financial concerns and system inefficiencies, in the context of growing and ageing populations with increasingly complex needs. Despite an expanding body of literature, there is little evidence yet to suggest that integrated care can achieve the benefits that its advocates claim for it. Researchers have often adopted rationalist and technocratic approaches to evaluation, treating integration as an intervention rather than a process. Results have usually been of limited use to practitioners responsible for health and social care integration. There is, therefore, a need to broaden the evidence base, exploring not onlywhatworks but alsohowintegrated care can most successfully be implemented and delivered. For this reason, we are carrying out a formative evaluation of the Waltham Forest and East London Collaborative (WELC) integrated care pioneer programme. Our expectation is that this will add value to the literature by focusing on the processes by which the vision and objectives of integrated care are translated through phases of development, implementation and delivery from a central to a local perspective, and from a strategic to an operational perspective.

Methods and analysis

The qualitative and process-oriented evaluation uses an innovative participative approach—the Researcher-in-Residence model. The evaluation is underpinned by a critical ontology, an interpretive epistemology and a critical discourse analysis methodology. Data will be generated using interviews, observations and documentary gathering.

Ethics and dissemination

Emerging findings will be interpreted and disseminated collaboratively with stakeholders, to enable the research to influence and optimise the effective implementation of integrated care across WELC. Presentations and publications will ensure that learning is shared as widely as possible. The study has received ethical approval from University College London's Research Ethics Committee and has all appropriate NHS governance clearances.
Improving the likelihood of neurology patients being examined using patient feedback
Authors: Appleton Jason Philip , Ilinca Andreea , Lindgren Arne , Puschmann Andreas , Hbahbih Majed , A. Siddiqui Khurram , de Silva Rajith , Jones Matthew , Butterworth Richard , willmot mark , Hayton Tom , Lunn Michael , Nicholl David
Published: November 2015

We aimed to establish whether recall of elements of the neurological examination can be improved by use of a simple patient assessment score.

In a previous study we demonstrated that in-patients referred to neurology at two United Kingdom (UK) hospitals were not fully examined prior to referral; we therefore designed a larger quality improvement report with 80% power to detect a 10% increase in tendon hammer or ophthalmoscope use following an educational intervention.

In-patients referred to neurology over a four month period (in hospitals in the UK (10), Jordan (1), Sweden (2), and the United Arab Emirates (1)) were asked whether they recalled being examined with a tendon hammer (T), ophthalmoscope (O), and stethoscope (S) since admission. The results were disseminated to local medical teams using various techniques (including Grand Round presentations, email, posters, discounted equipment). Data were then collected for a further four month period post-intervention.

Pre-intervention and post-intervention data were available for 11 centres with 407 & 391 patients in each arm respectively. Median age of patients was 51 (range 13-100) and 49 (range 16-95) years respectively, with 44.72% and 44.76% being male in each group. 264 patients (64.86%) recalled being examined with a tendon hammer in the pre-intervention arm, which significantly improved to 298 (76.21%) (p<0.001). Only 119 patients (29.24%) recollected examination with an ophthalmoscope pre-intervention, which significantly improved to 149 (38.11%)(p=0.009). The majority of patients (321 (78.87%)) pre-intervention recalled examination with a stethoscope, which significantly improved to 330 (84.4%) to a lesser extent (p=0.045).

Results indicate that most patients are not fully examined prior to neurology referral yet a simple assessment score and educational intervention can improve recall of elements of the neurological examination and thus the likelihood of patients being examined neurologically. This is the largest and - to our knowledge - only study to assess this issue. This has implications for national neurological educators.
Three-month validation of a turbuhaler electronic monitoring device: implications for asthma clinical trial use
Authors: Pilcher Janine , Shirtcliffe Philippa , Patel Mitesh , McKinstry Steve , Cripps Terrianne , Weatherall Mark , Beasley Richard
Published: November 2015

Background

Electronic monitoring of inhaled asthma therapy is suggested as the ‘gold standard’ for measuring patterns of medication use in clinical trials. The SmartTurbo (Adherium (NZ) Ltd, Auckland, New Zealand) is an electronic monitor for use with a turbuhaler device (AstraZeneca, UK). The aim of this study was to determine the accuracy of the SmartTurbo in recording Symbicort actuations over a 12-week period of use.

Methods

Twenty SmartTurbo monitors were attached to the base of 20 Symbicort turbuhalers. Bench testing in a research facility was undertaken on days 0, 5, 6, 7, 8, 9, 14, 21, 28, 56 and 84. Patterns of ‘low-use’ (2 sets of 2 actuations on the same day) and ‘high-use’ (2 sets of 8 actuations on the same day) were performed. The date and time of actuations were recorded in a paper diary and compared with data uploaded from the SmartTurbo monitors.

Results

2800 actuations were performed. Monitor sensitivity was 99.9% with a lower 97.5% confidence bound of 99.6%. The positive predictive value was 99.9% with a 97.5% lower confidence bound of 99.7%. Accuracy was not affected by whether the pattern of inhaler use was low or high, or whether there was a delay in uploading the actuation data.

Conclusions

The SmartTurbo monitor is highly accurate in recording and retaining electronic data in this 12-week bench study. It can be recommended for use in clinical trial settings, in which quality control systems are incorporated into study protocols to ensure accurate data acquisition.
Rule of 5: angiographic diameters of cervicocerebral arteries in children and compatibility with adult neurointerventional devices
Authors: He Lucy , Ladner Travis R , Pruthi Sumit , Day Matthew A , Desai Aditi A , Jordan Lori C , Froehler Michael T
Published: November 2015

Background and purpose

The safety of using adult-sized neuroendovascular devices in the smaller pediatric vasculature is not known. In this study we measure vessel diameters in the cervical and cranial circulation in children to characterize when adult-approved devices might be compatible in children.

Methods

For 54 children without vasculopathy (mean age 9.5±4.9 years (range 0.02–17.8), 20F/34M) undergoing catheter angiography, the diameters of the large vessels in the cervical and cranial circulation (10 locations, 611 total measurements) were assessed by three radiologists. Mean±SD diameter was calculated for the following age groups: 0–6 months, 1, 2, 3, 4, 5–9, 10–14, and 15–18 years. To compare with adult sizes, each vessel measurement was normalized to the respective region mean diameter in the oldest age group (15–18 years). Normalized measurements were compared with age and fitted to a segmented regression.

Results

Vessel diameters increased rapidly from 0 to 5 years of age (slope=0.069/year) but changed minimally beyond that (slope=0.005/year) (R2=0.2). The regression model calculated that, at 5 years of age, vessels would be 94% of the diameter of the oldest age group (compared with 59% at birth). In addition, most vessels in children under 5, while smaller, were still potentially large enough to be compatible with many adult devices.

Conclusions

The growth curve of the cervicocerebral vasculature displays rapid growth until age 5, at which point most children's vessels are nearly adult size. By age 5, most neuroendovascular devices are size-compatible, including thrombectomy devices for stroke. Under 5 years of age, some devices might still be compatible.
Testing a geographical information system for damage and evacuation assessment during an effusive volcanic crisis
Authors: Latutrie B. , Andredakis I. , De Groeve T. , Harris A. J. L. , Langlois E. , van Wyk de Vries B. , Saubin E. , Bilotta G. , Cappello A. , Crisci G. M. , D'ambrosio D. , Del Negro C. , Favalli M. , Fujita E. , Iovine G. , Kelfoun K. , Rongo R. , Spataro W. , Tarquini S. , Coppola D. , Ganci G. , Marchese F. , Pergola N. , Tramutoli V.
Published: November 2015

Using two hypothetical effusive events in the Chaîne des Puys (Auvergne, France), we tested two geographical information systems (GISs) set up to allow loss assessment during an effusive crisis. The first was a local system that drew on all immediately available data for population, land use, communications, utility and building type. The second was an experimental add-on to the Global Disaster Alert and Coordination System (GDACS) global warning system maintained by the Joint Research Centre (JRC) that draws information from open-access global data. After defining lava-flow model source terms (vent location, effusion rate, lava chemistry, temperature, crystallinity and vesicularity), we ran all available lava-flow emplacement models to produce a projection for the likelihood of impact for all pixels within the GIS. Next, inundation maps and damage reports for impacted zones were produced, with those produced by both the local system and by GDACS being in good agreement. The exercise identified several shortcomings of the systems, but also indicated that the generation of a GDACS-type global response system for effusive crises that uses rapid-response model projections for lava inundation driven by real-time satellite hotspot detection – and open-access datasets – is within the current capabilities of the community.
Cosmogenic
36
Cl geochronology of late Quaternary glaciers in the Bolkar Mountains, south central Turkey
Authors: Çiner Attila , Sarıkaya Mehmet Akif
Published: November 2015

We present the first quantitative late Quaternary cosmogenic
36
Cl glacial geochronology from the Bolkar Mountains of south central Turkey. Thirty samples were collected from three glaciated valleys. The geomorphological investigations indicate that the palaeoglaciers deposited their moraines between 3200 and 2200 m above sea level on the north- and south-facing valleys. We recognize four glacial periods, with the oldest one dating back to about 46.0±7.0 ka in the northern Karagöl Valley. Later, glaciers reached their maximum positions (∼5.5 km from cirque to snout) by 18.9±3.3 ka (during the local Last Glacial Maximum; LGM) in the Karagöl Valley. Late-glacial moraines were dated to between 15.2±1.6 and 12.6±2.3 ka in both northern Alagöl and southern Elmalı Valleys, respectively. The final deglaciation in the mountain commenced in the early Holocene (9.0±0.9 ka in the Karagöl Valley; 8.5±1.8 ka in the Elmalı Valley). A contemporaneous outwash plain dates to 8.4±1.0 ka at the outlet of the Alagöl Valley. Our results agree well with the glacial chronologies obtained from other Turkish and Mediterranean mountains.

Supplementary material:
Google Earth sample locations of this article are available at
http://www.geolsoc.org.uk/SUP18877
Role of the Insect Supervectors Bemisia tabaci and Frankliniella occidentalis in the Emergence and Global Spread of Plant Viruses
Authors: Gilbertson Robert L. , Batuman Ozgur , Webster Craig G. , Adkins Scott
Published: November 2015

Emergence of insect-transmitted plant viruses over the past 10–20 years has been disproportionately driven by two so-called supervectors: the whitefly, Bemisia tabaci, and the Western flower thrips, Frankliniella occidentalis. High rates of reproduction and dispersal, extreme polyphagy, and development of insecticide resistance, together with human activities, have made these insects global pests. These supervectors transmit a diversity of plant viruses by different mechanisms and mediate virus emergence through local evolution, host shifts, mixed infections, and global spread. Associated virus evolution involves reassortment, recombination, and component capture. Emergence of B. tabaci–transmitted geminiviruses (begomoviruses), ipomoviruses, and torradoviruses has led to global disease outbreaks as well as multiple paradigm shifts. Similarly, F. occidentalis has mediated tospovirus host shifts and global dissemination and the emergence of pollen-transmitted ilarviruses. The plant virus–supervector interaction offers exciting opportunities for basic research and global implementation of generalized disease management strategies to reduce economic and environmental impacts.
The Phage-Inducible Chromosomal Islands: A Family of Highly Evolved Molecular Parasites
Authors: Penadés José R. , Christie Gail E.
Published: November 2015

The phage-inducible chromosomal islands (PICIs) are a family of highly mobile genetic elements that contribute substantively to horizontal gene transfer, host adaptation, and virulence. Initially identified in Staphylococcus aureus, these elements are now thought to occur widely in gram-positive bacteria. They are molecular parasites that exploit certain temperate phages as helpers, using a variety of elegant strategies to manipulate the phage life cycle and promote their own spread, both intra- and intergenerically. At the same time, these PICI-encoded mechanisms severely interfere with helper phage reproduction, thereby enhancing survival of the bacterial population. In this review we discuss the genetics and the life cycle of these elements, with special emphasis on how they interact and interfere with the helper phage machinery for their own benefit. We also analyze the role that these elements play in driving bacterial and viral evolution.
Pathophysiological Consequences of Calcium-Conducting Viroporins
Authors: Hyser Joseph M. , Estes Mary K.
Published: November 2015

Eukaryotic cells have evolved a myriad of ion channels, transporters, and pumps to maintain and regulate transmembrane ion gradients. As intracellular parasites, viruses also have evolved ion channel proteins, called viroporins, which disrupt normal ionic homeostasis to promote viral replication and pathogenesis. The first viral ion channel (influenza M2 protein) was confirmed only 23 years ago, and since then studies on M2 and many other viroporins have shown they serve critical functions in virus entry, replication, morphogenesis, and immune evasion. As new candidate viroporins and viroporin-mediated functions are being discovered, we review the experimental criteria for viroporin identification and characterization to facilitate consistency within this field of research. Then we review recent studies on how the few Ca2+-conducting viroporins exploit host signaling pathways, including store-operated Ca2+entry, autophagy, and inflammasome activation. These viroporin-induced aberrant Ca2+signals cause pathophysiological changes resulting in diarrhea, vomiting, and proinflammatory diseases, making both the viroporin and host Ca2+signaling pathways potential therapeutic targets for antiviral drugs.
Bacteriophage Therapy: Advances in Formulation Strategies and Human Clinical Trials
Authors: Vandenheuvel Dieter , Lavigne Rob , Brüssow Harald
Published: November 2015

Recently, a number of phage therapy phase I and II safety trials have been concluded, showing no notable safety concerns associated with the use of phage. Though hurdles for efficient treatment remain, these trials hold promise for future phase III clinical trials. Interestingly, most phage formulations used in these clinical trials are straightforward phage suspensions, and not much research has focused on the processing of phage cocktails in specific pharmaceutical dosage forms. Additional research on formulation strategies and the stability of phage-based drugs will be of key importance, especially with phage therapy advancing toward phase III clinical trials.
The Legacy of Nat Sternberg: The Genesis of Cre-lox Technology
Authors: Yarmolinsky Michael , Hoess Ronald
Published: November 2015

Cre-lox of bacteriophage P1 has become one of the most widely used tools for genetic engineering in eukaryotes. The origins of this tool date to more than 30 years ago when Nat L. Sternberg discovered the recombinase, Cre, and its specific locus of crossover, lox, while studying the maintenance of bacteriophage P1 as a stable plasmid. Recombinations mediated by Cre assist in cyclization of the DNA of infecting phage and in resolution of prophage multimers created by generalized recombination. Early in vitro work demonstrated that, although it shares similarities with the well-characterized bacteriophage λ integration, Cre-lox is in many ways far simpler in its requirements for carrying out recombination. These features would prove critical for its development as a powerful and versatile tool in genetic engineering. We review the history of the discovery and characterization of Cre-lox and touch upon the present direction of Cre-lox research.
Flaviviridae Replication Organelles: Oh, What a Tangled Web We Weave
Authors: Paul David , Bartenschlager Ralf
Published: November 2015

Replication of positive-strand RNA viruses occurs in tight association with reorganized host cell membranes. In a concerted fashion, viral and cellular factors generate distinct organelle-like structures, designated viral replication factories. These virus-induced compartments promote highly efficient genome replication, allow spatiotemporal coordination of the different steps of the viral replication cycle, and protect viral RNA from the hostile cytoplasmic environment. The combined use of ultrastructural and functional studies has greatly increased our understanding of the architecture and biogenesis of viral replication factories. Here, we review common concepts and distinct differences in replication organelle morphology and biogenesis within the Flaviviridae family, exemplified by dengue virus and hepatitis C virus. We discuss recent progress made in our understanding of the complex interplay between viral determinants and subverted cellular membrane homeostasis in biogenesis and maintenance of replication factories of this virus family.
Retroviral Integrase: Then and Now
Authors: Andrake Mark D. , Skalka Anna Marie
Published: November 2015

The retroviral integrases are virally encoded, specialized recombinases that catalyze the insertion of viral DNA into the host cell's DNA, a process that is essential for virus propagation. We have learned a great deal since the existence of an integrated form of retroviral DNA (the provirus) was first proposed by Howard Temin in 1964. Initial studies focused on the genetics and biochemistry of avian and murine virus DNA integration, but the pace of discovery increased substantially with advances in technology, and an influx of investigators focused on the human immunodeficiency virus. We begin with a brief account of the scientific landscape in which some of the earliest discoveries were made, and summarize research that led to our current understanding of the biochemistry of integration. A more detailed account of recent analyses of integrase structure follows, as they have provided valuable insights into enzyme function and raised important new questions.
Koala Retroviruses: Evolution and Disease Dynamics
Authors: Xu Wenqin , Eiden Maribeth V.
Published: November 2015

A retroviral etiology for malignant neoplasias in koalas has long been suspected. Evidence for retroviral involvement was bolstered in 2000 by the isolation of a koala retrovirus (KoRV), now termed KoRV-A. KoRV-A is an endogenous retrovirus—a retrovirus that infects germ cells—a feature that makes it a permanent resident of the koala genome. KoRV-A lacks the genetic diversity of an exogenous retrovirus, a quality associated with the ability of a retrovirus to cause neoplasias. In 2013, a second KoRV isolate, KoRV-B, was obtained from koalas with lymphomas in the Los Angeles Zoo. Unlike KoRV-A, which is present in the genomes of all koalas in the United States, KoRV-B is restricted in its distribution and is associated with host pathology (neoplastic disease). Here, our current understanding of the evolution of endogenous and exogenous KoRVs, and the relationship between them, is reviewed to build a perspective on the future impact of these viruses on koala sustainability.
Matters of Size: Genetic Bottlenecks in Virus Infection and Their Potential Impact on Evolution
Authors: Zwart Mark P. , Elena Santiago F.
Published: November 2015

For virus infections of multicellular hosts, narrow genetic bottlenecks during transmission and within-host spread appear to be widespread. These bottlenecks will affect the maintenance of genetic variation in a virus population and the prevalence of mixed-strain infections, thereby ultimately determining the strength with which different random forces act during evolution. Here we consider different approaches for estimating bottleneck sizes and weigh their merits. We then review quantitative estimates of bottleneck size during cellular infection, within-host spread, horizontal transmission, and finally vertical transmission. In most cases we find that bottlenecks do regularly occur, although in many cases they appear to be virion-concentration dependent. Finally, we consider the evolutionary implications of genetic bottlenecks during virus infection. Although on average strong bottlenecks will lead to declines in fitness, we consider a number of scenarios in which bottlenecks could also be advantageous for viruses.
Continuous and Discontinuous RNA Synthesis in Coronaviruses
Authors: Sola Isabel , Almazán Fernando , Zúñiga Sonia , Enjuanes Luis
Published: November 2015

Replication of the coronavirus genome requires continuous RNA synthesis, whereas transcription is a discontinuous process unique among RNA viruses. Transcription includes a template switch during the synthesis of subgenomic negative-strand RNAs to add a copy of the leader sequence. Coronavirus transcription is regulated by multiple factors, including the extent of base-pairing between transcription-regulating sequences of positive and negative polarity, viral and cell protein–RNA binding, and high-order RNA-RNA interactions. Coronavirus RNA synthesis is performed by a replication-transcription complex that includes viral and cell proteins that recognize cis-acting RNA elements mainly located in the highly structured 5′ and 3′ untranslated regions. In addition to many viral nonstructural proteins, the presence of cell nuclear proteins and the viral nucleocapsid protein increases virus amplification efficacy. Coronavirus RNA synthesis is connected with the formation of double-membrane vesicles and convoluted membranes. Coronaviruses encode proofreading machinery, unique in the RNA virus world, to ensure the maintenance of their large genome size.