bluuebunny/crossref_metadata_2025 huggingface dataset:
High‐throughput sequencing of cerebrospinal fluid for diagnosis of chronic Propionibacterium acnes meningitis in an allogeneic stem cell transplant recipient
Authors: Wylie K.M. , Blanco‐Guzman M. , Wylie T.N. , Lawrence S.J. , Ghobadi A. , DiPersio J.F. , Storch G.A.
Published: February 2016

Background

A 40‐year‐old man with chronic myelogenous leukemia presented multiple times over a period of 3 years with episodes of confusion, wide‐based gait and falls because of recurrent hydrocephalus despite repeated therapeutic lumbar punctures. These problems occurred in the context of persistent cerebrospinal fluid (CSF) pleocytosis and leptomeningeal enhancement. Extensive diagnostic workups and therapeutic trials had failed to identify a clinically plausible cause or produce any significant improvement in the CSF and neuroimaging abnormalities.

Methods

We used high‐throughput metagenomic shotgun sequencing to identify microbes in 2 CSF samples collected from the patient during his illness. These results were compared to sequence data from 1 CSF sample collected during treatment and 5 control CSF samples from other patients.

Results

We found sequences representing 53% and 67% of the Propionibacterium acnes genome in 2 CSF samples collected from the patient during his illness. Directed antimicrobial therapy was administered for 6 weeks with resolution of CSF and neuroimaging abnormalities. Sequencing of a sample obtained during treatment demonstrated that the P. acnes levels were decreased to background levels. After insertion of a ventriculo‐peritoneal shunt, the patient returned to baseline status.

Conclusions

High‐throughput metagenomic shotgun sequencing revealed P. acnes as the cause of chronic meningitis that had eluded conventional attempts at diagnosis. Treatment directed at this organism resulted in cure of the infection and clinical improvement.
Experimental transfusion‐induced Babesia microti infection: dynamics of parasitemia and immune responses in a rhesus macaque model
Authors: Gumber Sanjeev , Nascimento Fernanda S. , Rogers Kenneth A. , Bishop Henry S. , Rivera Hilda N. , Xayavong Maniphet V. , Devare Sushil G. , Schochetman Gerald , Amancha Praveen K. , Qvarnstrom Yvonne , Wilkins Patricia P. , Villinger François
Published: February 2016

BACKGROUND

Babesiosis is an emerging tick‐borne infection in humans. The increasing numbers of reported cases of transfusion‐associated babesiosis (TAB), primarily caused by Babesia microti, represents a concern for the safety of the US blood supply.

STUDY DESIGN AND METHODS

This study investigated kinetics of parasitemia and innate immune responses and dynamics of antibody responses during B. microti infection in rhesus macaques (RMs) using blood smears, quantitative polymerase chain reaction (qPCR), flow cytometry, and indirect fluorescent antibody testing. A total of six monkeys were transfused with either hamster or monkey‐passaged B. microti–infected red blood cells (two and four monkeys, respectively) simulating TAB.

RESULTS

The prepatent period in monkeys inoculated with hamster‐passaged B. microti was 35 days compared with 4 days in monkeys transfused with monkey‐passaged B. microti; the latter monkeys also had markedly higher parasitemia levels. The duration of the window period from the first detected parasitemia by qPCR analysis to the first detected antibody response ranged from 10 to 17 days. Antibody responses fluctuated during the course of the infection. Innate responses assessed by the frequencies of monocytes and activated B cells correlated with the kinetics and magnitude of parasitemia. On Day 14, additional activation peaks were noted for CD14+CD16+ and CD14–CD16+ monocytes and for CD11c+ myeloid dendritic cells, but only in animals transfused with monkey‐passaged B. microti. Parasitemia persisted in these immunocompetent animals, similar to human infection.

CONCLUSION

The results suggest that transfusion‐associated transmission of B. microti leads to rapid onset of parasitemia (Day 4) in RMs, detectable antibody response 14 days later, and persistent parasitemia.
Epidemiology of Toxocariasis in England and Wales
Authors: Halsby K. , Senyonjo L. , Gupta S. , Ladbury G. , Suvari M. , Chiodini P. , Morgan D.
Published: February 2016

Toxocara infection occurs through ingestion of parasite eggs excreted by dogs and cats, and can cause severe morbidity. The burden of disease in England and Wales is not well described, and the impact of public health campaigns conducted in the mid‐1990s is uncertain. This paper uses data from two extensive databases to explore the trends in this disease in England and Wales from the 1970s to 2009.
Invasive Pasteurella multocida Infections – Report of Five Cases at a Minnesota Hospital, 2014
Authors: Talley P. , Snippes‐Vagnone P. , Smith K.
Published: February 2016

During October 2014, the Minnesota Department of Health was notified of five Hospital A patients with Pasteurella multocida bacteraemia; three had died. Human soft tissue infection with P. multocida typically results from cat or dog bites or scratches. Invasive infection, defined as a P. multocida isolate from a usually sterile site, is rare. We evaluated P. multocida isolations at Hospital A, compared with other Minnesota hospitals to understand invasive infection trends. A case was defined as clinically confirmed P. multocida in a Minnesota resident during 2012–2014. All hospital laboratories were queried; Fisher's exact test was used for comparison. Medical charts were reviewed for 2014 Hospital A patients with P. multocida infections. The Minnesota clinical laboratories survey response rate was 79% (63/80). At Hospital A, proportion of P. multocida isolates from usually sterile sites increased from 0% (0/2) during 2012 to 11% (1/9) during 2013, and to 86% (5/6) during 2014. The proportion of patients with P. multocida isolated from sterile sites was 35% (6/17) at Hospital A compared with 10% (58/583) statewide during 2012–2014 combined (P < 0.05). Among 2014 Hospital A patients with invasive P. multocida infection, all five were men; median age was 70 (range: 44–78) years. Four were temporally clustered within a 33‐day period; three of those had bacteraemia on admission, making hospital acquisition possible in only one. Among five bacteraemia patients, four had cirrhosis and/or skin ulcerations, and three died. The proportion of invasive P. multocida cases was substantially higher at Hospital A during 2014. No epidemiologic links between patients were found. Three had known pet exposure. Collaborative educational efforts of chronically ill pet owners by physicians and veterinarians can acknowledge the health benefits of pet ownership, while minimizing risk for serious invasive zoonotic infections, including those caused by P. multocida.
An acoustic study of nasal consonants in three Central Australian languages
Authors: Tabain Marija , Butcher Andrew , Breen Gavan , Beare Richard
Published: February 2016

This study presents nasal consonant data from 21 speakers of three Central Australian languages: Arrernte, Pitjantjatjara and Warlpiri. The six nasals considered are bilabial /m/, dental /n/, alveolar /n/, retroflex /ɳ/, alveo-palatal /ɲ/, and velar /ŋ/. Nasal formant and bandwidth values are examined, as are the locations of spectral minima. Several differences are found between the bilabial /m/ and the velar /ŋ/, and also the palatal /ɲ/. The remaining coronal nasals /n n ɳ/ are not well differentiated within the nasal murmur, but their average bandwidths are lower than for the other nasal consonants. Broader spectral shape measures (Centre of Gravity and Standard Deviation) are also considered, and comparisons are made with data for stops and laterals in these languages based on the same spectral measures. It is suggested that nasals are not as easily differentiated using the various measures examined here as are stops and laterals. It is also suggested that existing models of nasal consonants do not fully account for the observed differences between the various nasal places of articulation; and that oral formants, in addition to anti-formants, contribute substantially to the output spectrum of nasal consonants.
The pace of plant community change is accelerating in remnant prairies
Authors: Alstad Amy O. , Damschen Ellen I. , Givnish Thomas J. , Harrington John A. , Leach Mark K. , Rogers David A. , Waller Donald M.
Published: February 2016

Long-term legacy data reveal that the pace of plant community change in remnant prairies has accelerated.
Tomographic reconstruction of circularly polarized high-harmonic fields: 3D attosecond metrology
Authors: Chen Cong , Tao Zhensheng , Hernández-García Carlos , Matyba Piotr , Carr Adra , Knut Ronny , Kfir Ofer , Zusin Dimitry , Gentry Christian , Grychtol Patrik , Cohen Oren , Plaja Luis , Becker Andreas , Jaron-Becker Agnieszka , Kapteyn Henry , Murnane Margaret
Published: February 2016

Circularly polarized attosecond pulse trains in the EUV region were reconstructed using 3D attosecond metrology.
Reconsidering plant memory: Intersections between stress recovery, RNA turnover, and epigenetics
Authors: Crisp Peter A. , Ganguly Diep , Eichten Steven R. , Borevitz Justin O. , Pogson Barry J.
Published: February 2016

Have plants learned to forget stress? This review proposes benefits to forgetfulness and finds key roles for RNA turnover.
Effect of Dietary Oxalate on the Gut Microbiota of the Mammalian Herbivore Neotoma albigula
Authors: Miller Aaron W. , Oakeson Kelly F. , Dale Colin , Dearing M. Denise
Published: February 2016

Diet is one of the primary drivers that sculpts the form and function of the mammalian gut microbiota. However, the enormous taxonomic and metabolic diversity held within the gut microbiota makes it difficult to isolate specific diet-microbe interactions. The objective of the current study was to elucidate interactions between the gut microbiota of the mammalian herbivore
Neotoma albigula
and dietary oxalate, a plant secondary compound (PSC) degraded exclusively by the gut microbiota. We quantified oxalate degradation in
N. albigula
fed increasing amounts of oxalate over time and tracked the response of the fecal microbiota using high-throughput sequencing. The amount of oxalate degraded
in vivo
was linearly correlated with the amount of oxalate consumed. The addition of dietary oxalate was found to impact microbial species diversity by increasing the representation of certain taxa, some of which are known to be capable of degrading oxalate (e.g.,
Oxalobacter
spp.). Furthermore, the relative abundances of 117 operational taxonomic units (OTU) exhibited a significant correlation with oxalate consumption. The results of this study indicate that dietary oxalate induces complex interactions within the gut microbiota that include an increase in the relative abundance of a community of bacteria that may contribute either directly or indirectly to oxalate degradation in mammalian herbivores.
Metagenomic Analyses of the Autotrophic Fe(II)-Oxidizing, Nitrate-Reducing Enrichment Culture KS
Authors: He Shaomei , Tominski Claudia , Kappler Andreas , Behrens Sebastian , Roden Eric E.
Published: February 2016

Nitrate-dependent ferrous iron [Fe(II)] oxidation (NDFO) is a well-recognized chemolithotrophic pathway in anoxic sediments. The neutrophilic chemolithoautotrophic enrichment culture KS originally obtained from a freshwater sediment (K. L. Straub, M. Benz, B. Schink, and F. Widdel, Appl Environ Microbiol 62:1458–1460, 1996) has been used as a model system to study NDFO. However, the primary Fe(II) oxidizer in this culture has not been isolated, despite extensive efforts to do so. Here, we present a metagenomic analysis of this enrichment culture in order to gain insight into electron transfer pathways and the roles of different bacteria in the culture. We obtained a near-complete genome of the primary Fe(II) oxidizer, a species in the family
Gallionellaceae
, and draft genomes from its flanking community members. A search of the putative extracellular electron transfer pathways in these genomes led to the identification of a homolog of the MtoAB complex [a porin-multiheme cytochrome
c
system identified in neutrophilic microaerobic Fe(II)-oxidizing
Sideroxydans lithotrophicus
ES-1] in a
Gallionellaceae
sp., and findings of other putative genes involving cytochrome
c
and multicopper oxidases, such as Cyc2 and OmpB. Genome-enabled metabolic reconstruction revealed that this
Gallionellaceae
sp. lacks nitric oxide and nitrous oxide reductase genes and may partner with flanking populations capable of complete denitrification to avoid toxic metabolite accumulation, which may explain its resistance to growth in pure culture. This and other revealed interspecies interactions and metabolic interdependencies in nitrogen and carbon metabolisms may allow these organisms to cooperate effectively to achieve robust chemolithoautotrophic NDFO. Overall, the results significantly expand our knowledge of NDFO and suggest a range of genetic targets for further exploration.
Functional Metagenomics of a Biostimulated Petroleum-Contaminated Soil Reveals an Extraordinary Diversity of Extradiol Dioxygenases
Authors: Terrón-González Laura , Martín-Cabello Guadalupe , Ferrer Manuel , Santero Eduardo
Published: February 2016

A metagenomic library of a petroleum-contaminated soil was constructed in a fosmid vector that allowed heterologous expression of metagenomic DNA. The library, consisting of 6.5 Gb of metagenomic DNA, was screened for extradiol dioxygenase (Edo) activity using catechol and 2,3-dihydroxybiphenyl as the substrates. Fifty-eight independent clones encoding extradiol dioxygenase activity were identified. Forty-one different Edo-encoding genes were identified. The population of Edo genes was not dominated by a particular gene or by highly similar genes; rather, the genes had an even distribution and high diversity. Phylogenetic analyses revealed that most of the genes could not be ascribed to previously defined subfamilies of Edos. Rather, the Edo genes led to the definition of 10 new subfamilies of type I Edos. Phylogenetic analysis of type II enzymes defined 7 families, 2 of which harbored the type II Edos that were found in this work. Particularly striking was the diversity found in family I.3 Edos; 15 out of the 17 sequences assigned to this family belonged to 7 newly defined subfamilies. A strong bias was found that depended on the substrate used for the screening: catechol mainly led to the detection of Edos belonging to the I.2 family, while 2,3-dihydroxybiphenyl led to the detection of most other Edos. Members of the I.2 family showed a clear substrate preference for monocyclic substrates, while those from the I.3 family showed a broader substrate range and high activity toward 2,3-dihydroxybiphenyl. This metagenomic analysis has substantially increased our knowledge of the existing biodiversity of Edos.
Oxidation of Molecular Hydrogen by a Chemolithoautotrophic Beggiatoa Strain
Authors: Kreutzmann Anne-Christin , Schulz-Vogt Heide N.
Published: February 2016

A chemolithoautotrophic strain of the family
Beggiatoaceae
,
Beggiatoa
sp. strain 35Flor, was found to oxidize molecular hydrogen when grown in a medium with diffusional gradients of oxygen, sulfide, and hydrogen. Microsensor profiles and rate measurements suggested that the strain oxidized hydrogen aerobically when oxygen was available, while hydrogen consumption under anoxic conditions was presumably driven by sulfur respiration.
Beggiatoa
sp. 35Flor reached significantly higher biomass in hydrogen-supplemented oxygen-sulfide gradient media, but hydrogen did not support growth of the strain in the absence of reduced sulfur compounds. Nevertheless, hydrogen oxidation can provide
Beggiatoa
sp. 35Flor with energy for maintenance and assimilatory purposes and may support the disposal of internally stored sulfur to prevent physical damage resulting from excessive sulfur accumulation. Our knowledge about the exposure of natural populations of
Beggiatoaceae
to hydrogen is very limited, but significant amounts of hydrogen could be provided by nitrogen fixation, fermentation, and geochemical processes in several of their typical habitats such as photosynthetic microbial mats and submarine sites of hydrothermal fluid flow.

IMPORTANCE
Reduced sulfur compounds are certainly the main electron donors for chemolithoautotrophic
Beggiatoaceae
, but the traditional focus on this topic has left other possible inorganic electron donors largely unexplored. In this paper, we provide evidence that hydrogen oxidation has the potential to strengthen the ecophysiological plasticity of
Beggiatoaceae
in several ways. Moreover, we show that hydrogen oxidation by members of this family can significantly influence biogeochemical gradients and therefore should be considered in environmental studies.
Complementary Microorganisms in Highly Corrosive Biofilms from an Offshore Oil Production Facility
Authors: Vigneron Adrien , Alsop Eric B. , Chambers Brian , Lomans Bartholomeus P. , Head Ian M. , Tsesmetzis Nicolas
Published: February 2016

Offshore oil production facilities are frequently victims of internal piping corrosion, potentially leading to human and environmental risks and significant economic losses. Microbially influenced corrosion (MIC) is believed to be an important factor in this major problem for the petroleum industry. However, knowledge of the microbial communities and metabolic processes leading to corrosion is still limited. Therefore, the microbial communities from three anaerobic biofilms recovered from the inside of a steel pipe exhibiting high corrosion rates, iron oxide deposits, and substantial amounts of sulfur, which are characteristic of MIC, were analyzed in detail. Bacterial and archaeal community structures were investigated by automated ribosomal intergenic spacer analysis, multigenic (16S rRNA and functional genes) high-throughput Illumina MiSeq sequencing, and quantitative PCR analysis. The microbial community analysis indicated that bacteria, particularlyDesulfovibriospecies, dominated the biofilm microbial communities. However, other bacteria, such asPelobacter,Pseudomonas, andGeotoga, as well as various methanogenic archaea, previously detected in oil facilities were also detected. The microbial taxa and functional genes identified suggested that the biofilm communities harbored the potential for a number of different but complementary metabolic processes and that MIC in oil facilities likely involves a range of microbial metabolisms such as sulfate, iron, and elemental sulfur reduction. Furthermore, extreme corrosion leading to leakage and exposure of the biofilms to the external environment modify the microbial community structure by promoting the growth of aerobic hydrocarbon-degrading organisms.
Engineering Escherichia coli for Microbial Production of Butanone
Authors: Srirangan Kajan , Liu Xuejia , Akawi Lamees , Bruder Mark , Moo-Young Murray , Chou C. Perry
Published: February 2016

To expand the chemical and molecular diversity of biotransformation using whole-cell biocatalysts, we genetically engineered a pathway in
Escherichia coli
for heterologous production of butanone, an important commodity ketone. First, a 1-propanol-producing
E. coli
host strain with its sleeping beauty mutase (Sbm) operon being activated was used to increase the pool of propionyl-coenzyme A (propionyl-CoA). Subsequently, molecular heterofusion of propionyl-CoA and acetyl-CoA was conducted to yield 3-ketovaleryl-CoA via a CoA-dependent elongation pathway. Lastly, 3-ketovaleryl-CoA was channeled into the clostridial acetone formation pathway for thioester hydrolysis and subsequent decarboxylation to form butanone. Biochemical, genetic, and metabolic factors affecting relative levels of ketogenesis, acidogenesis, and alcohologenesis under selected fermentative culture conditions were investigated. Using the engineered
E. coli
strain for batch cultivation with 30 g liter
−1
glycerol as the carbon source, we achieved coproduction of 1.3 g liter
−1
butanone and 2.9 g liter
−1
acetone. The results suggest that approximately 42% of spent glycerol was utilized for ketone biosynthesis, and thus they demonstrate potential industrial applicability of this microbial platform.
Mechanisms of Bacterial (Serratia marcescens) Attachment to, Migration along, and Killing of Fungal Hyphae
Authors: Hover Tal , Maya Tal , Ron Sapir , Sandovsky Hani , Shadkchan Yana , Kijner Nitzan , Mitiagin Yulia , Fichtman Boris , Harel Amnon , Shanks Robert M. Q. , Bruna Roberto E. , García-Véscovi Eleonora , Osherov Nir
Published: February 2016

We have found a remarkable capacity for the ubiquitous Gram-negative rod bacteriumSerratia marcescensto migrate along and kill the mycelia of zygomycete molds. This migration was restricted to zygomycete molds and several basidiomycete species. No migration was seen on any molds of the phylum Ascomycota.S. marcescensmigration did not require fungal viability or surrounding growth medium, as bacteria migrated along aerial hyphae as well.S. marcescensdid not exhibit growth tropism toward zygomycete mycelium. Bacterial migration along hyphae proceeded only when the hyphae grew into the bacterial colony.S. marcescenscells initially migrated along the hyphae, forming attached microcolonies that grew and coalesced to generate a biofilm that covered and killed the mycelium. Flagellum-defective strains ofS. marcescenswere able to migrate along zygomycete hyphae, although they were significantly slower than the wild-type strain and were delayed in fungal killing. Bacterial attachment to the mycelium does not necessitate type 1 fimbrial adhesion, since mutants defective in this adhesin migrated equally well as or faster than the wild-type strain. Killing does not depend on the secretion ofS. marcescenschitinases, as mutants in which all three chitinase genes were deleted retained wild-type killing abilities. A better understanding of the mechanisms by whichS. marcescensbinds to, spreads on, and kills fungal hyphae might serve as an excellent model system for such interactions in general; fungal killing could be employed in agricultural fungal biocontrol.
A multidisciplinary approach to the management of traumatic intrusion in immature permanent teeth
Authors: Rai Pritika , Pandey Ramesh Kumar , Khanna Richa
Published: February 2016

Intrusion in a developing permanent tooth is an extremely complicated traumatic injury and is rarely seen in the permanent dentition. The damage caused by the trauma to the surrounding tooth structures results in a multitude of complications during the healing process. Careful repositioning of the intruded tooth by orthodontic means, revascularisation of the immature tooth to regain vitality, and periodontal treatment to provide the most acceptable aesthetic outcome are described in this case report. It outlines the treatment options to overcome the complications and variable outcomes. The present report emphasises the importance of a multidisciplinary approach to provide complete rehabilitation of a traumatically intruded developing tooth.
Pericarditis with anaemia as a herald syndrome in a fatal presentation of cardiac lymphoma
Authors: Sinha Aish , Davies Timothy , Saif Ahmad , Apps Andrew
Published: February 2016

Primary cardiac lymphoma (PCL) is rare, accounting for 2% of all primary cardiac malignancies. Diagnosis is sometimes slow due to the non-specific nature of symptoms, causing a delay to treatment with potentially curative anthracycline chemotherapy. We report an unusual presentation of primary cardiac lymphoma in an immunocompetent man presenting with subacute isolated right-sided heart failure with pericarditis on a background of chronic anaemia and constitutional upset. Echocardiography demonstrated a pericardial mass invading the right atrium and compressing the tricuspid annulus. Diffuse large B-cell lymphoma was diagnosed after biopsy. This case highlights the importance of early imaging and hospitalisation in pericarditis with high-risk features such as high inflammatory markers, myocardial involvement (with troponin elevation), fever, immunosuppression or evidence of heart failure. The differential and diagnostic pathway of an intracardiac mass, and the treatment and prognosis of PCL, are discussed.
Text messaging reminders for influenza vaccine in primary care: a cluster randomised controlled trial (TXT4FLUJAB)
Authors: Herrett Emily , Williamson Elizabeth , van Staa Tjeerd , Ranopa Michael , Free Caroline , Chadborn Tim , Goldacre Ben , Smeeth Liam
Published: February 2016

Objectives

(1) To develop methods for conducting cluster randomised trials of text messaging interventions utilising routine electronic health records at low cost; (2) to assess the effectiveness of text messaging influenza vaccine reminders in increasing vaccine uptake in patients with chronic conditions.

Design

Cluster randomised trial with general practices as clusters.

Setting

English primary care.

Participants

156 general practices, who used text messaging software, who had not previously used text message influenza vaccination reminders. Eligible patients were aged 18–64 in ‘at-risk’ groups.

Interventions

Practices were randomly allocated to either an intervention or standard care arm in the 2013 influenza season (September to December). Practices in the intervention arm were asked to send a text message influenza vaccination reminder to their at-risk patients under 65. Practices in the standard care arm were asked to continue their influenza campaign as planned.

Blinding

Practices were not blinded. Analysis was performed blinded to practice allocation.

Main outcome measures

Practice-level influenza vaccine uptake among at-risk patients aged 18–64 years.

Results

77 practices were randomised to the intervention group (76 analysed, n at-risk patients=51 121), 79 to the standard care group (79 analysed, n at-risk patients=51 136). The text message increased absolute vaccine uptake by 2.62% (95% CI −0.09% to 5.33%), p=0.058, though this could have been due to chance. Within intervention clusters, a median 21.0% (IQR 10.2% to 47.0%) of eligible patients were sent a text message. The number needed to treat was 7.0 (95% CI −0.29 to 14.3).

Conclusions

Patient follow-up using routine electronic health records is a low cost method of conducting cluster randomised trials. Text messaging reminders are likely to result in modest improvements in influenza vaccine uptake, but levels of patients being texted need to markedly increase if text messaging reminders are to have much effect.

Trial registration number

ISRCTN48840025.
STROBE-AMS: recommendations to optimise reporting of epidemiological studies on antimicrobial resistance and informing improvement in antimicrobial stewardship
Authors: Tacconelli Evelina , Cataldo Maria A , Paul M , Leibovici L , Kluytmans Jan , Schröder Wiebke , Foschi Federico , De Angelis Giulia , De Waure Chiara , Cadeddu Chiara , Mutters Nico T , Gastmeier Petra , Cookson Barry
Published: February 2016

Objectives

To explore the accuracy of application of the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) tool in epidemiological studies focused on the evaluation of the role of antibiotics in selecting resistance, and to derive and test an extension of STROBE to improve the suitability of the tool in evaluating the quality of reporting in these area.

Methods

A three-step study was performed. First, a systematic review of the literature analysing the association between antimicrobial exposure and acquisition of methicillin-resistantStaphylococcus aureusand/or multidrug-resistantAcinetobacter baumanniiwas performed. Second, articles were reviewed according to the STROBE checklist for epidemiological studies. Third, a set of potential new items focused on antimicrobial-resistance quality indicators was derived through an expert two-round RAND-modified Delphi procedure and tested on the articles selected through the literature review.

Results

The literature search identified 78 studies. Overall, the quality of reporting appeared to be poor in most areas. Five STROBE items, comprising statistical analysis and study objectives, were satisfactory in <25% of the studies. Informative abstract, reporting of bias, control of confounding, generalisability and description of study size were missing in more than half the articles. A set of 21 new items was developed and tested. The new items focused particularly on the study setting, antimicrobial usage indicators, and patients epidemiological and clinical characteristics. The performance of the new items in included studies was very low (<25%).

Conclusions

Our paper reveals that reporting in epidemiological papers analysing the association between antimicrobial usage and development of resistance is poor. The implementation of the newly developed STROBE for antimicrobial stewardship (AMS) tool should enhance appropriate study design and reporting, and therefore contribute to the improvement of evidence to be used for AMS programme development and assessment.
Germline mutations inPMS2andMLH1in individuals with solitary loss of PMS2 expression in colorectal carcinomas from the Colon Cancer Family Registry Cohort
Authors: Rosty Christophe , Clendenning Mark , Walsh Michael D , Eriksen Stine V , Southey Melissa C , Winship Ingrid M , Macrae Finlay A , Boussioutas Alex , Poplawski Nicola K , Parry Susan , Arnold Julie , Young Joanne P , Casey Graham , Haile Robert W , Gallinger Steven , Le Marchand Loïc , Newcomb Polly A , Potter John D , DeRycke Melissa , Lindor Noralane M , Thibodeau Stephen N , Baron John A , Win Aung Ko , Hopper John L , Jenkins Mark A , Buchanan Daniel D
Published: February 2016

Objectives

Immunohistochemistry for DNA mismatch repair proteins is used to screen for Lynch syndrome in individuals with colorectal carcinoma (CRC). Although solitary loss of PMS2 expression is indicative of carrying a germline mutation inPMS2, previous studies reportedMLH1mutation in some cases. We determined the prevalence ofMLH1germline mutations in a large cohort of individuals with a CRC demonstrating solitary loss ofPMS2expression.

Design

This cohort study included 88 individuals affected with a PMS2-deficient CRC from the Colon Cancer Family Registry Cohort. GermlinePMS2mutation analysis (long-range PCR and multiplex ligation-dependent probe amplification) was followed byMLH1mutation testing (Sanger sequencing and multiplex ligation-dependent probe amplification).

Results

Of the 66 individuals with complete mutation screening, we identified a pathogenicPMS2mutation in 49 (74%), a pathogenicMLH1mutation in 8 (12%) and aMLH1variant of uncertain clinical significance predicted to be damaging by in silico analysis in 3 (4%); 6 (9%) carried variants likely to have no clinical significance. Missense point mutations accounted for most alterations (83%; 9/11) inMLH1. TheMLH1c.113A> G p.Asn38Ser mutation was found in 2 related individuals. One individual who carried theMLH1intronic mutation c.677+3A>G p.Gln197Argfs*8 leading to the skipping of exon 8, developed 2 tumours, both of which retained MLH1 expression.

Conclusions

A substantial proportion of CRCs with solitary loss of PMS2 expression are associated with a deleteriousMLH1germline mutation supporting the screening forMLH1in individuals with tumours of this immunophenotype, when noPMS2mutation has been identified.
Performance and quality indicators for the management of non-cancer chronic pain: a scoping review protocol
Authors: Zidarov Diana , Visca Regina , Gogovor Amédé , Ahmed Sara
Published: February 2016

Introduction

Chronic pain is a public health problem of epidemic proportion in most countries with important physical, psychological, social and economic consequences. The management of chronic pain is complex and requires an integrated network approach between all levels of the healthcare system and the involvement of several health professionals from different disciplines. Measuring the performance of organisations that provide care to individuals with chronic pain is essential to improve quality of care and requires the use of relevant performance and quality indicators. A scoping review methodology will be used to synthesise the evidence on performance and quality indicators developed for non-cancer chronic pain management across the continuum of care.

Methods and analysis

The following electronic databases will be searched from 2000 onwards: Cochrane Effective Practice and Organisation of Care (EPOC) Review Group Specialised Register; Cochrane Library; EMBASE; PubMed; CINAHL; PsycINFO; ProQuest Dissertations and Theses. All types of studies will be included if these are concerned with performance or quality indicators in adults with chronic non-cancer pain. In addition, searches will be conducted on provincial, national and international health organisations as well as health professional and scientific associations’ websites. A qualitative descriptive approach will be used to describe characteristics of each indicator. All identified indicators will be classified according to dimensions covered by Donabedian and the Triple Aim frameworks.

Ethics and dissemination

The scoping review findings will inform the development of a performance measurement system comprising a list of performance indicators with their level of evidence which can be used by stakeholders to evaluate the quality of care for individuals with chronic non-cancer pain at the patient, institutional and system level. The results will be disseminated via several knowledge translation strategies, including 2 stakeholder meetings, publication and presentation at conferences.
Detection rate and predictive factors of sessile serrated polyps in an organised colorectal cancer screening programme with immunochemical faecal occult blood test: the EQuIPE study (Evaluating Quality Indicators of the Performance of Endoscopy)
Authors: Zorzi Manuel , Senore Carlo , Da Re Filippo , Barca Alessandra , Bonelli Luigina Ada , Cannizzaro Renato , de Pretis Giovanni , Di Furia Lucia , Di Giulio Emilio , Mantellini Paola , Naldoni Carlo , Sassatelli Romano , Rex Douglas K , Zappa Marco , Hassan Cesare
Published: February 2016

Objectives

To assess detection rate and predictive factors of sessile serrated polyps (SSPs) in organised colorectal cancer (CRC) screening programmes based on the faecal immunochemical test (FIT).

Design

Data from a case series of colonoscopies of FIT-positive subjects were provided by 44 Italian CRC screening programmes. Data on screening history, endoscopic procedure and histology results, and additional information on the endoscopy centre and the endoscopists were collected, including the age-standardised and sex-standardised adenoma detection rate (ADR) of the individual endoscopists. The SSP detection rate (SSP-DR) was assessed for the study population. To identify SSP-predictive factors, multilevel analyses were performed according to patient/centre/endoscopist characteristics.

Results

We analysed 72 021 colonoscopies, of which 1295 presented with at least one SSP (SSP-DR 1.8%; 95% CI 1.7% to 1.9%). At theper-patientlevel, SSP-DR was associated with males (OR 1.35; 95% CI 1.17 to 1.54) and caecal intubation (OR 3.75; 95% CI 2.22 to 6.34), but not with the FIT round. The presence of at least one advanced adenoma was more frequent among subjects with SSPs than those without (OR 2.08; 95% CI 1.86 to 2.33). At theper-endoscopistlevel, SSP-DR was associated with ADR (third vs first ADR quartile: OR 1.55; 95% CI 1.03 to 2.35; fourth vs first quartile: OR 1.89; 95% CI 1.24 to 2.90).

Conclusion

The low prevalence of SSPs and the lack of association with the FIT round argue against SSP as a suitable target for FIT-based organised programmes. Strict association of SSP-DR with the key colonoscopy quality indicators, namely caecal intubation rate and high ADR further marginalises the need for SSP-specific quality indicators in FIT-based programmes.
The determinants of transitions into sheltered accommodation in later life in England and Wales
Authors: Vlachantoni Athina , Maslovskaya Olga , Evandrou Maria , Falkingham Jane
Published: February 2016

Background

Population ageing is a global challenge and understanding the dynamics of living arrangements in later life and their implications for the design of appropriate housing and long-term care is a critical policy issue. Existing research has focused on the study of transitions into residential care in the UK. This paper investigates transitions into sheltered accommodation among older people in England and Wales between 1993 and 2008.

Methods

The study uses longitudinal data constructed from pooled observations across waves 2–18 of the British Household Panel Survey (BHPS) data, focusing on individuals aged 65 and over who lived in private housing at baseline and who were observed for two consecutive time points. A discrete-time logistic regression model was used to examine the association of transitioning into sheltered accommodation with a range of demographic, health and socioeconomic predictors.

Results

Demographic (age, region), socioeconomic factors (housing tenure, having a washing machine) and contact with health professionals (number of visits to the general practitioner, start in use of health visitor) were significant determinants of an older person's move into sheltered accommodation.

Conclusions

Transitions into sheltered accommodation are associated with a range of demographic and socioeconomic characteristics as well as service use but not with health. Such results indicate that this type of housing option may be accessible by individuals with relatively good health, but may be limited to those who are referred by gatekeepers. Policymakers could consider making such housing option available to everyone, as well as providing incentives for building lifecourse-sensitive housing in the future.
Registry report of structural and functional cardiac abnormalities diagnosed by echocardiography in an asymptomatic population
Authors: Missouris Constantinos G , Okonko Darlington O , Bharucha Apurva , Al-Obaidi Mohamed , Mandal Amit K , Highett-Smith Paul , Singer Donald R J
Published: February 2016

Background

The epidemiology of heart disease is changing, with rheumatic heart disease becoming less common but degenerative valve disorders, heart failure and atrial fibrillation (AF) increasing.

Objective

We sought to determine the prevalence of structural cardiac abnormalities in the apparently symptom-free adult population within our prospective echocardiography (echo) registry.

Methods

Our echo registry comprised echo studies and associated demographic and clinical data obtained prospectively from 362 consecutive asymptomatic subjects aged 50–74 years and without known heart disease referred between 2011 and 2012 from general practices in the South East of England.

Results

221 echo abnormalities were detected in 178 (49%) subjects (46% men; mean (±SD) age 63.9±9.2 years; 98% Caucasian). A major abnormality was detected in seven subjects: four had a large secundum atrial septal defect, one had critical aortic stenosis, one severe mitral regurgitation and one features of hypertrophic cardiomyopathy. Twelve subjects had left ventricular systolic dysfunction with an ejection fraction (EF) <50% (of whom 10 had EF <40%). Four subjects had AF. Minor echo abnormalities were evident in the remaining 171 (47%) subjects. Abnormalities were commoner in patients with cardiovascular risk factors or a history of cardiac disease than in those without (53% vs 38%). In multivariate analyses stratified by gender, for women, increased age (F=33.3, p<0.001) and systolic blood pressure (F=9.2, p=0.003) were associated with abnormal echo findings; for men, increased age (F=12.0, p<0.001) and lower cholesterol (F=4.2, p=0.042) predicted an increase in abnormal findings on echo.

Conclusions

Unrecognised cardiac abnormalities are very common in middle-aged men and women with no overt symptoms. Echo offers the potential to identify the need for early intervention and treatment to improve cardiovascular outcomes.
Dealing with discordance: a novel approach for analysing U–Pb detrital zircon datasets
Authors: Reimink Jesse R. , Davies Joshua H. F. L. , Waldron John W. F. , Rojas Xavier
Published: February 2016

Detrital zircon U–Pb geochronology is a rapidly expanding and useful technique for addressing the sedimentary rock record. However, because of difficulties in evaluating discordant analyses, common in most datasets, a high proportion of results may be discarded. These analyses, if interpreted correctly, can provide valuable information regarding the deformation, alteration or metamorphism of the zircon population, as these events are all capable of producing U–Pb discordance. A novel modelling procedure permits analysis of probabilistic relationships within U–Pb datasets to deconvolve the age information present within discordant analyses by assessing the relative likelihood of potential discordia lines. Additionally, because we retrieve useful information from discordant data, a stricter filter can be used to assess concordance, increasing confidence in those distributions. The validity of this modelling method is demonstrated using two previously published cases from the Caledonide orogen where clearly discordant analyses exist. In the Southern Uplands of Scotland, these analyses indicate resetting of the U–Pb systematics in metasedimentary rocks in the Grampian orogen prior to Ordovician erosion and redeposition. In the second case, from the Greenland Caledonides, discordant data provide additional constraints on previously proposed
in situ
resetting during Scandian deformation and fluid flow events.

Supplementary material:
The code used for writing the model, along with an instruction guide, is available at
http://doi.org/10.6084/m9.figshare.c.2182197
.
New structural and Re–Os geochronological evidence constraining the age of faulting and associated mineralization in the Devonian Orcadian Basin, Scotland
Authors: Dichiarante A. M. , Holdsworth R. E. , Dempsey E. D. , Selby D. , McCaffrey K. J. W. , Michie U. McL. , Morgan G. , Bonniface J.
Published: February 2016

The Devonian Orcadian Basin in northern Scotland belongs to a regionally linked system of post-Caledonian continental basins extending northwards to western Norway and eastern Greenland. Extensional fault systems that cut the Orcadian Basin sequences are commonly assumed to be Devonian, with some limited inversion and reactivation proposed during the Carboniferous and later times. We present a detailed structural study of the regionally recognized fault systems exposed in the Dounreay area of Caithness, which host significant amounts of authigenic mineralization (carbonate, base metal sulphides, bitumen). Structural and microstructural analyses combined with Re–Os geochronology have been used to date syndeformational fault infills (pyrite) suggesting that faulting, brecciation and fluid flow events are likely to have occurred during the Permian (267.5 ± 3.4 [3.5] Ma). Stress inversion of fault slickenline data associated with mineralization suggest NW–SE regional rifting, an episode also recognized farther west in Sutherland. Thus a dominant set of Permian age brittle faults is now recognized along the entire north coast of Scotland, forming part of the regional-scale North Coast Transfer Zone located on the southern margin of the offshore West Orkney Basin.

Supplementary material:
Onshore and offshore fault and fracture lineament data are available at
https://doi.org/10.6084/m9.figshare.c.2182433
.
Fault linkage across weak layers during extension: an experimental approach with reference to the Hoop Fault Complex of the SW Barents Sea
Authors: Gabrielsen Roy H. , Sokoutis Dimitrios , Willingshofer Ernst , Faleide Jan Inge
Published: February 2016

A series of analogue experiments utilizing sequences of sand with interlayered silicone polymer have been performed to investigate the effects of multistage extension on rock sequences of different strength, with particular reference to the Hoop Fault Complex of the Barents Sea.

It was found that the width and style of the graben systems as seen in map view depend strongly on the extension velocity. Wide areas of graben formation are promoted by fast extension, whereas narrowly constrained deep-graben structures are typical of slow extension rates. Furthermore, the decoupling strata are likely to be characterized by flow rather than by distinct detachment faults.

The scaled experiments produced units of contrasting fault frequencies and styles in individual sand layers positioned between layers of silicone polymer. It was also found that the fault segments developed from different levels were related to varying extents (hard-linked, soft-linked, firm-linked, unlinked).

The fault configurations and the general fault pattern obtained in the experiments is similar to that observed in natural faults where salt or unconsolidated mudstone separate sequences of sand.
FGFR1 Induces Glioblastoma Radioresistance through the PLCγ/Hif1α Pathway
Authors: Gouazé-Andersson Valérie , Delmas Caroline , Taurand Marion , Martinez-Gala Judith , Evrard Solène , Mazoyer Sandrine , Toulas Christine , Cohen-Jonathan-Moyal Elizabeth
Published: February 2016

FGF2 signaling in glioblastoma induces resistance to radiotherapy, so targeting FGF2/FGFR pathways might offer a rational strategy for tumor radiosensitization. To investigate this possibility, we evaluated a specific role for FGFR1 in glioblastoma radioresistance as modeled by U87 and LN18 glioblastomas in mouse xenograft models. Silencing FGFR1 decreased radioresistance in a manner associated with radiation-induced centrosome overduplication and mitotic cell death. Inhibiting PLCγ (PLCG1), a downstream effector signaling molecule for FGFR1, was sufficient to produce similar effects, arguing that PLCγ is an essential mediator of FGFR1-induced radioresistance. FGFR1 silencing also reduced expression of HIF1α, which in addition to its roles in hypoxic responses exerts an independent effect on radioresistance. Finally, FGFR1 silencing delayed the growth of irradiated tumor xenografts, in a manner that was associated with reduced HIF1α levels but not blood vessel alterations. Taken together, our results offer a preclinical proof of concept that FGFR1 targeting can degrade radioresistance in glioblastoma, a widespread problem in this tumor, prompting clinical investigations of the use of FGFR1 inhibitors for radiosensitization. Cancer Res; 76(10); 3036–44. ©2016 AACR.
Bap1 Is a Bona Fide Tumor Suppressor: Genetic Evidence from Mouse Models Carrying Heterozygous Germline Bap1 Mutations
Authors: Kadariya Yuwaraj , Cheung Mitchell , Xu Jinfei , Pei Jianming , Sementino Eleonora , Menges Craig W. , Cai Kathy Q. , Rauscher Frank J. , Klein-Szanto Andres J. , Testa Joseph R.
Published: February 2016

Individuals harboring inherited heterozygous germline mutations in BAP1 are predisposed to a range of benign and malignant tumor types, including malignant mesothelioma, melanoma, and kidney carcinoma. However, evidence to support a tumor-suppressive role for BAP1 in cancer remains contradictory. To test experimentally whether BAP1 behaves as a tumor suppressor, we monitored spontaneous tumor development in three different mouse models with germline heterozygous mutations in Bap1, including two models in which the knock-in mutations are identical to those reported in human BAP1 cancer syndrome families. We observed spontaneous malignant tumors in 54 of 93 Bap1-mutant mice (58%) versus 4 of 43 (9%) wild-type littermates. All three Bap1-mutant models exhibited a high incidence and similar spectrum of neoplasms, including ovarian sex cord stromal tumors, lung and mammary carcinomas, and spindle cell tumors. Notably, we also observed malignant mesotheliomas in two Bap1-mutant mice, but not in any wild-type animals. We further confirmed that the remaining wild-type Bap1 allele was lost in both spontaneous ovarian tumors and mesotheliomas, resulting in the loss of Bap1 expression. Additional studies revealed that asbestos exposure induced a highly significant increase in the incidence of aggressive mesotheliomas in the two mouse models carrying clinically relevant Bap1 mutations compared with asbestos-exposed wild-type littermates. Collectively, these findings provide genetic evidence that Bap1 is a bona fide tumor suppressor gene and offer key insights into the contribution of carcinogen exposure to enhanced cancer susceptibility. Cancer Res; 76(9); 2836–44. ©2016 AACR.