bluuebunny/crossref_metadata_2025 huggingface dataset:
Pneumococcal Neuraminidase A (NanA) Promotes Biofilm Formation and Synergizes with Influenza A Virus in Nasal Colonization and Middle Ear Infection
Authors: Wren John T. , Blevins Lance K. , Pang Bing , Basu Roy Ankita , Oliver Melissa B. , Reimche Jennifer L. , Wozniak Jessie E. , Alexander-Miller Martha A. , Swords W. Edward
Published: January 2017

Even in the vaccine era,
Streptococcus pneumoniae
(the pneumococcus) remains a leading cause of otitis media, a significant public health burden, in large part because of the high prevalence of nasal colonization with the pneumococcus in children. The primary pneumococcal neuraminidase, NanA, which is a sialidase that catalyzes the cleavage of terminal sialic acids from host glycoconjugates, is involved in both of these processes. Coinfection with influenza A virus, which also expresses a neuraminidase, exacerbates nasal colonization and disease by
S. pneumoniae
, in part via the synergistic contributions of the viral neuraminidase. The specific role of its pneumococcal counterpart, NanA, in this interaction, however, is less well understood. We demonstrate in a mouse model that NanA-deficient pneumococci are impaired in their ability to cause both nasal colonization and middle ear infection. Coinfection with neuraminidase-expressing influenza virus and
S. pneumoniae
potentiates both colonization and infection but not to wild-type levels, suggesting an intrinsic role of NanA. Using
in vitro
models, we show that while NanA contributes to both epithelial adherence and biofilm viability, its effect on the latter is actually independent of its sialidase activity. These data indicate that NanA contributes both enzymatically and nonenzymatically to pneumococcal pathogenesis and, as such, suggest that it is not a redundant bystander during coinfection with influenza A virus. Rather, its expression is required for the full synergism between these two pathogens.
PBP1B Glycosyltransferase and Transpeptidase Activities Play Different Essential Roles during the
De Novo
Regeneration of Rod Morphology in Escherichia coli
Authors: Ranjit Dev K. , Jorgenson Matthew A. , Young Kevin D.
Published: January 2017

Peptidoglycan is a vital component of nearly all cell wall-bearing bacteria and is a valuable target for antibacterial therapy. However, despite decades of work, there remain important gaps in understanding how this macromolecule is synthesized and molded into a three-dimensional structure that imparts specific morphologies to individual cells. Here, we investigated the particularly enigmatic area of how peptidoglycan is synthesized and shaped during the first stages of creating cell shape
de novo
, that is, in the absence of a preexisting template. We found that when lysozyme-induced (LI) spheroplasts of
Escherichia coli
were allowed to resynthesize peptidoglycan, the cells divided first and then elongated to recreate a normal rod-shaped morphology. Penicillin binding protein 1B (PBP1B) was critical for the first stage of this recovery process. PBP1B synthesized peptidoglycan
de novo
, and this synthesis required that PBP1B interact with the outer membrane lipoprotein LpoB. Surprisingly, when LpoB was localized improperly to the inner membrane, recovering spheroplasts synthesized peptidoglycan and divided but then propagated as amorphous spheroidal cells, suggesting that the regeneration of a normal rod shape depends on a particular spatial interaction. Similarly, spheroplasts carrying a PBP1B variant lacking transpeptidase activity or those in which PBP1A was overproduced could synthesize new peptidoglycan and divide but then grew as oddly shaped spheroids. We conclude that
de novo
cell wall synthesis requires the glycosyltransferase activity of PBP1B but that PBP1B transpeptidase activity is needed to assemble cell walls with wild-type morphology.

IMPORTANCE
Bacterial cell wall peptidoglycan is synthesized and modified by penicillin binding proteins (PBPs), which are targeted by about half of all currently prescribed antibiotics, including penicillin and its derivatives. Because antibiotic resistance is rising, it has become increasingly urgent that we fill the gaps in our knowledge about how PBPs create and assemble this protective wall. We report here that PBP1B plays an essential role in synthesizing peptidoglycan in the absence of a preexisting template: its glycosyltransferase activity is responsible for
de novo
synthesis, while its transpeptidase activity is required to construct cell walls of a specific shape. These results highlight the importance of this enzyme and distinguish its biological roles from those of other PBPs and peptidoglycan synthases.
Rpn (YhgA-Like) Proteins of Escherichia coli K-12 and Their Contribution to RecA-Independent Horizontal Transfer
Authors: Kingston Anthony W. , Ponkratz Christine , Raleigh Elisabeth A.
Published: January 2017

Bacteria use a variety of DNA-mobilizing enzymes to facilitate environmental niche adaptation via horizontal gene transfer. This has led to real-world problems, like the spread of antibiotic resistance, yet many mobilization proteins remain undefined. In the study described here, we investigated the uncharacterized family of YhgA-like transposase_31 (Pfam PF04754) proteins. Our primary focus was the genetic and biochemical properties of the five
Escherichia coli
K-12 members of this family, which we designate RpnA to RpnE, where Rpn represents
r
ecombination-
p
romoting
n
uclease. We employed a conjugal system developed by our lab that demanded RecA-independent recombination following transfer of chromosomal DNA. Overexpression of RpnA (YhgA), RpnB (YfcI), RpnC (YadD), and RpnD (YjiP) increased RecA-independent recombination, reduced cell viability, and induced the expression of reporter of DNA damage. For the exemplar of the family, RpnA, mutational changes in proposed catalytic residues reduced or abolished all three phenotypes in concert.
In vitro
, RpnA displayed magnesium-dependent, calcium-stimulated DNA endonuclease activity with little, if any, sequence specificity and a preference for double-strand cleavage. We propose that Rpn/YhgA-like family nucleases can participate in gene acquisition processes.

IMPORTANCE
Bacteria adapt to new environments by obtaining new genes from other bacteria. Here, we characterize a set of genes that can promote the acquisition process by a novel mechanism. Genome comparisons had suggested the horizontal spread of the genes for the YhgA-like family of proteins through bacteria. Although annotated as transposase_31, no member of the family has previously been characterized experimentally. We show that four
Escherichia coli
K-12 paralogs contribute to a novel RecA-independent recombination mechanism
in vivo
. For RpnA, we demonstrate
in vitro
action as a magnesium-dependent, calcium-stimulated nonspecific DNA endonuclease. The cleavage products are capable of providing priming sites for DNA polymerase, which can enable DNA joining by primer-template switching.
Comprehensive Essentiality Analysis of the
Mycobacterium tuberculosis
Genome via Saturating Transposon Mutagenesis
Authors: DeJesus Michael A. , Gerrick Elias R. , Xu Weizhen , Park Sae Woong , Long Jarukit E. , Boutte Cara C. , Rubin Eric J. , Schnappinger Dirk , Ehrt Sabine , Fortune Sarah M. , Sassetti Christopher M. , Ioerger Thomas R.
Published: January 2017

For decades, identifying the regions of a bacterial chromosome that are necessary for viability has relied on mapping integration sites in libraries of random transposon mutants to find loci that are unable to sustain insertion. To date, these studies have analyzed subsaturated libraries, necessitating the application of statistical methods to estimate the likelihood that a gap in transposon coverage is the result of biological selection and not the stochasticity of insertion. As a result, the essentiality of many genomic features, particularly small ones, could not be reliably assessed. We sought to overcome this limitation by creating a completely saturated transposon library in
Mycobacterium tuberculosis
. In assessing the composition of this highly saturated library by deep sequencing, we discovered that a previously unknown sequence bias of the
Himar1
element rendered approximately 9% of potential TA dinucleotide insertion sites less permissible for insertion. We used a hidden Markov model of essentiality that accounted for this unanticipated bias, allowing us to confidently evaluate the essentiality of features that contained as few as 2 TA sites, including open reading frames (ORF), experimentally identified noncoding RNAs, methylation sites, and promoters. In addition, several essential regions that did not correspond to known features were identified, suggesting uncharacterized functions that are necessary for growth. This work provides an authoritative catalog of essential regions of the
M. tuberculosis
genome and a statistical framework for applying saturating mutagenesis to other bacteria.

IMPORTANCE
Sequencing of transposon-insertion mutant libraries has become a widely used tool for probing the functions of genes under various conditions. The
Himar1
transposon is generally believed to insert with equal probabilities at all TA dinucleotides, and therefore its absence in a mutant library is taken to indicate biological selection against the corresponding mutant. Through sequencing of a saturated Himar1 library, we found evidence that TA dinucleotides are not equally permissive for insertion. The insertion bias was observed in multiple prokaryotes and influences the statistical interpretation of transposon insertion (TnSeq) data and characterization of essential genomic regions. Using these insights, we analyzed a fully saturated TnSeq library for
M. tuberculosis
, enabling us to generate a comprehensive catalog of
in vitro
essentiality, including ORFs smaller than those found in any previous study, small (noncoding) RNAs (sRNAs), promoters, and other genomic features.
Identification of Glutaminyl Cyclase Genes Involved in Pyroglutamate Modification of Fungal Lignocellulolytic Enzymes
Authors: Wu Vincent W. , Dana Craig M. , Iavarone Anthony T. , Clark Douglas S. , Glass N. Louise
Published: January 2017

The breakdown of plant biomass to simple sugars is essential for the production of second-generation biofuels and high-value bioproducts. Currently, enzymes produced from filamentous fungi are used for deconstructing plant cell wall polysaccharides into fermentable sugars for biorefinery applications. A post-translational N-terminal pyroglutamate modification observed in some of these enzymes occurs when N-terminal glutamine or glutamate is cyclized to form a five-membered ring. This modification has been shown to confer resistance to thermal denaturation for CBH-1 and EG-1 cellulases. In mammalian cells, the formation of pyroglutamate is catalyzed by glutaminyl cyclases. Using the model filamentous fungus
Neurospora crassa
, we identified two genes (
qc
-
1
and
qc
-
2
) that encode proteins homologous to mammalian glutaminyl cyclases. We show that
qc
-
1
and
qc
-
2
are essential for catalyzing the formation of an N-terminal pyroglutamate on CBH-1 and GH5-1. CBH-1 and GH5-1 produced in a
Δqc
-
1 Δqc
-
2
mutant, and thus lacking the N-terminal pyroglutamate modification, showed greater sensitivity to thermal denaturation, and for GH5-1, susceptibility to proteolytic cleavage. QC-1 and QC-2 are endoplasmic reticulum (ER)-localized proteins. The pyroglutamate modification is predicted to occur in a number of additional fungal proteins that have diverse functions. The identification of glutaminyl cyclases in fungi may have implications for production of lignocellulolytic enzymes, heterologous expression, and biotechnological applications revolving around protein stability.

IMPORTANCE
Pyroglutamate modification is the post-translational conversion of N-terminal glutamine or glutamate into a cyclized amino acid derivative. This modification is well studied in animal systems but poorly explored in fungal systems. In
Neurospora crassa
, we show that this modification takes place in the ER and is catalyzed by two well-conserved enzymes, ubiquitously conserved throughout the fungal kingdom. We demonstrate that the modification is important for the structural stability and aminopeptidase resistance of CBH-1 and GH5-1, two important cellulase enzymes utilized in industrial plant cell wall deconstruction. Many additional fungal proteins predicted in the genome of
N. crassa
and other filamentous fungi are predicted to carry an N-terminal pyroglutamate modification. Pyroglutamate addition may also be a useful way to stabilize secreted proteins and peptides, which can be easily produced in fungal production systems.
Dual sensory impairment in special schools in South-Eastern Nigeria
Authors: Aghaji Ada E , Bowman Richard , Ofoegbu Vincent C , Smith Andrew
Published: January 2017

In a cross-sectional study to determine the magnitude of dual sensory impairment (DSI-combined hearing and vision loss) in children in single-disability special education schools, children in schools for the blind and schools for the deaf in four states in South-East Nigeria were examined by an ophthalmologist and otorhinolaryngologist to determine the level of their disability and to identify other disabilities if any. Participants were all students with childhood blindness or childhood deafness. The magnitude and causes of DSI and the burden of undetected DSI were the main outcome measures. A total of 273 students were examined. About 7% of these students had DSI out of which over 60% (12/19) was previously undetected. There was more DSI in the blind schools than in the deaf schools (p=0.003). There is a large burden of undetected DSI in children in special schools in Nigeria. There is a need to create awareness of this problem and advocate appropriate screening, rehabilitative and educational strategies for children who have it.
Stentriever thrombectomy with distal protection device for carotid free floating thrombus: a technical case report
Authors: Giragani Suresh , Balani Ankit , Agrawal Vikas
Published: January 2017

We report the clinical details, imaging findings and management of a 45-year-old man who presented with recurrent transient ischemic attacks due to carotid free floating thrombus. Free floating thrombus of the carotid artery is a very rare condition with a high risk of distal embolic shower. The optimal treatment options are debatable and include medical management, surgical thrombectomy and endovascular thrombectomy. We describe the use of a stentriever with filter protection in the management of carotid free floating thrombus as a novel treatment option.
Acute mania after levothyroxine replacement for hypothyroid-induced heart block
Authors: Yu Marc Gregory , Flores Karen Marie , Isip-Tan Iris Thiele
Published: January 2017

Psychiatric disturbances can manifest after levothyroxine (LT4) treatment for severe hypothyroidism. We present the case of a young Filipino man with Hashimoto's thyroiditis and high-grade heart block, who was given a full replacement LT4 dose on admission. Twenty-four hours after this dose, he developed manic symptoms, which were addressed with sedatives and neuroleptics with gradual restoration of euthymia the following day. A comprehensive workup did not reveal any findings suggestive of another aetiology for either mania or heart block. We ultimately ascribed the mania as secondary to LT4, and the heart block to hypothyroidism. Although mania is more likely to be precipitated by high starting LT4 doses, reports have shown that symptoms can still arise even at lower doses and with more gradual titration, especially in long-standing hypothyroidism.
Natural language processing to extract symptoms of severe mental illness from clinical text: the Clinical Record Interactive Search Comprehensive Data Extraction (CRIS-CODE) project
Authors: Jackson Richard G , Patel Rashmi , Jayatilleke Nishamali , Kolliakou Anna , Ball Michael , Gorrell Genevieve , Roberts Angus , Dobson Richard J , Stewart Robert
Published: January 2017

Objectives

We sought to use natural language processing to develop a suite of language models to capture key symptoms of severe mental illness (SMI) from clinical text, to facilitate the secondary use of mental healthcare data in research.

Design

Development and validation of information extraction applications for ascertaining symptoms of SMI in routine mental health records using the Clinical Record Interactive Search (CRIS) data resource; description of their distribution in a corpus of discharge summaries.

Setting

Electronic records from a large mental healthcare provider serving a geographic catchment of 1.2 million residents in four boroughs of south London, UK.

Participants

The distribution of derived symptoms was described in 23 128 discharge summaries from 7962 patients who had received an SMI diagnosis, and 13 496 discharge summaries from 7575 patients who had received a non-SMI diagnosis.

Outcome measures

Fifty SMI symptoms were identified by a team of psychiatrists for extraction based on salience and linguistic consistency in records, broadly categorised under positive, negative, disorganisation, manic and catatonic subgroups. Text models for each symptom were generated using the TextHunter tool and the CRIS database.

Results

We extracted data for 46 symptoms with a median F1 score of 0.88. Four symptom models performed poorly and were excluded. From the corpus of discharge summaries, it was possible to extract symptomatology in 87% of patients with SMI and 60% of patients with non-SMI diagnosis.

Conclusions

This work demonstrates the possibility of automatically extracting a broad range of SMI symptoms from English text discharge summaries for patients with an SMI diagnosis. Descriptive data also indicated that most symptoms cut across diagnoses, rather than being restricted to particular groups.
Clinical management of unruptured intracranial aneurysm in Germany: a nationwide observational study over a 5-year period (2005–2009)
Authors: Walendy Victor , Stang Andreas
Published: January 2017

Objectives

Our aim was to provide nationwide age-standardised rates (ASR) on the usage of endovascular coiling and neurosurgical clipping for unruptured intracranial aneurysm (UIA) treatment in Germany.

Setting

Nationwide observational study using the Diagnosis-Related-Groups (DRG) statistics for the years 2005–2009 (overall 83 million hospitalisations).

Participants

From 2005 to 2009, overall 39 155 hospitalisations with a diagnosis of UIA occurred in Germany.

Primary outcome measures

Age-specific and age-standardised hospitalisation rates for UIA with the midyear population of Germany in 2007 as the standard.

Results

Of the 10 221 hospitalisations with UIA during the observation period, 6098 (59.7%) and 4123 (40.3%) included coiling and clipping, respectively. Overall hospitalisation rates for UIA increased by 39.5% (95% CI 24.7% to 56.0%) and 50.4% (95% CI 39.6% to 62.1%) among men and women, respectively. In 2005, the ASR per 100 000 person years for coiling was 0.7 (95% CI 0.62 to 0.78) for men and 1.7 (95% CI 1.58 to 1.82) for women. In 2009, the ASR was 1.0 (95% CI 0.90 to 1.10) and 2.4 (95% CI 2.24 to 2.56), respectively. Similarly, the ASR for clipping in 2005 amounted to 0.6 (95% CI 0.52 to 0.68) for men and 1.1 (95% CI 1.00 to 1.20) for women. These rates increased in 2009 to 0.8 (95% CI 0.72 to 0.88) and 1.7 (95% CI 1.58 to 1.82), respectively. We observed a marked geographical variation of ASR for coiling and less pronounced for clipping. For the federal state of Saarland, the ASR for coiling was 5.64 (95% CI 4.76 to 6.52) compared with 0.68 (95% CI 0.48 to 0.88; per 100 000 person years) in Saxony-Anhalt, whereas, ASR for clipping were highest in Rhineland-Palatinate (2.48, 95% CI 2.17 to 4.75) and lowest in Saxony-Anhalt (0.52, 95% CI 0.34 to 0.70).

Conclusions

To the best of our knowledge, we presented the first representative, nationwide analysis of the clinical management of UIA in Germany. The ASR increased markedly and showed substantial geographical variation among federal states for all treatment modalities during the observation period.
Understanding the importance of therapeutic relationships in the development of self-management behaviours during cancer rehabilitation: a qualitative research protocol
Authors: Wilkinson Wendy M , Rance Jaynie , Fitzsimmons Deborah
Published: January 2017

Introduction

Cancer is a growing health, social and economic problem. 1 in 3 people in the UK will develop cancer in their lifetime. With survival rates rising to over 50%, the long-term needs of cancer survivors are of growing importance. Cancer rehabilitation is tailored to address the physical or psychosocial decline in ability to engage in daily activities. Its use is supported by high-quality international, multicentre research. Incorporating strategies for self-management behaviour development into rehabilitation can prepare individuals for cancer survivorship. However, healthcare professionals will need to adjust their therapeutic interactions accordingly. Research is yet to clarify the impact of the therapeutic relationship on rehabilitation outcomes in cancer. This study aims to explore the impact of therapeutic relationships on self-management behaviours after cancer.

Methods and analysis

This qualitative study aims to understand cancer rehabilitation participants’ beliefs regarding the importance of therapeutic relationships in developing self-management behaviours. A sample representative of a local cancer rehabilitation cohort will be asked to complete a semistructured interview to identify their perspectives on the importance of therapeutic relationships in cancer rehabilitation. Data obtained from the interviews will be analysed, coded and entered into a Delphi questionnaire for circulation to a local cancer rehabilitation population to determine if the views expressed by the interviewees are supported by group consensus.

Ethics and dissemination

This study was approved by Wales Research Ethics Committee 6 (15/WA/0331) in April 2016. Findings will be disseminated through the first author's doctoral thesis; peer-reviewed journals; local, national and international conference presentations; and public events involving research participants and the general public.
Factors predicting antibiotic prescription and referral to hospital for children with respiratory symptoms: secondary analysis of a randomised controlled study at out-of-hours services in primary care
Authors: Rebnord Ingrid Keilegavlen , Sandvik Hogne , Mjelle Anders Batman , Hunskaar Steinar
Published: January 2017

Objectives

Acute respiratory infections and fever among children are highly prevalent in primary care. It is challenging to distinguish between viral and bacterial infections. Norway has a relatively low prescription rate of antibiotics, but it is still regarded as too high as the antimicrobial resistance is increasing. The aim of the study was to identify predictors for prescribing antibiotics or referral to hospital among children.

Design

Secondary analysis of a randomised controlled study.

Setting

4 out-of-hours services and 1 paediatric emergency clinic in Norwegian primary care.

Participants

401 children aged 0–6 years with respiratory symptoms and/or fever visiting the out-of-hours services.

Outcomes

2 main outcome variables were registered: antibiotic prescription and referral to hospital.

Results

The total prescription rate of antibiotics was 23%, phenoxymethylpenicillin was used in 67% of the cases. Findings on ear examination (OR 4.62; 95% CI 2.35 to 9.10), parents' assessment that the child has a bacterial infection (OR 2.45; 95% CI 1.17 to 5.13) and a C reactive protein (CRP) value >20 mg/L (OR 3.57; 95% CI 1.43 to 8.83) were significantly associated with prescription of antibiotics. Vomiting in the past 24 hours was negatively associated with prescription (OR 0.26; 95% CI 0.13 to 0.53). The main predictors significantly associated with referral to hospital were respiratory rate (OR 1.07; 95% CI 1.03 to 1.12), oxygen saturation <95% (OR 3.39; 95% CI 1.02 to 11.23), signs on auscultation (OR 5.57; 95% CI 1.96 to 15.84) and the parents' assessment before the consultation that the child needs hospitalisation (OR 414; 95% CI 26 to 6624).

Conclusions

CRP values >20 mg/L, findings on ear examination, use of paracetamol and no vomiting in the past 24 hours were significantly associated with antibiotic prescription. Affected respiration was a predictor for referral to hospital. The parents' assessment was also significantly associated with the outcomes.

Trial registration number

NCT02496559; Results.
Chronic symptoms in a representative sample of community-dwelling older people: a cross-sectional study in Switzerland
Authors: Henchoz Yves , Büla Christophe , Guessous Idris , Rodondi Nicolas , Goy René , Demont Maurice , Santos-Eggimann Brigitte
Published: January 2017

Objectives

The burden of multiple diagnoses is well documented in older people, but less is known about chronic symptoms, many of which are even not brought to medical attention. This study aimed to determine the prevalence of chronic symptoms, their relationships with disability in basic activities of daily living (BADL) and quality of life (QoL), and their public health impact.

Design

A large cross-sectional population-based study.

Setting

Community in 2 regions of French-speaking Switzerland.

Participants

Community-dwelling older adults aged 68 years and older in 2011 (N=5300).

Outcomes

Disability in BADL defined as difficulty or help needed with any of dressing, bathing, eating, getting in/out of bed or an arm chair, and using the toilet. Overall QoL dichotomised as favourable (ie, excellent or very good) or unfavourable (ie, good, fair or poor). Disturbance by any of the following 14 chronic symptoms for at least 6 months: joint pain, back pain, chest pain, dyspnoea, persistent cough, swollen legs, memory gaps, difficulty concentrating, difficulty making decisions, dizziness/vertigo, skin problems, stomach/intestine problems, urinary incontinence and impaired sexual life.

Results

Only 17.1% of participants did not report being disturbed by any of these chronic symptoms. Weighted prevalence ranged from 3.1% (chest pain) to 47.7% (joint pain). Most chronic symptoms were significantly associated with disability in BADL or unfavourable QoL, with substantial gender differences. The number of chronic symptoms was significantly associated with disability in BADL and unfavourable QoL, with gradients suggesting dose–response relationships. Joint pain and back pain had the highest population attributable fractions.

Conclusions

Chronic symptoms are highly prevalent in older people, and are associated with disability in BADL and unfavourable QoL, particularly when multiple chronic symptoms co-occur. Owing to their high public health impact, musculoskeletal chronic symptoms represent good targets for preventive interventions.
Intelligent Monitoring? Assessing the ability of the Care Quality Commission's statistical surveillance tool to predict quality and prioritise NHS hospital inspections
Authors: Griffiths Alex , Beaussier Anne-Laure , Demeritt David , Rothstein Henry
Published: January 2017

Background

The Care Quality Commission (CQC) is responsible for ensuring the quality of the health and social care delivered by more than 30 000 registered providers in England. With only limited resources for conducting on-site inspections, the CQC has used statistical surveillance tools to help it identify which providers it should prioritise for inspection. In the face of planned funding cuts, the CQC plans to put more reliance on statistical surveillance tools to assess risks to quality and prioritise inspections accordingly.

Objective

To evaluate the ability of the CQC's latest surveillance tool,Intelligent Monitoring(IM), to predict the quality of care provided by National Health Service (NHS) hospital trusts so that those at greatest risk of providing poor-quality care can be identified and targeted for inspection.

Methods

The predictive ability of the IM tool is evaluated through regression analyses and χ2testing of the relationship between the quantitative risk score generated by the IM tool and the subsequent quality rating awarded following detailed on-site inspection by large expert teams of inspectors.

Results

First, the continuous risk scores generated by the CQC's IM statistical surveillance tool cannot predict inspection-based quality ratings of NHS hospital trusts (OR 0.38 (0.14 to 1.05) for Outstanding/Good, OR 0.94 (0.80 to −1.10) for Good/Requires improvement, and OR 0.90 (0.76 to 1.07) for Requires improvement/Inadequate). Second, the risk scores cannot be used more simply to distinguish the trusts performing poorly—those subsequently rated either ‘Requires improvement’ or ‘Inadequate’—from the trusts performing well—those subsequently rated either ‘Good’ or ‘Outstanding’ (OR 1.07 (0.91 to 1.26)). Classifying CQC's risk bandings 1-3 as high risk and 4-6 as low risk, 11 of the high risk trusts were performing well and 43 of the low risk trusts were performing poorly, resulting in an overall accuracy rate of 47.6%. Third, the risk scores cannot be used even more simply to distinguish the worst performing trusts—those subsequently rated ‘Inadequate’—from the remaining, better performing trusts (OR 1.11 (0.94 to 1.32)). Classifying CQC's risk banding 1 as high risk and 2-6 as low risk, the highest overall accuracy rate of 72.8% was achieved, but still only 6 of the 13 Inadequate trusts were correctly classified as being high risk.

Conclusions

Since the IM statistical surveillance tool cannot predict the outcome of NHS hospital trust inspections, it cannot be used for prioritisation. A new approach to inspection planning is therefore required.
Evaluation of prediagnosis emergency department presentations in patients with active tuberculosis: the role of chest radiography, risk factors and symptoms
Authors: Appleton S C , Connell D W , Singanayagam A , Bradley P , Pan D , Sanderson F , Cleaver B , Rahman A , Kon O M
Published: January 2017

Introduction

London has a high rate of tuberculosis (TB) with 2572 cases reported in 2014. Cases are more common in non-UK born, alcohol-dependent or homeless patients. The emergency department (ED) presents an opportunity for the diagnosis of TB in these patient groups. This is the first study describing the clinico-radiological characteristics of such attendances in two urban UK hospitals for pulmonary TB (PTB) and extrapulmonary TB (EPTB).

Methods

We conducted a retrospective cohort study using the London TB Register (LTBR) and hospital records to identify patients who presented to two London ED's in the 6 months prior to their ultimate TB diagnosis 2011–2012.

Results

397 TB cases were identified. 39% (154/397) had presented to the ED in the 6 months prior to diagnosis. In the study population, the presence of cough, weight loss, fever and night sweats only had prevalence rates of 40%, 34%, 34% and 21%, respectively. Chest radiography was performed in 76% (117/154) of patients. For cases where a new diagnosis of TB was suspected, 73% (41/56) had an abnormal radiograph, compared with 36% (35/98) of patients where it was not. There was an abnormality on a chest radiograph in 73% (55/75) of PTB cases and also in 40% (21/52) of EPTB cases where a film was requested.

Conclusions

A large proportion of patients with TB present to ED. A diagnosis was more likely in the presence of an abnormal radiograph, suggesting opportunities for earlier diagnosis if risk factors, symptoms and chest radiograph findings are combined.
How well do we currently care for our dying patients in acute hospitals: the views of the bereaved relatives?
Authors: Mayland Catriona Rachel , Mulholland Helen , Gambles Maureen , Ellershaw John , Stewart Kevin
Published: January 2017

Background

The National Care of the Dying Audit—Hospitals (NCDAH) is used as a method to evaluate care for dying patients in England. An additional component to the 2013/2014 audit was the Local Survey of Bereaved Relatives Views using the ‘Care Of the Dying Evaluation’ (CODE) questionnaire.

Aim

Within the context of the NCDAH audit, to evaluate quality of care provided to dying patients and their families in acute hospitals from the perspective of bereaved relatives.

Design

Postbereavement survey to bereaved relatives.

Setting/participants

For acute hospitals wishing to participate, consecutive ‘expected’ adult deaths occurring between 1 May and 30 June 2013 were identified and the CODE questionnaire was sent to the next-of-kin.

Results

From 3414 eligible next-of-kin, 95 (2.8%) were excluded due to being involved in a complaint procedure and 1006 (29.5%) due to insufficient next-of-kin details. From the remaining 2313 potential participants, 858 returned a completed CODE questionnaire (37.1% response rate). Generally, symptoms were perceived to be well controlled with 769 (91%) participants reporting that either no pain was present or only there ‘some of the time’. Unmet information needs, however, was a recognised area for improvement, for example, 230 (29%) reporting having a discussion about hydration would have been beneficial.

Conclusions

Adopting a postbereavement survey to NCDAH appears to be feasible, acceptable and a valuable addition. On the whole, the majority of participants reported good or excellent care. A small but significant minority, however, perceived poor quality of patient care with clear and timely communication urgently needed.
Long-term (8–10 years) outcomes after biodegradable polymer-coated biolimus-eluting stent implantation
Authors: Ohya Masanobu , Kubo Shunsuke , Kuwayama Akimune , Miura Katsuya , Shimada Takenobu , Amano Hidewo , Hyodo Yusuke , Otsuru Suguru , Habara Seiji , Tada Takeshi , Tanaka Hiroyuki , Fuku Yasushi , Katoh Harumi , Goto Tsuyoshi , Kadota Kazushige
Published: January 2017

Objective

Efficacy and safety data on biodegradable polymer-coated biolimus-eluting stent (BP-BES) are currently limited to 5 years. We evaluated longer term (8–10 years) clinical and angiographic outcomes after BP-BES implantation.

Methods

Between 2005 and 2008, 243 patients (301 lesions) underwent BP-BES implantation. The primary clinical outcome measure was defined as any target lesion revascularisation (TLR). Absolute serial angiographic studies without any concomitant TLR within 2 years after the procedure were performed in 55 patients (65 lesions) at postprocedure, mid-term (within 1 year), late term (between 1 and 2 years) and very late term (beyond 2 years).

Results

The median follow-up duration was 9.4 years (IQR 8.2–10.2 years). The 8-year cumulative incidence of any TLR was 20.3%. The increase rate was approximately 7% per year in the first 2 years, but decelerated to approximately 1.2% per year beyond 2 years after the procedure. The minimal lumen diameter significantly decreased from postprocedure (2.63±0.44 mm) to mid-term (2.43±0.59 mm, p=0.002) and from late term (2.27±0.63 mm) to very late term (1.98±0.73 mm, p=0.002). The 8-year cumulative incidences of definite or probable stent thrombosis (ST) and major bleeding (Bleeding Academic Research Consortium (BARC) ≥3) were 0.5% and 12.0%, respectively. Definite ST was none within 10 years in the entire cohort.

Conclusions

The long-term clinical outcomes after BP-BES implantation were favourable, although angiographic late progression of luminal narrowing did not reach a plateau. The incidence of ST remained notably low, whereas that of major bleeding gradually increased.
Mortalin promotes cell proliferation and epithelial mesenchymal transition of intrahepatic cholangiocarcinoma cells in vitro
Authors: Kang Qiang , Cai Jia-Bin , Dong Rui-Zhao , Liu Li-Xin , Zhang Chi , Zhang Peng-Fei , Zou Hao , Xie Nan , Zhang Lu , Zhang Xin-Yu , Song Zheng-Ji , Dong Zhao-Ru , Hu Mei-Yu , Huang Xiao-Yong , Zhang Xiao-Wen , Ke Ai-Wu , Shi Guo-Ming
Published: January 2017

Aims

The prognosis of patients with intrahepatic cholangiocarcinoma (ICC) remains poor in terms of overall survival (OS) and recurrence rate. Mortalin, a stress chaperone, has been reported to be involved in carcinogenesis and metastasis. However, its role in ICC has not been defined.

Methods

Mortalin expression in tumour samples from patients with ICC was examined by Western blot and immunohistochemistry, and correlation between its expression and clinicopathological features was assessed. In addition, invasion, migration proliferation and apoptosis, and the expression of epithelial-mesenchymal transition (EMT)-related markers in ICC cells were assessed after mortalin depletion. Finally, the prognostic significance of mortalin in patients with ICC was further evaluated by Kaplan–Meier and Cox regression analysis.

Results

We provide evidence that expression of mortalin in human ICC tissues is higher than that in matched peritumoural tissues. The interference of mortalin expression inhibited the proliferation and invasion of ICC cells in vitro. Mechanistically, inhibition of mortalin expression in ICC cells upregulated E-cadherin expression and decreased vimentin and snail expression. Clinically, a high level of mortalin in ICC samples was associated with loss of E-cadherin, and increased expression of vimentin and snail. Patients with ICC and high mortalin expression had a shorter OS and a higher recurrence rate. Multivariate analysis revealed that mortalin overexpression was an independent prognostic indicator for patients with ICC.

Conclusions

Mortalin may promote cell proliferation and invasion via induction of EMT of ICC cells. A high level of mortalin may be used as a prognostic biomarker and therapeutic target for patients with ICC.
Demographic, procedural and 30-day safety results from the WEB Intra-saccular Therapy Study (WEB-IT)
Authors: Fiorella David , Molyneux Andrew , Coon Alexander , Szikora Istvan , Saatci Isil , Baltacioglu Feyyaz , Sultan Ali , Arthur Adam
Published: January 2017

Introduction

The Woven EndoBridge (WEB) represents a novel intrasaccular therapeutic option for the treatment of intracranial wide-necked bifurcation aneurysms (WNBAs). The WEB-IT Study is a pivotal Investigational Device Exemption (IDE) study to determine the safety and effectiveness of the WEB device for the treatment of WNBAs located in the anterior and posterior intracranial circulations. We present the patient demographics, procedural characteristics, and 30-day adverse event data for the US WEB-IT study.

Methods

WEB-IT is a prospective multicenter single-arm interventional study conducted at 25 US and 6 international centers. The study enrolled 150 adults with WNBAs of the anterior and posterior intracranial circulations. All patients were intended to receive a WEB device delivered via standard endovascular neurosurgical embolization techniques. The study was conducted under Good Clinical Practices and included independent adjudication effectiveness outcomes and all adverse events.

Results

One hundred and fifty patients enrolled at 27 investigational sites underwent attempted treatment with the WEB. Mean age was 59 years (range 29–79) and 110 (73.3%) of the patients were female. Treated aneurysms were located at the basilar apex (n=59, 39.3%), middle cerebral artery bifurcation (n=45, 30%), anterior communicating artery (n=40, 26.7%), and internal carotid artery terminus (n=6, 4%). Average aneurysm size was 6.4 mm (range 3.6–11.4) with a mean neck size of 4.8 mm (range 2.0–8.2, mean dome to neck ratio 1.34). Nine patients presented with ruptured aneurysms. Of the enrolled patients, 98.7% were treated successfully with WEB devices. Mean±SD fluoroscopy time was 30.2±15.7 min. One primary safety event (PSE) (0.7%)—a delayed parenchymal hemorrhage 22 days after treatment—occurred between the index procedure and 30-day follow-up. In addition to the single PSE, there were seven (4.7%) minor ischemic strokes (5 resolved without sequelae and 2 had a modified Rankin Scale score of 1 at 30 days), five (2.7%) transient ischemic attacks, and two (1.3%) minor subarachnoid hemorrhages, which did not meet the prospectively established criteria for PSEs.

Conclusions

The WEB device can be used to treat WNBAs with a high level of procedural safety and a high degree of technical success.

Trial registration number

NCT02191618; Pre-results.
U–Pb zircon geochronology and depositional history of the Montresor group, Rae Province, Nunavut, Canada
Authors: Percival John A. , Davis William J. , Hamilton Michael A.
Published: January 2017

Paleoproterozoic metasedimentary successions of the northwestern Canadian Shield provide records of tectonic events, but the definition of depositional ages has proved elusive. Although previously poorly understood, the Montresor belt of western Nunavut yields new insight into the 2.2–1.8 Ga time window. On the basis of U–Pb analyses of detrital zircon in sedimentary rocks and igneous zircon in sills, we conclude that arenite of the lower Montresor group was deposited between 2.194 and 2.045 Ga, and arkose of the upper Montresor group after 1.924 Ga, adding constraints on the Rae cover sequence. The lower Montresor arenite yielded an older group (3.05–2.58 Ga) and a younger, more tightly constrained group (2.194 ± 0.014 Ga). Four of six zircon grains analyzed from a gabbro sill within the lower Montresor have discordant 207Pb/206Pb ages (2.71, 2.66, 2.53, and 2.39 Ga) and are considered to be inherited, whereas two grains provide an age of 2045 ± 13 Ma, interpreted to date crystallization and providing a minimum age for the lower Montresor package. Upper Montresor arkose contains detrital zircon with probability density peaks at 2.55–2.25 and 2.1–1.92 Ga, together with scattered older grains (3.8–2.65 Ga). The youngest grain yields an age of 1924 ± 6 Ma, establishing a maximum age for sandstone deposition. Provenance is inferred to have been from the west, where igneous sources of 2.5–2.3 Ga (Queen Maud block) and 2.03–1.89 Ga (Thelon orogen) are known. Collectively, the new ages suggest a minimum 120 million year gap between deposition of the pre-2045 ± 13 Ma lower and post-1924 ± 6 Ma upper parts of the Montresor group. Similar age constraints may apply to other parts of the Rae cover sequence.
A fast and accurate method of detecting Aleutian mink disease virus in blood and tissues of chronically infected mink
Authors: Farid A.H. , Rupasinghe P.P.
Published: January 2017

The objective of this study was to assess the sensitivity of the Omni Klentaq-LA DNA polymerase for detecting Aleutian mink disease virus (AMDV) in mink blood and tissues by PCR without DNA extraction. The presence of AMDV DNA was directly tested by Klentaq in the plasma, serum, whole blood, and spleen homogenates of 188 mink 4 and 16 months after inoculation with the virus. Samples from bone marrow, small intestine, liver, lungs, kidneys, and lymph nodes of 20 of the same mink were also tested by Klentaq. DNA was extracted from paired samples of plasma and the aforesaid tissues by a commercial nucleic acid extraction kit (Dynabeads Silane) and tested by PCR. Compared with the extracted DNA, Klentaq detected a significantly greater number of samples in the whole blood, serum, plasma, spleen, and small intestine. It was concluded that Klentaq is a preferred system for directly detecting AMDV DNA in mink blood and tissues. The lower success rate of extracted DNA compared with Klentaq could be the result of DNA losses during the extraction process. This is an important factor in chronically infected mink, which have a low AMDV copy number in the bloodstream. Direct AMDV detection also reduces the cost of PCR amplification and lowers the risk of sample contamination.
Heavy exotic molecules
Authors: Liu Yizhuang , Zahed Ismail
Published: January 2017

We briefly review the formation of pion-mediated heavy-light exotic molecules with both charm and bottom, under the general structures of chiral and heavy quark symmetries. The charm isosinglet exotic molecules with [Formula: see text] binds, which we identify as the reported neutral [Formula: see text]. The bottom isotriplet exotic with [Formula: see text] binds, and is identified as a mixed state of the reported charged exotics [Formula: see text] and [Formula: see text]. The bound bottom isosinglet molecule with [Formula: see text] is a possible neutral [Formula: see text] to be observed.
Many-body Green functions in nuclear physics
Authors: Speth J. , Lyutorovich N.
Published: January 2017

Many-body Green functions are a very efficient formulation of the many-body problem. We review the application of this method to nuclear physics problems. The formulas which can be derived are of general applicability, e.g., in self-consistent as well as in nonself-consistent calculations. With the help of the Landau renormalization, one obtains relations without any approximations. This allows to apply conservation laws which lead to important general relations. We investigate the one-body and two-body Green functions as well as the three-body Green function and discuss their connection to nuclear observables. The generalization to systems with pair correlations are also presented. Numerical examples are compared with experimental data.
Profiling the Research Landscape in Emerging Areas Using Bibliometrics and Text Mining: A Case Study of Biomedical Engineering (BME) in Thailand
Authors: Gerdsri Nathasit , Kongthon Alisa , Puengrusme Sudatip
Published: January 2017

This study focuses on applying bibliometric analysis and text mining technique to generate technology intelligence from publication databases. The intelligence represents the research profile and landscape by highlighting active research areas and revealing professional communities along with their social networks. Professional communities can be not just existing networks, but also hidden ones. In this paper, the analysis of biomedical engineering (BME) field in Thailand is presented as the case study. The findings can be used as key inputs for the development of effective policies and incentives to promote the research activities as well as the collaboration among different groups of experts.
An Efficient Framework for Compressed Domain Watermarking in P Frames of High-Efficiency Video Coding (HEVC)--Encoded Video
Authors: Dutta Tanima , Gupta Hari Prabhat
Published: January 2017

Digital watermarking has received much attention in recent years as a promising solution to copyright protection. Video watermarking in compressed domain has gained importance since videos are stored and transmitted in a compressed format. This decreases the overhead to fully decode and re-encode the video for embedding and extraction of the watermark. High Efficiency Video Coding (HEVC/H.265) is the latest and most efficient video compression standard and a successor to H.264 Advanced Video Coding. In this article, we propose a robust watermarking framework for HEVC-encoded video using informed detector. A readable watermark is embedded invisibly in
P
frames for better perceptual quality. Our framework imposes security and robustness by selecting appropriate blocks using a random key and the spatio-temporal characteristics of the compressed video. A detail analysis of the strengths of different compressed domain features is performed for implementing the watermarking framework. We experimentally demonstrate the utility of the proposed work. The results show that the proposed work effectively limits the increase in video bitrate and degradation in perceptual quality. The proposed framework is robust against re-encoding and image processing attacks.