bluuebunny/crossref_metadata_2025 huggingface dataset:
The Evolution of Progressive Postoperative Weight Bearing After Autologous Chondrocyte Implantation in the Tibiofemoral Joint
Authors: Ebert Jay R. , Edwards Peter K.
Published: August 2014

Autologous chondrocyte implantation (ACI) has demonstrated good clinical success in the repair of articular cartilage defects in the knee. Postoperative rehabilitation after ACI is considered critical in returning the patient to an optimal level of function by attempting to create the appropriate mechanical environment for cartilage regrowth, and it involves a progressive program that emphasizes full motion, progressive partial weight bearing (PWB), and controlled exercises. While evidence-based research is clearly lacking in all components of ACI rehabilitation, one important element in this treatment algorithm that has been subjected to some early scientific study is the gradual progression of the patient back to full weight-bearing (WB) gait after surgery. With the continual advancement of ACI surgical techniques, along with clinical experience and improved knowledge of histology and of the maturation process of chondrocytes, proposed postoperative WB protocols have evolved to better reflect the nature of the specific ACI surgery. The purpose of this article is to present the varied PWB programs that have been practiced alongside the evolving ACI surgical technique, the experimental basis for such protocols, the issues pertinent to the accurate prescription of WB, and future directions for developing such methods to best return patients to an optimal level of function after ACI.
A Systematic Review of Reporting of Rehabilitation in Articular-Cartilage-Repair Studies of Third-Generation Autologous Chondrocyte Implantation in the Knee
Authors: Bright Philip , Hambly Karen
Published: August 2014

Context:

Autologous chondrocyte implantation (ACI) is a tissue-engineered surgical technique initially developed for articular cartilage repair of isolated chondral lesions of the knee. Third-generation techniques (ACI3) are now available that deliver autologous cultured chondrocytes into the defect using cell scaffolds. The successful outcomes of these techniques have some dependency on presurgical and postsurgical patient rehabilitation.

Objectives:

To determine if the standard of reporting for rehabilitation has improved in ACI3 studies; previous reviews in this field recommended describing the detail of this rehabilitation and patient compliance as integral elements.

Evidence Acquisition:

A computerized search was performed in March 2013. Criteria for inclusion were any studies that evaluated or described the process of ACI3 in the knee and subsequent rehabilitation. The modified Coleman Methodology Score (CMS) was used to rate the standard of reporting of rehabilitation and surgical procedures; review articles were also evaluated for quality using the Strength of Recommendation Taxonomy (SORT). Mean scores, odds ratios, 95% confidence intervals, and Mann-Whitney U statistics were calculated.

Evidence Synthesis:

An improvement in mean CMS was seen compared with previous reviews, but rehabilitation reporting scores were lower than their surgical equivalent; significant association was seen between studies with rehabilitator involvement and high scores in the individual CMS rehabilitation element. Predominant SORT scores of 2A indicated medium strength of recommendation.

Conclusions:

The CMS provides a general overview of methodological quality, but a more specialized tool to report on the quantitative and qualitative aspects of the rehabilitation process would help raise the standards. It is recommended that rehabilitation therapists be included as key members of research teams and be involved in the design, implementation, and reporting of future studies.
Intratumoral injection of
Clostridium novyi
-NT spores induces antitumor responses
Authors: Roberts Nicholas J. , Zhang Linping , Janku Filip , Collins Amanda , Bai Ren-Yuan , Staedtke Verena , Rusk Anthony W. , Tung David , Miller Maria , Roix Jeffrey , Khanna Kristen V. , Murthy Ravi , Benjamin Robert S. , Helgason Thorunn , Szvalb Ariel D. , Bird Justin E. , Roy-Chowdhuri Sinchita , Zhang Halle H. , Qiao Yuan , Karim Baktiar , McDaniel Jennifer , Elpiner Amanda , Sahora Alexandra , Lachowicz Joshua , Phillips Brenda , Turner Avenelle , Klein Mary K. , Post Gerald , Diaz Luis A. , Riggins Gregory J. , Papadopoulos Nickolas , Kinzler Kenneth W. , Vogelstein Bert , Bettegowda Chetan , Huso David L. , Varterasian Mary , Saha Saurabh , Zhou Shibin
Published: August 2014

Clostridium novyi
-NT targets aberrant tumor physiology and can produce a precise, robust, and reproducible antitumor response.
Lumpers and Splitters: A New Molecular Taxonomy for Cancer
Authors: Faltas Bishoy M.
Published: August 2014

Data analysis of 12 different cancer types yields a new molecular taxonomy for cancer.
Hybrid CARs for Cancer?
Authors: Maus Marcela V.
Published: August 2014

NKT cells, redirected by a chimeric antigen receptor, are a promising newcomer to the immunotherapy field.
Understanding the Genetic Risk of Sudden Cardiac Death
Authors: Stecker Eric C.
Published: August 2014

A disease mutation causes long QT syndrome and sudden cardiac death through a new genetic regulatory mechanism.
UDP-
N
-Acetylmuramic Acid
l
-Alanine Ligase (MurC) Inhibition in a
tolC
Mutant Escherichia coli Strain Leads to Cell Death
Authors: Humnabadkar Vaishali , Prabhakar K. R. , Narayan Ashwini , Sharma Sreevalli , Guptha Supreeth , Manjrekar Praveena , Chinnapattu Murugan , Ramachandran Vasanthi , Hameed Shahul P. , Ravishankar Sudha , Chatterji Monalisa
Published: August 2014

The Mur ligases play an essential role in the biosynthesis of bacterial peptidoglycan and hence are attractive antibacterial targets. A screen of the AstraZeneca compound library led to the identification of compound A, a pyrazolopyrimidine, as a potent inhibitor of
Escherichia coli
and
Pseudomonas aeruginosa
MurC. However, cellular activity against
E. coli
or
P. aeruginosa
was not observed. Compound A was active against efflux pump mutants of both strains. Experiments using an
E. coli
tolC
mutant revealed accumulation of the MurC substrate and a decrease in the level of product upon treatment with compound A
,
indicating inhibition of MurC enzyme in these cells. Such a modulation was not observed in the
E. coli
wild-type cells. Further, overexpression of MurC in the
E. coli
tolC
mutant led to an increase in the compound A MIC by ≥16-fold, establishing a correlation between MurC inhibition and cellular activity. In addition, estimation of the intracellular compound A level showed an accumulation of the compound over time in the
tolC
mutant strain. A significant compound A level was not detected in the wild-type
E. coli
strain even upon treatment with high concentrations of the compound. Therefore, the lack of MIC and absence of MurC inhibition in wild-type
E. coli
were possibly due to suboptimal compound concentration as a consequence of a high efflux level and/or poor permeativity of compound A.
Whole-Animal Chemical Screen Identifies Colistin as a New Immunomodulator That Targets Conserved Pathways
Authors: Cai Yun , Cao Xiou , Aballay Alejandro
Published: August 2014

The purpose of this study was to take advantage of the nematode
Caenorhabditis elegans
to perform a whole-animal chemical screen to identify potential immune activators that may confer protection against bacterial infections. We identified 45 marketed drugs, out of 1,120 studied compounds, that are capable of activating a conserved p38/PMK-1 mitogen-activated protein kinase pathway required for innate immunity. One of these drugs, the last-resort antibiotic colistin, protected against infections by the Gram-negative pathogens
Yersinia pestis
and
Pseudomonas aeruginosa
but not by the Gram-positive pathogens
Enterococcus faecalis
and
Staphylococcus aureus
. Protection was independent of the antibacterial activity of colistin, since the drug was administered prophylactically prior to the infections and it was also effective against antibiotic-resistant bacteria. Immune activation by colistin is mediated not only by the p38/PMK-1 pathway but also by the conserved FOXO transcription factor DAF-16 and the transcription factor SKN-1. Furthermore, p38/PMK-1 was found to be required in the intestine for immune activation by colistin. Enhanced p38/PMK-1-mediated immune responses by colistin did not reduce the bacterial burden, indicating that the pathway plays a role in the development of host tolerance to infections by Gram-negative bacteria.

IMPORTANCE
The innate immune system represents the front line of our defenses against invading microorganisms. Given the ever-increasing resistance to antibiotics developed by bacterial pathogens, the possibility of boosting immune defenses represents an interesting, complementary approach to conventional antibiotic treatments. Here we report that the antibiotic colistin can protect against infections by a mechanism that is independent of its microbicidal activity. Prophylactic treatment with colistin activates a conserved p38/PMK-1 pathway in the intestine that helps the host better tolerate a bacterial infection. Since p38/PMK-1-mediated immune responses appear to be conserved from plants to mammals, colistin may also activate immunity in higher organisms, including humans. Antibiotics with immunomodulatory properties have the potential of improving the long-term outcome of patients with chronic infectious diseases.
Influenza Virus A/Anhui/1/2013 (H7N9) Replicates Efficiently in the Upper and Lower Respiratory Tracts of Cynomolgus Macaques
Authors: de Wit Emmie , Rasmussen Angela L. , Feldmann Friederike , Bushmaker Trenton , Martellaro Cynthia , Haddock Elaine , Okumura Atsushi , Proll Sean C. , Chang Jean , Gardner Don , Katze Michael G. , Munster Vincent J. , Feldmann Heinz
Published: August 2014

In March 2013, three fatal human cases of infection with influenza A virus (H7N9) were reported in China. Since then, human cases have been accumulating. Given the public health importance of this virus, we performed a pathogenicity study of the H7N9 virus in the cynomolgus macaque model, focusing on clinical aspects of disease, radiographic, histological, and gene expression profile changes in the upper and lower respiratory tracts, and changes in systemic cytokine and chemokine profiles during infection. Cynomolgus macaques developed transient, mild to severe disease with radiographic evidence of pulmonary infiltration. Virus replicated in the upper as well as lower respiratory tract, with sustained replication in the upper respiratory tract until the end of the experiment at 6 days after inoculation. Virus shedding occurred mainly via the throat. Histopathological changes in the lungs were similar to those observed in humans, albeit less severe, with diffuse alveolar damage, infiltration of polymorphonuclear cells, formation of hyaline membranes, pneumocyte hyperplasia, and fibroproliferative changes. Analysis of gene expression profiles in lung lesions identified pathways involved in tissue damage during H7N9 infection as well as leads for development of therapeutics targeting host responses rather than virus replication. Overall, H7N9 infection was not as severe in cynomolgus macaques as in humans, supporting the possible role of underlying medical complications in disease severity as discussed for human H7N9 infection (H. N. Gao et al., N. Engl. J. Med. 368:2277–2285, 2013, doi:10.1056/NEJMoa1305584).

IMPORTANCE
Influenza A virus H7N9 emerged early in 2013, and human cases have continued to emerge since then. Although H7N9 virus-induced disease in humans is often very severe and even lethal, the majority of reported H7N9 cases occurred in older people and people with underlying medical conditions. To better understand the pathogenicity of this virus, healthy cynomolgus macaques were inoculated with influenza A virus H7N9. Cynomolgus macaques were used as a model because the receptor distribution for H7N9 virus in macaques was recently shown to be more similar to that in humans than that of other frequently used animal models. From comparison with previous studies, we conclude that the emerging H7N9 influenza virus was more pathogenic in cynomolgus macaques than seasonal influenza A viruses and most isolates of the pandemic H1N1 virus but less pathogenic than the 1918 Spanish influenza virus or highly pathogenic avian influenza (HPAI) H5N1 virus.
Differential Modulation by Akkermansia muciniphila and Faecalibacterium prausnitzii of Host Peripheral Lipid Metabolism and Histone Acetylation in Mouse Gut Organoids
Authors: Lukovac Sabina , Belzer Clara , Pellis Linette , Keijser Bart J. , de Vos Willem M. , Montijn Roy C. , Roeselers Guus
Published: August 2014

The gut microbiota is essential for numerous aspects of human health. However, the underlying mechanisms of many host-microbiota interactions remain unclear. The aim of this study was to characterize effects of the microbiota on host epithelium using a novel
ex vivo
model based on mouse ileal organoids. We have explored the transcriptional response of organoids upon exposure to short-chain fatty acids (SCFAs) and products generated by two abundant microbiota constituents,
Akkermansia muciniphila
and
Faecalibacterium prausnitzii
. We observed that
A. muciniphila
metabolites affect various transcription factors and genes involved in cellular lipid metabolism and growth, supporting previous
in vivo
findings. Contrastingly,
F. prausnitzii
products exerted only weak effects on host transcription. Additionally,
A. muciniphila
and its metabolite propionate modulated expression of Fiaf, Gpr43, histone deacetylases (HDACs), and peroxisome proliferator-activated receptor gamma (Pparγ), important regulators of transcription factor regulation, cell cycle control, lipolysis, and satiety. This work illustrates that specific bacteria and their metabolites differentially modulate epithelial transcription in mouse organoids. We demonstrate that intestinal organoids provide a novel and powerful
ex vivo
model for host-microbiome interaction studies.

IMPORTANCE
We investigated the influence of the gut microbiota and microbially produced short-chain fatty acids (SCFAs) on gut functioning. Many commensal bacteria in the gut produce SCFAs, particularly butyrate, acetate, and propionate, which have been demonstrated to reduce the risk of gastrointestinal disorders. Organoids—small crypt-villus structures grown from ileal intestinal stem cells—were exposed to SCFAs and two specific gut bacteria.
Akkermansia muciniphila
, found in the intestinal mucus, was recently shown to have a favorable effect on the disrupted metabolism associated with obesity.
Faecalibacterium prausnitzii
is a commensal gut bacterium, the absence of which may be associated with Crohn’s disease. We showed that in our model,
A. muciniphila
induces stronger effects on the host than
F. prausnitzii
. We observed that
A. muciniphila
and propionate affect the expression of genes involved in host lipid metabolism and epigenetic activation or silencing of gene expression. We demonstrated that organoids provide a powerful tool for host-microbe interaction studies.
Fur Is the Master Regulator of the Extraintestinal Pathogenic Escherichia coli Response to Serum
Authors: Huja Sagi , Oren Yaara , Biran Dvora , Meyer Susann , Dobrindt Ulrich , Bernhard Joerg , Becher Doerte , Hecker Michael , Sorek Rotem , Ron Eliora Z.
Published: August 2014

Drug-resistant extraintestinal pathogenic
Escherichia coli
(ExPEC) strains are the major cause of colisepticemia (colibacillosis), a condition that has become an increasing public health problem in recent years. ExPEC strains are characterized by high resistance to serum, which is otherwise highly toxic to most bacteria. To understand how these bacteria survive and grow in serum, we performed system-wide analyses of their response to serum, making a clear distinction between the responses to nutritional immunity and innate immunity. Thus, mild heat inactivation of serum destroys the immune complement and abolishes the bactericidal effect of serum (inactive serum), making it possible to examine nutritional immunity. We used a combination of deep RNA sequencing and proteomics in order to characterize ExPEC genes whose expression is affected by the nutritional stress of serum and by the immune complement. The major change in gene expression induced by serum—active and inactive—involved metabolic genes. In particular, the serum metabolic response is coordinated by three transcriptional regulators, Fur, BasR, and CysB. Fur alone was responsible for more than 80% of the serum-induced transcriptional response. Consistent with its role as a major serum response regulator, deletion of Fur renders the bacteria completely serum sensitive. These results highlight the role of metabolic adaptation in colisepticemia and virulence.

IMPORTANCE
Drug-resistant extraintestinal pathogenic
Escherichia coli
(ExPEC) strains have emerged as major pathogens, especially in community- and hospital-acquired infections. These bacteria cause a large spectrum of syndromes, the most serious of which is septicemia, a condition with a high mortality rate. These bacterial strains are characterized by high resistance to serum, otherwise highly toxic to most bacteria. To understand the basis of this resistance, we carried out system-wide analyses of the response of ExPEC strains to serum by using proteomics and deep RNA sequencing. The major changes in gene expression induced by exposure to serum involved metabolic genes, not necessarily implicated in relation to virulence. One metabolic regulator—Fur—involved in iron metabolism was responsible for more than 80% of the serum-induced response, and its deletion renders the bacteria completely serum sensitive. These results highlight the role of metabolic adaptation in virulence.
Phyllosphere Microbiota Composition and Microbial Community Transplantation on Lettuce Plants Grown Indoors
Authors: Williams Thomas R. , Marco Maria L.
Published: August 2014

The aerial surfaces of plants, or phyllosphere, are microbial habitats important to plant and human health. In order to accurately investigate microbial interactions in the phyllosphere under laboratory conditions, the composition of the phyllosphere microbiota should be representative of the diversity of microorganisms residing on plants in nature. We found that Romaine lettuce grown in the laboratory contained 10- to 100-fold lower numbers of bacteria than age-matched, field-grown lettuce. The bacterial diversity on laboratory-grown plants was also significantly lower and contained relatively higher proportions of
Betaproteobacteria
as opposed to the
Gammaproteobacteria-
enriched communities on field lettuce. Incubation of field-grown Romaine lettuce plants in environmental growth chambers for 2 weeks resulted in bacterial cell densities and taxa similar to those on plants in the field but with less diverse bacterial populations overall. In comparison, the inoculation of laboratory-grown Romaine lettuce plants with either freshly collected or cryopreserved microorganisms recovered from field lettuce resulted in the development of a field-like microbiota on the lettuce within 2 days of application. The survival of an inoculated strain of
Escherichia coli
O157:H7 was unchanged by microbial community transfer; however, the inoculation of
E. coli
O157:H7 onto those plants resulted in significant shifts in the abundance of certain taxa. This finding was strictly dependent on the presence of a field-associated as opposed to a laboratory-associated microbiota on the plants. Phyllosphere microbiota transplantation in the laboratory will be useful for elucidating microbial interactions on plants that are important to agriculture and microbial food safety.

IMPORTANCE
The phyllosphere is a habitat for a variety of microorganisms, including bacteria with significant relevance to plant and human health. Some indigenous epiphytic bacteria might affect the persistence of human food-borne pathogens in the phyllosphere. However, studies on human pathogens are typically performed on plants grown indoors. This study compares the phyllosphere microbiota on Romaine lettuce plants grown in a Salinas Valley, CA, field to that on lettuce plants grown in environmental chambers. We show that phyllosphere microbiota from laboratory-grown plants is distinct from that colonizing plants grown in the field and that the field microbiota can be successfully transferred to plants grown indoors. The microbiota transplantation method was used to examine alterations to the phyllosphere microbiota after
Escherichia coli
O157:H7 inoculation on lettuce plants in a controlled environment. Our findings show the importance and validity of phyllosphere microbiota transplantation for future phyllosphere microbiology research.
Cross Talk between the Cell Wall Integrity and Cyclic AMP/Protein Kinase A Pathways in Cryptococcus neoformans
Authors: Donlin Maureen J. , Upadhya Rajendra , Gerik Kimberly J. , Lam Woei , VanArendonk Laura G. , Specht Charles A. , Sharma Neil K. , Lodge Jennifer K.
Published: August 2014

Cryptococcus neoformans
 is a fungal pathogen of immunocompromised people that causes fatal meningitis. The fungal cell wall is essential to viability and pathogenesis of
C. neoformans
, and biosynthesis and repair of the wall is primarily controlled by the cell wall integrity (CWI) signaling pathway. Previous work has shown that deletion of genes encoding the four major kinases in the CWI signaling pathway, namely,
PKC1
,
BCK1
,
MKK2
, and
MPK1
results in severe cell wall phenotypes, sensitivity to a variety of cell wall stressors, and for Mpk1, reduced virulence in a mouse model. Here, we examined the global transcriptional responses to gene deletions of
BCK1
,
MKK2
, and
MPK1
compared to wild-type cells. We found that over 1,000 genes were differentially expressed in one or more of the deletion strains, with 115 genes differentially expressed in all three strains, many of which have been identified as genes regulated by the cyclic AMP (cAMP)/protein kinase A (PKA) pathway. Biochemical measurements of cAMP levels in the kinase deletion strains revealed significantly less cAMP in all of the deletion strains compared to the wild-type strain. The deletion strains also produced significantly smaller capsules than the wild-type KN99 strain did under capsule-inducing conditions, although the levels of capsule they shed were similar to those shed by the wild type. Finally, addition of exogenous cAMP led to reduced sensitivity to cell wall stress and restored surface capsule to levels near those of wild type. Thus, we have direct evidence of cross talk between the CWI and cAMP/PKA pathways that may have important implications for regulation of cell wall and capsule homeostasis.

IMPORTANCE
Cryptococcus neoformans
 is a fungal pathogen of immunocompromised people that causes fatal meningitis. The fungal cell wall is essential to viability and pathogenesis of
C. neoformans
, and biosynthesis and repair of the wall are primarily controlled by the cell wall integrity (CWI) signaling pathway. In this study, we demonstrate that deletion of any of three core kinases in the CWI pathway impacts not only the cell wall but also the amount of surface capsule. Deletion of any of the kinases results in significantly reduced cellular cyclic AMP (cAMP) levels, and addition of exogenous cAMP rescues the capsule defect and some cell wall defects, supporting a direct role for the CWI pathway in regulation of capsule in conjunction with the cAMP/protein kinase A pathway.
Methaemoglobinaemia in a G6PD-deficient child treated with rasburicase
Authors: Bontant Thomas , Le Garrec Sophie , Avran David , Dauger Stephane
Published: August 2014

A 5-year-old boy from the Congo, was admitted for hyperleucocytic acute lymphoblastic leukaemia, with a high risk of tumour lysis syndrome (TLS). He had splenomegaly and mediastinal lymphadenopathy on chest X-ray. We started steroids and hyperhydration with rasburicase to prevent TLS. Respiratory failure with mediastinal enlargement developed rapidly. A few hours after intensive care unit (ICU) admission, he was started on mechanical ventilation. Chemotherapy was started immediately given the strong suspicion of mediastinal compression. Low oxygen saturation with high partial arterial oxygen pressure persisted. Blood tests confirmed 20% methaemoglobinaemia and glucose-6-phosphate dehydrogenase (G6PD) deficiency. Allopurinol was substituted for rasburicase. The methaemoglobinaemia disappeared rapidly and he was discharged from the ICU after 72 h. In case of rasburicase use, a close clinical monitoring is mandatory, especially in populations where G6PD deficiency is highly prevalent. Methaemoglobinaemia must be suspected in case of low oxygen saturation when all other potential causes have been ruled out.
Tackle-related injury rates and nature of injuries in South African Youth Week tournament rugby union players (under-13 to under-18): an observational cohort study
Authors: Burger Nicholas , Lambert Mike I , Viljoen Wayne , Brown James C , Readhead Clint , Hendricks Sharief
Published: August 2014

Objectives

The tackle situation is most often associated with the high injury rates in rugby union. Tackle injury epidemiology in rugby union has previously been focused on senior cohorts but less is known about younger cohorts. The aim of this study was to report on the nature and rates of tackle-related injuries in South African youth rugby union players representing their provinces at national tournaments.

Design

Observational cohort study.

Setting

Four South African Youth Week tournaments (under-13 Craven Week, under-16 Grant Khomo Week, under-18 Academy Week, under-18 Craven Week).

Participants

Injury data were collected from 3652 youth rugby union players (population at risk) in 2011 and 2012.

Outcome measures

Tackle-related injury severity (‘time-loss’ and ‘medical attention’), type and location, injury rate per 1000 h (including 95% CIs). Injury rate ratios (IRR) were calculated and modelled using a Poisson regression. A χ2analysis was used to detect linear trends between injuries and increasing match quarters.

Results

The 2012 under-13 Craven Week had a significantly greater ‘time-loss’ injury rate when compared with the 2012 under-18 Academy Week (IRR=4.43; 95% CI 2.13 to 9.21, p<0.05) and under-18 Craven Week (IRR=3.52; 95% CI 1.54 to 8.00, p<0.05). The Poisson regression also revealed a higher probability of ‘overall’ (‘time-loss’ and ‘medical attention’ combined) and ‘time-loss’ tackle-related injuries occurring at the under-13 Craven Week. The proportion of ‘overall’ and ‘time-loss’ injuries increased significantly with each quarter of the match when all four tournaments were combined (p<0.05).

Conclusions

There was a difference in the tackle-related injury rate between the under-13 tournament and the two under-18 tournaments, and the tackle-related injury rate was higher in the final quarter of matches. Ongoing injury surveillance is required to better interpret these findings. Injury prevention strategies targeting the tackle may only be effective once the rate and nature of injuries have been accurately determined.
Developing a Platform for Learning from Mistakes: changing the culture of patient safety amongst junior doctors
Authors: Millwood Sinead
Published: August 2014

Junior doctors commonly make mistakes which may compromise patient safety. Despite the recent push by the NHS to encourage a “no blame” culture, mistakes are still viewed as shameful, embarrassing and demoralising events. The current model for learning from mistakes means that junior doctors only learn from their own errors.

A survey was designed by the author for all the Foundation Year 1 doctors (FY1s) at Yeovil District Hospital to understand better the culture surrounding mistakes, and the types of mistakes that were being made. Using the results of the survey and the support of senior staff, a “Near misses” session has been introduced for FY1s once a month at which mistakes that have been made are discussed, with a consultant present to facilitate the proceedings. The aims of these sessions are to promote a culture of no blame, feedback information to clinical governance, and share learning experiences.

100% of the FY1s had made a mistake that could compromise patient safety. 63% discussed their mistakes with colleagues, 44% with seniors, and only 13% with their educational supervisor. Barriers to discussing mistakes included shame, embarrassment, fear of judgement, and unapproachable seniors. 94% thought a “Near misses” session would be useful. After the third session 100% of the FY1s agreed that the sessions were useful; 53% had changed their practice as a result of something they learned at the sessions.

After discussing errors as a group we have worked with the clinical governance department, enacting strategies to avoid repetition of mistakes. Feedback from the junior doctors has been overwhelmingly positive and we have found these sessions to be a simple, inexpensive, and popular solution to cultural change in our organisation.
A guide to midgut neuroendocrine tumours (NETs) and carcinoid syndrome
Authors: Cheung Vincent T F , Khan Mohid S
Published: August 2014

Patients with midgut neuroendocrine tumours or carcinoid syndrome often face a delayed diagnosis. This article aims to highlight the different ways in which patients with midgut neuroendocrine tumours (NETs) present, the diagnostic approach to them, the current methods of management available and future considerations.
RESTORE: REcovery after Serious Trauma—Outcomes, Resource use and patient Experiences study protocol
Authors: Gabbe Belinda J , Braaf Sandra , Fitzgerald Mark , Judson Rodney , Harrison James E , Lyons Ronan A , Ponsford Jennie , Collie Alex , Ameratunga Shanthi , Attwood David , Christie Nicola , Nunn Andrew , Cameron Peter A
Published: August 2014

Background

Traumatic injury is a leading contributor to the overall global burden of disease. However, there is a worldwide shortage of population data to inform understanding of non-fatal injury burden. An improved understanding of the pattern of recovery following trauma is needed to better estimate the burden of injury, guide provision of rehabilitation services and care to injured people, and inform guidelines for the monitoring and evaluation of disability outcomes.

Objective

To provide a comprehensive overview of patient outcomes and experiences in the first 5 years after serious injury.

Design

This is a population-based, nested prospective cohort study using quantitative data methods, supplemented by a qualitative study of a seriously injured participant sample.

Participants

All 2547 paediatric and adult major trauma patients captured by the Victorian State Trauma Registry with a date of injury from 1 July 2011 to 30 June 2012 who survived to hospital discharge and did not opt-off from the registry.

Analysis

To analyse the quantitative data and identify factors that predict poor or good outcome, whether there is change over time, differences in rates of recovery and change between key participant subgroups, multilevel mixed effects regression models will be fitted. To analyse the qualitative data, thematic analysis will be used to identify important themes and the relationships between themes.

Contribution to the field

The results of this project have the potential to inform clinical decisions and public health policy, which can reduce the burden of non-fatal injury and improve the lives of people living with the consequences of severe injury.
Alterations of insulin-like growth factor-1 receptor gene copy number and protein expression are common in non-small cell lung cancer
Authors: Tran T N , Selinger C I , Yu B , Ng C C , Kohonen-Corish M R J , McCaughan B , Kennedy C , O'Toole S A , Cooper W A
Published: August 2014

Aims

Insulin-like growth factor-1 receptor (IGF1R) is a tyrosine kinase membrane receptor involved in tumourigenesis that may be a potential therapeutic target. We aimed to investigate the incidence and prognostic significance of alterations inIGF1Rcopy number, and IGF1R protein expression in resected primary non-small cell lung cancer (NSCLC), and lymph node metastases.

Methods

IGF1Rgene copy number status was evaluated by chromogenic silver in situ hybridisation and IGF1R protein expression was evaluated by immunohistochemistry in tissue microarray sections from a retrospective cohort of 309 surgically resected NSCLCs and results were compared with clinicopathological features, includingEGFRandKRASmutational status and patient survival.

Results

IGF1Rgene copy number status was positive (high polysomy or amplification) in 29.2% of NSCLC, and 12.1% exhibitedIGF1Rgene amplification. High IGF1R expression was found in 28.3%. There was a modest correlation betweenIGF1Rgene copy number and protein expression (r=0.2, p<0.05). Alterations ofIGF1Rgene copy number and protein expression in primary tumours were significantly associated with alterations in lymph node metastases (p<0.01). HighIGF1Rgene copy number and protein expression was significantly higher in squamous cell carcinomas (SCC) compared with other subtypes of NSCLC (p<0.05). There were no other associations between IGF1R status and other clinicopathological features including patient age, gender, smoking status, tumour size, stage, grade,EGFRorKRASmutational status or overall survival.

Conclusions

HighIGF1Rgene copy number and protein overexpression are frequent in NSCLC, particularly in SCCs, but they are not prognostically relevant.
Angiographic factors influencing the success of endovascular treatment of arteriovenous malformations involving the corpus callosum
Authors: Robert Thomas , Blanc Raphaël , Ciccio Gabriele , Gilboa Boaz , Fahed Robert , Redjem Hocine , Pistocchi Silvia , Bartolini Bruno , Piotin Michel
Published: August 2014

Objective

Arteriovenous malformations (AVMs) of the corpus callosum are rare lesions, accounting for 9–11% of brain AVMs. Microsurgical resection of such lesions is difficult because of their deep location, and also because of possible neuropsychological disasters resulting from extended callosal resection. The introduction of endovascular and radiation therapies has fundamentally changed the outcome of these lesions.

Methods

We prospectively collected clinical and angiographic data on cerebral AVMs from 1995. We reviewed data from patients treated for an AVM of the corpus callosum and identified the factors influencing the endovascular approach of such lesions.

Results

38 patients (mean age 31 years) were consecutively treated by endovascular techniques. 78.9% (30 cases) of patients presented with intracranial hemorrhage. 15 AVMs (39.5%) were anterior, 18 (47.4%) were posterior, and five (13.1%) were holocallosal. The Spetzler–Martin grade was I in two cases (5.2%), II in 20 cases (52.6%), III in nine cases (23.7%), IV in six cases (15.8%), and V in one case (2.6%). The nidus was compact in 19 cases (50%), diffuse in 13 (34.2%), and multifocal in six (15.8%). Both anterior and posterior circulation branches fed 14 nidi (36.8%). Venous drainage was superficial in three cases (7.9%), deep in 28 (73.7%), and both in seven cases (18.4%). 104 sessions were performed, with a procedural complication rate of 6.7%. Mean follow-up was 43.6 months, with the last modified Rankin Scale score <3 in 33 cases (86.8%). 22 patients (57.9%) were totally cured. Univariate analysis of factors influencing the success of endovascular treatment showed that Spetzler–Martin grade ≥3 (p=0.046), nidus >30 mm (p=0.02), extension in an eloquent area (p=0.03), and holocallosal type (p0.005) significantly diminished the chances of cure of the AVM.

Conclusions

AVMs of the corpus callosum seems to be difficult to treat with endovascular therapy alone. The goal of embolization should be prevention of (re) bleeding and a decrease in nidus size. Our experience regarding this sub-pathology suggests that a combination of endovascular therapy and radiotherapy may be the best option.
Balloon-augmented Onyx embolization of cerebral arteriovenous malformations using a dual-lumen balloon: a multicenter experience
Authors: Spiotta Alejandro M , James Robert F , Lowe Stephen R , Vargas Jan , Turk Aquilla S , Chaudry M Imran , Bhalla Tarun , Janjua Rashid M , Delaney John J , Quintero-Wolfe Stacey , Turner Raymond D
Published: August 2014

Introduction

Conventional Onyx embolization of cerebral arteriovenous malformations (AVMs) requires lengthy procedure and fluoroscopy times to form an adequate ‘proximal plug’ which allows forward nidal penetration while preventing reflux and non-targeted embolization. We review our experience with balloon-augmented Onyx embolization of cerebral AVMs using a dual-lumen balloon catheter technique designed to minimize these challenges.

Methods

Retrospectively acquired data for all balloon-augmented cerebral AVM embolizations performed between 2011 and 2014 were obtained from four tertiary care centers. For each procedure, at least one Scepter C balloon catheter was advanced into the AVM arterial pedicle of interest and Onyx embolization was performed through the inner lumen after balloon inflation via the outer lumen.

Results

Twenty patients underwent embolization with the balloon-augmented technique over 24 discreet treatment episodes. There were 37 total arterial pedicles embolized with the balloon-augmented technique, a mean of 1.9 per patient (range 1–5). The treated AVMs were heterogeneous in their location and size (mean 3.3±1.6 cm). Mean fluoroscopy time for each procedure was 48±26 min (28 min per embolized pedicle). Two Scepter C balloon catheter-related complications (8.3% of embolization sessions, 5.4% of pedicles embolized) were observed: an intraprocedural rupture of a feeding pedicle and fracture and retention of a catheter fragment.

Conclusions

This multicenter experience represents the largest reported series of balloon-augmented Onyx embolization of cerebral AVMs. The technique appears safe and effective in the treatment of AVMs, allowing more efficient and controlled injection of Onyx with a decreased risk of reflux and decreased fluoroscopy times.
The diagnostic and prognostic value of coronary CT angiography in asymptomatic high-risk patients: a cohort study
Authors: Plank Fabian , Friedrich Guy , Dichtl Wolfgang , Klauser Andrea , Jaschke Werner , Franz Wolfgang-Michael , Feuchtner Gudrun
Published: August 2014

Objective

To prospectively assess the value of coronary CT angiography (CTA) in asymptomatic patients with high ‘a priori’ risk of coronary artery disease (CAD).

Methods

711 consecutive asymptomatic patients (61.8 years; 40.1% female) with high ‘a priori’ risk of CAD were prospectively examined with a coronary calcium score (CCS) and CTA. Coronary arteries were evaluated for atherosclerotic plaque (non-calcified and calcified) and stenosis (mild <50%, intermediate 50–70% or high-grade >70%). Coronary Segment Involvement Score (SIS, total number of segments with plaque) and nc (non-calcified) SIS were calculated. Primary end points were major adverse cardiac events (ST-elevation MI, non-ST-elevation MI and cardiac death); secondary end points were coronary revascularisation and >50% stenosis by invasive angiography.

Results

Of 711 patients, 28.3% were negative for CAD and 71.7% positive (CAD+) by CTA (15.6% had plaques without stenosis, 23.9% mild, 10.7% intermediate and 21.5% high-grade stenosis). CCS zero prevalence was 306 (43%), out of those 100 (32.7%) had non-calcified plaque only. Mean follow-up period was 2.65 years. MACE rate was 0% in CAD negative and higher (1.2%) in CAD positive by CTA. Coronary revascularisation rate was 5.5%. Patients with SIS ≥5 had an HR of 6.5 (95% CI 1.6 to 25.8, p<0.013) for MACE, patients with ncSIS ≥1 had an HR of 2.4 (95% CI 1.2 to 4.6, p<0.01) for secondary end point. The sensitivity of CTA for stenosis >50% compared with invasive angiography was 92.9% (95% CI 83.0% to 98.1%). Negative predictive value of CTA was 99.4% (95% CI 98.3% to 99.8%) for combined end points.

Conclusions

CAD prevalence by CTA in asymptomatic high-risk patients is high. CCS zero does not exclude CAD. CTA is highly accurate to exclude CAD. Total coronary plaque burden and nc plaques, even if only one segment is involved, are associated with an increased risk of adverse outcome.
Ascites resulting from a ruptured perinephric pseudocyst associated with a renal cyst in a dog
Authors: Orioles M. , Di Bella A. , Merlo M. , Ter Haar G.
Published: August 2014

A three‐year‐old female spayed labrador retriever was presented with progressive abdominal enlargement due to ascites. Clinical examination, clinical pathology, diagnostic imaging and explorative laparotomy findings were suggestive of the contemporary presence of a ruptured perinephric pseudocyst, and an intraparenchymal renal cyst in the right kidney. The dog recovered well after exploratory celiotomy with complete resection of the pseudocyst and nephrectomy, and clinical signs resolved completely. Histopathology revealed the concomitant presence of a renal cyst, lined by epithelium of tubular origin, with a pseudocystic structure adjacent to the kidney. A congenital origin of these lesions was suggested. To the authors’ knowledge, this is the first report describing ascites as the clinical presentation of a ruptured perinephric pseudocyst in a dog. Although rare, it should be considered as a differential diagnosis in dogs presenting with ascites.
Epidemic spreading and immunization in node-activity networks
Authors: Wu Qingchu , Chen Shufang
Published: August 2014

In this paper, we study the epidemic spreading in node-activity networks, where an individual participates in social networks with a certain rate h. There are two cases for h: the state-independent case and the state-dependent case. We investigate the epidemic threshold as a function of h compared to the static network. Our results suggest the epidemic threshold cannot be exactly predicted by using the analysis approach in the static network. In addition, we further propose a local information-based immunization protocol on node-activity networks. Simulation analysis shows that the immunization can not only eliminate the infectious disease, but also change the epidemic threshold via increasing the immunization parameter.
A SURVEY OF AUTOMATIC PERSON RECOGNITION USING EYE MOVEMENTS
Authors: SAEED USMAN
Published: August 2014

The human eye is rich in physical and behavioral attributes that can be used for automatic person recognition. The physical attributes such as the iris attracted early attention and yielded significant recognition results, but like most physical biometrics, they have several disadvantages such as intrusive acquisition, vulnerability to spoofing attacks, etc. Consequently, during the last decade the behavioral attributes extracted from human eyes have steadily gained interest from the automatic person recognition research community. In this first of its kind survey, we present the studies utilizing the behavioral attributes of human eyes for automatic person recognition. We have proposed a unique classification based on the type of stimuli used to elicit behavioral attributes. In addition, for each approach we have carefully examined the common steps involved in automatic person recognition from database acquisition, feature extraction to classification. Lastly, we also present a comparison of the recognition results obtained by each approach.
Recent advances in paracontact metric geometry
Authors: Calvaruso Giovanni , Martín-Molina Verónica
Published: August 2014

In the last years, a growing number of researchers have studied paracontact metric geometry. We shall present here some of the recently obtained results in this topic.
Preparation of Y2O3:Eu3+, Tb3+ nanopowders with tunable luminescence by ammonium bicarbonate co-precipitation method
Authors: Shi Hui , Zhang Xi-Yan , Wang Neng-Li , Dong Wei-Li , Mi Xiao-Yun
Published: August 2014

Y 2 O 3: Eu 3+, Tb 3+ nanopowders were prepared by co-precipitation method with NH 4 HCO 3 as precipitant. The nanopowders with different calcined temperatures and Eu 3+/ Tb 3+ doped ratio were characterized by X-ray Diffraction (XRD), scanning electron microscopy (SEM) and fluorescence spectrophotometer. The results showed that the nanopowders calcined at 1100°C for 2 h had a uniform distribution, high purity and good dispersibility. The particle size was in the range of 60–80 nm. The excitation spectra of Eu 3+/ Tb 3+ co-doped phosphors were wide. The phosphors could emit the green light at the peak of 543 nm and the red light at the peak of 611 nm simultaneously under 276 nm or 300 nm excited. Because of the energy transfer between Tb 3+ and Eu 3+, the 543 nm emission of Tb 3+ ion was weakened while the 611 nm emission of Eu 3+ enhanced. The emissive colors of Y 2 O 3: Eu 3+, Tb 3+ nanopowders could be adjusted from yellow-green to orange-red by changing the Eu 3+/ Tb 3+ doping ratio.
Developing a plasma focus research training system for the fusion energy age
Authors: Lee S.
Published: August 2014

The 3 kJ UNU/ICTP Plasma Focus Facility is the most significant device associated with the AAAPT (Asian African Association for Plasma Training). In original and modified/upgraded form it has trained generations of plasma focus (PF) researchers internationally, producing many PhD theses and peer-reviewed papers. The Lee Model code was developed for the design of this PF. This code has evolved to cover all PF machines for design, interpretation and optimization, for derivation of radiation scaling laws; and to provide insights into yield scaling limitations, radiative collapse, speed-enhanced and current-stepped PF variants. As example of fresh perspectives derivable from this code, this paper presents new results on energy transfers of the axial and radial phases of generalized PF devices. As the world moves inexorably towards the Fusion Energy Age it becomes ever more important to train plasma fusion researchers. A recent workshop in Nepal shows that demand for such training continues. Even commercial project development consultants are showing interest. We propose that the AAAPT-proven research package be upgraded, by modernizing the small PF for extreme modes of operation, switchable from the typical strong-focus mode to a slow-mode which barely pinches, thus producing a larger, more uniform plasma stream with superior deposition properties. Such a small device would be cost-effective and easily duplicated, and have the versatility of a range of experiments from intense multi-radiation generation and target damage studies to superior advanced-materials deposition. The complementary code is used to reference experiments up to the largest existing machine. This is ideal for studying machine limitations and scaling laws and to suggest new experiments. Such a modernized versatile PF machine complemented by the universally versatile code would extend the utility of the PF experience; so that AAAPT continues to provide leadership in pulsed plasma research training in preparation for the Fusion Energy Age.
Correlation of measured neon soft X-ray pulses of the INTI plasma focus with the reflected shock phase at 12KV
Authors: Roy Federico A. , Chong Perk Lin , Saw Sor Heoh
Published: August 2014

The six-phase Lee Model Code is used to fit the computed current waveform to the measured waveform of the INTI Plasma Focus (PF;2.2 kJ at 12 kV), a T2 PF device, operated as a source of Neon soft X-ray (SXR) with optimum yield around 2.5 - 3 Torr of neon. The characteristic He-like and H-like neon line SXR pulse is measured using a pair of SXR detectors with selected filters that, by subtraction, have a photon energy window of 900 to 1550 eV covering the region of the characteristic neon SXR lines. The aim of this paper is to investigate the correlation between the time histories of the measured Neon soft X-ray pulse and the reflected shock phase of the computed current waveform which has been fitted to the measured current waveform. Results shows that the characteristic neon SXR measured at 3.17 J with a pulse duration of 249 ns starts typically after the radial inward shock phase and increases in magnitude few ns before the pinch phase. It tails unto the first anomalous resistance, and decays at the second anomalous resistance.