bluuebunny/crossref_metadata_2025 huggingface dataset:
Evolutionary Engineering Improves Tolerance for Replacement Jet Fuels in Saccharomyces cerevisiae
Authors: Brennan Timothy C. R. , Williams Thomas C. , Schulz Benjamin L. , Palfreyman Robin W. , Krömer Jens O. , Nielsen Lars K.
Published: March 2015

Monoterpenes are liquid hydrocarbons with applications ranging from flavor and fragrance to replacement jet fuel. Their toxicity, however, presents a major challenge for microbial synthesis. Here we evolved limonene-tolerant
Saccharomyces cerevisiae
strains and sequenced six strains across the 200-generation evolutionary time course. Mutations were found in the tricalbin proteins Tcb2p and Tcb3p. Genomic reconstruction in the parent strain showed that truncation of a single protein (tTcb3p
1-989
), but not its complete deletion, was sufficient to recover the evolved phenotype improving limonene fitness 9-fold. tTcb3p
1-989
increased tolerance toward two other monoterpenes (β-pinene and myrcene) 11- and 8-fold, respectively, and tolerance toward the biojet fuel blend AMJ-700t (10% cymene, 50% limonene, 40% farnesene) 4-fold. tTcb3p
1-989
is the first example of successful engineering of phase tolerance and creates opportunities for production of the highly toxic C
10
alkenes in yeast.
Mortality Caused by Bath Exposure of Zebrafish (Danio rerio) Larvae to Nervous Necrosis Virus Is Limited to the Fourth Day Postfertilization
Authors: Morick Danny , Faigenbaum Or , Smirnov Margarita , Fellig Yakov , Inbal Adi , Kotler Moshe
Published: March 2015

Nervous necrosis virus (NNV) is a member of the
Betanodavirus
genus that causes fatal diseases in over 40 species of fish worldwide. Mortality among NNV-infected fish larvae is almost 100%. In order to elucidate the mechanisms responsible for the susceptibility of fish larvae to NNV, we exposed zebrafish larvae to NNV by bath immersion at 2, 4, 6, and 8 days postfertilization (dpf). Here, we demonstrate that developing zebrafish embryos are resistant to NNV at 2 dpf due to the protection afforded by the egg chorion and, to a lesser extent, by the perivitelline fluid. The zebrafish larvae succumbed to NNV infection during a narrow time window around the 4th dpf, while 6- and 8-day-old larvae were much less sensitive, with mortalities of 24% and 28%, respectively.
Influence of Adhesion Force on
icaA
and
cidA
Gene Expression and Production of Matrix Components in Staphylococcus aureus Biofilms
Authors: Harapanahalli Akshay K. , Chen Yun , Li Jiuyi , Busscher Henk J. , van der Mei Henny C.
Published: March 2015

The majority of human infections are caused by biofilms. The biofilm mode of growth enhances the pathogenicity of
Staphylococcus
spp. considerably, because once they adhere, staphylococci embed themselves in a protective, self-produced matrix of extracellular polymeric substances (EPSs). The aim of this study was to investigate the influence of forces of staphylococcal adhesion to different biomaterials on
icaA
(which regulates the production of EPS matrix components) and
cidA
(which is associated with cell lysis and extracellular DNA [eDNA] release) gene expression in
Staphylococcus aureus
biofilms. Experiments were performed with
S. aureus
ATCC 12600 and its isogenic mutant,
S. aureus
ATCC 12600 Δ
pbp4
, deficient in peptidoglycan cross-linking. Deletion of
pbp4
was associated with greater cell wall deformability, while it did not affect the planktonic growth rate, biofilm formation, cell surface hydrophobicity, or zeta potential of the strains. The adhesion forces of
S. aureus
ATCC 12600 were the strongest on polyethylene (4.9 ± 0.5 nN), intermediate on polymethylmethacrylate (3.1 ± 0.7 nN), and the weakest on stainless steel (1.3 ± 0.2 nN). The production of poly-
N
-acetylglucosamine, eDNA presence, and expression of
icaA
genes decreased with increasing adhesion forces. However, no relation between adhesion forces and
cidA
expression was observed. The adhesion forces of the isogenic mutant
S. aureus
ATCC 12600 Δ
pbp4
(deficient in peptidoglycan cross-linking) were much weaker than those of the parent strain and did not show any correlation with the production of poly-
N
-acetylglucosamine, eDNA presence, or expression of the
icaA
and
cidA
genes. This suggests that adhesion forces modulate the production of the matrix molecule poly-
N
-acetylglucosamine, eDNA presence, and
icaA
gene expression by inducing nanoscale cell wall deformation, with cross-linked peptidoglycan layers playing a pivotal role in this adhesion force sensing.
Neospora caninum Recruits Host Cell Structures to Its Parasitophorous Vacuole and Salvages Lipids from Organelles
Authors: Nolan Sabrina J. , Romano Julia D. , Luechtefeld Thomas , Coppens Isabelle
Published: March 2015

Toxoplasma gondii
and
Neospora caninum
, which cause the diseases toxoplasmosis and neosporosis, respectively, are two closely related apicomplexan parasites. They have similar heteroxenous life cycles and conserved genomes and share many metabolic features. Despite these similarities,
T. gondii
and
N. caninum
differ in their transmission strategies and zoonotic potential. Comparative analyses of the two parasites are important to identify the unique biological features that underlie the basis of host preference and pathogenicity.
T. gondii
and
N. caninum
are obligate intravacuolar parasites; in contrast to
T. gondii
, events that occur during
N. caninum
infection remain largely uncharacterized. We examined the capability of
N. caninum
(Liverpool isolate) to interact with host organelles and scavenge nutrients in comparison to that of
T. gondii
(RH strain).
N. caninum
reorganizes the host microtubular cytoskeleton and attracts endoplasmic reticulum (ER), mitochondria, lysosomes, multivesicular bodies, and Golgi vesicles to its vacuole though with some notable differences from
T. gondii
. For example, the host ER gathers around the
N. caninum
parasitophorous vacuole (PV) but does not physically associate with the vacuolar membrane; the host Golgi apparatus surrounds the
N. caninum
PV but does not fragment into ministacks.
N. caninum
relies on plasma lipoproteins and scavenges cholesterol from NPC1-containing endocytic organelles. This parasite salvages sphingolipids from host Golgi Rab14 vesicles that it sequesters into its vacuole. Our data highlight a remarkable degree of conservation in the intracellular infection program of
N. caninum
and
T. gondii
. The minor differences between the two parasites related to the recruitment and rearrangement of host organelles around their vacuoles likely reflect divergent evolutionary paths.
Training in Self-Needling and Performing it as Part of a Clinical Trial: The Practitioner and Patient Experience
Authors: Bardy Joy , Mackereth Peter , Finnegan-John Jennifer , Molassiotis Alexander
Published: March 2015

Objective

To explore the experience of training and performing self-needling from both the practitioners’ and patients’ perspective.

Methods

A qualitative study was conducted using focus groups and interviews, nested within our multi-site randomised controlled trial, Acupuncture for Cancer-Related Fatigue in Patients with Breast Cancer. Patients allocated to self-needling across two UK study sites and all therapists who were involved in the trial were invited to participate. The interviews/focus groups were then transcribed verbatim and analysed thematically by the process of content analysis.

Results

Of the 67 eligible patients, 8 (12%) contributed to the focus groups and 15 practitioners (100%), contributed to the study by either attending a focus group or being interviewed. Themes identified for patients included: the allocation to self-needling, teaching techniques and practical considerations and whether they would self-needle again. Themes identified for practitioners included: views on self-needling, teaching self-needling and future implications of self-needling.

Conclusions

Self-needling was found to be acceptable to, and manageable by, patients, and enthusiastically adopted by most practitioners. Methods of teaching self-needling need to be developed and evaluated with guidelines recommended for best practice.
Knowledge, Attitude and Practice among Chinese Acupuncturists Receiving Sham And/Or Placebo Acupuncture: A Cross-Sectional Survey
Authors: Jin Chunlan , Zhou Xinyao , Pang Ran
Published: March 2015

Background

Placebo and sham acupuncture are common control strategies in acupuncture studies. However, the perception and practice of these approaches in acupuncturists are poorly documented.

Objective

To investigate knowledge of, attitude towards and practice of sham and/or placebo acupuncture among Chinese acupuncturists.

Method

A cross-sectional survey conducted in six different tertiary care hospitals of traditional Chinese medicine in Beijing, China. A total of 92 licensed acupuncturists were asked to complete a predesigned and structured questionnaire on-site.

Results

A response rate of 92.4% (n=85) was achieved. Almost all participants (99%, n=84) had moderate knowledge about sham and/or placebo acupuncture, but only a minority (27%, n=23) reported an excellent understanding. The general attitude towards sham and/or placebo acupuncture was positive. Most respondents (99%, n=84) thought such controls were necessary and the majority (81%, n=69) believed they were feasible in acupuncture research. More than two-thirds of participants (71%, n=60) had applied sham and/or placebo acupuncture, but only a few (8%, 5/60) used it as the most common control strategy in clinical trials.

Conclusions

The result of our survey suggests that Chinese acupuncturists have a moderate knowledge of, and a positive attitude towards, sham and/or placebo acupuncture. Research into sham and/or placebo acupuncture is limited in comparison with other control strategies. Therefore, an in-service education programme for acupuncturists and standardisation of sham and/or placebo acupuncture need to be developed.
Prevalence of shingles and its association with PTSD among HIV-infected women in Rwanda
Authors: Sinayobye Jean d'Amour , Hoover Donald R , Shi Qiuhu , Mutimura Eugene , Cohen Hillel W , Anastos Kathryn
Published: March 2015

Objective

To examine the prevalence of reported shingles in the last 6 months and its association with post-traumatic stress disorder (PTSD), depression and severity of HIV disease in Rwandan women with HIV.

Settings

This cross-sectional study was conducted as part of the Rwanda Women's Interassociation Study and Assessment (RWISA), an observational cohort study designed to assess the impact of HIV and residual factors from experiencing rape in the 1994 genocide in Rwandan women. Participants were recruited through grassroots women's associations of people living with HIV infection and clinical care sites for HIV infection. Most participants (58.5%, n=405/692) had PTSD.

Participants

This cross-sectional analysis was conducted in 710 HIV-infected women enrolled in RWISA. Inclusion criteria were: age >15 years, informed consent, HIV test, ability to complete the interview in the local language, travel to and from the research site and participate in a baseline outpatient visit, and being naive to antiretroviral therapy at enrolment.

Primary and secondary outcome measures

The outcome of interest was self-reported shingles in the past 6 months. The exposure was PTSD defined using the cross-culturally validated Harvard Trauma Questionnaire.

Results

Overall prevalence of reported shingles in the past 6 months was 12.5% (n=89/710). There was an inverse relationship between shingles prevalence and immunological status: 7.6%, 12.3% and 16.7% of women with CD4 >350, 200–350 and <200 cells/µL, respectively, reported singles (p=0.01). In multivariate analysis, PTSD (aOR 1.7; 95% CI 1.02 to 2.89) and low CD4 (aOR 2.4; 95% CI 1.23 to 4.81) were independently associated with reported shingles in the past 6 months.

Conclusions

Our study found a significant independent relationship between PTSD and reported shingles, suggesting that PTSD may be associated with immune compromise that can result in herpes zoster reactivation. Further study is needed. It also confirmed previous findings of a strong relationship between shingles and greater immunosuppression in women with HIV infection.
Assessing the validity of respondents’ reports of their partners’ ages in a rural South African population-based cohort
Authors: Harling Guy , Tanser Frank , Mutevedzi Tinofa , Bärnighausen Till
Published: March 2015

Objectives

This study evaluated the validity of using respondents’ reports of age disparity in their sexual relationships (perceived disparity), compared to age disparity based on each partner's report of their own date of birth (actual disparity).

Setting

The study was conducted using data from a longitudinal population-based cohort in rural KwaZulu-Natal, South Africa, between 2005 and 2012.

Participants

The study used 13 831 reports of partner age disparity within 7337 unique conjugal relationships. 10 012 (72.4%) reports were made by women.

Primary and secondary outcome measures

The primary outcome was the Lin concordance correlation of perceived and actual age disparities. Secondary outcomes included the sensitivity/specificity of perceived disparities to assess whether the man in the relationship was more than five or more than 10 years older than the woman.

Results

Mean relationship age disparity was 6 years. On average, respondents slightly underestimated their partners’ ages (male respondents: 0.50 years; female respondents: 0.85 years). Almost three-quarters (72.3%) of age disparity estimates fell within 2 years of the true values, although a small minority of reports were far from correct. The Lin concordance correlation of perceived and actual age disparities (men: ρ=0.61; women: ρ=0.78), and assessments of whether the man in the relationship was more than five, or more than 10 years older than the woman (sensitivity >60%; specificity >75%), were relatively high. Accuracy was higher for spouses and people living in the same household, but was not affected by relationship duration.

Conclusions

Rural South Africans reported their sexual partners’ ages imperfectly, but with less error than in some other African settings. Further research is required to determine how generalisable these findings are. Self-reported data on age disparity in sexual relationships can be used with caution for research, intervention design, and targeting in this and similar settings.
Adherence-adjusted estimates of benefits and harms from treatment with amoxicillin for LRTI: secondary analysis of a 12-country randomised placebo-controlled trial using randomisation-based efficacy estimators
Authors: Gillespie David , Hood Kerenza , Farewell Daniel , Butler Christopher C , Verheij Theo , Goossens Herman , Stuart Beth , Mullee Mark , Little Paul
Published: March 2015

Objectives

Estimate the efficacy of amoxicillin for acute uncomplicated lower-respiratory-tract infection (LRTI) in primary care and demonstrate the use of randomisation-based efficacy estimators.

Design

Secondary analysis of a two-arm individually-randomised placebo-controlled trial.

Setting

Primary care practices in 12 European countries.

Participants

Patients aged 18 or older consulting with an acute LRTI in whom pneumonia was not suspected by the clinician.

Interventions

Amoxicillin (two 500 mg tablets three times a day for 7 days) or matched placebo.

Main outcome measures

Clinician-rated symptom severity between days 2–4; new/worsening symptoms and presence of side effects at 4-weeks. Adherence was captured using self-report and tablet counts.

Results

2061 participants were randomised to the amoxicillin or placebo group. On average, 88% of the prescribed amoxicillin was taken. The original analysis demonstrated small increases in both benefits and harms from amoxicillin. Minor improvements in the benefits of amoxicillin were observed when an adjustments for adherence were made (mean difference in symptom severity −0.08, 95% CI −0.17 to 0.01, OR for new/worsening symptoms 0.81, 95% CI 0.66 to 0.98) as well as minor increases in harms (OR for side effects 1.32, 95% CI 1.12 to 1.57).

Conclusions

Adherence to amoxicillin was high, and the findings from the original analysis were robust to non-adherence. Participants consulting to primary care with an acute uncomplicated LRTI can on average expect minor improvements in outcome from taking amoxicillin. However, they are also at an increased risk of experiencing side effects.

Trial registration numbers

Eudract-CT 2007-001586-15 andISRCTN52261229.

The trial was registered at EudraCT in 2007 due to an administrative misunderstanding that EudraCT was a suitable registry—which it was not in 2007, but has become since. On discovery of this error, the trial was also registered at ISRCTN (January 2009). Trial procedures did not change between the two registrations.
Psychosocial deprivation in women with gestational diabetes mellitus is associated with poor fetomaternal prognoses: an observational study
Authors: Cosson Emmanuel , Bihan Hélène , Reach Gérard , Vittaz Laurence , Carbillon Lionel , Valensi Paul
Published: March 2015

Objective

To evaluate the prognoses associated with psychosocial deprivation in women with gestational diabetes mellitus (GDM).

Design

Observational study considering the 1498 multiethnic women with GDM who gave birth between January 2009 and February 2012.

Setting

Four largest maternity units in the northeastern suburban area of Paris.

Participants

The 994 women who completed the Evaluation of Precarity and Inequalities in Health Examination Centers (EPICES) questionnaire.

Main outcome measure

Main complications of GDM (large infant for gestational age (LGA), shoulder dystocia, caesarean section, pre-eclampsia).

Results

Psychosocial deprivation (EPICES score ≥30.17) affected 577 women (56%) and was positively associated with overweight/obesity, parity and non-European origin, and negatively associated with family history of diabetes, fruit and vegetable consumption and working status. The psychosocially deprived women were diagnosed with GDM earlier, received insulin treatment during pregnancy more often and were more likely to have LGA infants (15.1% vs 10.6%, OR=1.5 (95% CI 1.02 to 2.2), p<0.05) and shoulder dystocia (3.1% vs 1.2%, OR=2.7 (0.97 to 7.2), p<0.05). In addition to psychosocial deprivation, LGA was associated with greater parity, obesity, history of GDM, ethnicity, excessive gestational weight gain and insulin therapy. A multivariate analysis using these covariates revealed that the EPICES score was independently associated with LGA infants (per 10 units, OR=1.12 (1.03 to 1.20), p<0.01).

Conclusions

In our area, psychosocial deprivation is common in women with GDM and is associated with earlier GDM diagnoses and greater insulin treatment, an increased likelihood of shoulder dystocia and, independently of obesity, gestational weight gain and other confounders with LGA infants.
Is the promise of methadone Kenya’s solution to managing HIV and addiction? A mixed-method mathematical modelling and qualitative study
Authors: Rhodes Tim , Guise Andy , Ndimbii James , Strathdee Steffanie , Ngugi Elizabeth , Platt Lucy , Kurth Ann , Cleland Charles , Vickerman Peter
Published: March 2015

Background and objectives

Promoted globally as an evidence-based intervention in the prevention of HIV and treatment of heroin addiction among people who inject drugs (PWID), opioid substitution treatment (OST) can help control emerging HIV epidemics among PWID. With implementation in December 2014, Kenya is the third Sub-Saharan African country to have introduced OST. We combine dynamic mathematical modelling with qualitative sociological research to examine the ‘promise of methadone’ to Kenya.

Methods, setting and participants

We model the HIV prevention impact of OST in Nairobi, Kenya, at different levels of intervention coverage. We draw on thematic analyses of 109 qualitative interviews with PWID, and 43 with stakeholders, to chart their narratives of expectation in relation to the promise of methadone.

Results

The modelled impact of OST shows relatively slight reductions in HIV incidence (5–10%) and prevalence (2–4%) over 5 years at coverage levels (around 10%) anticipated in the planned roll-out of OST. However, there is a higher impact with increased coverage, with 40% coverage producing a 20% reduction in HIV incidence, even when accounting for relatively high sexual transmissions. Qualitative findings emphasise a culture of ‘rationed expectation’ in relation to access to care and a ‘poverty of drug treatment opportunity’. In this context, the promise of methadone may be narrated as a symbol of hope—both for individuals and community—in relation to addiction recovery.

Conclusions

Methadone offers HIV prevention potential, but there is a need to better model the effects of sexual HIV transmission in mediating the impact of OST among PWID in settings characterised by a combination of generalised and concentrated epidemics. We find that individual and community narratives of methadone as hope for recovery coexist with policy narratives positioning methadone primarily in relation to HIV prevention. Our analyses show the value of mixed methods approaches to investigating newly-introduced interventions.
Initiation rates of statin therapy for the primary prevention of cardiovascular disease: an assessment of differences between countries of the UK and between regions within England
Authors: O'Keeffe Aidan G , Petersen Irene , Nazareth Irwin
Published: March 2015

Objectives

To investigate the extent to which variation exists in the initiation rate of statin therapy for the primary prevention of cardiovascular disease between countries of the UK and between different regions within England.

Design

Cohort study using data from a large UK primary care database.

Setting

UK.

Participants

4 820 885 individuals from 554 general practices during the period 2004–2012.

Main outcome measures

Rate of statin therapy initiation per 1000 person-years.

Results

Relative to a fixed English rate of 1 initiation per 1000 person-years and accounting for gender, age and social deprivation level, the rate was similar for Scotland at 0.92 (95% CI 0.84 to 1.00) and rates for Northern Ireland and Wales were higher at 1.40 (95% CI 1.20 to 1.62) and 1.18 (95% CI 1.05 to 1.32), respectively. Within England, the regions could be classified into three groups with respect to statin therapy initiation rates (relative to a rate of 1 initiation per 1000 person-years for London): the South Central 0.73 (95% CI 0.64 to 0.83), South West 0.80 (95% CI 0.71 to 0.91), East of England 0.81 (95% CI 0.71 to 0.94) and South East Coast 0.83 (95% CI 0.73 to 0.95); strategic health authorities had similar low rates followed by the East Midlands 0.88 (95% CI 0.73 to 1.05), West Midlands 0.96 (95% CI 0.84 to 1.09), North East 0.96 (95% CI 0.79 to 1.16), Yorkshire and Humber 0.97 (95% CI 0.81 to 1.17) and London strategic health authorities. North West England exhibited the highest rate of statin therapy initiation of 1.16 (95% CI 1.02 to 1.31).

Conclusions

Considerable variation in the rate of statin therapy initiation was observed between the four countries of the UK and between different geographical regions within England.
Fix and forget or fix and report: a qualitative study of tensions at the front line of incident reporting
Authors: Hewitt Tanya Anne , Chreim Samia
Published: March 2015

Introduction

Practitioners frequently encounter safety problems that they themselves can resolve on the spot. We ask: when faced with such a problem, do practitioners fix it in the moment and forget about it, or do they fix it in the moment and report it? We consider factors underlying these two approaches.

Methods

We used a qualitative case study design employing in-depth interviews with 40 healthcare practitioners in a tertiary care hospital in Ontario, Canada. We conducted a thematic analysis, and compared the findings with the literature.

Results

‘Fixing and forgetting’ was the main choice that most practitioners made in situations where they faced problems that they themselves could resolve. These situations included (A) handling near misses, which were seen as unworthy of reporting since they did not result in actual harm to the patient, (B) prioritising solving individual patients’ safety problems, which were viewed as unique or one-time events and (C) encountering re-occurring safety problems, which were framed as inevitable, routine events. In only a few instances was ‘fixing and reporting’ mentioned as a way that the providers dealt with problems that they could resolve.

Conclusions

We found that generally healthcare providers do not prioritise reporting if a safety problem is fixed. We argue that fixing and forgetting patient safety problems encountered may not serve patient safety as well as fixing and reporting. The latter approach aligns with recent calls for patient safety to be more preventive. We consider implications for practice.
Pay-for-performance policy and data-driven decision making within nursing homes: a qualitative study
Authors: Abrahamson Kathleen , Miech Edward , Davila Heather Wood , Mueller Christine , Cooke Valerie , Arling Greg
Published: March 2015

Introduction

Health systems globally and within the USA have introduced nursing home pay-for-performance (P4P) programmes in response to the need for improved nursing home quality. Central to the challenge of administering effective P4P is the availability of accurate, timely and clinically appropriate data for decision making. We aimed to explore ways in which data were collected, thought about and used as a result of participation in a P4P programme.

Methods

Semistructured interviews were conducted with 232 nursing home employees from within 70 nursing homes that participated in P4P-sponsored quality improvement (QI) projects. Interview data were analysed to identify themes surrounding collecting, thinking about and using data for QI decision making.

Results

The term ‘data’ appeared 247 times in the interviews, and over 92% of these instances (228/247) were spontaneous references by nursing home staff. Overall, 34% of respondents (79/232) referred directly to ‘data’ in their interviews. Nursing home leadership more frequently discussed data use than direct care staff. Emergent themes included using data to identify a QI problem, gathering data in new ways at the local level, and measuring outcomes in response to P4P participation. Alterations in data use as a result of policy change were theoretically consistent with the revised version of the Promoting Action on Research Implementation in Health Services framework, which posits that successful implementation is a function of evidence, context and facilitation.

Conclusions

Providing a reimbursement context that facilitates the collection and use of reliable local evidence may be an important consideration to others contemplating the adaptation of P4P policies.
Application of a trigger tool in near real time to inform quality improvement activities: a prospective study in a general medicine ward
Authors: Wong Brian M , Dyal Sonia , Etchells Edward E , Knowles Sandra , Gerard Lauren , Diamantouros Artemis , Mehta Rajin , Liu Barbara , Baker G Ross , Shojania Kaveh G
Published: March 2015

Background

Retrospective record review using trigger tools remains the most widely used method for measuring adverse events (AEs) to identify targets for improvement and measure temporal trends. However, medical records often contain limited information about factors contributing to AEs. We implemented an augmented trigger tool that supplemented record review with debriefing front-line staff to obtain details not included in the medical record. We hypothesised that this would foster the identification of factors contributing to AEs that could inform improvement initiatives.

Method

A trained observer prospectively identified events in consecutive patients admitted to a general medical ward in a tertiary care academic medical centre (November 2010 to February 2011 inclusive), gathering information from record review and debriefing front-line staff in near real time. An interprofessional team reviewed events to identify preventable and potential AEs and characterised contributing factors using a previously published taxonomy.

Results

Among 141 patients, 14 (10%; 95% CI 5% to 15%) experienced at least one preventable AE; 32 patients (23%; 95% CI 16% to 30%) experienced at least one potential AE. The most common contributing factors included policy and procedural problems (eg, routine protocol violations, conflicting policies; 37%), communication and teamwork problems (34%), and medication process problems (23%). However, these broad categories each included distinct subcategories that seemed to require different interventions. For instance, the 32 identified communication and teamwork problems comprised 7 distinct subcategories (eg, ineffective intraprofessional handovers, poor interprofessional communication, lacking a shared patient care, paging problems). Thus, even the major categories of contributing factors consisted of subcategories that individually related to a much smaller subset of AEs.

Conclusions

Prospective application of an augmented trigger tool identified a wide range of factors contributing to AEs. However, the majority of contributing factors accounted for a small number of AEs, and more general categories were too heterogeneous to inform specific interventions. Successfully using trigger tools to stimulate quality improvement activities may require development of a framework that better classifies events that share contributing factors amenable to the same intervention.
The Handbook: an end to 'I wish I had known that before I started'
Authors: Davies Mike , Panchal Sonia , Misra Nikhil
Published: March 2015

The importance of an effective handover between clinicians is vital, particularly for junior doctors when commencing a new clinical rotation. When junior doctors commence a new rotation there is often a significant amount of new information and tasks that they must learn, whilst also maintaining a high level of care for patients. However, very little information is formally passed from the outgoing junior doctor to the incoming junior doctor when changing rotations, resulting in a gap in knowledge and information having to be relearned by each junior doctor for each ward.

Through a junior doctor led service improvement initiative we created an intranet-based, updateable, easily accessible, and secure resource to assist junior doctors during this transition period. Our project was not only beneficial to junior doctors when starting on a new rotation but also helped them understand their role within the ward environment and become more efficient in their clinical work. The project is an example of a sustainable service improvement project implemented with no cost that due to its format and low maintenance, could be easily adapted on a wider scale in other hospitals or Trusts.
Alterations to calling criteria for Between the Flags (an early warning system)
Authors: Davis Tessa , Nogajski Bec
Published: March 2015

Early warning systems aim to detect clinical deterioration of patients at an early stage. Between the Flags was introduced in New South Wales Health for this purpose. When patients are transferred from the emergency department to the ward, there are circumstances when the calling criteria need to be altered to take into account the clinical context. It is recognised that confusion exists among junior medical staff about the process of making alterations to the Between the Flags calling criteria.

A quality improvement project was implemented by undertaking a baseline survey of junior medical staff, providing education and training (to junior medical staff on the existing guidelines for making alteration to the calling criteria), and conducting a post-implementation survey.

A baseline survey demonstrated that 74% of junior medical staff had received no education on making alterations and only 5% knew how long their alterations would last once the patient was transferred to the ward. This has potentially serious consequences for patient safety following transfer.

After implementation of training, we found that 63% of junior medical staff were aware of the guidelines on making alterations and 50% knew how long their alterations would last once the patient was transferred to the ward. We conclude that educating junior medical staff improved knowledge on the guidelines for making alterations to calling criteria.
Role of inflammatory infiltrates in triple negative breast cancer
Authors: Matsumoto Hirofumi , Koo Si-lin , Dent Rebecca , Tan Puay Hoon , Iqbal Jabed
Published: March 2015

Triple negative breast cancer (TNBC) is a heterogenous disease often characterised by aggressive biology and poor prognosis. Efforts to precisely treat TNBC have been compounded by the lack of specific therapeutic molecular targets. Recent transcriptomic studies have revealed, among others, an immunomodulatory subtype of TNBC, whereby activated immune response genes are associated with good prognosis. Since then, a great deal of effort has been made to understand the immune microenvironment of some TNBC subtype, which comprises several immune cell populations including lymphocytes and macrophages. There is increasing evidence that the basal subtype may be significantly regulated by tumour-infiltrating T-cells and that high levels of tumour-infiltrating CD8+ T-cells may be a reflection of improved prognosis with chemotherapy sensitivity in TNBC. On the other hand, tumour-associated macrophages have been associated with a relatively poor outcome in TNBC. Comparison of the immune signatures in TNBC with non-TNBC may furthermore help us to understand these immune mechanisms potentially leading to new therapeutic approaches. Within this short review, we discuss the current scientific evidence regarding (a) the role of tumour-infiltrating lymphocytes in the clinical outcome in TNBC and (b) the newly discovered immunomodulatory genotype that may provide for a therapeutic target in TNBC.
Perivascular epithelioid tumours (PEComas) of the gynaecological tract
Authors: Conlon Niamh , Soslow Robert A , Murali Rajmohan
Published: March 2015

Perivascular epithelioid tumours (PEComas) of the gynaecological tract are rare tumours which were first recognised and diagnosed within the last 20 years. They represent a unique diagnostic challenge with regard to their accurate and reproducible distinction from more common entities such as smooth muscle tumours of the uterine corpus. In this review article, we trace the development of the concept of the PEComa tumour family, highlight what is known about extra-gynaecological tract PEComa at an immunohistochemical, molecular and therapeutic level and then present a summary of all reported cases of gynaecological tract PEComa to date. In the summary, we highlight rare subtypes of gynaecological tract PEComa and compare the performances of extant prognostic classification systems for malignancy in these tumours.
Fulminant amoebic colitis: a clinicopathological study of 30 cases
Authors: Chaturvedi Rachana , Gupte Prajakta A , Joshi Amita S
Published: March 2015

Aims

To review the clinical and pathological factors associated with fulminant amoebic colitis (FAC) requiring colonic resection and its outcome.

Methods

We retrospectively identified adult patients admitted to our centre between June 2007 and December 2011 with FAC who underwent colonic resection and were diagnosed with amoebic colitis based on the presence of trophozoites on histological examination. The clinical details were extracted from the medical notes and correlated with the pathological findings.

Results

Thirty patients (18 men and 12 women) met the inclusion criteria. Their mean age was 50.1 years (range 21–89). The most frequent symptoms were abdominal pain, vomiting and fever. More than half the patients (16/30) had underlying conditions associated with immunosuppression including diabetes mellitus and tuberculosis. Pathological investigation of colonic resections showed predominantly right-sided involvement with geographic colonic ulcers covered with a creamy-white pseudomembrane, perforations, gangrenous changes, amoeboma and lesions mimicking inflammatory bowel disease. All showed basophilic dirty necrosis with abundant nuclear debris and amoebic trophozoites on histological examination. 21/30 patients (70%) had involvement beyond the caecum. 17/30 patients (57%) died. Those with involvement beyond the caecum were more likely to die (15/21, 71.4%) than those with less extensive disease.

Conclusions

FAC presents as acute abdomen and can mimic appendicitis, ischaemic bowel disease, tuberculosis and malignancy. Comorbidities causing immunosuppression frequently associated. Mortality remains high despite surgery, so FAC should be suspected in every case of acute abdomen with colonic perforation if associated with typical gross and microscopic findings and a history of stay in an endemic area.
Geomicrobiology of carbonate microbialites in the Tahiti reef
Authors: Warthmann Rolf J. , Camoin Gilbert , McKenzie Judith A. , Vasconcelos Crisógono
Published: March 2015

Integrated Ocean Drilling Program (IODP) Expedition 310 (Tahiti Sea Level) offered an opportunity to study the geomicrobiology of a reef framework. Offshore drilling was conducted on the coastal reefs of Tahiti (French Polynesia) at 22 sites in water depths of up to 117 m. Up to 80% of the retrieved core material comprises authigenic grey microbial carbonates with laminated or thrombolitic morphologies, which are associated with corals. Microbialites infilled the cavities during reef development and stabilized the coral reef framework. Rock-surface analyses were performed to track ongoing microbial activity in biofilms that could represent a modern counterpart of the processes at the origin of the formation of fossil microbialites. Significant concentrations of adenosine 5′-triphosphate, indicative of the presence of living microorganisms, were detected at relatively shallow depths, 0–6 m below the seafloor. Exoenzyme activities confirmed the presence of an active metabolizing microbiota forming biofilms in reef cavities. Onshore investigations of the recovered microbes and biofilms completed our picture that the rapid postglacial formation of carbonate microbialites was mediated by the activity of anaerobic microbes, such as sulphate-reducing bacteria and iron-respiring organisms, stimulated by the highly productive reef environment.
Science and scientists from a child's point of view: an overview from drawings
Authors: Rubbia G. , D'Addezio G. , Marsili A. , Carosi A.
Published: March 2015

An analysis of the perceived image of science, scientists and inventions was conducted with hundreds of drawings made by children for a competition held in Italian schools. The ‘draw a scientist’ approach, as used in several studies, was used to analyse images of scientists. A coarse-grain, quantitative analysis of the prevalence of features exhibited stereotypes as well as new trends, suggesting a further fine-grain, qualitative analysis was necessary. A generally positive picture of the work of scientists emerged as well as a great level of confidence in the potential of science, which is capable of responding to the needs and problems of humanity and of the environment in which we live.
Communicating natural hazards: marine extreme events and the importance of variability and forecast errors
Authors: Marone Eduardo , Camargo R. , Salcedo-Castro J.
Published: March 2015

Scientific knowledge has to meet some necessary conditions. Among these, it has to be properly communicated. Usually, scientists (mis)understand this requirement and believe that publishing their results in peer-reviewed journals is enough. Society demands the availability of information in other formats. This is particularly relevant when dealing with natural hazards, which affect the life and fate of human beings. Natural hazards and extreme events are becoming more frequent and energetic, and future scenarios sustain that this tendency will remain or even increase. Furthermore, in trying to explain scientific results to untrained members of society, scientists usually focus more on forecasts than on the prediction errors. Talking about our forecast limitations outside of academia seems shameful, rather than being a logical limitation of sciences and regardless of the fact that discussing limitations is not something of which to be ashamed. Using numerical modelling combined with field observations to predict extreme marine events we hope to show here that it is possible to be less cryptic. Also, the general public needs to know enough to properly deal with variability and uncertainties. Scientists have the ethical responsibility of communicating the uncertainties of our results to society because these limitations are neither obvious nor irrelevant.
Changes in intestinal barrier function and gut microbiota in high-fat diet-fed rats are dynamic and region dependent
Authors: Hamilton M. Kristina , Boudry Gaëlle , Lemay Danielle G. , Raybould Helen E.
Published: March 2015

A causal relationship between the pathophysiological changes in the gut epithelium and altered gut microbiota with the onset of obesity have been suggested but not defined. The aim of this study was to determine the temporal relationship between impaired intestinal barrier function and microbial dysbiosis in the small and large intestine in rodent high-fat (HF) diet-induced obesity. Rats were fed HF diet (45% fat) or normal chow (C, 10% fat) for 1, 3, or 6 wk; food intake, body weight, and adiposity were measured. Barrier function ex vivo using FITC-labeled dextran (4,000 Da, FD-4) and horseradish peroxidase (HRP) probes in Ussing chambers, gene expression, and gut microbial communities was assessed. After 1 wk, there was an immediate but reversible increase in paracellular permeability, decrease in IL-10 expression, and decrease in abundance of genera within the class Clostridia in the ileum. In the large intestine, HRP flux and abundance of genera within the order Bacteroidales increased with time on the HF diet and correlated with the onset of increased body weight and adiposity. The data show immediate insults in the ileum in response to ingestion of a HF diet, which were rapidly restored and preceded increased passage of large molecules across the large intestinal epithelium. This study provides an understanding of microbiota dysbiosis and gut pathophysiology in diet-induced obesity and has identified IL-10 and Oscillospira in the ileum and transcellular flux in the large intestine as potential early impairments in the gut that might lead to obesity and metabolic disorders.
Myocyte TLR4 enhances enteric and systemic inflammation driving late murine endotoxic ileus
Authors: Buchholz Bettina M. , Shapiro Richard A. , Vodovotz Yoram , Billiar Timothy R. , Sodhi Chhinder P. , Hackam David J. , Bauer Anthony J.
Published: March 2015

Myocytes are nonhemopoietic in origin and functionally essential in generating gastrointestinal motility. In endotoxemia, a rapid-onset nonhemopoietic mechanism potently triggers early ileus in a Toll-like receptor 4 (TLR4)/myeloid differentiation primary response gene 88 (MyD88)-dependent manner. Moreover, synergistically with hemopoietic cells, nonhemopoietic cells escalate late ileus via an IL-6 receptor-dependent inflammation-driven pathway. We therefore specifically investigated the role of myocytes in TLR4-triggered inflammation and ileus. TLR4+/+, TLR4−/−, bmTLR4+/+/TLR4−/−chimera, SM22-Cre−/−TLR4flox/flox, and selective myocyte TLR4-deficient (SM22-Cre+/−TLR4flox/flox) mice were injected intraperitoneally with purified lipopolysaccharide. SM22-driven Cre recombinase activity was selectively detected in cardiac, gastrointestinal, skeletal, and vascular myocytes, of small-sized vessels in a two-color fluorescent Cre reporter mouse. In contrast to nonhemopoietic TLR4 deficiency, deletion of myocyte TLR4 signaling prevented neither endotoxin-induced suppression of spontaneous jejunal contractility in vitro nor early ileus in vivo at 6 h. Circulating plasma colony-stimulating factor 3 was greatly elevated during endotoxemia, independent of myocyte TLR4 signaling or time. TLR4 activation of myocytes contributed significantly to an early enteric IL-6 mRNA induction and systemic IL-6 release, as well as to a late increase in circulating chemokine (C-X-C motif) ligand 1 (CXCL1) and IL-17. Consequently, inhibition of myocyte TLR4 signaling allowed functional recovery of motility by preventing inflammation-driven late ileus at 24 h. Direct TLR4 activation of myocytes is not responsible for nonhemopoietic-mediated early ileus. However, myocytes are proinflammatory cells that potently drive enteric and systemic inflammation, subsequently fueling late mediator-triggered ileus. Specifically, the myocyte TLR4-dependent inflammatory signature of elevated plasma IL-6, CXCL1, and IL-17 is strongly associated with late rodent ileus.
Expression ofRegfamily genes in the gastrointestinal tract of mice treated with indomethacin
Authors: Sun Chao , Fukui Hirokazu , Hara Ken , Kitayama Yoshitaka , Eda Hirotsugu , Yang Mo , Yamagishi Hidetsugu , Tomita Toshihiko , Oshima Tadayuki , Watari Jiro , Takasawa Shin , Chiba Tsutomu , Miwa Hiroto
Published: March 2015

Regenerating gene ( Reg) family proteins, which are classified into four types, commonly act as trophic and/or antiapoptotic factors in gastrointestinal (GI) diseases. However, it remains unclear how these proteins coordinate their similar roles under such pathophysiological conditions. Here, we investigated the interrelationships of Reg family gene expression with mucosal cell proliferation and apoptosis in nonsteroidal anti-inflammatory drug (NSAID)-induced GI injury. GI injury was induced by subcutaneous injection of indomethacin into Reg I knockout (KO) and wild-type (WT) mice, and its severity was scored histopathologically. Temporal changes in the expression of Reg family genes, mucosal proliferation, and apoptosis were evaluated throughout the GI tract by real-time RT-PCR, Ki-67 immunoreactivity, and TUNEL assay, respectively. Reg I, Reg III family, and Reg IV were predominantly expressed in the upper, middle, and lower GI mucosa, respectively. Expression of Reg I and Reg III family genes was upregulated in specific portions of the GI tract after indomethacin treatment. Ki-67-positive epithelial cells were significantly decreased in the gastric and small-intestinal mucosa of Reg I KO mice under normal conditions. After treatment with indomethacin, the number of TUNEL-positive cells was significantly greater throughout the GI mucosa in Reg I KO mice than in WT mice. Expression of Reg I was independent of that of other Reg family genes in, not only normal GI tissues, but also indomethacin-induced GI lesions. Members of the Reg gene family show distinct profiles of expression in the GI tract, and Reg I independently plays a role in protecting the GI mucosa against NSAID-induced injury.
Activation of the GP130-STAT3 axis and its potential implications in nonalcoholic fatty liver disease
Authors: Min Hae-Ki , Mirshahi Faridoddin , Verdianelli Aurora , Pacana Tommy , Patel Vaishali , Park Chun-Geon , Choi Aejin , Lee Jeong-Hoon , Park Chung-Berm , Ren Shunlin , Sanyal Arun J.
Published: March 2015

The status of the GP130-STAT3 signaling pathway in humans with nonalcoholic fatty liver disease (NAFLD) and its relevance to disease pathogenesis are unknown. The expression of the gp130-STAT3 axis and gp130 cytokine receptors were studied in subjects with varying phenotypes of NAFLD including nonalcoholic steatohepatitis (NASH) and compared with lean and weight-matched controls without NAFLD. Gp130 and its downstream signaling element (Tyk2 and STAT3) expression were inhibited in obese controls whereas they were increased in NAFLD. IL-6 levels were increased in NASH and correlated with gp130 expression ( P < 0.01). Palmitate inhibited gp130-STAT3 expression and signaling. IL-6 and palmitate inhibited hepatic insulin signaling via STAT3-dependent and independent mechanisms, respectively. STAT3 overexpression reversed palmitate-induced lipotoxicity by increasing autophagy (ATG7) and decreasing endoplasmic reticulum stress. These data demonstrate that the STAT3 pathway is activated in NAFLD and can worsen insulin resistance while protecting against other lipotoxic mechanisms of disease pathogenesis.