bluuebunny/crossref_metadata_2025 huggingface dataset:
Amino Acid Catabolism in
Staphylococcus aureus
and the Function of Carbon Catabolite Repression
Authors: Halsey Cortney R. , Lei Shulei , Wax Jacqueline K. , Lehman Mckenzie K. , Nuxoll Austin S. , Steinke Laurey , Sadykov Marat , Powers Robert , Fey Paul D.
Published: February 2017

Staphylococcus aureus
must rapidly adapt to a variety of carbon and nitrogen sources during invasion of a host. Within a staphylococcal abscess, preferred carbon sources such as glucose are limiting, suggesting that
S. aureus
survives through the catabolism of secondary carbon sources.
S. aureus
encodes pathways to catabolize multiple amino acids, including those that generate pyruvate, 2-oxoglutarate, and oxaloacetate. To assess amino acid catabolism,
S. aureus
JE2 and mutants were grown in complete defined medium containing 18 amino acids but lacking glucose (CDM). A mutation in the
gudB
gene, coding for glutamate dehydrogenase, which generates 2-oxoglutarate from glutamate, significantly reduced growth in CDM, suggesting that glutamate and those amino acids generating glutamate, particularly proline, serve as the major carbon source in this medium. Nuclear magnetic resonance (NMR) studies confirmed this supposition. Furthermore, a mutation in the
ackA
gene, coding for acetate kinase, also abrogated growth of JE2 in CDM, suggesting that ATP production from pyruvate-producing amino acids is also critical for growth. In addition, although a functional respiratory chain was absolutely required for growth, the oxygen consumption rate and intracellular ATP concentration were significantly lower during growth in CDM than during growth in glucose-containing media. Finally, transcriptional analyses demonstrated that expression levels of genes coding for the enzymes that synthesize glutamate from proline, arginine, and histidine are repressed by CcpA and carbon catabolite repression. These data show that pathways important for glutamate catabolism or ATP generation via Pta/AckA are important for growth in niches where glucose is not abundant, such as abscesses within skin and soft tissue infections.

IMPORTANCE
S. aureus
is a significant cause of both morbidity and mortality worldwide. This bacterium causes infections in a wide variety of organ systems, the most common being skin and soft tissue. Within a staphylococcal abscess, levels of glucose, a preferred carbon source, are limited due to the host immune response. Therefore,
S. aureus
must utilize other available carbon sources such as amino acids or peptides to proliferate. Our results show that glutamate and amino acids that serve as substrates for glutamate synthesis, particularly proline, function as major carbon sources during growth, whereas other amino acids that generate pyruvate are important for ATP synthesis via substrate-level phosphorylation in the Pta-AckA pathway. Our data support a model whereby certain amino acid catabolic pathways, and acquisition of those particular amino acids, are crucial for growth in niches where glucose is not abundant.
A Novel Small-Molecule Inhibitor of the
Mycobacterium tuberculosis
Demethylmenaquinone Methyltransferase MenG Is Bactericidal to Both Growing and Nutritionally Deprived Persister Cells
Authors: Sukheja Paridhi , Kumar Pradeep , Mittal Nisha , Li Shao-Gang , Singleton Eric , Russo Riccardo , Perryman Alexander L. , Shrestha Riju , Awasthi Divya , Husain Seema , Soteropoulos Patricia , Brukh Roman , Connell Nancy , Freundlich Joel S. , Alland David
Published: February 2017

Active tuberculosis (TB) and latent
Mycobacterium tuberculosis
infection both require lengthy treatments to achieve durable cures. This problem has partly been attributable to the existence of nonreplicating
M. tuberculosis
“persisters” that are difficult to kill using conventional anti-TB treatments. Compounds that target the respiratory pathway have the potential to kill both replicating and persistent
M. tuberculosis
and shorten TB treatment, as this pathway is essential in both metabolic states. We developed a novel respiratory pathway-specific whole-cell screen to identify new respiration inhibitors. This screen identified the biphenyl amide GSK1733953A (DG70) as a likely respiration inhibitor. DG70 inhibited both clinical drug-susceptible and drug-resistant
M. tuberculosis
strains. Whole-genome sequencing of DG70-resistant colonies identified mutations in
menG
(
rv0558
), which is responsible for the final step in menaquinone biosynthesis and required for respiration. Overexpression of
menG
from wild-type and DG70-resistant isolates increased the DG70 MIC by 4× and 8× to 30×, respectively. Radiolabeling and high-resolution mass spectrometry studies confirmed that DG70 inhibited the final step in menaquinone biosynthesis. DG70 also inhibited oxygen utilization and ATP biosynthesis, which was reversed by external menaquinone supplementation. DG70 was bactericidal in actively replicating cultures and in a nutritionally deprived persistence model. DG70 was synergistic with the first-line TB drugs isoniazid, rifampin, and the respiratory inhibitor bedaquiline. The combination of DG70 and isoniazid completely sterilized cultures in the persistence model by day 10. These results suggest that MenG is a good therapeutic target and that compounds targeting MenG along with standard TB therapy have the potential to shorten TB treatment duration.

IMPORTANCE
This study shows that MenG, which is responsible for the last enzymatic step in menaquinone biosynthesis, may be a good drug target for improving TB treatments. We describe the first small-molecule inhibitor (DG70) of
Mycobacterium tuberculosis
MenG and show that DG70 has characteristics that are highly desirable for a new antitubercular agent, including bactericidality against both actively growing and nonreplicating mycobacteria and synergy with several first-line drugs that are currently used to treat TB.
Bacterial Topography of the Healthy Human Lower Respiratory Tract
Authors: Dickson Robert P. , Erb-Downward John R. , Freeman Christine M. , McCloskey Lisa , Falkowski Nicole R. , Huffnagle Gary B. , Curtis Jeffrey L.
Published: February 2017

Although culture-independent techniques have refuted lung sterility in health, controversy about contamination during bronchoscope passage through the upper respiratory tract (URT) has impeded research progress. We sought to establish whether bronchoscopic sampling accurately reflects the lung microbiome in health and to distinguish between two proposed routes of authentic microbial immigration, (i) dispersion along contiguous respiratory mucosa and (ii) subclinical microaspiration. During bronchoscopy of eight adult volunteers without lung disease, we performed seven protected specimen brushings (PSB) and bilateral bronchoalveolar lavages (BALs) per subject. We amplified, sequenced, and analyzed the bacterial 16S rRNA gene V4 regions by using the Illumina MiSeq platform. Rigorous attention was paid to eliminate potential sources of error or contamination, including a randomized processing order and the inclusion and analysis of exhaustive procedural and sequencing control specimens. Indices of mouth-lung immigration (mouth-lung community similarity, bacterial burden, and community richness) were all significantly greater in airway and alveolar specimens than in bronchoscope contamination control specimens, indicating minimal evidence of pharyngeal contamination. Ecological indices of mouth-lung immigration peaked at or near the carina, as predicted for a primary immigration route of microaspiration. Bacterial burden, diversity, and mouth-lung similarity were greater in BAL than PSB samples, reflecting differences in the sampled surface areas. (This study has been registered at ClinicalTrials.gov under registration no. NCT02392182.)

IMPORTANCE
This study defines the bacterial topography of the healthy human respiratory tract and provides ecological evidence that bacteria enter the lungs in health primarily by microaspiration, with potential contribution in some subjects by direct dispersal along contiguous mucosa. By demonstrating that contamination contributes negligibly to microbial communities in bronchoscopically acquired specimens, we validate the use of bronchoscopy to investigate the lung microbiome.
Spatial and Temporal Analysis of Alphavirus Replication and Assembly in Mammalian and Mosquito Cells
Authors: Jose Joyce , Taylor Aaron B. , Kuhn Richard J.
Published: February 2017

Sindbis virus (SINV [genus
Alphavirus
, family
Togaviridae
]) is an enveloped, mosquito-borne virus. Alphaviruses cause cytolytic infections in mammalian cells while establishing noncytopathic, persistent infections in mosquito cells. Mosquito vector adaptation of alphaviruses is a major factor in the transmission of epidemic strains of alphaviruses. Though extensive studies have been performed on infected mammalian cells, the morphological and structural elements of alphavirus replication and assembly remain poorly understood in mosquito cells. Here we used high-resolution live-cell imaging coupled with single-particle tracking and electron microscopy analyses to delineate steps in the alphavirus life cycle in both the mammalian host cell and insect vector cells. Use of dually labeled SINV in conjunction with cellular stains enabled us to simultaneously determine the spatial and temporal differences of alphavirus replication complexes (RCs) in mammalian and insect cells. We found that the nonstructural viral proteins and viral RNA in RCs exhibit distinct spatial organization in mosquito cytopathic vacuoles compared to replication organelles from mammalian cells. We show that SINV exploits filopodial extensions for virus dissemination in both cell types. Additionally, we propose a novel mechanism for replication complex formation around glycoprotein-containing vesicles in mosquito cells that produced internally released particles that were seen budding from the vesicles by live imaging. Finally, by characterizing mosquito cell lines that were persistently infected with fluorescent virus, we show that the replication and assembly machinery are highly modified, and this allows continuous production of alphaviruses at reduced levels.

IMPORTANCE
Reemerging mosquito-borne alphaviruses cause serious human epidemics worldwide. Several structural and imaging studies have helped to define the life cycle of alphaviruses in mammalian cells, but the mode of virus replication and assembly in the invertebrate vector and mechanisms producing two disease outcomes in two types of cells are yet to be identified. Using transmission electron microscopy and live-cell imaging with dual fluorescent protein-tagged SINV, we show that while insect and mammalian cells display similarities in entry and exit, they present distinct spatial and temporal organizations in virus replication and assembly. By characterizing acutely and persistently infected cells, we provide new insights into alphavirus replication and assembly in two distinct hosts, resulting in high-titer virus production in mammalian cells and continuous virus production at reduced levels in mosquito cells—presumably a prerequisite for alphavirus maintenance in nature.
Integrated Regulatory and Metabolic Networks of the Marine Diatom
Phaeodactylum tricornutum
Predict the Response to Rising CO
2
Levels
Authors: Levering Jennifer , Dupont Christopher L. , Allen Andrew E. , Palsson Bernhard O. , Zengler Karsten
Published: February 2017

Using a systems biology approach, we studied the response of the marine diatom
Phaeodactylum tricornutum
to changing atmospheric carbon concentrations on an ocean-wide scale. By integrating an available genome-scale metabolic model and a newly developed transcriptional regulatory network inferred from transcriptome sequencing expression data, we demonstrate that carbon metabolism and nitrogen metabolism are strongly connected and the genes involved are coregulated in this model diatom. These tight regulatory constraints could play a major role during the adaptation of
P. tricornutum
to increasing carbon levels. The transcriptional regulatory network developed can be further used to study the effects of different environmental perturbations on
P. tricornutum
’s metabolism.
Hyperactive delirium following administration of intra-articular corticosteroid
Authors: Lally Leona , McCarthy Geraldine , Meehan Karena
Published: February 2017

Intra-articular administration of corticosteroids is a commonly used treatment for osteoarthritis as well as other inflammatory disorders of the joints. It is well known that delirium and psychosis can arise following the administration of oral corticosteroids but there are few documented cases of the development of acute hyperactive delirium with psychosis following intra-articular administration. We describe a case of an 82-year-old female patient with moderate dementia who developed a delirium with psychosis which responded well to a first-generation antipsychotic.
Analysis of out-of-pocket costs associated with hospitalised injuries in Vietnam
Authors: Nguyen Ha , Ivers Rebecca , Jan Stephen , Pham Cuong
Published: February 2017

Background

In Vietnam, over 39 000 people die and millions are hospitalised due to injuries every year. Injuries create a significant financial burden for families. In this study, we estimated out-of-pocket payment for medical care of injuries and the role of health insurance in containing such costs.

Method

A prospective cohort study of 892 hospitalised injury patients admitted to a provincial general hospital in 2010 in Vietnam was conducted. Data on demographic, injury characteristics and costs by specific categories paid out-of-pocket by patients were included in the analyses. Generalised linear models with log link and γ distribution were employed to examine the associations between insurance status and total costs.

Results

The average total medical care costs paid out-of-pocket by patients during hospitalisation were over US$ 270. Major drivers of the costs related to surgery (nearly 25%), diagnostic test/examination (24%) and drugs (23%). Burns incurred the highest total costs during hospitalisation ($321) and assault incurred the lowest ($167). Total costs were higher for more severe injuries and those that required a more complex surgery. Patients using health insurance paid less those who did not. However, there were no statistically significant associations between health insurance and total costs, costs for surgery, diagnostic tests/examinations or drugs.

Conclusions

The study provides estimates and distribution of medical care costs for injuries in hospital. In addition to ongoing efforts in prevention, the study provides further evidence on the limited benefits of health insurance in protecting patients and their family from the high costs of hospitalisation in Vietnam.
Hysterectomy through the looking glass: iHysterectomy frugal by iPhone
Authors: Baekelandt Jan , Bosteels Jan
Published: February 2017

This study aims to demonstrate the feasibility of a frugal approach to an endoscopic hysterectomy: the iHysterectomy. An iPhone with endoscope-i adaptor and a portable light source were used instead of a laparoscopic camera, video processor, monitor and light source. A vaginally assisted natural orifice transluminal endoscopic surgery (NOTES) hysterectomy (VANH) was performed by Poor Man's NOTES technique using a self-constructed glove port and standard reusable instruments. Ten iHysterectomies were successfully performed by a single surgeon (JBa). No conversion to a laparoscopic tower, standard multi incision laparoscopy, or laparotomy was necessary. Mean operation time was 52 min (40–75); mean serum haemoglobin drop was 0.8 g/dL (0.2–2.1). There were no operative complications, and postoperative pain scores were low. The iHysterectomy technique enables surgeons to perform a minimally invasive hysterectomy in a low-resource setting without the need to invest in a laparoscopic tower. The investment required for endoscopic hardware is a fraction of that for conventional laparoscopy or robotic surgery. This is an Idea Development Exploration Assessment Long-term (IDEAL) stage 1 study: iHysterectomy is a novel approach requiring further validation. This is the first report on the use of an iPhone to perform a hysterectomy or any other major operation.
Multilayered and digitally structured presentation formats of trustworthy recommendations: a combined survey and randomised trial
Authors: Brandt Linn , Vandvik Per Olav , Alonso-Coello Pablo , Akl Elie A , Thornton Judith , Rigau David , Adams Katie , O'Connor Paul , Guyatt Gordon , Kristiansen Annette
Published: February 2017

Objectives

To investigate practicing physicians' preferences, perceived usefulness and understanding of a new multilayered guideline presentation format—compared to a standard format—as well as conceptual understanding of trustworthy guideline concepts.

Design

Participants attended a standardised lecture in which they were presented with a clinical scenario and randomised to view a guideline recommendation in a multilayered format or standard format after which they answered multiple-choice questions using clickers. Both groups were also presented and asked about guideline concepts.

Setting

Mandatory educational lectures in 7 non-academic and academic hospitals, and 2 settings involving primary care in Lebanon, Norway, Spain and the UK.

Participants

181 practicing physicians in internal medicine (156) and general practice (25).

Interventions

A new digitally structured, multilayered guideline presentation format and a standard narrative presentation format currently in widespread use.

Primary and secondary outcome measures

Our primary outcome was preference for presentation format. Understanding, perceived usefulness and perception of absolute effects were secondary outcomes.

Results

72% (95% CI 65 to 79) of participants preferred the multilayered format and 16% (95% CI 10 to 22) preferred the standard format. A majority agreed that recommendations (multilayered 86% vs standard 91%, p value=0.31) and evidence summaries (79% vs 77%, p value=0.76) were useful in the context of the clinical scenario. 72% of participants randomised to the multilayered format vs 58% for standard formats reported correct understanding of the recommendations (p value=0.06). Most participants elected an appropriate clinical action after viewing the recommendations (98% vs 92%, p value=0.10). 82% of the participants considered absolute effect estimates in evidence summaries helpful or crucial.

Conclusions

Clinicians clearly preferred a novel multilayered presentation format to the standard format. Whether the preferred format improves decision-making and has an impact on patient important outcomes merits further investigation.
Perineal resuturing versus expectant management following vaginal delivery complicated by a dehisced wound (PREVIEW): a pilot and feasibility randomised controlled trial
Authors: Dudley L , Kettle C , Thomas P W , Ismail K M K
Published: February 2017

Objective

To establish the feasibility of conducting a definitive randomised controlled trial (RCT) comparing the effectiveness of resuturing versus expectant management for dehisced perineal wounds.

Design

A multicentre pilot and feasibility RCT.

Setting

Ten UK maternity units from July 2011 to July 2013.

Population

Eligible women with a dehisced perineal wound within 2 weeks of childbirth.

Methods

The interventions were resuturing or expectancy. Randomisation was via web or telephone, stratified by participating centre. Blinding was not possible due to the nature of the interventions. Analysis was by intention-to-treat.

Outcome

The primary outcome measure was wound healing at 6–8 weeks.

Results

The study revealed a number of feasibility issues, particularly strong patient and clinician preference for treatment options at recruiting centres and the timing of the primary outcome measure. Thirty-four women were randomised (17 in each arm). Data from 33 women were analysed on an intention-to-treat analysis to obtain preliminary estimates of effect size. There was a difference in wound healing at 2 weeks favouring resuturing (OR 20.00, 95% CI 2.04 to 196.37, p=0.004). However, by 6–8 weeks all but one wound in both groups had healed.

Conclusions

PREVIEW revealed a number of feasibility issues, which impacted on recruitment rate. These will have to be taken into account in the design of any future definitive study. In this feasibility study, resuturing was associated with quicker wound healing and women reported higher satisfaction rates with the outcome at 3 months.

Trial registration number

ISRCTN05754020.
Individualised risk assessment for local recurrence and distant metastases in a retrospective transatlantic cohort of 687 patients with high-grade soft tissue sarcomas of the extremities: a multistate model
Authors: Willeumier Julie J , Rueten-Budde Anja J , Jeys Lee M , Laitinen Minna , Pollock Rob , Aston Will , Dijkstra P D Sander , Ferguson Peter C , Griffin Anthony M , Wunder Jay S , Fiocco Marta , van de Sande Michiel A J
Published: February 2017

Objectives

This study investigates the effect of surgical margins and radiotherapy, in the presence of individual baseline characteristics, on survival in a large population of high-grade soft tissue sarcoma of the extremities using a multistate model.

Design

A retrospective multicentre cohort study.

Setting

4 tertiary referral centres for orthopaedic oncology.

Participants

687 patients with primary, non-disseminated, high-grade sarcoma only, receiving surgical treatment with curative intent between 2000 and 2010 were included.

Main outcome measures

The risk to progress from ‘alive without disease’ (ANED) after surgery to ‘local recurrence’ (LR) or ‘distant metastasis (DM)/death’. The effect of surgical margins and (neo)adjuvant radiotherapy on LR and overall survival was evaluated taking patients' and tumour characteristics into account.

Results

The multistate model underlined that wide surgical margins and the use of neoadjuvant radiotherapy decreased the risk of LR but have little effect on survival. The main prognostic risk factors for transition ANED to LR are tumour size (HR 1.06; 95% CI 1.01 to 1.11 (size in cm)) and (neo)adjuvant radiotherapy. The HRs for patients treated with adjuvant or no radiotherapy compared with neoadjuvant radiotherapy are equal to 4.36 (95% CI 1.34 to 14.24) and 14.20 (95% CI 4.14 to 48.75), respectively. Surgical resection margins had a protective effect for the occurrence of LR with HRs equal to 0.61 (95% CI 0.33 to 1.12), and 0.16 (95% CI 0.07 to 0.41) for margins between 0 and 2 mm and wider than 2 mm, respectively. For transition ANED to distant metastases/Death, age (HR 1.64 (95% CI 0.95 to 2.85) and 1.90 (95% CI 1.09 to 3.29) for 25–50 years and >50 years, respectively) and tumour size (1.06 (95% CI 1.04 to 1.08)) were prognostic factors.

Conclusions

This paper underlined the alternating effect of surgical margins and the use of neoadjuvant radiotherapy on oncological outcomes between patients with different baseline characteristics. The multistate model incorporates this essential information of a specific patient's history, tumour characteristics and adjuvant treatment modalities and allows a more comprehensive prediction of future events.
Cohort profile: the Welsh Geriatric Registrar-Led Research Network (WeGeN): rationale, design and description
Authors: Jelley Benjamin , Long Sara , Butler John , Hewitt Jonathan
Published: February 2017

Purpose

Medical trainees are required to undertake audit and quality improvement projects. They must also have an understanding of the principles of research and are encouraged to participate in research projects. However, the constraints of time, a lack of formal training and rotation between different training posts create barriers to audit cycle completion and pursuing research. This leads to trainees being reluctant to undertake research, facilitates poor quality research and risks incomplete audit.

Participants

The Welsh Geriatricians Network (WeGeN) has been created with the aims of facilitating collaborative, trainee-led research within Geriatric Medicine in Wales, promoting research engagement and improving the research evidence base for older patients. By coordinating collaborative research projects across different sites within Wales, trainees continue existing projects at new sites, allowing completion of projects and establishing the long-term infrastructure and experienced personnel needed for high-quality research data to be gathered.

Findings

WeGeN has facilitated 4 national audits, all of which are intended for peer review publication. The first project considers the service provision for the older person in the emergency department, the second Parkinson's disease, the third reviews delirium management and the fourth project considers epidemiology of surgical disease in older people.

Future plans

The objective of this project is to further establish and develop WeGeN as a group which facilitates high-quality research and provides the opportunity for geriatric trainees to engage in research activity. It is anticipated that the establishment of this research platform will provide a blueprint for the development of other such networks in the UK and beyond.
Referral pathways for patients with TIA avoiding hospital admission: a scoping review
Authors: Evans Bridie Angela , Ali Khalid , Bulger Jenna , Ford Gary A , Jones Matthew , Moore Chris , Porter Alison , Pryce Alan David , Quinn Tom , Seagrove Anne C , Snooks Helen , Whitman Shirley , Rees Nigel
Published: February 2017

Objective

To identify the features and effects of a pathway for emergency assessment and referral of patients with suspected transient ischaemic attack (TIA) in order to avoid admission to hospital.

Design

Scoping review.

Data sources

PubMed, CINAHL Web of Science, Scopus.

Study selection

Reports of primary research on referral of patients with suspected TIA directly to specialist outpatient services.

Data extraction

We screened studies for eligibility and extracted data from relevant studies. Data were analysed to describe setting, assessment and referral processes, treatment, implementation and outcomes.

Results

8 international studies were identified, mostly cohort designs. 4 pathways were used by family doctors and 3 pathways by emergency department physicians. No pathways used by paramedics were found. Referrals were made to specialist clinic either directly or via a 24-hour helpline. Practitioners identified TIA symptoms and risk of further events using a checklist including the ABCD2 tool or clinical assessment. Antiplatelet medication was often given, usually aspirin unless contraindicated. Some patients underwent tests before referral and discharge. 5 studies reported reduced incident of stroke at 90 days, from 6–10% predicted rate to 1.3–2.1% actual rate. Between 44% and 83% of suspected TIA cases in these studies were referred through the pathways.

Conclusions

Research literature has focused on assessment and referral by family doctors and ED physicians to reduce hospitalisation of patients with TIA. No pathways for paramedical use were reported. We will use results of this scoping review to inform development of a paramedical referral pathway to be tested in a feasibility trial.

Trial registration number

ISRCTN85516498. Stage: pre-results.
Revalidation and quality assurance: the application of the MUSIQ framework in independent verification visits to healthcare organisations
Authors: Griffin Ann , McKeown Alex , Viney Rowena , Rich Antonia , Welland Trevor , Gafson Irene , Woolf Katherine
Published: February 2017

Objectives

We present a national evaluation of the impact of independent verification visits (IVVs) performed by National Health Service (NHS) England as part of quality assuring medical revalidation. Organisational visits are central to NHS quality assurance. They are costly, yet little empirical research evidence exists concerning their impact, and what does exist is conflicting.

Setting

The focus was on healthcare providers in the NHS (in secondary care) and private sector across England, who were designated bodies (DBs). DBs are healthcare organisations that have a statutory responsibility, via the lead clinician, the responsible officer (RO), to implement medical revalidation.

Participants

All ROs who had undergone an IVV in England in 2014 and 2015 were invited to participate. 46 ROs were interviewed. Ethnographic data were gathered at 18 observations of the IVVs and 20 IVV post visit reports underwent documentary analysis.

Primary and secondary outcome measures

Primary outcomes were the findings pertaining to the effectiveness of the IVV system in supporting the revalidation processes at the DBs. Secondary outcomes were methodological, relating to the Model for Understanding Success in Quality (MUSIQ) and how its application to the IVV reveals the relevance of contextual factors described in the model.

Results

The impact of the IVVs varied by DB according to three major themes: the personal context of the RO; the organisational context of the DB; and the visit and its impact. ROs were largely satisfied with visits which raised the status of appraisal within their organisations. Inadequate or untimely feedback was associated with dissatisfaction.

Conclusions

Influencing teams whose prime responsibility is establishing processes and evaluating progress was crucial for internal quality improvement. Visits acted as a nudge, generating internal quality review, which was reinforced by visit teams with relevant expertise. Diverse team membership, knowledge transfer and timely feedback made visits more impactful.
Improving theatre turnaround time
Authors: Fletcher Daniel , Edwards David , Tolchard Stephen , Baker Richard , Berstock James
Published: February 2017

The NHS Institute for Innovation and Improvement has determined that a £7 million saving can be achieved per trust by improving theatre efficiency. The aim of this quality improvement project was to improve orthopaedic theatre turnaround without compromising the patient safety.

We process mapped all the stages from application of dressing to knife to skin on the next patient in order to identify potential areas for improvement. Several suggestions arose which were tested in multiple PDSA cycles in a single theatre. These changes were either adopted, adapted or rejected on the basis of run chart data and theatre team feedback.

Successful ideas which were adopted included, the operating department practitioner (ODP) seeing and completing check-in paperwork during the previous case rather than during turnaround, a 15 minute telephone warning to ensure the next patient was fully ready, a dedicated cleaning team mobilised during wound closure, sending for the next patient as theatre cleaning begins.

Run charts demonstrate that as a result of these interventions the mean turnaround time almost halved from 66.5 minutes in July to 36.8 minutes over all PDSA cycles. This improvement has been sustained and rolled out into another theatre. As these improvements become more established we hope that additional cases will be booked, improving theatre output. The PDSA cycle continues as we believe that further gains may yet be made, and our improvements may be rolled out across other surgical specialities.
Randomised, prospective, non-blinded pilot study comparing the effect of intramuscular steroid injections and intralesional steroid injections in the management of tennis elbow
Authors: Tahir Hasan , Biro Izolda , Donnelly Simon , Greenwood Mandy
Published: February 2017

Background

Tennis elbow is an overuse injury affecting people performing repetitive forearm movements. It is a soft tissue disorder that causes significant disability and pain.

The aim of the study was to establish that an intramuscular steroid injection is effective in the short-term pain relief and functional improvement of tennis elbow. The severity of pain at the injection site was monitored to determine whether the intramuscular injection is better tolerated than the intralesional injection.

Methods and results

19 patients, who had no treatment for tennis elbow in the preceding 3 months, were recruited from Whipps Cross University Hospital, London, and were randomised to receive either 80 mg of intramuscular Depo-Medrone or 40 mg of intralesional Depo-Medrone injection. Blinding proved difficult as the injection sites differed and placebo arms were not included in the study. A Patient-Rated Tennis Elbow Evaluation (PRTEE) Questionnaire and a 10-point Likert scale were used to assess primary outcome. Six weeks after the treatment, there was a reduction in pain, improvement in function and total PRTEE scores in both intramuscular and intralesional groups (p=0.008) using a 95% CI for mean treatment difference of −26 to +16 points. A statistically significant result (p=0.001) in favour of intramuscular causing less pain at the injection site was noted.

Conclusion

Non-inferiority of intramuscular to intralesional injections was not confirmed; however, the intramuscular injection proved to be effective in reducing tennis elbow-related symptoms and was found less painful at the site of injection at the time of administration.

Trial registration number

EUDRACT Number: 2010-022131-11.

REC Number: 10/H0718/76 (NRES, Central London REC 1).
Clinical outcome after surgical clipping or endovascular coiling for cerebral aneurysms: a pragmatic meta-analysis of randomized and non-randomized trials with short- and long-term follow-up
Authors: Falk Delgado Alberto , Andersson Tommy , Falk Delgado Anna
Published: February 2017

Background

Two randomized trials have evaluated clipping and coiling in patients with ruptured aneurysms. Aggregated evidence for management of ruptured and unruptured aneurysms is missing.

Objective

To conduct a meta-analysis evaluating clinical outcome after aneurysm treatment.

Methods

PubMed, Cochrane Central Register of Controlled Trials, and Clinicaltrials.gov were searched for studies evaluating aneurysm treatment. The primary outcome measure was an independent clinical outcome (modified Rankin scale 0–2, Glasgow Outcome Scale 4–5, or equivalent). Secondary outcomes were poor outcome and mortality. ORs were calculated on an intention-to-treat basis with 95% CIs. Outcome heterogeneity was evaluated with Cochrane's Q test (significance level cut-off value at <0.10) and I2(significance cut-off value >50%) with the Mantel–Haenszel method for dichotomous outcomes. A p value <0.05 was regarded as statistically significant.

Results

Searches yielded 18 802 articles. All titles were assessed, 403 abstracts were evaluated, and 183 full-text articles were read. One-hundred and fifty articles were qualitatively assessed and 85 articles were included in the meta-analysis. Patients treated with coiling (randomized controlled trials (RCTs)) had higher independent outcome at short-term follow-up (OR=0.67, 95% CI 0.57 to 0.79). Independent outcome was favored for coiling at intermediate and long-term follow-up (RCTs and observational studies combined—OR=0.80, 0.68 to 0.94 and OR=0.81, 0.71 to 0.93, respectively). Independent outcome and lower mortality was favored after coiling in unruptured aneurysms (database registry studies) at short-term follow-up (OR=0.34, 0.29 to 0.41 and OR=1.74, 1.52 to 1.98, respectively).

Conclusions

This meta-analysis evaluating clinical outcome after coiling or clipping for intracranial aneurysms, indicates a higher independent outcome and lower mortality after coiling.
The cellular stress response of rat skeletal muscle following lengthening contractions
Authors: Pollock-Tahiri Evan , Locke Marius
Published: February 2017

The cellular stress response of the rat tibialis anterior (TA) muscle was investigated following 20, 40, or 60 lengthening contractions (LCs) using an in vivo model of electrical stimulation. Muscles were removed at 0, 1, 3, or 24 h after LCs and assessed for heat shock transcription factor (HSF) activation, heat shock protein (HSP) content, and/or morphological evidence of muscle fibre damage. When compared with the first muscle contraction, peak muscle torque was reduced by 26% (p < 0.05) after 20 LCs and further reduced to 56% and 60% (p < 0.001) after 40 and 60 LCs, respectively. Following 60 LCs, HSF activation was detected at 0, 1, and 3 h but was undetectable at 24 h. Hsp72 content was elevated at 24 h after 20 LCs (2.34 ± 0.37 fold, p < 0.05), 40 LCs (3.02 ± 0.31 fold, p < 0.01), and 60 LCs (3.37 ± 0.21 fold, p < 0.001). Hsp25 content increased after 40 (2.36 ± 0.24 fold, p < 0.01) and 60 LCs (2.80 ± 0.37 fold, p < 0.01). Morphological assessment of TA morphology revealed that very few fibres were damaged following 20 LCs while multiple sets of LCs (40 and 60) caused greater amounts of fibre damage. Electron microscopy showed disrupted Z-lines and sarcomeres were detectable in some muscles fibres following 20 LCs but were more prevalent and severe in muscles subjected to 40 or 60 LCs. These results suggest LCs elevate HSP content by an HSF-mediated mechanism (60 LC) and a single set of 20 LCs is capable of increasing muscle HSP content without causing significant muscle fibre damage.
New interaction model for vertical dynamic response of pipe piles considering soil plug effect
Authors: Wu Wenbing , El Naggar M. Hesham , Abdlrahem Maged , Mei Guoxiong , Wang Kuihua
Published: February 2017

A soil–pile interaction model is developed to better represent the actual behavior of pipe piles undergoing dynamic testing. To correctly investigate the dynamic interaction mechanism of the pipe piles, the developed model introduces an additional mass to account for the soil plug. The governing equations of motion for the soil–pile system subjected to small deformations and strains are established considering plane strain conditions for the soil and one-dimensional wave propagation in the pile. The analytical solution of the vertical dynamic response of the pipe pile in the frequency domain is then obtained by employing a Laplace transform and transfer function technique. The corresponding quasi-analytical solution in the time domain for the pipe pile subjected to a vertical semi-sinusoidal exciting force is subsequently derived by means of a Fourier transform. A parameter sensitivity analysis of the additional mass model is carried out to determine the approximate range of the parameter values. Utilizing the developed solution, a parametric study is performed to illustrate the influence of the properties of the soil–pile system on the vertical dynamic response of the pipe pile. Finally, the validity of the additional mass model is validated by conducting a set of model tests, based on which the concept of “apparent wave velocity of pipe pile” (AWVPP) is also proposed.
Entropy, energy, and entanglement of localized states in bent triatomic molecules
Authors: Yuan Qiang , Hou Xi-Wen
Published: February 2017

The dynamics of quantum entropy, energy, and entanglement is studied for various initial states in an important spectroscopic Hamiltonian of bent triatomic molecules H2O, D2O, and H2S. The total quantum correlation is quantified in terms of the mutual information and the entanglement by the concurrence borrowed from the theory of quantum information. The Pauli entropy and the intramolecular energy usually used in the theory of molecules are calculated to establish a possible relationship between both theories. Sections of two quantities among these four quantities are introduced to visualize such relationship. Analytic and numerical simulations demonstrate that if an initial state is taken to be the stretch- or the bend-vibrationally localized state, the mutual information, the Pauli entropy, and the concurrence are dominant-positively correlated while they are dominantly anti-correlated with the interacting energy among three anharmonic vibrational modes. In particular, such correlation is more distinct for the localized state with high excitations in the bending mode. The nice quasi-periodicity of those quantities in D2O molecule reveals that this molecule prepared in the localized state in the stretching or the bending mode can be more appreciated for molecular quantum computation. However, the dynamical correlations of those quantities behave irregularly for the dislocalized states. Moreover, the hierarchy of the mutual information and the Pauli entropy is explicitly proved. Quantum entropy and energy in every vibrational mode are investigated. Thereby, the relation between bipartite and tripartite entanglements is discussed as well. Those are useful for the understanding of quantum correlations in high-dimensional states in polyatomic molecules from quantum information and intramolecular dynamics.
Small Al and Ga clusters trapped inside the Bucky-ball (C60) — A DFT study
Authors: Dhiman Shobhna , Kumar Ranjan , Dharamvir Keya
Published: February 2017

In the present paper, we have done a systematic study of structural and electronic properties of endohedrally doped C[Formula: see text] with Al and Ga atoms using density functional theory (DFT) with the help of Spanish initiative for electronic simulation with thousands of atoms (SIESTA) package in the generalized gradient approximation (GGA). The parameters calculated are binding energy/dopant atom, vertical ionization potential (VIP), vertical electron affinity (VEA), HOMO–LUMO gap and charge transfer. The stabilized ground state structures of Al[Formula: see text]@C[Formula: see text] ([Formula: see text]–10) and Ga[Formula: see text]@C[Formula: see text] ([Formula: see text]–10) show that a maximum of nine Al or Ga atoms can be encapsulated in C[Formula: see text] without distorting the cage significantly. Mulliken charge analysis shows an electron transfer from the metal dopant to the cage surface, except for Al[Formula: see text] ([Formula: see text]–10). The endohedral metal clusters adopt a more compact shape when inside C[Formula: see text], compared to its free-state configuration and its symmetry. The study of HOMO–LUMO gap reveals that the gap decreases with the increase in number of dopant atoms inside C[Formula: see text].
A note on the electromagnetic irradiation in a holed spatial region: A space-time approach
Authors: Botelho Luiz C. L.
Published: February 2017

We study the role of the homological topological property of a space-time with holes (a multiple connected manifold) on the formal solution of the electromagnetic irradiation problem taking place on these “holed” space-times. In this paper, in addition to the main focus of study, we present as well important studies on this irradiation problem on other mathematical frameworks.
Back to the future! Revisiting the physiological cost of negative work as a team-based activity for exercise physiology students
Authors: Kilgas Matthew A. , Elmer Steven J.
Published: February 2017

We implemented a team-based activity in our exercise physiology teaching laboratory that was inspired from Abbott et al.’s classic 1952 Journal of Physiology paper titled “The physiological cost of negative work.” Abbott et al. connected two bicycles via one chain. One person cycled forward (muscle shortening contractions, positive work) while the other resisted the reverse moving pedals (muscle lengthening contractions, negative work), and the cost of work was compared. This study was the first to link human whole body energetics with isolated muscle force-velocity characteristics. The laboratory activity for our students ( n = 35) was designed to reenact Abbott et al.’s experiment, integrate previously learned techniques, and illustrate differences in physiological responses to muscle shortening and lengthening contractions. Students (11–12 students/laboratory section) were split into two teams (positive work vs. negative work). One student from each team volunteered to cycle against the other for ~10 min. The remaining students in each team were tasked with measuring: 1) O2consumption, 2) heart rate, 3) blood lactate, and 4) perceived exertion. Students discovered that O2consumption during negative work was about one-half that of positive work and all other physiological parameters were also substantially lower. Muscle lengthening contractions were discussed and applied to rehabilitation and sport training. The majority of students (>90%) agreed or strongly agreed that they stayed engaged during the activity and it improved their understanding of exercise physiology. All students recommended the activity be performed again. This activity was engaging, emphasized teamwork, yielded clear results, was well received, and preserved the history of classic physiological experiments.
Noninvasive stratification of postinfarction rats based on the degree of cardiac dysfunction using magnetic resonance imaging and echocardiography
Authors: Aronsen Jan Magnus , Espe Emil Knut Stenersen , Skårdal Kristine , Hasic Almira , Zhang Lili , Sjaastad Ivar
Published: February 2017

The myocardial infarction (MI) rat model plays a crucial role in modern cardiovascular research, but the inherent heterogeneity of this model represents a challenge. We sought to identify subgroups among the post-MI rats and establish simple noninvasive stratification protocols for such subgroups. Six weeks after induction of MI, 49 rats underwent noninvasive examinations using magnetic resonance imaging (MRI) and echocardiography. Twelve sham-operated rats served as controls. Increased end-diastolic left ventricular (LV) pressure and lung weight served as indicators for congestive heart failure (CHF). A clustering algorithm using 13 noninvasive and invasive parameters was used to identify distinct groups among the animals. The cluster analysis revealed four distinct post-MI phenotypes; two without congestion but with different degree of LV dilatation, and two with different degree of congestion and right ventricular (RV) affection. Among the MRI parameters, RV mass emerged as robust noninvasive marker of CHF with 100% specificity/sensitivity. Moreover, LV infarct size and RV ejection fraction further predicted subgroup among the non-CHF and CHF rats with excellent specificity/sensitivity. Of the echocardiography parameters, left atrial diameter predicted CHF. Moreover, LV end-diastolic diameter predicted the subgroups among the non-CHF rats. We propose two simple noninvasive schemes to stratify post-MI rats, based on the degree of heart failure; one for MRI and one for echocardiography.

NEW & NOTEWORTHY In vivo phenotyping of rats is essential for robust and reliable data. Here, we present two simple noninvasive schemes for the stratification of postinfarction rats based on the degree of heart failure: one using magnetic resonance imaging and one based on echocardiography.