bluuebunny/crossref_metadata_2025 huggingface dataset:
Cardiolipin Synthesis and Outer Membrane Localization Are Required for
Shigella flexneri
Virulence
Authors: Rossi Rachael M. , Yum Lauren , Agaisse Hervé , Payne Shelley M.
Published: August 2017

Cardiolipin, an anionic phospholipid that resides at the poles of the inner and outer membranes, is synthesized primarily by the putative cardiolipin synthase ClsA in
Shigella flexneri
. An
S. flexneri clsA
mutant had no cardiolipin detected within its membrane, grew normally
in vitro
, and invaded cultured epithelial cells, but it failed to form plaques in epithelial cell monolayers, indicating that cardiolipin is required for virulence. The
clsA
mutant was initially motile within the host cell cytoplasm but formed filaments and lost motility during replication and failed to spread efficiently to neighboring cells. Mutation of
pbgA
, which encodes the transporter for cardiolipin from the inner membrane to the outer membrane, also resulted in loss of plaque formation. The
S. flexneri pbgA
mutant had normal levels of cardiolipin in the inner membrane, but no cardiolipin was detected in the outer membrane. The
pbgA
mutant invaded and replicated normally within cultured epithelial cells but failed to localize the actin polymerization protein IcsA properly on the bacterial surface and was unable to spread to neighboring cells. The
clsA
mutant, but not the
pbgA
mutant, had increased phosphatidylglycerol in the outer membrane. This appeared to compensate partially for the loss of cardiolipin in the outer membrane, allowing some IcsA localization in the outer membrane of the
clsA
mutant. We propose a dual function for cardiolipin in
S. flexneri
pathogenesis. In the inner membrane, cardiolipin is essential for proper cell division during intracellular growth. In the outer membrane, cardiolipin facilitates proper presentation of IcsA on the bacterial surface.

IMPORTANCE
The human pathogen
Shigella flexneri
causes bacterial dysentery by invading colonic epithelial cells, rapidly multiplying within their cytoplasm, and then spreading intercellularly to neighboring cells. Worldwide,
Shigella
spp. infect hundreds of millions of people annually, with fatality rates up to 15%. Antibiotic treatment of
Shigella
infections is compromised by increasing antibiotic resistance, and there is no approved vaccine to prevent future infections. This has created a growing need to understand
Shigella
pathogenesis and identify new targets for antimicrobial therapeutics. Here we show a previously unknown role of phospholipids in
S. flexneri
pathogenesis. We demonstrate that cardiolipin is required in the outer membrane for proper surface localization of IcsA and in the inner membrane for cell division during growth in the host cell cytoplasm.
Rotavirus NSP1 Requires Casein Kinase II-Mediated Phosphorylation for Hijacking of Cullin-RING Ligases
Authors: Davis Kaitlin A. , Morelli Marco , Patton John T.
Published: August 2017

The rotavirus nonstructural protein NSP1 repurposes cullin-RING E3 ubiquitin ligases (CRLs) to antagonize innate immune responses. By functioning as substrate adaptors of hijacked CRLs, NSP1 causes ubiquitination and proteasomal degradation of host proteins that are essential for expression of interferon (IFN) and IFN-stimulated gene products. The target of most human and porcine rotaviruses is the β-transducin repeat-containing protein (β-TrCP), a regulator of NF-κB activation. β-TrCP recognizes a phosphorylated degron (DSGΦXS) present in the inhibitor of NF-κB (IκB); phosphorylation of the IκB degron is mediated by IκB kinase (IKK). Because NSP1 contains a C-terminal IκB-like degron (ILD; DSGXS) that recruits β-TrCP, we investigated whether the NSP1 ILD is similarly activated by phosphorylation and whether this modification is required to trigger the incorporation of NSP1 into CRLs. Based on mutagenesis and phosphatase treatment studies, we found that both serine residues of the NSP1 ILD are phosphorylated, a pattern mimicking phosphorylation of IκB. A three-pronged approach using small-molecule inhibitors, small interfering RNAs, and mutagenesis demonstrated that NSP1 phosphorylation is mediated by the constitutively active casein kinase II (CKII), rather than IKK. In coimmunoprecipitation assays, we found that this modification was essential for NSP1 recruitment of β-TrCP and induced changes involving the NSP1 N-terminal RING motif that allowed formation of Cul3-NSP1 complexes. Taken together, our results indicate a highly regulated stepwise process in the formation of NSP1-Cul3 CRLs that is initiated by CKII phosphorylation of NSP1, followed by NSP1 recruitment of β-TrCP and ending with incorporation of the NSP1–β-TrCP complex into the CRL via interactions dependent on the highly conserved NSP1 RING motif.

IMPORTANCE
Rotavirus is a segmented double-stranded RNA virus that causes severe diarrhea in young children. A primary mechanism used by the virus to inhibit host innate immune responses is to hijack cellular cullin-RING E3 ubiquitin ligases (CRLs) and redirect their targeting activity to the degradation of cellular proteins crucial for interferon expression. This task is accomplished through the rotavirus nonstructural protein NSP1, which incorporates itself into a CRL and serves as a substrate recognition subunit. The substrate recognized by the NSP1 of many human and porcine rotaviruses is β-TrCP, a protein that regulates the transcription factor NF-κB. In this study, we show that formation of NSP1 CRLs is a highly regulated stepwise process initiated by CKII phosphorylation of the β-TrCP recognition motif in NSP1. This modification triggers recruitment of the β-TrCP substrate and induces subsequent changes in a highly conserved NSP1 RING domain that allow anchoring of the NSP1–β-TrCP complex to a cullin scaffold.
Translational Repression of the RpoS Antiadapter IraD by CsrA Is Mediated via Translational Coupling to a Short Upstream Open Reading Frame
Authors: Park Hongmarn , McGibbon Louise C. , Potts Anastasia H. , Yakhnin Helen , Romeo Tony , Babitzke Paul
Published: August 2017

CsrA is a global regulatory RNA binding protein that has important roles in regulating carbon metabolism, motility, biofilm formation, and numerous other cellular processes. IraD functions as an antiadapter protein that inhibits RssB-mediated degradation of RpoS, the general stress response and stationary-phase sigma factor of
Escherichia coli
. Here we identified a novel mechanism in which CsrA represses
iraD
translation via translational coupling. Expression studies with quantitative reverse transcriptase PCR, Western blotting, and
lacZ
fusions demonstrated that CsrA represses
iraD
expression. Gel mobility shift, footprint, and toeprint studies identified four CsrA binding sites in the
iraD
leader transcript, all of which are far upstream of the
iraD
ribosome binding site. Computational modeling and RNA structure mapping identified an RNA structure that sequesters the
iraD
Shine-Dalgarno (SD) sequence. Three open reading frames (ORFs), all of which are translated, were identified in the
iraD
leader region. Two of these ORFs do not affect
iraD
expression. However, the translation initiation region of the third ORF contains three of the CsrA binding sites, one of which overlaps its SD sequence. Furthermore, the ORF stop codon overlaps the
iraD
start codon, a sequence arrangement indicative of translational coupling.
In vivo
expression and
in vitro
translation studies with wild-type and mutant reporter fusions demonstrated that bound CsrA directly represses translation initiation of this ORF. We further established that CsrA-dependent repression of
iraD
translation occurs entirely via translational coupling with this ORF, leading to accelerated
iraD
mRNA decay.

IMPORTANCE
CsrA posttranscriptionally represses gene expression associated with stationary-phase bacterial growth, often in opposition to the transcriptional effects of the stationary-phase sigma factor RpoS. We show that CsrA employs a novel regulatory mechanism to repress translation of
iraD
, which encodes an antiadapter protein that protects RpoS against proteolysis. CsrA binds to four sites in the
iraD
leader transcript but does not directly occlude ribosome binding to the
iraD
SD sequence. Instead, CsrA represses translation of a short open reading frame encoded upstream of
iraD
, causing repression of
iraD
translation via translational coupling. This finding offers a novel mechanism of gene regulation by the global regulator CsrA, and since RpoS can activate
csrA
transcription, this also highlights a new negative-feedback loop within the complex Csr and RpoS circuitry.
Impacts of Penicillin Binding Protein 2 Inactivation on β-Lactamase Expression and Muropeptide Profile in
Stenotrophomonas maltophilia
Authors: Huang Yi-Wei , Wang Yu , Lin Yun , Lin Chin , Lin Yi-Tsung , Hsu Cheng-Chih , Yang Tsuey-Ching
Published: August 2017

Inducible expression of chromosomally encoded β-lactamase(s) is a key mechanism for β-lactam resistance in
Enterobacter cloacae
,
Citrobacter freundii
,
Pseudomonas aeruginosa
, and
Stenotrophomonas maltophilia
. The muropeptides produced during the peptidoglycan recycling pathway act as activator ligands for β-lactamase(s) induction. The muropeptides 1,6-anhydromuramyl pentapeptide and 1,6-anhydromuramyl tripeptide are the known activator ligands for
ampC
β-lactamase expression in
E. cloacae
. Here, we dissected the type of muropepetides for L1/L2 β-lactamase expression in an
mrdA
deletion mutant of
S. maltophilia
. Distinct from the findings with the
ampC
system, 1,6-anhydromuramyl tetrapeptide is the candidate for
ΔmrdA
-mediated β-lactamase expression in
S. maltophilia
. Our work extends the understanding of β-lactamase induction and provides valuable information for combating the occurrence of β-lactam resistance.
Cyclopia: isolated and with agnathia–otocephaly complex
Authors: Wai Lin Tun , Chandran Suresh
Published: August 2017

Cyclopia is a rare form of lethal holoprosencephaly (HPE) due to incomplete cleavage of prosencephalon during embryogenesis, leading to failure of the orbits of the eye to divide into two cavities. We report two cases, one with cyclopia and another case of cyclopia with agnathia–otocephaly complex (AOC). AOC (also known as agnathia–microstomia–synotia syndrome) is a rare lethal congenital malformation of the first branchial arch characterised by the association of agnathia (agenesis of mandible) or mandibular hypoplasia, melotia (anteromedial malposition of ears), microstomia (small mouth), aglossia or microglossia (absent or rudimentary tongue). These two reported cases had in common a single eye and alobar HPE. The first case was live born and the second stillborn. Both mothers did not have antenatal care.
Higher health literacy is associated with better glycemic control in adults with type 1 diabetes: a cohort study among 1399 Danes
Authors: Olesen Kasper , F Reynheim Anne Louise , Joensen Lene , Ridderstråle Martin , Kayser Lars , Maindal Helle T , Osborne Richard H , Skinner Timothy , Willaing Ingrid
Published: August 2017

Aim

Self-management of diabetes is influenced by a range of factors including the ability to access, understand, appraise, and use of health information in everyday life, which can collectively be called health literacy. We investigated associations between nine domains of health literacy and HbA1c level in people with type 1 diabetes.

Methods

A cross-sectional study was conducted with 1399 people with type 1 diabetes attending a Danish specialist diabetes clinic. Health literacy was assessed using the nine-domain Health Literacy Questionnaire. The association between health literacy and HbA1c was analyzed using linear regression with adjustment for age, sex, educational attainment and diabetes duration.

Results

Of the 1399 participants, 50% were women, mean age was 54 years, and mean HbA1c was 61 mmol/mol (7.8%). Higher health literacy scores were associated with lower HbA1c levels across eight of nine health literacy domains. This association remained significant after adjusting for educational attainment. Among the domains, ‘Actively managing my health’ had the strongest impact on HbA1c. This was in turn predicted by ‘Appraising health information’, ‘Having sufficient information to manage health’, and ‘Social support for health’.

Conclusions

Higher health literacy levels are associated with lower HbA1c regardless of educational background. This study highlights the importance of healthcare provision to respond to the health literacy levels of people with diabetes and to the possible need to provide program designed to enhance health literacy.
A qualitative study exploring the factors influencing admission to hospital from the emergency department
Authors: Pope Ian , Burn Helen , Ismail Sharif A , Harris Tim , McCoy David
Published: August 2017

Objective

The number of emergency admissions to hospital in England and Wales has risen sharply in recent years and is a matter of concern to clinicians, policy makers and patients alike. However, the factors that influence this decision are poorly understood. We aimed to ascertain how non-clinical factors can affect hospital admission rates.

Method

We conducted semistructured interviews with 21 participants from three acute hospital trusts. Participants included 11 emergency department (ED) doctors, 3 ED nurses, 3 managers and 4 inpatient doctors. A range of seniority was represented among these roles. Interview questions were developed from key themes identified in a theoretical framework developed by the authors to explain admission decision-making. Interviews were recorded, transcribed and analysed by two independent researchers using framework analysis.

Findings

Departmental factors such as busyness, time of day and levels of senior support were identified as non-clinical influences on a decision to admit rather than discharge patients. The 4-hour waiting time target, while overall seen as positive, was described as influencing decisions around patient admission, independent of clinical need. Factors external to the hospital such as a patient’s social support and community follow-up were universally considered powerful influences on admission. Lastly, the culture within the ED was described as having a strong influence (either negatively or positively) on the decision to admit patients.

Conclusion

Multiple factors were identified which go some way to explaining marked variation in admission rates observed between different EDs. Many of these factors require further inquiry through quantitative research in order to understand their influence further.
Regional transarterial hypothermic infusion in combination with endovascular thrombectomy in acute ischaemic stroke with cerebral main arterial occlusion: protocol to investigate safety of the clinical trial
Authors: Tokairin Kikutaro , Osanai Toshiya , Abumiya Takeo , Kazumata Ken , Ono Kota , Houkin Kiyohiro
Published: August 2017

Introduction

Acute cerebral ischaemia with main cerebral artery occlusion requires treatment with intravenous tissue plasminogen activator administration and/or endovascular thrombectomy. However, some patients fail to recover even after recanalisation because of ischaemia/reperfusion (I/R) injury. We hypothesised that regional transarterial hypothermic infusion would be effective for patients with I/R injury. The aim of this study is to validate the safety of this procedure.

Methods and analysis

This is a clinical exploratory study to evaluate safety of regional transarterial hypothermic infusion in combination with endovascular thrombectomy. Patients with acute ischaemic stroke and a National Institutes of Health Stroke Scale (NIHSS) score of 5–29 who require endovascular thrombectomy are eligible for the study. When no improvement in NIHSS score after the recanalisation is achieved by thrombectomy, cold saline (15°C) will be administered through a microcatheter located in the ipsilateral internal carotid artery. The primary endpoints of this study are mortality and morbidity. The secondary endpoint is deleterious effects on clinical data such as symptoms, radiographic findings and physiological data. The primary and secondary endpoints will be accumulated as case series because this study will be conducted on a small sample of seven patients.

Ethics and dissemination

All protocols and the informed consent form comply with the Ethics Guideline for Clinical Research (Japanese Ministry of Health, Labour and Welfare). Ethics review committees at the Hokkaido University Hospital approved the study protocols. The results of the study will be disseminated at several research conferences and also contributed to peer-reviewed journals. The study will be implemented and reported in line with the SPIRIT statement.

Trial registration number

UMIN Clinical Trails Registry (UMIN000018255); pre-results
Antenatal antiarrhythmic treatment for fetal tachyarrhythmias: a study protocol for a prospective multicentre trial
Authors: Miyoshi Takekazu , Maeno Yasuki , Sago Haruhiko , Inamura Noboru , Yasukochi Satoshi , Kawataki Motoyoshi , Horigome Hitoshi , Yoda Hitoshi , Taketazu Mio , Shozu Makio , Nii Masaki , Hagiwara Akiko , Kato Hitoshi , Shimizu Wataru , Shiraishi Isao , Sakaguchi Heima , Ueda Keiko , Katsuragi Shinji , Ikeda Tomoaki , Yamamoto Haruko , Hamasaki Toshimitsu
Published: August 2017

Introduction

Several retrospective or single-centre studies demonstrated the efficacy of transplacental treatment of fetal tachyarrhythmias. Our retrospective nationwide survey showed that the fetal therapy will be successful at an overall rate of 90%. For fetuses with hydrops, the treatment success rate will be 80%. However, standard protocol has not been established. The objective of this study is to evaluate the efficacy and safety of the protocol-defined transplacental treatment of fetal tachyarrhythmias. Participant recruitment began in October 2010.

Methods and analysis

The current study is a multicentre, single-arm interventional study. A total of 50 fetuses will be enrolled from 15 Japanese institutions. The protocol-defined transplacental treatment is performed for singletons with sustained fetal tachyarrhythmia ≥180 bpm, with a diagnosis of supraventricular tachycardia or atrial flutter. Digoxin, sotalol, flecainide or a combination is used for transplacental treatment. The primary endpoint is disappearance of fetal tachyarrhythmias. The secondary endpoints are fetal death related to tachyarrhythmia, proportion of preterm birth, rate of caesarean section attributable to fetal arrhythmia, improvement in fetal hydrops, neonatal arrhythmia, neonatal central nervous system disorders and neonatal survival. Maternal, fetal and neonatal adverse events are evaluated at 1 month after birth. Growth and development are also evaluated at 18 and 36 months of corrected age.

Ethics and dissemination

The Institutional Review Board of the National Cerebral and Cardiovascular Center of Japan has approved this study. Our findings will be widely disseminated through conference presentations and peer-reviewed publications.

Trial registration number

UMIN Clinical Trials Registry UMIN000004270.
Organ damage in sickle cell disease study (ORDISS): protocol for a longitudinal cohort study based in Ghana
Authors: Anie Kofi A , Paintsil Vivian , Owusu-Dabo Ellis , Ansong Daniel , Osei-Akoto Alex , Ohene-Frempong Kwaku , Amissah Kofi Aikins , Addofoh Nicholas , Ackah Ezekiel Bonwin , Owusu-Ansah Amma Twumwa , Ofori-Acquah Solomon Fiifi
Published: August 2017

Introduction

Sickle cell disease is highly prevalent in Africa with a significant public health burden. Nonetheless, morbidity and mortality in sickle cell disease that result from the progression of organ damage is not well understood. The Organ Damage in Sickle Cell Disease Study (ORDISS) is designed as a longitudinal cohort study to provide critical insight into cellular and molecular pathogenesis of chronic organ damage for the development of future innovative treatment.

Methods and analysis

ORDISS aims to recruit children aged 0–15 years who attend the Kumasi Centre for Sickle Cell Disease based at the Komfo Anokye Teaching Hospital in Kumasi, Ghana. Consent is obtained to collect blood and urine samples from the children during specified clinic visits and hospitalisations for acute events, to identify candidate and genetic markers of specific organ dysfunction and end-organ damage, over a 3 year period. In addition, data concerning clinical history and complications associated with sickle cell disease are collected. Samples are stored in biorepositories and analysed at the Kumasi Centre for Collaborative Research in Tropical Medicine, Ghana and the Centre for Translational and International Haematology, University of Pittsburgh, USA. Appropriate statistical analyses will be performed on the data acquired.

Ethics and dissemination

Research ethics approval was obtained at all participating sites. Results of the study will be submitted for publication in peer-reviewed journals, and the key findings presented at national and international conferences.
Trends in disability of instrumental activities of daily living among older Chinese adults, 1997-2006: population based study
Authors: Liang Yajun , Welmer Anna-Karin , Möller Jette , Qiu Chengxuan
Published: August 2017

Background

Data on trends for disability in instrumental activity of daily living (IADL) are sparse in older Chinese adults.

Objectives

To assess trends in prevalence and incidence of IADL disability among older Chinese adults and to explore contributing factors.

Design

Population based study.

Setting

15 provinces and municipalities in China.

Subjects

Participants (age ≥60) were from four waves of the China Health and Nutrition Survey, conducted in 1997 (n=1533), 2000 (n=1581), 2004 (n=2028) and 2006 (n=2256), and from two cohorts constructed within the national survey: cohort 1997–2004 (n=712) and cohort 2000–2006 (n=823).

Measurements

IADL disability was defined as inability to perform one or more of the following: shopping, cooking, using transportation, financing and telephoning. Data were analysed with logistic regression and generalised estimating equation models.

Results

The prevalence of IADL disability significantly decreased from 1997 to 2006 in the total sample and in all of the subgroups by age, sex, living region and IADL items (all ptrend<0.05). The incidence of IADL disability remained stable from cohort 1997-2004 to cohort 2000-2006 in the total sample and in all of the subgroups (all p>0.10). The recovery rate from IADL disability significantly increased over time in those aged 60–69 years (p=0.03). Living in a rural area or access to local clinics for healthcare was less disabling over time (ptrend<0.02).

Conclusions

The prevalence of IADL disability decreased among older Chinese adults during 1997–2006, whereas the incidence remained stable. The declining prevalence of IADL disability might be partly due to the decreased duration of IADL disability, and to improvements in living conditions and healthcare facilities over time.
Determinants of severe acute malnutrition among children under 5 years of age in Nepal: a community-based case–control study
Authors: Pravana Nilesh Kumar , Piryani Suneel , Chaurasiya Surendra Prasad , Kawan Rasmila , Thapa Ram Krishna , Shrestha Sumina
Published: August 2017

Background

Malnutrition is one of the leading causes of morbidity and mortality among children under the age of 5 years in low and middle income countries like Nepal. Children with severe acute malnutrition (SAM) are nine times more likely to die than children without malnutrition. The prevalence of SAM has increased in Nepal over the past 15 years; however, the determinants of SAM have not been clearly assessed in the country.

Objective

To assess the determinants of SAM among children aged 6–59 months in the Bara district of Nepal.

Setting

A community-based case–control study was conducted in 12 randomly selected Village Development Committees (VDCs) of the Bara district of Nepal.

Participants

A random sample of 292 children aged 6–59 months (146 as cases and 146 as controls) from 12 VDCs were included in this study.

Results

The prevalence of SAM among children under the age of 5 years was 4.14%. The following factors were significantly associated with SAM: low socioeconomic status (adjusted odds ratio (AOR) 17.13, 95% CI 5.85 to 50.13); mother’s age at birth <20 or >35 years (AOR 3.21, 95% CI 1.30 to 7.94); birth interval <24 months (AOR 4.09, 95% CI 1.87 to 8.97); illiterate father (AOR 3.65, 95% CI 1.62 to 8.20); bottle feeding (AOR 2.19, 95% CI 1.73 to 12.03); and not initiating complementary feeding at the age of 6 months (AOR 2.91, 95% CI 1.73 to 12.03). Mother’s educational level, initiation of breastfeeding, colostrum feeding, and exclusive breastfeeding were not significantly associated with SAM.

Conclusion

The mother's age at birth, birth interval, socioeconomic status, father’s educational level and initiation of complementary feeding at the age of 6 months were important determinants of SAM among children. A multi-sector approach is essential to address SAM. There is a need for further studies not only focusing on SAM but also moderate acute malnutrition.
The Chinese version of the Severe Respiratory Insufficiency questionnaire for patients with chronic hypercapnic chronic obstructive pulmonary disease receiving non-invasive positive pressure ventilation
Authors: Chen Rongchang , Guan Lili , Wu Weiliang , Yang Zhicong , Li Xiaoying , Luo Qun , Liang Zhenyu , Wang Fengyan , Guo Bingpeng , Huo Yating , Yang Yuqiong , Zhou Luqian
Published: August 2017

Objectives

The Severe Respiratory Insufficiency (SRI) questionnaire is the best assessment tool for health-related quality of life in patients with chronic obstructive pulmonary disease (COPD) receiving non-invasive positive pressure ventilation (NIPPV). This study aimed to translate the SRI Questionnaire into Chinese and to validate it.

Design

Prospective validation study.

Setting and participants

A total of 149 participants with chronic hypercapnic COPD receiving NIPPV completed the study.

Methods

The SRI questionnaire was translated into Chinese using translation and back-translation. Reliability was gauged using Cronbach’s α coefficient. Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were used to assess construct validity. Content validity was confirmed by evaluating the relationship between the score of each item and the total score of the relevant subscale.

Results

Cronbach’s α coefficients for each subscale and summary scale were above 0.7. Using EFA, one factor was extracted from the anxiety and summary scales and two factors were extracted from the remaining six subscales. Based on the EFA results, subsequent CFA revealed a good model fit for each subscale, but the extracted factors of each subscale were correlated. Content validity was confirmed by the good relationship between the score of each item and the total score of the relevant subscale.

Conclusion

The Chinese version of the SRI questionnaire is valid and reliable for patients with chronic hypercapnic COPD receiving NIPPV in China.

Trial registration number

NCT02499718.
Improving MRCP PACES pass rates through the introduction of a regional multifaceted support framework
Authors: Jerrom Richard , Roper Tayeba , Murthy Narasimha
Published: August 2017

Introduction

Practical Assessment of Clinical Examination Skills (PACES) constitutes the final part of the mandatory Royal College of Physicians exam series for progression to higher specialty training. Pass rates were lower for core medical trainees (CMTs) in Coventry and Warwickshire in comparison to other regions within the West Midlands and nationally.

Objectives

Our aim was to improve pass rates in the region through the introduction of a stimulating and supportive teaching framework, designed to enhance the quality and frequency of PACES teaching.

Methods

To identify key areas for change a baseline questionnaire, including Likert Scale and free text questions related to PACES teaching, was distributed to all CMTs in the region. Many trainees highlighted concern over lack of PACES-orientated teaching and support, with particular emphasis on: lack of bedside-teaching with feedback; infrequent opportunities for practising communication skills; and difficulty identifying suitable patients in an efficient manner. To address these concerns the following interventions were implemented over two Plan, Do, Study, Act (PDSA) cycles which were analysed at 6 months and 12months: a digital forum to highlight relevant inpatients for examination practice; a peer-to-peer mentoring scheme; a consultant-led bedside-teaching rota; and classroom-based communication skills sessions.

Results

Pass rates at Annual Review of Competence Progression improved from baseline to the end of the first year of implementation, 56.3% to 77.3%, respectively. Furthermore, following analysis of questionnaires at each PDSA cycle, we demonstrated a progressive improvement in trainee satisfaction in exposure, quality and relevance of teaching.

Conclusion

Our innovative, cost-effective teaching framework for PACES preparation has improved exam outcomes and facilitated swift junior doctor career progression, while raising the profile of the trust. Furthermore, this innovation provides a template for potential adoption in other National Health Service institutions.
Accounting for variable recruitment and fishing mortality in length-based stock assessments for data-limited fisheries
Authors: Rudd Merrill B. , Thorson James T.
Published: August 2017

In fisheries with limited capacity for monitoring, it is often easier to collect length measurements from fishery catch than quantify total catch. Conventional stock assessment tools that rely on length measurements without total catch do not directly account for variable fishing mortality and recruitment over time. However, this equilibrium assumption is likely violated in almost every fishery, degrading estimation performance. We developed an extension of length-only approaches to account for time-varying recruitment and fishing mortality. This Length-based Integrated Mixed Effects (LIME) method at a minimum requires a single year of length data and basic biological information but can fit to multiple years of length data, catch, and an abundance index if available. We use simulation testing to demonstrate that LIME can estimate how much fishing has reduced spawning output in the most recent year across a variety of scenarios for recruitment and fishing mortality. LIME improves data-limited fisheries stock assessments by its flexibility to incorporate additional years or types of data if available and obviates the need for equilibrium assumptions.
Contemporary range expansion of the Virginia opossum (Didelphisvirginiana) impacted by humans and snow cover
Authors: Walsh L.L. , Tucker P.K.
Published: August 2017

Range expansions are key demographic events driven by factors such as climate change and human intervention that ultimately influence the genetic composition of peripheral populations. The expansion of the Virginia opossum (Didelphis virginiana Kerr, 1792) into Michigan has been documented over the past 200 years, indicating relatively new colonizations in northern Michigan. Although most contemporary expansions are a result of shifts in climate regimes, the opossum has spread beyond its hypothesized climate niche, offering an opportunity to examine the compounding influence that climate change and humans have on a species’ distribution. The genetic consequences of two range expansions were investigated using genotypic data for nine microsatellite markers from opossums collected in Michigan, Ohio, and Wisconsin, USA. Two genetic clusters were identified: one on either side of Lake Michigan. Using general linear models, we found that measurements of genetic diversity across 15 counties are best explained by days of snow on the ground. Next best models incorporate anthropogenic covariates including farm density. These models suggest that opossum expansion may be facilitated by agricultural land development and at the same time be limited by their inability to forage in snow.
Discrete Particle Methods for Simulating Quasi-Static Load and Hypervelocity Impact Phenomena
Authors: Steinhauser Martin O. , Watson Erkai
Published: August 2017

In this paper, we introduce a mesh-free computational model for the simulation of high-speed impact phenomena. Within the framework of particle dynamics simulations we model a macroscopic solid ceramic tile as a network of overlapping discrete particles of microscopic size. Using potentials of the Lennard–Jones type, we integrate the classical Newtonian equations of motion and perform uni-axial, quasi-static load simulations to customize our three model parameters to the typical tensile strength, Young’s modulus and the compressive strength of a ceramic. Subsequently we perform shock load simulations in a standard experimental setup, the edge-on impact (EOI) configuration. Our obtained results concerning crack initiation and propagation through the material agree well with corresponding high-speed EOI experiments with Aluminum Oxinitride (AlON), Aluminum Oxide [Formula: see text] and Silicon Carbide (SiC), performed at the Fraunhofer Ernst-Mach-Institute (EMI). Additionally, we present initial simulation results where we use our particle–based model to simulate a second type of high-speed impact experiments where an accelerated sphere strikes a thin aluminum plate. Such experiments are done at our institute to investigate the debris clouds arising from such impacts, which constitute a miniature model version of a generic satellite structure that is hit by debris in the earth’s orbit. Our findings are that a discrete particle based method leads to very stable, energy-conserving simulations of high–speed impact scenarios. Our chosen interaction model works particularly well in the velocity range where the local stresses caused by impact shock waves markedly exceed the ultimate material strength.
REWIMO
Authors: Dezfouli Behnam , Radi Marjan , Chipara Octav
Published: August 2017

Industrial applications and cyber-physical systems rely on real-time wireless networks to deliver data in a timely and reliable manner. However, existing solutions provide these guarantees only for stationary nodes. In this article, we present REWIMO, a solution for real-time and reliable communications in mobile networks. REWIMO has a two-tier architecture composed of (i) infrastructure nodes and (ii) mobile nodes that associate with infrastructure nodes as they move. REWIMO employs an on-join bandwidth reservation approach and benefits from a set of techniques to efficiently reserve bandwidth for each mobile node at the time of its admission and over its potential data forwarding paths. To ensure association of mobile nodes with infrastructure nodes over high-quality links, REWIMO uses the two-phase scheduling technique to coordinate neighbor discovery with data transmission. To mitigate the overhead of handling network dynamics, REWIMO employs an additive scheduling algorithm, which is capable of additive bandwidth reservation without modifying existing schedules. Compared to the algorithms used by static real-time wireless networks, the techniques and the algorithms employed by REWIMO result in a significant increase in real-time capacity, enhanced reliability, and considerably faster handling of network dynamics.
Agent-Based Models for Financial Crises
Authors: Bookstaber Richard
Published: August 2017

This article describes the agent-based approach to modeling financial crises. It focuses on the interactions of agents and on how these interactions feed back to change the financial environment. It explains how these models embody the contagion and cascades that occur owing to the financial leverage and market concentration of the agents and the liquidity of the markets. This article also compares agent-based models to the standard economic approach to crises and shows the ways in which agent-based models overcome limitations of economic models when dealing with financial crises. In particular, this article demonstrates how agent-based models replace homogeneous, representative agents with heterogeneous agents and optimization with heuristics, and how such models move away from a focus on equilibrium, allowing non-ergodic dynamics that are manifest during financial crises to emerge.
Origin and Evolution of the Universal Genetic Code
Authors: Koonin Eugene V. , Novozhilov Artem S.
Published: August 2017

The standard genetic code (SGC) is virtually universal among extant life forms. Although many deviations from the universal code exist, particularly in organelles and prokaryotes with small genomes, they are limited in scope and obviously secondary. The universality of the code likely results from the combination of a frozen accident, i.e., the deleterious effect of codon reassignment in the SGC, and the inhibitory effect of changes in the code on horizontal gene transfer. The structure of the SGC is nonrandom and ensures high robustness of the code to mutational and translational errors. However, this error minimization is most likely a by-product of the primordial code expansion driven by the diversification of the repertoire of protein amino acids, rather than a direct result of selection. Phylogenetic analysis of translation system components, in particular aminoacyl–tRNA synthetases, shows that, at a stage of evolution when the translation system had already attained high fidelity, the correspondence between amino acids and cognate codons was determined by recognition of amino acids by RNA molecules, i.e., proto-tRNAs. We propose an experimentally testable scenario for the evolution of the code that combines recognition of amino acids by unique sites on proto-tRNAs (distinct from the anticodons), expansion of the code via proto-tRNA duplication, and frozen accident.
Integration of Agrobacterium T-DNA into the Plant Genome
Authors: Gelvin Stanton B.
Published: August 2017

Agrobacterium strains transfer a single-strand form of T-DNA (T-strands) and Virulence (Vir) effector proteins to plant cells. Following transfer, T-strands likely form complexes with Vir and plant proteins that traffic through the cytoplasm and enter the nucleus. T-strands may subsequently randomly integrate into plant chromosomes and permanently express encoded transgenes, a process known as stable transformation. The molecular processes by which T-strands integrate into the host genome remain unknown. Although integration resembles DNA repair processes, the requirement of known DNA repair pathways for integration is controversial. The configuration and genomic position of integrated T-DNA molecules likely affect transgene expression, and control of integration is consequently important for basic research and agricultural biotechnology applications. This article reviews our current knowledge of the process of T-DNA integration and proposes ways in which this knowledge may be manipulated for genome editing and synthetic biology purposes.
The Properties and Antecedents of Hedonic Decline
Authors: Galak Jeff , Redden Joseph P.
Published: August 2017

We review the phenomenon of hedonic decline, whereby repeated exposure to a stimulus typically reduces the hedonic response (e.g., enjoyment). We first discuss the typical trajectory of hedonic decline and the common research paradigms used to study it. We next discuss the most popular theories regarding general mechanisms widely believed to underlie hedonic decline. We then propose a taxonomy to organize these various general theories and to incorporate more recent work on top-down, self-reflective theories. This taxonomy identifies three general classes of antecedents to hedonic decline: physiological feedback, perceptual changes, and self-reflection. For each class, we review the supporting evidence for specifically identified antecedents and recent developments on how each antecedent influences hedonic decline. Our review focuses especially on more recent work in the growing area of self-reflection.
An excitatory reflex from the superficial peroneal nerve to the bladder in cats
Authors: Yu Michelle , Uy Jamie , Jiang Xuewen , Li Xing , Jones Cameron , Shen Bing , Wang Jicheng , Roppolo James R. , de Groat William C. , Tai Changfeng
Published: August 2017

This study in α-chloralose-anesthetized cats discovered an excitatory peroneal nerve-to-bladder reflex. A urethral catheter was used to infuse the bladder with saline and record bladder pressure changes. Electrical stimulation was applied to the superficial peroneal nerve to trigger reflex bladder activity. With the bladder distended at a volume ~90% of bladder capacity, superficial peroneal nerve stimulation (PNS) at 1–3 Hz and threshold (T) intensity for inducing muscle twitching on the posterior thigh induced large-amplitude (40–150 cmH2O) bladder contractions. PNS (1–3 Hz, 1–2T) applied during cystometrograms (CMGs) when the bladder was slowly (1–3 ml/min) infused with saline significantly ( P < 0.01) reduced bladder capacity to ~80% of the control capacity and significantly ( P < 0.05) enhanced reflex bladder contractions. To determine the impact of PNS on tibial nerve stimulation (TNS)-induced changes in bladder function, PNS was delivered following TNS. TNS of 30-min duration produced long-lasting poststimulation inhibition and significantly ( P < 0.01) increased bladder capacity to 140.5 ± 7.6% of the control capacity. During the post-TNS inhibition period, PNS (1–3 Hz, 1–4T) applied during CMGs completely restored bladder capacity to the control level and significantly ( P < 0.05) increased the duration of reflex bladder contractions to ~200% of control. The excitatory peroneal nerve-to-bladder reflex could also be activated by transcutaneous PNS using skin surface electrodes attached to the dorsal surface of the foot. These results raise the possibility of developing novel neuromodulation therapies to treat underactive bladder and nonobstructive urinary retention.
Corticospinal excitability of the biceps brachii is shoulder position dependent
Authors: Collins Brandon Wayne , Cadigan Edward W. J. , Stefanelli Lucas , Button Duane C.
Published: August 2017

The purpose of this study was to examine the effect of shoulder position on corticospinal excitability (CSE) of the biceps brachii during rest and a 10% maximal voluntary contraction (MVC). Participants ( n = 9) completed two experimental sessions with four conditions: 1) rest, 0° shoulder flexion; 2) 10% MVC, 0° shoulder flexion; 3) rest, 90° shoulder flexion; and 4) 10% MVC, 90° shoulder flexion. Transcranial magnetic, transmastoid electrical, and Erb’s point stimulation were used to induce motor-evoked potentials (MEPs), cervicomedullary MEPs (CMEPs), and maximal muscle compound potentials (Mmax), respectively, in the biceps brachii in each condition. At rest, MEP, CMEP, and Mmax amplitudes increased ( P < 0.01) by 509.7 ± 118.3%, 113.3 ± 28.3%, and 155.1 ± 47.9%, respectively, at 90° compared with 0°. At 10% MVC, MEP amplitudes did not differ ( P = 0.08), but CMEP and Mmax amplitudes increased ( P < 0.05) by 32.3 ± 10.5% and 127.9 ± 26.1%, respectively, at 90° compared with 0°. MEP/Mmax increased ( P < 0.01) by 224.0 ± 99.1% at rest and decreased ( P < 0.05) by 51.3 ± 6.7% at 10% MVC at 90° compared with 0°. CMEP/Mmax was not different ( P = 0.22) at rest but decreased ( P < 0.01) at 10% MVC by 33.6 ± 6.1% at 90° compared with 0°. EMG increased ( P < 0.001) by 8.3 ± 2.0% at rest and decreased ( P < 0.001) by 21.4 ± 4.4% at 10% MVC at 90° compared with 0°. In conclusion, CSE of the biceps brachii was dependent on shoulder position, and the pattern of change was altered within the state in which it was measured. The position-dependent changes in Mmax amplitude, EMG, and CSE itself all contribute to the overall change in CSE of the biceps brachii.

NEW & NOTEWORTHY We demonstrate that when the shoulder is placed into two common positions for determining elbow flexor force and activation, corticospinal excitability (CSE) of the biceps brachii is both shoulder position and state dependent. At rest, when the shoulder is flexed from 0° to 90°, supraspinal factors predominantly alter CSE, whereas during a slight contraction, spinal factors predominantly alter CSE. Finally, the normalization techniques frequently used by researchers to investigate CSE may under- and overestimate CSE when shoulder position is changed.
Method to remove photoreceptors from whole mount retina in vitro
Authors: Walston Steven T. , Chang Yao-Chuan , Weiland James D. , Chow Robert H.
Published: August 2017

Patch clamp recordings of neurons in the inner nuclear layer of the retina are difficult to conduct in a whole mount retina preparation because surrounding neurons block the path of the patch pipette. Vertical slice preparations or dissociated retinal cells provide access to bipolar cells at the cost of severing the lateral connection between neurons. We have developed a technique to remove photoreceptors from the rodent retina that exposes inner nuclear layer neurons, allowing access for patch clamp recording. Repeated application to and removal of filter paper from the photoreceptor side of an isolated retina effectively and efficiently removes photoreceptor cells and, in degenerate retina, hypertrophied Müller cell end feet. Live-dead assays applied to neurons remaining after photoreceptor removal demonstrated mostly viable cells. Patch clamp recordings from bipolar cells reveal responses similar to those recorded in traditional slice and dissociated cell preparations. An advantage of the photoreceptor peel technique is that it exposes inner retinal neurons in a whole mount retina preparation for investigation of signal processing. A disadvantage is that photoreceptor removal alters input to remaining retinal neurons. The technique may be useful for investigations of extracellular electrical stimulation, photoreceptor DNA analysis, and nonpharmacological removal of light input.

NEW & NOTEWORTHY This study reports a method for removing photoreceptors from rodent whole mount retina while preserving the architecture of the inner retina. The method enables easier access to the inner retina for studies of neural processing, such as by patch clamp recording.
Liver Adiposity and Metabolic Profile in Individuals with Chronic Spinal Cord Injury
Authors: Rankin Kathleen C. , O’Brien Laura C. , Segal Liron , Khan M. Rehan , Gorgey Ashraf S.
Published: August 2017

Purpose. To quantify liver adiposity using magnetic resonance imaging (MRI) and to determine its association with metabolic profile in men with spinal cord injury (SCI).Materials and Methods. MRI analysis of liver adiposity by fat signal fraction (FSF) and visceral adipose tissue (VAT) was completed on twenty participants. Intravenous glucose tolerance test was conducted to measure glucose effectiveness(Sg)and insulin sensitivity (Si). Lipid panel, fasting glucose, glycated hemoglobin (HbA1c), and inflammatory cytokines were also analyzed.Results. Average hepatic FSF was3.7%±2.1. FSF was positively related to TG, non-HDL-C, fasting glucose, HbA1c, VAT, and tumor necrosis factor alpha (TNF-α). FSF was negatively related toSiand testosterone. FSF was positively related to VAT (r=0.48,p=0.032) and TNF-α(r=0.51,p=0.016) independent of age, level of injury (LOI), and time since injury (TSI). The associations between FSF and metabolic profile were independent of VAT.Conclusions. MRI noninvasively estimated hepatic adiposity in men with chronic SCI. FSF was associated with dysfunction in metabolic profile, central adiposity, and inflammation. Importantly, liver adiposity influenced metabolic profile independently of VAT. These findings highlight the significance of quantifying liver adiposity after SCI to attenuate the development of metabolic disorders.