bluuebunny/crossref_metadata_2025 huggingface dataset:
Observed and projected drivers of emerging infectious diseases in Europe
Authors: Semenza Jan C. , Rocklöv Joacim , Penttinen Pasi , Lindgren Elisabet
Published: July 2016

Emerging infectious diseases are of international concern because of the potential for, and impact of, pandemics; however, they are difficult to predict. To identify the drivers of disease emergence, we analyzed infectious disease threat events (IDTEs) detected through epidemic intelligence collected at the European Centre for Disease Prevention and Control (ECDC) between 2008 and 2013, and compared the observed results with a 2008 ECDC foresight study of projected drivers of future IDTEs in Europe. Among 10 categories of IDTEs, foodborne and waterborne IDTEs were the most common, vaccine‐preventable IDTEs caused the highest number of cases, and airborne IDTEs caused the most deaths. Observed drivers for each IDTE were sorted into three main groups: globalization and environmental drivers contributed to 61% of all IDTEs, public health system drivers contributed to 21%, and social and demographic drivers to 18%. A multiple logistic regression analysis showed that four of the top five drivers for observed IDTEs were in the globalization and environment group. In the observational study, the globalization and environment group was related to all IDTE categories, but only to five of eight categories in the foresight study. Directly targeting these drivers with public health interventions may diminish the chances of IDTE occurrence from the outset.
Dying and death within the culture of long‐term care facilities in Canada
Authors: Cable‐Williams Beryl , Wilson Donna M.
Published: July 2016

Aim and objective

To identify the influence of the culture in Canadian long‐term care facilities on the awareness of impending death and initiation of a palliative approach to care for residents aged 85 years and older.

Background

Many long‐term care residents die after long, dwindling dying trajectories, yet palliative care is often not provided until within a few hours or days of death.

Design

Focused ethnography.

Methods

Data were collected in three long‐term care facilities in south‐central Ontario, Canada, through interviews with residents, family members and staff members, observation, artefact review and a focus group. Data were analysed using a constant comparative technique.

Results

Four cultural influences on the awareness of impending death and consequent initiation of a palliative approach to care were identified: (i) the care demands in long‐term care facilities and the resources available to meet these demands; (ii) the belief that long‐term care facilities are for living; (iii) the belief that no one should die in pain; and (iv) the belief that no one should die alone.

Conclusions

Commonly held beliefs about the role of long‐term care facilities and what is viewed as acceptable care in them mediated the acknowledgement of dying. Late initiation of palliative care was the consequence. In addition, the contextual factors of a low staff‐to‐resident ratio and reduced staff preparation for palliative care were also influential for a delayed response to dying.

Implications for practice

Because strongly held long‐term care cultural beliefs underlie care, more timely palliative care for long‐term care residents is likely to require the development of an understanding that living and dying are not dichotomous, but rather unfold together from admission until death. Enhanced staff‐to‐resident ratios and staff training on palliative care will also be necessary to permit long‐term care facility staff to focus beyond the currently expected day‐to‐day care of living residents to provide high‐quality end‐of‐life care throughout the often protracted decline to death for residents of long‐term care facilities.
Is risk‐taking in talented junior tennis players related to overuse injuries?
Authors: Van der Sluis A. , Brink M. S. , Pluim B. , Verhagen E. A. , Elferink‐Gemser M. T. , Visscher C.
Published: July 2016

Overuse injuries are a serious problem in junior tennis. Gaining insight in age‐specific risk factors can contribute to prevention. The developmental cognitive processes that take place during adolescence make talented players more inclined to take risks. This may be even more pronounced in the high performance culture in which they move. Therefore, this study focuses on the relationship between risk‐taking and overuse injuries in talented tennis players. Seventy‐three talented tennis players (45 boys and 28 girls, age 11–14 years) were monitored for 32 weeks, using the Oslo Sports Trauma Research Centre Questionnaire on Health Problems. Risk‐taking was measured at the start of the season with the Iowa Gambling Task. Linear regression analyses were executed to predict (a) overuse injuries, (b) time loss overuse injuries and (c) overuse severity, by risk‐taking, exposure time, and injury history. In boys, risk‐taking contributed significantly to time loss overuse injuries [F(1,39) = 7.764, P = 0.008, R2 = 0.15] and to overuse severity [F(1,39) = 5.683, P = 0.022, with an R2 of 0.13] In girls, time loss overuse injuries [F(1,23) = 6.889, P = 0.018, R2 = 0.20] and overuse severity [F(1,23) = 7.287, P = 0.013, R2 = 0.24] were predicted by exposure time. Coaches and trainers should be aware that talented male tennis players who are inclined to take risks, are more likely to maintain risky behavioral patterns related to overuse injuries.
Dosages of cold‐water immersion post exercise on functional and clinical responses: a randomized controlled trial
Authors: Machado A. F. , Almeida A. C. , Micheletti J. K. , Vanderlei F. M. , Tribst M. F. , Netto Junior J. , Pastre C. M.
Published: July 2016

Cold‐water immersion (CWI) is one of the recovery techniques commonly used by athletes for post‐exercise recovery. Nevertheless, the effects of CWI using different temperatures and the dose–response relationship of this technique have not yet been investigated. The aims of this study were to compare the effects of two strategies of CWI, using different water temperatures with passive recovery post exercise in the management of some markers of muscle damage, and to observe whether any of the techniques used caused deleterious effects on performance. Sixty healthy male participants performed an eccentric protocol to induce muscle damage and were then randomized to one of three groups (CWI1: 15 min at 9 °C; CWI2: 15 min at 14 °C; CG: control group). Levels of creatine kinase, muscle soreness, pain threshold, perception of recovery, and maximal voluntary isometric contraction were monitored up to 96 h post exercise. A large effect for time for all outcomes was observed [P < 0.001; CK (ES = 0.516), muscle soreness (ES = 0.368); pain threshold (ES = 0.184); perception of recovery (ES = 0.565); MVIC (ES = 0.273)]. CWI groups presented an earlier recovery for muscle soreness with lower ratings immediately post recovery. For delayed effects, the application of CWI2 (15 min at 14 °C) presented earlier recovery compared with CWI1 and control condition for maximal voluntary isometric contraction (P < 0.05). There were no significant group and interaction (Group × Time) effects. CWI groups acted more efficiently for muscle soreness and performance considering the time of recovery was observed. No evidence was found to suggest dose–response relationship and deleterious effects.
Transcutaneous pneumatic injection of glucose solution: a morphometric evaluation of in vivo micropig skin and tissue‐mimicking phantom
Authors: Cho S. B. , Kwon T. R. , Yoo K. H. , Oh C. T. , Choi E. J. , Kim B. J.
Published: July 2016

Background

Needle‐free, transcutaneous pneumatic injection systems can be used to deliver therapeutic solutions to targeted layers of skin in a minimally invasive manner.

Methods

To evaluate jet infiltration patterns and tissue reactions, 5% isotonic and 20% hypertonic glucose solutions were pneumatically injected into in vivo micropig skin. Gelatin TM phantom was additionally prepared to analyze penetration and dispersion patterns for different experimental settings.

Results

As immediate tissue reactions in the in vivo micropig skin, distinct pneumatic injection injury zones (PIIZs) in the dermis, extending from the papillary dermis deep into the dermo‐subcutaneous junction, were generated with the 5% and 20% glucose solutions and with pneumatic pressures of 4.64 and 5.7 bars, respectively. PIIZs markedly decreased in appearance at 1 day after treatment, accompanied by inflammatory cell infiltration, and disappeared at 7 days post‐treatment with increased collagen and elastin production. In TM phantom study, the PIIZs created by 20% glucose mainly comprised a single, homogenous, round to oval zone, whereas those created by 5% glucose were irregular and multi‐lobular.

Conclusion

The present study suggests that transcutaneous pneumatic injection therapy may exert mechanical stimulatory effects, immediate tissue shrinkage via hypertonic solutions, and late tissue regeneration effects during wound healing.
The Myth of the “Two Souths?” Racial Resentment and White Party Identification in the Deep South and Rim South*
Authors: Knuckey Jonathan
Published: July 2016

Objectives

This article addresses a debate among scholars of southern politics concerning the relevance of the distinction between the Deep South and Rim South states. Specifically, it examines the effect of racial resentment on white party identification in both southern subregions.

Methods

Data from the 2010 and 2012 Cooperative Congressional Election Studies (CCES) are analyzed using a multivariate logistic regression model to examine subregional differences in the effect of racial resentment on southern white party identification.

Results

Although whites in the Deep South were more likely to identify as Republicans than whites in the Rim South, the effect of racial resentment on party identification in the Deep South was not statistically different from that of whites in the Rim South.

Conclusions

While it may be premature to completely discard the notion of the “Two Souths” it may behoove scholars of southern politics to also focus on individual state‐by‐state commonalities and differences, rather than be bound exclusively to the Deep/Rim South dichotomy.
Apology Speech Act Realization in the Sarawani Balochi Dialect: A Case Study of Female University Students
Authors: Ahangar Abbas Ali , Zeynali Dastuyi Seddigheh
Published: July 2016

This study aims at extracting and categorizing apology strategies in the Sarawani Balochi dialect. It also investigates the effect of the status and gender of addressees on the type and number of apology strategies employed by Sarawani Baloch female university students (SBFUS) based on a revised version of the Cross Cultural Speech Act Realization Project (CCSARP) proposed by Blum‐Kulka, House and Kasper (1989). The results show that while they used most of the apology strategies mentioned in CCSARP, which speaks to the universality of employing apology strategies, the participants also used new strategies reflecting the influence of their religious and cultural values. The results also show that although the status of the addressees significantly influenced the type and number of apology strategies used by the SBFUS in each type of apology situation, gender did not seem to have any such effect. Regarding the type and number of apology strategies, the most frequently used apology strategies were “illocutionary force indicating devices” and the “combination of 2” strategies.
Ten‐year follow‐up of two cohorts with an increased risk of variant CJD: donors to individuals who later developed variant CJD and other recipients of these at‐risk donors
Authors: Checchi M. , Hewitt P. E. , Bennett P. , Ward H. J. T. , Will R. G. , Mackenzie J. M. , Sinka K.
Published: July 2016

Background

Transmission of variant Creutzfeldt–Jakob disease (vCJD) through blood transfusion is implicated in three deaths and one asymptomatic infection. Based on this evidence, individuals assessed to be at increased risk of vCJD through donating blood transfused to individuals who later developed vCJD, or through being other recipients of such donors, are followed up to further understand the risks of vCJD transmission through blood.

Objectives

To provide a ten‐year follow‐up of these at‐risk cohorts.

Methods

Blood donors to patients who later died from vCJD were identified by the Transfusion Medicine Epidemiological Review (TMER) study. A reverse risk probability assessment quantified the risk of blood transfusion or exposure through diet as the source of vCJD in the recipients. Donors to these recipients, and these donors’ other recipients, with a probability risk above 1%, are classified as at increased risk of vCJD for public health purposes. These cohorts are monitored for any vCJD occurrences.

Results

A total of 112 donors and 33 other recipients of their donated blood have been classified as at increased risk. After 2397 and 492 vCJD‐free years of follow–up, respectively, no deaths in either at‐risk cohort were of vCJD‐related causes.

Conclusions

The at‐risk cohorts have survived disease‐free far longer than the estimated incubation time for dietary‐acquired vCJD (donors) and transfusion‐acquired disease (other recipients). However, due to our still limited understanding of, and a lack of a reliable test for, asymptomatic vCJD infection, public health follow‐up is necessary for continued monitoring of at‐risk cohorts.
Single-Machine Infinite-Bus Power System Excitation Control Design With Resilient Extended Kalman Filter
Authors: Wang Xin , Gu Patrick
Published: July 2016

To effectively control and maintain the transient stability of power systems, traditionally, the extended Kalman filter (EKF) is used as the real-time state estimator (RTSE) to provide the unmeasurable state information. However, the EKF estimation may degrade or even become unstable when the measurement data are inaccurate through random sensor failures, which is a widespread problem in data-intensive power system control applications. To address this issue, this paper proposes an improved EKF that is resilient against sensor failures. This work focuses on the resilient EKF’s (REKF’s) derivation with its application to single-machine infinite-bus (SMIB) power system excitation control. The sensor failure rate is modeled as a binomial distribution with a known mean value. The performance of REKF is compared with the traditional EKF for power system observer-based control under various chances of sensor failures. Computer simulation studies have shown the efficacy and superior performance of the proposed approach in power system control applications.
Whistle characteristics and daytime dive behavior in pantropical spotted dolphins (Stenella attenuata) in Hawai‘i measured using digital acoustic recording tags (DTAGs)
Authors: Silva Tammy L. , Mooney T. Aran , Sayigh Laela S. , Tyack Peter L. , Baird Robin W. , Oswald Julie N.
Published: July 2016

This study characterizes daytime acoustic and dive behavior of pantropical spotted dolphins (Stenella attenuata) in Hawai‘i using 14.58 h of data collected from five deployments of digital acoustic recording tags (DTAG3) in 2013. For each tagged animal, the number of whistles, foraging buzzes, dive profiles, and dive statistics were calculated. Start, end, minimum, and maximum frequencies, number of inflection points and duration were measured from 746 whistles. Whistles ranged in frequency from 9.7 ± 2.8 to 19.8 ± 4.2 kHz, had a mean duration of 0.7 ± 0.5 s and a mean of 1.2 ± 1.2 inflection points. Thirteen foraging buzzes were recorded across all tags. Mean dive depth and duration were 16 ± 9 m and 1.9 ± 1.0 min, respectively. Tagged animals spent the majority of time in the upper 10 m (76.9% ± 16.1%) of the water column. Both whistle frequency characteristics and dive statistics measured here were similar to previously reported values for spotted dolphins in Hawai‘i. Shallow, short dive profiles combined with few foraging buzzes provide evidence that little spotted dolphin feeding behavior occurs during daytime hours. This work represents one of the first successful DTAG3 studies of small pelagic delphinids, providing rare insights into baseline bioacoustics and dive behavior.
Selling Health and Fitness to Sporty Sisters: A Critical Feminist Multi-Modal Discourse Analysis of the Lorna Jane Retail Website
Authors: Nash Meredith
Published: July 2016

In this paper, I conduct a feminist multimodal critical discourse analysis (FMCDA) of the Lorna Jane (LJ) retail website (www.lornajane.com.au), an Australian fitness fashion company, to examine the discursive strategies used by the company to authorize a particular notion of “active living” for women. Specifically, I shall examine how the semiotic choices on the LJ website signify key discourses and themes related to health and fitness and how they are used to place the responsibility for fitness and health onto individual women. In particular, I focus on the discourses inscribed through the technologies, styles, fabrics, colors, cuts, and sizing of LJ clothing items. I am also interested in the underlying choices, assumptions, and biases of these constructions and the power relationships underpinning them. I conclude that “empowerment” for women on the LJ website is imagined in a limited, individualistic way.
RpoN Modulates Carbapenem Tolerance in Pseudomonas aeruginosa through Pseudomonas Quinolone Signal and PqsE
Authors: Viducic Darija , Murakami Keiji , Amoh Takashi , Ono Tsuneko , Miyake Yoichiro
Published: July 2016

The ability of
Pseudomonas aeruginosa
to rapidly modulate its response to antibiotic stress and persist in the presence of antibiotics is closely associated with the process of cell-to-cell signaling. The alternative sigma factor RpoN (σ
54
) is involved in the regulation of quorum sensing (QS) and plays an important role in the survival of stationary-phase cells in the presence of carbapenems. Here, we demonstrate that a Δ
rpoN
mutant grown in nutrient-rich medium has increased expression of
pqsA
,
pqsH
, and
pqsR
throughout growth, resulting in the increased production of the
Pseudomonas
quinolone signal (PQS). The link between
pqsA
and its role in carbapenem tolerance was studied using a Δ
rpoN
Δ
pqsA
mutant, in which the carbapenem-tolerant phenotype of the Δ
rpoN
mutant was abolished. In addition, we demonstrate that another mechanism leading to carbapenem tolerance in the Δ
rpoN
mutant is mediated through
pqsE
. Exogenously supplied PQS abolished the biapenem-sensitive phenotype of the Δ
rpoN
Δ
pqsA
mutant, and overexpression of
pqsE
failed to alter the susceptibility of the Δ
rpoN
Δ
pqsA
mutant to biapenem. The mutations in the Δ
rpoN
Δ
rhlR
mutant and the Δ
rpoN
Δ
pqsH
mutant led to susceptibility to biapenem. Comparison of the changes in the expression of the genes involved in QS in wild-type PAO1 with their expression in the Δ
rpoN
mutant and the Δ
rpoN
mutant-derived strains demonstrated the regulatory effect of RpoN on the transcript levels of
rhlR
,
vqsR
, and
rpoS
. The findings of this study demonstrate that RpoN negatively regulates the expression of PQS in nutrient-rich medium and provide evidence that RpoN interacts with
pqsA
,
pqsE
,
pqsH
, and
rhlR
in response to antibiotic stress.
Penetration of Ceftaroline into the Epithelial Lining Fluid of Healthy Adult Subjects
Authors: Riccobene Todd A. , Pushkin Richard , Jandourek Alena , Knebel William , Khariton Tatiana
Published: July 2016

Ceftaroline, the active metabolite of the prodrug ceftaroline fosamil, is a cephalosporin with bactericidal activity against Gram-positive organisms, including methicillin-resistant
Staphylococcus aureus
(MRSA). This study aimed to (i) evaluate ceftaroline concentrations in human plasma and epithelial lining fluid (ELF) and (ii) develop a population pharmacokinetic (PK) model for plasma and ELF to be used in PK/pharmacodynamic (PD) target attainment simulations. Ceftaroline concentrations in ELF and plasma at steady state (day 4) were measured in healthy adult subjects for two dosages: 600 mg every 12 h (q12h) and 600 mg every 8 h (q8h). Both were well tolerated with no serious adverse events. The penetration of free ceftaroline into ELF, assuming 20% protein binding in plasma and no protein binding in ELF, was ≈23%. The population PK model utilized a two-compartment model for both ceftaroline fosamil and ceftaroline. Goodness-of-fit criteria revealed the model was consistent with observed data and no systematic bias remained. At 600 mg q12h and a MIC of 1 mg/liter, 98.1% of simulated patients would be expected to achieve a target free drug concentration above the MIC (
f
T>MIC) in plasma of 42%, and in ELF 81.7% would be expected to achieve a target
f
T>MIC of 17%; at 600 mg q8h, 100% were predicted to achieve an
f
T>MIC in plasma of 42% and 94.7% to achieve an
f
T>MIC of 17% in ELF. The literature and data suggest the 600 mg q12h dose is adequate for MICs of ≤1 mg/liter. There is a need for clinical data in patients with MRSA pneumonia and data to correlate PK/PD relationships in ELF with clinical outcomes.
Rifampin Resistance
rpoB
Alleles or Multicopy Thioredoxin/Thioredoxin Reductase Suppresses the Lethality of Disruption of the Global Stress Regulator
spx
in Staphylococcus aureus
Authors: Villanueva Maite , Jousselin Ambre , Baek Kristoffer T. , Prados Julien , Andrey Diego O. , Renzoni Adriana , Ingmer Hanne , Frees Dorte , Kelley William L.
Published: July 2016

Staphylococcus aureus
is capable of causing a remarkable spectrum of disease, ranging from mild skin eruptions to life-threatening infections. The survival and pathogenic potential of
S. aureus
depend partly on its ability to sense and respond to changes in its environment. Spx is a thiol/oxidative stress sensor that interacts with the C-terminal domain of the RNA polymerase RpoA subunit, leading to changes in gene expression that help sustain viability under various conditions. Using genetic and deep-sequencing methods, we show that
spx
is essential in
S. aureus
and that a previously reported Δ
spx
strain harbored suppressor mutations that allowed it to grow without
spx
. One of these mutations is a single missense mutation in
rpoB
(a P-to-L change at position 519 encoded by
rpoB
[
rpoB
-P519L]) that conferred high-level resistance to rifampin. This mutation alone was found to be sufficient to bypass the requirement for
spx
. The generation of rifampin resistance libraries led to the discovery of an additional
rpoB
mutation, R484H, which supported strains with the
spx
disruption. Other rifampin resistance mutations either failed to support the Δ
spx
mutant or were recovered at unexpectedly low frequencies in genetic transduction experiments. The amino acid residues encoded by
rpoB
-P519L and -R484H map in close spatial proximity and comprise a highly conserved region of RpoB. We also discovered that multicopy expression of either
trxA
(encoding thioredoxin) or
trxB
(encoding thioredoxin reductase) supports strains with the deletion of
spx
. Our results reveal intriguing properties, especially of RNA polymerase, that compensate for the loss of an essential gene that is a key mediator of diverse processes in
S. aureus
, including redox and thiol homeostasis, antibiotic resistance, growth, and metabolism.

IMPORTANCE
The survival and pathogenicity of
S. aureus
depend on complex genetic programs. An objective for combating this insidious organism entails dissecting genetic regulatory circuits and discovering promising new targets for therapeutic intervention. In this study, we discovered that Spx, an RNA polymerase-interacting stress regulator implicated in many stress responses in
S. aureus
, including responses to oxidative and cell wall antibiotics, is essential. We describe two mechanisms that suppress the lethality of
spx
disruption. One mechanism highlights how only certain rifampin resistance-encoding alleles of RpoB confer new properties on RNA polymerase, with important mechanistic implications. We describe additional stress conditions where the loss of
spx
is deleterious, thereby highlighting Spx as a multifaceted regulator and attractive drug discovery target.
Who comes back with what: a retrospective database study on reasons for emergency readmission to hospital in children and young people in England
Authors: Wijlaars Linda P M M , Hardelid Pia , Woodman Jenny , Allister Janice , Cheung Ronny , Gilbert Ruth
Published: July 2016

Objective

To determine the proportion of children and young people (CYP) in England who are readmitted for the same condition.

Design

Retrospective cohort study.

Setting

National administrative hospital data (Hospital Episode Statistics).

Participants

CYP (0-year-olds to 24-year-olds) discharged after an emergency admission to the National Health Service in England in 2009/2010.

Main outcome measures

Coded primary diagnosis classified in six broad groups indicating reason for admission (infection, chronic condition, injury, perinatal related or pregnancy related, sign or symptom or other). We grouped readmissions as ≤30 days or between 31 days and 2 years after the index discharge. We used multivariable logistic regression to determine factors at the index admission that were predictive of readmission within 30 days.

Results

9% of CYP were readmitted within 30 days. Half of the 30-day readmissions and 40% of the recurrent admissions between 30 days and 2 years had the same primary diagnosis group as the original admission. These proportions were consistent across age, sex and diagnostic groups, except for infants and young women with pregnancy-related problems (15–24 years) who were more likely to be readmitted for the same primary diagnostic group. CYP with underlying chronic conditions were readmitted within 30 days twice as often (OR: 1.93, 95% CI 1.89 to 1.99) compared with CYP without chronic conditions.

Conclusions

Financial penalties for readmission are expected to incentivise more effective care of the original problem, thereby avoiding readmission. Our findings, that half of children come back with different problems, do not support this presumption.
Idiopathic choroidal neovascularisation in pregnancy: treatment options and a successful outcome
Authors: De Silva Samantha Roshani , Bibi Farhat , Sim Kuan , Bindra Mandeep Singh
Published: July 2016

Choroidal neovascularisation (CNV) is a major cause of visual loss and treatment options aim to halt progression and stabilise vision. We describe a 29-year-old woman who presented with blurred vision and distortion in her left eye while 26 weeks pregnant. She was diagnosed with idiopathic CNV and multiple treatment options were discussed. The patient did not want to undertake any risks from having an anti vascular endothelial growth factor agent during pregnancy. Therefore on discussion with the obstetric team, she elected to have early delivery at 32 weeks followed by a course of intravitreal bevacizumab. Subsequently there was resolution of symptoms and intraretinal and subretinal fluid. CNV is uncommonly seen in pregnancy and there remains no consensus on treatment. We describe the third reported case of idiopathic CNV in pregnancy. Careful patient counselling and close liaison between the ophthalmology and obstetric teams are necessary in this condition to obtain a safe outcome while maximising vision.
Predictive value of cell-surface markers in infections in critically ill patients: protocol for an observational study (ImmuNe FailurE in Critical Therapy (INFECT) Study)
Authors: Conway Morris Andrew , Datta Deepankar , Shankar-Hari Manu , Weir Christopher J , Rennie Jillian , Antonelli Jean , Rossi Adriano G , Warner Noel , Keenan Jim , Wang Alice , Brown K Alun , Lewis Sion , Mare Tracey , Simpson A John , Hulme Gillian , Dimmick Ian , Walsh Timothy S
Published: July 2016

Introduction

Critically ill patients are at high risk of nosocomial infections, with between 20% and 40% of patients admitted to the intensive care unit (ICU) acquiring infections. These infections result in increased antibiotic use, and are associated with morbidity and mortality. Although critical illness is classically associated with hyperinflammation, the high rates of nosocomial infection argue for an importance of effect of impaired immunity. Our group recently demonstrated that a combination of 3 measures of immune cell function (namely neutrophil CD88, monocyte HLA-DR and % regulatory T cells) identified a patient population with a 2.4–5-fold greater risk for susceptibility to nosocomial infections.

Methods and analysis

This is a prospective, observational study to determine whether previously identified markers of susceptibility to nosocomial infection can be validated in a multicentre population, as well as testing several novel markers which may improve the risk of nosocomial infection prediction. Blood samples from critically ill patients (those admitted to the ICU for at least 48 hours and requiring mechanical ventilation alone or support of 2 or more organ systems) are taken and undergo whole blood staining for a range of immune cell surface markers. These samples undergo analysis on a standardised flow cytometry platform. Patients are followed up to determine whether they develop nosocomial infection. Infections need to meet strict prespecified criteria based on international guidelines; where these criteria are not met, an adjudication panel of experienced intensivists is asked to rule on the presence of infection. Secondary outcomes will be death from severe infection (sepsis) and change in organ failure.

Ethics and dissemination

Ethical approval including the involvement of adults lacking capacity has been obtained from respective English and Scottish Ethics Committees. Results will be disseminated through presentations at scientific meetings and publications in peer-reviewed journals.

Trial registration number

NCT02186522; Pre-results.
Consultations in general practices with and without mental health nurses: an observational study from 2010 to 2014
Authors: Magnée Tessa , de Beurs Derek P , de Bakker Dinny H , Verhaak Peter F
Published: July 2016

Objectives

To investigate care for patients with psychological or social problems provided by mental health nurses (MHNs), and by general practitioners (GPs) with and without MHNs.

Design

An observational study with consultations recorded by GPs and MHNs.

Setting

Data were routinely recorded in 161–338 Dutch general practices between 2010 and 2014.

Participants

All patients registered at participating general practices were included: 624 477 patients in 2010 to 1 392 187 patients in 2014.

Outcome measures

We used logistic and Poisson multilevel regression models to test whether GPs recorded more patients with at least one consultation for psychological or social problems and to analyse the number of consultations over a 5-year time period. We examined the additional effect of an MHN in a practice, and tested which patient characteristics predicted transferral from GPs to MHNs.

Results

Increasing numbers of patients with psychological or social problems visit general practices. Increasing numbers of GPs collaborate with an MHN. GPs working in practices with an MHN record as many consultations per patient as GPs without an MHN, but they record slightly more patients with psychological or social problems (OR=1.05; 95% CI 1.02 to 1.08). MHNs most often treat adult female patients with common psychological symptoms such as depressive feelings.

Conclusions

MHNs do not seem to replace GP care, but mainly provide additional long consultations. Future research should study to what extent collaboration with an MHN prevents patients from needing specialised mental healthcare.
Competing risk analysis of factors related to long-term incidence of CHD
Authors: MacKenzie Gilbert , Greig Mary , Hay Iris , Pemberton John
Published: July 2016

Background

The 5-year follow-up results for the 1202 middle-aged men prospective study of coronary heart disease (CHD) incidence were published in 1980. This paper extends the follow-up, relating the development of CHD to 10 risk factors.

Methods

The population studied comprised all men born in the 10-year period 1909–1918 aged 45–64 years at baseline who were registered in 6 group practices in Belfast. Some 1202 CHD-free men entered the study. Study end points included: (a) the development of CHD, (b) the development of myocardial infarction, (c) the development of angina pectoris, (d) death from myocardial infarction and (e) death from other causes. The men were followed for an average of 6.9 years, and the influence of 10 risk factors was assessed by Cox's proportional hazards model in a competing risk framework.

Results

The analysis of first major CHD event identified four risk factors—diastolic blood pressure, serum cholesterol, T wave abnormality and tobacco index. First myocardial infarction depended on diastolic blood pressure, ST abnormality and tobacco index, while time to first angina pectoris depended on serum cholesterol, T abnormality, tobacco index and age at entry. These findings do not support the hypothesis of a common risk factor profile in the myocardial infarction and angina pectoris groups. The sensitivity of all models was poor.

Discussion

The study confirms the role of known risk factors in the development of first CHD event. It also suggests that the risk factors involved in developing myocardial infarction and angina pectoris differ. The poor sensitivity of models suggests the presence of unmeasured risk factors in the aetiology of CHD.
Single model establishing strength of dispersive clay treated with distinct binders
Authors: Consoli Nilo Cesar , Samaniego Rubén Alejandro Quiñónez , Marques Sérgio Filipe Veloso , Venson Guilherme Irineu , Pasche Eduardo , Velásquez Luís Enrique González
Published: July 2016

Dispersive clays experience deflocculation in the presence of somewhat clean still water and are extremely vulnerable to erosion. Lime or Portland cement usage is one of the most applied methods to amend such adverse characteristics and enhance mechanical properties. Present research is aimed at a single power function quantifying the effect of amounts of binder, porosity, and curing period in the assessment of unconfined compressive strength (qu) of dispersive clay–binder mixtures. Analysing quresults, it was found that a ratio between porosity and binder volumetric content controls the strength of blends. The quvalues of the specimens moulded for each binder type were also normalized (i.e., divided by the quattained at a specific porosity/binder ratio) reaching a single power function quantifying the influence of the binder’s amount, porosity, and curing time. From a pragmatic standpoint, this denotes that carrying out only one unconfined compression test with a specimen moulded with a specific binder, porosity, and cured for a given time period allows to determine an equation that controls the strength for a whole range of porosities and binder contents. The developed normalization was successfully extended to other fine-grained soils treated with cement, lime, and even pozzolan–lime, considering longer curing periods.
Elevated atmospheric CO2 interacts with drought and competition to produce complex results in plant quality and subsequent microbial aquatic decomposition
Authors: Monroy Silvia , Miranda-Apodaca Jon , Pérez-López Usue , Mena-Petite Amaia , Elosegi Arturo , Muñoz-Rueda Alberto , Pozo Jesús
Published: July 2016

Human activities enhance the atmospheric CO2 concentration and modify climatic patterns, which could change the growth and quality of plant materials, as well as their subsequent decomposition, thus altering stream ecosystem functioning. These effects could be modulated by interactions between plant species differing in biological traits and competitive capacity. We cultivated the forb Trifolium pratense and the grass Agrostis capillaris under different CO2 concentration (ambient or elevated), water availability (control or drought), and competition (monoculture or mixture). The material thus grown was conditioned in a stream for microbial colonization, and its subsequent decomposition was measured in laboratory microcosms. Elevated CO2 reduced the quality of T. pratense but not that of A. capillaris. Water shortage limited plant quality but did not interact with CO2 concentration. Interspecific competition only affected nitrogen concentration in A. capillaris. Elevated CO2 did not affect decomposition rate, and A. capillaris, the species richer in nutrients, decomposed more slowly. Our results showed that the decomposition rates of plant materials grown under elevated CO2 are difficult to predict due to species-specific responses and interactions with other factors.
A global profile of glucose-sensitive endothelial-expressed long non-coding RNAs
Authors: Singh Krishna K. , Mantella Laura-Eve , Pan Yi , Quan Adrian , Sabongui Sandra , Sandhu Paul , Teoh Hwee , Al-Omran Mohammed , Verma Subodh
Published: July 2016

Hyperglycemia-related endothelial dysfunction is believed to be the crux of diabetes-associated micro- and macro-vascular complications. We conducted a systematic transcriptional survey to screen for human endothelial long non-coding RNAs (lncRNAs) regulated by elevated glucose levels. lncRNAs and protein-coding transcripts from human umbilical vein endothelial cells (HUVECs) cultured under high (25 mmol/L) or normal (5 mmol/L) glucose conditions for 24 h were profiled with the Arraystar Human LncRNA Expression Microarray V3.0. Of the 30 586 lncRNAs screened, 100 were significantly upregulated and 186 appreciably downregulated (P < 0.05) in response to high-glucose exposure. In the same HUVEC samples, 133 of the 26 109 mRNAs screened were upregulated and 166 downregulated. Of these 299 differentially expressed mRNAs, 26 were significantly associated with 28 differentially expressed long intergenic non-coding RNAs (P < 0.05). Bioinformatics analyses indicated that the mRNAs most upregulated are primarily enriched in axon guidance signaling pathways; those most downregulated are notably involved in pathways targeting vascular smooth muscle cell contraction, dopaminergic signaling, ubiquitin-mediated proteolysis, and adrenergic signaling. This is the first lncRNA and mRNA transcriptome profile of high-glucose-mediated changes in human endothelial cells. These observations may prove novel insights into novel regulatory molecules and pathways of hyperglycemia-related endothelial dysfunction and, accordingly, diabetes-associated vascular disease.
Effects of estradiol on measurements of conduit artery endothelial function after ischemia and reperfusion in premenopausal women
Authors: Luca Mary Clare , Liuni Andrew , Harvey Paula , Mak Susanna , Parker John D.
Published: July 2016

In premenopausal women, ovarian steroids are felt to play a role in the prevention of cardiovascular disease. We aimed to assess whether menstrual cycle variations in estrogen can modify the response to ischemia–reperfusion (IR) injury in humans. In an investigator-blinded crossover study, 10 healthy premenopausal women with regular menstrual cycles were studied. They had flow-mediated dilatation (FMD) measured by ultrasound in the radial artery before and after IR (15 min of brachial artery ischemia, 15 min of reperfusion) during both the early and late follicular phases of the menstrual cycle. The order of these visits was not randomized. IR significantly blunted FMD in the early follicular phase (pre-IR: 7.1% ± 1.0%; post-IR: 3.6% ± 1.0%, P = 0.01) when estradiol levels were low (148.4 ± 19.8 pmol/L). Conversely, FMD was preserved after IR during the late follicular phase (pre-IR: 7.2% ± 0.9%; post-IR: 7.0% ± 0.8%, P = NS, P = 0.03 compared with early follicular) when estradiol levels were high (825.7 ± 85.8 pmol/L, P < 0.001 compared with early follicular). There was a significant inverse relationship between estradiol concentration and IR-induced endothelial dysfunction (i.e., change in FMD after IR) (r = 0.59, r2 = 0.36, P < 0.01). These findings demonstrate, for the first time in humans, a clear relationship between the cyclical changes in serum concentrations of estradiol and the endothelium’s response to IR.
Hyperoside ameliorates glomerulosclerosis in diabetic nephropathy by downregulating miR-21
Authors: Zhang Le , He Siyi , Yang Fan , Yu Hua , Xie Wei , Dai Qian , Zhang Di , Liu Xiaoqin , Zhou Shiwen , Zhang Kebin
Published: July 2016

The purpose of this study was to investigate the therapeutic effects of hyperoside (Hyp) on glomerulosclerosis in diabetic nephropathy and its underlying mechanisms. Blood glucose, kidney mass, and renal function of mice were measured. Renal morphology was observed using hematoxylin and eosin, periodic acid – Schiff’s, and Masson’s trichrome stain. Fibronectin (FN) and collagen IV (COL IV) in kidney were determined by Western blot and immunohistochemical studies. Matrix metalloproteinases (MMP)-2 and -9 and tissue inhibitors of metalloproteinase (TIMP)-1 in renal tissues were detected on both the mRNA and protein levels. miRNA expression and artificial alterations by miRNA agomir transfection were evaluated to investigate the protective mechanism of Hyp in mesangial cells. Hyp effectively improved renal function and physiologic features of db/db mice. Hyp also ameliorated glomerulosclerosis by suppressing FN, COL IV, and TIMP-1 expressions and promoting MMP-9 and MMP-2 expressions. The change in MMP-9 mRNA expression was inconsistent with that in protein levels in kidney, indicating that there was a post-transcriptional regulation. Further exploration in vitro showed that miR-21 was downregulated by Hyp, increasing expression of its target, MMP-9. These results suggest that Hyp can ameliorate glomerulosclerosis in diabetic nephropathy by downregulating miR-21 to increase expression of its target, MMP-9.
Deep COI sequencing of standardized benthic samples unveils overlooked diversity of Jordanian coral reefs in the northern Red Sea
Authors: Al-Rshaidat Mamoon M.D. , Snider Allison , Rosebraugh Sydney , Devine Amanda M. , Devine Thomas D. , Plaisance Laetitia , Knowlton Nancy , Leray Matthieu
Published: July 2016

High-throughput sequencing (HTS) of DNA barcodes (metabarcoding), particularly when combined with standardized sampling protocols, is one of the most promising approaches for censusing overlooked cryptic invertebrate communities. We present biodiversity estimates based on sequencing of the cytochrome c oxidase subunit 1 (COI) gene for coral reefs of the Gulf of Aqaba, a semi-enclosed system in the northern Red Sea. Samples were obtained from standardized sampling devices (Autonomous Reef Monitoring Structures (ARMS)) deployed for 18 months. DNA barcoding of non-sessile specimens >2 mm revealed 83 OTUs in six phyla, of which only 25% matched a reference sequence in public databases. Metabarcoding of the 2 mm – 500 μm and sessile bulk fractions revealed 1197 OTUs in 15 animal phyla, of which only 4.9% matched reference barcodes. These results highlight the scarcity of COI data for cryptobenthic organisms of the Red Sea. Compared with data obtained using similar methods, our results suggest that Gulf of Aqaba reefs are less diverse than two Pacific coral reefs but much more diverse than an Atlantic oyster reef at a similar latitude. The standardized approaches used here show promise for establishing baseline data on biodiversity, monitoring the impacts of environmental change, and quantifying patterns of diversity at regional and global scales.
Emodin Decreases Hepatic Hypoxia-Inducible Factor-1α by Inhibiting its Biosynthesis
Authors: Ma Feifei , Hu Lijuan , Yu Ming , Wang Feng
Published: July 2016

Hypoxia-inducible factor-1 (HIF-1) is an [Formula: see text] dimeric transcription factor. Because HIF-1[Formula: see text] is instable with oxygen, HIF-1 is scarce in normal mammalian cells. However, HIF-1[Formula: see text] is expressed in pathological conditions such as cancer and obesity. Inhibiting HIF-1[Formula: see text] may be of therapeutic value for these pathologies. Here, we investigated whether emodin, derived from the herb of Rheum palmatum L, which is also known as Chinese rhubarb, and is native to China, regulates HIF-1[Formula: see text] expression. Male C57BL/6 mice without or with diet-induced obesity were treated with emodin for two weeks, while control mice were treated with vehicle. HIF-1[Formula: see text] expression was determined by Western blot. We found that emodin inhibited obesity-induced HIF-1[Formula: see text] expression in liver and skeletal muscle but did not regulate HIF-1[Formula: see text] expression in the kidneys or in intra-abdominal fat. In vitro, emodin inhibited HIF-1[Formula: see text] expression in human HepG2 hepatic cells and Y1 adrenocortical cells. Further, we investigated the mechanisms of HIF-1[Formula: see text] expression in emodin-treated HepG2 cells. First, we found that HIF-1[Formula: see text] had normal stability in the presence of emodin. Thus, emodin did not decrease HIF-1[Formula: see text] by stimulating its degradation. Importantly, emodin decreased the activity of the signaling pathways that led to HIF-1[Formula: see text] biosynthesis. Interestingly, emodin increased HIF-1[Formula: see text] mRNA in HepG2 cells. This may be a result of feedback in response to the emodin-induced decrease in the protein of HIF-1[Formula: see text]. In conclusion, emodin decreases hepatic HIF-1[Formula: see text] by inhibiting its biosynthesis.
Modified Panax ginseng Extract Inhibits uPAR-Mediated α5β1-Integrin Signaling by Modulating Caveolin-1 to Induce Early Apoptosis in Lung Cancer Cells
Authors: Hwang In-Hu , Kwon Yong-Kyun , Cho Chong-Kwan , Lee Yeon-Weol , Sung Jung-Suk , Joo Jong-Cheon , Lee Kyung-Bok , Yoo Hwa-Seung , Jang Ik-Soon
Published: July 2016

Urokinase receptor (uPAR) is enhanced in many human cancer cells and is frequently an indicator of poor prognosis. Activation of [Formula: see text]1-integrin requires caveolin-1 and is regulated by uPAR. However, the underlying molecular mechanism responsible for the interaction between uPAR and [Formula: see text]1-integrin remains obscure. We found that modified regular Panax ginseng extract (MRGX) had a negative modulating effect on the uPAR/[Formula: see text]1-integrin interaction, disrupted the uPAR/integrin interaction by modulating caveoline-1, and caused early apoptosis in cancer cells. Additionally, we found that siRNA-mediated caveoline-1 downregulation inhibited uPAR-mediated [Formula: see text]1-integrin signaling, whereas caveoline-1 up-regulation stimulated the signaling, which suppressed p53 expression, thereby indicating negative crosstalk exists between the integrin [Formula: see text]1 and the p53 pathways. Thus, these findings identify a novel mechanism whereby the inhibition of [Formula: see text]1 integrin and the activation of p53 modulate the expression of the anti-apoptotic proteins that are crucially involved in inducing apoptosis in A549 lung cancer cells. Furthermore, MRGX causes changes in the expressions of members of the Bcl-2 family (Bax and Bcl-2) in a pro-apoptotic manner. In addition, MGRX-mediated inhibition of [Formula: see text]1 integrin attenuates ERK phosphorylation (p-ERK), which up-regulates caspase-8 and Bax. Therefore, ERK may affect mitochondria through a negative regulation of caspase-8 and Bax. Taken together, these findings reveal that MRGX is involved in uPAR-[Formula: see text]1-integrin signaling by modulating caveolin-1 signaling to induce early apoptosis in A549 lung-cancer cells and strongly indicate that MRGX might be useful as a herbal medicine and may lead to the development of new herbal medicine that would suppress the growth of lung-cancer cells.