bluuebunny/crossref_metadata_2025 huggingface dataset:
Experimental Study on the Effect of Diffuser Vane Setting Angle on Centrifugal Compressor Performance
Authors: Tamaki Hideaki
Published: November 2016

The effect of the diffuser vane setting angle on the performance of a centrifugal compressor was experimentally investigated. Seven different vaned diffusers were tested with the same impeller. In order to evaluate the vaned diffusers under the same flow range and diffuser inlet conditions, all the diffusers were designed to have the same throat area, the same diffuser height. and the same vane inlet position. The first tests were performed by a compressor with a volute. In this case, the diffuser outlet conditions were varied along the circumferential directions due to the nonaxisymmetric geometry of the volute. In the second tests, four of the seven vaned diffusers were tested using a compressor with a collector. In this case, the diffuser outlet conditions were more uniform along the circumferential directions compared to the tests using the compressor with the volute. The effect of the vane setting angle on the stage characteristics and diffuser performance as well as the effect of the circumferential distortion caused by the volute on the stage characteristics are presented. The impact of the incidence loss on the vaned diffuser performance is discussed using 1D vaned diffuser performance modeling. Comparisons of the 1D predictions and the tests results show the incidence loss has a strong influence on vaned diffuser performance.
Typhlodromus Scheuten (Acari: Phytoseiidae) from Shanxi province of China
Authors: Ma Min , Fan Qing-Hai , Li Sheng-Cai
Published: November 2016

The family Phytoseiidae is considered the most important beneficial mite family worldwide, but little is known about this family in Shanxi of China. To understand the phytoseiid fauna of this province, an extensive study was initiated in 2013. We present herein the description of a new species, Typhlodromus (Anthoseius) shanxi sp. nov., and the redescription of three new provincial records, Typhlodromus (Anthoseius) coryli Wu and Lan, 1991, Typhlodromus (Anthoseius) porus Wu, 1988, Typhlodromus (Anthoseius) ternatus Ehara, 1972, found on various plants in Shanxi. A key to the known species of Typhlodromus (Anthoseius) reported form Shanxi is also presented.
Activity cross‐calibration of unsealed radionuclides utilizing a portable ion chamber
Authors: Jans Hans‐Sonke
Published: November 2016

Purpose:

To present and evaluate an ion chamber‐based method for the cross‐calibration between sites of activity measurements of unsealed radionuclides. Notably, the method allows direct comparison of short lived (i.e., clinically used) radioisotopes and the cross‐calibration of radionuclide activity meters (also known as “dose calibrators”).

Methods:

A portable ion chamber has been designed which is easily shipped between sites, e.g., between a standards laboratory and a nuclear medicine department. The cylindrical chamber accommodates a syringe filled with unsealed radionuclide. Low background and staff shielding are achieved by designing the ion chamber small enough to fit into the well of a dose calibrator. The chamber's sensitivity for the clinically important unsealed radioisotopes 99mTc, 131I, and 18F was measured and compared to Monte Carlo calculations. The influence of syringe fill volume, positioning, and construction (wall diameter, length) was also investigated using Monte Carlo simulations. The chamber's linearity was measured over 5.5 orders of magnitude and its constancy tested over a period of >14.5 months. An overall uncertainty budget is presented.

Results:

Measured chamber sensitivity was 12.1 pA/100 MBq, 12.5 pA/100 MBq and 29.4 pA/100 MBq for 131I, 99mTc, and 18F, respectively. The uncertainty budget for the ion chamber alone yields an overall uncertainty of less than 1%, with the greatest contribution arising from constancy and linearity (0.5% each). Strategies to further reduce uncertainties are discussed.

Conclusions:

The investigation presented in this paper confirms the feasibility of the concept introduced here. To optimize its practical implementation, the concept would benefit from computerization for the purpose of data acquisition, evaluation, processing, and storage of measured values.
Technical Note: Magnetic field effects on Gafchromic‐film response in MR‐IGRT
Authors: Reynoso Francisco J. , Curcuru Austen , Green Olga , Mutic Sasa , Das Indra J. , Santanam Lakshmi
Published: November 2016

Purpose:

Magnetokinetic changes may affect crystal orientation and polymerization within the active layer of radiochromic film (RCF). This effect is investigated in a magnetic resonance image‐guided radiotherapy unit within the context of film dosimetry.

Methods:

Gafchromic EBT2 RCF was irradiated in a 30 × 30 × 30 cm3 solid water phantom using a Co‐60 MRI guided radiotherapy system (B = 0.35 T) under normal operating conditions, and under the exact conditions and setup without a magnetic field. Fifteen 20.3 × 25.4 cm2 EBT2 film sheets were placed at three different depths (d = 0.5, 5, and 10 cm) using five different treatment plans. The plans were computed using the MRIdian (ViewRay, Inc.) treatment planning system to deliver doses between 0 and 17.6 Gy. Films were analyzed before and after irradiation to obtain the net optical density (netOD) for each color channel separately. Scanning electron microscope (SEM) images were obtained to compare the active layer of selected samples.

Results:

The results indicated that the red channel netOD decreased between 0.013 and 0.123 (average of 0.060 ± 0.033) for doses above 2.8 Gy, with a linear increase in this effect for higher doses. Green channel netOD showed similar results with a decrease between 0.012 and 0.105 (average of 0.041 ± 0.027) for doses above 3.5 Gy. The blue channel showed the weakest effect with a netOD decrease between 0.013 and 0.029 (average of 0.020 ± 0.006) for doses above 8.0 Gy. SEM images show changes in crystal orientation within active layer in RCF exposed in a magnetic field.

Conclusions:

The presence of a magnetic field affects crystal orientation and polymerization during irradiation, where netOD decreased by an average of 8.7%, 8.0%, and 4.3% in the red, green, and blue channels, respectively. The under response was dependent on dose and differed by up to 15% at 17.6 Gy.
Acoustic modeling of a three-dimensional rectangular opened enclosure coupled with a semi-infinite exterior field at the baffled opening
Authors: Jin Guoyong , Shi Shuangxia , Liu Zhigang
Published: November 2016

A modeling method is proposed for the acoustic analysis of a three-dimensional (3D) rectangular opened enclosure coupled with a semi-infinite exterior field by a rectangular opening of arbitrary size, and with general wall impedance. In contrast to existing modeling methods that solve the differential equations, the energy principle in combination with a 3D modified Fourier cosine series is employed in the present method for the modeling of this system. Under this theoretical framework, the effect of an opening in the wall of a rectangular enclosure is taken into account via the work done by the sound pressure acting on the opening between the finite enclosure and exterior domain. The sound pressure inside the opened enclosure is expressed as the combination of a 3D trigonometric cosine series and one supplementary 2D expansion introduced to ensure uniform convergence of the solution over the entire solution domain including opening boundary. The acoustic responses of the opened enclosure are obtained based on the energy expressions for the enclosure system. The effectiveness and reliability of the current method are checked against the results obtained by the boundary element method and experimental results, and excellent agreement is achieved. The effects of sizes and positions of the opening and wall impedance on the acoustic behaviors of opened enclosure system are investigated.
Can weekly noise levels of urban road traffic, as predominant noise source, estimate annual ones?
Authors: Prieto Gajardo Carlos , Barrigón Morillas Juan Miguel , Rey Gozalo Guillermo , Vílchez-Gómez Rosendo
Published: November 2016

The effects of noise pollution on human quality of life and health were recognised by the World Health Organisation a long time ago. There is a crucial dilemma for the study of urban noise when one is looking for proven methodologies that can allow, on the one hand, an increase in the quality of predictions, and on the other hand, saving resources in the spatial and temporal sampling. The temporal structure of urban noise is studied in this work from a different point of view. This methodology, based on Fourier analysis, is applied to several measurements of urban noise, mainly from road traffic and one-week long, carried out in two cities located on different continents and with different sociological life styles (Cáceres, Spain and Talca, Chile). Its capacity to predict annual noise levels from weekly measurements is studied. The relation between this methodology and the categorisation method is also analysed.
The relationship between perceptual disturbances in dysarthric speech and automatic speech recognition performance
Authors: Tu Ming , Wisler Alan , Berisha Visar , Liss Julie M.
Published: November 2016

State-of-the-art automatic speech recognition (ASR) engines perform well on healthy speech; however recent studies show that their performance on dysarthric speech is highly variable. This is because of the acoustic variability associated with the different dysarthria subtypes. This paper aims to develop a better understanding of how perceptual disturbances in dysarthric speech relate to ASR performance. Accurate ratings of a representative set of 32 dysarthric speakers along different perceptual dimensions are obtained and the performance of a representative ASR algorithm on the same set of speakers is analyzed. This work explores the relationship between these ratings and ASR performance and reveals that ASR performance can be predicted from perceptual disturbances in dysarthric speech with articulatory precision contributing the most to the prediction followed by prosody.
In Vitro
Tolerance of Drug-Naive Staphylococcus aureus Strain FDA209P to Vancomycin
Authors: Singh Madhuri , Matsuo Miki , Sasaki Takashi , Morimoto Yuh , Hishinuma Tomomi , Hiramatsu Keiichi
Published: November 2016

The mechanisms underlying bacterial tolerance to antibiotics are unclear. A possible adaptation strategy was explored by exposure of drug-naive methicillin-susceptible
Staphylococcus aureus
strain FDA209P to vancomycin
in vitro
. Strains surviving vancomycin treatment (vancomycin survivor strains), which appeared after 96 h of exposure, were slow-growing derivatives of the parent strain. Although the vancomycin MICs for the survivor strains were within the susceptible range, the cytokilling effects of vancomycin at 20-fold the MIC were significantly lower for the survivor strains than for the parent strain. Whole-genome sequencing demonstrated that
ileS
, encoding isoleucyl-tRNA synthetase (IleRS), was mutated in two of the three vancomycin survivor strains. The IleRS Y723H mutation is located close to the isoleucyl-tRNA contact site and potentially affects the affinity of IleRS binding to isoleucyl-tRNA, thereby inhibiting protein synthesis and leading to vancomycin tolerance. Introduction of the mutation encoding IleRS Y723H into FDA209P by allelic replacement successfully transferred the vancomycin tolerance phenotype. We have identified mutation of
ileS
to be one of the bona fide genetic events leading to the acquisition of vancomycin tolerance in
S. aureus
, potentially acting via inhibition of the function of IleRS.
Safety, Tolerability, and Pharmacokinetics of Liposomal Amphotericin B in Immunocompromised Pediatric Patients
Authors: Seibel Nita L. , Shad Aziza T. , Bekersky Ihor , Groll Andreas H. , Gonzalez Corina , Wood Lauren V. , Jarosinski Paul , Buell Donald , Hope William W. , Walsh Thomas J.
Published: November 2016

The safety, tolerability, and pharmacokinetics of the liposomal formulation of amphotericin B (L-AMB) were evaluated in 40 immunocompromised children and adolescents. The protocol was an open-label, sequential-dose-escalation, multidose pharmacokinetic study with 10 to 13 patients in each of the four dosage cohorts. Each cohort received daily dosages of 2.5, 5.0, 7.5, or 10 mg of amphotericin B in the form of L-AMB per kg of body weight. Neutropenic patients between the ages of 1 and 17 years were enrolled to receive empirical antifungal therapy or treatment of documented invasive fungal infections. The pharmacokinetic parameters of L-AMB were measured as those of amphotericin B by high-performance liquid chromatography and calculated by noncompartmental methods. There were nine adverse-event-related discontinuations, four of which were related to infusions. Infusion-related side effects occurred for 63 (11%) of 565 infusions, with 5 patients experiencing acute infusion-related reactions (7.5- and 10-mg/kg dosage levels). Serum creatinine levels increased from 0.45 ± 0.04 mg/dl to 0.63 ± 0.06 mg/dl in the overall population (P= 0.003), with significant increases in dosage cohorts receiving 5.0 and 10 mg/kg/day. At the higher dosage level of 10 mg/kg, there was a trend toward greater hypokalemia and vomiting. The area under the concentration-time curve from 0 to 24 h (AUC0–24) values for L-AMB on day 1 increased from 54.7 ± 32.9 to 430 ± 566 μg · h/ml in patients receiving 2.5 and 10.0 mg/kg/day, respectively. These findings demonstrate that L-AMB can be administered to pediatric patients at dosages similar to those for adults and that azotemia may develop, especially in those receiving ≥5.0 mg/kg/day.
Long-Chain Fatty Acyl Coenzyme A Ligase FadD2 Mediates Intrinsic Pyrazinamide Resistance in Mycobacterium tuberculosis
Authors: Rosen Brandon C. , Dillon Nicholas A. , Peterson Nicholas D. , Minato Yusuke , Baughn Anthony D.
Published: November 2016

Pyrazinamide (PZA) is a first-line tuberculosis (TB) drug that has been in clinical use for 60 years yet still has an unresolved mechanism of action. Based upon the observation that the minimum concentration of PZA required to inhibit the growth of
Mycobacterium tuberculosis
is approximately 1,000-fold higher than that of other first-line drugs, we hypothesized that
M. tuberculosis
expresses factors that mediate intrinsic resistance to PZA. To identify genes associated with intrinsic PZA resistance, a library of transposon-mutagenized
Mycobacterium bovis
BCG strains was screened for strains showing hypersusceptibility to the active form of PZA, pyrazinoic acid (POA). Disruption of the long-chain fatty acyl coenzyme A (CoA) ligase FadD2 enhanced POA susceptibility by 16-fold on agar medium, and the wild-type level of susceptibility was restored upon expression of
fadD2
from an integrating mycobacterial vector. Consistent with the recent observation that POA perturbs mycobacterial CoA metabolism, the
fadD2
mutant strain was more vulnerable to POA-mediated CoA depletion than the wild-type strain. Ectopic expression of the
M. tuberculosis
pyrazinamidase PncA, necessary for conversion of PZA to POA, in the
fadD2
transposon insertion mutant conferred at least a 16-fold increase in PZA susceptibility under active growth conditions in liquid culture at neutral pH. Importantly, deletion of
fadD2
in
M. tuberculosis
strain H37Rv also resulted in enhanced susceptibility to POA. These results indicate that FadD2 is associated with intrinsic PZA and POA resistance and provide a proof of concept for the target-based potentiation of PZA activity in
M. tuberculosis
.
Prevalence of
mcr-1
in the Cecal Contents of Food Animals in the United States
Authors: Meinersmann Richard J. , Ladely Scott R. , Plumblee Jodie R. , Cook Kimberly L. , Thacker Eileen
Published: November 2016

A survey of 2,003 cecal content samples from chickens, turkeys, cattle, and swine at slaughter facilities in the United States was conducted to estimate the prevalence of the
mcr-1
gene conferring resistance to colistin in
Enterobacteriaceae
. Two cecal samples from swine had
Escherichia coli
with IncI2 plasmids bearing the
mcr-1
gene.
Modulation of Pertussis and Adenylate Cyclase Toxins by Sigma Factor RpoE in Bordetella pertussis
Authors: Barbier Mariette , Boehm Dylan T. , Sen-Kilic Emel , Bonnin Claire , Pinheiro Theo , Hoffman Casey , Gray Mary , Hewlett Erik , Damron F. Heath
Published: November 2016

Bordetella pertussis
is a human pathogen that can infect the respiratory tract and cause the disease known as whooping cough.
B. pertussis
uses pertussis toxin (PT) and adenylate cyclase toxin (ACT) to kill and modulate host cells to allow the pathogen to survive and persist.
B. pertussis
encodes many uncharacterized transcription factors, and very little is known about their functions. RpoE is a sigma factor which, in other bacteria, responds to oxidative, heat, and other environmental stresses. RseA is a negative regulator of RpoE that sequesters the sigma factor to regulate gene expression based on conditions. In
B. pertussis
, deletion of the
rseA
gene results in high transcriptional activity of RpoE and large amounts of secretion of ACT. By comparing parental
B. pertussis
to an
rseA
gene deletion mutant (PM18), we sought to characterize the roles of RpoE in virulence and determine the regulon of genes controlled by RpoE. Despite high expression of ACT, the
rseA
mutant strain did not infect the murine airway as efficiently as the parental strain and PM18 was killed more readily when inside phagocytes. RNA sequencing analysis was performed and 263 genes were differentially regulated by RpoE, and surprisingly, the
rseA
mutant strain where RpoE activity was elevated expressed very little pertussis toxin. Western blots and proteomic analysis corroborated the inverse relationship of PT to ACT expression in the high-RpoE-activity
rseA
deletion strain. Our data suggest that RpoE can modulate PT and ACT expression indirectly through unidentified mechanisms in response to conditions.
Calcium Enhances Bile Salt-Dependent Virulence Activation in Vibrio cholerae
Authors: Hay Amanda J. , Yang Menghua , Xia Xiaoyun , Liu Zhi , Hammons Justin , Fenical William , Zhu Jun
Published: November 2016

Vibrio cholerae
is the causative bacteria of the diarrheal disease cholera, but it also persists in aquatic environments, where it displays an expression profile that is distinct from that during infection. Upon entry into the host, a tightly regulated circuit coordinates the induction of two major virulence factors: cholera toxin and a toxin-coregulated pilus (TCP). It has been shown that a set of bile salts, including taurocholate, serve as host signals to activate
V. cholerae
virulence through inducing the activity of the transmembrane virulence regulator TcpP. In this study, we investigated the role of calcium, an abundant mental ion in the gut, in the regulation of virulence. We show that whereas Ca
2+
alone does not affect virulence, Ca
2+
enhances bile salt-dependent virulence activation for
V. cholerae
. The induction of TCP by murine intestinal contents is counteracted when Ca
2+
is depleted by the high-affinity calcium chelator EGTA, suggesting that the calcium present in the gut is a relevant signal for
V. cholerae
virulence induction
in vivo
. We further show that Ca
2+
enhances virulence by promoting bile salt-induced TcpP-TcpP interaction. Moreover, fluorescence recovery after photobleaching (FRAP) analysis demonstrated that exposure to bile salts and Ca
2+
together decreases the recovery rate for fluorescently labeled TcpP, but not for another inner membrane protein (TatA). Together, these data support a model in which physiological levels of Ca
2+
may result in altered bile salt-induced TcpP protein movement and activity, ultimately leading to an increased expression of virulence.
Contribution of Asparagine Catabolism to Salmonella Virulence
Authors: McLaughlin Patrick A. , McClelland Michael , Yang Hee-Jeong , Porwollik Steffen , Bogomolnaya Lydia , Chen Juei-Suei , Andrews-Polymenis Helene , van der Velden Adrianus W. M.
Published: November 2016

Salmonellae are pathogenic bacteria that cause significant morbidity and mortality in humans worldwide. Salmonellae establish infection and avoid clearance by the immune system by mechanisms that are not well understood. We previously showed that
l
-asparaginase II produced by
Salmonella enterica
serovar Typhimurium (
S
. Typhimurium) inhibits T cell responses and mediates virulence. In addition, we previously showed that asparagine deprivation such as that mediated by
l
-asparaginase II of
S
. Typhimurium causes suppression of activation-induced T cell metabolic reprogramming. Here, we report that
STM3997
, which encodes a homolog of disulfide bond protein A (
dsbA
) of
Escherichia coli
, is required for
l
-asparaginase II stability and function. Furthermore, we report that
l
-asparaginase II localizes primarily to the periplasm and acts together with
l
-asparaginase I to provide
S
. Typhimurium the ability to catabolize asparagine and assimilate nitrogen. Importantly, we determined that, in a murine model of infection,
S
. Typhimurium lacking both
l
-asparaginase I and II genes competes poorly with wild-type
S
. Typhimurium for colonization of target tissues. Collectively, these results indicate that asparagine catabolism contributes to
S
. Typhimurium virulence, providing new insights into the competition for nutrients at the host-pathogen interface.
Two Isoforms of Clp Peptidase in Pseudomonas aeruginosa Control Distinct Aspects of Cellular Physiology
Authors: Hall Branwen M. , Breidenstein Elena B. M. , de la Fuente-Núñez César , Reffuveille Fany , Mawla Gina D. , Hancock Robert E. W. , Baker Tania A.
Published: November 2016

Caseinolytic peptidases (ClpPs) regulate diverse aspects of cellular physiology in bacteria. Some species have multiple ClpPs, including the opportunistic pathogen
Pseudomonas aeruginosa
, in which there is an archetypical isoform, ClpP1, and a second isoform, ClpP2, about which little is known. Here, we use phenotypic assays to investigate the biological roles of ClpP1 and ClpP2 and biochemical assays to characterize purified ClpP1, ClpP2, ClpX, and ClpA. Interestingly, ClpP1 and ClpP2 have distinct intracellular roles for motility, pigment production, iron scavenging, and biofilm formation. Of particular interest, ClpP2, but not ClpP1, is required for microcolony organization, where multicellular organized structures first form on the pathway to biofilm production. We found that purified ClpP1 with ClpX or ClpA was enzymatically active, yet to our surprise, ClpP2 was inactive and not fully assembled
in vitro
; attempts to assist ClpP2 assembly and activation by mixing with the other Clp components failed to turn on ClpP2, as did solution conditions that have helped activate other ClpPs
in vitro
. We postulate that the active form of ClpP2 has yet to be discovered, and we present several potential models to explain its activation as well as the unique role ClpP2 plays in the development of the clinically important biofilms in
P. aeruginosa
.

IMPORTANCE
Pseudomonas aeruginosa
is responsible for severe infections of immunocompromised patients. Our work demonstrates that two different isoforms of the Clp peptidase, ClpP1 and ClpP2, control distinct aspects of cellular physiology for this organism. In particular, we identify ClpP2 as being necessary for microcolony organization. Pure active forms of ClpP1 and either ClpX or ClpA were characterized as assembled and active, and ClpP2 was incompletely assembled and inactive. By establishing both the unique biological roles of ClpP1 and ClpP2 and their initial biochemical assemblies, we have set the stage for important future work on the structure, function, and biological targets of Clp proteolytic enzymes in this important opportunistic pathogen.
Treating Primary Dysmenorrhoea with Acupuncture: A Narrative Review of the Relationship between Acupuncture ‘dose— and Menstrual Pain Outcomes
Authors: Armour Mike , Smith Caroline A
Published: November 2016

Objective

A number of randomised controlled trials have been performed to determine the effectiveness or efficacy of acupuncture in primary dysmenorrhoea. The objective of this review was to explore the relationship between the ‘dose’ of the acupuncture intervention and menstrual pain outcomes.

Methods

Eight databases were systematically searched for trials examining penetrating body acupuncture for primary dysmenorrhoea published in English up to September 2015. Dose components for each trial were extracted, assessed by the two authors and categorised by neurophysiological dose (number of needles, retention time and mode of stimulation), cumulative dose (total number and frequency of treatments), needle location and treatment timing.

Results

Eleven trials were included. Components of acupuncture dose were well reported across all trials. The relationship between needle location and menstrual pain demonstrated conflicting results. Treatment before the menses appeared to produce greater reductions in pain than treatment starting at the onset of menses. A single needle during menses may provide greater pain reduction compared to multiple needles. Conversely, multiple needles before menses were superior to a single needle. Electroacupuncture may provide more rapid pain reduction compared to manual acupuncture but may not have a significantly different effect on overall menstrual pain.

Conclusions

There appear to be relationships between treatment timing and mode of needle stimulation, and menstrual pain outcomes. Needle location, number of needles used and frequency of treatment show clear dose-response relationships with menstrual pain outcomes. Current research is insufficient to make definitive clinical recommendations regarding optimum dose parameters for treating primary dysmenorrhoea.
Pain, activities of daily living and sport function at different time points after hip arthroscopy in patients with femoroacetabular impingement: a systematic review with meta-analysis
Authors: Kierkegaard Signe , Langeskov-Christensen Martin , Lund Bent , Naal Florian D , Mechlenburg Inger , Dalgas Ulrik , Casartelli Nicola C
Published: November 2016

Aim

To investigate pain, activities of daily living (ADL) function, sport function, quality of life and satisfaction at different time points after hip arthroscopy in patients with femoroacetabular impingement (FAI).

Design

Systematic review with meta-analysis. Weighted mean differences between preoperative and postoperative outcomes were calculated and used for meta-analysis.

Data sources

EMBASE, MEDLINE, SportsDiscus, CINAHL, Cochrane Library, and PEDro.

Eligibility criteria for selecting studies

Studies that evaluated hip pain, ADL function, sport function and quality of life before and after hip arthroscopy and postoperative satisfaction in patients with symptomatic FAI.

Results

Twenty-six studies (22 case series, 3 cohort studies, 1 randomised controlled trial (RCT)) were included in the systematic review and 19 in the meta-analysis. Clinically relevant pain and ADL function improvements were first reported between 3 and 6 months, and sport function improvements between 6 months and 1 year after surgery. It is not clear when quality of life improvements were first achieved. On average, residual mild pain and ADL and sport function scores lower than their healthy counterparts were reported by patients following surgery. Postoperative patient satisfaction ranged from 68% to 100%.

Conclusions

On average, patients reported earlier pain and ADL function improvements, and slower sport function improvements after hip arthroscopy for FAI. However, average scores from patients indicate residual mild hip pain and/or hip function lower than their healthy counterparts after surgery. Owing to the current low level of evidence, future RCTs and cohort studies should investigate the effectiveness of hip arthroscopy in patients with FAI.

Trial registration number

CRD42015019649.
Perspectives of host faculty and trainees on international visiting faculty to paediatric academic departments in East Africa
Authors: Russ Christiana M , Ganapathi Lakshmi , Marangu Diana , Silverman Melanie , Kija Edward , Bakeera-Kitaka Sabrina , Laving Ahmed
Published: November 2016

Background

Investments in faculty exchanges to build physician workforce capacity are increasing. Little attention has been paid to the expectations of host institution faculty and trainees. This prospective qualitative research study explored faculty and resident perspectives about guest faculty in paediatric departments in East Africa, asking (1) What are the benefits and challenges of hosting guest faculty, (2) What factors influence the effectiveness of faculty visits and (3) How do host institutions prepare for faculty visits?

Methods

We recruited 36 faculty members and residents from among four paediatric departments in East Africa to participate in semistructured interviews which were audio recorded and transcribed. Data were qualitatively analysed using principles of open coding and thematic analysis. We achieved saturation of themes.

Results

Benefits of faculty visits varied based on the size and needs of host institutions. Emergent themes included the importance of guest faculty time commitment, and mutual preparation to ensure that visit goals and scheduling met host needs. We documented conflicts that developed around guest emotional responses and ethical approaches to clinical resource limitations, which some hosts tried to prepare for and mitigate. Imbalance in resources led to power differentials; some hosts sought partnerships to re-establish control over the process of having guests.

Conclusions

We identified that guest faculty can assist paediatric institutions in building capacity; however, effective visits require: (1) mutually agreed on goals with appropriate scheduling, visit length and commitment to ensure that the visits meet the host's needs, (2) careful selection and preparation of guest faculty to meet the host's goals, (3) emotional preparation by prospective guests along with host orientation to clinical work in the host's setting and (4) attention to funding sources for the visit and mitigation of resulting power differentials.
External validation of the Probability of repeated admission (Pra) risk prediction tool in older community-dwelling people attending general practice: a prospective cohort study
Authors: Wallace Emma , McDowell Ronald , Bennett Kathleen , Fahey Tom , Smith Susan M
Published: November 2016

Objectives

Emergency admission is associated with the potential for adverse events in older people and risk prediction models are available to identify those at highest risk of admission. The aim of this study was to externally validate and compare the performance of the Probability of repeated admission (Pra) risk model and a modified version (incorporating a multimorbidity measure) in predicting emergency admission in older community-dwelling people.

Setting

15 general practices (GPs) in the Republic of Ireland.

Participants

n=862, ≥70 years, community-dwelling people prospectively followed up for 2 years (2010–2012). Exposure: Pra risk model (original and modified) calculated for baseline year where ≥0.5 denoted high risk (patient questionnaire, GP medical record review) of future emergency admission.

Primary outcome

Emergency admission over 1 year (GP medical record review). Statistical analysis: descriptive statistics, model discrimination (c-statistic) and calibration (Hosmer-Lemeshow statistic).

Results

Of 862 patients, a total of 154 (18%) had ≥1 emergency admission(s) in the follow-up year. 63 patients (7%) were classified as high risk by the original Pra and of these 26 (41%) were admitted. The modified Pra classified 391 (45%) patients as high risk and 103 (26%) were subsequently admitted. Both models demonstrated only poor discrimination (original Pra: c-statistic 0.65 (95% CI 0.61 to 0.70); modified Pra: c-statistic 0.67 (95% CI 0.62 to 0.72)). When categorised according to risk-category model, specificity was highest for the original Pra at cut-point of ≥0.5 denoting high risk (95%), and for the modified Pra at cut-point of ≥0.7 (95%). Both models overestimated the number of admissions across all risk strata.

Conclusions

While the original Pra model demonstrated poor discrimination, model specificity was high and a small number of patients identified as high risk. Future validation studies should examine higher cut-points denoting high risk for the modified Pra, which has practical advantages in terms of application in GP. The original Pra tool may have a role in identifying higher-risk community-dwelling older people for inclusion in future trials aiming to reduce emergency admissions.
Narrowing mortality gap between men and women over two decades: a registry-based study in Ontario, Canada
Authors: Rosella Laura C , Calzavara Andrew , Frank John W , Fitzpatrick Tiffany , Donnelly Peter D , Henry David
Published: November 2016

Background

Historically, women have lower all-cause mortality than men. It is less understood that sex differences have been converging, particularly among certain subgroups and causes. This has implications for public health and health system planning. Our objective was to analyse contemporary sex differences over a 20-year period.

Methods

We analysed data from a population-based death registry, the Ontario Registrar's General Death file, which includes all deaths recorded in Canada's most populous province, from 1992 to 2012 (N=1 710 080 deaths). We calculated absolute and relative mortality sex differences for all-cause and cause-specific mortality, age-adjusted and age-specific, including the following causes: circulatory, cancers, respiratory and injuries. We used negative-binomial regression of mortality on socioeconomic status with direct age adjustment for the overall population.

Results

In the 20-year period, age-adjusted mortality dropped 39.2% and 29.8%, respectively, among men and women. The age-adjusted male-to-female mortality ratio dropped 41.4%, falling from 1.47 to 1.28. From 2000 onwards, all-cause mortality rates of high-income men were lower than those seen among low-income women. Relative mortality declines were greater among men than women for cancer, respiratory and injury-related deaths. The absolute decline in circulatory deaths was greater among men, although relative deciles were similar to women. The largest absolute mortality gains were seen among men over the age of 85 years.

Conclusions

The large decline in mortality sex ratios in a Canadian province with universal healthcare over two decades signals an important population shift. These narrowing trends varied according to cause of death and age. In addition, persistent social inequalities in mortality exist and differentially affect men and women. The observed change in sex ratios has implications for healthcare and social systems.
Atmospheric fine particulate matter and breast cancer mortality: a population-based cohort study
Authors: Tagliabue Giovanna , Borgini Alessandro , Tittarelli Andrea , van Donkelaar Aaron , Martin Randall V , Bertoldi Martina , Fabiano Sabrina , Maghini Anna , Codazzi Tiziana , Scaburri Alessandra , Favia Imma , Cau Alessandro , Barigelletti Giulio , Tessandori Roberto , Contiero Paolo
Published: November 2016

Objectives

Atmospheric fine particulate matter (PM2.5) has multiple adverse effects on human health. Global atmospheric levels of PM2.5increased by 0.55 μg/m3/year (2.1%/year) from 1998 through 2012. There is evidence of a causal relationship between atmospheric PM2.5and breast cancer (BC) incidence, but few studies have investigated BC mortality and atmospheric PM2.5. We investigated BC mortality in relation to atmospheric PM2.5levels among patients living in Varese Province, northern Italy.

Methods

We selected female BC cases, archived in the local population-based cancer registry, diagnosed at age 50–69 years, between 2003 and 2009. The geographic coordinates of each woman's place of residence were identified, and individual PM2.5exposures were assessed from satellite data. Grade, stage, age at diagnosis, period of diagnosis and participation in BC screening were potential confounders. Kaplan-Meir and Nelson-Aalen methods were used to test for mortality differences in relation to PM2.5quartiles. Multivariable Cox proportional hazards modelling estimated HRs and 95% CIs of BC death in relation to PM2.5exposure.

Results

Of 2021 BC cases, 325 died during follow-up to 31 December 2013, 246 for BC. Risk of BC death was significantly higher for all three upper quartiles of PM2.5exposure compared to the lowest, with HRs of death: 1.82 (95% CI 1.15 to 2.89), 1.73 (95% CI 1.12 to 2.67) and 1.72 (95% CI 1.08 to 2.75).

Conclusions

Our study indicates that the risk of BC mortality increases with PM2.5exposure. Although additional research is required to confirm these findings, they are further evidence that PM2.5exposure is harmful and indicate an urgent need to improve global air quality.
Incentives and disincentives for treating of depression and anxiety in Ontario Family Health Teams: protocol for a grounded theory study
Authors: Ashcroft Rachelle , Menear Matthew , Silveira Jose , Dahrouge Simone , McKenzie Kwame
Published: November 2016

Introduction

There is strong consensus that prevention and management of common mental disorders (CMDs) should occur in primary care and evidence suggests that treatment of CMDs in these settings can be effective. New interprofessional team-based models of primary care have emerged that are intended to address problems of quality and access to mental health services, yet many people continue to struggle to access care for CMDs in these settings. Insufficient attention directed towards the incentives and disincentives that influence care for CMDs in primary care, and especially in interprofessional team-based settings, may have resulted in missed opportunities to improve care quality and control healthcare costs. Our research is driven by the hypothesis that a stronger understanding of the full range of incentives and disincentives at play and their relationships with performance and other contextual factors will help stakeholders identify the critical levers of change needed to enhance prevention and management of CMDs in interprofessional primary care contexts. Participant recruitment began in May 2016.

Methods and analysis

An explanatory qualitative design, based on a constructivist grounded theory methodology, will be used. Our study will be conducted in the Canadian province of Ontario, a province that features a widely implemented interprofessional team-based model of primary care. Semistructured interviews will be conducted with a diverse range of healthcare professionals and stakeholders that can help us understand how various incentives and disincentives influence the provision of evidence-based collaborative care for CMDs. A final sample size of 100 is anticipated. The protocol was peer reviewed by experts who were nominated by the funding organisation.

Ethics and dissemination

The model we generate will shed light on the incentives and disincentives that are and should be in place to support high-quality CMD care and help stimulate more targeted, coordinated stakeholder responses to improving primary mental healthcare quality.
Implementing mobile devices to reduce non-rostered workload for junior doctors
Authors: Plant Allan , Round Suzanne , Bourne Joe
Published: November 2016

There is a large body of evidence demonstrating the detrimental effect of long work hours on the performance, mood, and job satisfaction of junior doctors. By extension these effects carry over into the realm of patient safety, compromising the quality of care provision.

House officers in the general surgery department of Tauranga Hospital, New Zealand are often required to arrive at work well before their rostered start time of 7.30am to hand write the results of clinical investigations on their patient lists. Baseline measurement demonstrated that each house officer was spending an average of 28 minutes a day of non-rostered time completing this task, increasing to 33 minutes on post-acute days. This quality improvement project trialed the use of a mobile device for accessing clinical results in real-time on surgical ward rounds with the ultimate aim of reducing non-rostered workload by one hour per house officer, per week.

A sustainable reduction to a median of 15 minutes non-rostered work per day for each house officer was achieved, translating into 75 minutes less non-rostered work for each house officer every week. Importantly, this result was sustained for more than seven working weeks and spanned a changeover in house officer rotation. Furthermore, the use of the devices was associated with a perceived improvement in the accuracy and timeliness of access to clinical results with no perceived detriment to the speed or flow of the ward round.
Identification of a fluorescent small-molecule enhancer for therapeutic autophagy in colorectal cancer by targeting mitochondrial protein translocase TIM44
Authors: Huang Yinghui , Zhou Jie , Luo Shenglin , Wang Yang , He Jintao , Luo Peng , Chen Zelin , Liu Tao , Tan Xu , Ou Juanjuan , Miao Hongming , Liang Houjie , Shi Chunmeng
Published: November 2016

Objective

As the modulation of autophagic processes can be therapeutically beneficial to cancer treatment, the identification of novel autophagic enhancers is highly anticipated. However, current autophagy-inducing anticancer agents exert undesired side effects owing to their non-specific biodistribution in off-target tissues. This study aims to develop a multifunctional agent to integrate cancer targeting, imaging and therapy and to investigate its mechanism.

Design

A series of mitochondria-targeting near-infrared (NIR) fluorophores were synthesised, screened and identified for their autophagy-enhancing activity. The optical properties and biological effects were tested both in vitro and in vivo. The underlying mechanism was investigated using inhibitors, small interfering RNA (siRNA), RNA sequencing, mass spectrometry and human samples.

Results

We have screened and identified a new NIR autophagy-enhancer, IR-58, which exhibits significant tumour-selective killing effects. IR-58 preferentially accumulates in the mitochondria of colorectal cancer (CRC) cells and xenografts, a process that is glycolysis-dependent and organic anion transporter polypeptide-dependent. IR-58 kills tumour cells and induces apoptosis via inducing excessive autophagy, which is mediated through the reactive oxygen species (ROS)-Akt-mammalian target of rapamycin (mTOR) pathway. RNA sequencing, mass spectrometry and siRNA interference studies demonstrate that translocase of inner mitochondrial membrane 44 (TIM44)-superoxide dismutase 2 (SOD2) pathway inhibition is responsible for the excessive ROS, autophagy and apoptosis induced by IR-58. TIM44 expression correlates positively with CRC development and poor prognosis in patients.

Conclusions

A novel NIR small-molecule autophagy-enhancer, IR-58, with mitochondria-targeted imaging and therapy capabilities was developed for CRC treatment. Additionally, TIM44 was identified for the first time as a potential oncogene, which plays an important role in autophagy through the TIM44-SOD2-ROS-mTOR pathway.
Palbociclib (PD-0332991), a selective CDK4/6 inhibitor, restricts tumour growth in preclinical models of hepatocellular carcinoma
Authors: Bollard Julien , Miguela Verónica , Ruiz de Galarreta Marina , Venkatesh Anu , Bian C Billie , Roberto Mark P , Tovar Victoria , Sia Daniela , Molina-Sánchez Pedro , Nguyen Christie B , Nakagawa Shigeki , Llovet Josep M , Hoshida Yujin , Lujambio Amaia
Published: November 2016

Objective

Advanced hepatocellular carcinoma (HCC) is a lethal malignancy with limited treatment options. Palbociclib, a well-tolerated and selective CDK4/6 inhibitor, has shown promising results in the treatment of retinoblastoma (RB1)-positive breast cancer. RB1 is rarely mutated in HCC, suggesting that palbociclib could potentially be used for HCC therapy. Here, we provide a comprehensive characterisation of the efficacy of palbociclib in multiple preclinical models of HCC.

Design

The effects of palbociclib on cell proliferation, cellular senescence and cell death were investigated in a panel of human liver cancer cell lines, in ex vivo human HCC samples, in a genetically engineered mouse model of liver cancer, and in human HCC xenografts in vivo. The mechanisms of intrinsic and acquired resistance to palbociclib were assessed in human liver cancer cell lines and human HCC samples by protein and gene expression analyses.

Results

Palbociclib suppressed cell proliferation in human liver cancer cell lines by promoting a reversible cell cycle arrest. Intrinsic and acquired resistance to palbociclib was determined by loss of RB1. A signature of ‘RB1 loss of function’ was found in <30% of HCC samples. Palbociclib, alone or combined with sorafenib, the standard of care for HCC, impaired tumour growth in vivo and significantly increased survival.

Conclusions

Palbociclib shows encouraging results in preclinical models of HCC and represents a novel therapeutic strategy for HCC treatment, alone or particularly in combination with sorafenib. Palbociclib could potentially benefit patients with RB1-proficient tumours, which account for 70% of all patients with HCC.
CR1 exon variants are associated with lowered CR1 expression and increased susceptibility to SLE in aPlasmodium falciparumendemic population
Authors: Panda Aditya K , Ravindran Balachandran , Das Bidyut K
Published: November 2016

Background

Complement receptor 1 (CR1) plays an important role in immune complex clearance by opsonisation and possibly protects subjects from development of autoantibodies. Lower CR1 expression has been associated with susceptibility to systemic lupus erythematosus (SLE). In contrast, subjects displaying lower CR1 expression are protected against severe manifestations of falciparum malaria. This study is the first of its kind to investigate the association of CR1 variants with development of SLE in aP. falciparumendemic population from Odisha, India.

Methods

CR1 polymorphisms (intron 27 (A>T), exon 22 (A>G) and exon 33 (G>C)) were typed by PCR and restriction length polymorphism in 297 cases of female patients with SLE and 300 age-matched and sex-matched healthy controls from malaria endemic areas in Odisha, India. CR1 expression on monocytes was quantified by flow cytometry.

Results

The homozygous mutants of CR1 exon 22 (GG) and exon 33 (GG) and their minor alleles were associated with susceptibility to SLE. Furthermore, patients with SLE who harboured the GG genotype of the exon 33 polymorphism had a 3.12-fold higher chance of developing lupus nephritis. CR1 exon (22 and 33) variants were associated with lowered CR1 expression on monocytes in patients with SLE and in healthy controls. Patients with lupus nephritis showed significantly diminished CR1 expression than those without renal involvement (p=0.01).

Conclusions

The results of the present study demonstrate that common CR1 exon variants are associated with diminished CR1 expression on monocytes and increased susceptibility to development of SLE and lupus nephritis in a malaria endemic area.