bluuebunny/crossref_metadata_2025 huggingface dataset:
Weld Strength Mismatch in Strain Based Flaw Assessment: Which Definition to Use?
Authors: Hertelé Stijn , De Waele Wim , Denys Rudi , Verstraete Matthias , Van Minnebruggen Koen , Horn Anthony
Published: September 2013

Weld strength mismatch is a key factor in the strain based assessment of flawed girth welds under tension. A strength overmatching weld shields potential flaws within the weld itself from remotely applied deformations and consequently reduces crack driving force. Although this effect has been recognized for decades, different weld strength overmatch definitions exist, and it is not yet fully established which of those is most relevant to a strain based flaw assessment. In an effort to clarify this unsolved question, the authors have performed a large series of parametric finite element analyses of curved wide plate tests. This paper provides an experimental validation of the model and subsequently discusses representative results. It is found that crack driving force is influenced by the shape of the pipe metals' stress–strain curves, which influences the representativeness of two common mismatch definitions (based on yield strength and on ultimate tensile strength). Effects of strength mismatch on strain capacity of a flawed girth weld are best described on the basis of a flow stress, defined as the average of yield and ultimate tensile strength. Based on the observations, a framework for a new strain capacity equation is proposed.
Distances, Luminosities, and Temperatures of the Coldest Known Substellar Objects
Authors: Dupuy Trent J. , Kraus Adam L.
Published: September 2013

Assessing Brown Dwarfs

The last 2 years have seen the detection of dozens of very cold brown dwarfs. At temperatures around 300 to 500 kelvin, brown dwarfs are expected to have masses comparable to those of gas-giant planets, but because their distances are unknown, it has not been possible to estimate their masses.
Dupuy and Kraus
(p.
1492
, published online 5 September) used data from the Spitzer Space Telescope to measure accurate distances to very cold brown dwarfs, which allowed them to determine the dwarfs' luminosities, temperatures, and masses. The results strengthen the connection between the coolest brown dwarfs and gas-giant exoplanets.
Structures and Receptor Binding of Hemagglutinins from Human-Infecting H7N9 Influenza Viruses
Authors: Shi Yi , Zhang Wei , Wang Fei , Qi Jianxun , Wu Ying , Song Hao , Gao Feng , Bi Yuhai , Zhang Yanfang , Fan Zheng , Qin Chengfeng , Sun Honglei , Liu Jinhua , Haywood Joel , Liu Wenjun , Gong Weimin , Wang Dayan , Shu Yuelong , Wang Yu , Yan Jinghua , Gao George F.
Published: September 2013

Two Viruses to Bind

Structural studies of two different H7N9 influenza viruses isolated from humans—A/Shanghai/1/2013 and A/Anhui/1/2013—which have different amino acid sequences in the receptor binding site, provide data indicating that the virus is in transition with respect to host adaptation. The Shanghai virus was one of the first isolated in humans that binds avian receptor glycans with high affinity, but binds poorly to human receptors. However, the later Anhui isolates can bind both avian and human receptors at high affinity.

Shi
et al.

(p.
243
, published online 5 September) show that four hydrophobic mutations contribute to acquisition of affinity for the human receptor by the virus hemagglutinin (HA) and confirm this effect in binding studies with virus particles. Further comparison of a mutant H7N9 A/Anhui/1/2013 HA with the bird flu H5N1 virus revealed the significance of some of the naturally occurring changes observed in circulating H7N9 viruses, which helps to explain how these viruses have been able to cause many severe human infections in a short time.
Insights into the Mode of Action of Benzyl Isothiocyanate on Campylobacter jejuni
Authors: Dufour Virginie , Stahl Martin , Rosenfeld Eric , Stintzi Alain , Baysse Christine
Published: September 2013

Campylobacter jejuni
is a widespread pathogen responsible for most of the food-borne gastrointestinal diseases in Europe. The use of natural antimicrobial molecules is a promising alternative to antibiotic treatments for pathogen control in the food industry. Isothiocyanates are natural antimicrobial compounds, which also display anticancer activity. Several studies described the chemoprotective effect of isothiocyanates on eukaryotic cells, but the antimicrobial mechanism is still poorly understood. We investigated the early cellular response of
C. jejuni
to benzyl isothiocyanate by both transcriptomic and physiological approaches. The transcriptomic response of
C. jejuni
to benzyl isothiocyanate showed upregulation of heat shock response genes and an impact on energy metabolism. Oxygen consumption was progressively impaired by benzyl isothiocyanate treatment, as revealed by high-resolution respirometry, while the ATP content increased soon after benzyl isothiocyanate exposition, which suggests a shift in the energy metabolism balance. Finally, benzyl isothiocyanate induced intracellular protein aggregation. These results indicate that benzyl isothiocyanate affects
C. jejuni
by targeting proteins, resulting in the disruption of major metabolic processes and eventually leading to cell death.
Resistance to Quorum-Quenching Compounds
Authors: García-Contreras Rodolfo , Maeda Toshinari , Wood Thomas K.
Published: September 2013

Bacteria have the remarkable ability to communicate as a group in what has become known as quorum sensing (QS), and this trait has been associated with important bacterial phenotypes, such as virulence and biofilm formation. Bacteria also have an incredible ability to evolve resistance to all known antimicrobials. Hence, although inhibition of QS has been hailed as a means to reduce virulence in a manner that is impervious to bacterial resistance mechanisms, this approach is unlikely to be a panacea. Here we review the evidence that bacteria can evolve resistance to quorum-quenching compounds.
Tomato Fruit and Seed Colonization by Clavibacter michiganensis subsp. michiganensis through External and Internal Routes
Authors: Tancos Matthew A. , Chalupowicz Laura , Barash Isaac , Manulis-Sasson Shulamit , Smart Christine D.
Published: September 2013

The Gram-positive bacterium
Clavibacter michiganensis
subsp.
michiganensis
, causal agent of bacterial wilt and canker of tomato, is an economically devastating pathogen that inflicts considerable damage throughout all major tomato-producing regions. Annual outbreaks continue to occur in New York, where
C. michiganensis
subsp.
michiganensis
spreads via infected transplants, trellising stakes, tools, and/or soil. Globally, new outbreaks can be accompanied by the introduction of contaminated seed stock; however, the route of seed infection, especially the role of fruit lesions, remains undefined. In order to investigate the modes of seed infection, New York
C. michiganensis
subsp.
michiganensis
field strains were stably transformed with a gene encoding enhanced green fluorescent protein (eGFP). A constitutively eGFP-expressing virulent
C. michiganensis
subsp.
michiganensis
isolate, GCMM-22, was used to demonstrate that
C. michiganensis
subsp.
michiganensis
could not only access seeds systemically through the xylem but also externally through tomato fruit lesions, which harbored high intra- and intercellular populations. Active movement and expansion of bacteria into the fruit mesocarp and nearby xylem vessels followed, once the fruits began to ripen. These results highlight the ability of
C. michiganensis
subsp.
michiganensis
to invade tomato fruits and seeds through multiple entry routes.
Efficient Production of Bacillus thuringiensis Cry1AMod Toxins under Regulation of
cry3Aa
Promoter and Single Cysteine Mutations in the Protoxin Region
Authors: García-Gómez Blanca I. , Sánchez Jorge , Martínez de Castro Diana L. , Ibarra Jorge E. , Bravo Alejandra , Soberón Mario
Published: September 2013

Bacillus thuringiensis
Cry1AbMod toxins are engineered versions of Cry1Ab that lack the amino-terminal end, including domain I helix α-1 and part of helix α-2. This deletion improves oligomerization of these toxins in solution in the absence of cadherin receptor and counters resistance to Cry1A toxins in different lepidopteran insects, suggesting that oligomerization plays a major role in their toxicity. However, Cry1AbMod toxins are toxic to
Escherichia coli
cells, since the
cry1A
promoter that drives its expression in
B. thuringiensis
has readthrough expression activity in
E. coli
, making difficult the construction of these CryMod toxins. In this work, we show that Cry1AbMod and Cry1AcMod toxins can be cloned efficiently under regulation of the
cry3A
promoter region to drive its expression in
B. thuringiensis
without expression in
E. coli
cells. However, p3A-Cry1Ab(c)Mod construction promotes the formation of Cry1AMod crystals in
B. thuringiensis
cells that were not soluble at pH 10.5 and showed no toxicity to
Plutella xylostella
larvae. Cysteine residues in the protoxin carboxyl-terminal end of Cry1A toxins have been shown to be involved in disulfide bond formation, which is important for crystallization. Six individual cysteine substitutions for serine residues were constructed in the carboxyl-terminal protoxin end of the p3A-Cry1AbMod construct and one in the carboxyl-terminal protoxin end of p3A-Cry1AcMod. Interestingly, p3A-Cry1AbMod C654S and C729S and p3A-Cry1AcMod C730S recover crystal solubility at pH 10.5 and toxicity to
P. xylostella
. These results show that combining the
cry3A
promoter expression system with single cysteine mutations is a useful system for efficient expression of Cry1AMod toxins in
B. thuringiensis
.
Isolation of Butanol- and Isobutanol-Tolerant Bacteria and Physiological Characterization of Their Butanol Tolerance
Authors: Kanno Manabu , Katayama Taiki , Tamaki Hideyuki , Mitani Yasuo , Meng Xian-Ying , Hori Tomoyuki , Narihiro Takashi , Morita Naoki , Hoshino Tamotsu , Yumoto Isao , Kimura Nobutada , Hanada Satoshi , Kamagata Yoichi
Published: September 2013

Despite their importance as a biofuel production platform, only a very limited number of butanol-tolerant bacteria have been identified thus far. Here, we extensively explored butanol- and isobutanol-tolerant bacteria from various environmental samples. A total of 16 aerobic and anaerobic bacteria that could tolerate greater than 2.0% (vol/vol) butanol and isobutanol were isolated. A 16S rRNA gene sequencing analysis revealed that the isolates were phylogenetically distributed over at least nine genera:
Bacillus
,
Lysinibacillus
,
Rummeliibacillus
,
Brevibacillus
,
Coprothermobacter
,
Caloribacterium
,
Enterococcus
,
Hydrogenoanaerobacterium
, and
Cellulosimicrobium
, within the phyla
Firmicutes
and
Actinobacteria
. Ten of the isolates were phylogenetically distinct from previously identified butanol-tolerant bacteria. Two relatively highly butanol-tolerant strains CM4A (aerobe) and GK12 (obligate anaerobe) were characterized further. Both strains changed their membrane fatty acid composition in response to butanol exposure, i.e., CM4A and GK12 exhibited increased saturated and cyclopropane fatty acids (CFAs) and long-chain fatty acids, respectively, which may serve to maintain membrane fluidity. The gene (
cfa
) encoding CFA synthase was cloned from strain CM4A and expressed in
Escherichia coli
. The recombinant
E. coli
showed relatively higher butanol and isobutanol tolerance than
E. coli
without the
cfa
gene, suggesting that
cfa
can confer solvent tolerance. The exposure of strain GK12 to butanol by consecutive passages even enhanced the growth rate, indicating that yet-unknown mechanisms may also contribute to solvent tolerance. Taken together, the results demonstrate that a wide variety of butanol- and isobutanol-tolerant bacteria that can grow in 2.0% butanol exist in the environment and have various strategies to maintain structural integrity against detrimental solvents.
Clonal Variants of Plasmodium falciparum Exhibit a Narrow Range of Rolling Velocities to Host Receptor CD36 under Dynamic Flow Conditions
Authors: Herricks Thurston , Avril Marion , Janes Joel , Smith Joseph D. , Rathod Pradipsinh K.
Published: September 2013

Cytoadhesion ofPlasmodium falciparumparasitized red blood cells (pRBCs) has been implicated in the virulence of malaria infection. Cytoadhesive interactions are mediated by the protein family ofPlasmodium falciparumerythrocyte membrane protein 1 (PfEMP1). The PfEMP1 family is under strong antibody and binding selection, resulting in extensive sequence and size variation of the extracellular domains. Here, we investigated cytoadhesion of pRBCs to CD36, a common receptor ofP. falciparumfield isolates, under dynamic flow conditions. Isogeneic parasites, predominantly expressing single PfEMP1 variants, were evaluated for binding to recombinant CD36 under dynamic flow conditions using microfluidic devices. We tested if PfEMP1 size (number of extracellular domains) or sequence variation affected the pRBC-CD36 interaction. Our analysis showed that clonal parasite variants varied ∼5-fold in CD36 rolling velocity despite extensive PfEMP1 sequence polymorphism. In addition, adherent pRBCs exhibited a characteristic hysteresis in rolling velocity at microvascular flow rates, which was accompanied by changes in pRBC shape and may represent important adaptations that favor stable binding.
Genome Sequence of Salt-Tolerant Bacillus safensis Strain VK, Isolated from Saline Desert Area of Gujarat, India
Authors: Kothari V. V. , Kothari R. K. , Kothari C. R. , Bhatt V. D. , Nathani N. M. , Koringa P. G. , Joshi C. G. , Vyas B. R. M.
Published: September 2013

Bacillus safensis
strain VK was isolated from the rhizosphere of a cumin plant growing in the saline desert of Radhanpar, Gujarat, India. Here, we provide the 3.68-Mb draft genome sequence of
B. safensis
VK, which might provide information about the salt tolerance and genes encoding enzymes for the strain's plant growth-promoting potential.
Draft Whole-Genome Sequence of VIM-1-Producing Multidrug-Resistant Enterobacter cloacae EC_38VIM1
Authors: Villa Jennifer , Viedma Esther , Otero Joaquín R. , Chaves Fernando
Published: September 2013

The VIM-1-producing multidrug-resistant strain
Enterobacter cloacae
was isolated from blood culture. The strain showed multiple resistances to clinically used antibiotics, including all β-lactams, fluoroquinolones, aminoglycosides, and sulfonamides. Sequence analysis showed the presence of 14 genes associated with resistance to antibiotics, including the metallo-β-lactamase VIM-1 gene, which was located in a class 1 integron.
Draft Genome Sequence of
Cladonia macilenta
KoLRI003786, a Lichen-Forming Fungus Producing Biruloquinone
Authors: Park Sook-Young , Choi Jaeyoung , Kim Jung A , Jeong Min-Hye , Kim Soonok , Lee Yong-Hwan , Hur Jae-Seoun
Published: September 2013

The lichen-forming fungus
Cladonia macilenta
strain KoLRI003786 is capable of producing an acetylcholinesterase inhibitor, biruloquinone, which effectively prevents neurodegeneration in Alzheimer's disease. Laying the foundation to unravel the biruloquinone biosynthetic pathway, we present the 37.11-Mb draft genome sequence of strain KoLRI003786.
Draft Genome Sequences of Helicobacter pylori Strains HPARG63 and HPARG8G, Cultured from Patients with Chronic Gastritis and Gastric Ulcer Disease
Authors: Armitano Rita Inés , Zerbetto De Palma Gerardo , Matteo Mario José , Revale Santiago , Romero Soledad , Traglia Germán Matías , Catalano Mariana
Published: September 2013

Helicobacter pylori
colonizes the human gastric mucosa, leading to a spectrum of gastric diseases in susceptible populations. Here we announce the draft genome sequences of strains HPARG8G and HPARG63. The data for both genome sequences provide insights regarding the diversity in gene content and rearrangement of the genomic islands commonly harbored by
H. pylori
.
Characterization of Fructose 1,6-Bisphosphatase and Sedoheptulose 1,7-Bisphosphatase from the Facultative Ribulose Monophosphate Cycle Methylotroph Bacillus methanolicus
Authors: Stolzenberger Jessica , Lindner Steffen N. , Persicke Marcus , Brautaset Trygve , Wendisch Volker F.
Published: September 2013

The genome of the facultative ribulose monophosphate (RuMP) cycle methylotroph
Bacillus methanolicus
encodes two bisphosphatases (GlpX), one on the chromosome (GlpX
C
) and one on plasmid pBM19 (GlpX
P
), which is required for methylotrophy. Both enzymes were purified from recombinant
Escherichia coli
and were shown to be active as fructose 1,6-bisphosphatases (FBPases). The FBPase-negative
Corynebacterium glutamicum
Δ
fbp
mutant could be phenotypically complemented with
glpX
C
and
glpX
P
from
B. methanolicus
. GlpX
P
and GlpX
C
share similar functional properties, as they were found here to be active as homotetramers
in vitro
, activated by Mn
2+
ions and inhibited by Li
+
, but differed in terms of the kinetic parameters. GlpX
C
showed a much higher catalytic efficiency and a lower

K
m

for fructose 1,6-bisphosphate (86.3 s
−1
mM
−1
and 14 ± 0.5 μM, respectively) than GlpX
P
(8.8 s
−1
mM
−1
and 440 ± 7.6 μM, respectively), indicating that GlpX
C
is the major FBPase of
B. methanolicus
. Both enzymes were tested for activity as sedoheptulose 1,7-bisphosphatase (SBPase), since a SBPase variant of the ribulose monophosphate cycle has been proposed for
B. methanolicus
. The substrate for the SBPase reaction, sedoheptulose 1,7-bisphosphate, could be synthesized
in vitro
by using both fructose 1,6-bisphosphate aldolase proteins from
B. methanolicus
. Evidence for activity as an SBPase could be obtained for GlpX
P
but not for GlpX
C
. Based on these
in vitro
data, GlpX
P
is a promiscuous SBPase/FBPase and might function in the RuMP cycle of
B. methanolicus
.
Predicting a biliary aetiology in paediatric acute pancreatitis
Authors: Coffey Michael J , Nightingale Scott , Ooi Chee Y
Published: September 2013

Objective

Acute biliary pancreatitis (ABP) is a common cause of pancreatitis which may require timely intervention. We aimed to identify routine laboratory parameters for early prediction of biliary aetiology in paediatric acute pancreatitis (AP).

Design

A retrospective review of children with AP (January 2000–July 2011) was performed at two tertiary paediatric hospitals in New South Wales, Australia. Predictors of ABP using laboratory parameters (measured within 48 h of presentation) were determined using a multivariate logistic regression model and evaluated.

Results

Of the 131 pancreatitis episodes reviewed, 21 (16%) were biliary-related. Raised serum lipase, alkaline phosphatase, γ-glutamyl transpeptidase (GGT), alanine aminotransferase (ALT) and aspartate aminotransferase were associated with biliary aetiology (all p<0.0016) on univariate analysis. In multiple logistic regression, serum GGT ≥40 U/L, ALT ≥150 U/L, and lipase ≥15×the upper limit of normal (ULN) were predictive of ABP. To improve clinical applicability, the predictive performance when at least two of the three ABP predictors (coined the ‘biliary pancreatitis triad’) were satisfied was evaluated. The triad performed with a specificity, sensitivity, positive predictive value and negative predictive value of 95, 89, 76 and 98%, respectively.

Conclusions

The biliary pancreatitis triad of serum GGT ≥40 U/L, ALT ≥150 U/L and lipase ≥15×ULN within 48 h of presentation may be used as simple clinical predictors of ABP in children. Children with values falling below 2 or 3 of these thresholds are very unlikely to have AP due to a biliary cause.
Intravitreal bevacizumab as an adjunct in the management of a vascular choroidal granuloma
Authors: Bansal Reema , Beke Nikhil , Sharma Aman , Gupta Amod
Published: September 2013

A 43-year-old woman with tubercular choroidal granuloma showed poor response to conventional first-line four-drug antitubercular therapy (ATT) and corticosteroids. A therapeutic trial with intravitreal bevacizumab (1.25 mg in 0.05 mL) injections as an adjunct to ATT and corticosteroids led to a prompt initial regression of granuloma with restoration of visual acuity that was sustained for almost 2 years. A subsequent recurrence of the same lesion with evidence of enhanced vascularity was treated with intravitreal bevacizumab alone, that led to a complete regression of the granuloma with no recurrence until 1 year of follow-up.
Return to play following injury: whose decision should it be?
Authors: Shrier Ian , Safai Parissa , Charland Lyn
Published: September 2013

Background

Return-to-play (RTP) decision-making is required for every injured athlete. However, these decisions often lead to conflict between sport medicine professionals, athletes, coaches and sport associations. This study explores differences in professionals’ opinion about which criteria should be used for RTP decisions, and who is best able to evaluate them.

Methods

We surveyed Canadian sport medicine physicians, physiotherapists, athletic therapists, chiropractors, massage therapists, athletes, coaches and representatives from three sport associations. The 10 min online survey asked respondents to rate criteria as mandatory to irrelevant on a five-point Likert scale, and to indicate which profession was best able to evaluate the criteria.

Results

In general, medical doctors, physiotherapists and athletic therapists were considered best able to assess factors related to risk of injury and complications from injury. Each clinician group (except sport massage therapists) generally believed their own profession has the best capacity to evaluate the criteria. Athletes, coaches and sport associations were considered to have the best capacity to assess factors related to competition (desire, psychological and financial impact and loss of competitive standing). There remained considerable heterogeneity both between and within stakeholder groups.

Conclusions

We found that differences in approach to RTP decisions were generally greater within versus between-stakeholder groups. If shared decision-making is to become the norm in clinical sport medicine, we need to begin a discussion on which discrepancies are due to lack of training (resolved through education) or scientific knowledge (resolved through research) or simply reflect the divergence of personal/societal values.
“I think this is maybe our Achilles heel…” exploring GPs’ responses to young people presenting with emotional distress in general practice: a qualitative study
Authors: Roberts Jane H , Crosland Ann , Fulton John
Published: September 2013

Objective

An exploratory study to investigate general practitioners’ (GPs’) views and experiences of consulting with young people (aged 12–19 years) presenting with emotional distress in general practice.

Design

A qualitative study using grounded theory and situational analysis. Empirical data were generated through in-depth interviews based on a topic guide developed from the literature, and augmented with a series of situational maps. Continuous field notes and theoretical memos were recorded during data collection and analysis.

The data were analysed using the constant comparative method of grounded theory. There were three levels of analysis. The first level developed the open codes and is presented here.

Setting

18 general practices located in the north east of England. The practices recruited included rural, urban and mixed populations of patients who were predominantly living in socioeconomically disadvantaged communities.

Participants

19 GPs (10 women) aged between 29 and 59 years participated. The modal age range was 40–49 years. Theoretical sampling was used to guide recruitment and continued until theoretical saturation was reached.

Results

The overarching finding was that anxiety about practice dominated clinical consultations involving young people presenting with emotional distress. GPs responded differently to anxiety and to related uncertainties about professional practice, independent of GP age or gender. Anxiety occurred in the consultation, at an external level, across disciplinary boundaries, in relation to communication with young people and secondary to the complexity of presentations.

Conclusions

Adolescent emotional distress presents professional challenges to GPs who feel ill-equipped and inadequately prepared to address early need. Medical education needs to prepare doctors better. More research is needed to look at what factors facilitate or prohibit greater GP engagement with emotionally distressed young people.
The work of commissioning: a multisite case study of healthcare commissioning in England's NHS
Authors: Shaw Sara E , Smith Judith A , Porter Alison , Rosen Rebecca , Mays Nicholas
Published: September 2013

Objective

To examine the work of commissioning care for people with long-term conditions and the factors inhibiting or facilitating commissioners making service change.

Design

Multisite mixed methods case study research, combining qualitative analysis of interviews, documents and observation of meetings.

Participants

Primary care trust managers and clinicians, general practice-based commissioners, National Health Service trust and foundation trust senior managers and clinicians, voluntary sector and local government representatives.

Setting

Three ‘commissioning communities’ (areas covered by a primary care trust) in England, 2010–2012.

Results

Commissioning services for people with long-term conditions was a long drawn-out process involving a range of activities and partners. Only some of the activities undertaken by commissioners, such as assessment of local health needs, coordination of healthcare planning and service specification, appeared in the official ‘commissioning cycle’ promoted by the Department of Health. Commissioners undertook a significant range of additional activities focused on reviewing and redesigning services and providing support for implementation of new services. These activities often involved partnership working with providers and other stakeholders and appeared to be largely divorced from contracting and financial negotiations. At least for long-term condition services, the time and effort involved in such work appeared to be disproportionate to the anticipated or likely service gains. Commissioners adopting an incremental approach to service change in defined and manageable areas of work appeared to be more successful in terms of delivering planned changes in service delivery than those attempting to bring about wide-scale change across complex systems.

Conclusions

Commissioning for long-term condition services challenges the conventional distinction between commissioners and providers with a significant amount of work focused on redesigning services in partnership with providers. Such work is labour-intensive and potentially unsustainable at a time of reduced finances. New clinical commissioning groups will need to determine how best to balance the relational and transactional elements of commissioning.
THE EPIDEMIOLOGY AND HEALTH SYSTEM IMPACT OF MEDIUM-CHAIN ACYL-COA DEHYDROGENASE DEFICIENCY AMONG AFFECTED CHILDREN AND THOSE WITH FALSE POSITIVE NEWBORN SCREENING RESULTS IN ONTARIO, CANADA
Authors: Karaceper Maria D , Chakraborty Pranesh , Coyle Doug , Wilson Kumanan , Potter Beth K
Published: September 2013

Introduction

Limited research has focused on the health system impact of rare genetic disorders, including inborn errors of metabolism (IEM). Investigating patterns of health services use and their association with social and geographic characteristics is important for understanding the burden of disease, including the impact of screening and clinical management; and for identifying potential inequities in access to care.

Objectives

We conducted an observational study to provide a comprehensive description of the epidemiology and health system impact of IEM in Ontario, beginning with medium-chain acyl-CoA dehydrogenase deficiency (MCADD).

Methods

The study cohorts consist of Ontario infants diagnosed with MCADD following a positive newborn screening result from April 2006 through March 2010 (n=45); and those who received a false positive screening result for MCADD during the same time period (n=51). The primary control population includes a random sample of infants with negative screening results. Two distinct secondary control groups were created by matching to the truly affected cohort and the false-positive cohort, respectively. Screening and confirmatory testing results are securely linked at the individual level with population-based administrative databases encompassing health services use (physician visits, hospitalizations, and emergency department care) for all insured Ontarians from April 2006 through March 2012. Based on the results of a literature review we conducted to identify existing approaches to addressing statistical reliability with small sample sizes, analyses are largely descriptive.

Results

We will describe: (i) the patterns of health care services use overall and by sociodemographic and geographic characteristics, (ii) the associations between types of service use and proxy health outcomes, and (iii) the costs of care.
SCOPE AND NATURE OF YOUNG SUDDEN CARDIAC DEATH IN NEWFOUNDLAND & LABRADOR
Authors: Hamilton Gina , Avis Simon , Curtis Fiona , Young Terry-Lynn , Connors Sean , Hodgkinson Kathleen
Published: September 2013

Introduction

Sudden cardiac death (SCD) in young people is a tragedy for families and communities alike. It is often due to an underlying genetic arrhythmic condition. In 2008, we identified a significant genetic defect (TMEM43; P358L) in patients and extended relatives from 22 unrelated families with Newfoundland ancestry. We showed that the clinical consequence of harboring the TMEM43 mutation is early SCD (50% of untreated males deceased by 40 years, 80% by 50 years). One study from Ontario using a 2008 cohort assessed the incidence of potential SCD in persons aged 2–40y to be 14.8 per 100,000. We hypothesize that NL may have a higher incidence of early SCD in this age category due to TMEM43 and possibly other underlying genetic causes, given the historical genetic isolation of the population.

Methods

Following local REB approval (#12.199) we ascertained cases of sudden death from the comprehensive Medical Examiners provincial database. Cases that satisfied the following three inclusion criteria were reviewed: 1) date of death in 2008, 2) age at death aged 2-40y inclusive, and 3) manner of death listed as “natural-cardiac”, “natural-other”, “accidental”, or “undetermined”. Each case was then individually analyzed by the research team to determine likelihood of SCD.

Results

All the 2008 NL cases were ascertained, and all (anonymous) data maintained on an SPSS dataset. There were 12 “natural-cardiac” cases, 8 “natural-other”, 48 “accidental”, and 2 “undetermined”, giving a total of 70 'potential' SCD cases in those aged 2–40y. The Ontario study yielded 976 'potential' cases. The 'potential' incidence of sudden death for Ontario of 14.8 per 100,000 compares with 30.1/100,000 in NL (with denominators of 6,602, 680 and 232,210 derived from statistics Canada for the provincial populations between 2–40y respectively). This represents a significant increase of potential SCD in NL (p=0.02).

Conclusion

These figures include cases which are likely not SCD's. However, the methodology used to compare the populations was exactly the same. It appears therefore that NL had more deaths in 2008 in this age cohort than Ontario. The reasons for this difference are yet to be determined.
SOCIO-DEMOGRAPHIC DETERMINANTS OF FAMILIAL AND PARTNER PRESSURES TO CONCEIVE IN HIV-POSITIVE WOMEN IN ONTARIO, CANADA
Authors: Mehta Sachin , Newmeyer Trent , Loutfy Mona , Faught Brent
Published: September 2013

Introduction

Access to antiretroviral therapy has improved quality of life, minimized vertical transmission, and reduced mortality and morbidity in HIV-infected women. With these advances, many HIV-infected women and their partners are deciding to have children or carry unplanned pregnancies to term.

Objective

To examine the relationship between socio-demographic factors and family and partner pressures to conceive in HIV-positive women in Ontario, Canada.

Methods

Cross-sectional design examined data from the HIV Pregnancy Planning Questionnaire conducted in Ontario, Canada between 2007 and 2009. HIV-positive women aged 18-52 years were included in the analysis. A total of 486 women and 336 women provided information on family and partner pressures to conceive, respectively. Step-wise logistic regression was used to examine the relationship between socio-demographic variables and family and partner pressures to conceive. Socio-demographic variables included age, ethnicity, religion, country of birth, marital status, annual household income, education, years lived in Canada, number of lifetime births, HIV medication, hepatitis C co-infection, CD4 cell count, and viral load.

Results

There is 0.95 (95% CI: 0.91-0.99; p-value: 0.0253) and 0.95 (95% CI: 0.93-0.98; p-value: <.0001) lower odds of family pressures to conceive with increased age and years lived in Canada, respectively. Women married or in common-law relationship have 3.08 (95% CI: 1.39–6.80; p-value: 0.0055) and women having 2 lifetime births have 1.98 (95% CI: 1.02–3.84; p-value: 0.0428) higher odds of family pressures to conceive. There is 0.96 (95% CI: 0.93-0.98; p-value: 0.0013) lower odds of partner pressure with increased years lived in Canada. Women married or in common-law relationship have 4.20 (95% CI: 1.58–11.17; p-value: 0.0040) and those living with partner (but are not married or in common-law relationship) have 4.47 (95% CI: 1.27–15.67; p-value: 0.0195) higher odds of partner pressures to conceive.

Conclusion

Results suggest that age, number of years lived in Canada, marital status, and number of lifetime births are associated with family and partner pressures to conceive. Identification of these factors will allow health care providers to assist HIV-positive women and their partners make informed reproductive decisions.
DEVELOPING AND TESTING A TOOL FOR ASSESSING PHARMACOECONOMIC EVALUATIONS
Authors: Sabarre Kelley-Anne , Coyle Doug , Lee Karen
Published: September 2013

Introduction

Manufacturers seeking reimbursement from publicly funded drug plans submit a drug submission to the Common Drug Review (CDR). This includes clinical data and a pharmacoeconomic evaluation (PE) which is assessed by clinical and economic teams. Clinical and pharmacoeconomic reports are used by the Canadian Drug Expert Committee (CDEC) in their deliberations, which could result in a “do not list”, “list with criteria” or “list” formulary listing recommendation (FLR). Given growing financial constraints, the need to economic information to inform FLR decision makers is critical. Therefore, understanding the quality and limitations with regards to economic submissions can assist FLR decision makers. This report focuses on the development and piloting of a PE appraisal instrument.

Objectives

To develop an instrument for assessing the quality of PEs in terms of adherence to guidelines, methodological quality and transparency of reporting, and use of indirect treatment comparisons.

Methods

An existing PE appraisal instrument was updated using a quality assessment framework (QAF). A literature review was conducted to identify additional key factors affecting methodological quality. Modifications to the tool were made upon consensus. The instrument was piloted by three investigators using 29 selected PEs and accompanying pharmacoeconomic reports. A pooled kappa statistic was calculated. The instrument was evaluated by identifying items met from QAF and comparing it to four highly-recognised appraisal tools.

Results

This tool includes 69 multiple-choice and short answer questions and covers: economic evaluation details, quality of pharmacoeconomic submissions, and use of pharmacoeconomic information by CDEC. The kappa statistic indicates substantial agreement [0.72(0.67–0.77)]. The tool fulfils all dimensions of QAF and is at least as comprehensive as other published appraisal instruments.

Conclusions

The steps in developing this PE quality appraisal instrument involved: quality assessment framework, literature review, draft tool, pretesting, re-drafted instrument, inter-rater reliability testing, and final instrument. Although this tool was created to examine PEs submitted to CDR, components of this instrument can be used beyond the realm of CDR PE assessments. Its practicality, reliability and parity to other appraisal tools demonstrate its potential application in the development and appraisal of PEs.
DISEASE, PATIENT AND HEALTHCARE SYSTEM LEVEL PREDICTORS OF ACCUMULATED INPATIENT DAYS AND HOME CARE USE FOR METASTATIC GASTRIC CANCER PATIENTS
Authors: Mahar Alyson L. , Viola Raymond , Johnson Ana P. , Coburn Natalie G.
Published: September 2013

Introduction

Home care has been proposed as a means of reducing costs in palliative care by decreasing inpatient stay without impacting quality of clinical care. Predictors of major cost drivers for end-of-life care are unknown for the management of metastatic gastric cancer.

Objectives

This study examined disease, patient and healthcare system predictors of inpatient hospital days and receipt of home care.

Methods

This is a population-based, retrospective cohort study of data on patients diagnosed in Ontario between 2005 and 2008. Chart review and administrative data were linked, using a twenty-six month time horizon and the healthcare system perspective. The cumulative inpatient hospital stay was defined using admission and discharge dates from hospitalizations in the Canadian Institute for Health Information database. Home care use was defined as yes/no, using data from the Ontario Home Care Database. Negative binomial regression was used to model the number of inpatient hospital days and modified poisson regression to model the receipt of home care.

Results

Patients with primary tumours in the gastroesophageal junction compared to the distal stomach, and younger age incurred significantly fewer inpatient days. Patients who underwent a gastrectomy were significantly less likely to accumulate inpatient hospital days (RR 0.65; 95% CI 0.55-0.76), as were patients who interacted with a high volume specialist (RR=0.54; 95% CI=0.46-0.63). Proximal compared to distal tumour location was associated with an increased likelihood of receiving homecare (RR=1.12; 95% CI: 1.04-1.20). Increasing age was significantly associated with not receiving a home care visit (p=0.0010). Patients in the high resource use category were 78% more likely to receive home care than healthy users (RR=1.78; 95% CI=1.02-3.08). Patients interacting with a high volume specialist were 15% more likely to receive home care than those who did not (RR=1.15; 95% CI=1.09-1.21).

Conclusion

A number of predictors of healthcare resource utilization were identified; however, not all were modifiable. Further research needs to examine how differences in home care use and inpatient hospital stay impact clinical outcomes such as symptom relief and quality of life, and how policies may be targeted to reduce costs to the healthcare system while maintaining optimal clinical care.
A NON-PARAMETRIC APPROACH TO SELECTION BIAS: EXAMINING THE ORGANIZATIONAL EFFECT OF FAMILY MEDICINE GROUPS ON ACCESS TO PRIMARY CARE AMONG DIABETICS IN QUEBEC
Authors: Carter Renee , Quesnel-Vallée Amélie , Lévesque Jean-Frédéric , Harper Sam , Strumpf Erin
Published: September 2013

Introduction

Within Canada, Quebecers experience the greatest barriers in accessing primary care with over 25% of the population without a regular family physician and the highest rate of emergency department (ED) use. Family Medicine Groups (FMGs) were introduced in 2002 to provide greater access to care, namely for individuals with chronic conditions such as diabetes. Some key characteristics of the FMG organizational reform are: (1) it is based on voluntary physician take-up; (2) its regional variation in implementation; (3) its gradual deployment across the province. These factors may produce selection bias between early and late physician implementers.

Objectives

To determine whether the regional rate of avoidable ED visits among diabetics co-varies with FMG wave of implementation distinguishing between early and late physician adopters of the model.

Methods

An ecological analysis will be conducted to meet this objective. The outcome is access to primary care measured by the regional rate of avoidable ED visits among diabetics between 2003 and 2012. Regions are defined on an urban to rural continuum according to each administrative region's distance from the province's main city centers, Montreal and Quebec City. The study will be conducted using linked administrative health databases for which access has already been granted. Non-parametric spline regression will be used to distinguish between waves of FMG implementation. The spline knots, denoting a significant change in the rate of avoidable ED visits, will be estimated from the data. To improve internal validity, the analysis will incorporate a control series examining trauma visits to the ED that should not be affected by the FMG reform.

Results

The analyses are in progress and results are expected by the end of May.

Conclusion

This study will be the first to empirically define waves of FMG implementation and their effects on access to primary care among diabetics. These findings will inform future studies examining access to primary care at an individual patient level where failure to control for FMG waves may produce biased estimates of the reform's organizational effect.
CLINICAL USE OF HEALTH-RELATED QUALITY OF LIFE OUTCOMES FROM CANCER CLINICAL TRIALS: PRELIMINARY RESULTS FROM A SURVEY OF ONCOLOGISTS
Authors: Rouette Julie , Blazeby Jane , Calvert Melanie , King Madeleine , Meyer Ralph , Peng Paul , Ringash Jolie , Walker Melanie , Brundage Michael D.
Published: September 2013

Introduction

There have been increasing efforts aimed at enhancing patient-centered care and incorporating patients' voice into clinical practice. As such, a growing body of literature has recognized the importance of Health-Related Quality of Life (HRQOL) outcomes from clinical trials. HRQOL outcomes are often collected in Phase III randomized controlled trials (RCTs), along with survival data, morbidity, and toxicity data. HRQOL outcomes are measures reported directly by the patient through a questionnaire and represent the patient's own evaluation of symptoms, physical functioning status, psychological well-being, and global health-related quality of life. In clinical practice, HRQOL outcomes from Phase III cancer clinical trials are key elements in treatment decision making, clinical outcomes interpretation, and determination of prognosis. However, several challenges to the use of HRQOL outcomes have led to difficulties for oncologists in interpreting HRQOL results and have contributed to their unfamiliarity with these outcomes, resulting in a difficulty understanding what a clinically meaningful finding is.

Objectives

To describe oncologists' knowledge, attitudes, experience, facilitators and perceived barriers in HRQOL outcomes and to determine the association between these attributes and their demographic variables.

Methods

A cross-sectional web-based survey was sent to all practicing oncologists from the NCIC Clinical Trials Group in Canada, the NCRI Clinical Trials Units in the United Kingdom and the Multi-site Collaborative National Cancer Clinical Trials Groups in Australia to collect information on the oncologists' attributes described above.

Results

Previous findings from a qualitative preliminary study showed that there was strong support for reporting HRQOL outcomes in cancer clinical trials, but that barriers to the uptake of HRQOL data in clinical practice included the accessibility, generalizability, and quality of the data; reporting methods; and oncologists' perceived lack of knowledge required to interpret the data.

Conclusion

The importance of HRQOL outcomes from RCTs to inform clinical practice is well described. However, there remain significant barriers to their uptake and use in clinical practice. Findings from this project will help develop future knowledge translation strategies in oncology and provide a basis for the design of effective ways to optimize the clinical applicability of these outcomes in the oncology practice.
TOPOLOGICAL FLAT BAND MODELS AND FRACTIONAL CHERN INSULATORS
Authors: BERGHOLTZ EMIL J. , LIU ZHAO
Published: September 2013

Topological insulators and their intriguing edge states can be understood in a single-particle picture and can as such be exhaustively classified. Interactions significantly complicate this picture and can lead to entirely new insulating phases, with an altogether much richer and less explored phenomenology. Most saliently, lattice generalizations of fractional quantum Hall states, dubbed fractional Chern insulators, have recently been predicted to be stabilized by interactions within nearly dispersionless bands with nonzero Chern number, C. Contrary to their continuum analogues, these states do not require an external magnetic field and may potentially persist even at room temperature, which make these systems very attractive for possible applications such as topological quantum computation. This review recapitulates the basics of tight-binding models hosting nearly flat bands with nontrivial topology, C≠0, and summarizes the present understanding of interactions and strongly correlated phases within these bands. Emphasis is made on microscopic models, highlighting the analogy with continuum Landau level physics, as well as qualitatively new, lattice specific, aspects including Berry curvature fluctuations, competing instabilities as well as novel collective states of matter emerging in bands with |C|>1. Possible experimental realizations, including oxide interfaces and cold atom implementations as well as generalizations to flat bands characterized by other topological invariants are also discussed.
DIELECTRIC FUNCTION, FRIEDEL OSCILLATION AND PLASMONS IN WEYL SEMIMETALS
Authors: LV MIN , ZHANG SHOU-CHENG
Published: September 2013

We calculate the dielectric function of a Weyl semimetal at arbitrary momentum q and frequency ω within the random-phase approximation. Taking the static limit, we calculated the Friedel oscillation and found that: (1) For a single Weyl point, the oscillation ~ sin (2kFr)/r4 falls off faster by an 1/r factor than the one in traditional 3D systems ~ cos (2kFr)/r3. This difference arises from the suppression of backward scattering in Weyl fermion systems; (2) For Weyl semimetal with two Weyl points, there are additional oscillations decaying as cos (Q ⋅ r)/r3 and cos (Q ± 2kF) ⋅ r/r3, where Q is the momentum difference between the two Weyl points. We also calculated the plasmon dispersion and found features distinct from those of conventional 3D metals.
A new proof of the Lie–Trotter–Kato formula in Hadamard spaces
Authors: Bačák Miroslav
Published: September 2013

The Lie–Trotter–Kato product formula has been recently extended into Hadamard spaces by Stojkovic [Approximation for convex functionals on non-positively curved spaces and the Trotter–Kato product formula, Adv. Calc. Var. 5 (2012) 77–216]. The aim of our short note is to give a simpler proof relying upon weak convergence instead of an ultrapower technique.
Some remarks on the solvability of non-local elliptic problems with the Hardy potential
Authors: Barrios B. , Medina M. , Peral I.
Published: September 2013

The aim of this paper is to study the solvability of the following problem, [Formula: see text] where (-Δ)s, with s ∈ (0, 1), is a fractional power of the positive operator -Δ, Ω ⊂ ℝN, N > 2s, is a Lipschitz bounded domain such that 0 ∈ Ω, μ is a positive real number, λ < ΛN,s, the sharp constant of the Hardy–Sobolev inequality, 0 < q < 1 and [Formula: see text], with αλa parameter depending on λ and satisfying [Formula: see text]. We will discuss the existence and multiplicity of solutions depending on the value of p, proving in particular that p(λ, s) is the threshold for the existence of solution to problem (Pμ).