bluuebunny/crossref_metadata_2025 huggingface dataset:
Intraspecies Transfer of the Chromosomal Acinetobacter baumannii
bla
NDM-1
Carbapenemase Gene
Authors: Krahn Thomas , Wibberg Daniel , Maus Irena , Winkler Anika , Bontron Séverine , Sczyrba Alexander , Nordmann Patrice , Pühler Alfred , Poirel Laurent , Schlüter Andreas
Published: March 2016

The species
Acinetobacter baumannii
is one of the most important multidrug-resistant human pathogens. To determine its virulence and antibiotic resistance determinants, the genome of the nosocomial
bla
NDM-1
-positive
A. baumannii
strain R2090 originating from Egypt was completely sequenced. Genome analysis revealed that strain R2090 is highly related to the community-acquired Australian
A. baumannii
strain D1279779. The two strains belong to sequence type 267 (ST267). Isolate R2090 harbored the chromosomally integrated transposon Tn
125
carrying the carbapenemase gene
bla
NDM-1
that is not present in the D1279779 genome. To test the transferability of the metallo-β-lactamase (MBL) gene region, the clinical isolate R2090 was mated with the susceptible
A. baumannii
recipient CIP 70.10, and the carbapenem-resistant derivative R2091 was obtained. Genome sequencing of the R2091 derivative revealed that it had received an approximately 66-kb region comprising the transposon Tn
125
embedding the
bla
NDM-1
gene. This region had integrated into the chromosome of the recipient strain CIP 70.10. From the four known mechanisms for horizontal gene transfer (conjugation, outer membrane vesicle-mediated transfer, transformation, and transduction), conjugation could be ruled out, since strain R2090 lacks any plasmid, and a type IV secretion system is not encoded in its chromosome. However, strain R2090 possesses three putative prophages, two of which were predicted to be complete and therefore functional. Accordingly, it was supposed that the transfer of the resistance gene region from the clinical isolate R2090 to the recipient occurred by general transduction facilitated by one of the prophages present in the R2090 genome. Hence, phage-mediated transduction has to be taken into account for the dissemination of antibiotic resistance genes within the species
A. baumannii
.
Ureolytic Biomineralization Reduces Proteus mirabilis Biofilm Susceptibility to Ciprofloxacin
Authors: Li Xiaobao , Lu Nanxi , Brady Hannah R. , Packman Aaron I.
Published: March 2016

Ureolytic biomineralization induced by urease-producing bacteria, particularly
Proteus mirabilis
, is responsible for the formation of urinary tract calculi and the encrustation of indwelling urinary catheters. Such microbial biofilms are challenging to eradicate and contribute to the persistence of catheter-associated urinary tract infections, but the mechanisms responsible for this recalcitrance remain obscure. In this study, we characterized the susceptibility of wild-type (ure+) and urease-negative (ure−)
P. mirabilis
biofilms to killing by ciprofloxacin. Ure+ biofilms produced fine biomineral precipitates that were homogeneously distributed within the biofilm biomass in artificial urine, while ure− biofilms did not produce biomineral deposits under identical growth conditions. Following exposure to ciprofloxacin, ure+ biofilms showed greater survival (less killing) than ure− biofilms, indicating that biomineralization protected biofilm-resident cells against the antimicrobial. To evaluate the mechanism responsible for this recalcitrance, we observed and quantified the transport of Cy5-conjugated ciprofloxacin into the biofilm by video confocal microscopy. These observations revealed that the reduced susceptibility of ure+ biofilms resulted from hindered delivery of ciprofloxacin into biomineralized regions of the biofilm. Further, biomineralization enhanced retention of viable cells on the surface following antimicrobial exposure. These findings together show that ureolytic biomineralization induced by
P. mirabilis
metabolism strongly regulates antimicrobial susceptibility by reducing internal solute transport and increasing biofilm stability.
Acquisition of Broad-Spectrum Cephalosporin Resistance Leading to Colistin Resistance in Klebsiella pneumoniae
Authors: Jayol Aurélie , Nordmann Patrice , Desroches Marine , Decousser Jean-Winoc , Poirel Laurent
Published: March 2016

An extended-spectrum β-lactamase (ESBL)-producing and colistin-resistant
Klebsiella pneumoniae
clinical isolate was recovered from a patient who was treated with cefotaxime. This isolate harbored a
bla
CTX-M-15
ESBL gene that was associated with an IS
Ecp1
insertion sequence. Transposition of that tandem occurred within the chromosomal
mgrB
gene, leading to inactivation of the
mgrB
gene and consequently to acquired resistance to colistin. We showed here a coselection of colistin resistance as a result of a broad-spectrum cephalosporin selective pressure.
Inhibition of Glutathione Biosynthesis Sensitizes Plasmodium berghei to Antifolates
Authors: Songsungthong Warangkhana , Koonyosying Pongpisid , Uthaipibull Chairat , Kamchonwongpaisan Sumalee
Published: March 2016

Glutathione plays a central role in maintaining cellular redox homeostasis, and modulations to this status may affect malaria parasite sensitivity to certain types of antimalarials. In this study, we demonstrate that inhibition of glutathione biosynthesis in the
Plasmodium berghei
ANKA strain through disruption of the γ-glutamylcysteine synthetase (γ-GCS) gene, which encodes the first and rate-limiting enzyme in the glutathione biosynthetic pathway, significantly sensitizes parasites
in vivo
to pyrimethamine and sulfadoxine, but not to chloroquine, artesunate, or primaquine, compared with control parasites containing the same pyrimethamine-resistant marker cassette. Treatment of mice infected with an antifolate-resistant
P. berghei
control line with a γ-GCS inhibitor, buthionine sulfoximine, could partially abrogate pyrimethamine and sulfadoxine resistance. The role of glutathione in modulating the malaria parasite's response to antifolates suggests that development of specific inhibitors against
Plasmodium
γ-GCS may offer a new approach to counter
Plasmodium
antifolate resistance.
Vancomycin 24-Hour Area under the Curve/Minimum Bactericidal Concentration Ratio as a Novel Predictor of Mortality in Methicillin-Resistant Staphylococcus aureus Bacteremia
Authors: Britt Nicholas S. , Patel Nimish , Horvat Rebecca T. , Steed Molly E.
Published: March 2016

While previous studies have examined the association between vancomycin (VAN) exposure and MIC with regard to outcomes in methicillin-resistant
Staphylococcus aureus
bacteremia (MRSA-B), none have explored if a relationship exists with the VAN minimum bactericidal concentration (MBC). The objective of this study was to evaluate the VAN 24-h area under the curve (AUC
24
)/MBC ratio as a pharmacodynamic predictor of mortality. This retrospective cohort study included patients treated with VAN for MRSA-B with the primary outcome of 30-day all-cause mortality. Data collected included patient demographics, comorbidities, antimicrobial treatment data, therapeutic drug levels, and laboratory and microbiological data. Vancomycin MICs and MBCs were determined by Etest (MIC only) and broth microdilution (BMD). The vancomycin AUC
24
was determined by pharmacokinetic maximum
a posteriori
probability Bayesian (MAP-Bayesian) analysis. The most significant breakpoint for 30-day mortality was determined by classification and regression tree (CART) analysis. The association between pharmacodynamic parameters (VAN AUC
24
/MIC
BMD
, VAN AUC
24
/MIC
Etest
, and AUC
24
/MBC
BMD
) and mortality were determined by χ
2
and multivariable Poisson regression. Overall mortality in this cohort (
n
= 53) was 20.8% (
n
= 11/53), and all corresponding MRSA blood isolates were VAN susceptible (MIC range, 0.5 to 2 μg/ml; MIC
50
, 1 μg/ml; MIC
90
, 1 μg/ml). The CART-derived breakpoints for mortality were 176 (VAN AUC
24
/MBC) and 334 (VAN AUC
24
/MIC
BMD
). In multivariable analysis, the association between a VAN AUC
24
/MBC of ≥176 and survival persisted, but VAN AUC
24
/MIC
BMD
values (≥334 or ≥400) were not associated with improved mortality. In conclusion, VAN AUC
24
/MBC was a more important predictor of 30-day mortality than VAN AUC
24
/MIC for MRSA-B.
First Report of
cfr
-Carrying Plasmids in the Pandemic Sequence Type 22 Methicillin-Resistant Staphylococcus aureus Staphylococcal Cassette Chromosome
mec
Type IV Clone
Authors: Shore Anna C. , Lazaris Alexandros , Kinnevey Peter M. , Brennan Orla M. , Brennan Gráinne I. , O'Connell Brian , Feßler Andrea T. , Schwarz Stefan , Coleman David C.
Published: March 2016

Linezolid is often the drug of last resort for serious methicillin-resistant
Staphylococcus aureus
(MRSA) infections. Linezolid resistance is mediated by mutations in 23S rRNA and genes for ribosomal proteins;
cfr
, encoding phenicol, lincosamide, oxazolidinone, pleuromutilin, and streptogramin A (PhLOPS
A
) resistance; its homologue
cfr
(B); or
optrA
, conferring oxazolidinone and phenicol resistance. Linezolid resistance is rare in
S. aureus
, and
cfr
is even rarer. This study investigated the clonality and linezolid resistance mechanisms of two MRSA isolates from patients in separate Irish hospitals. Isolates were subjected to
cfr
PCR, PhLOPS
A
susceptibility testing, 23S rRNA PCR and sequencing, DNA microarray profiling,
spa
typing, pulsed-field gel electrophoresis (PFGE), plasmid curing, and conjugative transfer. Whole-genome sequencing was used for single-nucleotide variant (SNV) analysis, multilocus sequence typing, L protein mutation identification,
cfr
plasmid sequence analysis, and
optrA
and
cfr
(B) detection. Isolates M12/0145 and M13/0401 exhibited linezolid MICs of 64 and 16 mg/liter, respectively, and harbored identical 23S rRNA and L22 mutations, but M12/0145 exhibited the mutation in 2/6 23S rRNA alleles, compared to 1/5 in M13/0401. Both isolates were sequence type 22 MRSA staphylococcal cassette chromosome
mec
type IV (ST22-MRSA-IV)/
spa
type t032 isolates, harbored
cfr
, exhibited the PhLOPS
A
phenotype, and lacked
optrA
and
cfr
(B). They differed by five PFGE bands and 603 SNVs. Isolate M12/0145 harbored
cfr
and
fexA
on a 41-kb conjugative pSCFS3-type plasmid, whereas M13/0401 harbored
cfr
and
lsa
(B) on a novel 27-kb plasmid. This is the first report of
cfr
in the pandemic ST22-MRSA-IV clone. Different
cfr
plasmids and mutations associated with linezolid resistance in genotypically distinct ST22-MRSA-IV isolates highlight that prudent management of linezolid use is essential.
Identification and Characterization of the Rhoptry Neck Protein 2 in Babesia divergens and B. microti
Authors: Ord Rosalynn L. , Rodriguez Marilis , Cursino-Santos Jeny R. , Hong Hyunryung , Singh Manpreet , Gray Jeremy , Lobo Cheryl A.
Published: March 2016

Apicomplexan parasites include those of the genera
Plasmodium
,
Cryptosporidium
, and
Toxoplasma
and those of the relatively understudied zoonotic genus
Babesia
. In humans, babesiosis, particularly transfusion-transmitted babesiosis, has been emerging as a major threat to public health. Like malaria, the disease pathology is a consequence of the parasitemia which develops through cyclical replication of
Babesia
parasites in host erythrocytes. However, there are no exoerythrocytic stages in
Babesia
, so targeting of the blood stage and associated proteins to directly prevent parasite invasion is the most desirable option for effective disease control. Especially promising among such molecules are the rhoptry neck proteins (RONs), whose homologs have been identified in many apicomplexan parasites. RONs are involved in the formation of the moving junction, along with AMA1, but no RON has been identified and characterized in any
Babesia
spp. Here we identify the RON2 proteins of
Babesia divergens
(BdRON2) and
B. microti
(BmRON2) and show that they are localized apically and that anti-BdRON2 antibodies are significant inhibitors of parasite invasion
in vitro
. Neither protein is immunodominant, as both proteins react only marginally with sera from infected animals. Further characterization of the direct role of both BdRON2 and BmRON2 in parasite invasion is required, but knowledge of the level of conformity of RON2 proteins within the apicomplexan phylum, particularly that of the AMA1-RON2 complex at the moving junction, along with the availability of an animal model for
B. microti
studies, provides a key to target this complex with a goal of preventing the erythrocytic invasion of these parasites and to further our understanding of the role of these conserved ligands in invasion.
STAT6 Signaling Attenuates Interleukin-17-Producing γδ T Cells during Acute Klebsiella pneumoniae Infection
Authors: Bloodworth Melissa H. , Newcomb Dawn C. , Dulek Daniel E. , Stier Matthew T. , Cephus Jacqueline Y. , Zhang Jian , Goleniewska Kasia , Kolls Jay K. , Peebles R. Stokes
Published: March 2016

γδ T cells are prevalent at mucosal and epithelial surfaces and are a critical first line of defense against bacterial and fungal pathogens. γδ17 cells are a subset of γδ T cells which, in the presence of IL-23 and IL-1β, produce large quantities of interleukin-17A (IL-17A), a cytokine crucial to these cells' antibacterial and antifungal function. STAT6, an important transcription factor in Th2 differentiation and inhibition of Th1 differentiation, is expressed at high levels in the T cells of people with parasitic infections and asthma. Our group and others have shown that STAT6 attenuates IL-17A protein expression by CD4+T cells. By extension, we hypothesized that STAT6 activation also inhibits innate γδ17 cell cytokine secretion. We show here that γδ17 cells expressed the type I IL-4 receptor (IL-4R), and IL-4 increased STAT6 phosphorylation in γδ T cells. IL-4 inhibited γδ17 cell production of IL-17A. IL-4 also decreased γδ17 cell expression of IL-23R as well as Sgk1. To determine whether STAT6 signaling regulates γδ17 cell numbersin vivo, we used a model ofKlebsiella pneumoniaein mice deficient in STAT6. We choseK. pneumoniaefor ourin vivomodel, sinceK. pneumoniaeincreases IL-17A expression and γδ17 numbers.K. pneumoniaeinfection of STAT6 knockout mice resulted in a statistically significant increase in the number of γδ17 cells compared to that of wild-type mice. These studies are the first to demonstrate that γδ17 cells express the type I IL-4R and that STAT6 signaling negatively regulates γδ17 cells, a cell population that plays a front-line role in mucosal immunity.
Distinct Roles of Myosins in Aspergillus fumigatus Hyphal Growth and Pathogenesis
Authors: Renshaw Hilary , Vargas-Muñiz José M. , Richards Amber D. , Asfaw Yohannes G. , Juvvadi Praveen R. , Steinbach William J.
Published: March 2016

Myosins are a family of actin-based motor proteins found in many organisms and are categorized into classes based on their structures. Class II and V myosins are known to be important for critical cellular processes, including cytokinesis, endocytosis, exocytosis, and organelle trafficking, in the model fungi
Saccharomyces cerevisiae
and
Aspergillus nidulans
. However, the roles of myosins in the growth and virulence of the pathogen
Aspergillus fumigatus
are unknown. We constructed single- and double-deletion strains of the class II and class V myosins in
A. fumigatus
and found that while the class II myosin (
myoB
) is dispensable for growth, the class V myosin (
myoE
) is required for proper hyphal extension; deletion of
myoE
resulted in hyperbranching and loss of hyphal polarity. Both
myoB
and
myoE
are necessary for proper septation, conidiation, and conidial germination, but only
myoB
is required for conidial viability. Infection with the Δ
myoE
strain in the invertebrate
Galleria mellonella
model and also in a persistently immunosuppressed murine model of invasive aspergillosis resulted in hypovirulence, while analysis of bronchoalveolar lavage fluid revealed that tumor necrosis factor alpha (TNF-α) release and cellular infiltration were similar compared to those of the wild-type strain. The Δ
myoE
strain showed fungal growth in the murine lung, while the Δ
myoB
strain exhibited little fungal burden, most likely due to the reduced conidial viability. These results show, for the first time, the important role these cytoskeletal components play in the growth of and disease caused by a known pathogen, prompting future studies to understand their regulation and potential targeting for novel antifungal therapies.
CotG-Like Modular Proteins Are Common among Spore-Forming Bacilli
Authors: Saggese Anella , Isticato Rachele , Cangiano Giuseppina , Ricca Ezio , Baccigalupi Loredana
Published: March 2016

CotG is an abundant protein initially identified as an outer component of the
Bacillus subtilis
spore coat. It has an unusual structure characterized by several repeats of positively charged amino acids that are probably the outcome of multiple rounds of gene elongation events in an ancestral minigene. CotG is not highly conserved, and its orthologues are present in only two
Bacillus
and two
Geobacillus
species. In
B. subtilis
, CotG is the target of extensive phosphorylation by a still unidentified enzyme and has a role in the assembly of some outer coat proteins. We report now that most spore-forming bacilli contain a protein not homologous to CotG of
B. subtilis
but sharing a central “modular” region defined by a pronounced positive charge and randomly coiled tandem repeats. Conservation of the structural features in most spore-forming bacilli suggests a relevant role for the CotG-like protein family in the structure and function of the bacterial endospore. To expand our knowledge on the role of CotG, we dissected the
B. subtilis
protein by constructing deletion mutants that express specific regions of the protein and observed that they have different roles in the assembly of other coat proteins and in spore germination.

IMPORTANCE
CotG of
B. subtilis
is not highly conserved in the
Bacillus
genus; however, a CotG-like protein with a modular structure and chemical features similar to those of CotG is common in spore-forming bacilli, at least when CotH is also present. The conservation of CotG-like features when CotH is present suggests that the two proteins act together and may have a relevant role in the structure and function of the bacterial endospore. Dissection of the modular composition of CotG of
B. subtilis
by constructing mutants that express only some of the modules has allowed a first characterization of CotG modules and will be the basis for a more detailed functional analysis.
Crystal Structure and Biochemical Characterization of a Mycobacterium smegmatis AAA-Type Nucleoside Triphosphatase Phosphohydrolase (Msm0858)
Authors: Unciuleac Mihaela-Carmen , Smith Paul C. , Shuman Stewart
Published: March 2016

AAA proteins (ATPases associated with various cellular activities) use the energy of ATP hydrolysis to drive conformational changes in diverse macromolecular targets. Here, we report the biochemical characterization and 2.5-Å crystal structure of a
Mycobacterium smegmatis
AAA protein Msm0858, the ortholog of
Mycobacterium tuberculosis
Rv0435c. Msm0858 is a magnesium-dependent ATPase and is active with all nucleoside triphosphates (NTPs) and deoxynucleoside triphosphates (dNTPs) as substrates. The Msm0858 structure comprises (i) an N-terminal domain (amino acids [aa] 17 to 201) composed of two β-barrel modules and (ii) two AAA domains, D1 (aa 212 to 473) and D2 (aa 476 to 744), each of which has ADP in the active site. Msm0858-ADP is a monomer in solution and in crystallized form. Msm0858 domains are structurally homologous to the corresponding modules of mammalian p97. However, the position of the N-domain modules relative to the AAA domains in the Msm0858-ADP tertiary structure is different and would impede the formation of a p97-like hexameric quaternary structure. Mutational analysis of the A-box and B-box motifs indicated that the D1 and D2 AAA domains are both capable of ATP hydrolysis. Simultaneous mutations of the D1 and D2 active-site motifs were required to abolish ATPase activity. ATPase activity was effaced by mutation of the putative D2 arginine finger, suggesting that Msm0858 might oligomerize during the ATPase reaction cycle. A truncated variant Msm0858 (aa 212 to 745) that lacks the N domain was characterized as a catalytically active homodimer.

IMPORTANCE
Recent studies have underscored the importance of AAA proteins (ATPases associated with various cellular activities) in the physiology of mycobacteria. This study reports the ATPase activity and crystal structure of a previously uncharacterized mycobacterial AAA protein, Msm0858. Msm0858 consists of an N-terminal β-barrel domain and two AAA domains, each with ADP bound in the active site. Msm0858 is a structural homolog of mammalian p97, with respect to the linear order and tertiary structures of their domains.
Acupuncture for Patients with Lumbar Spinal Stenosis: A Randomised Pilot Trial
Authors: Kim Kun Hyung , Kim Yu Ri , Baik Seung Kug , Noh Seung Hee , Kim Dae Hun , Lee Sang Weon , Yang Gi Young
Published: March 2016

Objective

To assess the safety and feasibility of acupuncture for participants with symptomatic lumbar spinal stenosis (LSS) in a pilot study.

Methods

50 participants with a clinical and radiological diagnosis of LSS were randomised to receive acupuncture combined with usual care (acupuncture group), or usual care alone (control group). Participants in the acupuncture group were offered 12–16 sessions of manual acupuncture±electroacupuncture over 6 weeks and maintained their usual self-management. The control group was provided with physical therapy as required and maintained their usual self-management. The primary outcome was the change in back-specific functional status, as measured by the Oswestry disability index (ODI) at the 3-month follow-up. Secondary outcomes included symptoms and other relevant domains. Outcome assessors were not blinded.

Results

39 participants (78%) completed the trial with 524 treatment visits. There were no significant differences between the two groups in back-specific function (ODI: mean difference −2.5, 95% CI −8.9 to 3.8). Pain in the back and/or leg showed small improvements at 3 months, while there were no significant differences in other secondary outcomes. The total number of adverse events was 61 (12% of 524 treatment visits). All but one were minor and transient. The one severe adverse event was deemed to be unrelated to acupuncture.

Conclusions

The study was feasible. Acupuncture combined with usual care did not confer significant functional improvements over usual care alone. Further randomised trials with adequate sample sizes and outcome assessor blinding are warranted to evaluate the role of acupuncture for LSS.

Trial Registration Number

NCT01987622.
Is it taking longer to die in paediatric intensive care in England and Wales?
Authors: Plunkett Adrian , Parslow Roger C
Published: March 2016

Introduction

All-cause infant and childhood mortality has decreased in the UK over the last 30 years. Advances in paediatric critical care have increased survival in paediatric intensive care units (PICUs) but may have affected how and when children die in PICU. We explored factors affecting length of stay (LOS) of children who died in PICU over an 11-year period.

Methods

We analysed demographic and clinical data of 165 473 admissions to PICUs in England and Wales, from January 2003 to December 2013. We assessed time trends in LOS for survivors and non-survivors and explored the effect of demographic and clinical characteristics on LOS for non-survivors.

Results

LOS increased 0.310 days per year in non-survivors (95% CI 0.169 to 0.449) and 0.064 days per year in survivors (95% CI 0.046 to 0.083). The proportion of early deaths (<24 h of admission) fell 0.44% points per year (95% CI −0.971 to 0.094), but the proportion of late deaths (>28 days of PICU stay) increased by 0.44% points per year (95% CI 0.185 to 0.691). The paediatric index of mortality score in early deaths increased by 0.77% points per year (95% CI 0.31% to 1.23%).

Discussion

Increased LOS in children who die in PICU is driven by a decreased proportion of early deaths and an increased proportion of late deaths. This trend, combined with an increase in the severity of illness in early deaths, is consistent with a reduction in early mortality for acutely ill children, but a prolongation of life for those children admitted to PICU with life-limiting illnesses.
Metastatic pancreatic cancer presenting as linitis plastica of the stomach
Authors: Garg Shivani , Mulki Ramzi , Sher Daniel
Published: March 2016

Metastatic disease from pancreatic carcinoma involving the stomach is an unusual event, and the pattern of spread in the form of linitis plastica, to our knowledge, has not been reported previously. Local recurrence after curative resection for pancreatic cancer is the most common pattern of disease. We report a case of metastatic pancreatic adenocarcinoma presenting as linitis plastica of the stomach 4 years after curative resection. A 52-year-old man presented with epigastric pain and melaena 4 years after undergoing a Whipple's procedure for a poorly-differentiated pancreatic adenocarcinoma, stage IB; T2N0M0. CT imaging of the abdomen revealed thickening of the gastric wall, and subsequent oesophagogastroduodenoscopy (OGD) revealed diffuse friable erythaematous tissue. The biopsy specimen obtained during the OGD revealed a poorly differentiated adenocarcinoma, with similar appearance to the prior specimen obtained from the pancreas.
Gender-informed, psychoeducational programme for couples to prevent postnatal common mental disorders among primiparous women: cluster randomised controlled trial
Authors: Fisher Jane , Rowe Heather , Wynter Karen , Tran Thach , Lorgelly Paula , Amir Lisa H , Proimos Jenny , Ranasinha Sanjeeva , Hiscock Harriet , Bayer Jordana , Cann Warren
Published: March 2016

Objectives

Interventions to prevent postpartum common mental disorders (PCMD) among unselected populations of women have had limited success. The aim was to determine whether What Were We Thinking (WWWT) a gender-informed, psychoeducational programme for couples and babies can prevent PCMD among primiparous women 6 months postpartum.

Design

Cluster-randomised controlled trial.

Setting

48 Maternal and Child Health Centres (MCHCs) from 6 Local Government Areas in Melbourne, Australia were allocated randomly to usual care (24) or usual care plus WWWT (24).

Participants

English-speaking primiparous women receiving primary care at trial MCHCs were recruited to the intervention (204) and control (196) conditions. Of these, 187 (91.7%) and 177 (90.3%) provided complete data.

Intervention

WWWT is a manualised programme comprising primary care from a trained nurse, print materials and a face-to-face seminar.

Main outcome measures

Data sources were standardised and study-specific measures collected in blinded computer-assisted telephone interviews at 6 and 26 weeks postpartum. The primary outcome was PCMD assessed by Composite International Diagnostic Interviews and Patient Health Questionnaire (PHQ) Depression and Generalised Anxiety Disorder modules.

Results

In intention-to-treat analyses the adjusted OR (AOR) of PCMD in the intervention compared to the usual care group was 0.78 (95% CI 0.38 to 1.63, ns), but mild to moderate anxiety symptoms (AOR 0.58, 95% CI 0.35 to 0.97) and poor self-rated health (AOR 0.46, 95% CI 0.22 to 0.97) were significantly lower. In a per protocol analysis, comparing the full (three component) intervention and usual care groups, the AOR of PCMD was 0.36, (95% CI 0.14 to 0.95). The WWWT seminar was appraised as salient, comprehensible and useful by >85% participants. No harms were detected.

Conclusions

WWWT is readily integrated into primary care, enables inclusion of fathers and addresses modifiable risks for PCMD directly. The full intervention appears a promising programme for preventing PCMD, optimising family functioning, and as the first component of a stepped approach to mental healthcare.

Trial registration number

ACTRN12613000506796; Results.
Do patients' disruptive behaviours influence the accuracy of a doctor's diagnosis? A randomised experiment
Authors: Schmidt H G , van Gog Tamara , CE Schuit Stephanie , Van den Berge Kees , LA Van Daele Paul , Bueving Herman , Van der Zee Tim , W Van den Broek Walter , LCM Van Saase Jan , Mamede Sílvia
Published: March 2016

Background

Literature suggests that patients who display disruptive behaviours in the consulting room fuel negative emotions in doctors. These emotions, in turn, are said to cause diagnostic errors. Evidence substantiating this claim is however lacking. The purpose of the present experiment was to study the effect of such difficult patients’ behaviours on doctors’ diagnostic performance.

Methods

We created six vignettes in which patients were depicted as difficult (displaying distressing behaviours) or neutral. Three clinical cases were deemed to be diagnostically simple and three deemed diagnostically complex. Sixty-three family practice residents were asked to evaluate the vignettes and make the patient's diagnosis quickly and then through deliberate reflection. In addition, amount of time needed to arrive at a diagnosis was measured. Finally, the participants rated the patient's likability.

Results

Mean diagnostic accuracy scores (range 0–1) were significantly lower for difficult than for neutral patients (0.54 vs 0.64; p=0.017). Overall diagnostic accuracy was higher for simple than for complex cases. Deliberate reflection upon the case improved initial diagnostic, regardless of case complexity and of patient behaviours (0.60 vs 0.68, p=0.002). Amount of time needed to diagnose the case was similar regardless of the patient's behaviour. Finally, average likability ratings were lower for difficult than for neutral-patient cases.

Conclusions

Disruptive behaviours displayed by patients seem to induce doctors to make diagnostic errors. Interestingly, the confrontation with difficult patients does however not cause the doctor to spend less time on such case. Time can therefore not be considered an intermediary between the way the patient is perceived, his or her likability and diagnostic performance.
Blood alcohol and injury in Bhutan: targeted surveillance in a national referral hospital emergency department
Authors: Dorji Gampo , Pradhan Sona , Tenzin Tashi , Miller Peter , Connor Jennie , Kypri Kypros
Published: March 2016

Bhutan is a low-middle-income country with poor roads, rapidly increasing motor vehicle use and heavy alcohol consumption. We estimated the proportion of emergency department patients presenting with injury who had positive blood alcohol. We sought to breathalyse and interview all adult patients (≥18 years) presenting with injury at the Jigme Dorji Wangchuck National Referral Hospital in the capital city Thimphu, from April to October 2015. Breath tests and interviews were conducted with 339 (91%) of 374 eligible adult patients. A third (34%) were alcohol-positive and 22% had blood alcohol concentrations >0.08 g/dL. The highest alcohol-positive fractions were for assault (71%), falls (31%) and traffic crashes (30%). Over a third (36%) of patients had a delay of >2 h between injury and breath test. The results underestimate blood alcohol concentrations at the time of injury so the true prevalence of pre-injury alcohol impairment is greater than our estimates suggest. Countermeasures are urgently needed, particularly roadside random breath testing and alcohol controls.
Kinetics of versican-expressing macrophages in bone marrow after cord blood stem cell transplantation for treatment of acute myelogenous leukaemia
Authors: Senda Miho , Fukuyama Ryuichi , Nagasaka Tetsuro
Published: March 2016

Aims

To determine versican-producing cells in normocellular bone marrow and to evaluate chronological alteration in the number of versican-producing macrophages in bone marrow of patients with acute myelogenous leukaemia (AML) after cord blood stem cell transplantation (CBSCT) to gain insight in the significance of versican in recovery of haematopoiesis.

Methods

We enrolled seven age-matched unrelated patients with normocellular bone marrow for determining versican-producing cells in bone marrow, CBSCT-treated patients with AML, 18 with fine and other four with poor engraftment, for determining chronological alteration of versican-expressing and CD68-expressing cells in transplanted bone marrow in reference to the total cells. Clot samples of patients with AML were collected from the +16 to +55 day after transplantation and separated into four groups. We included an AML case whose specimen was obtained on the +9 day. Cells positive in immunohistochemistry using antibodies to versican and CD68 were counted to obtain the mean±SD in a unit area of the bone marrow, plotted chronologically and compared with the numbers from the age-matched normocellular group.

Results

We determined by a double immunohistochemistry that the versican-expressing cells in bone marrow are macrophages. The time-course curve demonstrated an inverse relationship between the versican-positive macrophages and the total cells in the transplanted bone marrow for over 55 days. In bone marrow of poor engraftment cases, versican-positive macrophages appeared to be decreased in comparison with age-matched and sampling day-matched patients.

Conclusions

These results suggest that versican and/or versican-expressing macrophages positively contribute to bone marrow regeneration of patients with AML after CBSCT.
Stent-assisted coiling versus coiling alone of poor-grade ruptured intracranial aneurysms: a multicenter study
Authors: Zhao Bing , Tan Xianxi , Yang Hua , Zheng Kuang , Li Zequn , Xiong Ye , Zhong Ming
Published: March 2016

Introduction

Endovascular coiling is a valid treatment option for poor-grade ruptured aneurysms. However, little is known about stent-assisted coiling of poor-grade aneurysms.

Objective

To compare the safety and efficacy of stent-assisted coiling with coiling alone for poor-grade aneurysms.

Methods

Using multicenter data on poor-grade aneurysms, we performed a retrospective analysis of 131 consecutive patients treated with endovascular coiling within 14 days after ictus. Patients were split into two groups: stent-assisted coiling and coiling alone. Baseline characteristics, immediate angiographic results, perioperative complications, and clinical outcomes were compared between the two groups.

Results

Twenty-three (17.6%) patients were treated with stent-assisted coiling and 108 (82.4%) with coiling alone. There were no statistically significant differences in patient age, sex, clinical grade, Fisher grade, modified Fisher grade, aneurysm location, and size between the stent-assisted coiling and coiling alone groups. Intraprocedural aneurysm rupture, procedure-related ischemic complication, external ventricular drainage-related hemorrhagic complication, and symptomatic vasospasm did not differ between the two groups. Immediate angiographic results and clinical outcomes at discharge and at 6 and 12 months did not differ between the groups. Aneurysm rebleeding occurred in 4 (17.4%) patients after stent-assisted coiling compared with 2 (1.9%) patients after coiling alone (p<0.007). Multivariate analysis showed that incomplete aneurysm occlusion was independently associated with aneurysm rebleeding (p=0.016), and there was a trend toward aneurysm rebleeding after stent-assisted coiling (p=0.051).

Conclusions

Stent-assisted coiling of poor-grade aneurysms is feasible and safe compared with coiling alone. However, the hemorrhagic complication and aneurysm rebleeding may not be negligible.
Trial protocol for a randomised controlled trial of red cell washing for the attenuation of transfusion-associated organ injury in cardiac surgery: the REDWASH trial
Authors: Murphy G J , Verheyden V , Wozniak M , Sullo N , Dott W , Bhudia S , Bittar N , Morris T , Ring A , Tebbatt A , Kumar T
Published: March 2016

Introduction

It has been suggested that removal of proinflammatory substances that accumulate in stored donor red cells by mechanical cell washing may attenuate inflammation and organ injury in transfused cardiac surgery patients. This trial will test the hypotheses that the severity of the postoperative inflammatory response will be less and postoperative recovery faster if patients undergoing cardiac surgery receive washed red cells compared with standard care (unwashed red cells).

Methods and analysis

Adult (≥16 years) cardiac surgery patients identified at being at increased risk for receiving large volume red cell transfusions at 1 of 3 UK cardiac centres will be randomly allocated in a 1:1 ratio to either red cell washing or standard care. The primary outcome is serum interleukin-8 measured at 5 postsurgery time points up to 96 h. Secondary outcomes will include measures of inflammation, organ injury and volumes of blood transfused and cost-effectiveness. Allocation concealment, internet-based randomisation stratified by operation type and recruiting centre, and blinding of outcome assessors will reduce the risk of bias. The trial will test the superiority of red cell washing versus standard care. A sample size of 170 patients was chosen in order to detect a small-to-moderate target difference, with 80% power and 5% significance (2-tailed).

Ethics and dissemination

The trial protocol was approved by a UK ethics committee (reference 12/EM/0475). The trial findings will be disseminated in scientific journals and meetings.

Trial registration number

ISRCTN 27076315.
Physiological and performance consequences of heavy thoracic load carriage in females
Authors: Phillips Devin B. , Stickland Michael K. , Petersen Stewart R.
Published: March 2016

The purposes of this experiment were to study physiological responses to graded exercise to exhaustion (Part I) and ventilatory responses during 45 min of exercise (Part II) with and without a 25-kg backpack. In Part I, on separate days, 24 females completed randomly ordered modified Balke treadmill tests. Analysis revealed significant decreases in absolute peak oxygen uptake (3.5%), peak power output (20%), and test duration (40%) under load. There was a significant but modest negative relationship between body mass and the change in test duration between conditions (r = –0.44). While physiological responses to peak exercise were similar, exercise performance was negatively impacted under load. On separate days in Part II, 14 females completed randomly ordered, loaded and unloaded exercise challenges of submaximal treadmill walking at matched oxygen demands. Under load, breathing frequency, dead space, and minute ventilation were increased by 19.9%, 29.8%, and 11.6% (P < 0.05), respectively, while tidal volume and end-inspiratory lung volume decreased by 13.6% and 6.0% (P < 0.05), respectively. After loaded exercise, maximal inspiratory pressure was decreased by 11.5% (P < 0.05) with no changes in maximal expiratory pressure in either condition. Despite matched oxygen uptake between loaded and unloaded exercise challenges, perceived exertion and breathing discomfort were higher (P < 0.05) under load. With heavy load carriage, the altered breathing pattern led to increased dead space and minute ventilation, which likely contributed to higher perceptions of exercise stress and breathing discomfort. These results are similar to previous research in males and underscore the impact of heavy load carriage during exercise.
Quons in a quantum dissipative system
Authors: Lee Taejin
Published: March 2016

String theory proves to be an imperative tool to explore the critical behavior of the quantum dissipative system. We discuss the quantum particles moving in two dimensions, in the presence of a uniform magnetic field, subject to a periodic potential and a dissipative force, which are described by the dissipative Wannier–Azbel–Hofstadter (DWAH) model. Using string theory formulation of the model, we find that the elementary excitations of the system at the generic points of the off-critical regions, in the zero temperature limit are quons, which satisfy [Formula: see text]-deformed statistics.
Estimating the optimal number of communities by cluster analysis
Authors: Liu Dong , Wang Chuan , Jing Yun
Published: March 2016

How to identify community structure in complex network is of theoretical significance, which relates to help to analyze the network topology and understand the network works. Determining the optimal number of communities is a nontrivial problem in detecting community structure. In this paper, we propose a novel method for detecting the optimal number of communities. Based on the local random walk (LRW) measurement, the distance index between each pair of nodes of a network is calculated firstly. Then the optimal number of communities can be found based on the idea that community centers are characterized by a higher density than their neighbors and by a relatively large distance from nodes with higher densities. The experimental results show that the method is effective and efficient in both artificial and real-world networks.
Tripod and Lambda configurations in simulation of gauge potentials for ultracold atoms
Authors: Ye Ming-Yong , Lin Xiu-Min
Published: March 2016

It is known that gauge potentials/spin-orbit couplings can be simulated for ultracold atoms through their interaction with laser fields. Tripod and Lambda [Formula: see text] are two typical configurations of atom–field interaction in the simulations. We find that there is a similarity between the two configurations if we parametrize Rabi frequencies properly. Based on the similarity, we can transform a gauge potential/spin-orbit coupling simulation scheme in the tripod configuration into a scheme in the [Formula: see text] configuration.
Foraging efficiency of a predator flock for randomly moving prey: A simulation study
Authors: Lee Sang-Hee , Kwon Ohsung
Published: March 2016

Flocking behavior of animals is highly advantageous for taking food resources. The degree of the advantage is related to the ability of flock members to detect their prey and the mobility of prey individuals. In this study, to explore the relation, we constructed a model to simulate a predator flock and its randomly moving prey. The predator members have the prey detection ability, which was characterized as sensing distance, [Formula: see text], and a sensing angle, [Formula: see text]. The mobility of the prey individuals was characterized as the maximum traveling distance of an iteration time step, [Formula: see text]. The relative flock foraging efficiency, [Formula: see text], was defined as [Formula: see text]. [Formula: see text] and [Formula: see text] represent the spent time for the flock to eat all prey individuals and to uptake the last remaining 10% prey, respectively. Simulation results showed that [Formula: see text] increased, maximized, and decreased with the increase of [Formula: see text], regardless of [Formula: see text]. As the number of prey, [Formula: see text], increased, the tendency of the increasing and decreasing was diluted. The result was briefly discussed in relation to the flock foraging behavior and the development of the model toward applications for real ecosystems.
Low-Power Code Memory Integrity Verification Using Background Cyclic Redundancy Check Calculator Based on Binary Code Inversion Method
Authors: Park Daejin
Published: March 2016

The integrity verification of on-chip flash memory data as code memory is becoming important in microcontroller-based applications such as automotive systems. On-the-fly memory fail-detection requires a fast detection method in the seamless background mode without any interruption of CPU operation and low-power flash access hardware to provide safety-conscious execution of the user-programmed firmware during system operations. In this paper, newly-designed read-path architecture based on the binary inversion techniques is proposed for on-chip flash-embedded microcontrollers. The proposed binary inversion method also enables fail-safe, low-power memory access with zero hardware overhead by embedding the scramble flags on the cyclic redundancy check (CRC) protection code. Time-multiplexed CRC calculation for bit-inversion binary code is automatically executed with the silent background mode during CPU idle time without any CPU wait cost. The implementation result shows that the de-inversion procedure could be achieved with just an additional 1,024 bits CRC data in the case of 64 sectors for 4 KB flash memory by reducing 75% of the area of the previous work. The code memory integrity verification time in the seamless background mode is about 30% of the conventional foreground method. The total average current during the code execution for DhrystoneTM benchmark uses just 15% of the basement.
Higher Order Two-Point Efficient Family of Halley Type Methods for Simple Roots
Authors: Behl Ramandeep , Motsa S. S.
Published: March 2016

In this paper, we proposed a new highly efficient two-point sixth-order family of Halley type methods that do not require any second-order derivative evaluation for obtaining simple roots of nonlinear equations, numerically. In terms of computational cost, each member of the family requires two-function and two first-order derivative evaluations per iteration. On the account of the results obtained, it is found that our proposed methods are efficient and show better performance than existing sixth-order methods available in the literature. Further, it is also noted that larger basins of attraction belong to our methods as compared to the existing ones. On the other hand, the existing methods are slower and have darker basins while some of them are too sensitive upon the choice of the initial value.
Parallelizing the Chambolle Algorithm for Performance-Optimized Mapping on FPGA Devices
Authors: Beretta Ivan , Rana Vincenzo , Akin Abdulkadir , Nacci Alessandro Antonio , Sciuto Donatella , Atienza David
Published: March 2016

The performance and the efficiency of recent computing platforms have been deeply influenced by the widespread adoption of hardware accelerators, such as graphics processing units (GPUs) or field-programmable gate arrays (FPGAs), which are often employed to support the tasks of general-purpose processors (GPPs). One of the main advantages of these accelerators over their sequential counterparts (GPPs) is their ability to perform massive parallel computation. However, to exploit this competitive edge, it is necessary to extract the parallelism from the target algorithm to be executed, which generally is a very challenging task.

This concept is demonstrated, for instance, by the poor performance achieved on relevant multimedia algorithms, such as Chambolle, which is a well-known algorithm employed for the optical flow estimation. The implementations of this algorithm that can be found in the state of the art are generally based on GPUs but barely improve the performance that can be obtained with a powerful GPP. In this article, we propose a novel approach to extract the parallelism from computation-intensive multimedia algorithms, which includes an analysis of their dependency schema and an assessment of their data reuse. We then perform a thorough analysis of the Chambolle algorithm, providing a formal proof of its inner data dependencies and locality properties. Then, we exploit the considerations drawn from this analysis by proposing an architectural template that takes advantage of the fine-grained parallelism of FPGA devices. Moreover, since the proposed template can be instantiated with different parameters, we also propose a design metric, the expansion rate, to help the designer in the estimation of the efficiency and performance of the different instances, making it possible to select the right one before the implementation phase. We finally show, by means of experimental results, how the proposed analysis and parallelization approach leads to the design of efficient and high-performance FPGA-based implementations that are orders of magnitude faster than the state-of-the-art ones.