bluuebunny/crossref_metadata_2025 huggingface dataset:
Novel Approach To Optimize Synergistic Carbapenem-Aminoglycoside Combinations against Carbapenem-Resistant Acinetobacter baumannii
Authors: Yadav Rajbharan , Landersdorfer Cornelia B. , Nation Roger L. , Boyce John D. , Bulitta Jürgen B.
Published: February 2015

Acinetobacter baumannii
is among the most dangerous pathogens and emergence of resistance is highly problematic. Our objective was to identify and rationally optimize β-lactam-plus-aminoglycoside combinations via novel mechanism-based modeling that synergistically kill and prevent resistance of carbapenem-resistant
A. baumannii
. We studied combinations of 10 β-lactams and three aminoglycosides against four
A. baumannii
strains, including two imipenem-intermediate (MIC, 4 mg/liter) and one imipenem-resistant (MIC, 32 mg/liter) clinical isolate, using high-inoculum static-concentration time-kill studies. We present the first application of mechanism-based modeling for killing and resistance of
A. baumannii
using Monte Carlo simulations of human pharmacokinetics to rationally optimize combination dosage regimens for immunocompromised, critically ill patients. All monotherapies achieved limited killing (≤2.3 log
10
) of
A. baumannii
ATCC 19606 followed by extensive regrowth for aminoglycosides. Against this strain, imipenem-plus-aminoglycoside combinations yielded more rapid and extensive killing than other β-lactam-plus-aminoglycoside combinations. Imipenem at 8 mg/liter combined with an aminoglycoside yielded synergistic killing (>5 log
10
) and prevented regrowth of all four strains. Modeling demonstrated that imipenem likely killed the aminoglycoside-resistant population and vice versa and that aminoglycosides enhanced the target site penetration of imipenem. Against carbapenem-resistant
A. baumannii
(MIC, 32 mg/liter), optimized combination regimens (imipenem at 4 g/day as a continuous infusion plus tobramycin at 7 mg/kg of body weight every 24 h) were predicted to achieve >5 log
10
killing without regrowth in 98.2% of patients. Bacterial killing and suppression of regrowth were best achieved for combination regimens with unbound imipenem steady-state concentrations of at least 8 mg/liter. Imipenem-plus-aminoglycoside combination regimens are highly promising and warrant further evaluation.
Pyridodiazepine Amines Are Selective Therapeutic Agents for Helicobacter pylori by Suppressing Growth through Inhibition of Glutamate Racemase but Are Predicted To Require Continuous Elevated Levels in Plasma To Achieve Clinical Efficacy
Authors: de Jonge Boudewijn L. M. , Kutschke Amy , Newman Joseph V. , Rooney Michael T. , Yang Wei , Cederberg Christer
Published: February 2015

A pyridodiazepine amine inhibitor of
Helicobacter pylori
glutamate racemase (MurI) was characterized. The compound was selectively active against
H. pylori
, and growth suppression was shown to be mediated through the inhibition of MurI by several methods. In killing kinetics experiments, the compound showed concentration-independent activity, with about a 2-log loss of viability in 24 h. A demonstration of efficacy in a mouse infection model was attempted but not achieved, and this was attributed to the failure to attain extended exposure levels above the MIC for >95% of the time. This index and magnitude were derived from pharmacokinetic-pharmacodynamic (PK-PD) studies with amoxicillin, another inhibitor of peptidoglycan biosynthesis that showed slow killing kinetics similar to those of the pyridodiazepine amines. These studies indicate that MurI and other enzymes involved in peptidoglycan biosynthesis may be less desirable targets for monotherapy directed against
H. pylori
if once-a-day dosing is required.
Propensity-Matched Analysis To Compare the Therapeutic Efficacies of Cefuroxime versus Cefotaxime as Initial Antimicrobial Therapy for Community-Onset Complicated Nonobstructive Acute Pyelonephritis Due to Enterobacteriaceae Infection in Women
Authors: Chang U-Im , Kim Hyung Wook , Wie Seong-Heon
Published: February 2015

This study was performed to compare the therapeutic efficacy of cefuroxime with that of cefotaxime as initial antimicrobial therapies in women with complicated nonobstructive acute pyelonephritis (APN) caused by
Enterobacteriaceae
infections. The clinical characteristics and outcomes of a cefuroxime-treated group (
n
= 156) were compared with those of a cefotaxime-treated group (
n
= 166). Of these 322 women, 90 from each group were matched by propensity scores. The defervescence rates were not significantly different in the cefuroxime and cefotaxime groups at 72 h after the start of antimicrobial therapy (81.1% versus 78.9%,
P
= 0.709). The clinical and microbiological cure rates during the follow-up visits that were 4 to 14 days after the end of the antimicrobial therapies were not significantly different in the cefuroxime versus cefotaxime groups, which were 97.8% (87/89) versus 97.8% (87/89) (
P
> 0.999) and 89.5% (68/76) versus 90.7% (68/75) (
P
= 0.807), respectively. The median hospital stay duration and the median times to defervescence in the cefuroxime versus cefotaxime groups were 8 days (interquartile range [IQR], 7 to 10 days) versus 9 days (IQR, 7 to 11 days), respectively, and 55 h (IQR, 37 to 70 h) versus 55 h (IQR, 35 to 69 h), respectively. Bacteremia, extended-spectrum-β-lactamase-producing
Enterobacteriaceae
, C-reactive protein levels of ≥15 mg/dl, and white blood cell counts of ≥15,000/mm
3
of blood had independent effects on the rates of early clinical failure. Our data suggest that the effects of cefuroxime are not different from those of cefotaxime when they are used as an initial antimicrobial treatments for community-onset complicated nonobstructive APN in women.
Efficacy of ETI-204 Monoclonal Antibody as an Adjunct Therapy in a New Zealand White Rabbit Partial Survival Model for Inhalational Anthrax
Authors: Biron Bethany , Beck Katie , Dyer David , Mattix Marc , Twenhafel Nancy , Nalca Aysegul
Published: February 2015

Inhalational anthrax is characterized by extensive bacteremia and toxemia as well as nonspecific to mild flu-like symptoms, until the onset of hypotension, shock, and mortality. Without treatment, the mortality rate approaches 100%. Antibiotic treatment is not always effective, and alternative treatments are needed, such as monotherapy for antibiotic-resistant inhalational anthrax or as an adjunct therapy in combination with antibiotics. The
Bacillus anthracis
antitoxin monoclonal antibody (MAb) ETI-204 is a high-affinity chimeric deimmunized antibody which targets the anthrax toxin protective antigen (PA). In this study, a partial protection New Zealand White (NZW) rabbit model was used to evaluate the protective efficacy of the adjunct therapy with the MAb. Following detection of PA in the blood, NZW rabbits were administered either an antibiotic (doxycycline) alone or the antibiotic in conjunction with ETI-204. Survival was evaluated to compare the efficacy of the combination adjunct therapy with that of an antibiotic alone in treating inhalational anthrax. Overall, the results from this study indicate that a subtherapeutic regimen consisting of an antibiotic in combination with an anti-PA MAb results in increased survival compared to the antibiotic alone and would provide an effective therapeutic strategy against symptomatic anthrax in nonvaccinated individuals.
Ceftaroline Activity against Bacterial Pathogens Frequently Isolated in U.S. Medical Centers: Results from Five Years of the AWARE Surveillance Program
Authors: Sader Helio S. , Flamm Robert K. , Streit Jennifer M. , Farrell David J. , Jones Ronald N.
Published: February 2015

A total of 84,704 isolates were collected from 191 medical centers in 2009 to 2013 and tested for susceptibility to ceftaroline and comparator agents by broth microdilution methods. Ceftaroline inhibited all
Staphylococcus aureus
isolates at ≤2 μg/ml and was very active against methicillin-resistant strains (MIC at which 90% of the isolates tested are inhibited [MIC
90
], 1 μg/ml; 97.6% susceptible). Among
Streptococcus pneumoniae
isolates, the highest ceftaroline MIC was 0.5 μg/ml, and ceftaroline activity against the most common
Enterobacteriaceae
species (MIC
50
, 0.12 μg/ml; 78.9% susceptible) was similar to that of ceftriaxone (MIC
50
, ≤0.25 μg/ml; 86.8% susceptible).
Pharmacokinetics and Penetration of Ceftazidime and Avibactam into Epithelial Lining Fluid in Thigh- and Lung-Infected Mice
Authors: Berkhout Johanna , Melchers Maria J. , van Mil Anita C. , Seyedmousavi Seyedmojtaba , Lagarde Claudia M. , Nichols Wright W. , Mouton Johan W.
Published: February 2015

Ceftazidime and the β-lactamase inhibitor avibactam constitute a new, potentially highly active combination in the battle against extended-spectrum-β-lactamase (ESBL)-producing bacteria. To determine possible clinical use, it is important to know the pharmacokinetic profiles of the compounds related to each other in plasma and the different compartments of infection in experimentally infected animals and in humans. We used a neutropenic murine thigh infection model and lung infection model to study pharmacokinetics in plasma and epithelial lining fluid (ELF). Mice were infected with ca. 10
6
CFU of
Pseudomonas aeruginosa
intramuscularly into the thigh or intranasally to cause pneumonia and were given 8 different (single) subcutaneous doses of ceftazidime and avibactam in various combined concentrations, ranging from 1 to 128 mg/kg of body weight in 2-fold increases. Concomitant samples of serum and bronchoalveolar lavage fluid were taken at up to 12 time points until 6 h after administration. Pharmacokinetics of both compounds were linear and dose proportional in plasma and ELF and were independent of the infection type, with estimated half-lives (standard deviations [SD]) in plasma of ceftazidime of 0.28 (0.02) h and of avibactam of 0.24 (0.04) h and volumes of distribution of 0.80 (0.14) and 1.18 (0.34) liters/kg. The ELF-plasma (area under the concentration-time curve [AUC]) ratios (standard errors [SE]) were 0.24 (0.03) for total ceftazidime and 0.27 (0.03) for unbound ceftazidime; for avibactam, the ratios were 0.20 (0.02) and 0.22 (0.02), respectively. No pharmacokinetic interaction between ceftazidime and avibactam was observed. Ceftazidime and avibactam showed linear plasma pharmacokinetics that were independent of the dose combinations used or the infection site in mice. Assuming pharmacokinetic similarity in humans, this indicates that similar dose ratios of ceftazidime and avibactam could be used for different types and sites of infection.
Candida Infective Endocarditis: an Observational Cohort Study with a Focus on Therapy
Authors: Arnold Christopher J. , Johnson Melissa , Bayer Arnold S. , Bradley Suzanne , Giannitsioti Efthymia , Miró José M. , Tornos Pilar , Tattevin Pierre , Strahilevitz Jacob , Spelman Denis , Athan Eugene , Nacinovich Francisco , Fortes Claudio Q. , Lamas Cristiane , Barsic Bruno , Fernández-Hidalgo Nuria , Muñoz Patricia , Chu Vivian H.
Published: February 2015

Candida
infective endocarditis is a rare disease with a high mortality rate. Our understanding of this infection is derived from case series, case reports, and small prospective cohorts. The purpose of this study was to evaluate the clinical features and use of different antifungal treatment regimens for
Candida
infective endocarditis. This prospective cohort study was based on 70 cases of
Candida
infective endocarditis from the International Collaboration on Endocarditis (ICE)-Prospective Cohort Study and ICE-Plus databases collected between 2000 and 2010. The majority of infections were acquired nosocomially (67%). Congestive heart failure (24%), prosthetic heart valve (46%), and previous infective endocarditis (26%) were common comorbidities. Overall mortality was high, with 36% mortality in the hospital and 59% at 1 year. On univariate analysis, older age, heart failure at baseline, persistent candidemia, nosocomial acquisition, heart failure as a complication, and intracardiac abscess were associated with higher mortality. Mortality was not affected by use of surgical therapy or choice of antifungal agent. A subgroup analysis was performed on 33 patients for whom specific antifungal therapy information was available. In this subgroup, 11 patients received amphotericin B-based therapy and 14 received echinocandin-based therapy. Despite a higher percentage of older patients and nosocomial infection in the echinocandin group, mortality rates were similar between the two groups. In conclusion,
Candida
infective endocarditis is associated with a high mortality rate that was not impacted by choice of antifungal therapy or by adjunctive surgical intervention. Additionally, echinocandin therapy was as effective as amphotericin B-based therapy in the small subgroup analysis.
Antipseudomonal Agents Exhibit Differential Pharmacodynamic Interactions with Human Polymorphonuclear Leukocytes against Established Biofilms of Pseudomonas aeruginosa
Authors: Chatzimoschou Athanasios , Simitsopoulou Maria , Antachopoulos Charalampos , Walsh Thomas J. , Roilides Emmanuel
Published: February 2015

Pseudomonas aeruginosa
is the most common pathogen infecting the lower respiratory tract of cystic fibrosis (CF) patients, where it forms tracheobronchial biofilms.
Pseudomonas
biofilms are refractory to antibacterials and to phagocytic cells with innate immunity, leading to refractory infection. Little is known about the interaction between antipseudomonal agents and phagocytic cells in eradication of
P. aeruginosa
biofilms. Herein, we investigated the capacity of three antipseudomonal agents, amikacin (AMK), ceftazidime (CAZ), and ciprofloxacin (CIP), to interact with human polymorphonuclear leukocytes (PMNs) against biofilms and planktonic cells of
P. aeruginosa
isolates recovered from sputa of CF patients. Three of the isolates were resistant and three were susceptible to each of these antibiotics. The concentrations studied (2, 8, and 32 mg/liter) were subinhibitory for biofilms of resistant isolates, whereas for biofilms of susceptible isolates, they ranged between sub-MIC and 2 × MIC values. The activity of each antibiotic alone or in combination with human PMNs against 48-h mature biofilms or planktonic cells was determined by XTT [2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2
H
-tetrazolium-5-carboxanilide] assay. All combinations of AMK with PMNs resulted in synergistic or additive effects against planktonic cells and biofilms of
P. aeruginosa
isolates compared to each component alone. More than 75% of CAZ combinations exhibited additive interactions against biofilms of
P. aeruginosa
isolates, whereas CIP had mostly antagonistic interaction or no interaction with PMNs against biofilms of
P. aeruginosa
. Our findings demonstrate a greater positive interaction between AMK with PMNs than that observed for CAZ and especially CIP against isolates of
P. aeruginosa
from the respiratory tract of CF patients.
A Novel Antimycobacterial Compound Acts as an Intracellular Iron Chelator
Authors: Dragset Marte S. , Poce Giovanna , Alfonso Salvatore , Padilla-Benavides Teresita , Ioerger Thomas R. , Kaneko Takushi , Sacchettini James C. , Biava Mariangela , Parish Tanya , Argüello José M. , Steigedal Magnus , Rubin Eric J.
Published: February 2015

Efficient iron acquisition is crucial for the pathogenesis of
Mycobacterium tuberculosis
. Mycobacterial iron uptake and metabolism are therefore attractive targets for antitubercular drug development. Resistance mutations against a novel pyrazolopyrimidinone compound (PZP) that is active against
M. tuberculosis
have been identified within the gene cluster encoding the ESX-3 type VII secretion system. ESX-3 is required for mycobacterial iron acquisition through the mycobactin siderophore pathway, which could indicate that PZP restricts mycobacterial growth by targeting ESX-3 and thus iron uptake. Surprisingly, we show that ESX-3 is not the cellular target of the compound. We demonstrate that PZP indeed targets iron metabolism; however, we found that instead of inhibiting uptake of iron, PZP acts as an iron chelator, and we present evidence that the compound restricts mycobacterial growth by chelating intrabacterial iron. Thus, we have unraveled the unexpected mechanism of a novel antimycobacterial compound.
A Novel New Delhi Metallo-β-Lactamase Variant, NDM-14, Isolated in a Chinese Hospital Possesses Increased Enzymatic Activity against Carbapenems
Authors: Zou Dayang , Huang Yong , Zhao Xiangna , Liu Wei , Dong Derong , Li Huan , Wang Xuesong , Huang Simo , Wei Xiao , Yan Xiabei , Yang Zhan , Tong Yigang , Huang Liuyu , Yuan Jing
Published: February 2015

A novel New Delhi metallo-β-lactamase (NDM) variant, NDM-14, was identified in clinical isolate
Acinetobacter lwoffii
JN49-1, which was recovered from an intensive care unit patient at a local hospital in China. NDM-14, which differs from other existing enzymes by an amino acid substitution at position 130 (Asp130Gly), possesses enzymatic activity toward carbapenems that is greater than that of NDM-1. Kinetic data indicate that NDM-14 has a higher affinity for imipenem and meropenem.
The N Terminus of Type III Secretion Needle Protein YscF from Yersinia pestis Functions To Modulate Innate Immune Responses
Authors: Osei-Owusu Patrick , Jessen Condry Danielle L. , Toosky Melody , Roughead William , Bradley David S. , Nilles Matthew L.
Published: February 2015

The type III secretion system is employed by many pathogens, including the genera
Yersinia
,
Shigella
,
Pseudomonas
, and
Salmonella
, to deliver effector proteins into eukaryotic cells. The injectisome needle is formed by the polymerization of a single protein, e.g., YscF (
Yersinia pestis
), PscF (
Pseudomonas aeruginosa
), PrgI (
Salmonella enterica
SPI-1), SsaG (
Salmonella enterica
SPI-2), or MxiH (
Shigella flexneri
). In this study, we demonstrated that the N termini of some needle proteins, particularly the N terminus of YscF from
Yersinia pestis
, influences host immune responses. The N termini of several needle proteins were truncated and tested for the ability to induce inflammatory responses in a human monocytic cell line (THP-1 cells). Truncated needle proteins induced proinflammatory cytokines to different magnitudes than the corresponding wild-type proteins, except SsaG. Notably, N-terminally truncated YscF induced significantly higher activation of NF-κB and/or AP-1 and higher induction of proinflammatory cytokines, suggesting that a function of the N terminus of YscF is interference with host sensing of YscF, consistent with
Y. pestis
pathogenesis. To directly test the ability of the N terminus of YscF to suppress cytokine induction, a YscF-SsaG chimera with 15 N-terminal amino acids from YscF added to SsaG was constructed. The chimeric YscF-SsaG induced lower levels of cytokines than wild-type SsaG. However, the addition of 15 random amino acids to SsaG had no effect on NF-κB/AP-1 activation. These results suggest that the N terminus of YscF can function to decrease cytokine induction, perhaps contributing to a favorable immune environment leading to survival of
Y. pestis
within the eukaryotic host.
The Levels of Brachyspira hyodysenteriae Binding to Porcine Colonic Mucins Differ between Individuals, and Binding Is Increased to Mucins from Infected Pigs with
De Novo
MUC5AC Synthesis
Authors: Quintana-Hayashi Macarena P. , Mahu Maxime , De Pauw Nele , Boyen Filip , Pasmans Frank , Martel An , Premaratne Pushpa , Fernandez Harvey R. , Teymournejad Omid , Vande Maele Lien , Haesebrouck Freddy , Lindén Sara K.
Published: February 2015

Brachyspira hyodysenteriae
colonizes the pig colon, resulting in mucohemorrhagic diarrhea and growth retardation. Fecal mucus is a characteristic feature of swine dysentery; therefore, we investigated how the mucin environment changes in the colon during infection with
B. hyodysenteriae
and how these changes affect this bacterium's interaction with mucins. We isolated and characterized mucins, the main component of mucus, from the colon of experimentally inoculated and control pigs and investigated
B. hyodysenteriae
binding to these mucins. Fluorescence microscopy revealed a massive mucus induction and disorganized mucus structure in the colon of pigs with swine dysentery. Quantitative PCR (qPCR) and antibody detection demonstrated that the mucus composition of pigs with swine dysentery was characterized by
de novo
expression of MUC5AC and increased expression of MUC2 in the colon. Mucins from the colon of inoculated and control pigs were isolated by two steps of isopycnic density gradient centrifugation. The mucin densities of control and inoculated pigs were similar, whereas the mucin quantity was 5-fold higher during infection. The level of
B. hyodysenteriae
binding to mucins differed between pigs, and there was increased binding to soluble mucins isolated from pigs with swine dysentery. The ability of
B. hyodysenteriae
to bind, measured in relation to the total mucin contents of mucus in sick versus healthy pigs, increased 7-fold during infection. Together, the results indicate that
B. hyodysenteriae
binds to carbohydrate structures on the mucins as these differ between individuals. Furthermore,
B. hyodysenteriae
infection induces changes to the mucus niche which substantially increase the amount of
B. hyodysenteriae
binding sites in the mucus.
Aggregatibacter actinomycetemcomitans Cytolethal Distending Toxin Activates the NLRP3 Inflammasome in Human Macrophages, Leading to the Release of Proinflammatory Cytokines
Authors: Shenker Bruce J. , Ojcius David M. , Walker Lisa P. , Zekavat Ali , Scuron Monika Damek , Boesze-Battaglia Kathleen
Published: February 2015

The cytolethal distending toxin (Cdt) is produced from a number of bacteria capable of causing infection and inflammatory disease. Our previous studies withActinobacillus actinomycetemcomitansCdt demonstrate not only that the active toxin subunit functions as a phosphatidylinositol-3,4,5-triphosphate (PIP3) phosphatase but also that macrophages exposed to the toxin were stimulated to produce proinflammatory cytokines. We now demonstrate that the Cdt-induced proinflammatory response involves the activation of the NLRP3 inflammasome. Specific inhibitors and short hairpin RNA (shRNA) were employed to demonstrate requirements for NLRP3 and ASC as well as caspase-1. Furthermore, Cdt-mediated inflammasome activation is dependent upon upstream signals, including reactive oxygen species (ROS) generation and Cdt-induced increases in extracellular ATP levels. Increases in extracellular ATP levels contribute to the activation of the P2X7purinergic receptor, leading to K+efflux. The relationship between the abilities of the active toxin subunit CdtB to function as a lipid phosphatase, activate the NLRP3 inflammasome, and induce a proinflammatory cytokine response is discussed. These studies provide new insight into the virulence potential of Cdt in mediating the pathogenesis of disease caused by Cdt-producing organisms such asAggregatibacter actinomycetemcomitans.
Citrulline Protects Streptococcus pyogenes from Acid Stress Using the Arginine Deiminase Pathway and the F1Fo-ATPase
Authors: Cusumano Zachary T. , Caparon Michael G.
Published: February 2015

A common stress encountered by both pathogenic and environmental bacteria is exposure to a low-pH environment, which can inhibit cell growth and lead to cell death. One major defense mechanism against this stress is the arginine deiminase (ADI) pathway, which catabolizes arginine to generate two ammonia molecules and one molecule of ATP. While this pathway typically relies on the utilization of arginine, citrulline has also been shown to enter into the pathway and contribute to protection against acid stress. In the pathogenic bacteriumStreptococcus pyogenes, the utilization of citrulline has been demonstrated to contribute to pathogenesis in a murine model of soft tissue infection, although the mechanism underlying its role in infection is unknown. To gain insight into this question, we analyzed a panel of mutants defective in different steps in the ADI pathway to dissect how arginine and citrulline protectS. pyogenesin a low-pH environment. While protection provided by arginine utilization occurred through the buffering of the extracellular environment, citrulline catabolism protection was pH independent, requiring the generation of ATP via the ADI pathway and a functional F1Fo-ATP synthase. This work demonstrates that arginine and citrulline catabolism protect against acid stress through distinct mechanisms and have unique contributions to virulence during an infection.

IMPORTANCEAn important aspect of bacterial pathogenesis is the utilization of host-derived nutrients during an infection for growth and virulence. Previously published work from our lab identified a unique role for citrulline catabolism inStreptococcus pyogenesduring a soft tissue infection. The present article probes the role of citrulline utilization during this infection and its contribution to protection against acid stress. This work reveals a unique and concerted action between the catabolism of citrulline and the F1Fo-ATPase that function together to provide protection for bacteria in a low-pH environment. Dissection of these collaborative pathways highlights the complexity of bacterial infections and the contribution of atypical nutrients, such as citrulline, to pathogenesis.
Unidentified undescended testes in teenage boys with severe learning disabilities
Authors: Haire A R , Flavill Jenny , Groom W D , Dhandapani B
Published: February 2015

Nine boys of secondary school age were referred with undescended testes (UDT) to paediatric surgeons over a period of 8 years. All were referred from the same community paediatric clinic for children with severe learning disabilities. UDT cause concern because of a threefold increase in the incidence of cancer. Cosmesis and reduced fertility were seen as less relevant issues for these boys. The late identification and incidence of UDT are discussed. It is suggested that awareness of this issue should be raised and screening introduced. Advice is needed on the appropriate management of UDT in this group of boys.
The impact of economic austerity and prosperity events on suicide in Greece: a 30-year interrupted time-series analysis
Authors: Branas Charles C , Kastanaki Anastasia E , Michalodimitrakis Manolis , Tzougas John , Kranioti Elena F , Theodorakis Pavlos N , Carr Brendan G , Wiebe Douglas J
Published: February 2015

Objectives

To complete a 30-year interrupted time-series analysis of the impact of austerity-related and prosperity-related events on the occurrence of suicide across Greece.

Setting

Greece from 1 January 1983 to 31 December 2012.

Participants

A total of 11 505 suicides, 9079 by men and 2426 by women, occurring in Greece over the study period.

Primary and secondary outcomes

National data from the Hellenic Statistical Authority assembled as 360 monthly counts of: all suicides, male suicides, female suicides and all suicides plus potentially misclassified suicides.

Results

In 30 years, the highest months of suicide in Greece occurred in 2012. The passage of new austerity measures in June 2011 marked the beginning of significant, abrupt and sustained increases in total suicides (+35.7%, p<0.001) and male suicides (+18.5%, p<0.01). Sensitivity analyses that figured in undercounting of suicides also found a significant, abrupt and sustained increase in June 2011 (+20.5%, p<0.001). Suicides by men in Greece also underwent a significant, abrupt and sustained increase in October 2008 when the Greek recession began (+13.1%, p<0.01), and an abrupt but temporary increase in April 2012 following a public suicide committed in response to austerity conditions (+29.7%, p<0.05). Suicides by women in Greece also underwent an abrupt and sustained increase in May 2011 following austerity-related events (+35.8%, p<0.05). One prosperity-related event, the January 2002 launch of the Euro in Greece, marked an abrupt but temporary decrease in male suicides (−27.1%, p<0.05).

Conclusions

This is the first multidecade, national analysis of suicide in Greece using monthly data. Select austerity-related events in Greece corresponded to statistically significant increases for suicides overall, as well as for suicides among men and women. The consideration of future austerity measures should give greater weight to the unintended mental health consequences that may follow and the public messaging of these policies and related events.
A survey of major trauma centre staffing in England
Authors: Jansen Jan O , Morrison J J , Tai N R M , Midwinter M J
Published: February 2015

Introduction

Trauma care delivery in England has been transformed by the development of trauma networks, and the designation of trauma centres. A specialist trauma service is a key component of such centres. The aim of this survey was to determine to which extent, and how, the new major trauma centres (MTCs) have been able to implement such services.

Methods

Electronic questionnaire survey of MTCs in England.

Results

All 22 MTCs submitted responses. Thirteen centres have a dedicated major trauma service or trauma surgery service, and a further four are currently developing such a service. In 7 of these 17 centres, the service is or will be provided by orthopaedic surgeons, in 2 by emergency medicine departments, in another 2 by general or vascular surgeons, and in 6 by a multidisciplinary group of consultants.

Discussion

A large proportion of MTCs still do not have a dedicated major trauma service. Furthermore, the models which are emerging differ from other countries. The relative lack of involvement of surgeons in MTC trauma service provision is particularly noteworthy, and a potential concern. The impact of these different models of service delivery is not known, and warrants further study.
Heterotopic ossification in victims of the London 7/7 bombings
Authors: Edwards D S , Clasper J C , Patel H D L
Published: February 2015

Heterotopic ossification (HO) is the formation of bone at extraskeletal sites. Over 60% of amputees injured by improvised explosive devices in the recent conflict in Afghanistan have developed HO, resulting in functional impairment. It is hypothesised that a key aetiological factor is the blast wave; however, other environmental and medical risk factors, which the casualties have been exposed to, have also been postulated. The suicide terrorist bombings in London in 2005 resulted in many blast-related casualties, many of whom were managed by the Royal London Hospital. This cohort of severely injured patients whose injuries also included trauma-related amputations shared some, but not all, of the risk factors identified in the military population. We reviewed these patients, in particular to assess the presence or absence of military-established risk factors for the formation of HO in these casualties.
Education and Ebola: initiating the cascade of emergency healthcare training
Authors: Eardley Will , Bowley D , Hunt P , Round J , Tarmey N , Williams A
Published: February 2015

In response to the 2014 Ebola virus outbreak in West Africa, the UK deployed a Joint Inter-Agency Task Force to Sierra Leone. As well as constructing Ebola treatment units, the force supported a rapidly upscaled mass programme of training for host nation healthcare workers in basic knowledge of Ebola and personal protective equipment. A bespoke training course was developed in collaboration with the WHO and other partners over a period of 2 weeks, taught to 119 trainers the following week, and then cascaded to over 4000 Ebola workers over the following month. This article describes curriculum design, content delivery and assessment of this unique Training The Trainers course delivered in austere circumstances. Key learning points are highlighted andsupplementary materialis provided to inform future deployed clinical education initiatives.
The case for a milestone-based simulation curriculum in modern neuroendovascular training
Authors: Spiotta Alejandro M , Turner Raymond D , Turk Aquilla S , Chaudry M Imran
Published: February 2015

The role of simulation in formal neuroendovascular training has not been defined. This report details the general principles underlying the use of simulation in training, the critical aspects of the simulation environment which would aid it as a teaching tool specific to the field of neuroendovascular care, summarizes the available evidence to support a milestone-based curriculum, and outlines an example of what such a curriculum would entail. Building on these foundations, we articulate the rationale for the development and widespread adoption of a simulation curriculum for formal neuroendovascular training.
Clathrate hydrate equilibrium modeling: Do self-consistent cell models provide unique equilibrium solutions?
Authors: Lafond Patrick G. , Grim R. Gary , Sum Amadeu K.
Published: February 2015

When clathrate hydrates of xenon gas are formed deep within the stability field, anomalous melting behavior is readily observed in differential scanning calorimetry (DSC). In the DSC thermograms, multiple dissociation events may be observed, suggesting the presence of more than one solid phase. Following a suite of diffraction and NMR measurements, we are only able to detect the presence of simple structure I hydrate. Recognizing that hydrates are nonstoichiometric compounds, we look back to how the molar composition of a hydrate phase is determined. Making a mean-field improvement to current equilibrium models, we find that some conditions yield multiple solutions to the cage filling of the hydrate phase. Though the solutions are not truly stable, they would result in a kinetically trapped system. If such a case existed experimentally, this could explain the dissociation behavior observed for xenon hydrates. More importantly, this raises the question of how well defined the equilibrium condition is for a cell potential model, and whether or not multiple equilibrium solutions could exist.
Resolution of malic acid by (+)-cinchonine and (–)-cinchonidine
Authors: Báthori Nikoletta B. , Jacobs Ayesha , Mei Mawonga , Nassimbeni Luigi R.
Published: February 2015

(+)-Cinchonine and (–)-cinchonidine have been employed to resolve rac-malic acid. The resulting salts contain the D-malate anion in both cases. The cinchoninium and cinchonidinium L-malates were also crystallised, and the structures of all four salts were analysed in terms of their nonbonding interactions. All four structures display extensive hydrogen bonding, and it is shown that the D-malate salts are more efficiently packed.
Molecular dynamics simulation of halogen bonding in Cl2, BrCl, and mixed Cl2/Br2 clathrate hydrates
Authors: Dureckova Hana , Woo Tom K. , Alavi Saman , Ripmeester John A.
Published: February 2015

Clathrate hydrate phases of dihalogen molecules have properties that differ from those of other guest molecules of similar size. The water oxygen–chlorine distances in the structure I (sI) Cl2 hydrate are smaller than the sum of the van der Waals radii of oxygen and chlorine. Bromine hydrate forms a unique clathrate hydrate structure that is not seen in other guest substances. In mixed Cl2/Br2 structure I hydrate, the water oxygen–bromine distances are also smaller than the sum of the oxygen and bromine van der Waals radii. We previously studied the structure of three dihalogen clathrate hydrates using single crystal X-ray diffraction and described these structural features in terms of halogen bonding between the dihalogen and water molecules. In this work, we perform molecular dynamics simulations of cubic sI Cl2, mixed Cl2/Br2, and BrCl clathrate hydrate phases. We perform quantum chemical computations on the dihalogen molecules to determine the nature of σ-hole near the halogen atoms. We fit the electrostatic potential of the molecules to point charge models including dummy atoms that represent σ-holes adjacent to the halogen molecules. Molecular dynamics simulations are used to determine the lattice constants, radial distribution functions, and guest dynamics in these phases. We determine the effect of guest size and difference in halogen bonding on the properties of the clathrate hydrate phase. Simulations for the Cl2, BrCl, and mixed Cl2/Br2 hydrates are performed with small cages of the sI clathrate hydrate phases completely full or filled with experimental occupancies with Cl2 guests.
Magnetohydrodynamic flow of Newtonian fluid in a scraped surface heat exchanger
Authors: Siddiqui A.M. , Imran A. , Zeb M. , Rana M.A.
Published: February 2015

This paper aims to study a mathematical model of electrically conducting incompressible Newtonian fluid flow in a scraped surface heat exchanger in the presence of a transverse magnetic field. In our case the gap between the blades and the device wall is narrow so lubrication theory approximations work for the flow. Steady isothermal flow of an electrically conducting Newtonian fluid is considered around a periodic array of pivoted scraper blade in a channel in which the lower wall is moving and the upper wall is at rest. Two-dimensional flow in the transverse section of a scraped surface heat exchanger is taken. Details of the flow properties, including the possible presence of regions of reversed flow under the blades, the forces on the blades and walls, and the fluxes of fluid above and below the blades are calculated. Graphic representation for involved flow parameters is also given.
Detection of Shifts in GPS Measurements for a Long-Span Bridge Using CUSUM Chart
Authors: Yi Ting-Hua , Li Hong-Nan , Song Gangbing , Guo Qing
Published: February 2015

Timely and correctly evaluating the quality of Global Positioning System (GPS) data is essential for reduction in the number of false alarms and missed detection of a GPS-based bridge deformation monitoring system. This paper investigates how to use the statistical process control technique, known as the cumulative sum (CUSUM) chart, for the detection of small but persistent shifts in the high-rate GPS carrier-phase measurements. First, a mathematical model for the shift detection based on the continuous hypothesis testing is established. The main features and implementation procedure of the CUSUM chart for the shift detection are then summarized, and the corresponding parameter selection method is discussed in detail. To meet the normality requirement of the CUSUM chart, a novel method that transfers the data to the Q-statistic by the estimated cumulative distribution functions is proposed according to the probability integral transform theory. This is followed by a simulation carried out to evaluate the detection performance of the CUSUM chart and exploit its advantages to the commonly used Shewhart chart for the high-rate GPS monitoring data with different shift sizes. Experimental results have showed that the CUSUM chart is sensitive to small persistent shifts compared to the Shewhart chart although it has a delay problem. The integration of CUSUM chart and Shewhart chart would be a reliable approach for the shift detection. Finally, an on-site dynamic monitoring experiment is carried out on a long-span bridge to validate the proposed approach’s effectiveness in detecting an actual deformation shift, and the experimental results proved to be very encouraging.
Supramolecular photovoltaic cells utilizing inclusion complexes composed of Li+@C60 and cyclic porphyrin dimer
Authors: Sakai Hayato , Kamimura Takuya , Tani Fumito , Hasobe Taku
Published: February 2015

We have newly constructed supramolecular photovoltaic cells using inclusion complexes of lithium-ion-encapsulated [60]fullerene ( Li +@ C 60) and cyclic porphyrin dimers (M-CPDPy, M = H 4 and Ni 2). First, supramolecular inclusion complexes of Li +@ C 60 and M-CPDPy were prepared in MeCN/PhCN (3/1, v/v) by rapid injection method. The molecular aggregates with spherical nanoparticles demonstrated a broad absorption property in the visible region. The macroscopic structures were also estimated to be ca. 200 nm in diameter by transmission electron microscope (TEM) and dynamic light scattering (DLS) measurements. The photoelectrochemical solar cells composed of these assemblies on nanostructured SnO 2 electrode were fabricated by electrophoretic deposition method. The photoelectrochemical behavior of the nanostructured SnO 2 film of supramolecular nanoassemblies of Li +@ C 60 and M-CPDPy is significantly higher than those of the single component films ( Li +@ C 60 or M-CPDPy) and supramolecular inclusion complexes of pristine C 60 and M-CPDPy.
First-order topography of the Himalayan Mountain belt: a deep-crustal flow analysis
Authors: Mandal Nibir , Bose Santanu , Baruah Amiya , Sarkar Shamik
Published: February 2015

This study investigates the first-order Himalayan mountain topography from the perspective of deep-crustal flow patterns in the Indo-Asia collision zone. Using a thin-viscous-sheet model we theoretically predict that flat hinterland topography with a stable elevation (Type I) can develop only when the lithospheric slab underthrusts with a threshold velocity (
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*). For
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>
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*, the hinterland continuously gains in elevation, leading to Type II topography. This type is characterized by varying first-order surface slopes, but always facing the mountain front. Conversely, the elevated hinterland masses undergo gravity-driven subsidence, forming a topography (Type III) with characteristic backward surface slopes when
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<
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s
*. We evaluate
V
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* as a function of: (i) the regional slope of the initial first-order surface topography (α); (ii) the angle of underthrusting (β); and (iii) the relative width of foreland plain (λ), assuming little effects of surface erosion. Our model shows two characteristic deep-crustal flow patterns: corner flow and vortex flow. The corner flow pattern, described by upwardly pointed hyperbolic streamlines, is responsible for Type II topography. Conversely, the vortex flow leads to Type III, whereas the transition between the two gives rise to Type I. This corner-to-vortex type flow transition commences on decreasing
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.
Do-it-yourself textbook publishing
Authors: Fox Armando , Patterson David
Published: February 2015

Comparing experiences publishing textbooks using traditional publishers and do-it-yourself methods.
Incremental Learning of Daily Routines as Workflows in a Smart Home Environment
Authors: Carolis Berardina De , Ferilli Stefano , Redavid Domenico
Published: February 2015

Smart home environments should proactively support users in their activities, anticipating their needs according to their preferences. Understanding what the user is doing in the environment is important for adapting the environment's behavior, as well as for identifying situations that could be problematic for the user. Enabling the environment to exploit models of the user's most common behaviors is an important step toward this objective. In particular, models of the daily routines of a user can be exploited not only for predicting his/her needs, but also for comparing the actual situation at a given moment with the expected one, in order to detect anomalies in his/her behavior. While manually setting up process models in business and factory environments may be cost-effective, building models of the processes involved in people's everyday life is infeasible. This fact fully justifies the interest of the Ambient Intelligence community in automatically learning such models from examples of actual behavior. Incremental adaptation of the models and the ability to express/learn complex conditions on the involved tasks are also desirable. This article describes how process mining can be used for learning users’ daily routines from a dataset of annotated sensor data. The solution that we propose relies on a First-Order Logic learning approach. Indeed, First-Order Logic provides a single, comprehensive and powerful framework for supporting all the previously mentioned features. Our experiments, performed both on a proprietary toy dataset and on publicly available real-world ones, indicate that this approach is efficient and effective for learning and modeling daily routines in Smart Home Environments.
A Stimulus-Response Framework for Robot Control
Authors: Gianni Mario , Kruijff Geert-Jan M. , Pirri Fiora
Published: February 2015

We propose in this article a new approach to robot cognitive control based on a stimulus-response framework that models both a robot’s stimuli and the robot’s decision to switch tasks in response to or inhibit the stimuli. In an autonomous system, we expect a robot to be able to deal with the whole system of stimuli and to use them to regulate its behavior in real-world applications. The proposed framework contributes to the state of the art of robot planning and high-level control in that it provides a novel perspective on the interaction between robot and environment. Our approach is inspired by Gibson’s constructive view of the concept of a stimulus and by the cognitive control paradigm of task switching. We model the robot’s response to a stimulus in three stages. We start by defining the stimuli as perceptual functions yielded by the active robot processes and learned via an informed logistic regression. Then we model the stimulus-response relationship by estimating a score matrix that leads to the selection of a single response task for each stimulus, basing the estimation on low-rank matrix factorization. The decision about switching takes into account both an interference cost and a reconfiguration cost. The interference cost weighs the effort of discontinuing the current robot mental state to switch to a new state, whereas the reconfiguration cost weighs the effort of activating the response task. A choice is finally made based on the payoff of switching. Because processes play such a crucial role both in the stimulus model and in the stimulus-response model, and because processes are activated by actions, we address also the process model, which is built on a theory of action. The framework is validated by several experiments that exploit a full implementation on an advanced robotic platform and is compared with two known approaches to replanning. Results demonstrate the practical value of the system in terms of robot autonomy, flexibility, and usability.
Visualizing sound
Authors: Savage Neil
Published: February 2015

New techniques capture speech by looking for the vibrations it causes.
Using technology to help people
Authors: Kirkpatrick Keith
Published: February 2015

Companies are creating technological solutions for individuals, then generalizing them to broader populations that need similar assistance.
Introduction to the Special Issue on Activity Recognition for Interaction
Authors: Bulling Andreas , Blanke Ulf , Tan Desney , Rekimoto Jun , Abowd Gregory
Published: February 2015

This editorial introduction describes the aims and scope of the
ACM Transactions on Interactive Intelligent Systems
special issue on Activity Recognition for Interaction. It explains why activity recognition is becoming crucial as part of the cycle of interaction between users and computing systems, and it shows how the five articles selected for this special issue reflect this theme.
We need a building code for building code
Authors: Landwehr Carl
Published: February 2015

A proposal for a framework for code requirements addressing primary sources of vulnerabilities for building systems.
Japan's New Plan to Become a Hydrogen Society: Will Japan Succeed?
Authors: Behling Noriko
Published: February 2015

Japan’s government and industry have jointly decided to implement a Hydrogen Society plan, starting in 2015, with completion by or beyond 2040. This decision was made in the aftermath of the 2011 Earthquake and Tsunami disaster, which forced Japan to look for alternative sources of sustainable energy. The Hydrogen Society plan consists of three phases: Phase 1 is an extension of the current fuel cell program, which includes broader diffusion of fuel cells into the global market accompanied by dramatic cost reduction of both hydrogen and fuel cells. Phase 2 envisions the large-scale introduction of hydrogen power generation and the establishment of a wide-spread hydrogen supply infrastructure. Phase 3 would establish a zero-carbon emission hydrogen supply system throughout the manufacturing process. This article reviews the details of the plan, investigates the rationale for the decision, examines the implementation approach, and provides a brief look at possible outcomes.