bluuebunny/crossref_metadata_2025 huggingface dataset:
Blockchain Technology as an Institution of Property
Authors: Ishmaev G.
Published: October 2017

This paper argues that the practical implementation of blockchain technology can be considered an institution of property similar to legal institutions. Invoking Penner's theory of property and Hegel's system of property rights, and using the example of bitcoin, it is possible to demonstrate that blockchain effectively implements all necessary and sufficient criteria for property without reliance on legal means. Blockchains eliminate the need for a third‐party authority to enforce exclusion rights, and provide a system of universal access to knowledge and discoverability about the property rights of all participants and how the system functions. The implications of these findings are that traditional property relations in society could be replaced by or supplemented with blockchain models, and implemented in new domains.
Clinicomanometric factors associated with clinically relevant esophagogastric junction outflow obstruction from the Sandhill high‐resolution manometry system
Authors: Song B. G. , Min Y. W. , Lee H. , Min B.‐H. , Lee J. H. , Rhee P.‐L. , Kim J. J.
Published: October 2017

Background

Integrated relaxation pressure (IRP) is a key metric for diagnosing esophagogastric junction outflow obstruction (EGJOO). However, its normal value might be different according to the manufacturer of high‐resolution manometry (HRM). This study aimed to investigate optimal value of IRP for diagnosing EGJOO in Sandhill HRM and to find clinicomanometric variables to segregate clinically relevant EGJOO.

Methods

We analyzed 262 consecutive subjects who underwent HRM between June 2011 and December 2016 showing elevated median IRP (> 15 mm Hg) but did not satisfy criteria for achalasia. Clinically relevant subjects were defined as follows: (i) subsequent HRM met achalasia criteria during follow‐up (early achalasia); (ii) Eckardt score was decreased at least two points without exceeding a score of 3 after pneumatic dilatation (variant achalasia); and (iii) significant passage disturbance on esophagogram without structural abnormality (possible achalasia).

Key Results

Seven subjects were clinically relevant, including two subjects with early achalasia, four subjects with variant achalasia, and one subject with possible achalasia. All clinically relevant subjects had IRP 20 mm Hg or above. Among subjects (n = 122) with IRP 20 mm Hg or more, clinically relevant group (n = 7) had significantly higher rate of dysphagia (100% vs 24.3%, P < .001) and compartmentalized pressurization (85.7% vs 21.7%, P = .001) compared to clinically non‐relevant group (n = 115).

Conclusions & Inferences

Our results suggest that IRP of 20 mm Hg or higher could segregate clinically relevant subjects showing EGJOO in Sandhill HRM. Additionally, if subjects have both dysphagia and compartmentalized pressurization, careful follow‐up is essential.
Implantable cardioverter‐defibrillator in the elderly: Predictors of appropriate interventions and mortality at 12‐month follow‐up
Authors: Ferretto Sonia , Zorzi Alessandro , Dalla Valle Chiara , Migliore Federico , Leoni Loira , De Lazzari Manuel , Corrado Domenico , Iliceto Sabino , Bertaglia Emanuele
Published: October 2017

Background

The effectiveness of implantable cardioverter‐defibrillator (ICD) in the elderly is uncertain, given their competing risk of nonarrhythmic death. Guidelines state that an ICD should be implanted if the expectation of survival is at least 1 year. However, survival is not easy to predict in elderly patients with severe cardiac disease.

Aim

To assess 12‐month survival after ICD implantation in patients aged ≥75 years, to identify predictors of 12‐month mortality, and to evaluate the incidence of ICD therapy during follow‐up.

Methods

We retrospectively analyzed all clinical, instrumental, and survival data of patients ≥75 years old who received an ICD in our center from 2000 to 2013.

Results

We included 127 patients (mean age 78 years). ICD was implanted for primary prevention in 61%. The 12‐month survival rate was 87.4%. At both univariate and multivariate analyses, left ventricular ejection fraction (EF) ≤ 25%, and moderate to severe impaired renal function (IRF) independently predicted 12‐month mortality that was as high as 45.5% in patients with both risk factors. During a median follow‐up of 38 months, 30 patients (23.6%) received ≥1 appropriate ICD interventions, but only 3.1% of shocks occurred during the first year, and none in the subgroup of patients with EF ≤ 25% and IRF.

Conclusion

Twelve‐month survival in elderly patients after ICD implantation is good and the indication for ICD should not be based on age alone. However, the subgroup with EF ≤ 25% and IRF showed a high 12‐month nonarrhythmic mortality and did not benefit from ICD implantation.
Hemodynamic parameters and baroreflex sensitivity during head‐up tilt test in patients with neurally mediated syncope
Authors: Lee Sung Ho , Yang Ji Hyun , Yim Hye Ran , Park Jungwae , Park Seung‐Jung , Park Kyoung‐Min , On Young Keun , Kim June Soo
Published: October 2017

Background

We aimed to investigate differences in hemodynamic parameters and the role of baroreflex sensitivity (BRS) in patients with a history of neurally mediated syncope (NMS) compared with a control group.

Methods

Hemodynamic parameters and BRS were continuously measured noninvasively using a Finometer at rest and during passive head‐up tilt test (HUT) in patients with a history of NMS (n = 55) and a control group (n = 77). The tilting period was divided into pretest (resting supine position), initial (first 3 minutes of tilting), last (last 3 minutes of tilting), and recovery (3 minutes after tilting was complete) periods.

Results

Decrease in systolic blood pressure (− 14.7 ± 15.7 mm Hg vs − 7.6 ± 14.3 mm Hg, P < 0.01) was more prominent and increase in total systemic peripheral resistance was significantly smaller (67.6 ± 418.7 dyn.s/cm5 vs 189.4 ± 261.0 dyn.s/cm5, P = 0.04) from the initial to the last period of HUT in the patient group compared with the control group. BRS was significantly higher during the pretest period (20.1 ± 10.9 ms/mm Hg vs 13.0 ± 8.1 ms/mm Hg, P < 0.01) in the patient group, while the decrease in BRS from the pretest to the initial period was greater (−8.5 ± 6.0 ms/mm Hg vs − 3.2 ± 4.1 ms/mm Hg, P = 0.01).

Conclusions

Dysfunctional BRS in response to orthostatic stress might be involved in pathological autonomic cardiac modulation of NMS.
Correlation of head‐up tilt table test time interval with future risk of recurrent syncope
Authors: Singhania Priti K , Ranwa Bhanwar L. , Gupta Sajal
Published: October 2017

Background

Head‐up tilt table test (HUTT) is widely used for the investigation of syncope and presyncope. Time required for positive response has a probable relationship to the sensitivity of neural reflex mechanism underlying syncope.

Methods

We evaluated patients with history of syncope. Group A included patients with recurrent syncope defined as two or more episodes of syncope and group B included those with one episode of syncope. Time required for the test to become positive in both the groups was analyzed. Patients with positive HUTT were followed for 1 year.

Results

Of 80 patients, 68 eligible study patients were divided into group A (32.35%) and group B (67.65%). HUTT was positive in 41 patients (positivity rate  =  60.29%). Positivity rate was 100% in group A and 41.3% in group B. Median time interval for positive response in groups A and B were 12.5 and 30.0 minutes, respectively. An inverse association was found between recurrent syncope and time interval for positive response (R  =  − 0.282, P  =  0.002). Time interval of less than 19.5 minutes for positive response had 94.5% sensitivity and 97.89% specificity for recurrent syncope. On follow‐up, positive association was found between time interval for positive response less than 19.5 minutes and future recurrence of syncope (odds ratio  =  22.75, 95% confidence interval  =  4.37–118.34, P  =  0.000).

Conclusion

HUTT time interval of less than 19.5 minutes for positive response predicted future recurrence of syncope. Hence, it may serve as an important predictor of future recurrence of syncope.
Relationship quality influences attitudes toward and perceptions of infidelity
Authors: SILVA ANDRÉ , SARAIVA MAGDA , ALBUQUERQUE PEDRO B. , ARANTES JOANA
Published: October 2017

Do attitudes toward and perceptions of infidelity depend on perceived relationship quality? A prediction was made that there should be a positive correlation between perceived relationship quality and negative attitudes and perceptions of infidelity, and that these correlations should be stronger for males than for females. These predictions were confirmed. More specifically, strongly negative evaluations of infidelity were reported by females regardless of relationship quality, and for males with high relationship quality. Negative attitudes toward infidelity increased for both males and females in high‐quality committed relationships, but males who reported lower relationship quality had the most favorable attitudes toward infidelity. These results are consistent with an evolutionary rationale, which suggests that males' attitudes and perceptions of infidelity depend on their perceived risk of cuckoldry.
Autologistic Models for Benchmark Risk or Vulnerability Assessment of Urban Terrorism Outcomes
Authors: Liu Jingyu , Piegorsch Walter W. , Grant Schissler A. , Cutter Susan L.
Published: October 2017

We develop a quantitative methodology to characterize vulnerability among 132 US urban centres (‘cities’) to terrorist events, applying a place-based vulnerability index to a database of terrorist incidents and related human casualties. A centred autologistic regression model is employed to relate urban vulnerability to terrorist outcomes and also to adjust for auto-correlation in the geospatial data. Risk analytic ‘benchmark’ techniques are then incorporated in the modelling framework, wherein levels of high and low urban vulnerability to terrorism are identified. This new translational adaptation of the risk benchmark approach, including its ability to account for geospatial auto-correlation, is seen to operate quite flexibly in this sociogeographic setting.
Differentially Private Model Selection with Penalized and Constrained Likelihood
Authors: Lei Jing , Charest Anne-Sophie , Slavkovic Aleksandra , Smith Adam , Fienberg Stephen
Published: October 2017

In statistical disclosure control, the goal of data analysis is twofold: the information released must provide accurate and useful statistics about the underlying population of interest, while minimizing the potential for an individual record to be identified. In recent years, the notion of differential privacy has received much attention in theoretical computer science, machine learning and statistics. It provides a rigorous and strong notion of protection for individuals’ sensitive information. A fundamental question is how to incorporate differential privacy in traditional statistical inference procedures. We study model selection in multivariate linear regression under the constraint of differential privacy. We show that model selection procedures based on penalized least squares or likelihood can be made differentially private by a combination of regularization and randomization, and we propose two algorithms to do so. We show that our privacy procedures are consistent under essentially the same conditions as the corresponding non-privacy procedures. We also find that, under differential privacy, the procedure becomes more sensitive to the tuning parameters. We illustrate and evaluate our method by using simulation studies and two real data examples.
Estimation of Tail Risk Based on Extreme Expectiles
Authors: Daouia Abdelaati , Girard Stéphane , Stupfler Gilles
Published: October 2017

We use tail expectiles to estimate alternative measures to the value at risk and marginal expected shortfall, which are two instruments of risk protection of utmost importance in actuarial science and statistical finance. The concept of expectiles is a least squares analogue of quantiles. Both are M-quantiles as the minimizers of an asymmetric convex loss function, but expectiles are the only M-quantiles that are coherent risk measures. Moreover, expectiles define the only coherent risk measure that is also elicitable. The estimation of expectiles has not, however, received any attention yet from the perspective of extreme values. Two estimation methods are proposed here, either making use of quantiles or relying directly on least asymmetrically weighted squares. A main tool is first to estimate large values of expectile-based value at risk and marginal expected shortfall within the range of the data, and then to extrapolate the estimates obtained to the very far tails. We establish the limit distributions of both of the resulting intermediate and extreme estimators. We show via a detailed simulation study the good performance of the procedures and present concrete applications to medical insurance data and three large US investment banks.
Working memory and attention are still impaired after three years in patients with stress‐related exhaustion
Authors: Jonsdottir Ingibjörg H. , Nordlund Arto , Ellbin Susanne , Ljung Thomas , Glise Kristina , Währborg Peter , Sjörs Anna , Wallin Anders
Published: October 2017

Cognitive impairment is one of the most pronounced symptoms reported by patients with stress‐related mental health problems. Impairments related to executive function and to some extent speed and attention are therefore common in patients with stress‐related burnout/exhaustion. In this paper we present a follow‐up of cognitive performance in patients with stress‐related exhaustion several years after they initially sought medical care. Thirty patients and 27 healthy controls, mean age 49 years (SD 6.5) and 55 years (SD 6.7) respectively, were included, all of whom had undergone baseline measurements of neuropsychological functioning. The mean follow‐up time was three years. Half of the patients still reported mental health problems at follow‐up and over time no major changes in cognitive performance were noted. The patients still performed significantly poorer than controls with regard to cognitive functions, mainly related to speed, attention and memory function. Long‐lasting impairment of cognitive functions related to speed, attention and memory function noted in patients with stress‐related exhaustion should be acknowledged and taken into consideration during treatment and when discussing a return to work. Follow‐up periods longer than three years are needed to explore the persistence of the cognitive impairment.
What Partial Control Might Not Tell Us about Agreement: A Reply to Landau
Authors: Grano Thomas
Published: October 2017

Landau (2016b) draws on data from person mismatches in partial control to argue that agreement is (at least sometimes) a PF (Phonological Form) phenomenon. The argument depends in part on the premise that there is a reading of sentences such asThey wanted to prepare themselves and then meet for debatethat corresponds to a structure in which the VPmeet for debatehas a controlled PRO subject that is semantically first‐person but morphologically third‐person. I argue that according to Landau's own assumptions, PRO in such sentences is not semantically first‐person at any level of representation: Landau's premise relies on a problematic conflation between PRO and the output obtained by applying the group operator to PRO in Landau's approach to partial control. Consequently, Landau's argument for the PF status of agreement does not go through.
Brain abscesses caused by Cladophialophora bantiana in a lung transplant patient: A case report and review of the literature
Authors: Gschwend Anthony , Dégot Tristan , Denis Julie , Sabou Alina M. , Jeung Mi Young , Zapata Emilie , Porzio Michele , Renaud‐Picard Benjamin , Herbrecht Raoul , Kessler Romain
Published: October 2017

Cladophialophora bantiana brain abscesses are rare, but are frequently and quickly lethal in transplanted patients. We report the case of a 63‐year‐old man who had undergone lung transplantation for chronic obstructive pulmonary disease and presented with headaches and a neurological deficit. Magnetic resonance imaging revealed multiple brain abscesses. C. bantiana was identified by DNA sequencing performed directly on cerebral tissue obtained by surgical biopsy. After 6 months of antifungal treatment, the brain abscesses were replaced by ischemic sequelae. The patient died suddenly 2 months later from a pulmonary bacterial infection. This is the second reported case of C. bantiana brain abscesses in a lung transplant recipient, to our knowledge, who experienced a long survival period with medical antifungal treatment alone. We review the literature and discuss our treatment.
Subcutaneous phaeohyphomycosis in kidney transplant recipients: A series of seven cases
Authors: Haridasan Satish , Parameswaran Sreejith , Bheemanathi Srinivas Hanuman , Chandrasekhar Laxmisha , Suseela Bibilash Babu , Singh Rakesh , Rabindranath Jayasurya , Padhi Rajesh Kumar , Sampath Ezhilnilavan , Dubey Avinash Kumar , Puthenpurackal Priyamvada Sivan Pillai
Published: October 2017

Background

Superficial and deep fungal infections are more frequent in transplant recipients primarily because of the failure of cell‐mediated immunity and lesser amount of antigen‐presenting Langerhans cells in their epidermis. Here, we report seven cases of post‐renal transplant subcutaneous phaeohyphomycosis, all of which manifested within 1 year after transplantation and were unresponsive to prolonged courses of itraconazole. This is the first case series, to our knowledge, of phaeohyphomycosis in transplant recipients in India.

Method

We performed a retrospective review of cases of phaeohyphomycosis among kidney transplant recipients for type of transplant, immunosuppression, histopathology, and treatment, with prospective follow‐up of healed lesion.

Results

An overall incidence of 8.3% was noted, with a median duration of approximately 6 months post transplant to the onset of skin lesion. None of the lesions responded to itraconazole alone and 6/7 lesions were surgically excised. Histopathology showed various lesions and culture could isolate Neocytalidium and Exophiala jeanselmi in two cases.

Conclusion

Dematiaceous fungi are increasingly implicated in cutaneous lesions in transplant recipients. Histopathology and surgical excision are the appropriate tools for diagnosis and treatment, respectively.
Rare and unusual presentation of Cladophialophora infection in a pulmonary transplant cystic fibrosis patient
Authors: Reynaud Quitterie , Dupont Damien , Nove‐Josserand Raphaële , Durupt Stephane , Persat Florence , Ader Florence , Grenet Dominique , Durieu Isabelle
Published: October 2017

A 35‐year‐old woman with severe cystic fibrosis was admitted for sudden loss of strength in both legs, revealing a myelitis. The medullary lesion biopsy revealed phaeohyphomycosis caused by Cladophialophora species. Myelitis caused by Cladophialophora bantiana is a rare disease associated with high mortality.
The economic impact of the Trans‐Pacific Partnership: What have we learned from CGE simulation?
Authors: Gilbert John , Furusawa Taiji , Scollay Robert
Published: October 2017

The Trans‐Pacific Partnership (TPP) trade agreement, if were it to be successfully implemented, would be one of the largest regional agreements ever seen. It is the only exemplar to date of a “mega‐regional” FTA for which negotiations have been successfully concluded, and a landmark in evolving approaches to Asia–Pacific integration. As such, quantitative assessments of its potential effects are of considerable interest. One of the most widely used techniques for evaluating the economic impact of regional trading agreements is numerical simulation with computable general equilibrium, or CGE, models. There have now been a large number of papers written that use CGE methods to analyse the potential economic impact of the TPP agreement under varying theoretical and policy assumptions. In this paper we provide a synthesis of the key results that have emerged from the literature, and introduce some new simulation results of our own to anchor the discussion.
Empirical evaluation of river basin sustainability affected by inter‐basin water transfer using composite indicators
Authors: Kefayati Maryam , Saghafian Bahram , Ahmadi Azadeh , Babazadeh Hossein
Published: October 2017

In this study, a practical approach to evaluate the sustainability of river basins subjected to an inter‐basin water transfer project is developed. Selection of appropriate evaluation indicators is pivotal to such approach. To make use of huge amount of data, composite indicators of sustainability (CIS) should be utilised. The proposed approach relies on 15 sustainability indicators (SI) that cover three major criteria namely (economic, social and environmental), and aggregates them into eight different types of sustainability indices for a more robust outcome. Two scenarios were considered within the source and recipient basins. Furthermore, multivariate principal component analysis (PCA) was applied to determine principal and non‐principal indicators for the two river basins. The ability of CIS and PCA methods were verified via correlation and simple regression methods respectively. The results demonstrated that inter‐basin water transfer may improve sustainability, provided that a proper water resource management is enforced.
Plasma membrane Ca2+‐ATPase 1 is required for maintaining atrial Ca2+ homeostasis and electrophysiological stability in the mouse
Authors: Wang Yanwen , Wilson Claire , Cartwright Elizabeth J. , Lei Ming
Published: October 2017

Key points

The role of plasma membrane Ca2+‐ATPase 1 (PMCA1) in Ca2+ homeostasis and electrical stability in atrial tissue has been investigated at both organ and cellular levels in mice with cardiomyocyte‐specific deletion of PMCA1 (PMCA1cko)

The PMCA1cko hearts became more susceptible to atrial arrhythmic stress conditions than PMCA1loxP/loxP hearts.

PMCA1 deficiency alters cellular Ca2+ homeostasis under both baseline and stress conditions.

PMCA1 is required for maintaining cellular Ca2+ homeostasis and electrical stability in murine atria under stress conditions.

To determine the role of plasma membrane Ca2+‐ATPase 1 (PMCA1) in maintaining Ca2+ homeostasis and electrical stability in the atrium under physiological and stress conditions, mice with a cardiomyocyte‐specific deletion of PMCA1 (PMCA1cko) and their control littermates (PMCA1loxP/loxP) were studied at the organ and cellular levels. At the organ level, the PMCA1cko hearts became more susceptible to atrial arrhythmias under rapid programmed electrical stimulation compared with the PMCA1loxP/loxP hearts, and such arrhythmic events became more severe under Ca2+ overload conditions. At the cellular level, the occurrence of irregular‐type action potentials of PMCA1cko atrial myocytes increased significantly under Ca2+ overload conditions and/or at higher frequency of stimulation. The decay of Na+/Ca2+ exchanger current that followed a stimulation protocol was significantly prolonged in PMCA1cko atrial myocytes under basal conditions, with Ca2+ overload leading to even greater prolongation. In conclusion, PMCA1 is required for maintaining Ca2+ homeostasis and electrical stability in the atrium. This is particularly critical during fast removal of Ca2+ from the cytosol, which is required under stress conditions.
A Dynamic Stress Model Explains the Delayed Drug Effect in Artemisinin Treatment of Plasmodium falciparum
Authors: Cao Pengxing , Klonis Nectarios , Zaloumis Sophie , Dogovski Con , Xie Stanley C. , Saralamba Sompob , White Lisa J. , Fowkes Freya J. I. , Tilley Leann , Simpson Julie A. , McCaw James M.
Published: October 2017

Artemisinin resistance constitutes a major threat to the continued success of control programs for malaria, particularly in light of developing resistance to partner drugs. Improving our understanding of how artemisinin-based drugs act and how resistance manifests is essential for the optimization of dosing regimens and the development of strategies to prolong the life span of current first-line treatment options. Recent short-drug-pulse
in vitro
experiments have shown that the parasite killing rate depends not only on drug concentration but also the exposure time, challenging the standard pharmacokinetic-pharmacodynamic (PK-PD) paradigm in which the killing rate depends only on drug concentration. Here, we introduce a dynamic stress model of parasite killing and show through application to 3D7 laboratory strain viability data that the inclusion of a time-dependent parasite stress response dramatically improves the model's explanatory power compared to that of a traditional PK-PD model. Our model demonstrates that the previously reported hypersensitivity of early-ring-stage parasites of the 3D7 strain to dihydroartemisinin compared to other parasite stages is due primarily to a faster development of stress rather than a higher maximum achievable killing rate. We also perform
in vivo
simulations using the dynamic stress model and demonstrate that the complex temporal features of artemisinin action observed
in vitro
have a significant impact on predictions for
in vivo
parasite clearance. Given the important role that PK-PD models play in the design of clinical trials for the evaluation of alternative drug dosing regimens, our novel model will contribute to the further development and improvement of antimalarial therapies.
Choosing Optimal Antifungal Agents To Prevent Fungal Infections in Nonneutropenic Critically Ill Patients: Trial Sequential Analysis, Network Meta-analysis, and Pharmacoeconomic Analysis
Authors: Wang Yan , Xie Jiao , Xing Yuanming , Chen Lu , Li Ying , Meng Ti , Dong Weihua , Wang Xue , Dong Yalin
Published: October 2017

The use of antifungal interventions in critically ill patients prior to invasive fungal infection (IFI) being microbiologically confirmed and the preferred drug are still controversial. A systematic literature search was performed to identify randomized controlled trials (RCTs) that compared untargeted antifungal treatments applied to nonneutropenic critically ill patients. The primary outcomes were all-cause mortality and proven IFI rates. A random-effects model was used with trial sequential analyses (TSA), a network meta-analysis (NMA) was conducted to obtain indirect evidence, and a cost-effectiveness analysis using a decision-analytic model was completed from the patient perspective over a lifetime horizon. In total, 19 RCTs involving 2,556 patients (7 interventions) were included. Untargeted antifungal treatment did not significantly decrease the incidence of all-cause mortality (odds ratio [OR] = 0.89, 95% confidence interval [95%CI] = 0.70 to 1.14), but it did reduce the incidence of proven IFI (OR = 0.45, 95%CI = 0.29 to 0.71) relative to placebo/no intervention. The TSA showed that there was sufficient evidence supporting these findings. In the NMA, the only significant difference found for both primary outcomes was between fluconazole and placebo/no intervention in preventing proven IFI (OR = 0.35, 95%CI = 0.19 to 0.65). Based on drug and hospital costs in China, the incremental cost-effectiveness ratios per life-year saved for fluconazole, caspofungin, and micafungin relative to placebo/no intervention corresponded to US$889, US$9,994, and US$10,351, respectively. Untargeted antifungal treatment significantly reduced proven IFI rates in nonneutropenic critically ill patients but with no mortality benefits relative to placebo/no intervention. Among the well-tolerated antifungals, fluconazole remains the only one that is effective for IFI prevention and significantly cheaper than echinocandins.
Emergence of Various NDM-Type-Metallo-β-Lactamase-Producing Escherichia coli Clinical Isolates in Nepal
Authors: Shrestha Basudha , Tada Tatsuya , Shimada Kayo , Shrestha Shovita , Ohara Hiroshi , Pokhrel Bharat Mani , Sherchand Jeevan B. , Kirikae Teruo
Published: October 2017

Of 250 clinical isolates of
Escherichia coli
obtained in Nepal, 38 were carbapenem resistant, with MICs of imipenem or meropenem of ≥4 μg/ml. All 38 isolates harbored the following
bla
NDM
s:
bla
NDM-1
,
bla
NDM-3
,
bla
NDM-4
,
bla
NDM-5
,
bla
NDM-7
,
bla
NDM-12
, and
bla
NDM-13
. Most of these isolates also harbored the 16S rRNA methylase gene(s)
armA
,
rmtB
, and/or
rmtC
.
The Alternative Sigma Factors SigE and SigB Are Involved in Tolerance and Persistence to Antitubercular Drugs
Authors: Pisu Davide , Provvedi Roberta , Espinosa Dulce Mata , Payan Jorge Barrios , Boldrin Francesca , Palù Giorgio , Hernandez-Pando Rogelio , Manganelli Riccardo
Published: October 2017

The emergence and spread of drug-resistant
Mycobacterium tuberculosis
strains possibly threaten our ability to treat this disease in the future. Even though two new antitubercular drugs have recently been introduced, there is still the need to design new molecules whose mechanisms of action could reduce the length of treatment. We show that two alternative sigma factors of
M. tuberculosis
(SigE and SigB) have a major role in determining the level of basal resistance to several drugs and the amount of persisters surviving long-duration drug treatment. We also demonstrate that ethambutol, a bacteriostatic drug, is highly bactericidal for
M. tuberculosis
mutants missing either SigE or SigB. We suggest that molecules able to interfere with the activity of SigE or SigB not only could reduce
M. tuberculosis
virulence
in vivo
but also could boost the effect of other drugs by increasing the sensitivity of the organism and reducing the number of persisters able to escape killing.
Activity of Ceftolozane-Tazobactam and Ceftazidime-Avibactam against Beta-Lactam-Resistant Pseudomonas aeruginosa Isolates
Authors: Humphries Romney M. , Hindler Janet A. , Wong-Beringer Annie , Miller Shelley A.
Published: October 2017

Ceftolozane-tazobactam (C/T) and ceftazidime-avibactam (CZA) MICs were evaluated for a collection of 309 beta-lactam-resistant isolates of
Pseudomonas aeruginosa
recovered from three institutions in the area of Los Angeles, CA. Overall, 12.0% of isolates were susceptible to imipenem, 15.9% were susceptible to meropenem, 20.7% were susceptible to piperacillin-tazobactam, 24.6% were susceptible to ceftazidime, 25.9% were susceptible to cefepime, 72.5% were susceptible to C/T, and 61.8% were susceptible to CZA. Among C/T-resistant isolates, 9.1% were CZA susceptible, whereas 36.4% of CZA-resistant isolates were susceptible to C/T.
Acquired Protective Immunity in Atlantic Salmon Salmo salar against the Myxozoan Kudoa thyrsites Involves Induction of MHIIβ
+
CD83
+
Antigen-Presenting Cells
Authors: Braden Laura M. , Rasmussen Karina J. , Purcell Sara L. , Ellis Lauren , Mahony Amelia , Cho Steven , Whyte Shona K. , Jones Simon R. M. , Fast Mark D.
Published: October 2017

The histozoic myxozoan parasite
Kudoa thyrsites
causes postmortem myoliquefaction and is responsible for economic losses to salmon aquaculture in the Pacific Northwest. Despite its importance, little is known about the host-parasite relationship, including the host response to infection. The present work sought to characterize the immune response in Atlantic salmon during infection, recovery, and reexposure to
K. thyrsites
. After exposure to infective seawater, infected and uninfected smolts were sampled three times over 4,275 degree-days. Histological analysis revealed infection severity decreased over time in exposed fish, while in controls there was no evidence of infection. Following a secondary exposure of all fish, severity of infection in the controls was similar to that measured in exposed fish at the first sampling time but was significantly reduced in reexposed fish, suggesting the acquisition of protective immunity. Using immunohistochemistry, we detected a population of MHIIβ
+
cells in infected muscle that followed a pattern of abundance concordant with parasite prevalence. Infiltration of these cells into infected myocytes preceded destruction of the plasmodium and dissemination of myxospores. Dual labeling indicated a majority of these cells were CD83
+
/MHIIβ
+
. Using reverse transcription-quantitative PCR, we detected significant induction of cellular effectors, including macrophage/dendritic cells (
mhii
/
cd83
/
mcsf
), B cells (
igm
/
igt
), and cytotoxic T cells (
cd8
/
nkl
), in the musculature of infected fish. These data support a role for cellular effectors such as antigen-presenting cells (monocyte/macrophage and dendritic cells) along with B and T cells in the acquired protective immune response of Atlantic salmon against
K. thyrsites
.
The Electron Transport Chain Sensitizes Staphylococcus aureus and Enterococcus faecalis to the Oxidative Burst
Authors: Painter Kimberley L. , Hall Alex , Ha Kam Pou , Edwards Andrew M.
Published: October 2017

Small-colony variants (SCVs) of
Staphylococcus aureus
typically lack a functional electron transport chain and cannot produce virulence factors such as leukocidins, hemolysins, or the antioxidant staphyloxanthin. Despite this, SCVs are associated with persistent infections of the bloodstream, bones, and prosthetic devices. The survival of SCVs in the host has been ascribed to intracellular residency, biofilm formation, and resistance to antibiotics. However, the ability of SCVs to resist host defenses is largely uncharacterized. To address this, we measured the survival of wild-type and SCV
S. aureus
in whole human blood, which contains high numbers of neutrophils, the key defense against staphylococcal infection. Despite the loss of leukocidin production and staphyloxanthin biosynthesis, SCVs defective for heme or menaquinone biosynthesis were significantly more resistant to the oxidative burst than wild-type bacteria in human blood or the presence of purified neutrophils. Supplementation of the culture medium of the heme-auxotrophic SCV with heme, but not iron, restored growth, hemolysin and staphyloxanthin production, and sensitivity to the oxidative burst. Since
Enterococcus faecalis
is a natural heme auxotroph and cause of bloodstream infection, we explored whether restoration of the electron transport chain in this organism also affected survival in blood. Incubation of
E. faecalis
with heme increased growth and restored catalase activity but resulted in decreased survival in human blood via increased sensitivity to the oxidative burst. Therefore, the lack of functional electron transport chains in SCV
S. aureus
and wild-type
E. faecalis
results in reduced growth rate but provides resistance to a key immune defense mechanism.
Risk of rehospitalisation and death for vulnerable New Zealand children
Authors: Oliver Jane , Foster Tim , Kvalsvig Amanda , Williamson Deborah A , Baker Michael G , Pierse Nevil
Published: October 2017

Objectives

There is considerable need to improve the effectiveness of healthcare to reduce morbidity and mortality. Child hospitalisations are influenced by determinants of health, including the home environment. Our aims were: (1) To investigate whether children hospitalised with potentially avoidable conditions thought to be associated with the home have an increased risk of rehospitalisation and death, (2) To investigate whether children hospitalised with particular subgroups of potentially avoidable conditions have an increased risk of rehospitalisation and death, (3) To assess the usefulness of these subgroups for identifying at-risk children.

Design

We used four existing groups of potentially avoidable conditions developed based on expert opinion: 1. the potentially avoidable hospitalisations (PAH) group, associated with social/environmental conditions, 2. the potentially avoidable hospitalisations attributable (at least in part) to the home environment (PAHHE) group, 3. the crowding group, and 4. the Ministry of Health (MoH) group. We analysed national New Zealand hospital discharge data (2000–2014). Rehospitalisation and death were described using Kaplan-Meier curves. Group effectiveness for identifying at-risk children was assessed using Cox proportional hazard models with children hospitalised for non-PAH conditions as comparison.

Results

In total, 1425085 hospital admissions occurred, for 683115 unique children. Rehospitalisation was relatively common (71.0%). Death was rare (0.6%). All groups performed moderately well identifying at-risk children. Children with PAH have increased risk of rehospitalisation (adjusted HR (aHR):2.30–3.60) and death (aHR:3.07–10.44). PAH group had highest sensitivity (75.1%). The MoH group has the highest positive predictive value (rehospitalisation: 86.2%, death: 2.5%).

Conclusions

Children in the MoH group are very likely to benefit from housing interventions. Rehospitalisation and early mortality are useful assessment measures. Rehospitalisation exerts a considerable burden, and child deaths are catastrophic.
Observational study on the palatability and tolerability of oral prednisolone and oral dexamethasone in children in Saudi Arabia and the UK
Authors: Aljebab Fahad , Alanazi Mofadhi , Choonara Imti , Conroy Sharon
Published: October 2017

Background

Short-course oral corticosteroids are routinely used to treat acute asthma and croup. We evaluated their tolerability and palatability in Saudi Arabian (SA) and UK children.

Methods

Prospective observational/interview study (3 months in each country). Palatability was evaluated using a 5-point facial Hedonicscale and tolerability by direct questioning of patient/parents.

Results

In SA, of 122 patients (2–10 years) recruited, 52 received prednisolone base tablets, 37 prednisolone sodium phosphate syrup and 33 received dexamethasone elixir. In the UK, of 133 patients (2–16 years), 38 received prednisolone base tablets (mainly crushed and dispersed), 42 prednisolone sodium phosphate soluble tablets and 53 received dexamethasone sodium phosphate oral solution.

In both countries, dexamethasone had the highest palatability scores (SA mean: 1.97; UK mean: 3) and prednisolone base tablets had the lowest (SA mean: 1.12; UK mean: 1.39). Palatability scores improved for all formulations of prednisolone with each subsequent daily dose.

In SA, prednisolone base tablets were associated with more nausea (24vs7 patients) and vomiting (5vs0 patients) than sodium phosphate syrup (p=0.008 and p=0.073, respectively). In the UK, vomiting occurred more frequently with prednisolone base (8 patients) than sodium phosphate soluble tablets (2 patients) (p=0.041).

In both centres, dexamethasone was associated with less side effects. Vomiting (1vs0 patients), nausea (7vs3 patients) and abdominal pain (10vs8 patients) occurred more with dexamethasone sodium phosphate solution than dexamethasone elixir.

Conclusions

Dexamethasone sodium phosphate solution was the most palatable preparation. Prednisolone base tablets were rated least palatable and were least well tolerated. Palatability scores improved with each dose taken.
Early surgery and neurodevelopmental outcomes of children born extremely preterm
Authors: Hunt Rodney W , Hickey Leah M , Burnett Alice C , Anderson Peter J , Cheong Jeanie Ling Yoong , Doyle Lex W
Published: October 2017

Objectives

To (1) compare the neurodevelopmental outcomes at 8 years of age of children born extremely preterm (EP) who underwent surgical procedures during the course of their initial hospital admission with those who did not and (2) compare the outcomes across eras, from 1991 to 2005.

Design

Prospective observational cohort studies conducted over three different eras (1991-1992, 1997 and 2005). Surviving EP children, who required surgical intervention during the primary hospitalisation, were assessed for general intelligence (IQ) and neurosensory status at 8 years of age. Major neurosensory disability comprised any of moderate/severe cerebral palsy, IQ less than -2 SD relative to term controls, blindness or deafness.

Results

Overall, 29% (161/546) of survivors had surgery during the newborn period, with similar rates in each era. Follow-up rates at 8 years were high (91%; 499/546), and 17% (86/499) of survivors assessed had a major neurosensory disability. Rates of major neurosensory disability were substantially higher in the surgical group (33%; 52/158) compared with those who did not have surgery (10%; 34/341) (OR 4.28, 95% CI 2.61 to 7.03). Rates of disability in the surgical group did not improve over time. After adjustment for relevant confounders, no specific surgical procedure was associated with increased risk of disability.

Implications and relevance

Major neurosensory disability at 8 years was higher in children born EP who underwent surgery during their initial hospital admission compared with those who did not. The rates of major neurosensory disability in the surgical cohort are not improving over time.
Knee upside down
Authors: van der Aart Steven G J , Sonnega Remko J A , Hofstee Dirk-Jan
Published: October 2017

We present a case of a 19-year-old woman with a forced hyperextension trauma of the knee causing a posteromedial fracture, a medial meniscus root tear and rupture of the posterior cruciate ligament. The posteromedial fracture of the tibial plateau was treated operatively with open reduction and internal fixation. Anatomical reconstruction was achieved. Postoperative treatment included unlimited flexion and minimal weight bearing. After 3 months, the patient had minimal pain after weight bearing and returned to preoperative range of motion.
Elizabethkingia meningoseptica: emerging multidrug resistance in a nosocomial pathogen
Authors: Raghavan Sairam , Thomas Biji , Shastry B A
Published: October 2017

A 46-year-old male patient presented with complaints of burning micturition for 2 days. Initial history, physical examination and laboratory investigations were consistent with the diagnosis of congestive cardiac failure (CCF) and concomitant urinary tract infection. CCF was treated with diuretics and a urine culture/sensitivity (C/S) was sent which returned growingElizabethkingia meningosepticaresistant to all tested drugs. Intravenous cefotaxime which had been started empirically 3 days earlier was withheld at this point, and a repeat urine C/S was sent revealing resistance to all tested drugs (including reserved drugs) barring minocycline. The patient was treated with oral minocycline for 14 days after which he was symptomatically better with sterile urine. The patient was subsequently discharged.
Prevalence of and factors associated with fewer than 20 remaining teeth in Taiwanese adults with disabilities: a community-based cross-sectional study
Authors: Pan Mei-Yu , Hsieh Tsung-Cheng , Tai Hung-Cheng , Lin Ming-Shyan , Lin Yu-Chen , Chen Mei-Yen
Published: October 2017

Objectives

To examine the prevalence of and the factors associated with a number of remaining teeth (NRT) <20 among adults with disabilities.

Design

A community-based, cross-sectional descriptive study.

Setting

This study was part of a health promotion programme designed for community-dwelling adults with disabilities.

Participants

A total of 549 adults with disabilities, aged 20–80 years, living in the community in Chiayi County in Taiwan.

Outcome measures

Various parameters, including NRT, oral health behaviours (ie, oral hygiene, dietary habits and substance use), comorbidities, disability classification and capability for performing activities of daily living, were measured. Data were statistically analysed using descriptive statistics and multivariate logistic regression analysis.

Results

The mean NRT was 18.1 (SD=10.9); 44.8% of participants had NRT <20 (including 13.7% edentulous participants). Most participants had poor oral hygiene: 83.4% reported seldom using dental floss, 78% did not undergo regular 6-monthly dental check-ups and 77.4% seldom brushed their teeth after meal. After adjusting for potentially confounding variables, the intellectual disability group had a significantly higher risk of an NRT <20 than the physical disability group (OR 2.30, 95% CI 1.30 to 4.08). Additionally, the rare use of dental floss and hypertension significantly increased the possibility of an NRT <20 (OR 1.73–2.12, 95% CI 1.15 to 3.71).

Conclusions

An NRT <20 and edentulism were highly prevalent among adults with disabilities, who displayed poor oral hygiene behaviours. Adults with intellectual disabilities had a greater likelihood of having an NRT <20 than did those with physical disability. In addition to unmodifiable factors, the poor use of dental floss was significantly associated with an NRT <20.
Comparison of two methods to estimate adverse events in the IBEAS Study (Ibero-American study of adverse events): cross-sectional versus retrospective cohort design
Authors: Aranaz Andrés Jesus Maria , Limón Ramírez Ramon , Aibar Remón Carlos , Gea-Velázquez de Castro Maria Teresa , Bolúmar Francisco , Hernández-Aguado Ildefonso , López Fresneña Nieves , Díaz-Agero Pérez Cristina , Terol García Enrique , Michel Philippe , Sousa Paulo , Larizgoitia Jauregui Itziar
Published: October 2017

Background

Adverse events (AEs) epidemiology is the first step to improve practice in the healthcare system. Usually, the preferred method used to estimate the magnitude of the problem is the retrospective cohort study design, with retrospective reviews of the medical records. However this data collection involves a sophisticated sampling plan, and a process of intensive review of sometimes very heavy and complex medical records. Cross-sectional survey is also a valid and feasible methodology to study AEs.

Objectives

The aim of this study is to compare AEs detection using two different methodologies: cross-sectional versus retrospective cohort design.

Setting

Secondary and tertiary hospitals in five countries: Argentina, Colombia, Costa Rica, Mexico and Peru.

Participants

The IBEAS Study is a cross-sectional survey with a sample size of 11 379 patients. The retrospective cohort study was obtained from a 10% random sample proportional to hospital size from the entire IBEAS Study population.

Methods

This study compares the 1-day prevalence of the AEs obtained in the IBEAS Study with the incidence obtained through the retrospective cohort study.

Results

The prevalence of patients with AEs was 10.47% (95% CI 9.90 to 11.03) (1191/11 379), while the cumulative incidence of the retrospective cohort study was 19.76% (95% CI 17.35% to 22.17%) (215/1088). In both studies the highest risk of suffering AEs was seen in Intensive Care Unit (ICU) patients. Comorbid patients and patients with medical devices showed higher risk.

Conclusion

The retrospective cohort design, although requires more resources, allows to detect more AEs than the cross-sectional design.