bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single-Center Evaluation of an Agar-Based Screening for Azole Resistance in Aspergillus fumigatus by Using VIPcheck
Authors: Buil J. B. , van der Lee H. A. L. , Rijs A. J. M. M. , Zoll J. , Hovestadt J. A. M. F. , Melchers W. J. G. , Verweij P. E. 
Published: September 2017

ABSTRACT

Antifungal susceptibility testing is an essential tool for guiding therapy, although EUCAST and CLSI reference methods are often available only in specialized centers. We studied the performance of an agar-based screening method for the detection of azole resistance in
Aspergillus fumigatus
cultures. The VIPcheck consists of four wells containing voriconazole, itraconazole, posaconazole, or a growth control. Ninety-six
A. fumigatus
isolates were used. Thirty-three isolates harbored a known resistance mechanism: TR
34
/L98H (11 isolates), TR
46
/Y121F/T289A (6 isolates), TR
53
(2 isolates), and 14 isolates with other
cyp51A
gene point mutations. Eighteen resistant isolates had no
cyp51A
-mediated azole resistance. Forty-five isolates had a wild-type (WT) azole phenotype. Four technicians and two inexperienced interns, blinded to the genotype/phenotype, read the plates visually after 24 h and 48 h and documented minimal growth, uninhibited growth, and no growth. The performance was compared to the EUCAST method. After 24 h of incubation, the mean sensitivity and specificity were 0.54 and 1.00, respectively, with uninhibited growth as the threshold. After 48 h of incubation, the performance mean sensitivity and specificity were 0.98 and 0.93, respectively, with minimal growth. The performance was not affected by observer experience in mycology. The interclass correlation coefficient was 0.87 after 24 h and 0.85 after 48 h. VIPcheck enabled the selection of azole-resistant
A. fumigatus
colonies, with a mean sensitivity and specificity of 0.98 and 0.93, respectively. Uninhibited growth on any azole-containing well after 24 h and minimal growth after 48 h were indicative of resistance. These results indicate that the VIPcheck is an easy-to-use tool for azole resistance screening and the selection of colonies that require MIC testing.
In Vitro
Comparison of Ceftolozane-Tazobactam to Traditional Beta-Lactams and Ceftolozane-Tazobactam as an Alternative to Combination Antimicrobial Therapy for Pseudomonas aeruginosa
Authors: Goodlet Kellie J. , Nicolau David P. , Nailor Michael D. 
Published: September 2017

ABSTRACT

Guidelines for the treatment of sepsis, febrile neutropenia, and hospital-acquired pneumonia caused by
Pseudomonas aeruginosa
include empirical regimens incorporating two antibiotics from different classes with activity against
P. aeruginosa
for select at-risk patients to increase the likelihood that the organism will be susceptible to at least one agent. The activity against
P. aeruginosa
and the rates of cross-resistance of ceftolozane-tazobactam were compared to those of the β-lactam comparators cefepime, ceftazidime, piperacillin-tazobactam, and meropenem alone and cumulatively with ciprofloxacin or tobramycin. Nonurine
P. aeruginosa
isolates were collected from adult inpatients at 44 geographically diverse U.S. hospitals. MICs were determined using reference broth microdilution methods. Of the 1,257 isolates collected, 29% were from patients in intensive care units and 39% were from respiratory sites. The overall rate of susceptibility to ceftolozane-tazobactam was high at 97%, whereas it was 72 to 76% for cefepime, ceftazidime, piperacillin-tazobactam, and meropenem. The rate of nonsusceptibility to all four comparator β-lactams was 11%; of the isolates nonsusceptible to the four comparator β-lactams, 80% remained susceptible to ceftolozane-tazobactam. Among the isolates nonsusceptible to the tested β-lactam comparators, less than half were susceptible to ciprofloxacin. By comparison, approximately 80% of the β-lactam-nonsusceptible isolates were susceptible to tobramycin, for overall cumulative susceptibility rates of 94 to 95%, nearly 10% higher than that of the ciprofloxacin–β-lactam combinations and approaching that of ceftolozane-tazobactam as a single agent. The rates of susceptibility to ceftolozane-tazobactam were consistently high, with little observable cross-resistance. Ceftolozane-tazobactam monotherapy performed at or above the level of commonly utilized combination therapies on the basis of
in vitro
susceptibilities. Ceftolozane-tazobactam should be considered for use in patients at high risk for resistant
P. aeruginosa
infection and as an alternative to empirical combination therapy, especially for patients unable to tolerate aminoglycosides.
Pharmacological Inhibition of the Pseudomonas aeruginosa MvfR Quorum-Sensing System Interferes with Biofilm Formation and Potentiates Antibiotic-Mediated Biofilm Disruption
Authors: Maura Damien , Rahme Laurence G. 
Published: September 2017

ABSTRACT

Pseudomonas aeruginosa
biofilms contribute to its survival on biotic and abiotic surfaces and represent a major clinical threat due to their high tolerance to antibiotics. Therefore, the discovery of antibiofilm agents may hold great promise. We show that pharmacological inhibition of the
P. aeruginosa
quorum-sensing regulator MvfR (PqsR) using a benzamide-benzimidazole compound interferes with biofilm formation and potentiates biofilm sensitivity to antibiotics. Such a strategy could have great potential against
P. aeruginosa
persistence in diverse environments.
Changing Antimalarial Drug Sensitivities in Uganda
Authors: Rasmussen Stephanie A. , Ceja Frida G. , Conrad Melissa D. , Tumwebaze Patrick K. , Byaruhanga Oswald , Katairo Thomas , Nsobya Samuel L. , Rosenthal Philip J. , Cooper Roland A. 
Published: September 2017

ABSTRACT

Dihydroartemisinin-piperaquine (DP) has demonstrated excellent efficacy for the treatment and prevention of malaria in Uganda. However, resistance to both components of this regimen has emerged in Southeast Asia. The efficacy of artemether-lumefantrine, the first-line regimen to treat malaria in Uganda, has also been excellent, but continued pressure may select for parasites with decreased sensitivity to lumefantrine. To gain insight into current drug sensitivity patterns,
ex vivo
sensitivities were assessed and genotypes previously associated with altered drug sensitivity were characterized for 58 isolates collected in Tororo, Uganda, from subjects presenting in 2016 with malaria from the community or as part of a clinical trial comparing DP chemoprevention regimens. Compared to community isolates, those from trial subjects had lower sensitivities to the aminoquinolines chloroquine, monodesethyl amodiaquine, and piperaquine and greater sensitivities to lumefantrine and mefloquine, an observation consistent with DP selection pressure. Compared to results for isolates from 2010 to 2013, the sensitivities of 2016 community isolates to chloroquine, amodiaquine, and piperaquine improved (geometric mean 50% inhibitory concentrations [IC
50
] = 248, 76.9, and 19.1 nM in 2010 to 2013 and 33.4, 14.9, and 7.5 nM in 2016, respectively [
P
< 0.001 for all comparisons]), the sensitivity to lumefantrine decreased (IC
50
= 3.0 nM in 2010 to 2013 and 5.4 nM in 2016 [
P
< 0.001]), and the sensitivity to dihydroartemisinin was unchanged (IC
50
= 1.4 nM). These changes were accompanied by decreased prevalence of transporter mutations associated with aminoquinoline resistance and low prevalence of polymorphisms recently associated with resistance to artemisinins or piperaquine. Antimalarial drug sensitivities are changing in Uganda, but novel genotypes associated with DP treatment failure in Asia are not prevalent.
Staphylococcus aureus Strain Newman D2C Contains Mutations in Major Regulatory Pathways That Cripple Its Pathogenesis
Authors: Sause William E. , Copin Richard , O'Malley Aidan , Chan Rita , Morrow Brian J. , Buckley Peter T. , Fernandez Jeffrey , Lynch A. Simon , Shopsin Bo , Torres Victor J. 
Published: September 2017

ABSTRACT

Staphylococcus aureus
is a major human pathogen that imposes a great burden on the health care system. In the development of antistaphylococcal modalities intended to reduce the burden of staphylococcal disease, it is imperative to select appropriate models of
S. aureus
strains when assessing the efficacy of novel agents. Here, using whole-genome sequencing, we reveal that the commonly used strain Newman D2C from the American Type Culture Collection (ATCC) contains mutations that render the strain essentially avirulent. Importantly, Newman D2C is often inaccurately referred to as simply “Newman” in many publications, leading investigators to believe it is the well-described pathogenic strain Newman. This study reveals that Newman D2C carries a stop mutation in the open reading frame of the virulence gene regulator,
agrA
. In addition, Newman D2C carries a single-nucleotide polymorphism (SNP) in the global virulence regulator gene
saeR
that results in loss of protein function. This loss of function is highlighted by complementation studies, where the
saeR
allele from Newman D2C is incapable of restoring functionality to an
saeR
-null mutant. Additional functional assessment was achieved through the use of biochemical assays for protein secretion,
ex vivo
intoxications of human immune cells, and
in vivo
infections. Altogether, our study highlights the importance of judiciously screening for genetic changes in model
S. aureus
strains when assessing pathogenesis or the efficacy of novel agents. Moreover, we have identified a novel SNP in the virulence regulator gene
saeR
that directly affects the ability of the protein product to activate
S. aureus
virulence pathways.

IMPORTANCE
Staphylococcus aureus
is a human pathogen that imposes an enormous burden on health care systems worldwide. This bacterium is capable of evoking a multitude of disease states that can range from self-limiting skin infections to life-threatening bacteremia. To combat these infections, numerous investigations are under way to develop therapeutics capable of thwarting the deadly effects of the bacterium. To generate successful treatments, it is of paramount importance that investigators use suitable models for examining the efficacy of the drugs under study. Here, we demonstrate that a strain of
S. aureus
commonly used for drug efficacy studies is severely mutated and displays markedly reduced pathogenicity. As such, the organism is an inappropriate model for disease studies.
Prospective observational study to evaluate the performance of the BioSure HIV Self-Test in the hands of lay users
Authors: Saunders John , Brima Nataliya , Orzol Marzena , Phillips Laura , Milinkovic Ana , Carpenter Gary , Copas Andrew , Gilson Richard 
Published: September 2017

ObjectivesIn order to assess whether the BioSure HIV Self-Test could be reliably performed by users at home and to determine whether they were able to perform and correctly interpret the test, we carried out an evaluation study among attendees at a sexual health service.MethodsA prospective observational study of clinic attendees to determine their ability to follow the instructions, complete the test on themselves and correctly interpret the results. The evaluation included interpretation of three dummy (contrived) devices, chosen at random from a sample of 12 devices, to ensure that a sufficient number of all possible test outcomes were included.ResultsTwo hundred participants were recruited. 97.0% (95% CI 93.5 to 98.9) conducted the test so as to achieve a valid result. 99.5% correctly identified the test result. Participants correctly interpreted the result of 94.0% (95% CI 91.4 to 95.9) of 586 contrived devices.ConclusionsThe majority of participants were able to follow the instructions and perform the test in order to get a valid result. Interpretation of the test results was good and the majority of participants were able to correctly read the result of their own and contrived tests. The availability of HIV self-tests will provide another option to increase access to testing particularly for those who may not wish or are unable to access clinical services.
ITCZ Breakdown and Its Upscale Impact on the Planetary-Scale Circulation over the Eastern Pacific
Authors: Yang Qiu , Majda Andrew J. , Khouider Boualem 
Published: September 2017

Abstract
The eastern Pacific (EP) intertropical convergence zone (ITCZ) is sometimes observed to break down into several vortices on the synoptic time scale. It is still a challenge for present-day numerical models to simulate the ITCZ breakdown in the baroclinic modes. Also, the upscale impact of the associated mesoscale fluctuations on the planetary-scale circulation is not well understood. Here, a simplified multiscale model for the modulation of the ITCZ is used to study these issues. A prescribed two-scale heating drives the planetary-scale circulation through both planetary-scale mean heating and eddy flux divergence of zonal momentum, where the latter represents the upscale impact of mesoscale disturbances. In an idealized scenario where the heating only varies on the mesoscale, key features of the ITCZ breakdown in the baroclinic modes are captured. The eddy flux divergence of zonal momentum is characterized by midlevel (low level) eastward (westward) momentum forcing at subtropical latitudes of the Northern Hemisphere and opposite-signed midlevel momentum forcing at low latitudes. Such upscale impact of mesoscale fluctuations tends to accelerate (decelerate) planetary-scale zonal jets in the middle (lower) troposphere. Compared with deep heating, shallow heating induces stronger vorticity anomalies on the mesoscale and more significant eddy flux divergence of zonal momentum and acceleration–deceleration effects on the planetary-scale mean flow. In a more realistic scenario where the heating also varies on the planetary scale, the most significant zonal velocity anomalies are confined in the diabatic heating region.
Modeling of Aircraft Measurements of Ice Crystal Concentration in the Arctic and a Parameterization for Mixed-Phase Cloud
Authors: Fan Songmiao , Knopf Daniel A. , Heymsfield Andrew J. , Donner Leo J. 
Published: September 2017

Abstract
In this study, two parameterizations of ice nucleation rate on dust particles are used in a parcel model to simulate aircraft measurements of ice crystal number concentration Ni in the Arctic. The parcel model has detailed microphysics for droplet and ice nucleation, growth, and evaporation with prescribed vertical air velocities. Three dynamic regimes are considered, including large-scale ascent, cloud-top generating cells, and their combination. With observed meteorological conditions and aerosol concentrations, the parcel model predicts the number concentrations of size-resolved ice crystals, which may be compared to aircraft measurements. Model results show rapid changes with height/time in relative humidity, Ni, and thermodynamic phase partitioning, which is not resolved in current climate and weather forecasting models. Parameterizations for ice number and nucleation rate in mixed-phase stratus clouds are thus developed based on the parcel model results to represent the time-integrated effect of some microphysical processes in large-scale models.
A Mechanism of Mixed Layer Formation in the Indo–Western Pacific Southern Ocean: Preconditioning by an Eddy-Driven Jet-Scale Overturning Circulation
Authors: Li Qian , Lee Sukyoung 
Published: September 2017

AbstractThe formation of a narrow band of the deep winter mixed layer (hereinafter “mixed layer wedge”) in the Indo–western Pacific Southern Ocean is examined using an eddy-resolving Parallel Ocean Program (POP) model simulation. The mixed layer wedge starts to deepen in June, centered at 47.5°S, with a meridional scale of only ~2° latitude. Its center is located ~1° north of the model’s Subantarctic Front (SAF). The Argo-based observed mixed layer is similarly narrow and occurs adjacent to the observed SAF. In the small sector of 130°–142°E, where the SAF is persistent and the mixed layer is deepest, the formation of the narrow mixed layer wedge coincides with destratification underneath the mixed layer. This destratification can be attributed primarily to the downwelling branch of a jet-scale overturning circulation (JSOC). The JSOC, which was reported in an earlier study by the authors, is driven by eddy momentum flux convergence and is therefore thermally indirect: its descending branch occurs on the warmer equatorward flank of the SAF, promoting destratification during the warm season. The model-generated net air–sea heat flux reveals a similar wedge-like feature, indicating that the flux contributes to the mixed layer depth wedge, but again this feature is preconditioned by the JSOC. Ekman advection contributes to the formation of the mixed layer, but it occurs farther north of the region where the mixed layer initially deepens. These findings suggest that the eddy-driven JSOC associated with the SAF plays an important role in initiating the narrow, deep mixed layer wedge that forms north of the SAF.
A Noninterpolated Estimate of Horizontal Spatial Covariance from Nonorthogonally and Irregularly Sampled Scalar Velocities
Authors: Yoo Jang Gon , Kim Sung Yong , Cornuelle Bruce D. , Kosro P. Michael , Kurapov Alexander L. 
Published: September 2017

AbstractThis paper presents a least squares method to estimate the horizontal (isotropic or anisotropic) spatial covariance of two-dimensional orthogonal vector components, without introducing an intervening mapping step and biases, from the spatial covariance of the nonorthogonally and irregularly sampled raw scalar velocities. The field is assumed to be locally homogeneous in space and sampled in an ensemble so the unknown spatial covariance is a function of spatial lag only. The transformation between the irregular grid on which nonorthogonal scalar projections of the vector are sampled and the regular orthogonal grid on which they will be mapped is created using the geometry of the problem. The spatial covariance of the orthogonal velocity components of the field is parameterized by either the energy (power) spectrum in the wavenumber domain or the lagged covariance in the spatial domain. The energy spectrum is constrained to be nonnegative definite as part of the solution of the inverse problem. This approach is applied to three example sets of data, using nonorthogonally and irregularly sampled radial velocity data obtained from 1) a simple spectral model, 2) a regional numerical model, and 3) an array of high-frequency radars. In tests where the true covariance is known, the proposed direct approaches fitting to parameterizations of the nonorthogonally and irregularly sampled raw data in the wavenumber domain and spatial domain outperform methods that map the data to a regular grid before estimating the covariance.
Preoperative Positron Emission Tomography for Node‐Positive Head and Neck Cutaneous Squamous Cell Carcinoma
Authors: Hirshoren Nir , Olayos Elizabeth , Herschtal Alan , Ravi Kumar Aravind S. , Gyorki David E. 
Published: September 2017

ObjectivesSurgery is the primary treatment modality for node‐positive cutaneous squamous cell carcinoma of the head and neck with no distant disease (HNcSCC‐M0). The role of preoperative positron emission tomography/computed tomography (PET/CT) scan for these patients is unclear. We compared preoperative PET/CT with final histopathology among patients undergoing lymphadenectomy and/or parotidectomy for HNcSCC‐M0.Study DesignCase series with chart review.SettingSingle Australian center.Subjects and MethodsInvestigation included disease parameters and preoperative CT and PET/CT findings of 64 patients with node‐positive HNcSCC without distant metastatic disease. Fisher’s exact test was used to test for a difference in the proportion of patients with chronic lymphocytic leukemia between the false‐ and true‐negative PET/CT subgroups.ResultsOf 64 patients who underwent PET/CT prior to surgery for node‐positive HNcSCC‐M0, 56 underwent a neck dissection and 30, a parotidectomy. Of these, 13 neck dissections and 2 parotidectomies were performed in the absence of FDG‐avid (18F‐fludeoxyglucose) nodes in these nodal fields. The PET/CT positive predictive value of the neck was 91.1%. The negative predictive values in the neck and parotid regions were 60%. Of the false‐negative subgroup, 66.7% had chronic lymphocytic leukemia, compared with 11.1% of the true‐negative subgroup (P =. 09). Based on PET/CT findings, surgical plans according to preoperative CT were changed for 6.25% of patients.ConclusionUse of PET/CT for surgical candidates with node‐positive HNcSCC‐M0 has high specificity and positive predictive value with relatively low sensitivity and negative predictive value. A statistical trend toward a higher rate of chronic lymphocytic leukemia among patients with false‐negative results is suggested.
Preoperative psychosocial factors predicting patient’s functional recovery after total knee or total hip arthroplasty: a systematic review
Authors: Bletterman Anouck N , de Geest-Vrolijk Marcella E , Vriezekolk Johanna E , Nijhuis-van der Sanden Maria W , van Meeteren Nico LU , Hoogeboom Thomas J 
Published: September 2017

Objective: To evaluate the predictive value of preoperative psychosocial factors on the perceived and observed postoperative patient’s functional recovery during the post-hospital phase and up to 12 months after hospital discharge of patients who underwent total knee or total hip arthroplasty. Methods: A systematic review was performed. MEDLINE, CINAHL, EMBASE and PsychINFO were systematically screened in order to find prospective longitudinal studies. Risk of bias was assessed using a modified version of a 27-item checklist for prognostic studies, as previously used by Veerbeek. A qualitative analysis was performed using the method of Zwikker. Results: A total of 26 studies, with a total of 11,020 patients, were included. In total, 22 studies were judged as having a high risk of bias. Overall, no longitudinal association with perceived or observed functional recovery was found in all of the seven preoperative psychosocial categories: A: mental well-being, B: cognitions, C: beliefs, D: expectations, E: coping, F: social support or G: personality traits in total joint arthroplasty. Mental well-being seems to be the exception in one time period (>6 weeks through ≤3 months) and change score in observed functional recovery, but only in patients awaiting total knee arthroplasty (100% and 75% of the variables were significantly and consistently associated, respectively). Conclusion: Overall, the results of this systematic review suggest that there is no longitudinal association between preoperative psychosocial factors and perceived or observed patient’s postoperative functional recovery after total joint arthroplasty. The psychological category mental well-being is related to observed postoperative recovery >6 weeks through ≤3 months and to change score after total knee arthroplasty.
Patterns in Economics Journal Acceptances and Rejections
Authors: Clain Suzanne Heller , Leppel Karen 
Published: September 2017

This study surveyed a sample of authors of articles published in Economics journals to gain insight into their experiences in submitting their manuscripts for publication. We explored factors related to receiving a desk rejection (rejection by editor without the article being sent out for review by referees). We also examined characteristics linked to whether authors were asked by the journal publishing the article to make extensive revisions prior to acceptance. In addition, we studied whether, after rejection, authors were likely to make substantial revisions prior to submission to another journal. Characteristics considered included respondent’s academic rank and prior publishing history at a particular journal, presence of coauthors, authors’ genders, and journal rank. JEL Classifications: A140, J16