bluuebunny/crossref_metadata_2025_split huggingface dataset:
Act Versus Impact: Conservatives and Liberals Exhibit Different Structural Emphases in Moral Judgment
Authors: Hannikainen Ivar R. , Miller Ryan M. , Cushman Fiery A. 
Published: May 2017

AbstractConservatives and liberals disagree sharply on matters of morality and public policy. We propose a novel account of the psychological basis of these differences. Specifically, we find that conservatives tend to emphasize the intrinsic value of actions during moral judgment, in part by mentally simulating themselves performing those actions, while liberals instead emphasize the value of the expected outcomes of the action. We then demonstrate that a structural emphasis on actions is linked to the condemnation of victimless crimes, a distinctive feature of conservative morality. Next, we find that the conservative and liberal structural approaches to moral judgment are associated with their corresponding patterns of reliance on distinct moral foundations. In addition, the structural approach uniquely predicts that conservatives will be more opposed to harm in circumstances like the well‐known trolley problem, a result which we replicate. Finally, we show that the structural approaches of conservatives and liberals are partly linked to underlying cognitive styles (intuitive versus deliberative). Collectively, these findings forge a link between two important yet previously independent lines of research in political psychology: cognitive style and moral foundations theory.
Does Experimental Philosophy Have a Role to Play in Carnapian Explication?
Authors: Pinder Mark 
Published: May 2017

AbstractShepherd and Justus argue that experimental philosophy has an important role to play in the method of Carnapian explication, facilitating the preparatory stage during which the concept to be explicated is clarified. I raise concerns about their specific proposal, before sketching an alternative. In particular, I suggest that experimental philosophy can directly aid the construction of fruitful concepts. This provides a clear practical role for experimental philosophy, both within the sciences and theoretical inquiry more generally. In this respect, experimental philosophy may rightly be construed as one aspect of applied philosophy.
Presentism, Redemption, and Moral Development
Authors: Pezet Robert Edward 
Published: May 2017

AbstractThis paper explores what could justify some intuitive temporal asymmetries regarding redemption and the distribution of ills and goods throughout an agent's lifespan. After exposing the inadequacies of causal explanations – based on our differential ability to affect the future, but not the past – a metaphysical explanation is outlined in relation to three competing temporal‐ontological profiles of agents, and their varying accounts of a being's development. Only one of those conceptions of agents – supported byPresentism, the thesis that everything is present – offers an account justifying the intuitive temporal asymmetries. Finally, consequences are then drawn for the possibility of true redemption.
Water quality implications of hydrologic restoration alternatives in the Florida Everglades, United States
Authors: Naja Melodie , Childers Daniel L. , Gaiser Evelyn E. 
Published: May 2017

AbstractThe use of models to generate future scenarios is an important tool for restoration planning. We used a scenario modeling approach to examine water quality implications of five options for Everglades hydrologic restoration. In oligotrophic Everglades wetlands, phosphorus (P) inputs exceeding 10 µg/L cause P accumulation in soils and a shift to cattail marsh. Everglades restoration seeks to improve wetland hydrology while ensuring that delivered water contains no more than 10 µg P/L (long‐term average). Outputs from a landscape‐scale ecological model, the Everglades Landscape Model (ELM), showed that P concentrations in new water inputs will be controlled by P uptake by constructed treatment wetlands and by the movement of legacy P. Benthic periphyton responds quickly to changes in P, initiating a eutrophication response cascade, so we used ELM output to drive periphyton response models that predicted abundance, quality, and composition. All five restoration scenarios had similar effects on these three attributes in Everglades National Park, but variable responses across the other wetland units depended on water delivery and legacy P mobilization. Periphyton biomass was considerably reduced in scenarios that maximized freshwater delivery, but predicted values for periphyton total P were below the legal P concentration maximum in most of the Everglades. Benthic algal edibility increased more than 4‐fold, with the greatest increases in the deeper water areas. To meet water quality standards for the five restoration scenarios, we estimated that Everglades restoration should include an additional 105–156 km2 of treatment marshes upstream of surface water inflows to the landscape.
Population Pharmacokinetic Model Linking Plasma and Peripheral Blood Mononuclear Cell Concentrations of Efavirenz and Its Metabolite, 8-Hydroxy-Efavirenz, in HIV Patients
Authors: Habtewold Abiy , Aklillu Eleni , Makonnen Eyasu , Yimer Getnet , Bertilsson Leif , Burhenne Jürgen , Owen Joel S. 
Published: May 2017

ABSTRACT

The objectives of this study were to characterize the population pharmacokinetics (PK) of efavirenz (EFV) and 8-hydroxy-efavirenz (8OHEFV) in plasma and peripheral blood mononuclear cells (PBMCs) and to explore covariates affecting the PK parameters. Fifty-one patients had steady-state 0-to-24-h concentrations of EFV and 8OHEFV in plasma with corresponding concentrations in PBMCs, while 261 patients had one or two sparse concentrations at 16 ± 1 h postdose at weeks 4 and/or 16. The pharmacogenetic markers
CYP2B6*6
,
CYP3A5*3
,
CYP3A5*6
,
UGT2B7*2
,
ABCB1
(3435C→T, 3842A→G),
OATP1B1*1B
, and
OATP1B1*5
, the presence of a rifampin-based antituberculosis (anti-TB) regimen, baseline body weight and organ function values, and demographic factors were explored as covariates. EFV concentration data were well described by a two-compartment model with first-order absorption (

K
a

) and absorption lag time (
A
lag
) (

K
a

= 0.2 h
−1
;
A
lag
= 0.83 h; central compartment clearance [CL
c
/
F
] for
CYP2B6*1/*1
= 18 liters/h, for
CYP2B6*1/*6
= 14 liters/h, and for
CYP2B6*6/*6
= 8.6 liters/h) and PBMCs as a peripheral compartment. EFV transfer from plasma to PBMCs was first order (CL
p
/
F
= 32 liters/h), followed by capacity-limited return (
V
max
= 4,400 ng/ml/h;

K
m

= 710 ng/ml). Similarly, 8OHEFV displayed a first-order elimination and distribution to PBMCs, with a capacity-limited return to plasma. No covariate relationships resulted in a significant explanation of interindividual variability (IIV) on the estimated PK parameters of EFV and 8OHEFV, except for
CYP2B6*6
genotypes, which were consistent with prior evidence. Both EFV and 8OHEFV accumulated to higher concentrations in PBMCs than in plasma and were well described by first-order input and Michaelis-Menten kinetics removal from PBMCs.
CYP2B6*6
genotype polymorphisms were associated with decreased EFV and 8OHEFV clearance.
Aerosolized Polymyxin B for Treatment of Respiratory Tract Infections: Determination of Pharmacokinetic-Pharmacodynamic Indices for Aerosolized Polymyxin B against Pseudomonas aeruginosa in a Mouse Lung Infection Model
Authors: Lin Yu-Wei , Zhou Qi , Onufrak Nikolas J. , Wirth Veronika , Chen Ke , Wang Jiping , Forrest Alan , Chan Hak-Kim , Li Jian 
Published: May 2017

ABSTRACT

Pulmonary administration of polymyxins is increasingly used for the treatment of respiratory tract infections caused by multidrug-resistant Gram-negative bacteria, such as those in patients with cystic fibrosis. However, there is a lack of pharmacokinetics (PK), pharmacodynamics (PD), and toxicity data of aerosolized polymyxin B to inform rational dosage selection. The PK and PD of polymyxin B following pulmonary and intravenous dosing were examined in neutropenic infected mice, and the data were analyzed by a population PK model. Dose fractionation study was performed for total daily doses between 2.06 and 24.8 mg base/kg of weight against
Pseudomonas aeruginosa
ATCC 27853, PAO1, and FADDI-PA022 (MIC of 1 mg/liter for all three strains). Histopathological examination of the lung was undertaken at 24 h posttreatment in both healthy and neutropenic infected mice. A two-compartment PK model was required for both epithelial lining fluid (ELF) and plasma drug exposure. The model consisted of central and peripheral compartments and was described by bidirectional first-order distribution clearance. The ratio of the area under the curve to the MIC (AUC/MIC) was the most predictive PK/PD index to describe the antimicrobial efficacy of aerosolized polymyxin B in treating lung infections in mice (
R
2
of 0.70 to 0.88 for ELF and 0.70 to 0.87 for plasma). The AUC/MIC targets associated with bacteriostasis against the three
P. aeruginosa
strains were 1,326 to 1,506 in ELF and 3.14 to 4.03 in plasma. Histopathological results showed that polymyxin B aerosols significantly reduced lung inflammation and preserved lung epithelial integrity. This study highlights the advantageous PK/PD characteristics of pulmonary delivery of polymyxin B over intravenous administration in achieving high drug exposure in ELF.
Penicillin Dried Blood Spot Assay for Use in Patients Receiving Intramuscular Benzathine Penicillin G and Other Penicillin Preparations To Prevent Rheumatic Fever
Authors: Page-Sharp Madhu , Coward Jonathan , Moore Brioni R. , Salman Sam , Marshall Lewis , Davis Timothy M. E. , Batty Kevin T. , Manning Laurens 
Published: May 2017

ABSTRACTRheumatic heart disease (RHD) remains an important global health challenge. Administration of benzathine penicillin (BPG) every 3 to 4 weeks is recommended as a secondary prophylaxis to prevent recurrent episodes of acute rheumatic fever and subsequent RHD. Following intramuscular injection, BPG is hydrolyzed to penicillin G (benzylpenicillin). However, little is known of the pharmacokinetics (PK) of BPG in pediatric populations at high risk of RHD or of the pharmacokinetic-pharmacodynamic relationship between penicillin exposure and clinically relevant outcomes. Dried blood spot (DBS) assays can facilitate PK studies in situations where frequent venous blood sampling is logistically difficult. A liquid chromatography-mass spectroscopy assay for penicillin G in plasma and DBS was developed and validated. Application of the DBS assay for PK studies was confirmed using samples from adult patients receiving penicillin as part of an infection management plan. The limit of quantification for penicillin G in DBS was 0.005 mg/liter. Penicillin G is stable in DBS for approximately 12 h at room temperature (22°C), 6 days at 4°C, and >1 month at −20°C. Plasma and DBS penicillin G concentrations for patients receiving BPG and penicillin G given via bolus doses correlated well and had comparable time-concentration profiles. There was poor correlation for patients receiving penicillin via continuous infusions, perhaps as a result of the presence of residual penicillin in the peripherally inserted central catheter, from which the plasma samples were collected. The present DBS penicillin G assay can be used as a surrogate for plasma concentrations to provide valid PK data for studies of BPG and other penicillin preparations developed to prevent rheumatic fever and RHD.
Etest and Sensititre YeastOne Susceptibility Testing of Echinocandins against Candida Species from a Single Center in Austria
Authors: Aigner Maria , Erbeznik Thomas , Gschwentner Martin , Lass-Flörl Cornelia 
Published: May 2017

ABSTRACT

Candida
species were tested for susceptibility to caspofungin, anidulafungin, and micafungin in order to evaluate the roles of Etest and Sensititre YeastOne in antifungal susceptibility testing for daily routines and to survey resistance. A total of 104
Candida
species isolates detected from blood cultures were investigated. With EUCAST broth microdilution as the reference method, essential agreement (EA), categorical agreement (CA), very major errors (VME), major errors (ME), and minor (MIN) errors were assessed by reading MICs at 18, 24, and 48 h. By use of EUCAST broth microdilution and species-specific clinical breakpoints (CBPs), echinocandin resistance was not detected during the study period. Using EUCAST CBPs, MIC readings at 24 h for the Etest and Sensititre YeastOne resulted in CA levels of 99% and 93% for anidulafungin and 99% and 97% for micafungin. Using revised CLSI CBPs for caspofungin, CA levels were 92% and 99% for Etest and Sensititre YeastOne. The Etest proved an excellent, easy-to-handle alternative method for testing susceptibility to anidulafungin and micafungin. Due to misclassifications, the Etest is less suitable for testing susceptibility to caspofungin (8% of isolates falsely tested resistant). The CA levels of Sensititre YeastOne were 93% and 97% for anidulafungin and micafungin (24 h) by use of EUCAST CBPs and increased to 100% for both antifungals if CLSI CBPs were applied and to 100% and 99% if Sensititre YeastOne epidemiological cutoff values (ECOFFs) were applied. No one echinocandin could be demonstrated to be superior to another
in vitro
. Since resistance was lacking among our
Candida
isolates, we cannot derive any recommendation from accurate resistance detection by the Etest and Sensititre YeastOne.
A Lower Baseline CD4/CD8 T-Cell Ratio Is Independently Associated with Immunodiscordant Response to Antiretroviral Therapy in HIV-Infected Subjects
Authors: Rosado-Sánchez I. , Herrero-Fernández I. , Álvarez-Ríos A. I. , Genebat M. , Abad-Carrillo M. A. , Ruiz-Mateos E. , Pulido F. , González-García J. , Montero M. , Bernal-Morell E. , Vidal F. , Leal M. , Pacheco Y. M. 
Published: May 2017

ABSTRACT
We explored if baseline CD4/CD8 T-cell ratio is associated with immunodiscordant response to antiretroviral therapy in HIV-infected subjects. Comparing immunodiscordant and immunoconcordant subjects matched by pretreatment CD4 counts, we observed a lower pretreatment CD4/CD8 T-cell ratio in immunodiscordant subjects. Furthermore, pretreatment CD4/CD8 T-cell ratio, but not CD4 counts, correlated with the main immunological alterations observed in immunodiscordants, including increased regulatory T-cell (Treg) frequency and T-cell turnover-related markers. Then, in a larger cohort, only baseline CD4/CD8 T-cell ratio was independently associated with immunodiscordance, after adjusting by the viral CXCR4-tropic HIV variants. Our results suggest that the CD4/CD8 T-cell ratio could be an accurate biomarker of the subjacent immunological damage triggering immunodiscordance.
Simkania negevensis, an Example of the Diversity of the Antimicrobial Susceptibility Pattern among Chlamydiales
Authors: Vouga Manon , Baud David , Greub Gilbert 
Published: May 2017

ABSTRACT

In past years, several
Chlamydia
-related bacteria have been discovered, including
Simkania negevensis
, the founding member of the
Simkaniaceae
family. We evaluated the antimicrobial susceptibility patterns of this emerging intracellular bacterium and highlighted significant differences, compared with related
Chlamydiales
members.
S. negevensis
was susceptible to macrolides, clindamycin, cyclines, rifampin, and quinolones. Importantly, unlike other
Chlamydiales
members, treatment with β-lactams and vancomycin did not induce the formation of aberrant bodies, leading to a completely resistant phenotype.
Peripheral T-Cell Reactivity to Heat Shock Protein 70 and Its Cofactor GrpE from Tropheryma whipplei Is Reduced in Patients with Classical Whipple's Disease
Authors: Trotta Lucia , Weigt Kathleen , Schinnerling Katina , Geelhaar-Karsch Anika , Oelkers Gerrit , Biagi Federico , Corazza Gino Roberto , Allers Kristina , Schneider Thomas , Erben Ulrike , Moos Verena 
Published: May 2017

ABSTRACT

Classical Whipple's disease (CWD) is characterized by the lack of specific Th1 response toward
Tropheryma whipplei
in genetically predisposed individuals. The cofactor GrpE of heat shock protein 70 (Hsp70) from
T. whipplei
was previously identified as a B-cell antigen. We tested the capacity of Hsp70 and GrpE to elicit specific proinflammatory T-cell responses. Peripheral mononuclear cells from CWD patients and healthy donors were stimulated with
T. whipplei
lysate or recombinant GrpE or Hsp70 before levels of CD40L, CD69, perforin, granzyme B, CD107a, and gamma interferon (IFN-γ) were determined in T cells by flow cytometry. Upon stimulation with total bacterial lysate or recombinant GrpE or Hsp70 of
T. whipplei
, the proportions of activated effector CD4
+
T cells, determined as CD40L
+
IFN-γ
+
, were significantly lower in patients with CWD than in healthy controls; CD8
+
T cells of untreated CWD patients revealed an enhanced activation toward unspecific stimulation and
T. whipplei
-specific degranulation, although CD69
+
IFN-γ
+
CD8
+
T cells were reduced upon stimulation with
T. whipplei
lysate and recombinant
T. whipplei
-derived proteins. Hsp70 and its cofactor GrpE are immunogenic in healthy individuals, eliciting effective responses against
T. whipplei
to control bacterial spreading. The lack of specific T-cell responses against these
T. whipplei
-derived proteins may contribute to the pathogenesis of CWD.
The Disulfide Bond Formation Pathway Is Essential for Anaerobic Growth of Escherichia coli
Authors: Meehan Brian M. , Landeta Cristina , Boyd Dana , Beckwith Jonathan 
Published: May 2017

ABSTRACT

Disulfide bonds are critical to the stability and function of many bacterial proteins. In the periplasm of
Escherichia coli
, intramolecular disulfide bond formation is catalyzed by the two-component disulfide bond forming (DSB) system. Inactivation of the DSB pathway has been shown to lead to a number of pleotropic effects, although cells remain viable under standard laboratory conditions. However, we show here that
dsb
strains of
E. coli
reversibly filament under aerobic conditions and fail to grow anaerobically unless a strong oxidant is provided in the growth medium. These findings demonstrate that the background disulfide bond formation necessary to maintain the viability of
dsb
strains is oxygen dependent. LptD, a key component of the lipopolysaccharide transport system, fails to fold properly in
dsb
strains exposed to anaerobic conditions, suggesting that these mutants may have defects in outer membrane assembly. We also show that anaerobic growth of
dsb
mutants can be restored by suppressor mutations in the disulfide bond isomerization system. Overall, our results underscore the importance of proper disulfide bond formation to pathways critical to
E. coli
viability under conditions where oxygen is limited.

IMPORTANCE
While the disulfide bond formation (DSB) system of
E. coli
has been studied for decades and has been shown to play an important role in the proper folding of many proteins, including some associated with virulence, it was considered dispensable for growth under most laboratory conditions. This work represents the first attempt to study the effects of the DSB system under strictly anaerobic conditions, simulating the environment encountered by pathogenic
E. coli
strains in the human intestinal tract. By demonstrating that the DSB system is essential for growth under such conditions, this work suggests that compounds inhibiting Dsb enzymes might act not only as antivirulents but also as true antibiotics.
Cysteine Biosynthesis Controls Serratia marcescens Phospholipase Activity
Authors: Anderson Mark T. , Mitchell Lindsay A. , Mobley Harry L. T. 
Published: May 2017

ABSTRACT

Serratia marcescens
causes health care-associated opportunistic infections that can be difficult to treat due to a high incidence of antibiotic resistance. One of the many secreted proteins of
S. marcescens
is the PhlA phospholipase enzyme. Genes involved in the production and secretion of PhlA were identified by screening a transposon insertion library for phospholipase-deficient mutants on phosphatidylcholine-containing medium. Mutations were identified in four genes (
cyaA
,
crp
,
fliJ
, and
fliP
) that are involved in the flagellum-dependent PhlA secretion pathway. An additional phospholipase-deficient isolate harbored a transposon insertion in the
cysE
gene encoding a predicted serine
O
-acetyltransferase required for cysteine biosynthesis. The
cysE
requirement for extracellular phospholipase activity was confirmed using a fluorogenic phospholipase substrate. Phospholipase activity was restored to the
cysE
mutant by the addition of exogenous
l
-cysteine or
O
-acetylserine to the culture medium and by genetic complementation. Additionally,
phlA
transcript levels were decreased 6-fold in bacteria lacking
cysE
and were restored with added cysteine, indicating a role for cysteine-dependent transcriptional regulation of
S. marcescens
phospholipase activity.
S. marcescens
cysE
mutants also exhibited a defect in swarming motility that was correlated with reduced levels of
flhD
and
fliA
flagellar regulator gene transcription. Together, these findings suggest a model in which cysteine is required for the regulation of both extracellular phospholipase activity and surface motility in
S. marcescens
.

IMPORTANCE
Serratia marcescens
is known to secrete multiple extracellular enzymes, but PhlA is unusual in that this protein is thought to be exported by the flagellar transport apparatus. In this study, we demonstrate that both extracellular phospholipase activity and flagellar function are dependent on the cysteine biosynthesis pathway. Furthermore, a disruption of cysteine biosynthesis results in decreased
phlA
and flagellar gene transcription, which can be restored by supplying bacteria with exogenous cysteine. These results identify a previously unrecognized role for CysE and cysteine in the secretion of
S. marcescens
phospholipase and in bacterial motility.