bluuebunny/crossref_metadata_2025_split huggingface dataset:
Corticobasal degeneration initially developing motor versus non‐motor symptoms: a comparative clinicopathological study
Authors: Ikeda Chikako , Yokota Osamu , Nagao Shigeto , Ishizu Hideki , Morisada Yumi , Terada Seishi , Nakashima Yoshihiko , Akiyama Haruhiko , Uchitomi Yosuke 
Published: September 2014

AbstractBackgroundClinical presentations of pathologically confirmed corticobasal degeneration (CBD) vary, and the heterogeneity makes its clinical diagnosis difficult, especially when a patient lacks any motor disturbance in the early stage.MethodsWe compared clinical and pathological features of four pathologically confirmed CBD cases that initially developed non‐motor symptoms, including behavioural and psychiatric symptoms but without motor disturbance (CBD‐NM), and five CBD cases that initially developed parkinsonism and/or falls (CBD‐M). The age range at death for the CBD‐NM and CBD‐M subjects (58–85 years vs 45–67 years) and the range of disease duration (2–18 years vs 2–6 years) did not significantly differ between the groups.ResultsProminent symptoms in the early stage of CBD‐NM cases included self‐centred behaviours such as frontotemporal dementia (n = 1), apathy with and without auditory hallucination (n = 2), and aggressive behaviours with delusion and visual hallucination (n = 1). Among the four CBD‐NM cases, only one developed asymmetric motor disturbance, and two could walk without support throughout the course. Final clinical diagnoses of the CBD‐NM cases were frontotemporal dementia (n = 2), senile psychosis with delirium (n = 1), and schizophrenia (n = 1). Neuronal loss was significantly less severe in the subthalamic nucleus and substantia nigra in the CBD‐NM cases than in the CBD‐M cases. The severity of tau pathology in all regions examined was comparable in the two groups.ConclusionCBD cases that initially develop psychiatric and behavioural changes without motor symptoms may have less severe degenerative changes in the subthalamic nucleus and substantia nigra, and some CBD cases can lack motor disturbance not only in the early stage but also in the last stage of the course.
Multi‐Peer Disagreement and the Preface Paradox
Authors: Boyce Kenneth , Hazlett Allan 
Published: September 2014

AbstractThe problem of multi‐peer disagreement concerns the reasonable response to a situation in which you believeP1…Pnand disagree with a group of ‘epistemic peers’ of yours, who believe ∼P1… ∼Pn, respectively. However, the problem of multi‐peer disagreement is a variant on the preface paradox; because of this the problem poses no challenge to the so‐called ‘steadfast view’ in the epistemology of disagreement, on which it is sometimes reasonable to believePin the face of peer disagreement aboutP. After some terminology is defined (§1), Peter vanInwagen's challenge to the steadfast view will be presented (§2). The preface paradox will then be presented and diagnosed (§3), and it will be argued that vanInwagen's challenge relies on the same principle that generates the preface paradox (§4). The reasonable response to multi‐peer disagreement will be discussed (§5), and an objection addressed (§6).
A Decomposition Analysis of the Relationship Between Parental Income and Multiple Child Outcomes
Authors: Washbrook Elizabeth , Gregg Paul , Propper Carol 
Published: September 2014

SummaryThe paper explores the relationship between family income and a range of cognitive, socioemotional and health outcomes in mid-childhood. Child developmental outcomes are conceptualized as the result of an underlying set of associations or pathways running from distal factors (broad indicators of family characteristics and resources) to proximal factors (parental behaviours and aspects of the child's lived environment). We use a decomposition framework to compare the associations underpinning the raw income gradients in the different outcomes systematically. We find considerable variation in the extent of the income gradients, and in the factors that can account for them, across developmental domains.
Bayesian Estimation of Long-Term Health Consequences for Obese and Normal-Weight Elderly People
Authors: Hong Hyokyoung Grace , Yue Yu , Ghosh Pulak 
Published: September 2014

SummaryObesity is a rapidly growing public health problem even among the elderly. Understanding the disabling consequences of obesity in the elderly will help us to design better effective intervention management guidelines for the elderly obese. To examine the long-term health consequences of the obese elderly, we present a joint model consisting of two bivariate ordered responses observed at successive time points. The bivariate ordered response model corresponds to the subject's self-reporting health status outcomes including self-rated health and functional status. Although the joint model that we propose is generally suited for use in health and disease research, where the ordered value responses are observed at successive time points, we further extend it by addressing some of the challenges by incorporating the semiparametric features in the ordinal logistic model, by modelling the underlying latent states of health that are associated with self-rated health, by jointly modelling the bivariate ordinal outcomes to mitigate the variability of the single response and by accounting for the non-ignorable missing data due to different reasons through a multinomial logit model. The motivating data were obtained from the Second Longitudinal Study of Aging, which are longitudinal survey data from 1994–2000 providing various useful information on the health status of elderly people. Parameter estimation of our joint model was performed in a Bayesian framework via Markov chain Monte Carlo methods. Analytical results demonstrate the difference in longitudinal patterns of the health outcomes between the two weight groups, validating our hypothesis that different management strategies for the obese elderly should be employed.
Choice, Competition and Care – Developments in English Social Care and the Impacts on Providers and Older Users of Home Care Services
Authors: Rodrigues Ricardo , Glendinning Caroline 
Published: September 2014

AbstractThis article critically examines recent changes in markets for home (domiciliary) care services in England. During the 1990s, the introduction of competition between private (for‐profit and charitable) organizations and local authority providers of long‐term care services aimed to create a ‘mixed economy’ of supply. More recently, care markets have undergone further reforms through the introduction of direct payments and personal budgets. Underpinned by discourses of user choice, these mechanisms aim to offer older people increased control over the public resources for their care, thereby introducing further competitive pressures within local care markets.The article presents early evidence of these changes on:

The commissioning and contracting of home care services by local authorities and individual older people.
The experiences and outcomes for individual older people using home care services.
Drawing on evidence from two recent empirical studies, the article describes how the new emphasis on choice and competition is being operationalized within six local care markets. There are suggestions of small increases in user agency and in opportunities for older people to receive more personalized home care, in which the quality of care‐giving relationships can also be optimized. However, the article also presents early evidence of increases in risk and costs associated with the expansion of competition and choice, both for organizations providing home care services and for individual older service users.
Spatial variability of volcanic features in early‐stage rift settings: the case of the Tanzania Divergence, East African rift system
Authors: Isola Ilaria , Mazzarini Francesco , Bonini Marco , Corti Giacomo 
Published: September 2014

AbstractClose relationships between deformation and volcanism are well documented in relatively late evolutionary stages of continental rifting, whereas these are poorly constrained in less mature rifting stages. To investigate the control of inherited structures on faulting and volcanism, we present a statistical analysis of volcanic features, faults and pre‐rift fabric in the Tanzania Divergence, where volcanic features occur extensively in in‐rift and off‐rift areas. Our results show that in mature rift sectors (Natron), magma uprising is mostly controlled by fractures/faults responding to the far‐field stress, whereas the distribution of volcanism during initial rifting (Eyasi) is controlled by inherited structures oblique to the regional extension direction. Off‐rift sectors show a marked control of pre‐rift structures on magma emplacement, which may not respond to the regional stress field. Thus, the use of off‐rift magmatic features as stress indicators should take into account the role of pre‐existing structures.
Evaluation of acid–base disorders in dogs and cats presenting to an emergency room. Part 1: Comparison of three methods of acid–base analysis
Authors: Hopper Kate , Epstein Steven E. , Kass Philip H. , Mellema Matthew S. 
Published: September 2014

AbstractObjectiveTo compare the diagnostic performance of the traditional approach to acid–base analysis with the Stewart approach and a semiquantitative approach.DesignProspective cohort study.SettingUniversity teaching hospital.AnimalsA total number of 84 dogs and 14 cats presenting to a university teaching hospital emergency room.ProceduresAll dogs and cats in which venous blood samples for acid–base, lactate, and serum biochemical analysis were all collected within 60 minutes of each other, over a 5‐month enrollment period. Acid–base analysis was performed using the traditional approach, Stewart approach, and a semiquantitative approach.ResultsTraditional acid–base analysis identified respiratory acid–base abnormalities in 14/98 animals and metabolic acid–base abnormalities in 67/98. A mixed disorder of metabolic acidosis and respiratory alkalosis was most common occurring in 29/98 patients. The Stewart approach identified metabolic abnormalities in 82/98 patients; strong ion difference abnormalities were evident in 68/98 cases; an increased strong ion gap acidosis was identified in 49/98 cases; and changes in the quantity of weak acids in 25/98 cases. The semiquantitative approach identified abnormalities in all cases evaluated. Of the 14 patients with a primary respiratory acid–base abnormality, the Stewart approach identified metabolic abnormalities in 9 and the semiquantitative approach found abnormalities in all animals.Conclusions and Clinical RelevanceThe physicochemical approaches diagnosed more acid–base abnormalities in this population than the traditional approach although many of the abnormalities identified were small and of unknown clinical relevance. The physicochemical approaches may provide greater insight as to the underlying etiology of abnormalities, which maybe of particular relevance to cases with changes in albumin and/or phosphorus concentration.
Evaluation of Meropenem Regimens Suppressing Emergence of Resistance in Acinetobacter baumannii with Human Simulated Exposure in an
In Vitro
Intravenous-Infusion Hollow-Fiber Infection Model
Authors: Li Xin , Wang Lin , Zhang Xian-Jia , Yang Yang , Gong Wei-Tao , Xu Bin , Zhu Ying-Qun , Liu Wei 
Published: September 2014

ABSTRACT

The emergence of resistance to carbapenems in
Pseudomonas aeruginosa
can be suppressed by optimizing the administration of meropenem. However, whether the same is true for
Acinetobacter baumannii
is not fully understood. We assessed the bactericidal activity of meropenem and its potency to suppress the emergence of resistance in
A. baumannii
with human simulated exposure in an
in vitro
intravenous-infusion hollow-fiber infection model (HFIM). Two clinical strains of carbapenem-susceptible multidrug-resistant
A. baumannii
(CS-MDRAB), CSRA24 and CSRA91, were used, and their MICs and mutant prevention concentrations (MPCs) were determined. Six meropenem dosage regimens (0.5, 1.0, or 2.0 g given every 8 h [q8h] with a 0.5-h or 3-h infusion for seven consecutive days) were simulated and then evaluated in the HFIM. Both the total population and resistant subpopulations of the two strains were quantified. Drug concentrations were measured by high-performance liquid chromatography. All dosage regimens, except for the lowest dosage (0.5 g for both the 0.5-h and 3-h infusions), showed 3-log CFU/ml bacterial killing. Dosage regimens of 2.0 g with 0.5-h and 3-h infusions exhibited an obvious bactericidal effect and suppressed resistance. Selective amplification of subpopulations with reduced susceptibility to meropenem was suppressed with a percentage of the dosage interval in which meropenem concentrations exceeded the MPC (
T
>MPC) of ≥20% or with a ratio of
T
>MPC to the percentage of the dosage interval in which drug concentrations are within the mutant selection window of ≥0.25. Our
in vitro
data support the use of a high dosage of meropenem (2.0 g q8h) for the treatment of severe infection caused by CS-MDRAB.
Impact of Hypoalbuminemia on Voriconazole Pharmacokinetics in Critically Ill Adult Patients
Authors: Vanstraelen Kim , Wauters Joost , Vercammen Ine , de Loor Henriette , Maertens Johan , Lagrou Katrien , Annaert Pieter , Spriet Isabel 
Published: September 2014

ABSTRACT

Setting the adequate dose for voriconazole is challenging due to its variable pharmacokinetics. We investigated the impact of hypoalbuminemia (<35 g/liter) on voriconazole pharmacokinetics in adult intensive care unit (ICU) patients treated with voriconazole (20 samples in 13 patients) as well as in plasma samples from ICU patients that had been spiked with voriconazole at concentrations of 1.5 mg/liter, 2.9 mg/liter, and 9.0 mg/liter (66 samples from 22 patients). Plasma albumin concentrations ranged from 13.8 to 38.7 g/liter. Total voriconazole concentrations in adult ICU patients treated with voriconazole ranged from 0.5 to 8.7 mg/liter. Unbound and bound voriconazole concentrations were separated using high-throughput equilibrium dialysis followed by liquid chromatography-tandem mass spectrometry (LC-MSMS). Multivariate analysis revealed a positive relationship between voriconazole plasma protein binding and plasma albumin concentrations (
P
< 0.001), indicating higher unbound voriconazole concentrations with decreasing albumin concentrations. The correlation is more pronounced in the presence of elevated bilirubin concentrations (
P
= 0.05). We therefore propose to adjust the measured total voriconazole concentrations in patients with abnormal plasma albumin and total serum bilirubin plasma concentrations who show adverse events potentially related to voriconazole via a formula that we developed. Assuming 50% protein binding on average and an upper limit of 5.5 mg/liter for total voriconazole concentrations, the upper limit for unbound voriconazole concentrations is 2.75 mg/liter. Alterations in voriconazole unbound concentrations caused by hypoalbuminemia and/or elevated bilirubin plasma concentrations cannot be countered immediately, due to the adult saturated hepatic metabolism. Consequently, increased unbound voriconazole concentrations can possibly cause adverse events, even when total voriconazole concentrations are within the reference range.
Enterococcus faecium PBP5-S/R, the Missing Link between PBP5-S and PBP5-R
Authors: Pietta Ester , Montealegre Maria Camila , Roh Jung Hyeob , Cocconcelli Pier Sandro , Murray Barbara E. 
Published: September 2014

ABSTRACT

During a study to investigate the evolution of ampicillin resistance in
Enterococcus faecium
, we observed that a number of
E. faecium
strains, mainly from the recently described subclade A2, showed PBP5 sequences in between PBP5-S and PBP5-R. These hybrid PBP5-S/R patterns reveal a progression of amino acid changes from the S form to the R form of this protein; however, these changes do not strictly correlate with changes in ampicillin MICs.
Mutation-Driven β-Lactam Resistance Mechanisms among Contemporary Ceftazidime-Nonsusceptible Pseudomonas aeruginosa Isolates from U.S. Hospitals
Authors: Castanheira Mariana , Mills Janet C. , Farrell David J. , Jones Ronald N. 
Published: September 2014

ABSTRACT

OprD loss and hyperexpression of AmpC, MexAB-OprM, MexCD-OprJ, MexEF-OprN, and MexXY-OprM were evaluated among 120
Pseudomonas aeruginosa
isolates collected during 2012 in U.S. hospitals and selected based on ceftazidime MIC values (1 to >32 μg/ml). AmpC derepression (10-fold greater than that with the control) and OprD loss (decreased/no band) were the most prevalent resistance mechanisms: 47.5 and 45.8% of the isolates were considered positive, respectively. Elevated expression of the efflux pumps MexAB-OprM, MexCD-OprJ, MexEF-OprN, and MexXY-OprM was observed in 32.5, 8.3, 0.0, and 28.4% of the isolates, respectively. A total of 21 different combinations of resistance mechanisms were noted, and the most prevalent included AmpC derepression with OprD loss with and without efflux hyperexpression (38 and 10 isolates, respectively). A total of 26 isolates had no changes in the resistance mechanisms tested and had lower MIC values for all β-lactams or β-lactam/β-lactamase inhibitor combinations analyzed. OprD loss had a strong correlation with elevated MIC results for imipenem and meropenem (median MIC values of 8 and 4 μg/ml, respectively), with all combinations displaying OprD loss also displaying elevated median MIC values for these carbapenems (4 to >8 μg/ml). AmpC expression levels were greater in isolates displaying elevated cefepime, ceftazidime, or piperacillin-tazobactam MIC values (≥4, ≥4, and ≥16 μg/ml, respectively). Isolates displaying derepressed AmpC had ceftolozane-tazobactam MIC values ranging from 1 to 16 μg/ml. No strong correlation was noticed with MIC values for this β-lactam/β-lactamase inhibitor combination and OprD loss or hyperexpression of efflux systems. Two KPC-producing isolates were detected among 16 isolates displaying ceftolozane-tazobactam MIC values of ≥8 μg/ml.
The Type III Secretion Effector NleF of Enteropathogenic Escherichia coli Activates NF-κB Early during Infection
Authors: Pallett Mitchell A. , Berger Cedric N. , Pearson Jaclyn S. , Hartland Elizabeth L. , Frankel Gad 
Published: September 2014

ABSTRACT

The enteric pathogens enteropathogenic
Escherichia coli
(EPEC) and enterohemorrhagic
E. coli
employ a type 3 secretion system (T3SS) to manipulate the host inflammatory response during infection. Previously, it has been reported that EPEC, in a T3SS-dependent manner, induces an early proinflammatory response through activation of NF-κB via extracellular signal-regulated kinases 1 and 2 (ERK1/2) and protein kinase Cζ (PKCζ). However, the activation of NF-κB during infection has not yet been attributed to an effector. At later time points postinfection, NF-κB signaling is inhibited through the translocation of multiple effectors, including NleE and NleC. Here we report that the highly conserved non-LEE (locus of enterocyte effacement)-encoded effector F (NleF) shows both diffuse and mitochondrial localization during ectopic expression. Moreover, NleF induces the nuclear translocation of NF-κB p65 and the expression of interleukin 8 (IL-8) following ectopic expression and during EPEC infection. Furthermore, the proinflammatory activity and localization of NleF were dependent on the C-terminal amino acids LQCG. While the C-terminal domain of NleF has previously been shown to be essential for interaction with caspase-4, caspase-8, and caspase-9, the proinflammatory activity of NleF was independent of interaction with caspase-4, -8, or -9. In conclusion, EPEC, through the T3SS-dependent translocation of NleF, induces a proinflammatory response in an NF-κB-dependent manner in the early stages of infection.
Cross-Species Comparison of the Burkholderia pseudomallei, Burkholderia thailandensis, and Burkholderia mallei Quorum-Sensing Regulons
Authors: Majerczyk Charlotte D. , Brittnacher Mitchell J. , Jacobs Michael A. , Armour Christopher D. , Radey Matthew C. , Bunt Richard , Hayden Hillary S. , Bydalek Ryland , Greenberg E. Peter 
Published: September 2014

ABSTRACT

Burkholderia pseudomallei
,
Burkholderia thailandensis
, and
Burkholderia mallei
(the
Bptm
group) are close relatives with very different lifestyles:
B. pseudomallei
is an opportunistic pathogen,
B. thailandensis
is a nonpathogenic saprophyte, and
B. mallei
is a host-restricted pathogen. The acyl-homoserine lactone quorum-sensing (QS) systems of these three species show a high level of conservation. We used transcriptome sequencing (RNA-seq) to define the quorum-sensing regulon in each species, and we performed a cross-species analysis of the QS-controlled orthologs. Our analysis revealed a core set of QS-regulated genes in all three species, as well as QS-controlled factors shared by only two species or unique to a given species. This global survey of the QS regulons of
B. pseudomallei
,
B. thailandensis
, and
B. mallei
serves as a platform for predicting which QS-controlled processes might be important in different bacterial niches and contribute to the pathogenesis of
B. pseudomallei
and
B. mallei
.
Cell Separation in Vibrio cholerae Is Mediated by a Single Amidase Whose Action Is Modulated by Two Nonredundant Activators
Authors: Möll Andrea , Dörr Tobias , Alvarez Laura , Chao Michael C. , Davis Brigid M. , Cava Felipe , Waldor Matthew K. 
Published: September 2014

ABSTRACT

Synthesis and hydrolysis of septal peptidoglycan (PG) are critical processes at the conclusion of cell division that enable separation of daughter cells. Cleavage of septal PG is mediated by PG amidases, hydrolytic enzymes that release peptide side chains from the glycan strand. Most gammaproteobacteria, including
Escherichia coli
, encode several functionally redundant periplasmic amidases. However, members of the
Vibrio
genus, including the enteric pathogen
Vibrio cholerae
, encode only a single PG amidase, AmiB. Here, we show that
V. cholerae
AmiB is crucial for cell division and growth. Genetic and biochemical analyses indicated that AmiB is regulated by two activators, EnvC and NlpD, at least one of which is required for AmiB's localization to the cell division site. Localization of the activators (and thus of AmiB) is dependent upon the cell division protein FtsN. These factors mediate septal PG cleavage in
E. coli
as well; however, their precise roles vary between the two organisms in a number of ways. Notably, even though
V. cholerae
EnvC and NlpD appear to be functionally redundant under most growth conditions tested, NlpD is specifically required for intestinal colonization in the infant mouse model of cholera and for
V. cholerae
resistance against bile salts, perhaps due to environmental regulation of AmiB or its activators. Collectively, our findings reveal that although the cellular components that enable cleavage of septal PG appear to be generally conserved between
E. coli
and
V. cholerae
, they can be combined into diverse functional regulatory networks.