bluuebunny/crossref_metadata_2025_split huggingface dataset:
Real exchange rate assessment for Nigeria: an evaluation of determinants, strategies for identification and correction of misalignments
Authors: Ozsoz Emre , Akinkunmi Mustapha 
Published: February 2012

AbstractBy using monthly data for the 2004–2010 period and a vector error correction model approach, this paper evaluates the determinants of real exchange rates for the Nigerian Naira. Estimations suggest that oil prices, broad money supply, level of foreign reserves held by the Central Bank and interest rate differentials with trading partners can be used as good predictors of the long run Naira equilibrium real exchange rate. It is shown that the recent increases in the world price of oil have a significant appreciating effect in the real Naira rate, while increases in the money supply have the opposite impact. The study also uses the behavioural equilibrium exchange rate approach to identify the misalignments in the real Naira rate. Findings point out to the undervaluation of the Naira at the end of 2010.
PREGNANCY IN DIABETES AND KIDNEY DISEASE
Authors: Bramham Kate , Rajasingham Daghni 
Published: February 2012

SUMMARYWith appropriate multi‐disciplinary team care, most women with diabetic nephropathy will have successful pregnancy outcomes; however, pregnancy complications are increased compared to non‐diabetic individuals, particularly in those with poor glycaemic control. Women with more severe renal impairment, especially those with hypertension and proteinuria at are highest risk of worse pregnancy outcomes and deterioration in pre‐existing renal function. Pre‐pregnancy counselling should be offered to all women with diabetes in order to optimise diabetic care, and inform women of potential complications. Pregnancy is an indicator of long‐term health, and may indicate important issues for the future management of women with diabetic nephropathy.
CHANGING TRENDS IN END‐STAGE RENAL DISEASE DUE TO DIABETES IN THE UNITED KINGDOM
Authors: Hill C. J. , Fogarty D. G. 
Published: February 2012

SUMMARYBackground:In some countries, diabetic kidney disease (DKD) is responsible for half of all new patients requiring renal replacement therapy (RRT). Understanding the relationship between early and later stages of DKD is important as it is a preventable cause of renal failure. This review aims to establish the trends in end‐stage renal disease (ESRD) due to diabetes in the United Kingdom as the first step in this understanding.Methods:Using annual reports from the UK Renal Registry, we summarise the presentation, incidence, prevalence and survival of ESRD patients with diabetes over the last 10–15 years.Results:Between 1995 and 2009, initiation of RRT in diabetes patients increased from 12.3 to 27.6 patients per million population (pmp). These rates are approximately five times less than those of Caucasians in the United States suggesting fundamental differences in early DKD management. Survival of diabetic patients on dialysis has improved such that prevalent numbers on RRT increased from 47 to 117 pmp in a 12‐year period. A longer time to prepare patients for RRT is strongly related with better outcomes. In 2002, 23% of all patients with diabetic nephropathy were referred late, within 90 days of RRT start; by 2009, this figure had fallen to 11.2%. Access to renal transplantation, the best form of RRT, has improved with almost 12.5% of new transplants occurring in patients with diabetes compared to 8.3% in 1997.Conclusions:End Stage DKD is more extensively and better treated now than in the late 1990s and coincides with a time of rapid expansion of UK renal services. More diabetes patients start RRT, patients are referred earlier and survive longer. The prevalence of end‐stage DKD is 2.5 times what it was just over 10 years ago. However, across the United Kingdom, there still exists variation in the incidence and outcomes of end‐stage DKD. That these figures have grown so much but are still dwarfed by other countries’ burden of DKD merits further research. Further prevention of DKD is achievable for the United Kingdom and particularly critical for developing nations who can least afford the expensive ‘option’ of RRT.
DIABETIC FOOT CARE: PREVENTION IS BETTER THAN CURE
Authors: Meaney Beverley 
Published: February 2012

SUMMARYPatients receiving renal replacement therapy especially haemodialysis (HD) are at high risk of foot ulcers which can lead to amputation. With the increasing numbers of patients with diabetes now presenting with renal failure, renal nurses are in a pivotal position to educate patients and initiate and oversee good foot care. This paper describes the risk factors for these patients and discusses general care for prevention and treatment of these factors. Factors such as regular screening which can be done easily and effectively in an HD setting where patients attend regularly is the first method towards prevention. Care and treatment of foot wounds based on results from the author's unit are discussed. The creation of a diabetes care programme for the author's HD unit have resulted in a more holistic approach to the care of the patient with diabetes and renal disease with special attention to foot care, which in turn has lead to an improved standard of care and better management of the patients’ diabetes. This paper discusses information from this programme offering a summary of risks and treatments to assist those caring for these patients.
RENAL HEALTH AND TRANSPLANTATION: A FOCUS ON ETHNICITY
Authors: Randhawa Gurch 
Published: February 2012

SUMMARYIt is widely acknowledged within the United Kingdom that there are significant inequalities in renal health and transplant serv‐ices—in relation to demand for, access to and waiting times for these services—between minority ethnic groups in particular. This phenomenon is not unique to the United Kingdom and affects many other countries that have a strong tradition of immigration. The solutions to reducing these inequalities are multi‐faceted and require both short‐term and long‐term policy and resource‐driven initiatives. In the short term, there is an urgent need to increase the number of organ donors from minority ethnic groups which will positively impact upon improved access to transplantation and contribute to reduced waiting times. The increase in donor registration can only be achieved if there are evidence‐based, concerted and adequately resourced efforts to engage with minority ethnic communities at grass‐roots level. In the long term, public health interventions are required that proactively seek to prevent and manage long‐term conditions among the United Kingdom's multi‐ethnic and multi‐faith population, thereby reducing the demand for transplantation.
Techniques for the in vivo assessment of cardio‐renal function in zebrafish (Danio rerio) larvae
Authors: Rider Sebastien A. , Tucker Carl S. , del‐Pozo Jorge , Rose Kirsten N. , MacRae Calum A. , Bailey Matthew A. , Mullins John J. 
Published: February 2012

Key points
The anatomical structures and discrete nephric regions of the pronephric zebrafish kidney are similar to those of the mammalian nephron.
Renal blood supply and subsequent renal filtration rate are both key determinants of kidney function.
Our study developed classical functional assays for larval zebrafish that effectively model the effects of the nephrotoxin gentamicin and high salt loading.
The techniques demonstrate the disruption in ion and water balance resulting from reduced cardiovascular flow and renal filtration rate.
The ability to measure cardio‐renal function in zebrafish offers advantages associated with the fish model to gain a wider understanding of kidney physiology.
Prospective, Observational Study of Voriconazole Therapeutic Drug Monitoring among Lung Transplant Recipients Receiving Prophylaxis: Factors Impacting Levels of and Associations between Serum Troughs, Efficacy, and Toxicity
Authors: Mitsani Dimitra , Nguyen M. Hong , Shields Ryan K. , Toyoda Yoshiya , Kwak Eun J. , Silveira Fernanda P. , Pilewski Joseph M. , Crespo Maria M. , Bermudez Christian , Bhama Jay K. , Clancy Cornelius J. 
Published: February 2012

ABSTRACT

Voriconazole prophylaxis is common following lung transplantation, but the value of therapeutic drug monitoring is unknown. A prospective, observational study of lung transplant recipients (
n
= 93) receiving voriconazole prophylaxis was performed. Serum voriconazole troughs (
n
= 331) were measured by high-pressure liquid chromatography. The median initial and subsequent troughs were 1.91 and 1.46 μg/ml, respectively. The age of the patient directly correlated with initial troughs (
P
= 0.005). Patients that were ≥60 years old and cystic fibrosis patients were significantly more likely to have higher and lower initial troughs, respectively. In 95% (88/93) of patients, ≥2 troughs were measured. In 28% (25/88) and 32% (28/88) of these patients, all troughs were ≤1.5 μg/ml or >1.5 μg/ml, respectively. Ten percent (10/93) and 27% (25/93) of the patients developed invasive fungal infection (tracheobronchitis) and fungal colonization, respectively. The median troughs at the times of positive and negative fungal cultures were 0.92 and 1.72 μg/ml (
P
= 0.07). Invasive fungal infections or colonization were more likely with troughs of ≤1.5 μg/ml (
P
= 0.01) and among patients with no trough of >1.5 μg/ml (
P
= 0.007). Other cutoff troughs correlated less strongly with microbiologic outcomes. Troughs correlated directly with aspartate transferase levels (
P
= 0.003), but not with other liver enzymes. Voriconazole was discontinued due to suspected toxicity in 27% (25/93) of the patients. The troughs did not differ at the times of suspected drug-induced hepatotoxicity, central nervous system (CNS) toxicity, or nausea/vomiting and in the absence of toxicity. Voriconazole prophylaxis was most effective at troughs of >1.5 μg/ml. A cutoff for toxicity was not identified, but troughs of >4 μg/ml were rare. The data support a target range of >1.5 to 4 μg/ml.
Standardized Comparison of the Relative Impacts of HIV-1 Reverse Transcriptase (RT) Mutations on Nucleoside RT Inhibitor Susceptibility
Authors: Melikian George L. , Rhee Soo-Yon , Taylor Jonathan , Fessel W. Jeffrey , Kaufman David , Towner William , Troia-Cancio Paolo V. , Zolopa Andrew , Robbins Gregory K. , Kagan Ron , Israelski Dennis , Shafer Robert W. 
Published: February 2012

ABSTRACTDetermining the phenotypic impacts of reverse transcriptase (RT) mutations on individual nucleoside RT inhibitors (NRTIs) has remained a statistical challenge because clinical NRTI-resistant HIV-1 isolates usually contain multiple mutations, often in complex patterns, complicating the task of determining the relative contribution of each mutation to HIV drug resistance. Furthermore, the NRTIs have highly variable dynamic susceptibility ranges, making it difficult to determine the relative effect of an RT mutation on susceptibility to different NRTIs. In this study, we analyzed 1,273 genotyped HIV-1 isolates for which phenotypic results were obtained using the PhenoSense assay (Monogram, South San Francisco, CA). We used a parsimonious feature selection algorithm, LASSO, to assess the possible contributions of 177 mutations that occurred in 10 or more isolates in our data set. We then used least-squares regression to quantify the impact of each LASSO-selected mutation on each NRTI. Our study provides a comprehensive view of the most common NRTI resistance mutations. Because our results were standardized, the study provides the first analysis that quantifies the relative phenotypic effects of NRTI resistance mutations on each of the NRTIs. In addition, the study contains new findings on the relative impacts of thymidine analog mutations (TAMs) on susceptibility to abacavir and tenofovir; the impacts of several known but incompletely characterized mutations, including E40F, V75T, Y115F, and K219R; and a tentative role in reduced NRTI susceptibility for K64H, a novel NRTI resistance mutation.
Epidemiological Cutoff Values for Azoles and Aspergillus fumigatus Based on a Novel Mathematical Approach Incorporating
cyp51A
Sequence Analysis
Authors: Meletiadis J. , Mavridou E. , Melchers W. J. G. , Mouton J. W. , Verweij P. E. 
Published: February 2012

ABSTRACT

Epidemiological cutoff values (ECV) are commonly used to separate wild-type isolates from isolates with reduced susceptibility to antifungal drugs, thus setting the foundation for establishing clinical breakpoints for
Aspergillus fumigatus
. However, ECVs are usually determined by eye, a method which lacks objectivity, sensitivity, and statistical robustness and may be difficult, in particular, for extended and complex MIC distributions. We therefore describe and evaluate a statistical method of MIC distribution analysis for posaconazole, itraconazole, and voriconazole for 296
A. fumigatus
isolates utilizing nonlinear regression analysis, the normal plot technique, and recursive partitioning analysis incorporating
cyp51A
sequence data. MICs were determined by using the CLSI M38–A2 protocol (CLSI, CLSI document M38–A2, 2008) after incubation of the isolates for 48 h and were transformed into log
2
MICs. We found a wide distribution of MICs of all azoles, some ranging from 0.02 to 128 mg/liter, with median MICs of 32 mg/liter for itraconazole, 4 mg/liter for voriconazole, and 0.5 mg/liter for posaconazole. Of the isolates, 65% (192 of 296) had mutations in the
cyp51A
gene, and the majority of the mutants (90%) harbored tandem repeats in the promoter region combined with mutations in the
cyp51A
coding region. MIC distributions deviated significantly from normal distribution (D'Agostino-Pearson omnibus normality test
P
value, <0.001), and they were better described with a model of the sum of two Gaussian distributions (
R
2
, 0.91 to 0.96). The normal plot technique revealed a mixture of two populations of MICs separated by MICs of 1 mg/liter for itraconazole, 1 mg/liter for voriconazole, and 0.125 mg/liter for posaconazole. Recursive partitioning analysis confirmed these ECVs, since the proportions of isolates harboring
cyp51A
mutations associated with azole resistance were less than 20%, 20 to 30%, and >70% when the MICs were lower than, equal to, and higher than the above-mentioned ECVs, respectively.
Broad-Spectrum β-Lactam Antibiotics for Treating Experimental Peritonitis in Mice Due to Klebsiella pneumoniae Producing the Carbapenemase OXA-48
Authors: Mimoz Olivier , Grégoire Nicolas , Poirel Laurent , Marliat Manuella , Couet William , Nordmann Patrice 
Published: February 2012

ABSTRACT

A lethal peritonitis model was induced in mice with a
Klebsiella pneumoniae
isolate producing the carbapenemase OXA-48. Administration of a single dose (up to 100 mg/kg) of the antibiotic piperacillin-tazobactam, imipenem-cilastatin, ertapenem, or cefotaxime had little or no impact on lethality. Ceftazidime had the highest efficacy
in vivo
, which mirrored its
in vitro
activity; this was not the case for carbapenems. Therefore, ceftazidime may be recommended for the treatment of infections due to OXA-48 producers if they do not coproduce an extended-spectrum β-lactamase or a plasmid-mediated AmpC cephalosporinase.
Antimicrobial Action and Cell Agglutination by the Eosinophil Cationic Protein Are Modulated by the Cell Wall Lipopolysaccharide Structure
Authors: Pulido David , Moussaoui Mohammed , Andreu David , Nogués M. Victòria , Torrent Marc , Boix Ester 
Published: February 2012

ABSTRACT

Antimicrobial proteins and peptides (AMPs) are essential effectors of innate immunity, acting as a first line of defense against bacterial infections. Many AMPs exhibit high affinity for cell wall structures such as lipopolysaccharide (LPS), a potent endotoxin able to induce sepsis. Hence, understanding how AMPs can interact with and neutralize LPS endotoxin is of special relevance for human health. Eosinophil cationic protein (ECP) is an eosinophil secreted protein with high activity against both Gram-negative and Gram-positive bacteria. ECP has a remarkable affinity for LPS and a distinctive agglutinating activity. By using a battery of LPS-truncated
E. coli
mutant strains, we demonstrate that the polysaccharide moiety of LPS is essential for ECP-mediated bacterial agglutination, thereby modulating its antimicrobial action. The mechanism of action of ECP at the bacterial surface is drastically affected by the LPS structure and in particular by its polysaccharide moiety. We have also analyzed an N-terminal fragment that retains the whole protein activity and displays similar cell agglutination behavior. Conversely, a fragment with further minimization of the antimicrobial domain, though retaining the antimicrobial capacity, significantly loses its agglutinating activity, exhibiting a different mechanism of action which is not dependent on the LPS composition. The results highlight the correlation between the protein's antimicrobial activity and its ability to interact with the LPS outer layer and promote bacterial agglutination.
Preclinical Evaluation of the HIV-1 Fusion Inhibitor L'644 as a Potential Candidate Microbicide
Authors: Harman Sarah , Herrera Carolina , Armanasco Naomi , Nuttall Jeremy , Shattock Robin J. 
Published: February 2012

ABSTRACT

Topical blockade of the gp41 fusogenic protein of HIV-1 is one possible strategy by which microbicides could prevent HIV transmission, working early against infection, by inhibiting viral entry into host cells. In this study, we examined the potential of gp41 fusion inhibitors (FIs) as candidate anti-HIV microbicides. Preclinical evaluation of four FIs, C34, T20, T1249, and L'644, was performed using cellular and
ex vivo
genital and colorectal tissue explant models. Increased and sustained activity was detected for L'644, a cholesterol-derivatized version of C34, relative to the other FIs. The higher potency of L'644 was further increased with sustained exposure of cells or tissue to the compound. The activity of L'644 was not affected by biological fluids, and the compound was still active when tissue explants were treated after viral exposure. L'644 was also more active than other FIs against a viral escape mutant resistant to reverse transcriptase inhibitors (RTIs), demonstrating the potential of L'644 to be included as part of a multiactive antiretroviral (ARV) combination-based microbicide. These data support the further development of L'644 for microbicide application.
Acyclovir Achieves a Lower Concentration in African HIV-Seronegative, Herpes Simplex Virus 2-Seropositive Women than in Non-African Populations
Authors: Lu Yanhui , Celum Connie , Wald Anna , Baeten Jared M. , Cowan Frances , Delany-Moretlwe Sinead , Reid Stewart E. , Hughes James P. , Wilcox Ellen , Corey Lawrence , Hendrix Craig W. 
Published: February 2012

ABSTRACT
Acyclovir pharmacokinetics was evaluated in 68 HIV-seronegative, herpes simplex virus 2 (HSV-2)-seropositive African women, who received a single oral 400-mg dose of acyclovir, with plasma acyclovir concentrations measured over 8 h. Geometric mean peak concentration and area under the concentration-time curve were 0.31 μg/ml and 1.59 h · μg/ml, respectively, 54% and 52% lower than values from non-Africans. Lower acyclovir concentrations may partly explain the reduced acyclovir suppression of HSV-2 genital ulcer recurrence in HPTN 039 African women participants.
Artemisinin-Naphthoquine Combination Therapy for Uncomplicated Pediatric Malaria: a Tolerability, Safety, and Preliminary Efficacy Study
Authors: Benjamin John , Moore Brioni , Lee Sook Ting , Senn Michèle , Griffin Susan , Lautu Dulci , Salman Sam , Siba Peter , Mueller Ivo , Davis Timothy M. E. 
Published: February 2012

ABSTRACT

Artemisinin-naphthoquine (ART-NQ) is a fixed-dose coformulated antimalarial therapy recommended as a single-dose treatment and marketed in Papua New Guinea among other tropical countries. We conducted a tolerability, safety, and efficacy study of ART-NQ for Papua New Guinean children aged 5 to 12 years with uncomplicated malaria, comparing single-dose ART-NQ (15 and 6 mg/kg of body weight) given with water (group 1;
n
= 15), single-dose ART-NQ (22 and 9 mg/kg) given with milk (group 2;
n
= 17), or two daily doses of 22 and 9 mg/kg given with water (group 3;
n
= 16). Of the 48 children (45 with
Plasmodium falciparum
malaria, 2 with
Plasmodium vivax
malaria, and 1 with mixed-species malaria), 2 in group 2 did not attend all follow-up assessments. All regimens were well tolerated, with no serious adverse events. There were no clinically significant changes in pulse, blood pressure, rate-corrected electrocardiographic QT, routine biochemistry/hematology, or hearing after treatment. Fever clearance was prompt. Mean 50% parasite clearance times were 4, 4, and 5 h for groups 1, 2, and 3, respectively. One group 1 patient had PCR-confirmed
P. falciparum
recrudescence at day 23; four had PCR-confirmed
P. falciparum
reinfections on day 28 or 42; and three had
P. vivax
infections detected on day 42. The only recurrent parasitemia in groups 2 and 3 occurred in a group 2 child who developed a
P. vivax
infection on day 42. Day 14 gametocyte positivity levels were 20%, 27%, and 9% in groups 1, 2, and 3, respectively. The lower single ART-NQ dose was associated with relatively frequent recurrence of parasitemia, but the prolonged gametocytemia in all three groups has implications for the transmission of malaria.
Efficacy of Human Simulated Exposures of Ceftaroline against Phenotypically Diverse Enterobacteriaceae Isolates
Authors: Housman Seth T. , Keel Rebecca A. , Crandon Jared L. , Williams Gregory , Nicolau David P. 
Published: February 2012

ABSTRACT

Ceftaroline fosamil, a new broad-spectrum cephalosporin, exhibits potent bactericidal activity against common Gram-negative pathogens, including
Enterobacteriaceae
, and Gram-positive pathogens, including methicillin-resistant
Staphylococcus aureus
and penicillin-resistant
Streptococcus pneumoniae
. The purpose of this study was to evaluate the efficacy of a human simulated dose of ceftaroline fosamil against clinical
Enterobacteriaceae
in both neutropenic and immunocompetent mouse thigh infection models. Thirty-five
Enterobacteriaceae
isolates with ceftaroline MICs ranging from 0.25 to 32 μg/ml were selected for the neutropenic model, and five
Escherichia coli
isolates were also tested in the immunocompetent model. Two hours after inoculation, the ceftaroline fosamil human simulated regimen of 600 mg intravenously (i.v.) every 12 h was administered. The change in log
10
CFU after 24 h was compared to that in 0 h controls. The human simulated regimen produced predictable efficacy against 18 of 20 isolates with a MIC of ≤1 μg/ml. Similar efficacy was seen in the immunocompetent model against isolates with a MIC of ≤2 μg/ml, and enhanced efficacy was observed against the isolate with a MIC of 4 μg/ml. Human simulated exposures to ceftaroline fosamil at 600 mg every 12 h provided predictable efficacy against
Enterobacteriaceae
with MICs of ≤1 μg/ml and enhanced efficacy within the immunocompetent model, supporting the clinical utility of ceftaroline fosamil against these organisms.