bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optimization of Polyene-Azole Combination Therapy against Aspergillosis Using an
In Vitro
Pharmacokinetic-Pharmacodynamic Model
Authors: Siopi Maria , Siafakas Nikolaos , Vourli Sophia , Zerva Loukia , Meletiadis Joseph 
Published: April 2015

ABSTRACT

Although amphotericin B-azole combination therapy has traditionally been questioned due to potential antagonistic interactions, it is often used successfully to treat refractory invasive aspergillosis. So far, pharmacodynamic (PD) interactions have been assessed with conventional
in vitro
tests, which do not mimic human serum concentrations and animal models using limited doses. We therefore simulated the human serum concentration profiles of amphotericin B and voriconazole in an
in vitro
dialysis/diffusion closed pharmacokinetic-pharmacodynamic (PK-PD) model and studied the pharmacodynamic interactions against an azole-resistant and an azole-susceptible
Aspergillus fumigatus
isolate, using Bliss independence and canonical mixture response surface analyses. Amphotericin B dosing regimens with the drug administered every 24 h (q24h) were combined with voriconazole q12h dosing regimens.
In vitro
PK-PD combination data were then combined with human PK data by using Monte Carlo analysis. The target attainment rate and the serum concentration/MIC ratio were calculated for isolates with different MICs. Synergy (20 to 31%) was observed at low amphotericin B-high voriconazole exposures, whereas antagonism (−6 to −16%) was found at high amphotericin B-low voriconazole exposures for both isolates. Combination therapy resulted in 17 to 48% higher target attainment rates than those of monotherapy regimens for isolates with voriconazole/amphotericin B MICs of 1 to 4 mg/liter. Optimal activity was found for combination regimens with a 1.1 total minimum concentration of drug in serum (
tC
min
)/MIC ratio for voriconazole and a 0.5 total maximum concentration of drug in serum (
tC
max
)/MIC ratio for amphotericin B, whereas the equally effective monotherapy regimens required a voriconazole
tC
min
/MIC ratio of 1.8 and an amphotericin B
tC
max
/MIC ratio of 2.8. Amphotericin B-voriconazole combination regimens were more effective than monotherapy regimens. Therapeutic drug monitoring can be employed to optimize antifungal combination therapy with low-dose (≤0.6 mg/kg) amphotericin B-based combination regimens against resistant isolates for minimal toxicity.
Replication of Salmonella enterica Serovar Typhimurium in Human Monocyte-Derived Macrophages
Authors: Lathrop Stephanie K. , Binder Kelsey A. , Starr Tregei , Cooper Kendal G. , Chong Audrey , Carmody Aaron B. , Steele-Mortimer Olivia 
Published: April 2015

ABSTRACT

Salmonella enterica
serovar Typhimurium is a common cause of food-borne gastrointestinal illness, but additionally it causes potentially fatal bacteremia in some immunocompromised patients. In mice, systemic spread and replication of the bacteria depend upon infection of and replication within macrophages, but replication in human macrophages is not widely reported or well studied. In order to assess the ability of
Salmonella
Typhimurium to replicate in human macrophages, we infected primary monocyte-derived macrophages (MDM) that had been differentiated under conditions known to generate different phenotypes. We found that replication in MDM depends greatly upon the phenotype of the cells, as M1-skewed macrophages did not allow replication, while M2a macrophages and macrophages differentiated with macrophage colony-stimulating factor (M-CSF) alone (termed M0) did. We describe how additional conditions that alter the macrophage phenotype or the gene expression of the bacteria affect the outcome of infection. In M0 MDM, the temporal expression of representative genes from
Salmonella
pathogenicity islands 1 and 2 (SPI1 and SPI2) and the importance of the PhoP/Q two-component regulatory system are similar to what has been shown in mouse macrophages. However, in contrast to mouse macrophages, where replication is SPI2 dependent, we observed early SPI2-independent replication in addition to later SPI2-dependent replication in M0 macrophages. Only SPI2-dependent replication was associated with death of the host cell at later time points. Altogether, our results reveal a very nuanced interaction between
Salmonella
and human macrophages.
Abolishing Cell Wall Glycosylphosphatidylinositol-Anchored Proteins in Candida albicans Enhances Recognition by Host Dectin-1
Authors: Shen Hui , Chen Si Min , Liu Wei , Zhu Fang , He Li Juan , Zhang Jun Dong , Zhang Shi Qun , Yan Lan , Xu Zheng , Xu Guo Tong , An Mao Mao , Jiang Yuan Ying 
Published: April 2015

ABSTRACTFungi can shield surface pathogen-associated molecular patterns (PAMPs) for evading host immune attack. The most common and opportunistic human pathogen,Candida albicans, can shield β-(1 3)-glucan on the cell wall, one of the major PAMPs, to avoid host phagocyte Dectin-1 recognition. The way to interfere in the shielding process for more effective antifungal defense is not well established. In this study, we found that deletion of theC. albicansGPI7gene, which was responsible for adding ethanolaminephosphate to the second mannose in glycosylphosphatidylinositol (GPI) biosynthesis, could block the attachment of most GPI-anchored cell wall proteins (GPI-CWPs) to the cell wall and subsequently unmask the concealed β-(1,3)-glucan. Neutrophils could kill the uncloakedgpi7mutant more efficiently with an augmented respiratory burst. Thegpi7mutant also stimulated Dectin-1-dependent immune responses of macrophages, including activation of nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) pathways and secretion of specific cytokines, such as tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), and IL-12p40. Furthermore, thegpi7null mutant could induce an enhanced inflammatory response through promoting significant recruitment of neutrophils and monocytes and could stimulate stronger Th1 and Th17 cell responses to fungal infectionsin vivo. Thesein vivophenotypes also were Dectin-1 dependent. Thus, we assume that GPI-CWPs are involved in the immune mechanism ofC. albicansescaping from host recognition by Dectin-1. Our studies also indicate that the blockage of GPI anchor synthesis is a strategy to inhibitC. albicansevading host recognition.
Community-linked maternal death review (CLMDR) to measure and prevent maternal mortality: a pilot study in rural Malawi
Authors: Bayley Olivia , Chapota Hilda , Kainja Esther , Phiri Tambosi , Gondwe Chelmsford , King Carina , Nambiar Bejoy , Mwansambo Charles , Kazembe Peter , Costello Anthony , Rosato Mikey , Colbourn Tim 
Published: April 2015

BackgroundIn Malawi, maternal mortality remains high. Existing maternal death reviews fail to adequately review most deaths, or capture those that occur outside the health system. We assessed the value of community involvement to improve capture and response to community maternal deaths.MethodsWe designed and piloted a community-linked maternal death review (CLMDR) process in Mchinji District, Malawi, which partnered community and health facility stakeholders to identify and review maternal deaths and generate actions to prevent future deaths. The CLMDR process involved five stages: community verbal autopsy, community and facility review meetings, a public meeting and bimonthly reviews involving both community and facility representatives.ResultsThe CLMDR process was found to be comparable to a previous research-driven surveillance system at identifying deaths in Mchinji District (population 456 500 in 2008). 52 maternal deaths were identified between July 2011 and June 2012, 27 (52%) of which would not have been identified without community involvement. Based on district estimates of population (500 000) and crude birth rate (35 births per 1000 population), the maternal mortality ratio was around 300 maternal deaths per 100 000 live births. Of the 41 cases that started the CLMDR process, 28 (68%) completed all five stages. We found the CLMDR process to increase the quantity of information available and to involve a wider range of stakeholders in maternal death review (MDR). The process resulted in high rates of completion of community-planned actions (82%), and district hospital (67%) and health centre (65%) actions to prevent maternal deaths.ConclusionsCLMDR is an important addition to the established forms of MDR. It shows potential as a maternal death surveillance system, and may be applicable to similar contexts with high maternal mortality.
Nutritional support and follow‐up of a puppy with chronic kidney disease
Authors: Dupont Sofie , Van de Maele Isabel , Lourenço Marta , Hesta Myriam 
Published: April 2015

A five months old, Flat‐Coated Retriever puppy with poor body condition diagnosed with pyelonephritis and chronic kidney disease (CKD) was referred for a nutritional consult. The conflicting protein and phosphorus requirements for growth and poor body condition versus CKD were scrutinised. To maximise the quality of life (QoL) despite the poor prognosis, several diet plans were advised taking into account the different growth periods of this medium breed puppy. At 15 months of age, body condition was still below target and the creatinine level had increased consistently since the first consult. Despite the progressive decline in kidney function, serum urea concentration decreased compared with seven months before, whereas serum concentrations of total protein, albumin and phosphate remained normal at all times. With the different adjusted diet plans, the QoL of the puppy was improved, allowing for a normal and exceptionally energetic life until the age of nearly three years.
Stability of Hyperbolic Equilibrium Solution of Second Order Nonlinear Rational Difference Equation
Authors: Atawna S. , Abu-Saris R. , Ismail E. S. , Hashim I. 
Published: April 2015

Our goal in this paper is to investigate the global asymptotic stability of the hyperbolic
equilibrium solution of the second order rational difference equation
xn+1=α+βxn+γxn-1/A+Bxn+Cxn-1, n=0,1,2,…, where the parameters A≥0 and B, C, α, β, γ are positive real numbers and the initial conditions x-1, x0 are nonnegative real numbers such that A+Bx0+Cx-1>0.
In particular, we solve Conjecture 5.201.1 proposed by Camouzis and Ladas in their book (2008) which appeared previously in Conjecture 11.4.2 in Kulenović and Ladas monograph (2002).
Prolonged Nightly Fasting and Breast Cancer Risk: Findings from NHANES (2009–2010)
Authors: Marinac Catherine R. , Natarajan Loki , Sears Dorothy D. , Gallo Linda C. , Hartman Sheri J. , Arredondo Elva , Patterson Ruth E. 
Published: April 2015

Abstract
Background: A novel line of research has emerged, suggesting that daily feeding–fasting schedules that are synchronized with sleep-wake cycles have metabolic implications that are highly relevant to breast cancer. We examined associations of nighttime fasting duration with biomarkers of breast cancer risk among women in the 2009–2010 U.S. National Health and Nutrition Examination Survey.
Methods: Dietary, anthropometric, and HbA1c data were available for 2,212 women, and 2-hour postprandial glucose concentrations were available for 1,066 women. Nighttime fasting duration was calculated using 24-hour food records. Separate linear regression models examined associations of nighttime fasting with HbA1c and 2-hour glucose concentrations. Logistic regression modeled associations of nighttime fasting with elevated HbA1c (HbA1c ≥ 39 mmol/mol or 5.7%) and elevated 2-hour glucose (glucose ≥ 140 mg/dL). All models adjusted for age, education, race/ethnicity, body mass index, total kcal intake, evening kcal intake, and the number of eating episodes per day.
Results: Each 3-hour increase in nighttime fasting (roughly 1 SD) was associated with a 4% lower 2-hour glucose measurement [β, 0.96; 95% confidence interval (CI), 0.93–1.00; P &lt; 0.05], and a nonstatistically significant decrease in HbA1c. Logistic regression models indicate that each 3-hour increase in nighttime fasting duration was associated with roughly a 20% reduced odds of elevated HbA1c (OR, 0.81; 95% CI, 0.68–0.97; P &lt; 0.05) and nonsignificantly reduced odds of elevated 2-hour glucose.
Conclusions: A longer nighttime duration was significantly associated with improved glycemic regulation.
Impact: Randomized trials are needed to confirm whether prolonged nighttime fasting could improve biomarkers of glucose control, thereby reducing breast cancer risk. Cancer Epidemiol Biomarkers Prev; 24(5); 783–9. ©2015 AACR.
The Scientific Revolution Revisited
Authors: Teich Mikuláš 
Published: April 2015

The Scientific Revolution Revisited brings Mikuláš Teich back to the great movement of thought and action that transformed European science and society in the seventeenth century. Drawing on a lifetime of scholarly experience in six penetrating chapters, Teich examines the ways of investigating and understanding nature that matured during the late Middle Ages and the Renaissance, charting their progress towards science as we now know it and insisting on the essential interpenetration of such inquiry with its changing social environment. The Scientific Revolution was marked by the global expansion of trade by European powers and by interstate rivalries for a stake in the developing world market, in which advanced medieval China, remarkably, did not participate. It is in the wake of these happenings, in Teich's original retelling, that the Thirty Years War and the Scientific Revolution emerge as products of and factors in an uneven transition in European and world history: from natural philosophy to modern science, feudalism to capitalism, the late medieval to the early modern period.
With a narrative that moves from pre-classical thought to the European institutionalisation of science – and a scope that embraces figures both lionised and neglected, such as Nicole Oresme, Francis Bacon, Thomas Hobbes, Isaac Newton, René Descartes, Thaddeus Hagecius, Johann Joachim Becher – The Scientific Revolution Revisited illuminates the social and intellectual sea changes that shaped the modern world.
A Reanalysis of Hurricane Camille
Authors: Kieper Margaret E. , Landsea Christopher W. , Beven John L. 
Published: April 2015

Abstract
A reanalysis of 1969’s Hurricane Camille has been completed as part of the Atlantic Hurricane Database Reanalysis Project. The reanalysis of Hurricane Camille has been expedited to allow for a homogeneous comparison of all four of the U.S.-landfalling Saffir–Simpson hurricane wind scale category 5 hurricanes since 1900. A review of the available ship, station, radar, aircraft, and satellite observations is presented, along with the reanalysis methodology. Highlights of the Best-Track Change Committee approved changes to Camille’s genesis, track, intensity, and dissipation are discussed. As part of the preparation for the reanalysis, research on Hurricane Camille uncovered new data useful to the reanalysis. Focus was placed on understanding the internal structure in a modern context, especially whether eyewall replacement cycles occurred, including comparisons with a similar hurricane used as a proxy. A more detailed understanding was gained of the tropical wave and genesis phases. In addition, a 901-mb dropsonde that was later rejected was reanalyzed to find out why and to see if an accurate central pressure could be determined. New landfall surface pressures along the Mississippi coast were discovered and a significant revision is made to the U.S.-landfall central pressure and intensity (maximum sustained surface winds). Additionally, a radar “loop” was constructed from archived Weather Surveillance Radar-1957 (WSR-57) film, including landfall, marking the very first time that this historic hurricane can be viewed in a time-lapse movie format.
Climate-Relevant Land Use and Land Cover Change Policies
Authors: Mahmood Rezaul , Pielke Roger A. , McAlpine Clive A. 
Published: April 2015

Abstract
Both observational and modeling studies clearly demonstrate that land-use and land-cover change (LULCC) play an important biogeophysical and biogeochemical role in the climate system from the landscape to regional and even continental scales. Without comprehensively considering these impacts, an adequate response to the threats posed by human intervention into the climate system will not be adequate.
Public policy plays an important role in shaping local- to national-scale land-use practices. An array of national policies has been developed to influence the nature and spatial extent of LULCC. Observational evidence suggests that these policies, in addition to international trade treaties and protocols, have direct effects on LULCC and thus the climate system.
However, these policies, agreements, and protocols fail to adequately recognize these impacts. To make these more effective and thus to minimize climatic impacts, we propose several recommendations: 1) translating international treaties and protocols into national policies and actions to ensure positive climate outcomes; 2) updating international protocols to reflect advancement in climate–LULCC science; 3) continuing to invest in the measurements, databases, reporting, and verification activities associated with LULCC and LULCC-relevant climate monitoring; and 4) reshaping Reducing Emissions from Deforestation and Forest Degradation+ (REDD+) to fully account for the multiscale biogeophysical and biogeochemical impacts of LULCC on the climate system.
An NARR-Derived Climatology of Southerly and Northerly Low-Level Jets over North America and Coastal Environs
Authors: Doubler Dana L. , Winkler Julie A. , Bian Xindi , Walters Claudia K. , Zhong Shiyuan 
Published: April 2015

AbstractThe North American Regional Reanalysis (NARR) was used to develop an expanded, long-term (1979–2009) climatology of meridional (southerly and northerly) low-level jets over North America and surrounding coastal environs. NARR has greater spatial coverage and finer temporal (3 hourly) and horizontal (32 km) resolutions than do routine rawinsonde wind measurements. The NARR climatology focuses on jet frequency and average speed and elevation by month and 3-hourly time step. To evaluate the plausibility of the climatology, jet characteristics were compared with those obtained from prior climatological analyses, case studies, field campaigns, and numerical simulations. Strong agreement was found with many of the previously documented characteristics of well-known jets, including the northerly Pacific coast jet and southerly Great Plains jet. The NARR climatology provides additional insights into the spatial extent and seasonal shifts of large jet frequencies and into diurnal fluctuations in frequency, speed, and elevation. Weaker and/or less spatially extensive jets are also well depicted in the NARR climatology, including the southerly Gulf of California jet, summertime southerly jets and autumn northerly jets off the mid-Atlantic coast, and northerly jets in the high plains. Furthermore, several new areas of relatively frequent jet occurrence, most of which align with shallow thermal gradients, are seen in the NARR climatology. The NARR climatology supplements and enhances our understanding of North American low-level jets and points to the need for additional research on both the climatological characteristics of these jets and on the processes contributing to their formation.
The Annual-Cycle Modulation of Meridional Asymmetry in ENSO’s Atmospheric Response and Its Dependence on ENSO Zonal Structure
Authors: Zhang Wenjun , Li Haiyan , Jin Fei-Fei , Stuecker Malte F. , Turner Andrew G. , Klingaman Nicholas P. 
Published: April 2015

Abstract
Previous studies documented that a distinct southward shift of central Pacific low-level wind anomalies occurring during the ENSO decaying phase is caused by an interaction between the western Pacific annual cycle and El Niño–Southern Oscillation (ENSO) variability. The present study finds that the meridional movement of the central Pacific wind anomalies appears only during traditional eastern Pacific El Niño (EP El Niño) events rather than in central Pacific El Niño (CP El Niño) events in which sea surface temperature (SST) anomalies are confined to the central Pacific. The zonal structure of ENSO-related SST anomalies therefore has an important effect on meridional asymmetry in the associated atmospheric response and its modulation by the annual cycle. In contrast to EP El Niño events, the SST anomalies of CP El Niño events extend farther west toward the warm pool region with its climatological warm SSTs. In the warm pool region, relatively small SST anomalies are thus able to excite convection anomalies on both sides of the equator, even with a meridionally asymmetric SST background state. Therefore, almost meridionally symmetric precipitation and wind anomalies are observed over the central Pacific during the decaying phase of CP El Niño events. The SST anomaly pattern of La Niña events is similar to CP El Niño events with a reversed sign. Accordingly, no distinct southward displacement of the atmospheric response occurs over the central Pacific during the La Niña decaying phase. These results have important implications for ENSO climate impacts over East Asia, since the anomalous low-level anticyclone over the western North Pacific is an integral part of the annual cycle–modulated ENSO response.
Teaching tools to engage Anishinaabek First Nations women in cervical cancer screening: Report of an educational workshop
Authors: Zehbe Ingeborg , Wood Brianne , Wakewich Pamela , Maar Marion , Escott Nicholas , Jumah Naana , Little Julian ,   on behalf of the ACCSS group, Severini Alberto , Burchell Ann , Ogilvie Gina , Graham Ian , Zehbe Ingeborg , Little Julian , Maar Marion , Escott Nicholas , Wakewich Pamela , Sameshima Pauline 
Published: April 2015

Objective: To explore educational strategies for engaging First Nations women in Canada to attend cervical cancer screening. Design: Within a participatory action research framework, semi-structured interviews with health-care providers in First Nations communities revealed that education about the value of screening is perceived as being a key factor to promote cervical cancer screening. Setting: To obtain feedback from workshop informants, a 1-day educational workshop was held to identify appropriate educational intervention strategies, which would be applied in a forthcoming randomised controlled cervical screening trial. Methods: Common discussion and discussion groups, which were facilitated by a First Nations workshop moderator and a note taker. Results: This workshop helped to strengthen the ethical space dialogue with the First Nations communities with whom the study team had established research partnerships. The workshop atmosphere was relaxed and the invited informants decided that an educational health promotion event for community women needed to be held prior to inviting them to the cervical screening trial. Such an event would provide an opportunity to communicate the importance of attending regular cervical screening allowing women to make informed decisions about screening participation. Complementary promotional items, including an eye-catching pamphlet and storytelling, were also suggested. Conclusion: The key messages from the events and promotional items can help to de-stigmatise women who develop a type of cancer that is caused by a sexually transmitted virus that affects both men and women. Developing and implementing positive health education that respectfully depicts female bodies, sexuality and health behaviours through a First Nations lens is strongly warranted.