bluuebunny/crossref_metadata_2025_split huggingface dataset:
Telaprevir and Ribavirin Interaction: Higher Ribavirin Levels Are Not Only Due to Renal Dysfunction during Triple Therapy
Authors: Gutierrez-Valencia Alicia , Ruiz-Valderas Rosa , Ben-Marzouk-Hidalgo Omar J. , Torres-Cornejo Almudena , Espinosa Nuria , Castillo-Ferrando Juan R. , Viciana Pompeyo , Lopez-Cortes Luis F. 
Published: March 2015

ABSTRACTA higher incidence of anemia has been observed during the treatment of hepatitis C virus genotype 1 (HCV-1) infection with pegylated alpha interferon (pegIFN-α), ribavirin, and telaprevir. We assessed the impacts that concomitant administration of telaprevir and changes in the glomerular filtration rate have on ribavirin plasma levels. The minimum concentrations of ribavirin in plasma (ribavirinCmin) determined during triple therapy including telaprevir were compared with those observed after telaprevir withdrawal and those observed in the same subjects and in a large cohort during a previous course of pegIFN-α plus ribavirin. Intensive pharmacokinetic sampling for ribavirin was performed at steady state during the triple-therapy phase. Ribavirin levels were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Twenty-seven HCV-1/HIV-coinfected patients were enrolled. The median ribavirinCminfor triple therapy (4.08 μg/ml; range, 2.14 to 5.56 μg/ml) was higher than that observed after telaprevir withdrawal (1.96 μg/ml; range, 0.41 to 3.45 μg/ml) (P< 0.001) and that observed for 125 HCV-1/HIV-coinfected patients treated only with pegIFN-α plus ribavirin (1.65 μg/ml; range, 0.41 to 5.56 μg/ml) (P< 0.001). The estimated glomerular filtration rate (eGFR) decreased >20% from the baseline value in 11 of 27 patients and became normal after telaprevir removal in almost all cases. There was a negative correlation between eGFR and ribavirin clearance (r2= 0.257;P= 0.064) but not the ribavirin area under the concentration-time curve from 0 to 12 h (AUC0–12) (r2= 0.001;P= 0.455). Thus, there is a significant pharmacokinetic interaction between telaprevir and ribavirin that results in very high ribavirin levels, which explains the excess of toxicity observed with this drug combination. A blockade of the proximal tubular transporters might be implicated in both the increase in plasma creatinine and the high ribavirin levels. (This study has been registered at ClinicalTrials.gov under registration no. NCT01818856.)
Development and Validation of a Clinical Score for Predicting Risk of Adenoma at Screening Colonoscopy
Authors: Shaukat Aasma , Church Timothy R. , Shanley Ryan , Kauff Noah D. , O'Brien Michael J. , Mills Glenn M. , Jordan Paul A. , Allen John A. , Kim Adam , Feld Andrew D. , Zauber Ann Graham , Winawer Sidney J. 
Published: March 2015

Abstract
Background: Currently, no clinical tools use demographic and risk factor information to predict the risk of finding an adenoma in individuals undergoing colon cancer screening. Such a tool would be valuable for identifying those who would most benefit from screening colonoscopy.
Methods: We used baseline data from men and women who underwent screening colonoscopy from the randomized, multicenter National Colonoscopy Study (NCS) to develop and validate an adenoma risk model. The study, conducted at three sites in the United States (Minneapolis, MN; Seattle, WA; and Shreveport, LA) asked all participants to complete baseline questionnaires on clinical risk factors and family history. Model parameters estimated from logistic regression yielded an area under the receiver operating characteristic curve (AUROCC) used to assess prediction.
Results: Five hundred forty-one subjects were included in the development model, and 1,334 in the validation of the risk score. Variables in the prediction of adenoma risk for colonoscopy screening were age (likelihood ratio test for overall contribution to model, P &lt; 0.001), male sex (P &lt; 0.001), body mass index (P &lt; 0.001), family history of at least one first-degree relative with colorectal cancer (P = 0.036), and smoking history (P &lt; 0.001). The adjusted AUROCC of 0.67 [95% confidence interval (CI), 0.61–0.74] for the derivation cohort was not statistically significantly different from that in the validation cohort. The adjusted AUROCC for the entire cohort was 0.64 (95% CI, 0.60–0.67).
Conclusion: We developed and validated a simple well-calibrated risk score.
Impact: This tool may be useful for estimating risk of adenomas in screening eligible men and women Cancer Epidemiol Biomarkers Prev; 24(6); 913–20. ©2015 AACR.
The Fallopian Tube: From Back Stage to Center Stage
Authors: Greene Mark H. , Mai Phuong L. 
Published: March 2015

Abstract
The recognition that a significant fraction of what historically has been classified as ovarian cancer is, in fact, a malignancy that arises in the fallopian tube mucosa comprises a paradigm shift in our understanding of these neoplasms. New etiologic and management opportunities have been created by this insight, both for women at increased genetic risk of ovarian cancer by virtue of being BRCA1/2 mutation carriers and, perhaps, for women in the general population as well. Cancer Prev Res; 8(5); 339–41. ©2015 AACR.
See related article by Daly et al., p. 342
Cardiac Magnetic Resonance Myocardial Perfusion Reserve Index Is Reduced in Women With Coronary Microvascular Dysfunction
Authors: Thomson Louise E.J. , Wei Janet , Agarwal Megha , Haft-Baradaran Afsaneh , Shufelt Chrisandra , Mehta Puja K. , B. Gill Edward , Johnson B. Delia , Kenkre Tanya , M. Handberg Eileen , Li Debiao , Sharif Behzad , Berman Daniel S. , W. Petersen John , Pepine Carl J. , Bairey Merz C. Noel 
Published: March 2015

Background—
Women with signs and symptoms of ischemia and no obstructive coronary artery disease often have coronary microvascular dysfunction (CMD), diagnosed by invasive coronary reactivity testing (CRT). Although traditional noninvasive stress imaging is often normal in CMD, cardiac MRI may be able to detect CMD in this population.

Methods and Results—

Vasodilator stress cardiac MRI was performed in 118 women with suspected CMD who had undergone CRT and 21 asymptomatic reference subjects. Semi-quantitative evaluation of the first-pass perfusion images was completed to determine myocardial perfusion reserve index (MPRI). The relationship between CRT findings and MPRI was examined by Pearson correlations, logistic regression, and sensitivity/specificity. Symptomatic women had lower mean pharmacological stress MPRI compared with reference subjects (1.71±0.43 versus 2.23±0.37;
P
<0.0001). Lower MPRI was predictive of ≥1 abnormal CRT variables (odds ratio =0.78 [0.70, 0.88],
P
<0.0001, c-statistic 0.78 [0.68, 0.88]). An MPRI threshold of 1.84 predicted CRT abnormality with sensitivity 73% and specificity 74%.

Conclusions—
Noninvasive cardiac MRI MPRI can detect CMD defined by invasive CRT. Further work is aimed to optimize the noninvasive identification and management of CMD patients.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00832702.
Differential Time Trends of Outcomes and Costs of Care for Acute Myocardial Infarction Hospitalizations by ST Elevation and Type of Intervention in the United States, 2001–2011
Authors: Sugiyama Takehiro , Hasegawa Kohei , Kobayashi Yasuki , Takahashi Osamu , Fukui Tsuguya , Tsugawa Yusuke 
Published: March 2015

Background

Little is known whether time trends of in‐hospital mortality and costs of care for acute myocardial infarction (
AMI
) differ by type of
AMI
(
ST
‐elevation myocardial infarction [
STEMI
] vs. non‐
ST
‐elevation [
NSTEMI
]) and by the intervention received (percutaneous coronary intervention [
PCI
], coronary artery bypass grafting [
CABG
], or no intervention) in the
United States
.

Methods and Results

We conducted a serial cross‐sectional study of all hospitalizations for
AMI
aged 30 years or older using the Nationwide Inpatient Sample, 2001–2011 (1 456 154 discharges; a weighted estimate of 7 135 592 discharges). Hospitalizations were stratified by type of
AMI
and intervention, and the time trends of in‐hospital mortality and hospital costs were examined for each combination of the
AMI
type and intervention, after adjusting for both patient‐ and hospital‐level characteristics. Compared with 2001, adjusted in‐hospital mortality improved significantly for
NSTEMI
patients in 2011, regardless of the intervention received (
PCI
odds ratio [
OR
] 0.68, 95%
CI
0.56 to 0.83;
CABG OR
0.57, 0.45 to 0.72; without intervention
OR
0.61, 0.57 to 0.65). As for
STEMI
, a decline in adjusted in‐hospital mortality was significant for those who underwent
PCI
(
OR
0.83; 0.73 to 0.94); however, no significant improvement was observed for those who received
CABG
or without intervention. Hospital costs per hospitalization increased significantly for patients who underwent intervention, but not for those without intervention.

Conclusions

In the
United States
, the decrease in in‐hospital mortality and the increase in costs differed by the
AMI
type and the intervention received. These non‐uniform trends may be informative for designing effective health policies to reduce the health and economic burdens of
AMI
.
Occipital Cortex of Blind Individuals Is Functionally Coupled with Executive Control Areas of Frontal Cortex
Authors: Deen Ben , Saxe Rebecca , Bedny Marina 
Published: March 2015

Abstract
In congenital blindness, the occipital cortex responds to a range of nonvisual inputs, including tactile, auditory, and linguistic stimuli. Are these changes in functional responses to stimuli accompanied by altered interactions with nonvisual functional networks? To answer this question, we introduce a data-driven method that searches across cortex for functional connectivity differences across groups. Replicating prior work, we find increased fronto-occipital functional connectivity in congenitally blind relative to blindfolded sighted participants. We demonstrate that this heightened connectivity extends over most of occipital cortex but is specific to a subset of regions in the inferior, dorsal, and medial frontal lobe. To assess the functional profile of these frontal areas, we used an n-back working memory task and a sentence comprehension task. We find that, among prefrontal areas with overconnectivity to occipital cortex, one left inferior frontal region responds to language over music. By contrast, the majority of these regions responded to working memory load but not language. These results suggest that in blindness occipital cortex interacts more with working memory systems and raise new questions about the function and mechanism of occipital plasticity.
A new species of Lovenula Schmeil (Copepoda, Calanoida, Diaptomidae) from the Eastern Cape Province of South Africa
Authors: Suárez-Morales E. , Wasserman R. J. , Dalu T. 
Published: March 2015

Recent collections from the Eastern Cape Province of South Africa yielded an undescribed species of the freshwater diaptomid copepod genus Lovenula. It is probably the largest paradiaptomine known and closely resembles L. falcifera (Lovén, 1845). This species, L. raynerae n. sp., differs in several characters, including the shape of the female genital operculum, but particularly in details of the male and female leg 5: on the female the size of the endopod, a distinctive protuberance on the first exopodal segment; on male leg 5, the features of the seta adjacent to the claw of the right leg, a subdistal endopodal spine of the same ramus and details of the claw, with a middle gap on the inner margin. As with L. falcifera, the new species was collected from an ephemeral habitat. A record of L. falcifera from Ethiopia probably represents an undescribed species. A key to the species of the genus is provided.
An Anomaly-Based Method for Identifying Signals of Spring and Autumn Low-Temperature Events in the Yangtze River Valley, China
Authors: Qian Weihong , Chen Yun , Jiang Man , Hu Qi 
Published: March 2015

AbstractAbnormally low temperature (LT) events in spring and autumn can cause severe damage to spring and autumn rice production in the mid- to lower Yangtze River valley in China. Advanced predictions of such events can help mitigate their damage. However, the current methods have limited success in describing and predicting those weather events. In this study, a new method is proposed to decompose any one of the meteorological variables into its climatic component and an anomaly, and the anomaly is used in identifying signals of the LT events. The method is used in 20 strong spring LT events and 44 autumn events during 1960–2008. The results show the advanced ability of this method to clearly describe the LT events as compared with the vague indications of such events that are produced by conventional methods currently in practice in China. In addition, the composite profile of vertical anomalies shows that a negative center of geopotential height anomalies at around 300 hPa, coexisting with a strong cold center of temperature anomalies at 850 hPa, is a signature for LT events. For the 44 autumn LT events and 20 spring LT events during 1960–2008, their early disturbances were identified up to 10.2 days and 6.9 days, respectively, before the occurrence of the LT events in the valley. This result suggests that identifying the early disturbances and extracting anomalous signals from the products of current medium-range weather forecast models may be a potential way to improve the prediction skill for LT events in the valley.
A Hybrid Dynamical–Statistical Downscaling Technique. Part II: End-of-Century Warming Projections Predict a New Climate State in the Los Angeles Region
Authors: Sun Fengpeng , Walton Daniel B. , Hall Alex 
Published: March 2015

Abstract
Using the hybrid downscaling technique developed in part I of this study, temperature changes relative to a baseline period (1981–2000) in the greater Los Angeles region are downscaled for two future time slices: midcentury (2041–60) and end of century (2081–2100). Two representative concentration pathways (RCPs) are considered, corresponding to greenhouse gas emission reductions over coming decades (RCP2.6) and to continued twenty-first-century emissions increases (RCP8.5). All available global climate models from phase 5 of the Coupled Model Intercomparison Project (CMIP5) are downscaled to provide likelihood and uncertainty estimates. By the end of century under RCP8.5, a distinctly new regional climate state emerges: average temperatures will almost certainly be outside the interannual variability range seen in the baseline. Except for the highest elevations and a narrow swath very near the coast, land locations will likely see 60–90 additional extremely hot days per year, effectively adding a new season of extreme heat. In mountainous areas, a majority of the many baseline days with freezing nighttime temperatures will most likely not occur. According to a similarity metric that measures daily temperature variability and the climate change signal, the RCP8.5 end-of-century climate will most likely be only about 50% similar to the baseline. For midcentury under RCP2.6 and RCP8.5 and end of century under RCP2.6, these same measures also indicate a detectable though less significant climatic shift. Therefore, while measures reducing global emissions would not prevent climate change at this regional scale in the coming decades, their impact would be dramatic by the end of the twenty-first century.
The Magnitude and Causes of Global Drought Changes in the Twenty-First Century under a Low–Moderate Emissions Scenario
Authors: Zhao Tianbao , Dai Aiguo 
Published: March 2015

Abstract
Atmospheric demand for moisture and dry days are expected to increase, leading to drying over land in the twenty-first century. Here, the magnitude and key drivers of this drying are investigated using model simulations under a low–moderate scenario, RCP4.5. The self-calibrated Palmer drought severity index with the Penman–Monteith potential evapotranspiration (PET) (sc_PDSI_pm), top 10-cm soil moisture (SM), and runoff (R) from 14 models are analyzed. The change patterns are found to be comparable while the magnitude differs among these measures of drought. The frequency of the SM-based moderate (severe) agricultural drought could increase by 50%–100% (100%–200%) in a relative sense by the 2090s over most of the Americas, Europe, and southern Africa and parts of East and West Asia and Australia. Runoff-based hydrological drought frequency could also increase by 10%–50% over most land areas despite increases in mean runoff. The probability density functions (PDFs) flatten, enhancing the drought increases induced primarily by decreases in the mean. Precipitation (P) and evapotranspiration (E) changes contribute to the SM change; whereas decreases in sc_PDSI_pm result from ubiquitous PET increases of 10%–20% with contributions from decreased P over subtropical areas. Rising temperatures and vapor deficits explain most of the PET increase, which in turn explains most of the E increases over Asia and northern North America while decreased SM leads to lower E over the rest of the world. Radiation and wind speed changes have only small effects on future PET and drought. Globally, runoff ratio changes little while P, E, and R all increase by about 4%–5% in the twenty-first century.
Usability and Safety in Electronic Medical Records Interface Design
Authors: Zahabi Maryam , Kaber David B. , Swangnetr Manida 
Published: March 2015

Objective The objectives of this study were to (a) review electronic medical record (EMR) and related electronic health record (EHR) interface usability issues, (b) review how EMRs have been evaluated with safety analysis techniques along with any hazard recognition, and (c) formulate design guidelines and a concept for enhanced EMR interfaces with a focus on diagnosis and documentation processes. Background A major impact of information technology in health care has been the introduction of EMRs. Although numerous studies indicate use of EMRs to increase health care quality, there remain concerns with usability issues and safety. Method A literature search was conducted using Compendex, PubMed, CINAHL, and Web of Science databases to find EMR research published since 2000. Inclusion criteria included relevant English-language papers with subsets of keywords and any studies (manually) identified with a focus on EMR usability. Results Fifty studies met the inclusion criteria. Results revealed EMR and EHR usability problems to include violations of natural dialog, control consistency, effective use of language, effective information presentation, and customization principles as well as a lack of error prevention, minimization of cognitive load, and feedback. Studies focusing on EMR system safety made no objective assessments and applied only inductive reasoning methods for hazard recognition. Conclusion On the basis of the identified usability problems and structure of safety analysis techniques, we provide EMR design guidelines and a design concept focused on the diagnosis process and documentation. Application The design guidelines and new interface concept can be used for prototyping and testing enhanced EMRs.
Conceptualising psychological distress in families in palliative care: Findings from a systematic review
Authors: Carolan Clare M , Smith Annetta , Forbat Liz 
Published: March 2015

Background: Adult palliative care patients and their family members experience significant psychological distress and morbidity. Psychosocial interventions adopting a systemic approach may provide a cogent model to improve the psychosocial care of families in palliative care. To facilitate design of these interventions, the construct of psychological distress in families in palliative care should be empirically derived. Aim: To ascertain how psychological distress is conceptualised in families receiving palliative care. Design: A systematic review of the literature; this was followed by a thematic analysis and narrative synthesis. Data sources: Using pre-defined search terms, four electronic databases (MEDLINE, CINAHL, PsycINFO and Behavioural Sciences collections) were searched with no date restrictions imposed. Pre-determined inclusion and exclusion criteria were then applied. Results: A total of 32 papers were included in the review. Two findings emerged from data synthesis. First, distress is conceptualised as a multi-dimensional construct but little consensus exists as to how to capture and measure distress. Second, distress in the families within these studies can be conceptualised using a tiered approach, moving from individual non-interactive depictions of distress through gradations of interaction to convey a systemic account of distress within the family system. Thus, distress shifts from a unitary to a systemic construct. Conclusion: Currently, there is a paucity of research examining distress informed by family systems theories. This review proposes that distress in families in palliative care can be conceptualised and illustrated within a tiered model of distress. Further research is merited to advance current explanatory frameworks and theoretical models of distress.
Value and goals of treat-to-target in systemic lupus erythematosus: knowledge and foresight
Authors: Doria A , Gatto M , Iaccarino L , Punzi L 
Published: March 2015

Treat-to-target is a therapeutic strategy aimed at improving disease outcome through the achievement of shared treatment goals, which has dramatically ameliorated the prognosis of widespread disorders, such as hypertension or diabetes. Conversely, efforts to delineate treat-to-target in systemic lupus erythematosus (SLE) have failed in pinpointing common goals and treatment strategies, probably because of disease heterogeneity and lack of measurable biomarkers predicting disease course and ensuring a safe treatment tapering during quiescence. Given the detrimental effects of persistent disease activity and protracted corticosteroid therapy on patients’ outcome in lupus, disease remission should be pursued whenever possible. Fortunately, clinical remission is currently realistic for a greater number of patients than it was in the past, yet tight monitoring is required in order for patients to benefit from disease- and corticosteroid-free intervals, while minimizing the risk of disease flares. In everyday practice, patients should be brought to the lowest level of disease activity ensuring a significant benefit over a persistently active disease, being either clinical remission or low disease activity.
Oxidatively altered IgG with increased immunoreactivity to β2-glycoprotein I and its peptide clusters influence human coronary artery endothelial cells
Authors: Artenjak A , Omersel J , Ahlin Grabnar P , Mlinarič-Raščan I , Shoenfeld Y , Sodin-Semrl S , Božič B , Čučnik S 
Published: March 2015

Oxidative stress has been shown to play a role in modifying antibodies in favor of higher auto-immunoreactivity. We studied the immunoreactivity of oxidized IgG (oxIgG) to β2-glycoprotein I (β2GPI), six peptide sequences corresponding to amino acid clusters on its different domains, to determine their effects on human coronary artery endothelial cells (HCAEC). Human IgG was purified from seven donors, electro-oxidized and checked for immunoreactivity and avidity to β2GPI and to peptides by ELISA. Conformational stability and antibody-antigen complex formation of oxIgG was analyzed by fluorescence spectroscopy and dynamic light scattering. Resting and activated sub-confluent HCAEC were stimulated with oxIgG or IgG. Secreted cytokines were measured by ELISA. Immunoreactivity of seven oxIgG samples increased to 7.5-fold against β2GPI and to 3.8-fold against six peptides as compared to IgG. oxIgG showed low avidity “properties.” Conformational changes and exposure of protein hydrophobic regions were confirmed by an elevation in fluorescence (2.4- to 5.0-fold) on bis-ANS dye binding to oxIgG. oxIgG significantly elevated the release of GROα and IL-8 in resting and activated states of HCAEC. Oxidation alters IgG in favor of autoreactivity toward whole β2GPI and corresponding peptides on different domains of β2GPI and could lead to dysfunction of arterial endothelium by upregulation of chemokines.