bluuebunny/crossref_metadata_2025 huggingface dataset:
Probability Distribution and Deviation Information Fusion Driven Support Vector Regression Model and Its Application
Authors: Fan Changhao , Yan Xuefeng
Published: October 2017

In modeling, only information from the deviation between the output of the support vector regression (SVR) model and the training sample is considered, whereas the other prior information of the training sample, such as probability distribution information, is ignored. Probabilistic distribution information describes the overall distribution of sample data in a training sample that contains different degrees of noise and potential outliers, as well as helping develop a high‐accuracy model. To mine and use the probability distribution information of a training sample, a new support vector regression model that incorporates probability distribution information weight SVR (PDISVR) is proposed. In the PDISVR model, the probability distribution of each sample is considered as the weight and is then introduced into the error coefficient and slack variables of SVR. Thus, the deviation and probability distribution information of the training sample are both used in the PDISVR model to eliminate the influence of noise and outliers in the training sample and to improve predictive performance. Furthermore, examples with different degrees of noise were employed to demonstrate the performance of PDISVR, which was then compared with those of three SVR‐based methods. The results showed that PDISVR performs better than the three other methods.
Uncertainty Analysis in the Calibration of an Emission Tomography System for Quantitative Imaging
Authors: D’Arienzo Marco , Cox Maurice
Published: October 2017

It is generally acknowledged that calibration of the imaging system (be it a SPECT or a PET scanner) is one of the critical components associated with in vivo activity quantification in nuclear medicine. The system calibration is generally performed through the acquisition of a source with a known amount of radioactivity. The decay-corrected calibration factor is the “output” quantity in a measurement model for the process. This quantity is a function of a number of “input” variables, including total counts in the volume of interest (VOI), radionuclide activity concentration, source volume, acquisition duration, radionuclide half-life, and calibration time of the radionuclide. Uncertainties in the input variables propagate through the calculation to the “combined” uncertainty in the output quantity. In the present study, using the general formula given in the GUM (Guide to the Expression of Uncertainty in Measurement) for aggregating uncertainty components, we derive a practical relation to assess the combined standard uncertainty for the calibration factor of an emission tomography system. At a time of increasing need for accuracy in quantification studies, the proposed approach has the potential to be easily implemented in clinical practice.
Moxibustion for Chemotherapy‐Induced Nausea and Vomiting: A Systematic Review and Meta‐Analysis
Authors: Huang Ziling , Qin Zongshi , Yao Qin , Wang Yuanxuan , Liu Zhishun
Published: October 2017

Nausea and vomiting are distressing symptoms for patients receiving chemotherapy. Moxibustion, which involves the use of burning moxa to generate heat and stimulate acupoints, has been reported to potentially ameliorate chemotherapy‐induced side effects, particularly nausea and vomiting. This systematic review evaluated current evidence on the effectiveness of moxibustion against chemotherapy‐induced nausea and vomiting (CINV). We searched eight online databases and two trial registries for relevant trials. The random‐effects model was used to conduct a meta‐analysis. Furthermore, the risk ratio (RR) and mean difference (MD) were used to explain dichotomous and continuous outcomes, respectively; the outcomes were within 95% confidence intervals (CIs). The results revealed that moxibustion might more favorably relieve the severity and frequency of CINV, compared with no treatment (RR: 2.04, 95% CI: 1.42–2.93); moxibustion might have stronger effects than antiemetic drugs (RR: 1.87, 95% CI: 1.27–2.76). There is no robust result that moxibustion could enhance the effects of antiemetic drugs administered as a complementary treatment. Actual moxibustion (8.10 ± 10.98) may have more favorable effects than placebo moxibustion (46.67 ± 23.32). However, the evidence obtained is not sufficient because of the lack of strict clinical trials. Protocol Registration. This trial is registered with PROSPERO CRD42016030037.
Antibiofilm Treatment for Onychomycosis and Chronic Fungal Infections
Authors: Gupta Aditya K. , Carviel Jessie , Shear Neil H.
Published: October 2017

Onychomycosis is a difficult-to-treat chronic fungal infection of the nail. The chronic nature of onychomycosis, with relevance to current treatment practices, could be attributed to host anergy, development of increased virulence in causal agents (multidrug resistance efflux pump), and biofilms. Biofilms must be disrupted prior to antifungal treatment suggesting the necessity of combination treatment. Once the biofilm has been disrupted, further techniques in addition to antifungal usage are suggested to ensure a positive prognosis including use of antimicrobial photodynamic therapy or low-frequency surface acoustic waves. Overall, with continued success in developing antibiofilm treatment for bacterial and yeast pathogens, therapy can be more quickly expanded to dermatophytes. With a rise in predisposing factors, it is important to preemptively address treatment for this disease with continued investigation into antibiofilm therapy including optimal treatment combinations and dosages targeted specifically at dermatophytes.
Screening Performance of Placental Growth Factor for the Prediction of Low Birth Weight and Adverse Intrapartum and Neonatal Outcomes in a Term Low-Risk Population
Authors: Bligh Larissa N. , Greer Ristan M. , Kumar Sailesh
Published: October 2017

Introduction: Fetuses who fail to reach their genetic growth potential are thought to have sub-optimal placental function. Low placental growth factor (PlGF) levels have been shown to be predictive of placentally mediated conditions, such as pre-eclampsia or fetal growth restriction. We investigated the screening performance of PlGF for the prediction of low birth weight (<10th centile for gestation) and adverse intrapartum and neonatal outcomes in apparently low-risk term pregnancies. Materials and Methods: Maternal PlGF levels were measured fortnightly in a blinded, prospective, observational study from 36 weeks of pregnancy. Women and clinicians were blinded to PlGF results, and pregnancies were managed according to local policies and guidelines. Intrapartum and neonatal outcomes were recorded. PlGF was analysed for association with, and predictive capacity for, low birth weight, caesarean section for intrapartum fetal compromise (CS-IFC) and adverse neonatal outcomes. Results: A total of 438 women were included in the final analysis. Lower PlGF levels were associated with low birth weight, CS-IFC and adverse neonatal outcome. For a false-positive rate of 10 and 20%, respectively, the corresponding sensitivities were 9.7-11.1% and 22.2-26.8%. Conclusion: As a sole predictor for low birth weight, CS-IFC and adverse neonatal outcome, PlGF was poor as a test.
pTis and pT1a Ipsilateral Breast Tumor Recurrence Is Associated with Good Prognosis after Salvage Surgery
Authors: Ishitobi Makoto , Fukui Reiko , Hashimoto Yoko , Kittaka Nobuyoshi , Nakayama Takahiro , Tamaki Yasuhiro
Published: October 2017

Objectives: Patients with ipsilateral breast tumor recurrence (IBTR) after breast-conserving surgery have a poor prognosis. There is little information regarding the prognostic impact of the tumor size in patients with IBTR. Methods: A total of 143 patients who had histologically confirmed IBTR without distant metastases and who underwent salvage surgery between 1989 and 2013 in our hospital were included. Distant disease-free survival (DDFS) was calculated according to the invasive tumor size of IBTR. The median follow-up period was 4.6 years. Results: Patients with pT1b or more advanced IBTR have a high (≥20%) 5-year distant recurrence risk. There were significant differences in DDFS between patients with pTis or pT1a and those with pT1b or a more advanced stage (5-year DDFS: 94.4 vs. 70.1%, respectively, p value = 0.006). This significance remained after adjusting for other clinicopathological factors (p value = 0.04). Conclusion: Patients with pTis or pT1a IBTR have a good prognosis after salvage surgery for IBTR, and the omission of adjuvant chemotherapy could be considered. Further research and validation studies are needed.
Obesity and Type 2 Diabetes: Two Diseases with a Need for Combined Treatment Strategies - EASO Can Lead the Way
Authors: Leitner Deborah R. , Frühbeck Gema , Yumuk Volkan , Schindler Karin , Micic Dragan , Woodward Euan , Toplak Hermann
Published: October 2017

Obesity is a chronic metabolic disease affecting adults and children worldwide. It has become one of the leading causes of death, as obesity is known to be the main risk factor for a number of non-communicable diseases, in particular type 2 diabetes. This close relationship led to the connotation ‘diabesity', highlighting the fact that the majority of individuals with diabetes are overweight or obese. Until today the BMI is still used to classify overweight and obesity. Since reduced muscle mass is highly prevalent throughout the BMI range, the measurement of body composition is strongly recommended. Moreover, it is essential for monitoring the course of weight reduction, which is part of every effective anti-obesity treatment. Weight reduction can be achieved via different weight loss strategies, including lifestyle intervention (diet and exercise), pharmacotherapy, or bariatric surgery. However, not all of these strategies are suitable for all patients, and any further needs should be considered. Besides, attention should also be drawn to concomitant therapies. These therapies may promote additional weight gain and further trigger the deterioration of blood glucose control. Thus, therapeutic strategies are warranted, which can be easily used for the management of obese patients with type 2 diabetes to achieve their glycemic and weight loss goals.
Action Potential Shortening and Impairment of Cardiac Function by Ablation of
Slc26a6
Authors: Sirish Padmini , Ledford Hannah A. , Timofeyev Valeriy , Thai Phung N. , Ren Lu , Kim Hyo Jeong , Park Seojin , Lee Jeong Han , Dai Gu , Moshref Maryam , Sihn Choong-Ryoul , Chen Wei Chun , Timofeyeva Maria Valeryevna , Jian Zhong , Shimkunas Rafael , Izu Leighton T. , Chiamvimonvat Nipavan , Chen-Izu Ye , Yamoah Ebenezer N. , Zhang Xiao-Dong
Published: October 2017

Background

Intracellular pH (pH
i
) is critical to cardiac excitation and contraction; uncompensated changes in pH
i
impair cardiac function and trigger arrhythmia. Several ion transporters participate in cardiac pH
i
regulation. Our previous studies identified several isoforms of a solute carrier Slc26a6 to be highly expressed in cardiomyocytes. We show that Slc26a6 mediates electrogenic Cl
−
/HCO
3
−
exchange activities in cardiomyocytes, suggesting the potential role of Slc26a6 in regulation of not only pH
i
, but also cardiac excitability.

Methods and Results

To test the mechanistic role of Slc26a6 in the heart, we took advantage of
Slc26a6
knockout (
Slc26a6

−/

−

) mice using both in vivo and in vitro analyses. Consistent with our prediction of its electrogenic activities, ablation of
Slc26a6
results in action potential shortening. There are reduced Ca
2+
transient and sarcoplasmic reticulum Ca
2+
load, together with decreased sarcomere shortening in
Slc26a6
−/
−
cardiomyocytes. These abnormalities translate into reduced fractional shortening and cardiac contractility at the in vivo level. Additionally, pH
i
is elevated in
Slc26a6
−/
−
cardiomyocytes with slower recovery kinetics from intracellular alkalization, consistent with the Cl
−
/HCO
3
−
exchange activities of Slc26a6. Moreover,
Slc26a6

−/

−

mice show evidence of sinus bradycardia and fragmented QRS complex, supporting the critical role of Slc26a6 in cardiac conduction system.

Conclusions

Our study provides mechanistic insights into Slc26a6, a unique cardiac electrogenic Cl
−
/HCO
3
−
transporter in ventricular myocytes, linking the critical roles of Slc26a6 in regulation of pH
i
, excitability, and contractility. pH
i
is a critical regulator of other membrane and contractile proteins. Future studies are needed to investigate possible changes in these proteins in
Slc26a6
−/
−
mice.
Predicting the Functional Impact of KCNQ1 Variants of Unknown Significance
Authors: Li Bian , Mendenhall Jeffrey L. , Kroncke Brett M. , Taylor Keenan C. , Huang Hui , Smith Derek K. , Vanoye Carlos G. , Blume Jeffrey D. , George Alfred L. , Sanders Charles R. , Meiler Jens
Published: October 2017

Background—

An emerging standard-of-care for long-QT syndrome uses clinical genetic testing to identify genetic variants of the KCNQ1 potassium channel. However, interpreting results from genetic testing is confounded by the presence of variants of unknown significance for which there is inadequate evidence of pathogenicity.

Methods and Results—

In this study, we curated from the literature a high-quality set of 107 functionally characterized KCNQ1 variants. Based on this data set, we completed a detailed quantitative analysis on the sequence conservation patterns of subdomains of KCNQ1 and the distribution of pathogenic variants therein. We found that conserved subdomains generally are critical for channel function and are enriched with dysfunctional variants. Using this experimentally validated data set, we trained a neural network, designated Q1VarPred, specifically for predicting the functional impact of KCNQ1 variants of unknown significance. The estimated predictive performance of Q1VarPred in terms of Matthew’s correlation coefficient and area under the receiver operating characteristic curve were 0.581 and 0.884, respectively, superior to the performance of 8 previous methods tested in parallel. Q1VarPred is publicly available as a web server at
http://meilerlab.org/q1varpred
.

Conclusions—

Although a plethora of tools are available for making pathogenicity predictions over a genome-wide scale, previous tools fail to perform in a robust manner when applied to KCNQ1. The contrasting and favorable results for Q1VarPred suggest a promising approach, where a machine-learning algorithm is tailored to a specific protein target and trained with a functionally validated data set to calibrate informatics tools.
Characterization of a Human Induced Pluripotent Stem Cell–Derived Cardiomyocyte Model for the Study of Variant Pathogenicity
Authors: Gélinas Roselle , El Khoury Nabil , Chaix Marie-A. , Beauchamp Claudine , Alikashani Azadeh , Ethier Nathalie , Boucher Gabrielle , Villeneuve Louis , Robb Laura , Latour Frédéric , Mondesert Blandine , Rivard Lena , Goyette Philippe , Talajic Mario , Fiset Céline , Rioux John David
Published: October 2017

Background—

Long-QT syndrome is a potentially fatal condition for which 30% of patients are without a genetically confirmed diagnosis. Rapid identification of causal mutations is thus a priority to avoid at-risk situations that can lead to fatal cardiac events. Massively parallel sequencing technologies are useful for the identification of sequence variants; however, electrophysiological testing of newly identified variants is crucial to demonstrate causality. Long-QT syndrome could, therefore, benefit from having a standardized platform for functional characterization of candidate variants in the physiological context of human cardiomyocytes.

Methods and Results—

Using a variant in Kir2.1 (Gly52Val) revealed by whole-exome sequencing in a patient presenting with symptoms of long-QT syndrome as a proof of principle, we demonstrated that commercially available human induced pluripotent stem cell–derived cardiomyocytes are a powerful model for screening variants involved in genetic cardiac diseases. Immunohistochemistry experiments and whole-cell current recordings in human embryonic kidney cells expressing the wild-type or the mutant Kir2.1 demonstrated that Kir2.1-52V alters channel cellular trafficking and fails to form a functional channel. Using human induced pluripotent stem cell–derived cardiomyocytes, we not only confirmed these results but also further demonstrated that Kir2.1-52V is associated with a dramatic prolongation of action potential duration with evidence of arrhythmic activity, parameters which could not have been studied using human embryonic kidney cells.

Conclusions—

Our study confirms the pathogenicity of Kir2.1-52V in 1 patient with long-QT syndrome and also supports the use of isogenic human induced pluripotent stem cell–derived cardiomyocytes as a physiologically relevant model for the screening of variants of unknown function.
Activation of Autophagy Ameliorates Cardiomyopathy in
Mybpc3
-Targeted Knockin Mice
Authors: Singh Sonia R. , Zech Antonia T.L. , Geertz Birgit , Reischmann-Düsener Silke , Osinska Hanna , Prondzynski Maksymilian , Krämer Elisabeth , Meng Qinghang , Redwood Charles , van der Velden Jolanda , Robbins Jeffrey , Schlossarek Saskia , Carrier Lucie
Published: October 2017

Background:

Alterations in autophagy have been reported in hypertrophic cardiomyopathy (HCM) caused by Danon disease, Vici syndrome, or LEOPARD syndrome, but not in HCM caused by mutations in genes encoding sarcomeric proteins, which account for most of HCM cases.
MYBPC3
, encoding cMyBP-C (cardiac myosin-binding protein C), is the most frequently mutated HCM gene.

Methods and Results:

We evaluated autophagy in patients with HCM carrying
MYBPC3
mutations and in a
Mybpc3
-targeted knockin HCM mouse model, as well as the effect of autophagy modulators on the development of cardiomyopathy in knockin mice. Microtubule-associated protein 1 light chain 3 (LC3)-II protein levels were higher in HCM septal myectomies than in nonfailing control hearts and in 60-week-old knockin than in wild-type mouse hearts. In contrast to wild-type, autophagic flux was blunted and associated with accumulation of residual bodies and glycogen in hearts of 60-week-old knockin mice. We found that Akt-mTORC1 (mammalian target of rapamycin complex 1) signaling was increased, and treatment with 2.24 mg/kg·d rapamycin or 40% caloric restriction for 9 weeks partially rescued cardiomyopathy or heart failure and restored autophagic flux in knockin mice.

Conclusions:

Altogether, we found that (1) autophagy is altered in patients with HCM carrying
MYBPC3
mutations, (2) autophagy is impaired in
Mybpc3
-targeted knockin mice, and (3) activation of autophagy ameliorated the cardiac disease phenotype in this mouse model. We propose that activation of autophagy might be an attractive option alone or in combination with another therapy to rescue HCM caused by
MYBPC3
mutations.
Risk Stratification of Severe Aortic Stenosis With Preserved Left Ventricular Ejection Fraction Using Peak Aortic Jet Velocity
Authors: Bohbot Yohann , Rusinaru Dan , Delpierre Quentin , Marechaux Sylvestre , Tribouilloy Christophe
Published: October 2017

Background—

Current guidelines consider aortic valve replacement reasonable in asymptomatic patients with very severe aortic stenosis (AS); however, the definition of very severe AS based on peak aortic jet velocity (Vmax) remains unclear with a 5-m/s cutoff in US guidelines and 5.5 m/s in European guidelines. Because ≈20% of patients with severe AS and preserved left ventricular ejection fraction have Vmax in this range, we aimed to assess the relationship between Vmax and mortality and determine the best threshold to define very severe AS.

Methods and Results—

A total of 1140 patients with severe AS (aortic valve area ≤1 cm
2
, Vmax ≥4 m/s) and preserved left ventricular ejection fraction were included. The population was divided into 4 groups according to Vmax (4–4.49, 4.5–4.99, 5–5.49, and ≥5.5 m/s). After adjustment for covariates (including surgery), there was no difference in all-cause mortality between Vmax 4 to 4.49 m/s and Vmax 4.5 to 4.99 m/s (
P
=0.64). Both Vmax 5 to 5.49 m/s and Vmax ≥5.5 m/s exhibited significant excess mortality compared with Vmax 4 to 4.49 m/s (adjusted hazard ratio=1.34 [1.18–1.52];
P
<0.001, and 1.28 [1.16–1.41];
P
<0.001, respectively). Mortality risk was similar for Vmax 5 to 5.49 m/s and Vmax ≥5.5 m/s (
P
=0.93). Compared with Vmax <5 m/s, patients with Vmax ≥5 m/s had greater mortality risk (adjusted hazard ratio=1.86 [1.55–2.54];
P
<0.001), even in the subgroup of asymptomatic even in the subgroup of asymptomatic patients (adjusted hazard ratio=2.08 [1.25-3.46];
P
=0.005).

Conclusions—

Our results demonstrate the strong relationship between Vmax and mortality in patients with severe AS and preserved left ventricular ejection fraction irrespective of symptoms. Vmax ≥5 m/s at the time of AS diagnosis identifies patients with very severe AS at high risk of death.
Pathologic Stimulus Determines Lineage Commitment of Cardiac C-kit
+
Cells
Authors: Chen Zhongming , Zhu Wuqiang , Bender Ingrid , Gong Wuming , Kwak Il-Youp , Yellamilli Amritha , Hodges Thomas J. , Nemoto Natsumi , Zhang Jianyi , Garry Daniel J. , van Berlo Jop H.
Published: October 2017

Background:

Although cardiac c-kit
+
cells are being tested in clinical trials, the circumstances that determine lineage differentiation of c-kit
+
cells in vivo are unknown. Recent findings suggest that endogenous cardiac c-kit
+
cells rarely contribute cardiomyocytes to the adult heart. We assessed whether various pathological stimuli differentially affect the eventual cell fates of c-kit
+
cells.

Methods:

We used single-cell sequencing and genetic lineage tracing of c-kit
+
cells to determine whether various pathological stimuli would result in different fates of c-kit
+
cells.

Results:

Single-cell sequencing of cardiac CD45
-
c-kit
+
cells showed innate heterogeneity, indicative of the existence of vascular and mesenchymal c-kit
+
cells in normal hearts. Cardiac pressure overload resulted in a modest increase in c-kit-derived cardiomyocytes, with significant increases in the numbers of endothelial cells and fibroblasts. Doxorubicin-induced acute cardiotoxicity did not increase c-kit-derived endothelial cell fates but instead induced cardiomyocyte differentiation. Mechanistically, doxorubicin-induced DNA damage in c-kit
+
cells resulted in expression of p53. Inhibition of p53 blocked cardiomyocyte differentiation in response to doxorubicin, whereas stabilization of p53 was sufficient to increase c-kit-derived cardiomyocyte differentiation.

Conclusions:

These results demonstrate that different pathological stimuli induce different cell fates of c-kit
+
cells in vivo. Although the overall rate of cardiomyocyte formation from c-kit
+
cells is still below clinically relevant levels, we show that p53 is central to the ability of c-kit
+
cells to adopt cardiomyocyte fates, which could lead to the development of strategies to preferentially generate cardiomyocytes from c-kit
+
cells.
Tai Chi Is a Promising Exercise Option for Patients With Coronary Heart Disease Declining Cardiac Rehabilitation
Authors: Salmoirago‐Blotcher Elena , Wayne Peter M. , Dunsiger Shira , Krol Julie , Breault Christopher , Bock Beth C. , Wu Wen‐Chih , Yeh Gloria Y.
Published: October 2017

Background

More than 60% of patients decline participation in cardiac rehabilitation after a myocardial infarction. Options to improve physical activity (
PA
) and other risk factors in these high‐risk individuals are limited. We conducted a phase 2 randomized controlled trial to determine feasibility, safety, acceptability, and estimates of effect of tai chi on
PA
, fitness, weight, and quality of life.

Methods and Results

Patients with coronary heart disease declining cardiac rehabilitation enrollment were randomized to a “
LITE
” (2 sessions/week for 12 weeks) or to a “
PLUS
” (3 sessions/week for 12 weeks, then maintenance classes for 12 additional weeks) condition.
PA
(accelerometry), weight, and quality of life (Health Survey Short Form) were measured at baseline and 3, 6, and 9 months after baseline; aerobic fitness (stress test) was measured at 3 months. Twenty‐nine participants (13
PLUS
and 16
LITE
) were enrolled. Retention at 9 months was 90% (
LITE
) and 88% (
PLUS
). No serious tai chi–related adverse events occurred. Significant mean between group differences in favor of the
PLUS
group were observed at 3 and 6 months for moderate‐to‐vigorous
PA
(100.33 min/week [95% confidence interval, 15.70–184.95 min/week] and 111.62 min/week; [95% confidence interval, 26.17–197.07 min/week], respectively, with a trend toward significance at 9 months), percentage change in weight, and quality of life. No changes in aerobic fitness were observed within and between groups.

Conclusions

In this community sample of patients with coronary heart disease declining enrollment in cardiac rehabilitation, a 6‐month tai chi program was safe and improved
PA
, weight, and quality of life compared with a 3‐month intervention. Tai chi could be an effective option to improve PA in this high‐risk population.

Clinical Trial Registration

URL
:
http://www.clinicaltrials.gov
. Unique identifier:
NCT
02165254.
Economic Impact of Subsequent Depression in Patients With a New Diagnosis of Stable Angina: A Population‐Based Study
Authors: Szpakowski Natalie , Qiu Feng , Masih Shannon , Kurdyak Paul , Wijeysundera Harindra C.
Published: October 2017

Background

Depression is strongly linked to increased morbidity and mortality in patients with chronic stable angina; however, its associated healthcare costs have been less well studied. Our objective was to identify the characteristics of chronic stable patients found to have depression and to determine the impact of an occurrence of depression on healthcare costs within 1 year of a diagnosis of stable angina.

Methods and Results

In this population‐based study conducted in Ontario, Canada, we identified patients diagnosed with stable angina based on angiogram between October 1, 2008, and September 30, 2013. Depression was ascertained by physician billing codes and hospital admission diagnostic codes contained within administrative databases. The primary outcome was cumulative mean 1‐year healthcare costs following index angiogram. Generalized linear models were developed with a logarithmic link and γ distribution to determine predictors of cost. Our cohort included 22 917 patients with chronic stable angina. Patients with depression had significantly higher mean 1‐year healthcare costs ($32 072±$41 963) than patients without depression ($23 021±$25 741). After adjustment for baseline comorbidities, depression was found to be a significant independent predictor of cost, with a cost ratio of 1.33 (95% confidence interval, 1.29–1.37). Higher costs in depressed patients were seen in all healthcare sectors, including acute and ambulatory care.

Conclusions

Depression is an important driver of healthcare costs in patients following a diagnosis of chronic stable angina. Further research is needed to understand whether improvements in the approach to diagnosis and treatment of depression will translate to reduced expenditures in this population.
Afterword
Authors: Gellner David N.
Published: October 2017

In reflecting on the contributions to this collection, the afterword outlines three ways of understanding violence—direct physical force, structural violence and cultural or symbolic violence—and relates these to Steven Lukes’ three faces of power. It revisits Weber’s definition of the modern state as claiming a monopoly of the legitimate use of the first kind of violence, and contrasts that with the ways in which the actual practice of South Asian politics implies or requires violence. The example of state and non-state violence in Nepal in 2015 is used to illustrate these themes. This example brings out, as several contributions do, the importance of borders as violence-provoking sites of state sensitivity.
Taxonomic and morphological revision of butterfly rays of the Gymnura micrura (Bloch & Schneider 1801) species complex, with the description of two new species (Myliobatiformes: Gymnuridae)
Authors: YOKOTA LEANDRO , CARVALHO MARCELO RODRIGUES DE
Published: October 2017

An extensive taxonomic revision of Gymnura micrura based on external and internal morphology, and considering specimens from its entire geographical distribution in the Atlantic Ocean, is presented. Gymnura micrura is redescribed and a neotype is designated; its distributional range is limited to the Southwestern Atlantic. Two new species of butterfly rays are described: Gymnura lessae, sp. nov., occurring in the North and Central Western Atlantic, and Gymnura sereti, sp. nov., found in the Eastern Central Atlantic. The three species are morphologically very similar (with G. micrura most similar to G. lessae, sp. nov.) and cannot be distinguished based on the primary diagnostic characters typically utilized for butterfly rays. The dorsal color, smaller size and eventual presence of a dorsal fin in some males may be helpful to distinguish G. micrura, whereas the size and morphology of the clasper are the main external characters separating G. sereti, sp. nov., from the other two species, although the shape of disc (especially among adult males) and contour of the lower lip are also helpful. Despite the skeleton being conservative among the species, we found consistent variations that support the validity of the new species described. Due to similarity in external morphology these internal characters were fundamental to discriminate the new species. The scapulocoracoid was an important diagnostic skeletal structure, exhibiting a series of variations that separated the three species. Variations in the synarcual, outline of the dorsal cranial fontanelle, number and shape of mesopterygia, and small differences in the mandibular arches and pelvic girdle were useful to diagnose G. sereti, sp. nov. The contour of the hyomandibula was an important diagnostic character distinguishing G. lessae, sp. nov., from the other two species. Meristic data were also useful, with G. sereti, sp. nov., presenting a lower number of radials in the second element of the mesopterygium and a higher number of diplospondylous vertebrae. In contrast, G. lessae, sp. nov., presented a higher number of pectoral-fin radials. Subtle, but consistent differences, were also found in the design of the ventral lateral-line system. A Canonical Discriminant Analysis provides strong statistical support for the validity of the new species, significantly distinguishing the three species groupings (p < 0.00001). External morphology, ventral lateral-line system and skeleton are described and illustrated for all three valid species.
Quantifying the Effects of Horizontal Grid Length and Parameterized Convection on the Degree of Convective Organization Using a Metric of the Potential for Convective Interaction
Authors: White B. A. , Buchanan A. M. , Birch C. E. , Stier P. , Pearson K. J.
Published: October 2017

The organization of deep convection and its misrepresentation in many global models is the focus of much current interest. A new method is presented for quantifying convective organization based on the identification of convective objects and subsequent derivation of object numbers, areas, and separation distances to describe the degree of convective organization. These parameters are combined into a “convection organization potential” based on the physical principle of an interaction potential between pairs of convective objects. This technique is applied to simulated and observed fields of outgoing longwave radiation (OLR) over the West African monsoon region using data from Met Office Unified Model simulations and satellite observations made by the Geostationary Earth Radiation Budget (GERB) instrument. The method is evaluated by using it to quantify differences between models with different horizontal grid lengths and representations of convection. Distributions of OLR, precipitation and organization parameters, the diurnal cycle of convection, and relationships between the meteorology in different states of organization are compared. Switching from a configuration with parameterized convection to one that allows the model to resolve convective processes at the model grid scale is the leading-order factor improving some aspects of model performance, while increased model resolution is the dominant factor for others. However, no single model configuration performs best compared to observations, indicating underlying deficiencies in both model scaling and process understanding.
On the Impact of Unmanned Aerial System Observations on Numerical Weather Prediction in the Coastal Zone
Authors: Flagg David D. , Doyle James D. , Holt Teddy R. , Tyndall Daniel P. , Amerault Clark M. , Geiszler Daniel , Haack Tracy , Moskaitis Jonathan R. , Nachamkin Jason , Eleuterio Daniel P.
Published: October 2017

The Trident Warrior observational field campaign conducted off the U.S. mid-Atlantic coast in July 2013 included the deployment of an unmanned aerial system (UAS) with several payloads on board for atmospheric and oceanic observation. These UAS observations, spanning seven flights over 5 days in the lowest 1550 m above mean sea level, were assimilated into a three-dimensional variational data assimilation (DA) system [the Naval Research Laboratory Atmospheric Variational Data Assimilation System (NAVDAS)] used to generate analyses for a numerical weather prediction model [the Coupled Ocean–Atmosphere Mesoscale Prediction System (COAMPS)] with a coupled ocean model [the Naval Research Laboratory Navy Coastal Ocean Model (NCOM)]. The impact of the assimilated UAS observations on short-term atmospheric prediction performance is evaluated and quantified. Observations collected from 50 radiosonde launches during the campaign adjacent to the UAS flight paths serve as model forecast verification. Experiments reveal a substantial reduction of model bias in forecast temperature and moisture profiles consistently throughout the campaign period due to the assimilation of UAS observations. The model error reduction is most substantial in the vicinity of the inversion at the top of the model-estimated boundary layer. Investigations reveal a consistent improvement to prediction of the vertical position, strength, and depth of the boundary layer inversion. The relative impact of UAS observations is explored further with experiments of systematic denial of data streams from the NAVDAS DA system and removal of individual measurement sources on the UAS platform.
Assimilation of ZDR Columns for Improving the Spinup and Forecast of Convective Storms in Storm-Scale Models: Proof-of-Concept Experiments
Authors: Carlin Jacob T. , Gao Jidong , Snyder Jeffrey C. , Ryzhkov Alexander V.
Published: October 2017

Achieving accurate storm-scale analyses and reducing the spinup time of modeled convection is a primary motivation for the assimilation of radar reflectivity data. One common technique of reflectivity data assimilation is using a cloud analysis, which inserts temperature and moisture increments and hydrometeors deduced from radar reflectivity via empirical relations to induce and sustain updraft circulations. Polarimetric radar data have the ability to provide enhanced insight into the microphysical and dynamic structure of convection. Thus far, however, relatively little has been done to leverage these data for numerical weather prediction. In this study, the Advanced Regional Prediction System’s cloud analysis is modified from its original reflectivity-based formulation to provide moisture and latent heat adjustments based on the detection of differential reflectivity columns, which can serve as proxies for updrafts in deep moist convection and, subsequently, areas of saturation and latent heat release. Cycled model runs using both the original cloud analysis and above modifications are performed for two high-impact weather cases: the 19 May 2013 central Oklahoma tornadic supercells and the 25 May 2016 north-central Kansas tornadic supercell. The analyses and forecasts of convection qualitatively and quantitatively improve in both cases, including more coherent analyzed updrafts, more realistic forecast reflectivity structures, a better correspondence between forecast updraft helicity tracks and radar-derived rotation tracks, and improved frequency biases and equitable threat scores for reflectivity. Based on these encouraging results, further exploration of the assimilation of dual-polarization radar data into storm-scale models is warranted.
Aquinas and the ‘Genius of Woman’
Authors: Newton William
Published: October 2017

Aquinas views women as inferior to men at a natural level in some respects. While affirming unity of species and hence an essential equality, he views women as intellectually inferior. This article considers the root cause of this position and argues that we must make a distinction between a twofold inheritance that was bequeathed by Aristotle to Aquinas. It is the erroneous embryology of Aristotle that is the underlying cause of Aquinas’s judgment of the inferiority of women because it divides the sexes into passive and active principles of human generation. Given Aquinas’s metaphysical commitment to the superiority of act over potency, this necessarily leads to a judgment of inferiority and has far-reaching implications vis-a-vis a negative view of the intellectual capacity of women. However, there is an important metaphysical inheritance from Aristotle that, if carefully separated from the erroneous physics (i.e. from the embryology), has the power to give credibility to the idea of the ‘genius of woman’, as popularized by John Paul II. A key element of this positive inheritance is the hylomorphic theory understood to include the notion of matter having some determinative impact on the substantial form.
St Benedict’s Priory, Saint-Malo, 1611–1669
Authors: Scott Geoffrey
Published: October 2017

Over the last few years, the 400th anniversaries of the foundations of three of the earliest monasteries of the revived English Benedictine Congregation have been celebrated: St Gregory’s, Douai (1606), St Laurence’s, Dieulouard (1608) and St Edmund’s, Paris (1615). There have been no similar celebrations for the one monastery which did not survive, that of St Benedict in Saint-Malo, which was founded in 1611 and ended its days as an English Benedictine monastery in 1669, when it was handed over to the French Congregation of Saint-Maur. This article is a delayed attempt to record briefly the story of the priory of St Benedict in Saint-Malo.
ISMP Adverse Drug Reactions: Levofloxacin-Induced Neuroexcitation and Hallucinations; Statin-Induced Muscle Rupture; Mefloquine-Induced Rhabdomyolysis; Methimazole-Induced Cholestatic Hepatitis; Decitabine-Induced Hand and Foot Syndrome
Authors: Mancano Michael A.
Published: October 2017

The purpose of this feature is to heighten awareness of specific adverse drug reactions (ADRs), discuss methods of prevention, and promote reporting of ADRs to the US Food and Drug Administration’s (FDA) MedWatch program (800-FDA-1088). If you have reported an interesting, preventable ADR to MedWatch, please consider sharing the account with our readers. Write to Dr. Mancano at ISMP, 200 Lakeside Drive, Suite 200, Horsham, PA 19044 (phone: 215-707-4936; e-mail: mmancano@temple.edu ). Your report will be published anonymously unless otherwise requested. This feature is provided by the Institute for Safe Medication Practices (ISMP) in cooperation with the FDA’s MedWatch program and Temple University School of Pharmacy. ISMP is an FDA MedWatch partner.
Critical Care Pharmacist Market Perceptions: Comparison of Critical Care Program Directors and Directors of Pharmacy
Authors: Hager David R. , Persaud Rosemary A. , Naseman Ryan W. , Choudhary Kavish , Carter Kristen E. , Hansen Amanda
Published: October 2017

Background: While hospital beds continue to decline as patients previously treated as inpatients are stabilized in ambulatory settings, the number of critical care beds available in the United States continues to rise. Growth in pharmacy student graduation, postgraduate year 2 critical care (PGY2 CC) residency programs, and positions has also increased. There is a perception that the critical care trained pharmacist market is saturated, yet this has not been evaluated since the rise in pharmacy graduates and residency programs. Purpose: To describe the current perception of critical care residency program directors (CC RPDs) and directors of pharmacy (DOPs) on the critical care pharmacist job market and to evaluate critical care postresidency placement and anticipated changes in PGY2 CC programs. Methods: Two electronic surveys were distributed from October 2015 to November 2015 through Vizient/University HealthSystem Consortium, American Society of Health-System Pharmacists (ASHP), Society of Critical Care Medicine, and American College of Clinical Pharmacy listservs to target 2 groups of respondents: CC RPDs and DOPs. Questions were based on the ASHP Pharmacy Forecast and the Pharmacy Workforce Center’s Aggregate Demand Index and were intended to identify perceptions of the critical care market of the 2 groups. Results: Of 116 CC RPDs, there were 66 respondents (56.9% response rate). Respondents have observed an increase in applicants; however, they do not anticipate increasing the number of positions in the next 5 years. The overall perception is that there is a balance in supply and demand in the critical care trained pharmacist market. A total of 82 DOPs responded to the survey. Turnover of critical care pharmacists within respondent organizations is expected to be low. Although a majority of DOPs plan to expand residency training positions, only 9% expect to increase positions in critical care PGY2 training. Overall, DOP respondents indicated a balance of supply and demand in the critical care trained pharmacist market. In comparing RPD and DOP perceptions of the demand for critical care pharmacists, DOPs perceived demand to be higher than RPDs (mean, 3.2 vs 2.8; P = .032). Conclusion: Although there is a perception of the oversupply of critical care trained pharmacists, a survey of DOPs and CC RPDs found a market with positions available, rapid hiring, stable salaries, and plans for expanded hiring of critical care trained pharmacists.
ISMP Adverse Drug Reactions: Allergic Angina Caused by Fluconazole Rhabdomyolysis Caused by Risperidone High Incidence of Hyponatremia With High-Dose Trimethoprim-Sulfamethoxazole Lithium Carbonate-Induced Hypersalivation Persistent Hemorrhage After Idarucizumab Administration
Authors: Mancano Michael A.
Published: October 2017

The purpose of this feature is to heighten awareness of specific adverse drug reactions (ADRs), discuss methods of prevention, and promote reporting of ADRs to the US Food and Drug Administration’s (FDA) MedWatch program (800-FDA-1088). If you have reported an interesting, preventable ADR to MedWatch, please consider sharing the account with our readers. Write to Dr. Mancano at ISMP, 200 Lakeside Drive, Suite 200, Horsham, PA 19044 (phone: 215-707-4936; e-mail: mmancano@temple.edu ). Your report will be published anonymously unless otherwise requested. This feature is provided by the Institute for Safe Medication Practices (ISMP) in cooperation with the FDA’s MedWatch program and Temple University School of Pharmacy. ISMP is an FDA MedWatch partner.
Cancer Chemotherapy Update: Bevacizumab, Etoposide, and Cisplatin Regimen for Refractory Brain Metastases
Authors: Mayer Seth A. , Solimando Dominic A. , Waddell J. Aubrey
Published: October 2017

The complexity of cancer chemotherapy requires pharmacists be familiar with the complicated regimens and highly toxic agents used. This column reviews various issues related to preparation, dispensing, and administration of antineoplastic therapy, and the agents, both commercially available and investigational, used to treat malignant diseases. Questions or suggestions for topics should be addressed to Dominic A. Solimando, Jr, President, Oncology Pharmacy Services, Inc, 4201 Wilson Blvd #110-545, Arlington, VA 22203, email: OncRxSvc@comcast.net ; or J. Aubrey Waddell, Professor, University of Tennessee College of Pharmacy; Oncology Pharmacist, Pharmacy Department, Blount Memorial Hospital, 907 E. Lamar Alexander Parkway, Maryville, TN 37804, email: waddfour@charter.net .

Regimen Name: Bevacizumab, etoposide, and cisplatin (BEEP)

Origin of Name: The regimen is named for the medications it contains: bevacizumab, etoposide, and cisplatin.
Significant Published Articles for Pharmacy Nutrition Support Practice in 2016
Authors: Dickerson Roland N. , Kumpf Vanessa J. , Bingham Angela L. , Cogle Sarah V. , Blackmer Allison B. , Tucker Anne M. , Chan Lingtak-Neander , Canada Todd W.
Published: October 2017

Purpose: To assist the pharmacist engaged in nutrition support therapy in staying current with pertinent literature. Methods: Several clinical pharmacists engaged in nutrition support therapy compiled a list of articles published in 2016 considered important to their clinical practice. The citation list was compiled into a single spreadsheet where the author participants were asked to assess whether the paper was considered important to nutrition support pharmacy practice. A culled list of publications was then identified whereby the majority of author participants (at least 5 out of 8) considered the paper to be important. Guideline and consensus papers from professional organizations, important to practice but not scored, were also included. Results: A total of 103 articles were identified; 10 from the primary literature were voted by the group to be of high importance. An additional 11 organizational guidelines, position, recommendation, or consensus papers were also identified. The top-ranked articles from the primary literature were reviewed. Conclusion: It is recommended that pharmacists, engaged in nutrition support therapy, be familiar with the majority of these articles as it pertains to their practice.
Impact of Developing Adult Ketamine Order Panels for the Emergency Department
Authors: Baird Haley , Rumbarger Rachel
Published: October 2017

Background: Ketamine in adults has been identified as a safe and effective alternative for multiple indications, each with specific evidence-based dosing ranges. Emergency department (ED) providers are tasked with appropriate ordering of ketamine. A multi-institutional retrospective analysis within EDs at a large health system from November 2013 to October 2015 reviewed ED adult ketamine prescribing patterns for procedural sedation (PS), rapid sequence intubation (RSI), and analgesia. Retrospective cohort results revealed 56% (84 of 150) of PS, 64% (16 of 25) of RSI, and 81.5% (53 of 65) of analgesia ketamine doses fell within indication-specific dosing ranges. Objective: The study purpose was to evaluate the impact of standardizing ED ordering processes to increase appropriate dosing of ketamine. Methodology: Indication-specific adult ED ketamine order panels based on available clinical trial data were implemented in the electronic medical record and ED provider education conducted. Adults at least 18 years of age who received ketamine in the ED for PS, RSI, or analgesia from March 2016 to May 2016 were included. Patients were excluded if no weight or indication was documented. The primary outcome was percentage change in frequency of appropriately dosed ketamine versus the retrospective cohort. The secondary outcome was use of ketamine order panels. Mantel-Haenszel tests were used for statistical analysis. Results: Ketamine for prospective cohort adult ED patients was significantly more likely to be dosed appropriately than in the retrospective cohort (odds ratio: 2.94, 95% confidence interval: 1.1-7.8; P = .0231). Conclusion: Results suggest increased standardization with added decision support increased appropriate indication-specific dosing of ketamine for adults in the ED.