bluuebunny/crossref_metadata_2025 huggingface dataset:
Transfusion of Platelets Loaded With Recombinant ADAMTS13 (A Disintegrin and Metalloprotease With Thrombospondin Type 1 Repeats-13) Is Efficacious for Inhibiting Arterial Thrombosis Associated With Thrombotic Thrombocytopenic Purpura
Authors: Abdelgawwad Mohammad S. , Cao Wenjing , Zheng Liang , Kocher Nicole K. , Williams Lance A. , Zheng X. Long
Published: October 2018

Objective—

ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 repeats-13) cleaves VWF (von Willebrand factor). This process is essential for hemostasis. Severe deficiency of plasma ADAMTS13 activity, most commonly resulting from autoantibodies against ADAMTS13, causes thrombotic thrombocytopenic purpura. Therapeutic plasma exchange is the standard of care to date, which removes autoantibodies and replenishes ADAMTS13. However, such a therapy is often ineffective to raise plasma ADAMTS13 activity, and in-hospital mortality rate remains as high as 20%.

Approach and Results—

To overcome the inhibition by autoantibodies, we developed a novel approach by delivering rADAMTS13 (recombinant ADAMTS13 ) using platelets as vehicles. We show that both human and murine platelets can uptake rADAMTS13 ex vivo. The endocytosed rADAMTS13 within platelets remains intact, active, and is stored in α-granules. Under arterial shear (100 dyne/cm
2
), the rADAMTS13 in platelets is released and effectively inhibits platelet adhesion and aggregation on a collagen-coated surface in a concentration-dependent manner. Transfusion of rADAMTS13-loaded platelets into
Adamts13
−/−
mice dramatically reduces the rate of thrombus formation in the mesenteric arterioles after FeCl
3
injury. An ex vivo transfusion of rADAMTS13-loaded platelets to a reconstituted whole blood containing plasma from a patient with immune-mediated thrombotic thrombocytopenic purpura and the cellular components (eg, erythrocytes and leukocytes) from a healthy individual, as well as a fresh whole blood obtained from a patient with congenital or immune-mediated thrombotic thrombocytopenic purpura also dramatically reduces the rate of thrombus formation under arterial flow.

Conclusions—

Our results demonstrate that transfusion of rADAMTS13-loaded platelets may be a novel and potentially effective therapeutic approach for arterial thrombosis, associated with congenital and immune-mediated thrombotic thrombocytopenic purpura.
Distinct Proteomic Signatures in 16 HDL (High-Density Lipoprotein) Subspecies
Authors: Furtado Jeremy D. , Yamamoto Rain , Melchior John T. , Andraski Allison B. , Gamez-Guerrero Maria , Mulcahy Patrick , He Zeling , Cai Tianxi , Davidson W. Sean , Sacks Frank M.
Published: October 2018

Objective—

HDL (high-density lipoprotein) in plasma is a heterogeneous group of lipoproteins typically containing apo AI as the principal protein. Most HDLs contain additional proteins from a palate of nearly 100 HDL-associated polypeptides. We hypothesized that some of these proteins define distinct and stable apo AI HDL subspecies with unique proteomes that drive function and associations with disease.

Approach and Results—

We produced 17 plasma pools from 80 normolipidemic human participants (32 men, 48 women; aged 21–66 years). Using immunoaffinity isolation techniques, we isolated apo AI containing species from plasma and then used antibodies to 16 additional HDL protein components to isolate compositional subspecies. We characterized previously described HDL subspecies containing apo AII, apo CIII, and apo E; and 13 novel HDL subspecies defined by presence of apo AIV, apo CI, apo CII, apo J, α-1-antitrypsin, α-2-macroglobulin, plasminogen, fibrinogen, ceruloplasmin, haptoglobin, paraoxonase-1, apo LI, or complement C3. The novel species ranged in abundance from 1% to 18% of total plasma apo AI. Their concentrations were stable over time as demonstrated by intraclass correlations in repeated sampling from the same participants over 3 to 24 months (0.33–0.86; mean 0.62). Some proteomes of the subspecies relative to total HDL were strongly correlated, often among subspecies defined by similar functions: lipid metabolism, hemostasis, antioxidant, or anti-inflammatory. Permutation analysis showed that the proteomes of 12 of the 16 subspecies differed significantly from that of total HDL.

Conclusions—

Taken together, correlation and permutation analyses support speciation of HDL. Functional studies of these novel subspecies and determination of their relation to diseases may provide new avenues to understand the HDL system of lipoproteins.
Myeloid HMG-CoA (3-Hydroxy-3-Methylglutaryl-Coenzyme A) Reductase Determines Atherosclerosis by Modulating Migration of Macrophages
Authors: Sakai Kent , Nagashima Shuichi , Wakabayashi Tetsuji , Tumenbayar Bayasgalan , Hayakawa Hiroko , Hayakawa Morisada , Karasawa Tadayoshi , Ohashi Ken , Yamazaki Hisataka , Takei Akihito , Takei Shoko , Yamamuro Daisuke , Takahashi Manabu , Yagyu Hiroaki , Osuga Jun-ichi , Takahashi Masafumi , Tominaga Shin-ichi , Ishibashi Shun
Published: October 2018

Objective—

Inhibition of HMGCR (3-hydroxy-3-methylglutaryl-coenzyme A reductase) is atheroprotective primarily by decreasing plasma LDL (low-density lipoprotein)-cholesterol. However, it is unknown whether inhibition of HMGCR in myeloid cells contributes to this atheroprotection. We sought to determine the role of myeloid HMGCR in the development of atherosclerosis.

Approach and Results—

We generated mice with genetically reduced
Hmgcr
in myeloid cells (
Hmgcr

m−

/m

−
) using LysM (Cre) and compared various functions of their macrophages to those of
Hmgcr

fl/fl

control mice. We further compared the extent of atherosclerosis in
Hmgcr

m
−/
m
−

and
Hmgcr

fl/fl

mice in the absence of
Ldlr
(LDL receptor).
Hmgcr

m
−/
m
−

macrophages and granulocytes had significantly lower
Hmgcr
mRNA expression and cholesterol biosynthesis than
Hmgcr

fl/fl

cells. In vitro,
Hmgcr

m
−/
m
−

monocytes/macrophages had reduced ability to migrate, proliferate, and survive compared with
Hmgcr

fl/fl

monocytes/macrophages. However, there was no difference in ability to adhere, phagocytose, store lipids, or polarize to M1 macrophages between the 2 types of macrophages. The amounts of plasma membrane–associated small GTPase proteins, such as RhoA (RAS homolog family member A), were increased in
Hmgcr

m
−/
m
−

macrophages. In the setting of
Ldlr
deficiency,
Hmgcr

m
−/
m
−

mice developed significantly smaller atherosclerotic lesions than
Hmgcr

fl/fl

mice. However, there were no differences between the 2 types of mice either in plasma lipoprotein profiles or in the numbers of proliferating or apoptotic cells in the lesions in vivo. The in vivo migration of
Hmgcr

m
−/
m
−

macrophages to the lesions was reduced compared with
Hmgcr

fl/fl

macrophages.

Conclusions—

Genetic reduction of HMGCR in myeloid cells may exert atheroprotective effects primarily by decreasing the migratory activity of monocytes/macrophages to the lesions.
Endothelial FN (Fibronectin) Deposition by α5β1 Integrins Drives Atherogenic Inflammation
Authors: Al-Yafeai Zaki , Yurdagul Arif , Peretik Jonette M. , Alfaidi Mabruka , Murphy Patrick A. , Orr A. Wayne
Published: October 2018

Objective—

Alterations in extracellular matrix quantity and composition contribute to atherosclerosis, with remodeling of the subendothelial basement membrane to an FN (fibronectin)-rich matrix preceding lesion development. Endothelial cell interactions with FN prime inflammatory responses to a variety of atherogenic stimuli; however, the mechanisms regulating early atherogenic FN accumulation remain unknown. We previously demonstrated that oxLDL (oxidized low-density lipoprotein) promotes endothelial proinflammatory gene expression by activating the integrin α5β1, a classic mediator of FN fibrillogenesis.

Approach and Results—

We now show that oxLDL drives robust endothelial FN deposition and inhibiting α5β1 (blocking antibodies, α5 knockout cells) completely inhibits oxLDL-induced FN deposition. Consistent with this, inducible endothelial-specific α5 integrin deletion in ApoE knockout mice significantly reduces atherosclerotic plaque formation, associated with reduced early atherogenic inflammation. Unlike TGFβ (transforming growth factor β)-induced FN deposition, oxLDL does not induce FN expression (mRNA, protein) or the endothelial-to-mesenchymal transition phenotype. In addition, we show that cell-derived and plasma-derived FN differentially affect endothelial function, with only cell-derived FN capable of supporting oxLDL-induced VCAM-1 (vascular cell adhesion molecule 1) expression, despite plasma FN deposition by oxLDL. The inclusion of alternative exon EIIIA (EDA) of FN (EIIIA) and alternative exon EIIIB (EDB) of FN (EIIIB) domains in cell-derived FN mediates this effect, as EIIIA/EIIIB knockout endothelial cells show diminished oxLDL-induced inflammation. Furthermore, our data suggest that EIIIA/EIIIB-positive cellular FN is required for maximal α5β1 recruitment to focal adhesions and FN fibrillogenesis.

Conclusions—

Taken together, our data demonstrate that endothelial α5 integrins drive oxLDL-induced FN deposition and early atherogenic inflammation. Additionally, we show that α5β1-dependent endothelial FN deposition mediates oxLDL-dependent endothelial inflammation and FN fibrillogenesis.
V-ATPase (Vacuolar ATPase) Activity Required for ABCA1 (ATP-Binding Cassette Protein A1)-Mediated Cholesterol Efflux
Authors: Lorkowski Shuhui Wang , Brubaker Gregory , Gulshan Kailash , Smith Jonathan D.
Published: October 2018

Objective—

We have shown that ABCA1 (ATP-binding cassette protein A1) mediates unfolding of the apoA1 (apolipoprotein A1) N-terminal helical hairpin during apoA1 lipidation. Others have shown that an acidic pH exposes the hydrophobic surface of apoA1. We postulated that the V-ATPase (vacuolar ATPase) proton pump facilitates apoA1 unfolding and promotes ABCA1-mediated cholesterol efflux.

Approach and Results—

We found that V-ATPase inhibitors dose-dependently decreased ABCA1-mediated cholesterol efflux to apoA1 in baby hamster kidney cells and RAW264.7 cells; and similarly, siRNA knockdown of ATP6V
0
C inhibited ABCA1-mediated cholesterol efflux to apoA1 in RAW264.7 cells. Although ABCA1 expression did not alter total cellular levels of V-ATPase, ABCA1 increased the cell surface levels of the V
0
A1 and V
1
E1 subunits of V-ATPase. We generated a fluorescein isothiocyanate/Alexa647 double-labeled fluorescent ratiometric apoA1 pH indicator whose fluorescein isothiocyanate/Alexa647 emission ratio decreased as the pH drops. We found that ABCA1 induction in baby hamster kidney cells led to acidification of the cell-associated apoA1 pH indicator, compared with control cells without ABCA1 expression. The V-ATPase inhibitor bafilomycin A1 dose-dependently inhibited the apoA1 pH shift in ABCA1-expressing cells, without affecting the levels of cell-associated apoA1. However, we were not able to detect ABCA1-mediated extracellular proton release. We showed that acidic pH facilitated apoA1 unfolding, apoA1 solubilization of phosphatidycholine:phosphatidyserine liposomes, and increased lipid fluidity of these liposomes.

Conclusions—

Our results support a model that ABCA1 recruits V-ATPase to the plasma membrane where V-ATPase mediates apoA1 acidification and membrane remodeling that promote apoA1 unfolding and ABCA1-mediated HDL (high-density lipoprotein) biogenesis and lipid efflux.
Sin1 (Stress-Activated Protein Kinase-Interacting Protein) Regulates Ischemia-Induced Microthrombosis Through Integrin αIIbβ3-Mediated Outside-In Signaling and Hypoxia Responses in Platelets
Authors: Xu Yanyan , Ouyang Xinxing , Yan Lichong , Zhang Mingliang , Hu Zhenlei , Gu Jianmin , Fan Xuemei , Zhang Lin , Zhang Junfeng , Xue Song , Chen Guoqiang , Su Bing , Liu Junling
Published: October 2018

Objective—

Microthrombosis as a serious consequence of myocardial infarction, impairs the microvascular environment and increases the occurrences of heart failure, arrhythmia, and death. Sin1 (stress-activated protein kinase-interacting protein) as an essential component of mTORC2 (mammalian target of rapamycin complex 2) is required for cell proliferation and metabolism in response to nutrients, stress, and reactive oxygen species and activates Akt and PKC (protein kinase C). However, the activation and function of Sin1/mTORC2 in ischemia-induced microthrombosis remain poorly understood.

Approach and Results—

The phosphorylation of the mTORC2 target Akt at S473 (serine 473) was significantly elevated in platelets from the distal end of left anterior descending obstructions from patients who underwent off-pump coronary artery bypass grafting compared with platelets from healthy subjects. Consistent with this finding, phosphorylation of T86 in Sin1 was also dramatically increased. Importantly, the augmented levels of phosphorylated Sin1 and Akt in platelets from 61 preoperative patients with ST-segment—elevation myocardial infarction correlated well with the no-reflow phenomena observed after revascularization. Platelet-specific Sin1 deficiency mice and Sin1 T86 phosphorylation deficiency mice were established to explore the underlying mechanisms in platelet activation. Mechanistically, Sin1 T86 phosphorylation amplifies mTORC2-mediated downstream signals; it is also required for αIIbβ3-mediated outside-in signaling and plays a role in generating hypoxia/reactive oxygen species through NAD
+
/Sirt3 (sirtuin 3)/SOD2 (superoxide dismutase 2) pathway. Importantly, Sin1 deletion in platelets protected mice from ischemia-induced microvascular embolization and subsequent heart dysfunction in a mouse model of myocardial infarction.

Conclusions—

Together, the results of our study reveal a novel role for Sin1 in platelet activation. Thus, Sin1 may be a valuable therapeutic target for interventions for ischemia-induced myocardial infarction deterioration.
Collagen Biomarkers and Incidence of New Onset of Atrial Fibrillation in Subjects With No Overt Cardiovascular Disease at Baseline
Authors: Duprez Daniel A. , Heckbert Susan R. , Alonso Alvaro , Gross Myron D. , Ix Joachim H. , Kizer Jorge R. , Tracy Russell P. , Kronmal Richard , Jacobs David R.
Published: October 2018

Background:

Atrial fibrosis is a hallmark of structural remodeling in atrial fibrillation (AF). Plasma procollagen type III N-terminal propeptide (PIIINP) reflects collagen synthesis and degradation while collagen type I carboxy-terminal telopeptide (ICTP) reflects collagen degradation. We aimed to study baseline plasma PIIINP and ICTP and their associations with incident AF in participants initially free of overt cardiovascular disease.

Methods:

In a stratified sample of the Multi-Ethnic Study of Atherosclerosis, initially aged 45–84 years, 3071 participants had both PIIINP and ICTP measured at baseline. Incident AF in 10-year follow-up was based on a hospital
International Classification of Diseases
code for AF or atrial flutter, in- or outpatient Medicare claims through 2011 (primarily in those aged 65–84 years), or ECG 10 years after baseline (n=357). The associations of PIIINP and ICTP with incident AF were estimated using Poisson regression with follow-up time offset.

Results:

Baseline PIIINP (5.50±1.55 µg/L) and ICTP (mean±SD, 3.41±1.37 µg/L) were positively related (both
P
<0.0001) to incident AF in a model adjusting for age, race/ethnicity, and sex, with an apparent threshold (relative incidence density 2.81 [1.94–4.08] for PIIINP ≥8.5 µg/L [3.5% of the sample] and 3.46 [2.36–5.07] for ICTP ≥7 µg/L [1.7% of the sample]). Findings were attenuated but remained statistically significant after further adjustment for systolic blood pressure, height, body mass index, smoking, and renal function. Additional adjustment for other risk factors and biomarkers of inflammation did not alter conclusions.

Conclusions:

Plasma collagen biomarkers, particularly at elevated levels, were associated with excess risk for AF.
Covered CP Stent for Treatment of Right Ventricular Conduit Injury During Melody Transcatheter Pulmonary Valve Replacement
Authors: Delaney Jeffrey W. , Goldstein Bryan H. , Bishnoi Ram N. , Bisselou Karl S.M. , McEnaney Kerry , Minahan Matthew , Ringel Richard E. ,   for the PARCS Investigators
Published: October 2018

Background:

High-pressure balloon and stent angioplasty are frequently necessary to prepare the dysfunctional right ventricular outflow tract conduit before transcatheter pulmonary valve replacement (TPVR). Conduit injury can result, which may be catastrophic to the patient or prevent successful TPVR.

Methods and Results:

The PARCS trial (Pulmonary Artery Repair With Covered Stent) was a pivotal, prospective multicenter trial to evaluate the safety and efficacy of the NuMED Covered CP Stent (CCPS) for treatment of conduit injury occurring during TPVR. The study also evaluated immediate and short-term TPVR function in patients receiving covered stents. A total of 616 patients were consented; 120 (19.5%) had a wall injury identified and were treated with CCPS. Severe conduit injuries were uncommon (5%), but predictors for severe injury were not identified. Stenotic homografts had the highest incidence of injury (29%), compared with other conduit substrates. Among patients receiving CCPS implant, 96% required no further therapy for conduit injury, and 94% underwent TPVR at that procedure. Only 2 patients (1.6%) required urgent surgery for conduit injury, despite CCPS implant. There were few CCPS-related complications. TPVR function was similar between CCPS and non-CCPS groups at follow-up.

Conclusions:

Conduit injury during TPVR is common, although severe injury is rare. The CCPS was a safe and effective treatment for right ventricular outflow tract conduit injury during preparation for TPVR, allowing nearly all patients to complete the procedure without identifiable impact on valve performance.

Clinical Trial Registration:

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT01824160.
Clinical Model to Predict 90-Day Risk of Readmission After Acute Myocardial Infarction
Authors: Kini Vinay , Peterson Pamela N. , Spertus John A. , Kennedy Kevin F. , Arnold Suzanne V. , Wasfy Jason H. , Curtis Jeptha P. , Bradley Steven M. , Amin Amit P. , Ho P. Michael , Masoudi Frederick A.
Published: October 2018

Background:

Readmissions within 30 days after acute myocardial infarction have been used as a performance metric for hospitals. However, evolving concepts of value-based reimbursement have shifted the focus to 90 days after hospital discharge. Tools are needed to determine risk for 90-day readmission to identify patients who might benefit from enhanced transitional healthcare resources.

Methods and Results:

In this cohort study, we identified all Medicare beneficiaries with a primary diagnosis of acute myocardial infarction who were discharged from hospitals participating in National Cardiovascular Data Registry ACTION registry between 2008 and 2014. Among a random 70% sample (derivation cohort), we performed hierarchical proportional hazards regression, accounting for death as a competing risk, to assess predictors of all-cause readmission within 90 days. Models were validated in the remaining 30%. Among 86 849 unique patients, 23 912 (27.5%) were readmitted within 90 days. Of the readmissions, 55% occurred within 30 days and 81% occurred within 60 days. Predictors of readmission included older age and a history of diabetes mellitus or heart failure. Coronary revascularization was associated with a lower risk of readmission. A simple risk score incorporating patient demographic and clinical characteristics known before discharge identified groups of patients with readmission risks ranging from 13.1% to 42.9%. Model discrimination was moderate (C statistic=0.662), and calibration was excellent (slope=0.97, intercept=−0.04).

Conclusions:

Readmission within 90 days of hospitalization for acute myocardial infarction can be predicted by variables known before discharge and offers the potential to prospectively design transitional care to the risks of individual patients.
Advanced Imaging to Phenotype Patients With a Systemic Right Ventricle
Authors: Helsen Frederik , Claus Piet , Van De Bruaene Alexander , Claessen Guido , La Gerche André , De Meester Pieter , Claeys Mathias , Gabriels Charlien , Petit Thibault , Santens Béatrice , Troost Els , Voigt Jens‐Uwe , Bogaert Jan , Budts Werner
Published: October 2018

Background

Reduced ventricular function and decreased exercise capacity are widespread in adults with complete transposition of the great arteries after atrial switch (
TGA
‐Mustard/Senning) and congenitally corrected
TGA
(cc
TGA
). Advanced imaging techniques may help to better phenotype these patients and evaluate exercise cardiac response.

Methods and Results

Thirty‐three adults with a systemic right ventricle (70%
TGA
‐Mustard/Senning, 37±9 years of age, 24% female, 94% New York Heart Association class I‐
II
) underwent echocardiogram, cardiopulmonary exercise testing, and cardiovascular magnetic resonance imaging at rest and during a 4‐stage free‐breathing bicycle test. They were compared with 12 healthy controls (39±10 years of age, 25% female, all New York Heart Association class I).
TGA
‐Mustard/Senning patients had a higher global circumferential strain (−15.8±3.6 versus −11.2±5.2%,
P
=0.008) when compared with cc
TGA
, whereas global longitudinal strain and systemic right ventricle contractility during exercise were similar in both groups. Septal extracellular volume (
ECV
) in cc
TGA
was significantly higher than in
TGA
‐Mustard/Senning (30.2±2.0 versus 27.1±2.7%,
P
=0.005). During exercise,
TGA
‐Mustard/Senning had a fall in end‐diastolic volume and stroke volume (11% and 8%, respectively; both
P
≤0.002), whereas cc
TGA
could increase their stroke volume in the same way as healthy controls. Because of a greater heart rate reserve in
TGA
‐Mustard/Senning (
P
for interaction=0.010), cardiac index and peak oxygen uptake were similar between both patient groups.

Conclusions

Caution should be exercised when evaluating pooled analyses of systemic right ventricle patients, given the differences in myocardial contraction pattern, septal extracellular volume, and the exercise response of
TGA
‐Mustard/Senning versus cc
TGA
patients. Longitudinal follow‐up will determine whether abnormal exercise cardiac response is a marker of earlier failure.
Classification, annotated list and keys for the black flies (Diptera: Simuliidae) of Peninsular Malaysia
Authors: TAKAOKA HIROYUKI , YA’COB ZUBAIDAH , SOFIAN-AZIRUN MOHD
Published: October 2018

The classification, annotated list and keys for the black fly species from Peninsular Malaysia are updated. The number of black fly species increased from 38 in 1995 to 62 (including a new species herein described) in 2018. The 62 species are classified in four subgenera of the genus Simulium: one species in Daviesellum, 35 species in Gomphostilbia, five species in Nevermannia and 21 species in Simulium. Species in the latter three subgenera are further placed in species-groups or subgroups. Keys are provided for females, males, pupae and mature larvae. Simulium (S.) perakense sp. nov. is described and placed in the S. striatum species-group. The males of S. (G.) decuplum, S. (G.) tahanense, S. (S.) malayense, the female of S. (G.) adleri, and the female and larva of S. (G.) varicorne are described for the first time. The female, male, pupa and larva of S. (G.) trangense, the male and pupa of S. (G.) varicorne and the pupa of S. (G.) adleri are redescribed. Simulium (G.) sp. A is identified as S. (G.) pegalanense. Brief notes for each species are given on morphological characteristics, aquatic habitats and geographical distributions.
100 Years of the Ocean General Circulation
Authors: Wunsch Carl , Ferrari Raffaele
Published: October 2018

The central change in understanding of the ocean circulation during the past 100 years has been its emergence as an intensely time-dependent, effectively turbulent and wave-dominated, flow. Early technologies for making the difficult observations were adequate only to depict large-scale, quasi-steady flows. With the electronic revolution of the past 50+ years, the emergence of geophysical fluid dynamics, the strongly inhomogeneous time-dependent nature of oceanic circulation physics finally emerged. Mesoscale (balanced), submesoscale oceanic eddies at 100-km horizontal scales and shorter, and internal waves are now known to be central to much of the behavior of the system. Ocean circulation is now recognized to involve both eddies and larger-scale flows with dominant elements and their interactions varying among the classical gyres, the boundary current regions, the Southern Ocean, and the tropics.
The South Pacific Meridional Mode and Its Role in Tropical Pacific Climate Variability
Authors: You Yujia , Furtado Jason C.
Published: October 2018

The Pacific meridional mode, a thermodynamically coupled mode of variability, links extratropical Pacific oceanic and atmospheric anomalies to the tropical Pacific and may give rise to El Niño–Southern Oscillation (ENSO) events. While mechanistic studies on the impacts of the North Pacific meridional mode (NPMM) are prevalent in the literature, the South Pacific meridional mode (SPMM) has only recently been examined. Reanalysis and models from the archive of phase 5 of the Coupled Model Intercomparison Project (CMIP5) are used in this study to investigate further the SPMM and its role in ENSO predictability. Akin to the NPMM, the SPMM features anomalous subtropical South Pacific sea surface temperature (SST) warming in response to a weakened South Pacific subtropical high and relaxed trade winds. However, as opposed to the NPMM, the seasonality of the SPMM SST and wind components vary out of phase, in part because of the seasonal cycle of local mixed layer depth. Thus, the SPMM and the associated wind–evaporation–SST feedback are most energetic during austral summer, facilitating interaction with the concurrent NPMM conditions to regulate the occurrence, evolution, amplitude, and diversity of ENSO events. Parallel analyses with the CMIP5 models indicate that the models reasonably capture the temporal statistics and physical processes of the observed SPMM. Nonetheless, ENSO predictability within the models relies more on the slowly evolving equatorial ocean heat content than on the meridional modes. These findings reveal how the SPMM energizes components of ENSO variability, providing an additional benchmark for model evaluation of Pacific climate variability across multiple time scales.
Evaluation of Remotely Sensed Snow Water Equivalent and Snow Cover Extent over the Contiguous United States
Authors: Dawson Nicholas , Broxton Patrick , Zeng Xubin
Published: October 2018

Global snow water equivalent (SWE) products derived at least in part from satellite remote sensing are widely used in weather, climate, and hydrometeorological studies. Here we evaluate three such products using our recently developed daily 4-km SWE dataset available from October 1981 to September 2017 over the conterminous United States. This SWE dataset is based on gridded precipitation and temperature data and thousands of in situ measurements of SWE and snow depth. It has a 0.98 correlation and 30% relative mean absolute deviation with Airborne Snow Observatory data and effectively bridges the gap between small-scale lidar surveys and large-scale remotely sensed data. We find that SWE products using remote sensing data have large differences (e.g., the mean absolute difference from our SWE data ranges from 45.8% to 59.3% of the mean SWE in our data), especially in forested areas (where this percentage increases up to 73.5%). Furthermore, they consistently underestimate average maximum SWE values and produce worse SWE (including spurious jumps) during snowmelt. Three additional higher-resolution satellite snow cover extent (SCE) products are used to compare the SCE values derived from these SWE products. There is an overall close agreement between these satellite SCE products and SCE generated from our SWE data, providing confidence in our consistent SWE, snow depth, and SCE products based on gridded climate and station data. This agreement is also stronger than that between satellite SCE and those derived from the three satellite SWE products, further confirming the deficiencies of the SWE products that utilize remote sensing data.
Latent Heat Nudging in the Canadian Regional Deterministic Prediction System
Authors: Jacques Dominik , Michelson Daniel , Caron Jean-François , Fillion Luc
Published: October 2018

This study reports on the progress toward operational weather radar data assimilation in Canada. As a first step, the latent heat nudging (LHN) technique has been tested for a period of 1 month. It is the first time that LHN is used across the North American continent, a domain significantly larger than that of other LHN studies. Other novel aspects of this study include the use of a quality index associated with individual reflectivity measurements and a discussion on matching the effective resolution of the modeled precipitation for a reduction of the representation errors. Various verification scores indicate that LHN has a positive influence on instantaneous precipitation rates for lead times up to 3 h. In comparison, the nowcasting of precipitation rates by a simple Lagrangian extrapolation method yields improvements that last up to approximately 4 h. Verifications against aircraft measurements indicate small but statistically significant improvements throughout the troposphere for lead times up to 24 h.
Diagnostic Accuracy, Prescription Behavior, and Watchful Waiting Efficacy for Pediatric Acute Otitis Media
Authors: Brinker David L. , MacGeorge Erina L. , Hackman Nicole
Published: October 2018

Current guidelines recommend “watchful waiting” (WW) as an alternative to immediate antibiotic treatment. Continued high rates of antibiotic use suggest that WW may be underutilized. We conducted a retrospective chart review of 474 pediatric acute otitis media (AOM) cases at a clinic in central Pennsylvania. We assessed physical examination findings, diagnostic behavior, WW utilization, prescription writing, and filling in cases of pediatric AOM to evaluate the underutilization of WW. We evaluate diagnostic consistency with published guidelines and rates of antibiotic prescription resulting from misdiagnosis. We report WW instructions and compliance, and prescription filling behaviors. Fifty percent of AOM diagnoses in this sample were not supported by physical examination findings. The majority of these AOM diagnoses received antibiotic prescriptions, suggesting that unsupported diagnoses translated to injudicious prescribing. WW instructions corresponded to 57% fewer filled prescriptions and longer fill delay. We discuss the implications and recommendations to improve antibiotic stewardship.
Response and failure of fiber metal laminates subjected to high strain rate tensile loading
Authors: Sharma Ankush P , Khan Sanan H , Parameswaran Venkitanarayanan
Published: October 2018

The tensile behavior of fiber metal laminates consisting of layers of aluminum 2024-T3 alloy and glass fiber reinforced composites under high strain rate loading is investigated. Fiber metal laminates having four different layups, but all having the same total metal layer thickness, were fabricated using a combined hand lay-up cum vacuum bagging method. The fiber metal laminate specimens were loaded in high strain rate tension using a split Hopkinson tensile bar. The rate-dependent behavior of the glass fiber composite was also obtained as baseline data. The strain on the gage area of the specimen was measured directly using high-speed digital image correlation. Another high-speed camera was used to capture the sequence of damage by viewing the specimen edgewise. The results indicated that the strength of the fiber metal laminates increased at high strain rates primarily due to the rate-dependent behavior of the composite used. The response was also influenced by the distribution of the metallic layers in the fiber metal laminates. The failure in the case where the individual composite layers were separated by metallic layers was more progressive in nature.
The Long Reach of Sponsorship: How Fan Isolation and Identification Jointly Shape Sponsorship Performance
Authors: Mazodier Marc , Henderson Conor M. , Beck Joshua T.
Published: October 2018

Globalization and technology have expanded the reach of sports teams, giving brand sponsors new opportunities to engage and build relationships in real time with fans outside a team’s home market. This research investigates the role of fan isolation, or the experience of feeling separated from the team community, in shaping sponsorship effectiveness. The authors posit that such isolation increases the desire to affiliate with the team community, which can increase preferences for team-linked brands. However, the effect of isolation on sponsor performance depends on the strength of fan identification. Isolation increases strong fans’ desire to affiliate with the team community, thereby enhancing sponsorship performance; by contrast, isolation causes weak fans to avoid team-linked brands. Two field studies and four quasi experiments conducted across three countries (N = 1,412) confirm these predictions. Isolated strong fans exhibit increased recall, attitudes, purchase intentions, and word of mouth for sponsors, while isolated weak fans display the opposite effects. For brand managers, the proposed framework reveals whether isolated fans provide the best or worst returns on their sponsorships.
The New Harvard Doctor of Public Health: Lessons From the Design and Implementation of an Innovative Program in Advanced Professional Leadership
Authors: Berman Peter , Frenk Julio
Published: October 2018

We documented lessons learned in the initial design and development of the new Harvard doctor of public health (DrPH) degree, an innovative professional public health doctorate designed to provide advanced education in the field of public health. Using data from program documents, personal participation in the development and administration of the degree, and initial students’ results, we present key learnings from this experience and describe the program’s goals and processes. Now entering its fifth year, the new Harvard DrPH program has enrolled about 70 students and graduated its first 2 classes in a program that combines advanced public health study with leadership development and field engagement. Development of this transformational innovation in advanced public health education required creative approaches to competency development and curriculum design, engagement of faculty to become supportive stakeholders, and substantial support for educational administration. Demand for a program of this type is strong. Continuous improvement is ongoing.
In Search of a Problem: Mapping Controversies over NHS (England) Patient Data with Digital Tools
Authors: Moats David , McFall Liz
Published: October 2018

There is a long history in science and technology studies (STS) of tracking problematic objects, such as controversies, matters of concern, and issues, using various digital tools. But what happens when public problems do not play out in these familiar ways? In this paper, we will think through the methodological implications of studying “problems” in relation to recent events surrounding the sharing of patient data in the National Health Service in the United Kingdom. When a data sharing agreement called care.data was announced in 2013, nearly 1.5 million citizens chose to opt out. Yet, in subsequent years, there has been little evidence of a robust public mobilising around data sharing. We will attempt to track this elusive ‘non problem’ using some digital tools developed in STS for the purpose of mapping issues and problem definitions within science. Although we find these digital tools are unable to capture the “problem,” the process of searching helps us map the terrain of the case and forces us to consider wider definitions.
Comparing the Bonded Concrete Overlays of Asphalt-Mechanistic Empirical Design Procedure and the Short Jointed Plain Concrete Pavement Module in the Pavement Mechanistic Empirical Design Procedure
Authors: Alland Kevin , Vandenbossche Julie M. , DeSantis John W. , Snyder Mark B. , Khazanovich Lev
Published: October 2018

Bonded concrete overlays of asphalt pavements (BCOA) consist of a concrete overlay placed on an existing asphalt or composite pavement. This technique is intended as a cost-effective rehabilitation solution for marginally distressed in-service asphalt or composite pavements. BCOA with panel sizes between 4.5 ft and 8.5 ft have become popular as they reduce curling stresses while keeping the longitudinal joints out of the wheelpath. The BCOA-ME (mechanistic empirical) design procedure and Pavement ME short jointed plain concrete pavement (SJPCP) module can both be used to design BCOA with mid-size panels. However, these design procedures differ in the assumptions used to develop the mechanistic computational model, fatigue models used to predict failure, treatment of environmental conditions, estimate of asphalt stiffness, consideration of structural fibers, the application of traffic loading, and the calibration process. This results in the procedures producing different overlay thicknesses and predicted distresses. The strengths and limitations of each procedure are evaluated and comparisons are made between the design thicknesses obtained from them.
Allogenic Pure Platelet-Rich Plasma Therapy for Rotator Cuff Disease: A Bench and Bed Study
Authors: Jo Chris Hyunchul , Lee Seung Yeon , Yoon Kang Sup , Oh Sohee , Shin Sue
Published: October 2018

Background:

Although platelet-rich plasma (PRP) is a popular option for rotator cuff disease, the underlying mechanism of PRP and its clinical indications are unclear. Further, some kinds of PRP might be detrimental to patients. Allogenic PRP prepared through a standardized process and fully characterized could eliminate variations in PRP as well as uncertainties regarding its use in each patient, which could provide clues about its mechanism of action and indications for its use.

Purpose:

To assess the effects of pure PRP on tenocytes with or without inflammation in an in vitro study and to evaluate the safety and efficacy of a fully characterized pure PRP injection in patients with rotator cuff disease in a clinical study.

Study Design:

Controlled laboratory study and cohort study; Level of evidence, 3.

Methods:

For the in vitro study, tenocytes were enzymatically isolated and cultured from patients with rotator cuff tear and treated with or without interleukin 1β (IL-1β) and PRP. Gene expression and protein synthesis of pro- and anti-inflammatory cytokines, enzymes and their inhibitors, matrix synthesis, and cell viability were evaluated. For the clinical study, a total of 17 patients with rotator cuff disease received ultrasonography-guided subacromial PRP injection and were followed for 6 months. Pain, range of motion, muscle strength, shoulder function, and overall satisfaction in patients were compared with the results in a propensity score–matched control group who received corticosteroid (triamcinolone acetonide 40 mg).

Results:

PRP induced inflammation in the absence of inflammation and ameliorated inflammation in IL-1β-induced tendinopathic conditions by regulation of cytokines such as IL-1β, cyclooxygenase 2, microsomal prostaglandin E synthase 1, vasoactive intestinal peptide, and downstream matrix metalloproteinases. No general or local adverse events were noted with regard to allogenic PRP injection. Whereas steroid injection showed earlier improvement in some kinds of pain and functional scores, PRP generally showed comparable effects with steroid injection in all clinical outcomes at 6 months.

Conclusion:

This study showed that allogenic pure PRP had pleiotropic effects on tenocytes depending on inflammation and that it did not cause adverse events but rather decreased pain and improved shoulder function to a degree comparable with steroid injection in patients with rotator cuff disease.

Clinical Relevance:

Allogenic PRP could be a treatment option for rotator cuff disease.
Who Helps Build Mexican-Origin Female College Students’ Self-Efficacy? The Role of Important Others in Student Success
Authors: Alfaro Edna C. , Weimer Amy A. , Castillo Edith
Published: October 2018

The present study examined interrelations among sociocultural factors, communication, and academic support from mothers, fathers, sisters, brothers, professors, romantic partners, and close friends and Mexican-origin female college students’ ( n = 205) college self-efficacy. Findings revealed that students communicated the most with their close friends and perceived that mothers provided the most academic support. In general, students who espoused behaviors and values that closely aligned with the Mexican culture were more likely to communicate with others. In addition, higher levels of communication related to higher levels of academic support, but relations between academic support and college self-efficacy differed by source of support. Notably, while academic support from mothers, professors, and romantic partners were positively related to college self-efficacy, academic support from fathers, sisters, brothers, and close friends were not related to college self-efficacy. Findings confirm that a focus on the unique roles of important others is warranted.
Novel Homozygous Deletion in STRADA Gene Associated With Polyhydramnios, Megalencephaly, and Epilepsy in 2 Siblings: Implications for Diagnosis and Treatment
Authors: Nelson Katherine , Jackman Christopher , Bell Jennifer , Shih Chie-Schin , Payne Katelyn , Dlouhy Stephen , Walsh Laurence
Published: October 2018

Mutations in the STE20-related kinase adaptor α ( STRADA) gene have been reported to cause an autosomal recessive neurodevelopmental disorder characterized by infantile-onset epilepsy, developmental delay, and craniofacial dysmorphisms. To date, there have been 17 reported individuals diagnosed with STRADA mutations, 16 of which are from a single Old Order Mennonite cohort and share a deletion of exons 9-13. The remaining individual is of consanguineous Indian descent and has a homozygous single–base pair duplication. We report a novel STRADA gene deletion of exons 7-9 in 2 sisters from nonconsanguineous parents, as well as an improvement in seizure control in 1 sibling following treatment with sirolimus, an m-Tor inhibitor of potential benefit to patients with this genetic mutation.
Dynamic Assessment of Fluid Responsiveness in Surgical ICU Patients Through Stroke Volume Variation is Associated With Decreased Length of Stay and Costs: A Systematic Review and Meta-Analysis
Authors: Dave Chintan , Shen Jennifer , Chaudhuri Dipayan , Herritt Brent , Fernando Shannon M. , Reardon Peter M. , Tanuseputro Peter , Thavorn Kednapa , Neilipovitz David , Rosenberg Erin , Kubelik Dalibor , Kyeremanteng Kwadwo
Published: October 2018

Static indices, such as the central venous pressure, have proven to be inaccurate predictors of fluid responsiveness. An emerging approach uses dynamic assessment of fluid responsiveness (FT-DYN), such as stroke volume variation (SVV) or surrogate dynamic variables, as more accurate measures of volume status. Recent work has demonstrated that goal-directed therapy guided by FT-DYN was associated with reduced intensive care unit (ICU) mortality; however, no study has specifically assessed this in surgical ICU patients. This study aimed to conduct a systematic review and meta-analysis on the impact of employing FT-DYN in the perioperative care of surgical ICU patients on length of stay in the ICU. As secondary objectives, we performed a cost analysis of FT-DYN and assessed the impact of FT-DYN versus standard care on hospital length of stay and mortality. We identified all randomized controlled trials (RCTs) through MEDLINE, EMBASE, and CENTRAL that examined adult patients in the ICU who were randomized to standard care or to FT-DYN from inception to September 2017. Two investigators independently reviewed search results, identified appropriate studies, and extracted data using standardized spreadsheets. A random effect meta-analysis was carried out. Eleven RCTs were included with a total of 1015 patients. The incorporation of FT-DYN through SVV in surgical patients led to shorter ICU length of stay (weighted mean difference [WMD], −1.43d; 95% confidence interval [CI], −2.09 to −0.78), shorter hospital length of stay (WMD, −1.96d; 95% CI, −2.34 to −1.59), and trended toward improved mortality (odds ratio, 0.55; 95% CI, 0.30-1.03). There was a decrease in daily ICU-related costs per patient for those who received FT-DYN in the perioperative period (WMD, US$ −1619; 95% CI, −2173.68 to −1063.26). Incorporation of FT-DYN through SVV in the perioperative care of surgical ICU patients is associated with decreased ICU length of stay, hospital length of stay, and ICU costs.
Model Victims of Hate: Victim Blaming in the Context of Islamophobic Hate Crime
Authors: Erentzen Caroline , Schuller Regina A. , Gardner Robert C.
Published: October 2018

Prior research has explored victim blaming in the context of hate, often depicting hate crime victims as relatively passive recipients of harassment and violence. In reality, victims often do engage with their perpetrators, and the present research explored the effect that victim behavior might have on observer reactions to Islamophobic hate crimes. Participants completed a measure of Islamophobia and read a scenario in which a White man verbally harassed a victim in the park before physically assaulting him. We manipulated both the victim’s identity (White or South Asian Muslim) and the victim’s response to the perpetrator’s verbal harassment (the victim either ignored the offensive comments, verbally reacted to them, or became physically confrontational). When the victim was portrayed as passive and nonresponding, the South Asian Muslim victim attracted lower victim blame, higher perpetrator blame, and increased certainty that the offense was a hate crime. As the victim’s behavior became more aggressive, victim blaming increased and perpetrator blaming decreased, but only for the South Asian Muslim victim. It appeared that observers scrutinized the behavior of the South Asian Muslim victim in a way they did not for the White victim, such that sympathy toward the Muslim hate crime victim was tied to his “good behavior.” We propose that observers hold expectations of the model hate crime victim, one who is a racialized, religious, or sexual minority who accepts harassment passively and with good behavior; deviation from this script results in a loss of sympathy and an increase in victim blaming. Finally, those higher in Islamophobia displayed reduced perpetrator blame, guilt, and sentences but greater victim blame when the crime targeted a South Asian Muslim as opposed to White victim.