bluuebunny/crossref_metadata_2025 huggingface dataset:
Immunoglobulin A Nephropathy: Advances in Understanding of Pathogenesis and Treatment
Authors: Lafayette Richard A. , Kelepouris Ellie
Published: May 2018

Background: Immunoglobulin A (IgA) nephropathy is the most common form of primary glomerulonephritis and has clinical associations with a wide range of inflammatory and infectious diseases. There is a substantial variation in clinical course and outcomes, with many patients not diagnosed until they present with sequelae, which may include gross hematuria, hypertension, renal insufficiency, and/or significant proteinuria. Treatment options are currently limited and directed mainly toward control of these sequelae and have limited ability to reduce the incidence of end-stage renal disease or treat the primary IgA defect. Summary: Growing knowledge about the pathogenesis of IgA nephropathy and research into its genetic basis are helping to elucidate the course of this widely variable disease. IgA accumulation in the kidneys is thought to be the result of a number of different pathways in a “multi-hit” process that includes an initial traumatic trigger (often infection related) and subsequent memory responses that are amplified in those with a genetic predisposition to the disease and lead to an inflammatory response in susceptible individuals. Genome-wide association studies are providing new insights into the genetic variance of this autoimmune disease and are yielding information that may address both its causes and consequences. Key Messages: New treatment approaches are urgently required for the management of patients with IgA nephropathy. Novel interventions based around its inflammatory nature and “multi-hit” pathogenesis are being investigated to potentially limit disease progression.
Monitoring Neonatal Resuscitation: Why Is It Needed?
Authors: Morley Colin J.
Published: May 2018

Stabilisation and resuscitation of babies at birth is one of the most frequently performed procedures and requires considerable skill. If it is not done well, the baby may suffer prolonged hypoxia and bradycardia. Over the last few years there has been a growing interest in carefully evaluating an infant’s condition at birth and the details of what is happening during resuscitation. Clinical assessment of an infant at this time is difficult and often inaccurate. Assessments of heart rate, colour, chest excursions, mask leak, tidal volume, inflation and expiration times, endotracheal intubation, and spontaneous breathing are imprecise. Detailed monitoring of gas flow in and out of the baby, integrated to tidal volume and used to calculate the leak around the face mask or endotracheal tube, together with ventilation pressures, pulse oximetry, ECG, and capnography add objectivity to the clinical assessments. These physiological parameters can be used directly to guide care but are also very useful for debriefing, feedback, audit, teaching, and research. With simultaneous video recording of the resuscitation it is possible to see exactly what is happening during the procedure. Endotracheal intubation is a difficult skill to learn and teach. However, this is now much easier with video laryngoscopy showing the intubator and supervisors exactly what is happening at the larynx.
Perinatal Origins of Adult Disease
Authors: Simeoni Umberto , Armengaud Jean-Baptiste , Siddeek Benazir , Tolsa Jean-François
Published: May 2018

Epidemiological and experimental studies have shown that the peri-conception period, pregnancy, and infancy are windows of particular sensibility to environmental clues which influence lifelong trajectories across health and disease. Nutrition, stress, and toxins induce epigenetic marks that control long-term gene expression patterns and can be transmitted transgenerationally. Chronic diseases of adulthood such as hypertension, diabetes, and obesity thus have early, developmental origins in the perinatal period. The early epigenome, in interaction with other actors such as the microbiome, add powerful layers of diversity to the biological predisposition generated by the genome. Such “programming” is a normal, adaptive component of development, including in normal pregnancies and births. However, perinatal disease, either maternal (such as pre-eclampsia, ges­tational diabetes, or inflammatory disease) or fetal, and neonatal diseases (such as intrauterine growth restriction and preterm birth) are major conditions of altered programming, translated into an increased risk for chronic disease in these patients when they reach adulthood. Early prevention, optimal perinatal nutrition, and specific follow-up measures are key factors in the early preservation of long-term health.
The Genetic Background of Neonatal Disease
Authors: Göpel Wolfgang , Westermann Eva , Pagel Friederike
Published: May 2018

More than 27,000 human genes have been sequenced and described. Only a few of these genes are relevant for common human diseases with regard to diagnostic or therapeutic purposes. This review describes the genetics of common traits and diseases with a particular focus on perspectives for drug discovery and drug therapy in neonates.
Clinical Metabolomics in Neonatology: From Metabolites to Diseases
Authors: Fanos Vassilios , Pintus Roberta , Dessì Angelica
Published: May 2018

Today, disorders that affect the newborn remain a challenge for physicians because of the enigmatic pathophysiology and difficulties in treating such delicate patients. Metabolomics, the “omics” science that studies the metabolome, namely the metabolites present in biological fluids, such as saliva, blood, sweat, and breast milk in a given time or condition, can be useful in helping neonatologists to prevent, diagnose, and treat diseases affecting the neonate, especially those with higher mortality rates. Since it is a relatively new technology, studies of its application in neonatology are limited. The aims of this review are to present metabolomics data on relevant neonatal disorders and to identify and discuss the most important 5 metabolites and their clinical significance rather than focusing on each disorder. The preliminary data are promising but further studies on metab­olomics in neonatology are needed together with the standardization of results before their application in clinical practice.
Transcription Elongation Factor P-TEFb Is Involved in IL-17F Signaling in Airway Smooth Muscle Cells
Authors: Nakajima Masayuki , Kawaguchi Mio , Matsuyama Masashi , Ota Kyoko , Fujita Junichi , Matsukura Satoshi , Huang Shau-Ku , Morishima Yuko , Ishii Yukio , Satoh Hiroaki , Sakamoto Tohru , Hizawa Nobuyuki
Published: May 2018

Background: IL-17F is involved in the pathogenesis of several inflammatory diseases, including asthma and COPD. However, the effects of steroids on the function of IL-17F signaling mechanisms are largely unknown. One of the transcription elongation factors, positive transcription elongation factor b (P-TEFb) composed of cyclin T1 and cyclin-dependent kinase 9 (CDK9), is known as a novel checkpoint regulator of gene expression via bromodomain-containing protein 4 (Brd4). Methods: Human airway smooth muscle cells were stimulated with IL-17F and the expression of IL-8 was evaluated by real-time PCR and ELISA. Next, the phosphorylation of CDK9 was determined by Western blotting. The CDK9 inhibitor and short interfering RNAs (siRNAs) targeting Brd4, cyclin T1, and CDK9 were used to identify the effect on IL-17F-induced IL-8 expression. Finally, the effect of steroids and its signaling were evaluated. Results: IL-17F markedly induced the transcription of the IL-8 gene and the expression of the protein. Pretreatment of CDK9 inhibitor and transfection of siRNAs targeting CDK9 markedly abrogated IL-17F-induced IL-8 production. Transfection of siRNAs targeting Brd4 and cyclin T1 diminished IL-17F-induced phosphorylation of CDK9 and IL-8 production. Moreover, budesonide decreased CDK9 phosphorylation and markedly inhibited IL-17F-induced IL-8 production. Conclusions: This is the first report that P-TEFb is involved in IL-17F-induced IL-8 expression and that steroids diminish it via the inhibition of CDK9 phosphorylation. IL-17F and P-TEFb might be novel therapeutic targets for airway inflammatory diseases.
Statin Use during Hospitalization and Short-Term Mortality in Acute Ischaemic Stroke with Chronic Kidney Disease
Authors: Zhang Xinmiao , Jing Jing , Zhao Xingquan , Liu Liping , Wang Chunxue , Pan Yuesong , Meng Xia , Wang Yilong , Wang Yongjun
Published: May 2018

Objectives: Statin use during hospitalization improves prognosis in patients with ischaemic stroke. However, it remains uncertain whether acute ischaemic stroke patients with chronic kidney disease (CKD) benefit from statin therapy. We investigated the effect of statin use during hospitalization in reducing short-term mortality of patients with ischaemic stroke and CKD. Methods: Data of first-ever ischaemic stroke patients without a history of pre-stroke statin treatment was derived from the China National Stroke Registry. Patients were stratified according to estimated glomerular filtration rate (eGFR): normal renal function (eGFR ≥90 mL/min/1.73 m2), mild CKD (eGFR 60–90 mL/min/1.73 m2) and moderate CKD (eGFR < 60 mL/min/1.73 m2). Multivariate logistic regression analysis was used to evaluate the association between statin use during hospitalization and all-cause mortality with different renal functions at 3-month follow-up. Results: Among 5,951 patients included, 2,595 (43.6%) patients were on statin use during hospitalization after stroke (45.7% in patients with normal renal function, 42.0% in patients with mild CKD, and 39.0% in patients with moderate CKD). Compared with the non-statin group, statin use during hospitalization was associated with decreased all-cause mortality in patients with normal renal function (OR 0.65, 95% CI 0.43–0.97, p = 0.04), mild CKD (OR 0.59, 95% CI 0.38–0.91, p = 0.02) and moderate CKD (OR 0.41, 95% CI 0.23–0.75, p = 0.004) at 3-month follow-up. Conclusions: Statin use during hospitalization was associated with decreased 3-month mortality of ischaemic stroke patients with mild and moderate CKD. However, the conclusion should be confirmed in further studies with larger population, especially with moderate CKD.
Successful Treatment of Pulmonary Pleomorphic Carcinoma with Nivolumab: A Case Report
Authors: Fujimoto Eriko , Yokoi Takashi , Mikami Koji , Kanemura Shingo , Shibata Eisuke , Horio Daisuke , Koda Yuichi , Negi Yoshiki , Akano Yumiko , Tada Akio , Minami Toshiyuki , Kuribayashi Kozo , Kijima Takashi
Published: May 2018

Pulmonary pleomorphic carcinoma (PPC) has a poor prognosis due to the poor results of treatment with systemic chemotherapy. We report the case of a 73-year-old woman with PPC who showed a favorable response to nivolumab. As first-line treatment for postoperative recurrence, she received carboplatin and nanoparticle albumin-bound paclitaxel. However, 12 months later, a new metastatic lymph node appeared. Nivolumab was administered as second-line treatment, and the patient showed a favorable prolonged response. The effects of treatment of PPC with nivolumab seem promising. The results of a future prospective study are expected to identify indicators for the treatment of PPC.
Paraneoplastic Pemphigus as a First Manifestation of an Intra-Abdominal Follicular Dendritic Cell Sarcoma: Rare Case and Review of the Literature
Authors: Akel Reem , Fakhri Ghina , Salem Rana , Boulos Fouad , Habib Khaled , Tfayli Arafat
Published: May 2018

Background: Follicular dendritic cell sarcoma (FDCS) is an extremely rare malignant tumor caused by proliferation of antigen-presenting follicular dendritic cells. The tumor most commonly arises in lymph nodes, with fewer than 30% of cases originating in extranodal sites. Case Presentation: We report the case of a 39-year-old previously healthy male patient who presented with paraneoplastic pemphigus in the setting of a large intraperitoneal mass with no associated lymphadenopathy. The biopsy results showed a cellular proliferation of mildly to moderately atypical oval-to-spindle-shaped cells admixed with a variably dense lymphoplasmacytic infiltrate suggestive of FDCS versus inflammatory myofibroblastic tumor. A pathology review following total resection of the abdominal mass confirmed the diagnosis of FDCS. The tumor cells showed positivity for CD35, CD21, CD45, and CD68, negative ALK staining, and limited smooth muscle actin immunoreactivity. The surgery was complicated by severe pneumonia and acidosis, resulting in a prolonged ICU stay and death. Conclusion: It is essential to maintain a high index of suspicion for FDCS and include it in the differential diagnosis of a spindle cell neoplasm, especially in the setting of paraneoplastic pemphigus. The histological and immunohistochemical features should be sufficient to confirm the diagnosis of FDCS.
Naturally Occurring Variants in LRP1 (Low-Density Lipoprotein Receptor–Related Protein 1) Affect HDL (High-Density Lipoprotein) Metabolism Through ABCA1 (ATP-Binding Cassette A1) and SR-B1 (Scavenger Receptor Class B Type 1) in Humans
Authors: Oldoni Federico , van Capelleveen Julian C. , Dalila Nawar , Wolters Justina C. , Heeren Joerg , Sinke Richard J. , Hui David Y. , Dallinga-Thie Geesje M. , Frikke-Schmidt Ruth , Hovingh Kees G. , van de Sluis Bart , Tybjærg-Hansen Anne , Kuivenhoven Jan Albert
Published: May 2018

Objective—

Studies into the role of LRP1 (low-density lipoprotein receptor–related protein 1) in human lipid metabolism are scarce. Although it is known that a common variant in
LRP1
(rs116133520) is significantly associated with HDL-C (high-density lipoprotein cholesterol), the mechanism underlying this observation is unclear. In this study, we set out to study the functional effects of 2 rare
LRP1
variants identified in subjects with extremely low HDL-C levels.

Approach and Results—

In 2 subjects with HDL-C below the first percentile for age and sex and moderately elevated triglycerides, we identified 2 rare variants in
LRP1
: p.Val3244Ile and p.Glu3983Asp. Both variants decrease LRP1 expression and stability. We show in a series of translational experiments that these variants culminate in reduced trafficking of ABCA1 (ATP-binding cassette A1) to the cell membrane. This is accompanied by an increase in cell surface expression of SR-B1 (scavenger receptor class B type 1). Combined these effects may contribute to low HDL-C levels in our study subjects. Supporting these findings, we provide epidemiological evidence that rs116133520 is associated with apo (apolipoprotein) A1 but not with apoB levels.

Conclusions—

This study provides the first evidence that rare variants in
LRP1
are associated with changes in human lipid metabolism. Specifically, this study shows that LRP1 may affect HDL metabolism by virtue of its effect on both ABCA1 and SR-B1.
In Situ Blood Vessel Regeneration Using SP (Substance P) and SDF (Stromal Cell–Derived Factor)-1α Peptide Eluting Vascular Grafts
Authors: Shafiq Muhammad , Zhang Qiuying , Zhi Dengke , Wang Kai , Kong Deling , Kim Dong-Hwee , Kim Soo Hyun
Published: May 2018

Objective—

The objective of this study was to develop small-diameter vascular grafts capable of eluting SDF (stromal cell–derived factor)-1α–derived peptide and SP (substance P) for in situ vascular regeneration.

Approach and Results—

Polycaprolactone (PCL)/collagen grafts containing SP or SDF-1α–derived peptide were fabricated by electrospinning. SP and SDF-1α peptide-loaded grafts recruited significantly higher numbers of mesenchymal stem cells than that of the control group. The in vivo potential of PCL/collagen, SDF-1, and SP grafts was assessed by implanting them in a rat abdominal aorta for up to 4 weeks. All grafts remained patent as observed using color Doppler and stereomicroscope. Host cells infiltrated into the graft wall and the neointima was formed in peptides-eluting grafts. The lumen of the SP grafts was covered by the endothelial cells with cobblestone-like morphology, which were elongated in the direction of the blood flow, as discerned using scanning electron microscopy. Moreover, SDF-1α and SP grafts led to the formation of a confluent endothelium as evaluated using immunofluorescence staining with von Willebrand factor antibody. SP and SDF-1α grafts also promoted smooth muscle cell regeneration, endogenous stem cell recruitment, and blood vessel formation, which was the most prominent in the SP grafts. Evaluation of inflammatory response showed that 3 groups did not significantly differ in terms of the numbers of proinflammatory macrophages, whereas SP grafts showed significantly higher numbers of proremodeling macrophages than that of the control and SDF-1α grafts.

Conclusions—

SDF-1α and SP grafts can be potential candidates for in situ vascular regeneration and are worthy for future investigations.
Metformin and AMP Kinase Activation Increase Expression of the Sterol Transporters ABCG5/8 (ATP-Binding Cassette Transporter G5/G8) With Potential Antiatherogenic Consequences
Authors: Molusky Matthew M. , Hsieh Joanne , Lee Samuel X. , Ramakrishnan Rajasekhar , Tascau Liana , Haeusler Rebecca A. , Accili Domenico , Tall Alan R.
Published: May 2018

Objective—

The mechanisms underlying the cardiovascular benefit of the anti-diabetic drug metformin are poorly understood. Recent studies have suggested metformin may upregulate macrophage reverse cholesterol transport. The final steps of reverse cholesterol transport are mediated by the sterol transporters, ABCG5 (ATP-binding cassette transporter G5) and ABCG8 (ATP-binding cassette transporter G8), which facilitate hepato-biliary transport of cholesterol. This study was undertaken to assess the possibility that metformin induces
Abcg5
and
Abcg8
expression in liver and to elucidate the underlying mechanisms.

Approach and Results—

Metformin-treated mouse or human primary hepatocytes showed increased expression of
Abcg5/8
and the bile salt export pump,
Bsep
. Administration of metformin to Western-type diet–fed mice showed significant upregulation of
Abcg5/8
and
Bsep
. This resulted in increased initial clearance of
3
H-cholesteryl ester HDL (high-density lipoprotein) from plasma. However, fecal
3
H-cholesterol output was only marginally increased, possibly reflecting increased hepatic
Ldlr
(low-density lipoprotein receptor) expression, which would increase nonradiolabeled cholesterol uptake.
Abcg5/8
undergo strong circadian variation. Available chromatin immunoprecipitation-Seq data suggested multiple binding sites for Period 2, a transcriptional repressor, within the Abcg5/8 locus. Addition of AMPK (5′ adenosine monophosphate-activated protein kinase) agonists decreased Period 2 occupancy, suggesting derepression of
Abcg5/8
. Inhibition of ATP citrate lyase, which generates acetyl-CoA from citrate, also decreased Period 2 occupancy, with concomitant upregulation of
Abcg5/8
. This suggests a mechanistic link between feeding-induced acetyl-CoA production and decreased cholesterol excretion via Period 2, resulting in inhibition of
Abcg5/8
expression.

Conclusions—

Our findings provide partial support for the concept that metformin may provide cardiovascular benefit via increased reverse cholesterol transport but also indicate increased
Ldlr
expression as a potential additional mechanism. AMPK activation or ATP citrate lyase inhibition may mediate antiatherogenic effects through increased ABCG5/8 expression.
Testosterone Protects Against Atherosclerosis in Male Mice by Targeting Thymic Epithelial Cells—Brief Report
Authors: Wilhelmson Anna S. , Lantero Rodriguez Marta , Svedlund Eriksson Elin , Johansson Inger , Fogelstrand Per , Stubelius Alexandra , Lindgren Susanne , Fagman Johan B. , Hansson Göran K. , Carlsten Hans , Karlsson Mikael C.I. , Ekwall Olov , Tivesten Åsa
Published: May 2018

Objective—

Androgen deprivation therapy has been associated with increased cardiovascular risk in men. Experimental studies support that testosterone protects against atherosclerosis, but the target cell remains unclear. T cells are important modulators of atherosclerosis, and deficiency of testosterone or its receptor, the AR (androgen receptor), induces a prominent increase in thymus size. Here, we tested the hypothesis that atherosclerosis induced by testosterone deficiency in male mice is T-cell dependent. Further, given the important role of the thymic epithelium for T-cell homeostasis and development, we hypothesized that depletion of the AR in thymic epithelial cells will result in increased atherosclerosis.

Approach and Results—

Prepubertal castration of male atherosclerosis-prone apoE
−/−
mice increased atherosclerotic lesion area. Depletion of T cells using an anti-CD3 antibody abolished castration-induced atherogenesis, demonstrating a role of T cells. Male mice with depletion of the AR specifically in epithelial cells (E-ARKO [epithelial cell-specific AR knockout] mice) showed increased thymus weight, comparable with that of castrated mice. E-ARKO mice on an apoE
−/−
background displayed significantly increased atherosclerosis and increased infiltration of T cells in the vascular adventitia, supporting a T-cell–driven mechanism. Consistent with a role of the thymus, E-ARKO apoE
−/−
males subjected to prepubertal thymectomy showed no atherosclerosis phenotype.

Conclusions—

We show that atherogenesis induced by testosterone/AR deficiency is thymus- and T-cell dependent in male mice and that the thymic epithelial cell is a likely target cell for the antiatherogenic actions of testosterone. These insights may pave the way for new therapeutic strategies for safer endocrine treatment of prostate cancer.
Macrophages Shed Excess Cholesterol in Unique Extracellular Structures Containing Cholesterol Microdomains
Authors: Jin Xueting , Dimitriadis Emilios K. , Liu Ying , Combs Christian A. , Chang Janet , Varsano Neta , Stempinski Erin , Flores Rhonda , Jackson Shelley N. , Muller Ludovic , Woods Amina S. , Addadi Lia , Kruth Howard S.
Published: May 2018

Objective—

Cells use various mechanisms to maintain cellular cholesterol homeostasis including efflux of cholesterol from the cellular plasma membrane to cholesterol acceptors such as HDLs (high-density lipoproteins). Little is known about the transfer of cholesterol from cells into the extracellular matrix. Using a unique monoclonal antibody that detects ordered cholesterol arrays (ie, cholesterol micro[or nano]-domains), we previously identified that particles containing these cholesterol domains accumulate in the extracellular matrix during cholesterol enrichment of human monocyte-derived macrophages and are found in atherosclerotic lesions. In this study, we further investigate these deposited particles containing cholesterol microdomains and discover their unexpected morphology.

Approach and Results—

Although appearing spherical at the resolution of the conventional fluorescence microscope, super-resolution immunofluorescence and atomic force microscopy of in situ cholesterol microdomains, and immunoelectron microscopy of isolated cholesterol microdomains revealed that the microdomains are not vesicles or 3-dimensional crystals but rather appear as branching irregularly shaped deposits of varying size. These cholesterol microdomain-containing deposits are shed from the plasma membrane into the extracellular matrix.

Conclusions—

To date, research on cellular excretion of excess cholesterol has demonstrated cellular cholesterol efflux in the form of membranous vesicles and discoidal HDL particles released into the fluid-phase medium. Shedding of plasma membrane cholesterol microdomains provides an additional mechanism for cells such as macrophages to maintain plasma membrane cholesterol homeostasis. Furthermore, recognition that macrophages shed cholesterol microdomains into the extracellular matrix is important to our understanding of extracellular buildup of cholesterol in atherosclerosis.
Cardiac Phenotype of Prehypertrophic Fabry Disease
Authors: Nordin Sabrina , Kozor Rebecca , Baig Shanat , Abdel-Gadir Amna , Medina-Menacho Katia , Rosmini Stefania , Captur Gabriella , Tchan Michel , Geberhiwot Tarekegn , Murphy Elaine , Lachmann Robin , Ramaswami Uma , Edwards Nicola C. , Hughes Derralynn , Steeds Richard P. , Moon James C.
Published: May 2018

Background:

Fabry disease (FD) is a rare and treatable X-linked lysosomal storage disorder. Cardiac involvement determines outcomes; therefore, detecting early changes is important. Native T1 by cardiovascular magnetic resonance is low, reflecting sphingolipid storage. Early phenotype development is familiar in hypertrophic cardiomyopathy but unexplored in FD. We explored the prehypertrophic cardiac phenotype of FD and the role of storage.

Methods and Results:

A prospective, international multicenter observational study of 100 left ventricular hypertrophy–negative FD patients (mean age: 39±15 years; 19% male) and 35 age- and sex-matched healthy volunteers (mean age: 40±14 years; 25% male) who underwent cardiovascular magnetic resonance, including native T1 and late gadolinium enhancement, and 12-lead ECG. In FD, 41% had a low native T1 using a single septal region of interest, but this increased to 59% using a second slice because early native T1 lowering was patchy. ECG abnormalities were present in 41% and twice as common with low native T1 (53% versus 24%;
P
=0.005). When native T1 was low, left ventricular maximum wall thickness, indexed mass, and ejection fraction were higher (maximum wall thickness 9±1.5 versus 8±1.4 mm,
P
<0.005; indexed left ventricular mass 63±10 versus 58±9 g/m
2
,
P
<0.05; and left ventricular ejection fraction 73±8% versus 69±7%,
P
<0.01). Late gadolinium enhancement was more likely when native T1 was low (27% versus 6%;
P
=0.01). FD had higher maximal apical fractal dimensions compared with healthy volunteers (1.27±0.06 versus 1.24±0.04;
P
<0.005) and longer anterior mitral valve leaflets (23±2 mm versus 21±3 mm;
P
<0.005).

Conclusions:

There is a detectable prehypertrophic phenotype in FD consisting of storage (low native T1), structural, functional, and ECG changes.
Exploring the Healthcare Value of Percutaneous Coronary Intervention
Authors: Alyesh Daniel M. , Seth Milan , Miller David C. , Dupree James M. , Syrjamaki John , Sukul Devraj , Dixon Simon , Kerr Eve A. , Gurm Hitinder S. , Nallamothu Brahmajee K.
Published: May 2018

Background:

Assessments of healthcare value have largely focused on measuring outcomes of care at a given level of cost with less attention paid to appropriateness. However, understanding how appropriateness relates to outcomes and costs is essential to determining healthcare value.

Methods AND RESULTS:

In a retrospective cohort study design, administrative data from fee-for-service Medicare patients undergoing percutaneous coronary intervention (PCI) in Michigan hospitals between June 30, 2010, and December 31, 2014, were linked with clinical data from a statewide PCI registry to calculate hospital-level measures of (1) appropriate use criteria scores, (2) 90-day risk-standardized readmission and mortality rates, and (3) 90-day risk-standardized episode costs. We then used Spearman correlation coefficients to assess the relationship between these measures. A total of 29 839 PCIs were performed at 33 PCI hospitals during the study period. A total of 13.3% were for ST-segment–elevation myocardial infarction, 25.0% for non–ST-segment–elevation myocardial infarction, 47.1% for unstable angina, 9.8% for stable angina, and 4.7% for other. The overall hospital-level mean appropriate use criteria score was 8.4±0.2. Ninety-day risk-standardized readmission occurred in 23.7%±3.7% of cases, 90-day risk-standardized mortality in 4.3%±0.6%, and mean risk-standardized episode costs were $26 159±$1074. Hospital-level appropriate use criteria scores did not correlate with 90-day readmission, mortality, or episode costs.

Conclusions:

Among Medicare patients undergoing PCI in Michigan, we found hospital-level appropriate use criteria scores did not correlate with 90-day readmission, mortality, or episode costs. This finding suggests that a comprehensive understanding of healthcare value requires multidimensional consideration of appropriateness, outcomes, and costs.
Cardiorespiratory Fitness (Peak Oxygen Uptake): Safe and Effective Measure for Cardiovascular Screening Before Kidney Transplant
Authors: Chakkera Harini A. , Angadi Siddhartha S. , Heilman Raymond L. , Kaplan Bruce , Scott Robert L. , Bollempalli Harini , Cha Stephen S. , Khamash Hasan A. , Huskey Janna L. , Mour Girish K. , Sukumaran Nair Sumi , Singer Andrew L. , Reddy Kunam S. , Mathur Amit K. , Moss Adyr A. , Hewitt Winston R. , Qaqish Ibrahim , Behmen Senaida , Keddis Mira T. , Unzek Samuel , Steidley D. Eric
Published: May 2018

Background

Significant heterogeneity exists in practice patterns and algorithms used for cardiac screening before kidney transplant. Cardiorespiratory fitness, as measured by peak oxygen uptake (VO
2peak
), is an established validated predictor of future cardiovascular morbidity and mortality in both healthy and diseased populations. The literature supports its use among asymptomatic patients in abrogating the need for further cardiac testing.

Methods and Results

We outlined a pre–renal transplant screening algorithm to incorporate
VO
2peak
testing among a population of asymptomatic high‐risk patients (with diabetes mellitus and/or >50 years of age). Only those with
VO
2peak
<17 mL/kg per minute (equivalent to <5 metabolic equivalents) underwent further noninvasive cardiac screening tests. We conducted a retrospective study of the
a priori
dichotomization of the
VO
2peak
<17 versus ≥17 mL/kg per minute to determine negative and positive predictive value of future cardiac events and all‐cause mortality. We report a high (>90%) negative predictive value, indicating that
VO
2peak
≥17 mL/kg per minute is effective to rule out future cardiac events and all‐cause mortality. However, lower
VO
2peak
had low positive predictive value and should not be used as a reliable metric to predict future cardiac events and/or mortality. In addition, a simple mathematical calculation documented a cost savings of ≈$272 600 in the cardiac screening among our study cohort of 637 patients undergoing evaluation for kidney and/or pancreas transplant.

Conclusions

We conclude that incorporating an objective measure of cardiorespiratory fitness with
VO
2peak
is safe and allows for a cost savings in the cardiovascular screening protocol among higher‐risk phenotype (with diabetes mellitus and >50 years of age) being evaluated for kidney transplant.
Redescription of Bursaphelenchus eucarpus Rühm, 1956 (Nematoda: Aphelenchoididae) associated with the apple bark beetle, Scolytus mali Bechstein, and the shothole borer, S. rugulosus Müller
Authors: Gu Jianfeng , Tomalak Marek , Braasch Helen , Fang Yiwu
Published: May 2018

New morphological, molecular and bionomic data are added to update the description of Bursaphelenchus eucarpus. The nematode was isolated from larval galleries and adults of the apple bark beetle, Scolytus mali, and the shothole borer, S. rugulosus, present under the bark of the bird cherry, Prunus padus, and the common European plum, P. domestica, in Poland. Detailed male, female and dispersal juvenile morphology and morphometrics are documented and compared with the original description. From partial 18S, ITS1/2 and partial 28S D2-D3 sequences and morphological features (three lateral lines, position of caudal papillae, shape of the delicate spicules with dorsally bent condylus, lack of vulval flap, a long post-uterine branch and a hyaline region at the female tail tip) it can be concluded that B. eucarpus belongs to the eremus group of Bursaphelenchus. The differentiation from related species of the eremus group is discussed.
Road Traffic Nuisance in Slovenia: State Liability for Non-pecuniary Damage
Authors: Možina Damjan
Published: May 2018

This paper presents and critically analyses the case law of the Slovenian courts with regard to mass individual claims against the state due to nuisance from public roads and railroads. The courts have largely upheld these claims. In awarding monetary compensation for non-pecuniary loss, they have considered the fundamental right to a healthy environment to be a personality right. Moreover, they have held that the state is under a guarantee-like obligation towards the population in that noise arising from public roads and railways will not exceed the limit levels set by the Regulation on Limit Values of Environmental Noise Indicators. As a consequence, new mass claims are being filed, exposing the state to considerable liability. The author considers the approach taken by the civil courts in Slovenia to be misguided on several levels. A fair balance between should be sought public and individual interests. Upholding claims in full by individuals who did nothing to mitigate noise is inappropriate. The problem would be better dealt with by way of regulating noise protection; compensation by way of analogy to (partial) expropriation in the public interest should only be sought if noise protection measures are ineffective or disproportionate.
Translingual Events
Authors: Helgesson Stefan , Kullberg Christina
Published: May 2018

This article outlines a theory of world literary reading that takes language and the making of boundaries between languages as its point of departure. A consequence of our discussion is that world literature can be explored as uneven translingual events that make linguistic tensions manifest either at the micro level of the individual text or at the macro level of publication and circulation—or both. Two case studies exemplify this. The first concerns an episode in the institutionalization of Shakespeare as a global canonical figure in 1916, with a specific focus on the South African writer Sol Plaatje’s Setswana contribution to A Book of Homage to Shakespeare. The second case discusses how Edwidge Danticat’s novel The Farming of Bones (1998) evokes the bodily and affective charge of boundary-making by troubling the border between Haitian and Dominican speech.
Translating a Translingual Tongue
Authors: Robinson Douglas
Published: May 2018

The paper examines Chantal Wright’s “experimental” English translation of Yoko Tawada’s “Porträt einer Zunge” as Portrait of a Tongue in terms of the interplay between translinguality and translationality, especially in terms of what Deleuze and Guattari call “majoritizing” and “minoritizing” impulses in literature, and what David Damrosch calls “hypercanonization” and “countercanonization.” The goal is to explore not so much whether Tawada gains or loses in Wright’s translation, as whether any gains in translation tend to transmajoritize and so to hypercanonize her or to transminoritize and so to countercanonize her.
Two new eriophyoid mites from Iran in the subfamilies Phyllocoptinae and Eriophyinae (Acari: Trombidiformes: Eriophyidae)
Authors: KAMALI HASHEM , DORYANIZADEH NAZANIN , AKRAMI MOHAMMAD ALI
Published: May 2018

Two new species of eriophyoid mites from Fars province, Iran, are described and illustrated, namely: Tetra aparinea n. sp. causing distortion of Galium aparine L. (Rubiaceae) and representing the first record of the genus Tetra on plants of the family Rubiaceae; and Acaralox shiraziensis n. sp. from Tragopogon graminifolius DC. (Asteraceae), causing no visible damage except for slight wilting.
A new genus and five new species of Anostostomatidae from the Lesser Antilles (Orthoptera: Ensifera)
Authors: HUGEL SYLVAIN , DESUTTER-GRANDCOLAS LAURE
Published: May 2018

Most high volcanic islands of Lesser Antilles harbor one single genus of Anostostomatidae: Rhumosa n. gen: Rhumosa bolognei n. gen. n. sp. in Guadeloupe, Rhumosa macoucheriei n. gen. n. sp. in Dominica, Rhumosa depazei n. gen. n. sp. in Martinique, Rhumosa admiralrodneyei n. gen. n. sp. in Saint Lucia, Rhumosa captainblighei n. gen. n. sp., in Saint Vincent. These species are restricted to well preserved rainforests; species from northern islands apparently occurring at higher elevation than species of southern islands. The distribution and generic position of Rhumosa n. gen. species is discussed, as well as the generic position of Lutosa cubaensis (Haan, 1843).
Pseudotibiozus Demange, 1970—millipedes of the Eastern Arc Mountains, Tanzania (Diplopoda, Spirostreptida, Spirostreptidae)
Authors: ENGHOFF HENRIK , LARSSON TOBIAS BERGLUND
Published: May 2018

The genus Pseudotibiozus Demange, 1970, is discussed, its type species, P. cerasopus (Attems, 1914) is re-described based on type and new material, and P. zophoribates sp. nov. is described from the West Usambara Mountains, Tanzania. The millipede faunas of the West and East Usambara Mts are compared.
On the Dynamics of Tropical Cyclone and Trough Interactions
Authors: Komaromi William A. , Doyle James D.
Published: May 2018

The interaction between a tropical cyclone (TC) and an upper-level trough is simulated in an idealized framework using Coupled Ocean–Atmosphere Mesoscale Prediction System (COAMPS) for Tropical Cyclones (COAMPS-TC) on a β plane. We explore the effect of the trough on the environment, structure, and intensity of the TC. In a simulation that does not have a trough, environmental inertial stability is dominated by Coriolis, and outflow remains preferentially directed equatorward throughout the simulation. In the presence of a trough, negative storm-relative tangential wind in the base of the trough reduces the inertial stability such that the outflow shifts from equatorward to poleward. This interaction results in a ~24-h period of enhanced upper-level divergence coincident with intensification of the TC. Sensitivity tests reveal that if the TC is too far from the trough, favorable interaction does not occur. If the TC is too close to the trough, the storm weakens because of enhanced vertical wind shear. Only when the relative distance between the TC and the trough is 0.2–0.3 times the wavelength of the trough in x and 0.8–1.2 times the amplitude of the trough in y does favorable interaction and TC intensification occur. However, stochastic effects make it difficult to isolate the intensity change associated directly with the trough interaction. Outflow is found to be predominantly ageostrophic at small radii and deflects to the right (in the Northern Hemisphere) since it is unbalanced. The outflow becomes predominantly geostrophic at larger radii but not before a rightward deflection has already occurred. This finding sheds light on why the outflow accelerates toward but generally never reaches the region of lowest inertial stability.
A New Look at the Identification of Low-Level Jets in South America
Authors: Oliveira Maurício I. , Nascimento Ernani L. , Kannenberg Carolina
Published: May 2018

Criteria currently employed in algorithms that identify low-level jets (LLJs) in South America utilizing rawinsonde and gridded model data fail to detect an important number of LLJ events. This study discusses shortcomings in the existing approaches for LLJ identification in South America and proposes modifications to the criteria regarding layer depth for LLJ identification and wind direction. Episodes of southerly LLJs, which have received less attention in the La Plata basin, are also included in the investigation. A sensitivity analysis of LLJ detection in South America upon the choice of the criteria applied to a sample period of 15 years (1996–2010) of gridded numerical data from the National Centers for Environmental Prediction (NCEP) Climate Forecast System Reanalysis (CFSR), and to a 20-yr dataset (1996–2015) of actual rawinsondes for the La Plata basin, reveals the benefits of revising the criteria. The modified criteria allow for the characterization of a wider spectrum of LLJs over key regions of South America, such as over the Bolivian–Paraguayan border, Sierras de Córdoba in Argentina, and southern-southeastern Brazil. This wider range of events includes elevated LLJs, mostly with strong zonal components, that account for approximately 20% of the full sample of LLJs identified in the rawinsonde dataset investigated here. The revised criteria have the advantage of retaining the identification of episodes that meet the consecrated definition of the South American LLJ, while at the same time providing an augmented sample of such wind systems. Our results provide further insights into the forcing mechanisms of distinct types of LLJs in South America, ranging from topographic to baroclinic effects.
High-performance liquid chromatography methods for the analysis of endogenous cortisol and cortisone in human urine: comparison of mass spectrometry and fluorescence detection
Authors: Kosicka Katarzyna , Siemiątkowska Anna , Szpera-Goździewicz Agata , Krzyścin Mariola , Bręborowicz Grzegorz , Główka Franciszek
Published: May 2018

Background

The analysis of steroids in biological matrices is challenging. One can apply immunoassay as well as gas and liquid chromatography with various types of detection, depending on the available equipment and the experience of the analyst. The question is how the methods are interchangeable between themselves. Doubts were reported having compared immunoassays and chromatography-mass spectrometry, but there are scarce data on chromatographic methods with detection types other than mass spectrometry.

Methods

Here, we present the detailed comparison of two liquid chromatographic methods for the determination of free urinary cortisol and cortisone: one with fluorescence detection (high-performance liquid chromatography [HPLC-FLD]) and the other with tandem mass spectrometry (HPLC-MS/MS). The comparison was made with 199 human urine samples. The data analysis included Passing–Bablok and Deming regression, Bland–Altman test, Wilcoxon test, mountain plot and Lin’s concordance correlation coefficient.

Results

The validation data indicated that both methods met the requirements of the European Medicines Agency. However, the statistical analysis revealed the systematic bias between the two assays. The Passing–Bablok and the Deming tests showed that the HPLC-FLD method overestimated results for cortisol and underestimated measurements for cortisone. The Bland–Altman analysis estimated the mean differences between the methods: 18.8 nmol/L for cortisol and −16.9 nmol/L for cortisone measurement.

Conclusions

Both methods’ results led to the same conclusion in observational studies, but the techniques are not interchangeable. The literature data, the observations from the clinical setting and our experience clearly indicate that the future of steroid measurements will belong to chromatography coupled with mass spectrometry.
New-Technology Startups Seeking Pilot Customers: Crafting a Pair of Value Propositions
Authors: Wouters Marc , Anderson James C. , Kirchberger Markus
Published: May 2018

A corporation that employs an “outside-in” startup program needs to screen a large number of potential startups and assess each time: What is the value of the startup’s offering to our business, and what resources and support will the startup need so we can actually obtain its offering? However, many startups are not very good at communicating their customer value proposition in a way that helps the customer firm making such assessments. This article recommends that startups construct two sequential value propositions. The Innovative Offering Value Proposition communicates how the startup’s offering creates superior value for the customer. It answers the question: What is extraordinary about the startup’s offering that will enable the customer to solve a significant problem it has or achieve a top priority it has? The Leveraging Assistance Value Proposition conveys what the customer firm will get in return for providing support and resources to the startup. It answers the question: What will make it worthwhile from the customer’s perspective to support the startup to realize its innovative offering?
Global Governance, Tax Treaties, and Credible Commitments
Authors: Johnson Austin P.
Published: May 2018

The international tax regime appears to be a weak system of global governance on the surface; however, I find that this system remains effective. This governance structure is built upon the thousands of tax treaties that function as policy instruments for advancing the implementation of global tax policy. Yet there is conflicting evidence in relation to the efficacy of these treaties, necessitating further exploration. In this article, I offer an accessible introduction to some of the key dynamics of the international tax regime and, in doing so, systematically address whether tax treaties may have the capacity to spur cross-border investment in securities. Using augmented gravity models, I find strong empirical evidence in favor of my theory that tax treaties function as credible commitments to international tax norms, potentially increasing portfolio holdings of some foreign securities. My findings should be of significant importance to scholars of international organizations, global governance, and international tax policy.
Sources of Students’ Anxiety in a Multidisciplinary Social Statistics Course
Authors: Condron Dennis J. , Becker Jacob H. , Bzhetaj Linda
Published: May 2018

To what extent, and why, do social science undergraduates experience anxiety about taking statistics courses? Despite holding assumptions of rampant statistics anxiety among students, sociologists have conducted few empirical studies of this issue. We extend the literature by analyzing data from a survey of sociology, social work, and criminal justice students enrolled in seven sections of our department’s Social Statistics with Computer Applications course in the winter 2018 semester. Two thirds of respondents are anxious or very anxious about taking the course. They experience statistics anxiety primarily due to their lack of confidence in their ability to succeed in the course and their more general test-taking anxiety. This article offers a framework for instructors of social statistics courses to measure student anxiety and to address it in class in a way that aims to alleviate anxiety among the anxious while not alienating those who are comfortable in the course.
Introduction to Psychology
Authors: Pfund Rory A. , Norcross John C. , Hailstorks Robin , Stamm Karen E. , Christidis Peggy
Published: May 2018

A robust literature has explored multiple facets of the introductory psychology course, but few studies have examined its purposes, student learning outcomes (SLOs), and assessment practices. The second iteration of the Undergraduate Study in Psychology gathered data on these facets in a nationally representative sample of associate ( n = 62) and baccalaureate psychology programs ( n = 161). Most department chairs indicated that their intro course served as both an introduction to the major and a general education function. Approximately one third of programs incorporated the American Psychological Association Guidelines for the Undergraduate Psychology Major 2.0 in their entirety or with minor changes to develop their SLOs for the introductory course. Written assignments and professor-developed quizzes/exams were the most frequently used assessment methods. Discussion centers on how these results may be used by teachers of introductory psychology.
Test-Enhanced Learning
Authors: Collins Dylan P. , Rasco Danney , Benassi Victor A.
Published: May 2018

Test-enhanced learning is a technique instructors can use to increase recall on summative assessments (e.g., exams) via formative assessments (e.g., quizzes). The present research examined recommendations based on the transfer-appropriate processing and level-of-processing (LOP) perspectives to assess the question, does deeper processing on quizzes (i.e., using application questions compared to factual) benefit exam performance? Students were more likely to correctly answer application questions on the exam when quizzes required a deeper LOP, and students appeared to gain a relatively equivalent definitional understanding using either factual or application questions on quizzes. Consequently, the present research supports the use of quiz questions that require a deeper LOP, especially when students are expected to learn beyond rote memorization.