bluuebunny/crossref_metadata_2025 huggingface dataset:
Current Standard and Future Perspectives in the Treatment of Gastrointestinal Stromal Tumors
Authors: Cameron Silke , Beham Alexander , Schildhaus Hans-Ulrich
Published: April 2017

The origin of gastrointestinal stromal tumors (GIST) from interstitial cells of Cajal or their precursor cells has been understood since the early 1990s. The first mutations within the KIT-gene have been described in the late 1990s. Even though these mutations were the breakthrough of small molecular therapy, we still do not know the factors responsible for their malignant transformation. Until then, we can only speak of recurrence risk. This review gives an introduction on the current understanding of GIST and highlights the remaining questions for diagnosis, tumor progression, and treatment in progressive disease.
MicroRNA-155 and Anti-Müllerian Hormone: New Potential Markers of Subfertility in Men with Chronic Kidney Disease
Authors: Eckersten Dag , Tsatsanis Christos , Giwercman Aleksander , Bruun Laila , Pihlsgård Mats , Christensson Anders
Published: April 2017

Background/Aims: Men with terminal renal failure are often infertile. Anti-müllerian hormone (AMH), a marker of Sertoli cell function, is decreased among men with chronic kidney disease (CKD). Recently, a microRNA, miR-155, has been shown to be a potential marker for subfertility. We studied miR-155 and semen parameters in patients with CKD who were not yet on dialysis. We also aimed to study possible associations between AMH, miR-155, and semen parameters to evaluate them as markers of fertility. Methods: Thirty male patients with CKD 1–4 as well as 18 healthy controls were enrolled. Results: Serum levels of miR-155 were significantly higher among men with CKD stages 1–2 (4.51 ± 3.81 [p = 0.01]) and stages 3–4 (2.75 ± 1.77 [p = 0.006]) than in controls (1.09 ± 0.44). Sperm concentration was significantly lower among men with CKD 3–4 (42 ± 29) ×106/mL compared to controls (88 ± 42) ×106/mL (p = 0.011). High levels of miR-155 were associated with a relatively low sperm concentration (p = 0.02) and with a low total sperm number (p = 0.005). Low AMH levels were associated with a decreased percentage of motile sperm cells (p = 0.02). Conclusions: We conclude that men with stage 3–4 CKD had lower sperm concentrations than healthy fertile men and that increased serum miR-155 in men with stage 1–4 CKD was associated with semen parameters that indicate subfertility. Low AMH levels were associated with a low percentage of the total number of motile sperm cells. miR-155 and AMH may be potential markers of subfertility in men with CKD.
In-Office Application of Fluoride Gel or Varnish: Cost-Effectiveness and Expected Value of Perfect Information Analysis
Authors: Schwendicke Falk , Stolpe Michael
Published: April 2017

Application of fluoride gel/varnish (FG/FV) reduces caries increments but generates costs. Avoiding restorative treatments by preventing caries might compensate for these costs. We assessed the cost-effectiveness of dentists applying FG/FV in office and the expected value of perfect information (EVPI). EVPI analyses estimate the economic value of having perfect knowledge, assisting research resource allocation. A mixed public-private-payer perspective in Germany was adopted. A population of 12-year-olds was followed over their lifetime, with caries increments modelled using wide intervals to reflect the uncertainty of caries risk. Biannual application of FV/FG until age 18 years was compared to no fluoride application. Effectiveness parameters and their uncertainty were derived from systematic reviews. The health outcome was caries increment (decayed, missing, or filled teeth; DMFT). Cost calculations were based on fee catalogs or microcosting, including costs for individual-prophylactic fluoridation and, for FG, an individualized tray, plus material costs. Microsimulations, sensitivity, and EVPI analyses were performed. On average and applied to a largely low-risk population, no application of fluoride was least costly but also least effective (EUR 230; 11 DMFT). FV was more costly and effective (EUR 357; 7 DMFT). FG was less effective than FV and also more costly when using individualized trays. FV was the best choice for payers willing to invest EUR 39 or more per avoided DMFT. This cost-effectiveness will differ in different settings/countries or if FG/FV is applied by other care professionals. The EVPI was mainly driven by the individual's caries risk, as FV/FG were significantly more cost-effective in high-risk populations than in low-risk ones. Future studies should focus on caries risk prediction.
Incidence of and Risk Factors and Reinterventions for Post-Pancreatoduodenectomy Hemorrhage: Retrospective Analysis
Authors: Wang Wei-Guo , Fu Lan , Babu Shah Ram , Wang Li , Liang Cui-Ping , Tian Bo-Le
Published: April 2017

Aims: To analyze the incidence of and risk factors for post-pancreatoduodenectomy (PD) hemorrhage (PPH) and to evaluate the outcomes of reinterventions for PPH. Methods: All PDs between January 2009 and December 2014 were retrospectively evaluated. PPH was evaluated according to the criteria of the International Study Group of Pancreatic Surgery. Both univariate and multivariate analyses of risk factors for PPH and mortality were performed. Reinterventions were also evaluated. Results: Of the 1,056 PDs during the study period, 78 (7.4%) developed PPH, including 36 with grade B and 42 with grade C. Of these 78 patients, 24 (30.8%) died of PPH-related causes. Multivariate analysis showed that older age, higher total bilirubin concentration, and postoperative pancreatic fistula (POPF) were independent risk factors for PPH. Patients who died of PPH were significantly older and had lower preoperative hemoglobin and albumin concentrations than patients who did not die of PPH. Of the 78 patients with PPH, 58 underwent reintervention, including 27 who underwent angiography, 24 who underwent endoscopy, 24 who underwent re-laparotomy, and 15 who underwent more than one reintervention. Conclusions: Older age, total bilirubin, and POPF are independent risk factors for PPH. Higher mortality are associated with advanced PPH and poor nutritional conditions.
Efficacy and Tolerance of Cetuximab Alone or Combined with Chemotherapy in Locally Advanced or Metastatic Cutaneous Squamous Cell Carcinoma: An Open Study of 14 Patients
Authors: Dereure Olivier , Missan Hamoudeh , Girard Céline , Costes Valérie , Guillot Bernard
Published: April 2017

Background/Aims: Previous reports highlighted the potential interest of cetuximab alone or in combination with chemotherapy in locally advanced or metastatic cutaneous squamous cell carcinomas (cSCC) care. Material and Methods: To further evaluate the efficiency and safety of cetuximab in advanced cSCC, a single-center retrospective study including all patients treated with cetuximab alone or combined with carboplatin for locally advanced or metastatic cSCC was conducted in a tertiary referral center. The primary end point was the overall response rate (ORR) after 2 cycles of treatment. Secondary end points were best overall disease control rate (DCR), overall survival (OS), best response duration, progression-free survival (PFS), and toxicity profile. Results: Of the 14 enrolled patients, no complete response was obtained after 2 cycles of treatment, but 3 partial responses and 6 stable diseases were observed. ORR and DCR were 21.4 and 64.3%, respectively. Median OS and PFS were 9.25 and 2.65 months, respectively. Median PFS was longer with combined treatment compared with cetuximab monotherapy (9.03 vs. 3.55 months). The safety profile was acceptable with a trend toward a relationship between acne-like rash and longer response (median PFS 5.2 vs. 2.2 months). Discussion/Conclusion: In all series including ours, disease control is usually rapidly obtained with cetuximab alone or combined with conventional chemotherapy, although with a minority of partial responses and no complete response. However, this control is of short duration in most cases. The safety profile is acceptable. A randomized phase III trial is warranted to better assess the benefit/risk ratio.
Inverse Correlation of Venous Brain Natriuretic Peptide Levels with Body Mass Index Is due to Decreased Production
Authors: Shah Zubair , Wiley Mark , Sridhar Arun Mahankali , Masoomi Reza , Biria Mazda , Lakkireddy Dhananjay , Dawn Buddhadeb , Gupta Kamal
Published: April 2017

Objective: The aim of this paper was to study the association between body mass index (BMI) and coronary sinus (CS) brain natriuretic peptide (BNP) levels in patients with heart failure and reduced systolic function (HFrEF). Background: There is an inverse relationship between systemic venous BNP (V-BNP) levels and BMI in patients with HFrEF. It is unclear whether this finding is due to decreased production or due to an increased metabolism of BNP. Since CS-BNP levels reflect BNP production, we hypothesized that assessing the correlation of CS-BNP levels with BMI would provide insight into the mechanism of this inverse relationship of V-BNP and BMI. Methods: We prospectively enrolled 54 subjects with HFrEF who were to undergo cardiac resynchronization device implantation. CS-BNP, V-BNP, and arterial BNP (A-BNP) levels were measured during the implant procedure. Subjects were divided into 2 groups based on their BMI (group 1: BMI <30 and group 2: BMI ≥30). Results: The mean age of the overall study group was 64 ± 10 years. Average BMI for group 1 was 25.8 ± 2.8 and 36.8 ± 4.6 for group 2 (p < 0.03). A history of hypertension was present in 55% (n = 26) of the subjects, while diabetes was reported in 31% (n = 15). Serum creatinine was 1.0 ± 0.2 mg/dL and TSH 2.1 ± 1.4 mIU/L. 79% of the subjects were receiving β-blockers, while 94% were receiving angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. The mean CS-BNP, V-BNP, and A-BNP levels in group 2 were significantly lower than in group 1 (286.2 ± 170.5 vs. 417.5 ± 247.5 pg/mL, p = 0.04; 126.6 ± 32.5 vs. 228 ± 96.4 pg/mL, p = 0.01; and 151.9 ± 28.6 vs. 242 ± 88.8 pg/mL, p = 0.04, respectively). Univariate analysis and multivariate regression adjusted for age, diabetes mellitus, sex, glomerular filtration rate, and left atrial size confirmed BMI as an independent predictor of CS-BNP levels (β = -0.372, p = 0. 03) in our study. Conclusions: In this study, we demonstrate an inverse relationship between CS-BNP levels and BMI in patients with HFrEF. These findings suggest that the previously established inverse relationship between V-BNP and BMI is due to a decreased cardiac production of BNP in obese patients rather than from increased peripheral metabolism.
Self-Amputation of the Extra Digit in a Fetus with Polydactyly: First Ultrasound Demonstration
Authors: Volpe Nicola , Franchi Laura , Mazzone Eleonora , Migliavacca Costanza , Raboni Stefano , Percesepe Antonio , Kaihura Christine Tita , Frusca Tiziana , Ghi Tullio
Published: April 2017

We herein report the first ultrasound evidence of the self-amputation of an extra digit in case of fetal polydactyly. The prenatal evidence of fetal polydactyly is not always followed by postnatal confirmation. This is not always due to ultrasound misdiagnosis, but often to an in utero self-amputation phenomenon. We demonstrate that there is the detachment of part of the digit, leading to the evidence of a neonatal bump on the site of the prenatal extra digit. This demonstration has been possible by the direct visualization of the remnant by ultrasound.
Primary Conjunctival Tuberculosis Presenting as Dry Eye: A Rare Case Report and Review of the Literature
Authors: Brar Rupinder Kaur , Singh Ashok , Deshpande Archana Hemant , Gargade Chitrawati Bal , Das Sujit
Published: April 2017

Primary conjunctival tuberculosis is very rare in the developed countries. In an endemic country like India, it should be considered in the differential diagnosis of any unusual conjunctival lesion with unilaterality, chronicity, and nonresolution of symptoms after steroid use. We present the case of a 52-year-old female who presented with unilateral itching and blurring of vision for 20 days. There were irregular nodular elevated areas with shrinkage of the lower palpebral conjunctiva. A biopsy of the lesion revealed necrotizing epithelioid cell granulomas along with Langhans type of giant cells. However, no acid-fast bacilli were seen on Ziehl-Neelsen stain. Systemic examination of the patient was normal, and there was no evidence of pulmonary tuberculosis. Polymerase chain reaction of conjunctival scrapings was positive for Mycobacterium tuberculosis. The patient was started on antitubercular drugs. We present this very rare case of primary tuberculosis of the conjunctiva presenting with dryness of the eye.
Optic Nerve Obscuration in Retinoblastoma: A Risk Factor for Optic Nerve Invasion
Authors: Berry Jesse L. , Zolfaghari Emily , Chen Alexander , Murphree A. Linn , Jubran Rima , Kim Jonathan W.
Published: April 2017

Background: The objective of this study is to evaluate the risk of optic nerve invasion associated with optic nerve obscuration at diagnosis or persisting during treatment. Methods: Retrospective review from 2011-2016 of patients with advanced retinoblastoma (Group D/E) with complete obscuration of the nerve at diagnosis and a second group of patients with persistent, complete obscuration throughout treatment. Results: Advanced retinoblastoma was diagnosed in 102 eyes of 86 patients. The optic nerve was obscured in 69 eyes (68%) at diagnosis. Of these, 30 (43%) underwent salvage therapy and 39 (57%) primary enucleation. Histopathologic analysis of primarily enucleated eyes showed 41% prelaminar and 15% postlaminar invasion. Four eyes in the salvage group demonstrated persistent nerve obscuration; 2 were subsequently enucleated without evidence of nerve invasion. Average follow-up was 23.5 months (range 1-62 months). Conclusions and Relevance: Optic nerve obscuration at diagnosis may be associated with postlaminar optic nerve invasion. While persistent, complete obscuration of the optic nerve by retinoblastoma during treatment is a poor prognostic sign for both globe salvage and vision, it does not appear, in this small cohort, to increase the risk of optic nerve invasion. With appropriate control of the intraocular tumor, these eyes can be salvaged.
Primary Scarring Alopecia: Clinical-Pathological Review of 72 Cases and Review of the Literature
Authors: Villablanca Salvador , Fischer Cristián , García-García S. Cecilia , Mascaró-Galy J. Manuel , Ferrando Juan
Published: April 2017

Purpose of the Study: To analyze the epidemiologic, demographic, clinical, and histological characteristics of primary scarring alopecia (PSA) cases diagnosed over a 7-year period at the Department of Dermatology, Hospital Clinic, Barcelona, Spain. Procedures: Seventy-two patients diagnosed with PSA between 2006 and 2012 were included. Age, sex, ethnic group, clinical pattern, predominant histological infiltrate, final clinical diagnosis, time of onset, treatments used, and clinical evolution were evaluated and correlated. Results: The ethnic groups were distributed as follows: 93% European-Caucasian, 5% Mestizo-American, 1% oriental, and 1% Afro-American. Most cases were females (71%), and mean age was 51 ± 6 years. The follicular pattern was the most common, and the predominant inflammatory infiltrate was lymphocytic. Lichen planopilaris and frontal fibrosing alopecia were the main diagnoses. When correlating clinical aspects and histopathology, lymphocytic PSAs had a subacute onset and resulted in a nonchanging, more stable form, while neutrophilic PSAs had a more acute onset with an evolution of acute outbreaks. PSAs in a late stage with an absent/mild infiltrate had a subclinical onset and a slowly progressive or stable evolution. Conclusions: The PSAs are severe trichological conditions. Their high clinical and histopathological variability make them a diagnostic and therapeutic challenge. Message of the Paper: Knowing the clinical and histopathological aspects of PSAs should be of crucial importance to the dermatologist.
Effect of the Sonas Programme on Communication in People with Dementia: A Randomized Controlled Trial
Authors: Strøm Benedicte Sørensen , Engedal Knut , Benth Jurate Saltyte , Grov Ellen-Karine
Published: April 2017

Background: Strategies to improve communication in people with dementia are warranted. We examined the effect of the Sonas programme on communication ability in persons with moderate to severe dementia. Methods: A 24-week 3-armed (Sonas, reading, and control group) randomized controlled trial including 120 nursing home residents with dementia was conducted; 105 completed the follow-up assessments. The main outcome was change in communication abilities measured by the Holden Communication Scale (HCS). Results: We found no overall significant effect of the Sonas programme with regard to communication ability as measured by the HCS. However, an effect between the Sonas group and the reading group and between the Sonas group and the control group from T0 to T1 and T2 was found, as well as a significant improvement in communication in the Sonas group. Among people with severe dementia, the Sonas group scored significantly better on the HCS compared to the reading group after 12 weeks, but not after 24 weeks. Conclusion: This study failed to document an overall effect of the Sonas programme on communication; however, the findings indicate that the Sonas programme has a significant effect on communication among those with severe dementia.
Estrogen and Progesterone Integration in an in vitro Model of RP3V Kisspeptin Neurons
Authors: Mittelman-Smith Melinda A. , Wong Angela M. , Micevych Paul E.
Published: April 2017

Positive feedback on gonadotropin release requires not only estrogen but also progesterone to activate neural circuits. In rodents, ovarian estradiol (E2) stimulates progesterone synthesis in hypothalamic astrocytes (neuroP), needed for the luteinizing hormone (LH) surge. Kisspeptin (kiss) neurons are the principal stimulators of gonadotropin-releasing hormone neurons, and disruption of kiss signaling abrogates the LH surge. Similarly, blocking steroid synthesis in the hypothalamus or deleting classical progesterone receptor (PGR) selectively in kiss neurons prevents the LH surge. These results suggest a synergistic action of E2 and progesterone in kiss neurons to affect gonadotropin release. The mHypoA51, immortalized kiss-expressing neuronal cell line derived from adult female mice, is a tractable model for examining integration of steroid signaling underlying estrogen positive feedback. Here, we report that kiss neurons in vitro integrate E2 and progesterone signaling to increase levels of kiss translation and release. mHypoA51 neurons expressed nonclassical membrane progesterone receptors (mPRα and mPRβ) and E2-inducible PGR, required for progesterone-augmentation of E2-induced kiss expression. With astrocyte-conditioned media or in mHypoA51-astrocyte co-culture, neuroP augmented stimulatory effects of E2 on kiss protein. Progesterone activation of classical, membrane-localized PGR led to activation of MAPK and Src kinases. Importantly, progesterone or Src activation induced release of kiss from E2-primed mHypoA51 neurons. Consistent with previous studies, the present results provide compelling evidence that the interaction of E2 and progesterone stimulates kiss expression and release. Further, these results demonstrate a mechanism though which peripheral E2 may prime kiss neurons to respond to neuroP, mediating estrogen positive feedback.
Salvianolic Acid A Protects H9c2 Cells from Arsenic Trioxide-Induced Injury via Inhibition of the MAPK Signaling Pathway
Authors: Zhang Jing-yi , Sun Gui-bo , Luo Yun , Wang Min , Wang Wei , Du Yu-yang , Yu Ying-li , Sun Xiao-bo
Published: April 2017

Background/Aims: This study aimed to investigate whether Salvianolic acid A (Sal A) conferred cardiac protection against Arsenic trioxide (ATO)-induced cardiotoxicity in H9c2 cells by inhibiting MAPK pathways activation. Methods: H9c2 cardiac cells were exposed to 10 µM ATO for 24 h to induce cytotoxicity. The cells were pretreated with Sal A for 4 h before exposure to ATO. Cell viability was determined utilizing the MTT assay. The percentage of apoptosis was measured by a FITC-Annexin V/PI apoptosis kit for flow cytometry. Mitochondrial membrane potential (∆Ψm) was detected by JC-1. The intracellular ROS levels were measured using an Image-iTTM LIVE Green Reactive Oxygen Species Detection Kit. The apoptosis-related proteins and the MAPK signaling pathways proteins expression were quantified by Western blotting. Results: Sal A pretreatment increased cell viability, suppressed ATO-induced mitochondrial membrane depolarization, and significantly altered the apoptotic rate by enhancing endogenous antioxidative enzyme activity and ROS generation. Signal transduction studies indicated that Sal A suppressed the ATO-induced activation of the MAPK pathway. More importantly, JNK, ERK, and p38 inhibitors mimicked the cytoprotective activity of Sal A against ATO-induced injury in H9c2 cells by increasing cell viability, up-regulating Bcl-2 protein expression, and down-regulating both Bax and caspase-3 protein expression. Conclusion: Sal A decreases the ATO-induced apoptosis and necrosis of H9c2 cells, and the underlying mechanisms of this protective effect of Sal A may be connected with the MAPK pathways.
LincRNA-p21 Inhibits the Wnt/β-Catenin Pathway in Activated Hepatic Stellate Cells via Sponging MicroRNA-17-5p
Authors: Yu Fujun , Guo Yong , Chen Bicheng , Shi Liang , Dong Peihong , Zhou Mengtao , Zheng Jianjian
Published: April 2017

Background/Aims: It is known that the activation of hepatic stellate cells (HSCs) is a pivotal step in the initiation and progression of liver fibrosis. Aberrant activated Wnt/β-catenin pathway is known to accelerate the development of liver fibrosis. microRNAs (miRNAs)-mediated Wnt/β-catenin pathway has been reported to be involved in HSC activation during liver fibrosis. However, whether long noncoding RNAs (lncRNAs) regulate Wnt/β-catenin pathway during HSC activation still remains unclear. Methods: Long intergenic noncoding RNA-p21 (lincRNA-p21) expression was detected in Salvianolic acid B (Sal B)-treated cells. Effects of lincRNA-p21 knockdown on HSC activation and Wnt/β-catenin pathway activity were analyzed in Sal B-treated cells. In lincRNA-p21-overexpressing cells, effects of miR-17-5p on HSC activation and Wnt/β-catenin pathway activity were examined. Results: LincRNA-p21 expression was up-regulated in HSCs after Sal B treatment. In primary HSCs, lincRNA-p21 expression was down-regulated at Day 5 relative to Day 2. Sal B-inhibited HSC activation including the reduction of cell proliferation, α-smooth muscle actin (α-SMA) and type I collagen was inhibited by lincRNA-p21 knockdown. Sal B-induced Wnt/β-catenin pathway inactivation was blocked down by loss of lincRNA-p21. Notably, lincRNA-p21, confirmed as a target of miR-17-5p, suppresses miR-17-5p level. Lack of the miR-17-5p binding site in lincRNA-p21 prevents the suppression of miR-17-5p expression. In addition, the suppression of HSC activation and Wnt/β-catenin pathway induced by lincRNA-p21 overexpression was almost inhibited by miR-17-5p. Conclusion: We demonstrate that lincRNA-p21-inhibited Wnt/β-catenin pathway is involved in the effects of Sal B on HSC activation and lincRNA-p21 suppresses HSC activation, at least in part, via miR-17-5p-mediated-Wnt/β-catenin pathway.
Ambient PM
2.5
and Stroke
Authors: Lin Hualiang , Guo Yanfei , Di Qian , Zheng Yang , Kowal Paul , Xiao Jianpeng , Liu Tao , Li Xing , Zeng Weilin , Howard Steven W. , Nelson Erik J. , Qian Zhengmin , Ma Wenjun , Wu Fan
Published: April 2017

Background and Purpose—

Short-term exposure to ambient fine particulate pollution (PM
2.5
) has been linked to increased stroke. Few studies, however, have examined the effects of long-term exposure.

Methods—

A total of 45 625 participants were interviewed and included in this study, the participants came from the Study on Global Ageing and Adult Health, a prospective cohort in 6 low- and middle-income countries. Ambient PM
2.5
levels were estimated for participants’ communities using satellite data. A multilevel logistic regression model was used to examine the association between long-term PM
2.5
exposure and stroke. Potential effect modification by physical activity and consumption of fruit and vegetables was assessed.

Results—

The odds of stroke were 1.13 (95% confidence interval, 1.04–1.22) for each 10 μg/m
3
increase in PM
2.5
. This effect remained after adjustment for confounding factors including age, sex, smoking, and indoor air pollution (adjusted odds ratio=1.12; 95% confidence interval, 1.04–1.21). Further stratified analyses suggested that participants with higher levels of physical activity had greater odds of stroke, whereas those with higher consumption of fruit and vegetables had lower odds of stroke. These effects remained robust in sensitivity analyses. We further estimated that 6.55% (95% confidence interval, 1.97%–12.01%) of the stroke cases could be attributable to ambient PM
2.5
in the study population.

Conclusions—

This study suggests that ambient PM
2.5
may increase the risk of stroke and may be responsible for the astounding stroke burden in low- and middle-income countries. In addition, greater physical activity may enhance, whereas greater consumption of fruit and vegetables may mitigate the effect.
Empagliflozin and Cerebrovascular Events in Patients With Type 2 Diabetes Mellitus at High Cardiovascular Risk
Authors: Zinman Bernard , Inzucchi Silvio E. , Lachin John M. , Wanner Christoph , Fitchett David , Kohler Sven , Mattheus Michaela , Woerle Hans J. , Broedl Uli C. , Johansen Odd Erik , Albers Gregory W. , Diener Hans Christoph
Published: April 2017

Background and Purpose—

In the EMPA-REG OUTCOME trial (Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients), empagliflozin added to standard of care in patients with type 2 diabetes mellitus and high cardiovascular risk reduced the risk of 3-point major adverse cardiovascular events, driven by a reduction in cardiovascular mortality, with no significant difference between empagliflozin and placebo in risk of myocardial infarction or stroke. In a modified intent-to-treat analysis, the hazard ratio for stroke was 1.18 (95% confidence interval, 0.89–1.56;
P
=0.26). We further investigated cerebrovascular events.

Methods—

Patients were randomized to empagliflozin 10 mg, empagliflozin 25 mg, or placebo; 7020 patients were treated. Median observation time was 3.1 years.

Results—

The numeric difference in stroke between empagliflozin and placebo in the modified intent-to-treat analysis was primarily because of 18 patients in the empagliflozin group with a first event >90 days after last intake of study drug (versus 3 on placebo). In a sensitivity analysis based on events during treatment or ≤90 days after last dose of drug, the hazard ratio for stroke with empagliflozin versus placebo was 1.08 (95% confidence interval, 0.81–1.45;
P
=0.60). There were no differences in risk of recurrent, fatal, or disabling strokes, or transient ischemic attack, with empagliflozin versus placebo. Patients with the largest increases in hematocrit or largest decreases in systolic blood pressure did not have an increased risk of stroke.

Conclusions—

In patients with type 2 diabetes mellitus and high cardiovascular risk, there was no significant difference in the risk of cerebrovascular events with empagliflozin versus placebo.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT01131676.
Nongated Cardiac Computed Tomographic Angiograms for Detection of Embolic Sources in Acute Ischemic Stroke
Authors: Yeo Leonard L.L. , Holmin Staffan , Andersson Tommy , Lundström Erik , Gopinathan Anil , Lim Er Luen , Leong Benjamin S.H. , Kuan Win Sen , Ting Eric , Tan Benjamin Y.Q. , Eide Sterling Ellis , Tay Edgar L.K.
Published: April 2017

Background and Purpose—

We assessed the feasibility of obtaining diagnostic quality images of the heart and thoracic aorta by extending the
z
axis coverage of a non–ECG-gated computed tomographic angiogram performed in the primary evaluation of acute stroke without increasing the contrast dose.

Methods—

Twenty consecutive patients with acute ischemic stroke within the 4.5 hours of symptom onset were prospectively recruited. We increased the longitudinal coverage to the domes of the diaphragm to include the heart. Contrast administration (Omnipaque 350) remained unchanged (injected at 3–4 mL/s; total 60–80 mL, triggered by bolus tracking). Images of the heart and aorta, reconstructed at 5 mm slice thickness in 3 orthogonal planes, were read by a radiologist and cardiologist, findings conveyed to the treating neurologist, and correlated with the transthoracic or transesophageal echocardiogram performed within the next 24 hours.

Results—

Of 20 patients studied, 3 (15%) had abnormal findings: a left ventricular thrombus, a Stanford type A aortic dissection, and a thrombus of the left atrial appendage. Both thrombi were confirmed by transesophageal echocardiography, and anticoagulation was started urgently the following day. None of the patients developed contrast-induced nephropathy on follow-up. The radiation dose was slightly increased from a mean of 4.26 mSV (range, 3.88–4.70 mSV) to 5.17 (range, 3.95 to 6.25 mSV).

Conclusions—

Including the heart and ascending aorta in a routine non–ECG-gated computed tomographic angiogram enhances an existing imaging modality, with no increased incidence of contrast-induced nephropathy and minimal increase in radiation dose. This may help in the detection of high-risk cardiac and aortic sources of embolism in acute stroke patients.
Encoding of Predictable and Unpredictable Stimuli by Inferior Temporal Cortical Neurons
Authors: Kumar Susheel , Kaposvari Peter , Vogels Rufin
Published: April 2017

Animals and humans learn statistical regularities that are embedded in sequences of stimuli. The neural mechanisms of such statistical learning are still poorly understood. Previous work in macaque inferior temporal (IT) cortex demonstrated suppressed spiking activity to visual images of a sequence in which the stimulus order was defined by transitional probabilities (labeled as “standard” sequence), compared with a sequence in which the stimulus order was random (“random” sequence). Here, we asked whether IT neurons encode the images of the standard sequence more accurately compared with images of the random sequence. Previous human fMRI studies in different sensory modalities also found a suppressed response to expected relative to unexpected stimuli but obtained various results regarding the effect of expectation on encoding, with one study reporting an improved classification accuracy of expected stimuli despite the reduced activation level. We employed a linear classifier to decode image identity from the spiking responses of the recorded IT neurons. We found a greater decoding accuracy for images of the standard compared with the random sequence during the early part of the stimulus presentation, but further analyses suggested that this reflected the sustained, stimulus-selective activity from the previous stimulus of the sequence, which is typical for IT neurons. However, the peak decoding accuracy was lower for the standard compared with the random sequence, in line with the reduced response to the former compared with the latter images. These data suggest that macaque IT neurons represent less accurately predictable compared with unpredictable images.
Potential distribution of the endemic imbricate alligator lizard (Barisia imbricata imbricata) in highlands of central Mexico
Authors: Sunny Armando , González-Fernández Andrea , D’Addario Maristella
Published: April 2017

Barisia imbricata imbricatais an endemic anguid lizard living in the highlands of central Mexico, mainly in the Trans-Mexican Volcanic Belt, but its current distribution is not well defined. For this reason, it is critical to make a systematic study in order to determine the potential distribution of this subspecies. We considered 13 environmental and anthropogenic variables recognized to be important to determine the presence ofB. i. imbricata; we also used eight presence-only modeling methods and selected three to generate an ensemble model. The Maxent algorithm was used to obtain the most important variables. The variables with highest contribution to the model were: maximum temperature of the warmest month, altitude,Abiesforest andPinusforest. From the estimated potential distribution (9614.1 km2), 8053.4 km2(83.8%) are located in the Trans-Mexican Volcanic Belt, 3821.4 km2(39.7%) are located in natural protected areas and 2418.2 km2(25.2%) are in crop fields. The whole potential distribution is highly fragmented and characterized by the presence of human activities, which could have long-term consequences, increasing extinction risk.
Statehood and Refugees: Patterns of Integration and Segregation of Refugee Populations in Lebanon from a Comparative Perspective
Authors: Dionigi Filippo
Published: April 2017

Scholarly debate has persuasively highlighted the inherent tension between refugees and the modern state. Yet, how do state-refugee relations unfold in practice when considering the historical and social specificity of a single state? Is there a heuristic value in going beyond the premises of a general state-refugee binary and adopt a state-specific approach? These questions are addressed through an analysis based on the modelling of statehood in Lebanon and comparing five cases of refugee-state relations in this country. This method allows explaining the variation in degrees of segregation or integration of refugees and shows that the mode of politicization of refugees is the key factor in understanding this variation. Not all refugees and not all states are the same; the variance of state-refugee relations is best explained from a perspective that considers the historically situated nature of statehood.
The family Blechnaceae (Polypodiopsida) in Brazil: key to the genera and taxonomic treatment of Austroblechnum, Cranfillia, Lomaridium, Neoblechnum and Telmatoblechnum for southern and southeastern Brazil
Authors: DITTRICH VINÍCIUS ANTONIO DE OLIVEIRA , SALINO ALEXANDRE , MONTEIRO REINALDO , GASPER ANDRÉ LUÍS DE
Published: April 2017

A taxonomic study of the fern genera Austroblechnum, Cranfillia, Neoblechnum, Lomaridium, and Telmatoblechnum, formerly Blechnum s.l. (Blechnaceae, Polypodiopsida), was conducted in southern and southeastern Brazil (Minas Gerais, Espírito Santo, Rio de Janeiro, São Paulo, Paraná, Santa Catarina, and Rio Grande do Sul) and 11 species were recognized (six of Austroblechnum, two of Cranfillia, one of Neoblechnum, one of Lomaridium, and one of Telmatoblechnum). One species has a circum-Antarctic distribution (plus Mexico), three species have a broadly Neotropical distribution, six species are restricted or almost restricted to South America and one is endemic to Brazil. New records are presented for six species in states from southeastern Brazil, in other regions of the country, as well as in other countries. Taxonomic descriptions, synonymies, lectotypifications, geographical distributions, and comments are presented for all genera and species occurring in the study area. We also give keys for the identification of Brazilian genera of Blechnaceae and for species of the genera treated here.
Laurobasidium hachijoense, comb. nov. (Cryptobasidiaceae) causing aerialroot-like galls on Cinnamomum japonicum in Japan
Authors: KAKISHIMA MAKOTO , NAGAO HIDEYUKI , DENCHEV CVETOMIR M.
Published: April 2017

A new combination, Laurobasidium hachijoense, is proposed to accommodate Exobasidium hachijoense from Japan, producing aerialroot-like galls on stems of Cinnamomum japonicum. This combination is based on the presence of a gastroid-like sporulation on the surface of the galls, and is supported also by the host-plant specialization and molecular data.
A new species of Dianthus (Caryophyllaceae) from Republic of Korea
Authors: SON DONG CHAN , KIM HYUN-JUN , CHANG KAE SUN , LEE DONG-HYUK , LEE KANG-HYUP
Published: April 2017

Dianthus koreanus sp. nov., from Gyeongsangbuk-do, Republic of Korea, is described and illustrated. It is a chasmophyte growing on the rocks on the seashore in the eastern coast of Korea. The new species is similar to D. chinensis by its vegetative and floral morphology. Differential characters refer to the leaves (oblanceolate to oblong and greenish-gray coriaceous), and the bracts (3 pairs, each bract being elliptic to obovate with apex acute). The conservation status of D. koreanus was assessed according to the IUCN Red List criteria.
A new species of Buenia (Teleostei: Gobiidae) from the western Mediterranean Sea, with the description of this genus
Authors: KOVAČIĆ MARCELO , ORDINES FRANCES , SCHLIEWEN ULRICH K.
Published: April 2017

A new miniature gobiid species, Buenia massutii sp. nov. (Teleostei: Gobiidae) is described from the circalittoral bottom off the Balearic Islands, western Mediterranean. Phylogenetic analysis of the mitochondrial COI-barcoding fragment supports its species-level distinctiveness and the monophyly of the genus Buenia. A description and diagnosis of the genus Buenia is for the first time provided. Material of the new species was collected in 57–67 m depth from beam trawl samples carried out on red algae beds. The traits that differentiate the new species from two congeneric species are: anterior oculoscapular canal only semiclosed with pores σ, λ, κ, ω, α, ρ and additional pores and open furrows from interorbital part to pore ρ; posterior oculoscapular canal absent; suborbital row c with 5 papillae; scales in lateral series 26–28; pectoral fin rays 16; the second spine of the first dorsal fin the longest, reaching to or behind posterior end of the second dorsal fin in males when folded down; pelvic fin anterior membrane one sixth or less of length of spinous ray in midline depth; head length 31.2–32.5% of standard length; eye 32.8–35.7% of head length; caudal fin length 21.5–24.0% of standard length.
Calibration and Cross Validation of a Global Wind and Wave Database of Altimeter, Radiometer, and Scatterometer Measurements
Authors: Young I. R. , Sanina E. , Babanin A. V.
Published: April 2017

A combined satellite dataset consisting of nine altimeter, 12 radiometer, and two scatterometer missions of wind speed and wave height is calibrated in a consistent manner against NDBC data and independently validated against a separate buoy dataset. The data are investigated for stability as a function of time. Instances where there are discontinuities or drift in the data are identified and accounted for in the calibration. The performance of each of the instruments at extreme values is investigated using quantile–quantile comparisons with buoy data. The various instruments are cross validated at matchup locations where satellite ground tracks cross. The resulting calibrated and cross-validated dataset is believed to represent the largest global oceanographic dataset of its type, which includes multiple instrument types calibrated in a similar fashion.
Implementing Quality Control of High-Frequency Radar Estimates and Application to Gulf Stream Surface Currents
Authors: Haines Sara , Seim Harvey , Muglia Mike
Published: April 2017

Quality control procedures based on nonvelocity parameters for use with a short-range radar system are applied with slight modification to long-range radar data collected offshore of North Carolina. The radar footprint covers shelf and slope environments and includes a segment of the Gulf Stream (GS). Standard processed and quality controlled (QCD) radar data are compared with 4 months of acoustic Doppler current profiler (ADCP) time series collected at three different sites within the radar footprint. Two of the ADCP records are from the shelf and the third is on the upper slope and is frequently within the GS. Linear regression and Bland–Altman diagrams are used to quantify the comparison. QCD data at all sites have reduced scatter and improved correlation with ADCP observations relative to standard processed data. Uncertainty is reduced by approximately 20%, and linear regression slopes and correlation coefficients increase by about 0.1. At the upper slope site, the QCD data also produced a significant increase in the mean speed. Additionally, a significant increase, averaging roughly 20%, in mean speed in the GS is apparent when comparing standard processed data and QCD data, concentrated at large range and at the azimuthal extremes of radial site coverage. Shifts in the distributions of the standard processed and QCD velocity estimates are consistent with the removal of zero-mean noise from the observations, which has minimal impact where the radial site range is <70 km and a large impact at greater range in the GS where mean currents exceed 1 m s−1.
Gender Variations in In-Hospital Mortality in Patients Hospitalized With Dizziness: A Retrospective Study
Authors: Salam Amar M. , AlBinali Hajar A. , Singh Rajvir , Al-Qahtani Awad , Asaad Nidal , Al Suwaidi Jassim
Published: April 2017

Women with cardiac diseases generally have a higher mortality than men. Suggested reasons include delay in reporting to hospital, less aggressive management, and higher cardiovascular risk profiles in women. We assessed gender differences in patients hospitalized with dizziness. We retrospectively reviewed the database of patients hospitalized with acute cardiac disease in Qatar from 1991 to the end of 2010. Patients hospitalized with dizziness were analyzed; 1611 (3.8%; 95% confidence interval [CI]: 3.6%-4%) of the total N = 42 144 patients were hospitalized with dizziness during the 20 years: 410 (25.5%) females and 1201 (74.5%) males. Mean age (female 55 [16] and male 53 [16] years) was comparable ( P = .06). Women had more hypertension, diabetes mellitus, palpitation, and arrhythmia compared with men. In-hospital mortality was 3.8% (women 5.6% vs men 3.2%, P = .03). After adjusting for potential confounders, female gender remained an independent factor for increased in-hospital mortality (adjusted odds ratio: 2.2, 95% CI: 1.21-4, P = .01). In this 20-year data set from a Middle Eastern country, female gender was an independent factor associated with increased in-hospital mortality in patients hospitalized with dizziness after adjusting for confounders. Further research is warranted to confirm this novel gender difference.
Macrophage Response to Allogeneic Adipose Tissue-Derived Stromal Cells in Hyaluronan-Based Hydrogel in a Porcine Vocal Fold Injury Model
Authors: King Suzanne N. , Woo Joo Hyun , Tang Sharon , Thibeault Susan L.
Published: April 2017

Objective:

Adipose tissue-derived stromal cells (ASC) embedded in hyaluronan scaffold is a beneficial prophylactic treatment for vocal fold (VF) surgical scar. Here, we investigated the macrophage inflammatory response to allogeneic ASC-constructs and identified changes in lamina propria extracellular matrix.

Method:

Pig ASC were characterized and transfected with GFP+ lentivirus. Thirty-three pigs underwent VF biopsies, and after 3 days, gel alone, gel+pASC, placebo, or pASC alone was injected into wound bed. Animals were sacrificed 3, 7, or 26 days post-injection. Flow cytometry; qPCR for NF-α, TGFβ, IL-10, IL-4, IFNγ, IL-12, FGF2, Col1A1, and HGF; and immunohistochemistry for collagen, elastin, HA, and fibronectin were performed to characterize macrophage phenotype, quantify cytokine transcription, analyze extracellular matrix remodeling, and track GFP+ cells.

Results:

No significant differences were found in SWC3+/SWC9+ phenotype or mRNA expression between cells+gel, gel, or placebo. The ASC alone exhibited significantly greater collagen, gel alone resulted in significantly less hyaluronan, and gel+pASC significantly more fibronectin (all P < .05). The pASC-GFP+ were detected 26 days post-injection.

Conclusions:

The ASC-constructs were biocompatible; they did not influence the macrophage inflammatory response or provoke increases in collagen expression. Long-term engraftment was confirmed.
Seeding, Referral, and Recommendation
Authors: Haenlein Michael , Libai Barak
Published: April 2017

In recent years, word-of-mouth (WOM) marketing has been the subject of considerable interest among managers and academics alike. However, there is very little common knowledge on what drives the value of WOM programs and how they should be designed to optimize value. Firms therefore frequently rely on relatively simple metrics to measure the success of their WOM marketing efforts and mainly use rules of thumb when making crucial program design decisions. This article proposes a new method to measure WOM program value that is based on the impact of WOM on the firm’s customer equity. It then provides recommendations for the five main questions managers face when planning a WOM program: Who to target? When to launch the program? Where to launch it? Which incentives to offer? and How many participants to include?
Supervising Projects You Don’t (Fully) Understand
Authors: Loch Christoph , Mähring Magnus , Sommer Svenja
Published: April 2017

Strategically important projects involve high stakes, uncertainty, and stakeholder complexity, with contingencies and risks typically surfacing repeatedly as the project evolves. This is challenging not only for the project team (PT) but also in particular for the steering committee (SC), the top management oversight structure typically used to align a project with the organization’s strategic goals. This article explores how senior executives on SCs can exercise leadership and effective oversight of strategic projects, although they have only limited time and often incomplete expertise. The SC can keep a project aligned, even with limited time, through focused understanding of the key logic and drivers of the project. The SC needs to manage the surprises and crises that inevitably arise in a difficult project through proactive analysis that goes to the bottom of the problem and by working with the PT to generate solutions.
Misspecification of Attribute Structure in Diagnostic Measurement
Authors: Liu Ren
Published: April 2017

Attribute structure is an explicit way of presenting the relationship between attributes in diagnostic measurement. The specification of attribute structures directly affects the classification accuracy resulted from psychometric modeling. This study provides a conceptual framework for understanding misspecifications of attribute structures. Under the framework, each attribute structure can be represented through an external shape and an internal organization. A simulation study and an application example were used to investigate how misspecification of external shapes and internal organizations affects model fit and item fit assessments, and respondent classification. The proposed framework and simulation results aim to support using attribute structures to (a) develop better diagnostic assessments and (b) inform theories of constructs.
D'Annunzio’s Il piacere: A Generational Gaze on New Values
Authors: Di Mauro-Jackson Moira
Published: April 2017

This paper centers on the nature of Gabriele d’Annunzio’s first, and very influential novel, Il piacere, and its influence on Italian thought at the time. I argue that Il piacere is truly a breviary, to borrow Cevasco’s term, a bible—or in socio-economic terms, a manifesto—for its time. I draw from Charles Altieri’s Radical Poetics and from Martin Puchner’s Poetry of the Revolution: Marx, Manifestos and the Avant-Gardes to prove that Il piacere is indeed a social critique of its time, an attempt by D’Annunzio to bridge the gap that Italian Unification produced by projecting a mostly agricultural country—which had long lost its epic stature, dating back to the Renaissance years—into modern thought and society.