bluuebunny/crossref_metadata_2025 huggingface dataset:
Particulate matter emissions over the oil sands regions in Alberta, Canada
Authors: Xing Zhenyu , Du Ke
Published: June 2017

Particulate matter (PM) emissions from the expanded oil sands development in Alberta are becoming a focus among the aerosol science community because of its significant negative impact on the regional air quality and climate change. Open-pit mining, petroleum coke (petcoke) dust, and the transportation of oil sands and waste materials by heavy-duty trucks on unpaved roads could release PM into the air. Incomplete combustion of fossil fuels by engines and stationary boilers leads to the formation of carbonaceous aerosols. In addition, wildfire and biogenic emissions surrounding the oil sands regions also have the potential to contribute primary PM to the ambient air. Secondary organic aerosol formation has been revealed as an important source of PM over nearby and distant areas from the oil sands regions. This review summarizes the primary PM sources and some secondary aerosol formation mechanisms that are linked to oil sands development. It also reviews the approaches that can be applied in aerosol source apportionment. Meteorological condition is an important factor that may influence the primary PM emission and secondary aerosol formation in Alberta’s oil sands regions. Current concern should not be limited to the primary emission of atmospheric PM. Secondary formation of aerosols, especially secondary organic aerosol originating from photochemical reaction, should also be taken into consideration. To obtain a more comprehensive understanding of the sources and amount of PM emissions based on the bottom-up emission inventory approach, investigations on how to reduce the uncertainty in determination of real-world PM emission factors for the variable sources are needed. Long-range transport trajectories of fine PM from Alberta’s oil sands regions remain unknown.
Microbiome and NAFLD: potential influence of aerobic fitness and lifestyle modification
Authors: Panasevich Matthew R. , Peppler Willem T. , Oerther Daniel B. , Wright David C. , Rector R. Scott
Published: June 2017

Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease with prevalence rates that are on the rise in the US and worldwide. NAFLD encompasses a spectrum of liver pathologies including simple steatosis to nonalcoholic steatohepatitis (NASH) with inflammation and fibrosis. The gut microbiome has emerged as a potential therapeutic target in combating metabolic diseases including obesity, Type 2 diabetes, and NAFLD/NASH. Diet-induced obesity/Western style diet feeding causes severe microbial dysbiosis initiating a microbiome signature that promotes metabolite production that directly impacts hepatic metabolism. Changes in lifestyle (i.e., diet, exercise, and aerobic fitness) improve NAFLD outcomes and can significantly influence the microbiome. However, directly linking lifestyle-induced remodeling of the microbiome to NAFLD pathogenesis is not well understood. Understanding the reshaping of the microbiome and the metabolites produced and their subsequent actions on hepatic metabolism are vital in understanding the gut-liver axis. In this review, we 1) discuss microbiome-derived metabolites that significantly contribute to the gut-liver axis and are directly linked to NAFLD/NASH and 2) present evidence on lifestyle modifications reshaping the microbiome and the potential therapeutic aspects in combating the disease.
Precision Medicine in Pediatric Oncology: Translating Genomic Discoveries into Optimized Therapies
Authors: Tran Thai Hoa , Shah Avanthi Tayi , Loh Mignon L.
Published: June 2017

Survival of children with cancers has dramatically improved over the past several decades. This success has been achieved through improvement of combined modalities in treatment approaches, intensification of cytotoxic chemotherapy for those with high-risk disease, and refinement of risk stratification incorporating novel biologic markers in addition to traditional clinical and histologic features. Advances in cancer genomics have shed important mechanistic insights on disease biology and have identified “driver” genomic alterations, aberrant activation of signaling pathways, and epigenetic modifiers that can be targeted by novel agents. Thus, the recently described genomic and epigenetic landscapes of many childhood cancers have expanded the paradigm of precision medicine in the hopes of improving outcomes while minimizing toxicities. In this review, we will discuss the biologic rationale for molecularly targeted therapies in genomically defined subsets of pediatric leukemias, solid tumors, and brain tumors. Clin Cancer Res; 23(18); 5329–38. ©2017 AACR.
Human Papillomavirus DNA Methylation Predicts Response to Treatment Using Cidofovir and Imiquimod in Vulval Intraepithelial Neoplasia 3
Authors: Jones Sadie E.F. , Hibbitts Samantha , Hurt Christopher N. , Bryant Dean , Fiander Alison N. , Powell Ned , Tristram Amanda J.
Published: June 2017

Purpose: Response rates to treatment of vulval intraepithelial neoplasia (VIN) with imiquimod and cidofovir are approximately 57% and 61%, respectively. Treatment is associated with significant side effects and, if ineffective, risk of malignant progression. Treatment response is not predicted by clinical factors. Identification of a biomarker that could predict response is an attractive prospect. This work investigated HPV DNA methylation as a potential predictive biomarker in this setting.

Experimental Design: DNA from 167 cases of VIN 3 from the RT3 VIN clinical trial was assessed. HPV-positive cases were identified using Greiner PapilloCheck and HPV 16 type-specific PCR. HPV DNA methylation status was assessed in three viral regions: E2, L1/L2, and the promoter, using pyrosequencing.

Results: Methylation of the HPV E2 region was associated with response to treatment. For cidofovir (n = 30), median E2 methylation was significantly higher in patients who responded (P ≤ 0.0001); E2 methylation >4% predicted response with 88.2% sensitivity and 84.6% specificity. For imiquimod (n = 33), median E2 methylation was lower in patients who responded to treatment (P = 0.03; not significant after Bonferroni correction); E2 methylation <4% predicted response with 70.6% sensitivity and 62.5% specificity.

Conclusions: These data indicate that cidofovir and imiquimod may be effective in two biologically defined groups. HPV E2 DNA methylation demonstrated potential as a predictive biomarker for the treatment of VIN with cidofovir and may warrant investigation in a biomarker-guided clinical trial. Clin Cancer Res; 23(18); 5460–8. ©2017 AACR.
Phase Ib Study of Lumretuzumab Plus Cetuximab or Erlotinib in Solid Tumor Patients and Evaluation of HER3 and Heregulin as Potential Biomarkers of Clinical Activity
Authors: Meulendijks Didier , Jacob Wolfgang , Voest Emile E. , Mau-Sorensen Morten , Martinez-Garcia Maria , Taus Alvaro , Fleitas Tania , Cervantes Andres , Lolkema Martijn P. , Langenberg Marlies H.G. , De Jonge Maja J. , Sleijfer Stefan , Han Ji-Youn , Calles Antonio , Felip Enriqueta , Kim Sang-We , Schellens Jan H.M. , Wilson Sabine , Thomas Marlene , Ceppi Maurizio , Meneses-Lorente Georgina , James Ian , Vega-Harring Suzana , Dua Rajiv , Nguyen Maitram , Steiner Lori , Adessi Celine , Michielin Francesca , Bossenmaier Birgit , Weisser Martin , Lassen Ulrik N.
Published: June 2017

Purpose: This study investigated the safety, clinical activity, and target-associated biomarkers of lumretuzumab, a humanized, glycoengineered, anti-HER3 monoclonal antibody (mAb), in combination with the EGFR-blocking agents erlotinib or cetuximab in patients with advanced HER3-positive carcinomas.

Experimental Design: The study included two parts: dose escalation and dose extension phases with lumretuzumab in combination with either cetuximab or erlotinib, respectively. In both parts, patients received lumretuzumab doses from 400 to 2,000 mg plus cetuximab or erlotinib according to standard posology, respectively. The effect of HRG mRNA and HER3 mRNA and protein expression were investigated in a dedicated extension cohort of squamous non–small cell lung cancer (sqNSCLC) patients treated with lumretuzumab and erlotinib.

Results: Altogether, 120 patients were treated. One dose-limiting toxicity (DLT) in the cetuximab part and two DLTs in the erlotinib part were reported. The most frequent adverse events were gastrointestinal and skin toxicities, which were manageable. The objective response rate (ORR) was 6.1% in the cetuximab part and 4.2% in the erlotinib part. In the sqNSCLC extension cohort of the erlotinib part, higher tumor HRG and HER3 mRNA levels were associated with a numerically higher disease control rate but not ORR.

Conclusions: The toxicity profile of lumretuzumab in combination with cetuximab and erlotinib was manageable, but only modest clinical activity was observed across tumor types. In the sqNSCLC cohort, there was no evidence of meaningful clinical benefit despite enriching for tumors with higher HRG mRNA expression levels. Clin Cancer Res; 23(18); 5406–15. ©2017 AACR.
Unmetabolized Folic Acid, Tetrahydrofolate, and Colorectal Adenoma Risk
Authors: Rees Judy R. , Morris Carolyn B. , Peacock Janet L. , Ueland Per M. , Barry Elizabeth L. , McKeown-Eyssen Gail E. , Figueiredo Jane C. , Snover Dale C. , Baron John A.
Published: June 2017

In a randomized trial of folic acid supplementation for the prevention of colorectal adenomas, we previously found indications of increased risk during later treatment and follow-up. This could have been due to the unmetabolized folic acid (UFA) or natural reduced and methylated folates (mF) to which it is metabolized. In post hoc analyses, we measured mF (the sum of 5-methyl-tetrahydrofolate and 4-alfa-hydroxy-5-methyl-THF) and UFA concentrations in the serum of 924 participants. Using binomial regression models with a log link, we assessed the associations between plasma mF or UFA and adenoma occurrence. We found no association between plasma mF or UFA and overall adenoma risk. However, during later follow-up, the prespecified, composite endpoint of high-risk findings (advanced or multiple adenomas) was positively associated with plasma mF (Plinear trend = 0.009), with a 58% increased risk for participants in the upper versus lowest quartile. An irregular association was seen with plasma UFA, with suggestions of an inverse trend (Plinear trend=0.049). A modest, significant inverse association was also seen between mF and risk of serrated lesions, with a 39% lower risk for upper versus lower quartile participants (Plinear trend = 0.03). In conclusion, during the later follow-up period in which folic acid supplementation was previously seen to increase the risk of advanced and multiple adenomas, higher serum mF was associated with a higher risk of multiple and/or advanced adenomas, but no clear indication that UFA played a direct role. There were indications that higher mF was associated with reduced risk of serrated polyps. Cancer Prev Res; 10(8); 451–8. ©2017 AACR.
A Hepatitis C Virus-Associated Cirrhotic Patient Developing Interstitial Pneumonia during the Course of Antiviral Therapy with Ombitasvir/Paritaprevir/Ritonavir
Authors: Tarao Kazuo , Yamada Kouzo
Published: June 2017

Oral direct-acting antivirals (DAAs) are the main therapy for hepatitis C virus (HCV)-associated liver disease in Japan. Daclatasvir/asunaprevir is the first agent and sofosbuvir/ledipasvir is the secondary agent for HCV genotype 1b. More recently, ombitasvir/paritaprevir/ritonavir is also recommended as a potent therapy for HCV genotype 1b. Among the adverse events associated with these oral DAAs, interstitial pneumonia is one of the most severe ones. Regarding treatment with daclatasvir plus asunaprevir or sofosbuvir plus ledipasvir, a few cases have already been reported in a postmarketing surveillance. Recently, we have encountered a HCV-associated genotype 1b cirrhosis patient who developed interstitial pneumonia during treatment with ombitasvir/paritaprevir/ritonavir and who recovered after drug discontinuation without corticosteroid therapy. Interstitial pneumonia was confirmed by chest x-ray and chest computed tomography. The serum KL-6 level was elevated to 1,180 U/mL. The total duration of the drug administration was 7 weeks, and she achieved SVR24. This is the first detailed report in the literature on the development of interstitial pneumonia during treatment with ombitasvir/paritaprevir/ritonavir. When dry cough appeared in the treatment with DAAs, chest computed tomography and the evaluation of serum KL-6 level were recommended.
Perinatal Factors Affecting Serum Hepcidin Levels in Low-Birth-Weight Infants
Authors: Ichinomiya Kenji , Maruyama Kenichi , Inoue Takahiro , Koizumi Aya , Inoue Fumitaka , Fukuda Kazuyo , Yamazaki Yu , Arakawa Hirokazu
Published: June 2017

Background: Hepcidin, an iron-regulatory hormone, plays a key role in preventing iron overload. Few studies have investigated the regulation of hepcidin in low-birth-weight (LBW) infants who are vulnerable to iron imbalance. Objectives: To identify perinatal factors associated with serum hepcidin levels in LBW infants. Methods: Ninety-two LBW infants with a median gestational age (GA) of 32.6 weeks and birth weight of 1,587 g were prospectively enrolled. Serum hepcidin-25 (Hep25) levels were measured from umbilical cord blood using liquid chromatography-tandem mass spectrometry. The relationship between Hep25 levels and prematurity or other possible hepcidin-regulatory factors was evaluated. Results: The median Hep25 level was 7.3 ng/mL (interquartile range: 2.85-16.38). log(Hep25) correlated with birth weight (r = 0.229, p = 0.028), log(interleukin-6 [IL-6]) (r = 0.408, p < 0.001), log(erythropoietin) (r = -0.302, p = 0.004), transferrin saturation (r = 0.29, p = 0.005), soluble transferrin receptor (r = -0.500, p < 0.001), and log(ferritin) (r = 0.696, p < 0.001). Serum iron and hemoglobin levels did not correlate with log(Hep25). Hep25 levels were higher among infants with chorioamnionitis and infants born vaginally and lower among infants born to mothers with pregnancy-induced hypertension than among infants without the respective characteristics. Stepwise multiple linear regression analysis confirmed the significant association of log(Hep25) with GA, log(IL-6), log(erythropoietin), and soluble transferrin receptor. Conclusions: Among LBW infants, GA, IL-6, erythropoietin, and soluble transferrin receptor were associated with Hep25 levels. Therefore, prematurity, inflammation, hypoxia, and erythropoietic activity may be important perinatal factors that affect hepcidin levels.
AUNA2: A Novel Type of Non-Syndromic Slowly Progressive Auditory Synaptopathy/Auditory Neuropathy with Autosomal-Dominant Inheritance
Authors: Lang-Roth Ruth , Fischer-Krall Eva , Kornblum Cornelia , Nürnberg Gudrun , Meschede Dieter , Goebel Ingrid , Nürnberg Peter , Beutner Dirk , Kubisch Christian , Walger Martin , Volk Alexander E.
Published: June 2017

Background: Auditory synaptopathy/neuropathy (AS/AN) is a heterogeneous disorder, which may be caused by environmental factors like postnatal hyperbilirubinemia or by genetic factors. The genetic forms are subdivided into syndromic and non-syndromic types, and show different inheritance patterns with a strong preponderance of autosomal-recessive forms. To date, only a single locus for non-syndromic autosomal-dominant AS/AN (AUNA1) has been reported in a single family, in which a non-coding DIAPH3 mutation was subsequently described as causative. Materials and Methods: Here, we report detailed clinical data on a large German AS/AN family with slowly progressive postlingual hearing loss. Affected family members developed their first symptoms in their second decade. Moderate hearing loss in the fourth decade then progressed to profound hearing impairment in older family members. Comprehensive audiological and neurological tests were performed in the affected family members. Genetic testing comprised linkage analyses with polymorphic markers and a genome-wide linkage analysis using the Affymetrix GeneChip® Human Mapping 250K. Results and Conclusion: We identified a large family with autosomal-dominant AS/AN. By means of linkage analyses, the AUNA1 locus was excluded, and putatively linked regions on chromosomal bands 12q24 and 13q34 were identified as likely carrying the second locus for autosomal-dominant AS/AN (AUNA2). AUNA2 is associated with a slowly progressive postlingual hearing loss without any evidence for additional symptoms in other organ systems.
Disappearance of the Hemorrhagic Component of the Frontal Contusion Possibly due to Redistribution of the Hematoma within the Subarachnoid Space: A Case Report
Authors: Faheem Mohd , Jaiswal Manish , Ojha Bal Krishna , Chandra Anil , Singh Sunil Kumar , Srivastava Chhitij , Saba Noor Us
Published: June 2017

Posttraumatic hemorrhagic contusions are a common sequel of traumatic brain injuries. They occur in around 8% of all traumatic brain injuries. Spontaneous resolution of acute subdural and acute extradural hematomas, although rare, is a recognized entity, but spontaneous resolution of the hemorrhagic component of a contusion within 24 h has not been reported in the literature. We present a patient in whom the hemorrhagic component of her contusion resolved spontaneously over a period of 24 h after injury. The rarity of this case prompted us to this study.
Outcomes in Melanoma Patients Treated with BRAF/MEK-Directed Therapy or Immune Checkpoint Inhibition Stratified by Clinical Trial versus Standard of Care
Authors: Goldman Chloe , Tchack Jeremy , Robinson Eric M. , Han Sung Won , Moran Una , Polsky David , Berman Russell S. , Shapiro Richard L. , Ott Patrick A. , Osman Iman , Zhong Hua , Pavlick Anna C. , Wilson Melissa Ann
Published: June 2017

Objectives: Since 2011, metastatic melanoma treatment has evolved with commercial approval of BRAF- and MEK-targeted therapy and CTLA-4- and PD-1-blocking antibodies (immune checkpoint inhibitors, ICI). While novel therapies have demonstrated improved prognosis in clinical trials, few studies have examined the evolution of prognosis and toxicity of these drugs among an unselected population. We assess whether survival and toxicity reported in trials, which typically exclude most patients with brain metastases and poor performance status, are recapitulated within a commercial access population. Methods: 182 patients diagnosed with stage IV melanoma from July 2006 to December 2013 and treated with BRAF- and/or MEK-targeted therapy or ICI were prospectively studied. Outcomes and clinicopathologic differences between trial and commercial cohorts were assessed. Results: Patients receiving commercial therapy (vs. on trial) had poorer prognostic features (i.e., brain metastases) and lower median overall survival (mOS) when assessed across all treatments (9.2 vs. 17.5 months, p = 0.0027). While toxicity within trial and commercial cohorts did not differ, patients who experienced toxicity had increased mOS (p < 0.001), irrespective of stratification by trial status or therapy. Conclusion: Metastatic melanoma patients receiving commercial treatment may represent a different clinical population with poor prognostic features compared to trial patients. Toxicity may prognosticate treatment benefit.
Small Cell Cancer of the Genitourinary Tract: A Case Report and Review of the Literature
Authors: Yeung Ho Man , Jeurkar Chetan , Pompa Tiffany , Styler Michael
Published: June 2017

Small cell carcinoma of the urinary tract is an extremely rare disease with very few cases reported in the literature. Its clinical course is aggressive, and the prognosis is poor. Here, we present a case of metastatic extrapulmonary small cell carcinoma of the upper urinary tract in a 74-year-old African-American male. He initially presented with gross hematuria, 20-pound weight loss, and abdominal pain for 2 months. CT imaging showed a 14.0 × 7.0 × 16.0 cm retroperitoneal mass within the left renal fossa; biopsy revealed a carcinoma which was positive for synaptophysin and chromogranin. The patient also had detectable neuroendocrine cells in his urine cytology, confirming the diagnosis of small cell carcinoma. He was treated with carboplatin and etoposide as extrapolated from the treatment of its pulmonary counterpart. Due to the rarity of urinary tract small cell carcinoma, no randomized studies exist to guide therapy or management.
Safety and Efficacy of Intravesical Bacillus Calmette-Guérin Immunotherapy in Patients with Non-Muscle-Invasive Bladder Cancer Presenting with Asymptomatic Bacteriuria: A Systematic Review
Authors: Poletajew Sławomir , Zapała Piotr , Radziszewski Piotr
Published: June 2017

Intravesical Bacillus Calmette-Guérin (BCG) immunotherapy in bladder cancer patients with asymptomatic bacteriuria (ABU) remains a matter of debate. The aim of this systematic review was to present available evidence on the safety and efficacy of BCG immunotherapy in patients with ABU. A literature search within the Medline and the Embase databases was conducted with the following search terms: adverse events, bacteriuria, BCG, bladder cancer, cystitis, infection, pyuria, side effects and urinary tract infection (UTI). Sixteen relevant original articles were identified, including 6 articles directly presenting the safety or efficacy of BCG therapy in patients with ABU. None of them was a randomized controlled trial. Intravesical BCG instillations in patients with ABU were not associated with the increased risk of symptomatic UTI and did not affect negatively the recurrence- or progression-free survival. Routine urine analysis before BCG instillation created increased cost and potentially unnecessary delays in BCG therapy. ABU does not affect negatively the safety and efficacy of intravesical BCG immunotherapy. There is no evidence to support routine screening and treatment of ABU in patients scheduled for intravesical BCG instillations due to bladder cancer. However, this issue was not addressed adequately and needs further research.
Activities of MSCs Derived from Transgenic Mice Seeded on ADM Scaffolds in Wound Healing and Assessment by Advanced Optical Techniques
Authors: Wang Ning , Liu Hanping , Li Xuefeng , Zhang Qilei , Chen Maosheng , Jin Ying , Deng Xiaoyuan
Published: June 2017

Background/Aims: Bone marrow Mesenchymal stem cells (MSCs) are promising for promoting cutaneous wound healing through reinforcing cellular processes. We evaluated the effect of GFP-tagged MSCs transplantation on skin regeneration in excisional wounds in mice. Methods: MSCs from GFP-labeled transgenic mice were co-cultured with acellular dermal matrix (ADM) scaffolds, and MSC-ADM scaffolds were transplanted into surgical skin wounds of BALB/c mice. After implantation, the survival and behavior of MSCs were examined by second harmonic generation and two-photon excitation fluorescence imaging, western blotting and DNA amplification and sequencing. Results: GFP-tagged MSCs were retained inside the regenerating skin until day 14 post-transplantation. Alpha-smooth muscle actin (α-SMA) and vimentin (VIM) were detected at 3, 5, 7, and 14 days post-transplantation by immunofluorescence double labeling. Although the GFP+/α-SMA+- and GFP+/VIM+-cell numbers decreased gradually with healing time, α-SMA+- and VIM+-cell numbers significantly increased, most of them were endogenous functional cells which were related to angiogenesis and collagen fiber structural remodeling. Conclusion: Therefore, in the initial stage of wound healing, transplanted MSCs differentiated into functional cells and played paracrine roles to recruit more endogenous cells for tissue remodeling. With the disappearance of exogenous cells, endogenous cells were responsible for the latter stage of cutaneous wound healing.
Genetic Testing in the Evaluation of Unexplained Cardiac Arrest
Authors: Mellor Greg , Laksman Zachary W.M. , Tadros Rafik , Roberts Jason D. , Gerull Brenda , Simpson Christopher S. , Klein George J. , Champagne Jean , Talajic Mario , Gardner Martin , Steinberg Christian , Arbour Laura , Birnie David H. , Angaran Paul , Leather Richard , Sanatani Shubhayan , Chauhan Vijay S. , Seifer Colette , Healey Jeffrey S. , Krahn Andrew D.
Published: June 2017

Background—

Unexplained cardiac arrest may be because of an inherited arrhythmia syndrome. The role of genetic testing in cardiac arrest survivors without a definite clinical phenotype is unclear.

Methods and Results—

The CASPER (Cardiac Arrest Survivors with Preserved Ejection Fraction Registry) is a large registry of cardiac arrest survivors where initial assessment reveals normal coronary arteries, left ventricular function, and resting ECG. Of 375 cardiac arrest survivors in CASPER from 2006 to 2015, 174 underwent genetic testing. Patients were classified as phenotype-positive (n=72) or phenotype-negative (n=102). Genetic testing was performed at treating physicians’ discretion in line with contemporary guidelines and availability. All genetic variants identified from original laboratory reports were reassessed by the investigators in line with modern criteria. Pathogenic variants were identified in 29 (17%) patients (60% channelopathy-associated and 40% cardiomyopathy-associated genes) and 70 variants of unknown significance were identified in 32 (18%) patients. Prior syncope (odds ratio, 4.0; 95% confidence interval, 1.6–9.7) and a family history of sudden death (odds ratio, 3.2; 95% confidence interval, 1.1–9.4) were independently associated with the presence of a pathogenic variant. In phenotype-negative patients, broad multiphenotype genetic testing led to higher yields (21% versus 8%;
P
=0.04) but was associated with more variants of unknown significance (55% versus 5%;
P
<0.01).

Conclusions—

Genetic testing identifies a pathogenic variant in a significant proportion of unexplained cardiac arrest survivors. Prior syncope and family history of sudden death are predictors of a positive genetic test. Both arrhythmia and cardiomyopathy genes are implicated. Broad, multiphenotype testing revealed the highest frequency of pathogenic variants in phenotype-negative patients.

Clinical Trial Registration—

https://www.clinicaltrials.gov
. Unique Identifier: NCT00292032
Quantifying the Shift Toward Transcatheter Aortic Valve Replacement in Low-Risk Patients
Authors: De Sciscio Paolo , Brubert Jacob , De Sciscio Michele , Serrani Marta , Stasiak Joanna , Moggridge Geoff D.
Published: June 2017

Background—

In recent years, use of transcatheter aortic valve replacement has expanded to include patients at intermediate- and low-risk cohorts. We sought to determine disease prevalence and treatment distribution including transcatheter aortic valve replacement eligibility in low-risk patients across 37 advanced economies.

Methods and Results—

Four systematic searches were conducted across MEDLINE, EMBASE, and the Cochrane database for studies evaluating disease prevalence, severity, decision making, and survival in patients with aortic stenosis. Estimates of disease prevalence and treatment eligibility were calculated using stochastic simulation and population data for the 37 countries comprising the International Monetary Fund’s advanced economies index. Fifty-six studies comprising 42 965 patients were included across 5 domains: prevalence, severity, symptom status, treatment modality, and outcome. The pooled prevalence in the general population aged 60 to 74 years and >75 years was 2.8% (95% confidence interval [CI], 1.4%–4.1%) and 13.1% (95% CI, 8.2%–17.9%), respectively—corresponding to an estimated 16.1 million (95% CI, 12.2–20.3) people in 37 advanced economies. Of these, an estimated 3.2 million (95% CI, 2.2–4.4) patients have severe aortic stenosis with 1.9 million (95% CI, 1.3–2.6) eligible for surgical aortic valve replacement. There are ≈485 230 (95% CI, 284 550–66 7350) high-risk/inoperable patients, 152 690 (95% CI, 73 410–263 000) intermediate-risk patients, and 378 890 (95% CI, 205 130–610 210) low-risk patients eligible for transcatheter aortic valve replacement.

Conclusions—

With a prevalence of 4.5%, an estimated 16.1 million people aged ≥60 years across 37 advanced economies have aortic stenosis. Of these, there are ≈1.9 million patients eligible for surgical aortic valve replacement and 1.0 million patients eligible for transcatheter aortic valve replacement.
Comparison of a Drug‐Free Early Programmed Dismantling PDLLA Bioresorbable Scaffold and a Metallic Stent in a Porcine Coronary Artery Model at 3‐Year Follow‐Up
Authors: Yahagi Kazuyuki , Yang Yi , Torii Sho , Mensah Johanne , White Roseann M. , Mathieu Marion , Pacheco Erica , Nakano Masataka , Barakat Abdul , Sharkawi Tahmer , Vert Michel , Joner Michael , Finn Aloke V. , Virmani Renu , Lafont Antoine
Published: June 2017

Background

Arterial Remodeling Technologies bioresorbable scaffold (
ART
‐
BRS
), composed of
l
‐ and
d
‐lactyl units without drug, has shown its safety in a porcine coronary model at 6 months. However, long‐term performance remains unknown. The aim of this study was to evaluate the
ART
‐
BRS
compared to a bare metal stent (
BMS
) in a healthy porcine coronary model for up to 3 years.

Methods and Results

Eighty‐two
ART
‐
BRS
and 66
BMS
were implanted in 64 Yucatan swine, and animals were euthanatized at intervals of 1, 3, 6, 9, 12, 18, 24, and 36 months to determine the vascular response using quantitative coronary angiography, optical coherence tomography, light and scanning electron microscopy, and molecular weight analysis. Lumen enlargement was observed in
ART
‐
BRS
as early as 3 months, which progressively increased up to 18 months, whereas
BMS
showed no significant difference over time. Percentage area stenosis by optical coherence tomography was greater in
ART
‐
BRS
than in
BMS
at 1 and 3 months, but this relationship reversed beyond 3 months. Inflammation peaked at 6 months and thereafter continued to decrease up to 36 months. Complete re‐endothelialization was observed at 1 month following implantation in both
ART
‐
BRS
and
BMS
. Scaffold dismantling started at 3 months, which allowed early vessel enlargement, and bioresorption was complete by 24 months.

Conclusions

ART
‐
BRS
has the unique quality of early programmed dismantling accompanied by vessel lumen enlargement with mild to moderate inflammation. The main distinguishing feature of the
ART
‐
BRS
from other scaffolds made from poly‐
l
‐lactic acid may result in early and long‐term vascular restoration.
Direct Estimation of the Derivative of Quadratic Mutual Information with Application in Supervised Dimension Reduction
Authors: Tangkaratt Voot , Sasaki Hiroaki , Sugiyama Masashi
Published: June 2017

A typical goal of linear-supervised dimension reduction is to find a low-dimensional subspace of the input space such that the projected input variables preserve maximal information about the output variables. The dependence-maximization approach solves the supervised dimension-reduction problem through maximizing a statistical dependence between projected input variables and output variables. A well-known statistical dependence measure is mutual information (MI), which is based on the Kullback-Leibler (KL) divergence. However, it is known that the KL divergence is sensitive to outliers. Quadratic MI (QMI) is a variant of MI based on the [Formula: see text] distance, which is more robust against outliers than the KL divergence, and a computationally efficient method to estimate QMI from data, least squares QMI (LSQMI), has been proposed recently. For these reasons, developing a supervised dimension-reduction method based on LSQMI seems promising. However, not QMI itself but the derivative of QMI is needed for subspace search in linear-supervised dimension reduction, and the derivative of an accurate QMI estimator is not necessarily a good estimator of the derivative of QMI. In this letter, we propose to directly estimate the derivative of QMI without estimating QMI itself. We show that the direct estimation of the derivative of QMI is more accurate than the derivative of the estimated QMI. Finally, we develop a linear-supervised dimension-reduction algorithm that efficiently uses the proposed derivative estimator and demonstrate through experiments that the proposed method is more robust against outliers than existing methods.
Implementing a Bayes Filter in a Neural Circuit: The Case of Unknown Stimulus Dynamics
Authors: Sokoloski Sacha
Published: June 2017

In order to interact intelligently with objects in the world, animals must first transform neural population responses into estimates of the dynamic, unknown stimuli that caused them. The Bayesian solution to this problem is known as a Bayes filter, which applies Bayes' rule to combine population responses with the predictions of an internal model. The internal model of the Bayes filter is based on the true stimulus dynamics, and in this note, we present a method for training a theoretical neural circuit to approximately implement a Bayes filter when the stimulus dynamics are unknown. To do this we use the inferential properties of linear probabilistic population codes to compute Bayes' rule and train a neural network to compute approximate predictions by the method of maximum likelihood. In particular, we perform stochastic gradient descent on the negative log-likelihood of the neural network parameters with a novel approximation of the gradient. We demonstrate our methods on a finite-state, a linear, and a nonlinear filtering problem and show how the hidden layer of the neural network develops tuning curves consistent with findings in experimental neuroscience.
Recurrent Information Optimization with Local, Metaplastic Synaptic Dynamics
Authors: Liu Sensen , Ching ShiNung
Published: June 2017

We consider the problem of optimizing information-theoretic quantities in recurrent networks via synaptic learning. In contrast to feedforward networks, the recurrence presents a key challenge insofar as an optimal learning rule must aggregate the joint distribution of the whole network. This challenge, in particular, makes a local policy (i.e., one that depends on only pairwise interactions) difficult. Here, we report a local metaplastic learning rule that performs approximate optimization by estimating whole-network statistics through the use of several slow, nested dynamical variables. These dynamics provide the rule with both anti-Hebbian and Hebbian components, thus allowing for decorrelating and correlating learning regimes that can occur when either is favorable for optimality. We demonstrate the performance of the synthesized rule in comparison to classical BCM dynamics and use the networks to conduct history-dependent tasks that highlight the advantages of recurrence. Finally, we show the consistency of the resultant learned networks with notions of criticality, including balanced ratios of excitation and inhibition.
Jewish Philosophy, Science of Judaism and Philology in Salomon Munk and Samuel David Luzzatto’s Letters Exchange
Authors: Adorisio Chiara
Published: June 2017

The correspondence of the Italian Hebraist Samuel David Luzzatto (1800–1865) and the German-Jewish Orientalist Salomon Munk (1803–1867) sheds light on the trans-European dimension of the movement known as the Science of Judaism. This article is based on the reconstruction of the friendship between Luzzatto and Munk as reflected in Luzzatto’s letters to Munk in Paris. Their relationship was personal as well as intellectual: Luzzatto sent his son Philoxène, a promising Orientalist, to study under Munk’s supervision. Together with Munk’s letter to Philoxène, these letters provide us with details central to an understanding of the relationship between the two scholars. Although differing in their attitude toward Jewish faith and philosophy, Munk and Luzzatto shared a common interest in Hebrew and Oriental languages. Through their philological and linguistic studies, they challenged the Orientalistic attitude prevalent among European scholars and historians of philosophy in the first half of the nineteenth century.
Planning the Socialist Housing District in Bucharest and the Soviet influence, 1947–1960
Authors: Maxim Juliana
Published: June 2017

This article details some of the processes through which Romanian architectural culture transformed under Soviet influence in the 1950s and through which architects came to redefine the organization of the profession, the planning of the city, and methods of design.

The urban housing district (referred to as cvartal) and the rationalization of architectural design through type-solutions (tipizare or typization) were two architectural themes of particular political consequence and thus especially subjected to the pressures of Soviet precedent. The article shows, however, that the Soviet principles and policies brought to bear on the design of architectural types and the planning of the cvartal belonged in large part to a set of generic modernist principles that crossed political lines.

The article aims to nuance the negative view of Sovietization as the imposition of entirely foreign concerns: archival sources, publications of the time, and architectural examples show that Soviet models reoriented but continued preexisting Romanian preoccupations with the planning of the modern city. Furthermore, Sovietization was not an isolationist phenomenon that hindered innovation: rather than standing as an obstacle to modernization, Soviet models connected Romania’s architectural culture to international postwar debates on mass housing and new urban forms.
Ernest Weissmann’s “World City”
Authors: Tolic Ines
Published: June 2017

On July 26, 1963, the city of Skopje was struck by a powerful earthquake which left behind almost nothing but ruins. Financially precarious, technically unprepared and politically non-aligned, the Yugoslav government needed neutral, long-term and specialized technical assistance if the Macedonian capital was to be rebuilt. Thanks to mediation of Ernest Weissmann, an architect of Croatian origins and a un officer at ecosoc, the United Nations joined in the reconstruction on October 14, 1963, and, in the following years, some of the most renowned contemporary architects and urban planners were invited to present their vision for the New Skopje. According to Weissmann, the city was to became nothing less than a “world city,” providing solutions to the contemporary “urban crisis,” prescribing a cure for “sick cities,” and showing the way for the “humanization” of the built environment. Even though mostly unattained, these ambitious goals gave birth to an international debate about the future of both cities and city planning, which was decisive for the definition of the un’s later interventions. The goal of this paper is to deal with Skopje’s reconstruction, highlighting Ernest Weissmann’s role in it, and to describe the city as a node of knowledge within a network of specialists in urban matters established by the United Nations during and – most of all – in spite of the Cold War context.
Urban School District–University Research Collaboration: Challenges and Strategies for Success
Authors: Hartman Jenifer J.
Published: June 2017

School district–university research collaborations represent one strategy to increase educators’ ability to use current, research-based information in program decision making and efforts to improve student achievement. However, differences in organizational structures, goals, values, and prior collaborative experiences have made successful school–university research partnerships challenging. This project intentionally structured and examined a mutually beneficial research collaboration between one small urban university with a significant percentage of first-generation college-going students and two local school districts (P-12) to examine high school math achievement and subsequent college math success. One partnership successfully conducted the study and identified actions to increase student success. The other was successful only to the point of partial data collection. This article describes the structures, mechanisms, and conditions that led to the successful partnership and compares them with the unsuccessful one. It contributes to our understanding of developing effective, mutually beneficial school–university research collaborations to improve student outcomes.
A Right to Housing in the Suburbs: James v. Valtierra and the Campaign against Economic Discrimination
Authors: Cavin Aaron
Published: June 2017

In the landmark 1971 case of James v. Valtierra, the Supreme Court ruled that municipalities could block housing for the poor, bolstering a trend toward exclusionary zoning and economic segregation in suburban America. Scholarship on this trend has focused on the racial impacts of putatively nonracial policies, echoing activists at the time who saw economic exclusion as a disguised means of forestalling racial desegregation. This article, however, argues that a focus on racial desegregation misinterprets the campaign of affordable housing in the suburbs and obscures key claims made by affordable housing activists. It examines the history of James v. Valtierra, showing that the plaintiffs were a racially diverse group of women who already lived in the suburbs; they sought not desegregation but better housing conditions for single mothers and their families. The article suggests the importance of analyzing suburban diversity, gender, and economic discrimination in struggles for affordable housing.
Branch School Buildings in the St. Louis Public Schools District: Tools to Support the Segregative Neighborhood School Policy of the St. Louis Board of Education
Authors: Weathersby Claude , Weathersby Yolanda
Published: June 2017

During and after World War II, large numbers of African Americans from the former Confederate States migrated to St. Louis, Missouri. The pace of this migration placed a strain on the St. Louis Public Schools district. The district responded to the facilities shortage by constructing small branch school buildings in its compliance with de jure segregation laws in Missouri before 1954, and after 1954, in its efforts to covertly maintain a pseudo-integrated public school district’s neighborhood school policy.
Agency and Institutions in Organization Studies
Authors: Abdelnour Samer , Hasselbladh Hans , Kallinikos Jannis
Published: June 2017

Agency and institutions are essential concepts within institutional theory. In this Perspectives issue, we draw on a select group of Organization Studies articles to provide an overview of the topic of agency and institutions. We first consider different ways of defining agency and institutions and examine their implications for institutional theory. We then analyse the relationship of actors and institutions through four lenses – the wilful actor, collective intentionality, patchwork institutions and modular individuals. Our analysis leads us to dissociate agency from individuals and view it as a capacity or quality that stems from resources, rights and obligations tied to the roles and social positions actors occupy. Roles and social positions are institutionally engineered. It is social actors qua occupants of roles and positions (not individuals) that enter the social ‘stage’ and exercise agency.
In praise of chaotic research pathways: A feminist response to planetary urbanization
Authors: McLean Heather
Published: June 2017

This intervention contributes to feminist and queer responses to Brenner and Schmid’s ‘planetary urbanization’ thesis. I discuss the generative potential of their attempts to craft alternative urban research pathways and their critique of urban age discourse, a body of work that defines cities as static sites of ‘innovation’, ‘creativity’, and ‘sustainability’. However, echoing critics of the planetary urbanization approach, I contend that Brenner and Schmid’s research schema risks reproducing exclusionary analytical hierarchies by promoting a totalizing, ‘god-trick-like’ standpoint and ignoring marginalized feminist, queer, and praxis-oriented urban studies approaches. As a result, planetary urbanization ignores situated and relational knowledges and lived experience. Moreover, I question Brenner and Schmid’s efforts to bring order to what they perceive as ‘chaotic’ urban research. I then reflect on the feminist analytic tool kit I employ in my arts-based research in Glasgow, including performing with Fail Better, a cabaret that makes space for politicized artists and under-represented artists of colour, queer artists, and working class artists. I argue that planetary urbanization offers useful strategies for interrogating the globalized geo-economic processes propelling contemporary efforts to re-invent cities into sites of competitive creativity. But I also argue that this approach cannot account for the intersectional inequalities neoliberal regimes reproduce or uncover artists’ and activists’ efforts to forge solidarities. I conclude by calling for feminist, queer, and arts-based research journeys that embrace humility, dialogue, taking risks, and possibly failing in our efforts to chart alternative research pathways.
Modularity, working memory and language acquisition
Authors: Baddeley Alan D
Published: June 2017

The concept of modularity is used to contrast the approach to working memory proposed by Truscott with the Baddeley and Hitch multicomponent model. This proposes four sub components comprising the central executive, an executive control system of limited attentional capacity that utilises storage based on separate but interlinked temporary storage subsystems. One, the phonological loop, is concerned with the temporary storage of verbal materials and another, the visuo-spatial sketchpad stores visual information. A fourth component, the episodic buffer, allows the various components to interact and enables their content to become available to conscious awareness. After a brief description of the relevance of the model to language acquisition, an account is given of the way in which it has developed in recent years and its relationship to other approaches to working memory.
Antimicrobial and bone-forming activity of a copper coated implant in a rabbit model
Authors: Prinz Cornelia , Elhensheri Mohamed , Rychly Joachim , Neumann Hans-Georg
Published: June 2017

Current strategies in implant technology are directed to generate bioactive implants that are capable to activate the regenerative potential of the surrounding tissue. On the other hand, implant-related infections are a common problem in orthopaedic trauma patients. To meet both challenges, i.e. to generate a bone implant with regenerative and antimicrobial characteristics, we tested the use of copper coated nails for surgical fixation in a rabbit model. Copper acetate was galvanically deposited with a copper load of 1 µg/mm2 onto a porous oxide layer of Ti6Al4V nails, which were used for the fixation of a tibia fracture, inoculated with bacteria. After implantation of the nail the concentration of copper ions did not increase in blood which indicates that copper released from the implant was locally restricted to the fracture site. After four weeks, analyses of the extracted implants revealed a distinct antimicrobial effect of copper, because copper completely prevented both a weak adhesion and firm attachment of biofilm-forming bacteria on the titanium implant. To evaluate fracture healing, radiographic examination demonstrated an increased callus index in animals with copper coated nails. This result indicates a stimulated bone formation by releasing copper ions. We conclude that the use of implants with a defined load of copper ions enables both prevention of bacterial infection and the stimulation of regenerative processes.