bluuebunny/crossref_metadata_2025 huggingface dataset:
Enhanced Cancer Immunotherapy by Chimeric Antigen Receptor–Modified T Cells Engineered to Secrete Checkpoint Inhibitors
Authors: Li Si , Siriwon Natnaree , Zhang Xiaoyang , Yang Shuai , Jin Tao , He Feng , Kim Yu Jeong , Mac John , Lu Zhengfei , Wang Sijie , Han Xiaolu , Wang Pin
Published: September 2017

Purpose: Despite favorable responses of chimeric antigen receptor (CAR)-engineered T-cell therapy in patients with hematologic malignancies, the outcome has been far from satisfactory in the treatment of solid tumors, partially owing to the development of an immunosuppressive tumor microenvironment. To overcome this limitation, we engineered CAR T cells secreting checkpoint inhibitors (CPI) targeting PD-1 (CAR.αPD1-T) and evaluated their efficacy in a human lung carcinoma xenograft mouse model.

Experimental Design: To evaluate the effector function and expansion capacity of CAR.αPD1-T cells in vitro, we measured the production of IFNγ and T-cell proliferation following antigen-specific stimulation. Furthermore, the antitumor efficacy of CAR.αPD1-T cells, CAR T cells, and CAR T cells combined with anti–PD-1 antibody was determined using a xenograft mouse model. Finally, the underlying mechanism was investigated by analyzing the expansion and functional capacity of TILs.

Results: Human anti–PD-1 CPIs secreted by CAR.αPD1-T cells efficiently bound to PD-1 and reversed the inhibitory effect of PD-1/PD-L1 interaction on T-cell function. PD-1 blockade by continuously secreted anti–PD-1 attenuated the inhibitory T-cell signaling and enhanced T-cell expansion and effector function both in vitro and in vivo. In the xenograft mouse model, we demonstrated that the secretion of anti–PD-1 enhanced the antitumor activity of CAR T cells and prolonged overall survival.

Conclusions: With constitutive anti–PD-1 secretion, CAR.αPD1-T cells are more functional and expandable, and more efficient at tumor eradication than parental CAR T cells. Collectively, our study presents an important and novel strategy that enables CAR T cells to achieve better antitumor immunity, especially in the treatment of solid tumors. Clin Cancer Res; 23(22); 6982–92. ©2017 AACR.
Customized Viral Immunotherapy for HPV-Associated Cancer
Authors: Atherton Matthew J. , Stephenson Kyle B. , Pol Jonathan , Wang Fuan , Lefebvre Charles , Stojdl David F. , Nikota Jake K. , Dvorkin-Gheva Anna , Nguyen Andrew , Chen Lan , Johnson-Obaseki Stephanie , Villeneuve Patrick J. , Diallo Jean-Simon , Dimitroulakos Jim , Wan Yonghong , Lichty Brian D.
Published: September 2017

The viral-transforming proteins E6 and E7 make human papillomavirus–positive (HPV+) malignancies an attractive target for cancer immunotherapy. However, therapeutic vaccination exerts limited efficacy in the setting of advanced disease. We designed a strategy to induce substantial specific immune responses against multiple epitopes of E6 and E7 proteins based on an attenuated transgene from HPV serotypes 16 and 18 that is incorporated into MG1-Maraba virotherapy (MG1-E6E7). Mutations introduced to the transgene abrogate the ability of E6 and E7 to perturb p53 and retinoblastoma, respectively, while maintaining the ability to invoke tumor-specific, multifunctional CD8+ T-cell responses. Boosting with MG1-E6E7 significantly increased the magnitude of T-cell responses compared with mice treated with a priming vaccine alone (greater than 50 × 106 E7-specific CD8+ T cells per mouse was observed, representing a 39-fold mean increase in boosted animals). MG1-E6E7 vaccination in the HPV+ murine model TC1 clears large tumors in a CD8+-dependent manner and results in durable immunologic memory. MG1-Maraba can acutely alter the tumor microenvironment in vivo and exploit molecular hallmarks of HPV+ cancer, as demonstrated by marked infection of HPV+ patient tumor biopsies and is, therefore, ideally suited as an oncolytic treatment against clinical HPV+ cancer. This approach has the potential to be directly translatable to human clinical oncology to tackle a variety of HPV-associated neoplasms that cause significant morbidity and mortality globally. Cancer Immunol Res; 5(10); 847–59. ©2017 AACR.
Medical Therapy of Gastrointestinal Neuroendocrine Tumors
Authors: Öberg Kjell
Published: September 2017

Intestinal neuroendocrine tumors (NETs) constitute a heterogeneous group with duodenal, small intestinal, colonic and rectal NETs. They constitute more than half of all NETs, with the highest frequencies in the rectum, small intestine, and colon. The tumor biology varies with the location of the primary tumor as well as with the grade and staging of the tumor. Small intestinal NETs usually present low proliferation and are treated in the first line with somatostatin analogs according to current guidelines. If progression occurs, one can add interferon alpha or change the treatment to everolimus. Peptide receptor radionuclide therapy (PRRT) with Lutetium177-DOTATATE can be an option in the future after registration of the compound. Rectal tumors are usually small when they metastasize; they can be treated with somatostatin analogs but more so with PRRT, while another option is of course everolimus. Colonic NETs are more aggressive than the rest of intestinal NETs and will be treated with everolimus, sometimes in combination with somatostatin analogs based on positive scintigraphy. Another option is a cytotoxic agent such as streptozotocin plus 5-fluorouracil (5-FU) or temozolomide plus capecitabine. The most aggressive tumors, i.e. neuroendocrine carcinoma G3, are treated with a platin-based therapy plus etoposide; if they present with a lower proliferation, i.e. <50%, temozolomide plus capecitabine plus bevacizumab can also be attempted. Duodenal NETs are mostly treated similar to pancreatic NETs, either with cytotoxic agents, streptozotocin plus 5-FU, or temozolomide plus capecitabine, or with targeted agents such as everolimus.
Systemic Inflammatory Response Is a Prognostic Marker in HIV-Infected Patients with Hepatocellular Carcinoma
Authors: Pinato David J. , Merli Marco , Dalla Pria Alessia , Jamshaid Shiraz , Parker Kizzy , Pagani Nicole , Hasson Hamid , Uberti Foppa Caterina , Messina Emanuela , Sharma Rohini , Nelson Mark , Bower Mark
Published: September 2017

Background: Hepatocellular carcinoma (HCC) is increasingly prevalent in people living with HIV. Systemic inflammation is a prognostic factor requiring validation in HIV-associated HCC. Aims: Using a multi-centre database of consecutive HCC cases, we investigated the prognostic role of a panel of inflammatory markers, including neutrophil to lymphocyte ratio (NLR), using univariate and multivariate survival analyses. Results: Fifty-nine patients with HIV-associated HCC secondary to hepatitis C (69%) or B virus infection (32%) were identified. The median survival was 22 months. A raised NLR independently predicted patients' survival and was correlated with advanced Barcelona Clinic Liver Cancer stage (p = 0.003) and poor performance status (p < 0.001) but not with HIV RNA or CD4 counts. Conclusion: Systemic inflammation, as measured by NLR, is a prognostic determinant associated with adverse pathological features of malignancy, but not coexisting HIV infection, suggesting a tumour-promoting role of the innate immune response that warrants further investigation in mechanistic studies.
Dose Distributions and Treatment Margins in Ocular Brachytherapy with 106Ru Eye Plaques
Authors: Stöckel Erik , Eichmann Marion , Flühs Dirk , Sommer Holger , Biewald Eva , Bornfeld Norbert , Spaan Bernhard , Sauerwein Wolfgang
Published: September 2017

Brachytherapy with 106Ru eye plaques is the most common treatment modality for small to medium-sized uveal melanomas in Europe. So far, no standardized or widely accepted dose prescription protocol for the irradiation of intraocular tumors with 106Ru eye plaques has been defined. For 125I plaques, the minimum dose required for tumor control should be at least 85 Gy. Concerning 106Ru plaques, the dose prescriptions at the University Hospital of Essen foresees minimum doses of 700 Gy to the tumor base and 130 Gy to the tumor apex. These dose prescriptions are expected to ensure sufficient treatment margins. We apply these dose prescriptions to different eye plaque types and tumor sizes and discuss the resulting treatment margins. These investigations are based on Monte Carlo simulations of dose distributions of 3 different eye plaque types. The treatment margin in apical direction has an expansion of at least 0.8 mm for all investigated eye plaques. For symmetrically formed eye plaques, the treatment margin at the base of the tumor goes beyond the visible edge of the plaque. This study focuses on the shape of 85-Gy isodose lines and on treatment margins for different eye plaque types and tumor sizes and shall help exchange knowledge for ocular brachytherapy.
Aortic Isthmus Flow Recording Predicts the Outcome of the Recipient Twin after Laser Coagulation in Twin-Twin Transfusion Syndrome
Authors: Leduc France , Delabaere Amélie , Gendron Roxanne , Fuchs Florent , Wavrant Sandrine , Raboisson Marie-Josée , Fouron Jean-Claude , Audibert François
Published: September 2017

Introduction: The objective was to assess the prognostic value of the systolic flow through the aortic isthmus in monochorionic pregnancies complicated by twin-twin transfusion syndrome (TTTS) treated by placental laser ablation. Material and Methods: Fetal echocardiography and outcome data of 105 cases of TTTS treated by laser photocoagulation of placental anastomoses were reviewed. Hemodynamic parameters were collected before and after treatment. The isthmic systolic index (ISI) was calculated as the peak systolic velocity/systolic nadir ratio. Results: A total of 105 laser coagulations were studied. Fetal echocardiography pre- and post-laser were available in 68 cases, including 55 with data on aortic isthmic Doppler. Survival rates were 17, 22, and 61% for 0, 1, or 2 twins, respectively. At least 1 twin was delivered alive in 83% of the pregnancies. The mean gestational age at surgery was 21 weeks (range 16-26). Median ISI values were similar for donor and recipient twins, before and after laser ablation (all p > 0.05). A lower recipient ISI before laser was related to early recipient demise within 24 h (p = 0.04). Discussion: A lower ISI before placental laser ablation for TTTS is associated with postoperative demise of the recipient twin.
Atypical Retinal Pigment Epithelial Hyperplasia and Glial Proliferation Masquerading as Progressive Recurrent Retinoblastoma: A Case Report Review and Clinicopathologic Correlation
Authors: Zolfaghari Emily , Kim Jonathan W. , Krishnan Subramanian , Chévez-Barrios Patricia , Berry Jesse L.
Published: September 2017

Background: Recurrences of retinoblastoma tumors, particularly scar recurrences, are a common phenomenon in the management of this cancer. Consolidative treatment with laser and cryotherapy are required for local control of disease. It is known that consolidative therapy can induce retinal pigment epithelium (RPE) hyperplasia and gliosis. Herein we report extensive RPE hyperplasia and gliosis during laser therapy for a focal scar recurrence, which presented as a progressive retinal opacification mimicking active retinoblastoma. Method: This is a retrospective case review. Results: A 2-month-old premature male was diagnosed with sporadic bilateral retinoblastoma (International Intraocular Retinoblastoma Classification [IIRC] group B in the right eye and IIRC group A in the left eye). The patient underwent laser therapy for a focal recurrence which demonstrated a white lesion during therapy and was subsequently enucleated. While there was a focal recurrence and infiltration of the retina (seen both on optical coherence tomography and histopathologic section), the majority of the white, progressive lesion was from extensive RPE hyperplasia and gliosis secondary to laser therapy. Conclusion: Clinicopathologic correlation of the active recurrence and adjacent gliosis is demonstrated.
Representativity of the genus Asphondylia Loew, 1850 (Diptera, Cecidomyiidae) in Brazil
Authors: Flor Ismael Cividini , Maia Valéria Cid
Published: September 2017

Representativity of the genus Asphondylia Loew, 1850 (Diptera, Cecidomyiidae) in Brazil. This cosmopolitan genus includes 272 galling species described, of which about 100 occur in the Neotropical Region. The present study goal to evaluate the richness of Asphondylia in Brazil, to provide an updated list of the host plant species, to determine the plant organs where galls are induced, to update the geographic distribution of the genus, to verify it distribution in the Brazilian biomes, and to the list the associated fauna. The survey data was carried out by consulting the Cecidomyiidae collection of the Museu Nacional/UFRJ, the database “Web of Science” using Asphondylia and Brasil/Brazil as keywords, 51 Brazilian inventories and two catalogues. Asphondylia is represented by 58 species in Brazil, among them, twenty are already known and 38 are still undetermined. The Brazilian described species represent 8% of the total of known species of Asphondylia in the world and 21% of species of the Neotropical fauna. This genus is associated with 51 plant species and 20 plant families in Brazil. Asteraceae comprise the greatest richness of Asphondylia species. This genus was found in five biomes, among them the Atlantic forest has the highest species richness. The associated fauna comprises parasitoids (Hymenoptera) and inquilines (Lepidoptera, Coleoptera and Diptera).
Levantamento florístico de plantas aquáticas e palustres na Represa Guarapiranga, São Paulo, Brasil
Authors: Rodrigues Maria Estefânia Fernandes , Souza Vinicius Castro , Pompêo Marcelo Luiz Martins
Published: September 2017

O objetivo desse trabalho foi verificar a composição de plantas aquáticas e palustres no reservatório Guarapiranga, além de contribuir para o conhecimento taxonômico das espécies. Foram realizadas coletas mensais de julho/2008 a junho/2009, em 20 bancos de plantas aquáticas distribuídos ao longo de todo o reservatório. Em cada banco foram coletadas e registradas as espécies presentes. A comunidade de plantas aquáticas e palustres do reservatório é composta por 133 espécies, pertencentes a 89 gêneros, distribuídos em 45 famílias, sendo 127 de Angiospermas, 5 de Samambaias e 1 de Hepática. As famílias mais representativas foram Cyperaceae com 27 espécies, seguida de Poaceae (14) e Asteraceae (10). Das 67 espécies consideradas plantas daninhas ou infestantes, apenas 14 são subespontâneas ou naturalizadas, as demais 120 espécies são nativas, sendo 6 endêmicas do Brasil. O presente trabalho contribuiu significativamente para a Flora de plantas aquáticas e palustres, bem como para Lista da Flora do Brasil, registrando espécies que não haviam sido referidas anteriormente para o estado de São Paulo, além da apresentação de uma chave de identificação e descrições para as espécies presentes na área de estudo. Foi possível concluir que a Represa Guarapiranga possui uma elevada riqueza de plantas aquáticas e palustres.
Novel Pathological Role of hnRNPA1 (Heterogeneous Nuclear Ribonucleoprotein A1) in Vascular Smooth Muscle Cell Function and Neointima Hyperplasia
Authors: Zhang Li , Chen Qishan , An Weiwei , Yang Feng , Maguire Eithne Margaret , Chen Dan , Zhang Cheng , Wen Guanmei , Yang Mei , Dai Bin , Luong Le Anh , Zhu Jianhua , Xu Qingbo , Xiao Qingzhong
Published: September 2017

Objective—

hnRNPA1 (heterogeneous nuclear ribonucleoprotein A1) plays a variety of roles in gene expression. However, little is known about the functional involvement of hnRNPA1 in vascular smooth muscle cell (VSMC) function and neointima hyperplasia. In this study, we have attempted to investigate the functional roles of hnRNPA1 in the contexts of VSMC function, injury-induced vessel remodeling, and human atherosclerotic lesions, as well as discern the molecular mechanisms involved.

Approach and Results—

hnRNPA1 expression levels were consistently modulated during VSMC phenotype switching and neointimal lesion formation induced by wire injury. Functional studies showed that VSMC-specific gene expression, proliferation, and migration were regulated by hnRNPA1. Our data show that hnRNPA1 exerts its effects on VSMC functions through modulation of IQGAP1 (IQ motif containing GTPase activating protein 1). Mechanistically, hnRNPA1 regulates IQGAP1 mRNA degradation through 2 mechanisms: upregulating microRNA-124 (miR-124) and binding to AU-rich element of IQGAP1 gene. Further evidence suggests that hnRNPA1 upregulates miR-124 by modulating miR-124 biogenesis and that IQGAP1 is the authentic target gene of miR-124. Importantly, ectopic overexpression of hnRNPA1 greatly reduced VSMC proliferation and inhibited neointima formation in wire-injured carotid arteries. Finally, lower expression levels of hnRNPA1 and miR-124, while higher expression levels of IQGAP1, were observed in human atherosclerotic lesions.

Conclusions—

Our data show that hnRNPA1 is a critical regulator of VSMC function and behavior in the context of neointima hyperplasia, and the hnRNPA1/miR-124/IQGAP1 regulatory axis represents a novel therapeutic target for the prevention of cardiovascular diseases.
Clinical Yield of Familial Screening After Sudden Death in Young Subjects
Authors: Quenin Pauline , Kyndt Florence , Mabo Philippe , Mansourati Jacques , Babuty Dominique , Thollet Aurélie , Guyomarch Béatrice , Redon Richard , Barc Julien , Schott Jean-Jacques , Sacher Frederic , Probst Vincent , Gourraud Jean Baptiste
Published: September 2017

Background:

After sudden cardiac death with negative autopsy, clinical screening of relatives identifies a high proportion of inherited arrhythmia syndrome. However, the efficacy of this screening in families not selected by autopsy has never been assessed. We aim to investigate the value of clinical screening in relatives of all subjects who died suddenly before 45 years of age.

Methods and results:

One hundred and three consecutive families who experienced unexplained sudden cardiac death before 45 years of age were included from May 2009 to December 2014 in a prospective multicenter registry. Clinical screening was provided to all relatives and performed in 64 families (230 relatives, 80 unexplained sudden cardiac death). Diagnosis was established in 16 families (25%), including Brugada syndrome (7), long QT syndromes (5), dilated cardiomyopathy (2), and hypertrophic cardiomyopathy (2). The diagnostic yield was mainly dependent on the number of screened relatives (3.8±3.4 screened relatives in diagnosed families versus 2.0±1.5;
P
<0.005) rising to 47% with at least 3 relatives. It additionally increased from 3 of 32 (9%) to 9 of 22 (41%) when both parents were screened (
P
=0.01). Diagnostic performance was also dependent on the exhaustiveness of screening (70% of complete screening in the diagnosed families versus 25%;
P
<0.0001) with 17 Brugada syndromes and 15 long QT syndromes diagnosed based on pharmacological tests.

Conclusions:

Even without autopsy, familial screening after sudden death in young patients is effective. Broad screening of relatives and systematic tests, including pharmacological challenges, greatly increases the likelihood of diagnosis in families.
NOD2 (Nucleotide-Binding Oligomerization Domain 2) Is a Major Pathogenic Mediator of Coxsackievirus B3-Induced Myocarditis
Authors: Tschöpe Carsten , Müller Irene , Xia Yu , Savvatis Konstantinos , Pappritz Kathleen , Pinkert Sandra , Lassner Dirk , Heimesaat Markus M. , Spillmann Frank , Miteva Kapka , Bereswill Stefan , Schultheiss Heinz-Peter , Fechner Henry , Pieske Burkert , Kühl Uwe , Van Linthout Sophie
Published: September 2017

Background:

The cytoplasmatic pattern recognition receptor, NOD2 (nucleotide-binding oligomerization domain 2), belongs to the innate immune system and is among others responsible for the recognition of single-stranded RNA. With Coxsackievirus B3 (CVB3) being a single-stranded RNA virus, and the recent evidence that the NOD2 target, NLRP3 (NOD-like receptor family, pyrin domain containing 3) is of importance in the pathogenesis of CVB3-induced myocarditis, we aimed to unravel the role of NOD2 in CVB3-induced myocarditis.

Methods and Results:

Endomyocardial biopsy NOD2 mRNA expression was higher in CVB3-positive patients compared with patients with myocarditis but without evidence of persistent CVB3 infection. Left ventricular NOD2 mRNA expression was also induced in CVB3-induced myocarditis versus healthy control mice. NOD2 knockdown
(−/−
)
mice were rescued from the detrimental CVB3-mediated effects as shown by a reduced cardiac inflammation (less cardiac infiltrates and suppression of proinflammatory cytokines), cardiac fibrosis, apoptosis, lower CAR (Coxsackievirus and adenovirus receptor) expression and CVB3 copy number, and an improved left ventricular function in NOD2
−/−
CVB3 mice compared with wild-type CVB3 mice. In agreement, NOD2
−/−
decreased the CVB3-induced inflammatory response, CVB3 copy number, and apoptosis in vitro. NOD2
−/−
was further associated with a reduction in CVB3-induced NLRP3 expression and activity as evidenced by lower ASC (apoptosis-associated speck-like protein containing a CARD) expression, caspase 1 activity, or IL-1β (interleukin-1β) protein expression under in vivo and in vitro CVB3 conditions.

Conclusions:

NOD2 is an important mediator in the viral uptake and inflammatory response during the pathogenesis of CVB3 myocarditis.
Preoperative Pectoralis Muscle Quantity and Attenuation by Computed Tomography Are Novel and Powerful Predictors of Mortality After Left Ventricular Assist Device Implantation
Authors: Teigen Levi M. , John Ranjit , Kuchnia Adam J. , Nagel Emily M. , Earthman Carrie P. , Kealhofer Jessica , Martin Cindy , Cogswell Rebecca
Published: September 2017

Background:

Skeletal muscle mass decreases in end-stage heart failure and is predictive of clinical outcomes in several disease states. Skeletal muscle attenuation and quantity as quantified on preoperative chest computed tomographic scans may be predictive of mortality after continuous flow (CF) left ventricular assist device (LVAD) implantation.

Methods and Results:

A single-center continuous flow-LVAD database (n=354) was used to identify patients with chest computed tomographies performed in the 3 months before LVAD implantation (n=143). Among patients with computed tomography data available, unilateral pectoralis muscle mass indexed to body surface area and attenuation (approximated by mean Hounsfield units [PHU
m
]) were measured in each patient with a high intrarater and inter-rater reliability (intraclass correlation coefficients 0.98 and 0.97, respectively). Multivariate Cox regression analyses were performed, censoring at cardiac transplantation, to assess the impact of preoperative pectoralis muscle index and pectoralis muscle mean Hounsfield unit on survival after LVAD implantation. Each unit increase in pectoralis muscle index was associated with a 27% reduction in the hazard of death after LVAD (adjusted hazard ratio, 0.73; 95% confidence interval, 0.58–0.92;
P
=0.007). Each 5-U increase in pectoralis muscle mean Hounsfield unit was associated with a 22% reduction in the hazard of death after LVAD (adjusted hazard ratio, 0.78; 95% confidence interval, 0.68–0.89;
P
<0.0001). Pectoralis muscle index and pectoralis muscle mean Hounsfield unit outperformed other traditional measures in the data set, including the HeartMate II risk score.

Conclusions:

Pectoralis muscle size and attenuation were powerful predictors of outcomes after LVAD implantation in this data set. This one time, repeatable, internal assessment of patient substrate added valuable prognostic information that was not available on standard preoperative testing.
Diastolic Pressure Difference to Classify Pulmonary Hypertension in the Assessment of Heart Transplant Candidates
Authors: Wright Stephen P. , Moayedi Yasbanoo , Foroutan Farid , Agarwal Suhail , Paradero Geraldine , Alba Ana C. , Baumwol Jay , Mak Susanna
Published: September 2017

Background:

The diastolic pressure difference (DPD) is recommended to differentiate between isolated postcapillary and combined pre-/postcapillary pulmonary hypertension (Cpc-PH) in left heart disease (PH-LHD). However, in usual practice, negative DPD values are commonly calculated, potentially related to the use of mean pulmonary artery wedge pressure (PAWP). We used the ECG to gate late-diastolic PAWP measurements. We examined the method’s impact on calculated DPD, PH-LHD subclassification, hemodynamic profiles, and mortality.

Methods and Results:

We studied patients with advanced heart failure undergoing right heart catheterization to assess cardiac transplantation candidacy (N=141). Pressure tracings were analyzed offline over 8 to 10 beat intervals. Diastolic pulmonary artery pressure and mean PAWP were measured to calculate the DPD as per usual practice (diastolic pulmonary artery pressure–mean PAWP). Within the same intervals, PAWP was measured gated to the ECG QRS complex to calculate the QRS-gated DPD (diastolic pulmonary artery pressure–QRS-gated PAWP). Outcomes occurring within 1 year were collected retrospectively from chart review. Overall, 72 of 141 cases demonstrated PH-LHD. Within PH-LHD, the QRS-gated DPD yielded higher calculated DPD values (3 [−1 to 6] versus 0 [−4 to 3] mm Hg;
P
<0.01) and a greater proportion of Cpc-PH (24% versus 8%;
P
<0.01) versus the usual practice DPD. Cases reclassified as Cpc-PH based on QRS-gated DPD demonstrated higher pulmonary arterial pressures versus isolated postcapillary pulmonary hypertension (
P
<0.05). One-year mortality was similar between PH-LHD groups.

Conclusions:

The DPD calculated in usual practice is underestimated in PH-LHD, which may classify Cpc-PH patients as isolated postcapillary pulmonary hypertension. The QRS-gated DPD reclassifies a subset of PH-LHD patients from isolated postcapillary pulmonary hypertension to Cpc-PH, which is characterized by an adverse hemodynamic profile.
How Prior Expectations Influence Older Adults’ Perception and Action During Object Interaction
Authors: Buckingham Gavin , Reid Darren , Potter Lauren M.
Published: September 2017

The apparent size of an object can influence how we interact with and perceive the weight of objects in our environment. Little is known, however, about how this cue affects behaviour across the lifespan. Here, in the context of the size–weight illusion, we examined how visual size cues influenced the predictive application of fingertip forces and perceptions of heaviness in a group of older participants. We found that our older sample experienced a robust size–weight illusion, which did not differ from that experienced by younger participants. Older and young participants also experienced a real weight difference to a similar degree. By contrast, compared to younger participants our older group showed no evidence that size cues influenced the way they initially gripped and lifted the objects. These results highlight a unique dissociation between how perception and action diverge across the lifespan, and suggest that deficits in the ability to use prediction to guide actions might underpin some of the manual interaction difficulties experienced by the older adults.
Data van Dagboeken
Authors: Zeldenrust Douwe A. , Wijsbek Nina A. , Windhouwer Menzo A.
Published: September 2017

Since 2014, the Nederlands Dagboekarchief (Dutch Diary Archive) is a part of the Meertens Institute. In the dans-financed project ‘Data from Diaries’ (2016), the paper metadata from the collection of ego documents have been made digitally accessible for researchers in a sustainable way. To this end, the Meertens Institute created a relational database in which the metadata can be stored. The database has been deposited at dans. Additionally, cmdi-metadata have been created, which enable technical and content-level interchange between different European diary archives.
Manfreda occidentalis (Agavoideae, Asparagaceae) a new species from western Mexico
Authors: CASTRO-CASTRO ARTURO , MUNGUÍA-LINO GUADALUPE , CARRILLO-REYES PABLO , RODRIGUEZ AARÓN
Published: September 2017

The genus Manfreda (Asparagaceae) contains 35 species. A species complex includes plants similar to M. gutttata, which are characterized by the protrusion of the ovary into the perigone tube. This feature was found in specimens recently collected in western Mexico. After a morphological analysis, we found that some of the plants differ from the other species in this complex. Hence, we describe a new species named M. occidentalis morphologically similar to M. planifolia but can be distinguished from it by the oblong-ovoid corm, channeled leaves, which are papillate on both sides, perigone 1.8–2.5 cm long, funnel-shaped, yellowish and light purple striate, perigone tube 0.3–0.7 × 0.2–0.4 cm, filaments adnate to the perigone and arising 0.3–0.7 cm above the ovary apex, anthers 0.9–1.1 cm long, and style 2.1–3.5 cm long, exceeding the perigone tube by 1.8–3 cm at anthesis. Manfreda occidentalis also resembles M. chamelensis; however, phenologic asynchrony is a notable difference between them as well as the shape of the leaves and the length and shape of perigone tube and lobes. A distribution map, photographs, and a key to identify species of Manfreda which grow in western Mexico accompany the description.
A new species of Begonia section Casparya from the Colombian Eastern Cordillera and a key to the Colombian Casparya
Authors: JARA-MUÑOZ ORLANDO A. , RICHARDSON JAMES E. , MADRIÑAN SANTIAGO
Published: September 2017

A new species, Begonia solaniflora Jara is described from Colombia. This species belongs to section Casparya as evident by the fruit type, but is also easily distinguished from other Casparya species by the undivided or rarely bifid styles, the stamens erect with the anthers connivent and the nearly symmetrical leaves. We provide illustrations, photographs, a distribution map of the species and after an assessment of its conservation status we propose to place it in the Critically Endangered (CR) category.
Case Study and Climatological Analysis of Upper-Tropospheric Jet Stream and Stratosphere–Troposphere Exchanges Using VHF Profilers and Radionuclide Measurements in France
Authors: Baray Jean-Luc , Pointin Yves , Van Baelen Joël , Lothon Marie , Campistron Bernard , Cammas Jean-Pierre , Masson Olivier , Colomb Aurélie , Hervier Claude , Bezombes Yannick , Banson Sandra , Duroure Christophe , Hadad Dany , Tridon Frédéric
Published: September 2017

The authors present a climatological analysis of tropospheric horizontal wind profiles and jet stream events using long series of wind profiles from two VHF profilers located in France: Lannemezan (2001–14) and Opme (1999–2014). A case study of jet stream and stratospheric intrusion of air into the troposphere that occurred in January 2013 is first described and demonstrates the capability of the VHF profilers to detect jet stream events. The climatology study over the two sites reveals the strongest values of seasonal wind during winter (21.4 m s−1at 8.7-km height at Opme; 25.1 m s−1at 9.6-km height at Lannemezan). A methodology based on the automatic detection of maximum winds on a decadal series of hourly wind profiles allows the detection of jet stream events and establishes its climatology for each site. A frequency analysis of jet stream events of westerly winds over 50 m s−1presents a clear seasonality at the two sites, with a maximum in winter (3.5%–9.7% of hourly profiles) and a minimum in summer (near 1%). Cosmogenic radionuclides sampled at Opme also exhibit a clear seasonal variation with maximum in spring and minimum in the cold seasons; the7Be/22Na activity ratio confirms stratosphere-to-troposphere exchanges for the studied cases. The mean interannual variability of the frequency of jet stream events is 1.5% in Opme and 2.9% in Lannemezan. Positive decadal trends are observed for the two sites: +1.6 ± 1.2% decade−1for Opme and +2.4 ± 2.2% decade−1for Lannemezan.
Extreme Precipitation in the West African Cities of Dakar and Ouagadougou: Atmospheric Dynamics and Implications for Flood Risk Assessments
Authors: Engel Thomas , Fink Andreas H. , Knippertz Peter , Pante Gregor , Bliefernicht Jan
Published: September 2017

Two extreme, high-impact events of heavy rainfall and severe floods in West African urban areas (Ouagadougou on 1 September 2009 and Dakar on 26 August 2012) are investigated with respect to their atmospheric causes and statistical return periods. In terms of the synoptic–convective dynamics, the Ouagadougou case is truly extraordinary. A succession of two slow-moving African easterly waves (AEWs) caused record-breaking values of tropospheric moisture. The second AEW, one of the strongest in recent decades, provided the synoptic forcing for the nighttime genesis of mesoscale convective systems (MCSs). Ouagadougou was hit by two MCSs within 6 h, as the strong convergence and rotation in the AEW-related vortex allowed a swift moisture refueling. An AEW was also instrumental in the overnight development of MCSs in the Dakar case, but neither the AEW vortex nor the tropospheric moisture content was as exceptional as in the Ouagadougou case. Tropical Rainfall Measuring Mission (TRMM) 3B42 precipitation data show some promise in estimating centennial return values (RVs) using the “peak over threshold” approach with a generalized Pareto distribution fit, although indications for errors in estimating extreme rainfall over the arid Sahel are found. In contrast, the Precipitation Estimation from Remotely Sensed Information Using Artificial Neural Networks–Climate Data Record (PERSIANN-CDR) dataset seems less suitable for this purpose despite the longer record. Notably, the Ouagadougou event demonstrates that highly unusual dynamical developments can create extremes well outside of RV estimates from century-long rainfall observations. Future research will investigate whether such developments may become more frequent in a warmer climate.
Repeated Iron–Soot Exposure and Nose-to-brain Transport of Inhaled Ultrafine Particles
Authors: Hopkins Laurie E. , Laing Emilia A. , Peake Janice L. , Uyeminami Dale , Mack Savannah M. , Li Xueting , Smiley-Jewell Suzette , Pinkerton Kent E.
Published: September 2017

Particulate exposure has been implicated in the development of a number of neurological maladies such as multiple sclerosis, amyotrophic lateral sclerosis, Alzheimer’s disease, and idiopathic Parkinson’s disease. Only a few studies have focused on the olfactory pathway as a portal through which combustion-generated particles may enter the brain. The primary objective of this study was to define the deposition, uptake, and transport of inhaled ultrafine iron–soot particles in the nasal cavities of mice to determine whether combustion-generated nanoparticles reach the olfactory bulb via the olfactory epithelium and nerve fascicles. Adult female C57B6 mice were exposed to iron–soot combustion particles at a concentration of 200 μg/m3, which included 40 μg/m3 of iron oxide nanoparticles. Mice were exposed for 6 hr/day, 5 days/week for 5 consecutive weeks (25 total exposure days). Our findings visually demonstrate that inhaled ultrafine iron–soot reached the brain via the olfactory nerves and was associated with indicators of neural inflammation.
Perceptions of Corruption: An Empirical Study Controlling for Survey Bias
Authors: Friesenbichler Klaus S. , Selenko Eva , Clarke George
Published: September 2017

Survey data on corruption are widely used to construct corruption indices, but are hardly questioned. How do individual experiences shape perceptions of corruption? Do more work-engaged respondents perceive corruption as a bigger obstacle to business operations than others? What role does answer bias play in corruption surveys? This article brings together several strands of literature to discuss these questions, and tests them empirically with survey data from Bangladesh and Sri Lanka. We find that individuals who are more work engaged report corruption as a bigger obstacle. So did respondents who were previously exposed to corruption. We control for possible answer bias by implementing a randomized response technique, and find that corruption tends to be under-reported. The effects of work engagement and prior exposure to corruption are more pronounced when the bias indicator is considered, and again become stronger once we control for answer bias affecting past experiences with corruption.

JEL: C83, D03, D73, O12
The ‘living wage’ and low income: Can adequate pay contribute to adequate family living standards?
Authors: Hirsch Donald
Published: September 2017

The success of the contemporary ‘living wage’ movement has been highlighted by the UK government’s decision to increase the statutory minimum wage for over-25s sharply, in the name of improving living standards. This breaks with neoliberal reluctance to intervene in labour markets, yet raises difficult issues centring around whether minimum hourly pay rates are suited to promoting adequate household incomes. At worst, ‘living wages’ could distract from other policies with this objective. This article acknowledges recent critiques of the living wage as an anti-poverty measure, but demonstrates that, in combination with other policies, wage floors can play a crucial role. It shows that low pay and inadequate working incomes overlap substantially. The article argues that governments promising that work will deliver adequate living standards need a clearer narrative in which pay, public transfers/subsidies and sufficient levels of employment combine to deliver minimum acceptable living standards for working families.
Effect of myofascial techniques for treatment of persistent arm pain after breast cancer treatment: randomized controlled trial
Authors: De Groef An , Van Kampen Marijke , Vervloesem Nele , Dieltjens Evi , Christiaens Marie-Rose , Neven Patrick , Vos Lore , De Vrieze Tessa , Geraerts Inge , Devoogdt Nele
Published: September 2017

Objective:

To investigate the effect of myofascial therapy in addition to a standard physical therapy program for treatment of persistent arm pain after finishing breast cancer treatment.

Design:

Double-blinded (patient and assessor) randomized controlled trial.

Setting:

University Hospitals Leuven, Belgium.

Patients:

A total of 50 patients with persistent arm pain and myofascial dysfunctions after breast cancer treatment.

Intervention:

Over three months, all patients received a standard physical therapy program. The intervention group received in addition 12 sessions of myofascial therapy, and the control group received 12 sessions of placebo therapy.

Main measurements:

Main outcome parameters were pain intensity (primary outcome) (maximum visual analogue scale (VAS) (0–100)), prevalence rate of arm pain, pressure hypersensitivity (pressure pain thresholds (kg/cm2) and pain quality (McGill Pain Questionnaire). Measures were taken before and after the intervention and at long term (6 and 12 months follow-up).

Results:

Patients in the intervention group had a significantly greater decrease in pain intensity compared to the control group (VAS −44/100 vs. −24/100, P = 0.046) with a mean difference in change after three months between groups of 20/100 (95% confidence interval, 0.4 to 39.7). After the intervention, 44% versus 64% of patients still experienced pain in the intervention and control group, respectively ( P = 0.246). No significant differences were found for the other outcomes.

Conclusion:

Myofascial therapy is an effective physical therapy modality to decrease pain intensity at the arm in breast cancer survivors at three months, but no other benefits at that time were found. There were no long-term effects at 12 months either.
Irrelevance of “Public Use” in State Eminent Domain Reforms
Authors: Olejarski Amanda M.
Published: September 2017

“Public use” is a constitutional limitation on the governmental authority to take private property using eminent domain. This study finds that it is irrelevant, an artifact of the federal constitution, in state reforms enacted in the last decade. Expansive language permitting economic development and private development have rendered public use to be merely symbolic. Forty-six states enacted takings reforms following Kelo v. New London, a landmark U.S. Supreme Court decision in 2005; approximately 80% of those states allow economic or private takings while also invoking the public use. This mixed-method analysis and normative theoretical grounding explain stark contradictions in the prevailing reforms nationwide, resulting in substantive implementation challenges that may be mitigated by sensitivity to regime values, one of which is property.
You are where you go, the commodification of daily life through ‘location’
Authors: Thatcher Jim
Published: September 2017

Recent years have seen an explosion in the investment into and valuation of mobile spatial applications. With multiple applications currently valued at well over one billion U.S. dollars, mobile spatial applications and the data they generate have come to play an increasingly significant role in the function of late capitalism. Empirically based upon a series of interviews conducted with mobile application designers and developers, this article details the creation of a digital commodity termed ‘location.’ ‘Location’ is developed through three discursive poles: Its storing of space and time as digital data object manipulable by code, its spatial and temporal immediacy, and its ability to ‘add value’ or ‘tell a story’ to both end-users and marketers. As a commodity it represents the sum total of targeted marking information, including credit profiles, purchase history, and a host of other information available through data mining or sensor information, combined with temporal immediacy, physical location, and user intent. ‘Location’ is demonstrated to exist as a commodity from its very inception and, as such, to be a key means through which everyday life is further entangled with processes of capitalist exploitation.
Li (禮), or Ritual Propriety: A Preface to a Confucian Philosophy of Human Action
Authors: Nam Kyung-Hee
Published: September 2017

In this paper, I propose an interpretation of the Confucian concept of li or Ritual Propriety, and suggest a new philosophy of action and mind on the basis of the concept. To achieve this aim, I focus upon and analyze passages in The Analects, and try to establish major Confucian theses on human action. By comparing Confucian views on human action with Western ones, I shed light on the originality of the concept of li.

Major theses on li in The Analects are as follows: (1) As an essential characteristic of human behavior, li is ordinary and ubiquitous. (2) Li is a socialized form of our mind, is the outside of an inside, and as such presupposes the unity of the mind and body. (3) Li is a social medium through which we interact with others in order to achieve common values and to turn our society into a harmonious and aesthetic space. To argue for the above theses, I focus on the centrality of language in our life, and utilize Russian psychologist Vygotsky's theory of language learning as well as Wittgenstein's concept of language game, together with the Confucian theory of correct names.
Safety and Efficacy of Repeat Open-Label AbobotulinumtoxinA Treatment in Pediatric Cerebral Palsy
Authors: Delgado Mauricio R. , Bonikowski Marcin , Carranza Jorge , Dabrowski Edward , Matthews Dennis , Russman Barry , Tilton Ann , Velez Juan Carlos , Grandoulier Anne-Sophie , Picaut Philippe
Published: September 2017

This was a prospective, repeat-treatment, open-label study (NCT01251380) of abobotulinumtoxinA for the management of lower limb spasticity in children who had completed a double-blind study. Children (2-17 years) received injections into the gastrocnemius-soleus complex, and other distal and proximal muscles as required (maximum total dose per injection cycle: 30 U/kg or 1000U). A total of 216 of the 241 double-blind patients entered the extension study and 207 received ≥1 open label injection into the gastrocnemius-soleus; 17-24% of patients also had injections into the hamstrings. The most frequent adverse events were related to common childhood infections and the most frequent treatment-related adverse event was injection site pain (n = 10). There was no evidence of a cumulative effect on adverse events. Sustained significant clinical improvements in muscle tone (Modified Ashworth Scale), spasticity (Tardieu Scale), overall clinical benefit (Physicians Global Assessment), and goal attainment (Goal Attainment Scale) were also observed across treatment cycles.
Flow matching with combined control of the pump and the valves for the independent metering swing system of a hydraulic excavator
Authors: Huang Weinan , Quan Long , Huang Jiahai , Yang Jing
Published: September 2017

Because of the throttling loss of the control valves and the overflow loss in the frequently accelerating and decelerating motion with a large inertia, the swing system of a hydraulic excavator has a high energy consumption; also, it has a poor controllability. To solve these problems, this paper proposes flow matching with combined control of the pump and the valves and an independent metering method for the swing system of the hydraulic excavator. The inlet pressure and the outlet pressure of the hydraulic motor can be controlled independently. With combined control of the pump and the valves, the flow rate can match the rotational speed of the hydraulic motor so that the overflow loss is avoided. Furthermore, we also develop a simulation model consisting of the mechanical structure of the hydraulic excavator with multi-body dynamics and an electrohydraulic system for analysing the feasibility of this swing system, and the simulation results demonstrate that this system works smoothly. After using the presented control strategies, the results of experiments show that the energy efficiency is improved and that the system can reduce the throttling loss and can obviously suppress the swing vibrations.
A novel piezoelectric actuator with two operating modes
Authors: Liu Yingxiang , Shi Shengjun , Yan Jipeng , Chen Weishan , Xu Dongmei
Published: September 2017

A novel piezoelectric actuator with two operating modes is proposed and tested in this work, whose unique feature is that it has different mechanical output performances under two bending resonance frequencies. The proposed actuator is fabricated by bonded eight pieces of lead zirconate titanate ceramic plates on an aluminum alloy beam symmetrically. When the ceramic plates are excited by signals with resonance frequency of the first bending mode of the actuator, two bending vibrations will be superimposed to form elliptical movements on the two driving tips, which is the first operating mode. The other operating mode can be realized easily by changing the working frequency to the second bending mode of the actuator. These two operating modes are calculated and compared in detail. The prototype achieves a maximum no-load speed of 171 mm/s and maximum thrust force of 0.6 N using the first operating mode, whereas these two values are increased to be about 208 mm/s and 0.76 N under the second operating mode. The weight of the proposed piezoelectric actuator is about 17.7 g, and the maximum force weight ratio is tested to be about 42.9 N/kg.