bluuebunny/crossref_metadata_2025 huggingface dataset:
Home‐based high‐intensity interval training reduces barriers to exercise in people with type 1 diabetes
Authors: Scott Sam N. , Shepherd Sam O. , Strauss Juliette A. , Wagenmakers Anton J. M. , Cocks Matt
Published: October 2019

New Findings

What is the topic of this review?

This symposium review provides an overview of the recent work investigating whether a virtually monitored home‐based high‐intensity interval training (Home‐HIT) intervention reduces the fear of hypoglycaemia and other common barriers to exercise in people with type 1 diabetes.

What advances does it highlight?

Home‐HIT seems to offer a strategy to reduce fear of hypoglycaemia, while simultaneously removing other known barriers that prevent people with type 1 diabetes from taking up exercise, because it is time efficient, requires no travel time or costs associated with gym memberships, and allows people to exercise in their chosen environment.

People with type 1 diabetes (T1D) are recommended to engage in regular exercise for a variety of health and fitness reasons. However, many lead a sedentary lifestyle and fail to meet the physical activity guidelines, in part because of the challenge of managing blood glucose concentration and fear of hypoglycaemia. A number of strategies designed to help people with T1D to manage their blood glucose during and after exercise have been investigated. Although many of these strategies show promise in facilitating blood glucose management during and after exercise, they do not target the many other common barriers to exercise that people with T1D face, such as difficulty with cost and travel time to gyms, limited access to exercise bikes and treadmills, and a possible dislike of exercising in front of others in public places. In this symposium review, we provide an overview of ongoing research into a virtually monitored home‐based high‐intensity interval training (Home‐HIT) programme that is designed to reduce these other common barriers to exercise. The conclusion of this review is that Home‐HIT seems to offer a strategy to reduce fear of hypoglycaemia, while simultaneously removing other known barriers preventing people with T1D from taking up exercise, such as being time efficient, requiring no travel time or costs associated with gym memberships, and giving them the opportunity to exercise in their chosen environment, reducing the embarrassment experienced by some when exercising in public.
Desplazamiento climático de 2010-2011 en el municipio de Campo de la Cruz: reflexiones para la adaptación y el cuidado 8 años después
Authors: De la Hoz-Del Real Clara Inés , Amar-Amar José Juan , López-Muñoz Laura , Martínez-González Marina Begoña
Published: October 2019

La ola invernal que experimentó Colombia entre los años 2010 y 2011 produjo una inundación sin precedentes en el municipio de Campo de la Cruz, Atlántico. A partir de un trabajo etnográfico que comprendió entrevistas, grupos focales y observación participante, se aborda la movilización humana originada por este desastre desde las nociones de desplazamiento climático, adaptación y prácticas de cuidado. Además, se analizan los cambios que se originaron en las costumbres y rutinas de la comunidad desplazada como respuesta a la fragmentación familiar y a la escasez de recursos y espacio. Asimismo, se discute la relevancia de la promoción e inclusión de la población en el manejo gubernamental de estos fenómenos.
La política exterior de Chile y su ideología desde 1990
Authors: González Pizarro Sergio Andrés
Published: October 2019

El objetivo del presente trabajo es en analizar la política exterior de Chile desde 1990, enfocándose particularmente en sus aspectos ideacionales, discursivos y materiales. Mediante el lente de la Teoría Crítica en las Relaciones Internacionales, se tiene en consideración una amalgama de ideas, discursos, estrategias y acciones que encierran la ideología orgánica de la política exterior de Chile desde 1990. Este artículo ofrece un recorrido cronológico y un breve análisis sobre la ideología orgánica de esta política exterior, que se caracteriza por una autopercepción de superioridad nacional, el valor por el territorio y la ley, como también el aislacionismo regional y su apertura comercial monoproductiva con las grandes potencias, entre otras características. En definitiva, Chile en un estilo pragmático y camaleónico, se ha moldeado a un contexto hegemónico transnacional, en virtud de los intereses ideológicos, económicos y políticos de dominación de elites.
Populismo y política exterior: los casos de los gobiernos de Hugo Chávez (Venezuela) y Rafael Correa (Ecuador)
Authors: Díaz González José Andrés
Published: October 2019

El presente artículo compara las políticas exteriores desarrolladas por los gobiernos de Hugo Chávez (Venezuela) y Rafael Correa (Ecuador), para determinar cómo fueron afectadas por el tipo de populismo desarrollado por ellos. Se concluye que, en el caso de Hugo Chávez, al recurrir a un populismo de corte tradicional, adopta una política exterior confrontativa que se concentra en promover su imagen a nivel internacional. En el caso de Rafael Correa, su gobierno es tecnopopulista, por lo que en la mayoría de las ocasiones adopta una política exterior menos confrontativa y más orientada a la obtención de beneficios a corto y mediano plazo.
Extreme biomimetics: Preservation of molecular detail in centimeter-scale samples of biological meshes laid down by sponges
Authors: Petrenko Iaroslav , Summers Adam P. , Simon Paul , Żółtowska-Aksamitowska Sonia , Motylenko Mykhailo , Schimpf Christian , Rafaja David , Roth Friedrich , Kummer Kurt , Brendler Erica , Pokrovsky Oleg S. , Galli Roberta , Wysokowski Marcin , Meissner Heike , Niederschlag Elke , Joseph Yvonne , Molodtsov Serguei , Ereskovsky Alexander , Sivkov Viktor , Nekipelov Sergey , Petrova Olga , Volkova Olena , Bertau Martin , Kraft Michael , Rogalev Andrei , Kopani Martin , Jesionowski Teofil , Ehrlich Hermann
Published: October 2019

We report a strategy for preserving the structural features of collagen triple helix in turbostratic graphite.
Rapid laser solver for the phase retrieval problem
Authors: Tradonsky C. , Gershenzon I. , Pal V. , Chriki R. , Friesem A. A. , Raz O. , Davidson N.
Published: October 2019

An optical system solves the phase retrieval problem by exploiting the natural mode competition inside a degenerate laser cavity.
Stimulated transformation of soft helix among helicoidal, heliconical, and their inverse helices
Authors: Yuan Cong-long , Huang Wenbin , Zheng Zhi-gang , Liu Binghui , Bisoyi Hari Krishna , Li Yannian , Shen Dong , Lu Yanqing , Li Quan
Published: October 2019

Dynamic manipulation of a helical superstructure among the helicoidal, heliconical, and their inverse counterparts is achieved.
Extending electron paramagnetic resonance to nanoliter volume protein single crystals using a self-resonant microhelix
Authors: Sidabras Jason W. , Duan Jifu , Winkler Martin , Happe Thomas , Hussein Rana , Zouni Athina , Suter Dieter , Schnegg Alexander , Lubitz Wolfgang , Reijerse Edward J.
Published: October 2019

Self-resonant microhelix provides sensitivity for X-band electron paramagnetic resonance on protein crystals with <27-nl volume.
Arcobacter peruensis
sp. nov., a Chemolithoheterotroph Isolated from Sulfide- and Organic-Rich Coastal Waters off Peru
Authors: Callbeck Cameron M. , Pelzer Chris , Lavik Gaute , Ferdelman Timothy G. , Graf Jon S. , Vekeman Bram , Schunck Harald , Littmann Sten , Fuchs Bernhard M. , Hach Philipp F. , Kalvelage Tim , Schmitz Ruth A. , Kuypers Marcel M. M.
Published: October 2019

Our multidisciplinary approach provides new insights into the ecophysiology of a newly isolated environmental
Arcobacter
species, as well as the physiological flexibility within the
Arcobacter
genus and sulfide-oxidizing, denitrifying microbial communities within oceanic oxygen minimum zones (OMZs). The chemolithoheterotrophic species
Arcobacter peruensis
may play a substantial role in the diverse consortium of bacteria that is capable of coupling denitrification and fixed nitrogen loss to sulfide oxidation in eutrophic, sulfidic coastal waters. With increasing anthropogenic pressures on coastal regions, e.g., eutrophication and deoxygenation (D. Breitburg, L. A. Levin, A. Oschlies, M. Grégoire, et al., Science 359:eaam7240, 2018,
https://doi.org/10.1126/science.aam7240
), niches where sulfide-oxidizing, denitrifying heterotrophs such as
A. peruensis
thrive are likely to expand.
Determining responsiveness and meaningful changes for the Musculoskeletal Health Questionnaire (MSK-HQ) for use across musculoskeletal care pathways
Authors: Price Andrew James , Ogollah Reuben , Kang Sujin , Hay Elaine , Barker Karen L , Benedetto Elena , Smith Stephanie , Smith James , Galloway James B , Ellis Benjamin , Rees Jonathan , Glyn-Jones Sion , Beard David , Fitzpatrick Ray , Hill Jonathan C
Published: October 2019

Objectives

We have previously developed and validated the Arthritis Research UK Musculoskeletal Health Questionnaire (MSK-HQ) for use across musculoskeletal care pathways, showing encouraging psychometric test results. The objective of this study was to determine the responsiveness of MSK-HQ following MSK treatments and to determine the minimally important change (MIC).

Setting

We collected data in four cohorts from community physiotherapy and secondary-care orthopaedic hip, knee and shoulder clinics.

Participants

592 individuals were recruited; 210 patients treated with physiotherapy for a range of MSK conditions in primary care; 150 patients undergoing hip replacement, 150 patients undergoing knee replacement and 82 undergoing shoulder surgery in secondary care.

Outcome measures

Preoperative data were collected including the MSK-HQ, European Quality of Life-5D (EQ-5D) and the OHS, OKS or OSS in each joint-specific group. The same scores, together with anchor questions, were collected postintervention at 3 months for the physiotherapy group and 6 months for all others. Following COnsensus-based Standards for the selection of health status Measurement INstruments (COSMIN) guidelines, responsiveness was assessed using correlation between scores and the MIC was calculated for the entire cohort using receiver operating characteristic curve analysis.

Results

The MSK-HQ demonstrated strong correlation (R=0.73) with EQ-5D across the entire cohort and with each of the joint-specific Oxford scores (hip R=0.87, knee R=0.92 and shoulder R=0.77). Moderate correlation was seen between MSK-HQ and EQ-5D across each individual group (R value range 0.60–0.68), apart from the hip group where correlation was strong (R=0.77). The effect size with MSK-HQ was 0.93, in the entire cohort, double that measured with EQ-5D (0.43). In all subgroups, MSK-HQ measured a greater treatment effect compared with EQ-5D. The MIC is 5.5 (95% CI 2.7 to 8.3).

Conclusion

Our study demonstrates that the MSK-HQ questionnaire is responsive to change across a range of musculoskeletal conditions, supporting its use as a generic MSK measurement instrument.
Association between continued residence in temporary prefabricated housing and musculoskeletal pain in survivors of the Great East Japan Earthquake: a longitudinal study
Authors: Sogi Yasuhito , Yabe Yutaka , Hagiwara Yoshihiro , Sekiguchi Takuya , Sugawara Yumi , Tsuchiya Masahiro , Koide Masashi , Itaya Nobuyuki , Yoshida Shinichirou , Yano Toshihisa , Tsuji Ichiro , Itoi Eiji
Published: October 2019

Objective

Prolonged periods of living in prefabricated houses (PHs) may increase the risk of musculoskeletal (MSK) symptoms; however, the association is not clear. This study aimed to investigate the association between continued residence in PHs and MSK pain in a population affected by a natural disaster, the Great East Japan Earthquake (GEJE) survivors.

Design, setting and participants

A panel study was conducted including 1059 and 792 survivors at 2 and 4 years, respectively, after the GEJE, using a self-reported questionnaire. Those with no response on living status and those who did not live in a PH were excluded. Participants were classified into two groups by living status: continued residence in a PH (lived in a PH during both periods) or moving out of a PH (lived in a PH in the first period and did not live in a PH in the second).

Primary outcome measure

MSK pain included lower back, shoulder, knee, hand or foot, and neck pain. Changes in the occurrence of MSK pain during the two periods were assessed and defined as ‘new-onset’ and ‘continuing’ MSK pain. Multiple logistic regression analysis was used to examine the influence of continued residence in a PH on new-onset and continuing MSK pain.

Results

Continued residence in a PH was significantly associated with new-onset MSK pain, even after adjustment for covariates (adjusted OR 2.18, 95% CI 1.25 to 3.79, p=0.006). Participants who continued living in a PH had higher rates of continuing MSK pain than those who moved out; however, the difference was not significant (adjusted OR 1.69, 95% CI 0.94 to 3.05, p=0.079).

Conclusion

Continued residence in a PH was associated with new-onset MSK pain among survivors. Public support should be provided to such people to ensure a more comfortable life.
Clinical and genomic features of adult and paediatric acute leukaemias with ophthalmic manifestations
Authors: Skarsgård Lisa Stenman , Andersson Mattias K. , Persson Marta , Larsen Ann-Cathrine , Coupland Sarah E. , Stenman Göran , Heegaard Steffen
Published: October 2019

Objective

To describe the clinicopathological and genomic features of nine patients with primary and secondary orbital/ocular manifestations of leukaemia.

Methods

All orbital/ocular leukaemic specimens from 1980 to 2009 were collected from the Danish Register of Pathology. In six cases, medical records and formalin-fixed, paraffin-embedded blocks were available. Three cases from the Department of Pathology, Royal Liverpool University Hospital, were also included. Immunophenotypes and MYB oncoprotein expression were ascertained by immunohistochemistry. Genomic imbalances were analysed with comparative genomic hybridisation arrays and oncogene rearrangements with fluorescence in situ hybridisation.

Results

Four patients had B-cell precursor acute lymphoblastic leukaemia (BCP-ALL) and five had acute myeloid leukaemia (AML). Two patients with BCP-ALL and one with AML had primary orbital manifestations of leukaemia. Common symptoms were proptosis, displacement of the eye, and reduced eye mobility in patients with orbital leukaemias and pain, and reduced visual acuity in patients with ocular leukaemias. All patients with primary orbital lesions were alive up to 18 years after diagnosis. All but one patient with secondary ophthalmic manifestations died of relapse/disseminated disease.ETV6andRUNX1were rearranged in BCP-ALL, andRUNX1andKMT2Ain AML. Genomic profiling revealed quiet genomes (0–7 aberrations/case). The MYB oncoprotein was overexpressed in the majority of cases.

Conclusions

Leukaemias with and without ophthalmic manifestations have similar immunophenotypes, translocations/gene fusions and copy number alterations. Awareness of the clinical spectrum of leukaemic lesions of the eye or ocular region is important to quickly establish the correct diagnosis and commence prompt treatment.
Cost-effectiveness of a video game versus live simulation for disaster training
Authors: Whitfill Travis , Auerbach Marc , Diaz Maria Carmen G , Walsh Barbara , Scherzer Daniel J , Gross Isabel T , Cicero Mark X
Published: October 2019

Introduction

Disaster triage training for emergency medical service (EMS) providers is unstandardised. We hypothesised that disaster triage training with the paediatric disaster triage (PDT) video game‘60 s to Survival’would be a cost-effective alternative to live simulation-based PDT training.

Methods

We synthesised data for a cost-effectiveness analysis from two previous studies. The video game data were from the intervention arm of a randomised controlled trial that compared triage accuracy in a live simulation scenario of exposed vs unexposed groups to the video game. The live simulation and feedback data were from a prospective cohort study evaluating live simulation and feedback for improving disaster triage skills. Postintervention scores of triage accuracy were measured for participants via live simulations and compared between both groups. Cost-effectiveness between the live simulation and video game groups was assessed using (1) A net benefit regression model at various willingness-to-pay (WTP) values. (2) A cost-effectiveness acceptability curve (CEAC).

Results

The total cost for the live simulation and feedback training programme was $81 313.50 and the cost for the video game was $67 822. Incremental net benefit values at various WTP values revealed positive incremental net benefit values, indicating that the video game is more cost-effective compared with live simulation and feedback. Moreover, the CEAC revealed a high probability (>0.6) at various WTP values that the video game is more cost-effective.

Conclusions

A video game-based simulation disaster triage training programme was more cost-effective than a live simulation and feedback-based programme. Video game-based training could be a simple, scalable and sustainable solution to training EMS providers.
SLE clinical trials: impact of missing data on estimating treatment effects
Authors: Kim Mimi , Merrill Joan T , Wang Cuiling , Viswanathan Shankar , Kalunian Ken , Hanrahan Leslie , Izmirly Peter
Published: October 2019

Objective

A common problem in clinical trials is missing data due to participant dropout and loss to follow-up, an issue which continues to receive considerable attention in the clinical research community. Our objective was to examine and compare current and alternative methods for handling missing data in SLE trials with a particular focus on multiple imputation, a flexible technique that has been applied in different disease settings but not to address missing data in the primary outcome of an SLE trial.

Methods

Data on 279 patients with SLE randomised to standard of care (SoC) and also receiving mycophenolate mofetil (MMF), azathioprine or methotrexate were obtained from the Lupus Foundation of America-Collective Data Analysis Initiative Database. Complete case analysis (CC), last observation carried forward (LOCF), non-responder imputation (NRI) and multiple imputation (MI) were applied to handle missing data in an analysis to assess differences in SLE Responder Index-5 (SRI-5) response rates at 52 weeks between patients on SoC treated with MMF versus other immunosuppressants (non-MMF).

Results

The rates of missing data were 32% in the MMF and 23% in the non-MMF groups. As expected, the NRI missing data approach yielded the lowest estimated response rates. The smallest and least significant estimates of differences between groups were observed with LOCF, and precision was lowest with the CC method. Estimated between-group differences were magnified with the MI approach, and imputing SRI-5 directly versus deriving SRI-5 after separately imputing its individual components yielded similar results.

Conclusion

The potential advantages of applying MI to address missing data in an SLE trial include reduced bias when estimating treatment effects, and measures of precision that properly reflect uncertainty in the imputations. However, results can vary depending on the imputation model used, and the underlying assumptions should be plausible. Sensitivity analysis should be conducted to demonstrate robustness of results, especially when missing data proportions are high.
On the mean anomaly and the mean longitude in tests of post-Newtonian gravity
Authors: Iorio Lorenzo
Published: October 2019

The distinction between the mean anomaly $${\mathcal {M}}(t)$$M(t) and the mean anomaly at epoch $$\eta $$η, and the mean longitude l(t) and the mean longitude at epoch $$\epsilon $$ϵ is clarified in the context of a their possible use in post-Keplerian tests of gravity, both Newtonian and post-Newtonian. In particular, the perturbations induced on $${\mathcal {M}}(t),\,\eta ,\,l(t),\,\epsilon $$M(t),η,l(t),ϵ by the post-Newtonian Schwarzschild and Lense–Thirring fields, and the classical accelerations due to the atmospheric drag and the oblateness $$J_2$$J2 of the central body are calculated for an arbitrary orbital configuration of the test particle and a generic orientation of the primary’s spin axis $$\varvec{{\hat{S}}}$$S^. They provide us with further observables which could be fruitfully used, e.g., in better characterizing astrophysical binary systems and in more accurate satellite-based tests around major bodies of the Solar System. Some erroneous claims by Ciufolini and Pavlis appeared in the literature are confuted. In particular, it is shown that there are no net perturbations of the Lense–Thirring acceleration on either the semimajor axis a and the mean motion $$n_{\mathrm{b}}$$nb. Furthermore, the quadratic signatures on $${\mathcal {M}}(t)$$M(t) and l(t) due to certain disturbing non-gravitational accelerations like the atmospheric drag can be effectively disentangled from the post-Newtonian linear trends of interest provided that a sufficiently long temporal interval for the data analysis is assumed. A possible use of $$\eta $$η along with the longitudes of the ascending node $$\Omega $$Ω in tests of general relativity with the existing LAGEOS and LAGEOS II satellites is suggested.
Effect of a strong axial magnetic field on swirling flow in a cylindrical cavity with a top rotating lid
Authors: Dash Subas Chandra , Singh Navtej
Published: October 2019

Behavior of swirling flow in a cylindrical container with top rotating lid has been investigated under the influence of a strong axial magnetic field. The flow is assumed to be axisymmetric for the parameters considered in the study. The flow domain consists of a cylindrical cavity with a top rotating lid packed with viscous incompressible electrically conducting fluid, e.g. liquid metal. A steady magnetic field acts perpendicular to the bottom wall of the cavity. When the top rotating lid rotates an Ekman boundary layer develops in vicinity to the top rotating lid. However, the presence of a Hartmann boundary layer not only restrains the vortex breakdown but also shifts its position to some extent. All the walls of the cavity are assumed to be electrically insulated.
Prediction of magnesium tetraethynylporphyrin’s solubility by theoretical calculation
Authors: Ogumi Keisuke , Matsuo Yutaka
Published: October 2019

To investigate the solubility of porphyrin derivatives, their intermolecular interaction energies were calculated by the counterpoise method at the B97D3/6-31G(d) level. It was found that the calculated intermolecular interaction energies corresponded to the solubility measured by UV-vis spectroscopy. This correlation was consistent with differences in substituents and in the metals in the porphyrin core.
Synthesis of new water soluble silicon phthalocyanine substituted by linker sulfur atom and photophysicochemical studies for photodynamic therapy
Authors: Atmaca Göknur Yaşa , Erdoğmuş Ali
Published: October 2019

In this work, 5-(trifluoromethyl)-2-thiopyridine substituted SiPc (1) and its quaternized derivative (2) were synthesized, and the effect of the linker sulfur atom on silicon phthalocyanines has been investigated for the first time in the literature. Both of the complexes have been characterized by standard spectroscopy methods. The complexes have good solubility in organic solvents and showed monomeric tendencies in all studied solvents. Only complex 2 had some aggregation in water because of solvent effects, as expected. In order to determine the therapeutic effect for cancer treatment, photophysicochemical properties were investigated in DMSO, DMF, toluene and water (for complex 2). The synthesized complexes were found to have about 3.5 times higher singlet oxygen quantum yields than the yields of unsubstituted SiPcCl2 ([Formula: see text] = 0.15 (in DMSO), 0.12 (in DMF), 0.10 (in toluene)) because of the effects of bulky axial groups.
The spectral properties of a continuous family of zeta functions
Authors: Hajli Mounir
Published: October 2019

We study a family of zeta functions [Formula: see text] parametrized by a continuous variable [Formula: see text]. When [Formula: see text], [Formula: see text] corresponds to the zeta function of a conformal Laplacian on the [Formula: see text]-sphere. We prove that [Formula: see text] is holomorphic at the origin, for [Formula: see text] We explicitly compute the values of [Formula: see text] and [Formula: see text]. We recover and generalize results of Quine–Choi and Kumagai.
Universal Fourier expansions of Bianchi modular forms
Authors: Wong Tian An
Published: October 2019

We generalize Merel’s work on universal Fourier expansions to Bianchi modular forms over Euclidean imaginary quadratic fields, under the assumption of the nondegeneracy of a pairing between Bianchi modular forms and Bianchi modular symbols. Among the key inputs is a computation of the action of Hecke operators on Manin symbols, building upon the Heilbronn–Merel matrices constructed by Mohamed.
Absence of HIF1A Leads to Glycogen Accumulation and an Inflammatory Response That Enables Pancreatic Tumor Growth
Authors: Maruggi Marco , Layng Fabiana Izidro , Lemos Robert , Garcia Guillermina , James Brian P. , Sevilla Monica , Soldevilla Ferran , Baaten Bas J. , de Jong Petrus R. , Koh Mei Yee , Powis Garth
Published: October 2019

Cancer cells respond to hypoxia by upregulating the hypoxia-inducible factor 1α (HIF1A) transcription factor, which drives survival mechanisms that include metabolic adaptation and induction of angiogenesis by VEGF. Pancreatic tumors are poorly vascularized and severely hypoxic. To study the angiogenic role of HIF1A, and specifically probe whether tumors are able to use alternative pathways in its absence, we created a xenograft mouse tumor model of pancreatic cancer lacking HIF1A. After an initial delay of about 30 days, the HIF1A-deficient tumors grew as rapidly as the wild-type tumors and had similar vascularization. These changes were maintained in subsequent passages of tumor xenografts in vivo and in cell lines ex vivo. There were many cancer cells with a "clear-cell" phenotype in the HIF1A-deficient tumors; this was the result of accumulation of glycogen. Single-cell RNA sequencing (scRNA-seq) of the tumors identified hypoxic cancer cells with inhibited glycogen breakdown, which promoted glycogen accumulation and the secretion of inflammatory cytokines, including interleukins 1β (IL1B) and 8 (IL8). scRNA-seq of the mouse tumor stroma showed enrichment of two subsets of myeloid dendritic cells (cDC), cDC1 and cDC2, that secreted proangiogenic cytokines. These results suggest that glycogen accumulation associated with a clear-cell phenotype in hypoxic cancer cells lacking HIF1A can initiate an alternate pathway of cytokine and DC-driven angiogenesis. Inhibiting glycogen accumulation may provide a treatment for cancers with the clear-cell phenotype.

Significance:

These findings establish a novel mechanism by which tumors support angiogenesis in an HIF1α-independent manner.
Neoadjuvant Therapy Remodels the Pancreatic Cancer Microenvironment via Depletion of Protumorigenic Immune Cells
Authors: Mota Reyes Carmen , Teller Steffen , Muckenhuber Alexander , Konukiewitz Björn , Safak Okan , Weichert Wilko , Friess Helmut , Ceyhan Güralp O. , Demir Ihsan Ekin
Published: October 2019

Purpose:

Neoadjuvant therapy (neoTx) has dramatically improved the prognosis of patients with locally advanced and borderline resectable pancreatic ductal adenocarcinoma, yet its mechanisms of action on tumor cells and the tumor microenvironment are still unknown. Here, we aimed to characterize the multiple facets of neoTx-induced alterations in the pancreatic cancer microenvironment.

Experimental Design:

We performed the currently most comprehensive histopathologic analysis of desmoplasia, angiogenesis, neural invasion, and immune cell infiltration at the tumor–host interface of pancreatic cancer after neoTx (n = 37) versus after primary resection (n = 37) through quantitative IHC and double immunofluorescence using automated and software-based quantification algorithms.

Results:

We demonstrate that, independently of the applied pretreatment, neoadjuvant regimes are able to reverse the immunosuppressive behavior of malignant cells on pancreatic cancer microenvironment. Here, neoTx-driven selective depletion of regulatory T cells and myeloid-derived suppressor cells was associated with enrichment of antitumor immune cells in the peritumoral niche, decreased stromal activation, and less neural invasion. Importantly, the degree of this antitumor immune remodeling correlates to the degree of histopathologic response to neoTx. Survival analysis revealed that the tumor proliferation rate together with the activation of the stroma and the intratumoral infiltration with CD4+ T cells and natural killer cells constitute as independent prognostic factors for neoadjuvantly treated pancreatic cancer.

Conclusions:

NeoTx is not only cytotoxic but has pleiotropic, beneficial effects on all cellular and noncellular components of pancreatic cancer. Combinational approaches including immunotherapy may unleash long-term and more effective antitumor responses and improve prognosis of pancreatic cancer.
Facts and New Hopes on Selective FGFR Inhibitors in Solid Tumors
Authors: Facchinetti Francesco , Hollebecque Antoine , Bahleda Rastislav , Loriot Yohann , Olaussen Ken A. , Massard Christophe , Friboulet Luc
Published: October 2019

Precision oncology relies on the identification of molecular alterations, responsible for tumor initiation and growth, which are suitable targets of specific inhibitors. The development of FGFR inhibitors represents an edifying example of the rapid evolution in the field of targeted oncology, with 10 different FGFR tyrosine kinase inhibitors actually under clinical investigation. In parallel, the discovery of FGFR activating molecular alterations (mainly FGFR3 mutations and FGFR2 fusions) across many tumor types, especially urothelial carcinomas and intrahepatic cholangiocarcinomas, widens the selection of patients that might benefit from selective FGFR inhibitors. The ongoing concomitant clinical evaluation of selective FGFR inhibitors in molecularly selected solid tumors brings new hopes for patients with metastatic cancer, for tumors so far excluded from molecularly guided treatments. Matching molecularly selected tumors with selective FGFR inhibitors has indeed led to promising results in phase I and II trials, justifying their registration to be expected in a near future, such as the recent accelerated approval of erdafitinib granted by the FDA for urothelial cancer. Widening our knowledge of the activity, efficacy, and toxicities relative to the selective FGFR tyrosine kinase inhibitors under clinical investigation, according to the exact FGFR molecular alteration, will be crucial to determine the optimal therapeutic strategy for patients suffering from FGFR-driven tumors. Similarly, identifying with appropriate molecular diagnostic, every single tumor harboring targetable FGFR alterations will be of utmost importance to attain the best outcomes for patients with FGFR-driven cancer.
Analysis of Cardiovascular Fitness, Sleep Quality, Depression, Fatigue, and Quality of Life among Individuals with Respect to the Glycated Hemoglobin Level in Type 2 Diabetes Mellitus
Authors: Pathak Swetank , Shenoy Shweta
Published: October 2019

Background: Diabetes as a metabolic disorder can affect the various systems of the body, resulting in a decrease in cardiovascular fitness, sleep quality, and life quality that can lead to depression and fatigue. Aim: We analyzed cardiovascular fitness, sleep quality, depression, fatigue, and quality of life among individuals with a glycated hemoglobin (HBA1C) level >6.5% and ≤6.5%, as well as the relationship among glycated hemoglobin, maximal oxygen consumption (VO2max), obesity, sleep quality, depression, and duration of diabetes. Method: HBA1C (mean: 5.90 ± 0.93%) was studied in a total of 70 subjects (mean age: 62.37 ± 7.5 years). The 2 study groups were as follows: group A, HBA1C >6.5%, and group B, HBA1C ≤6.5%. BMI, VO2max, quality of sleep and life, depression, and fatigue were assessed in both groups. Results: There was a statistically significant difference between the groups at a significance level of p < 0.001. Group A had a lower cardiovascular fitness, a poor sleep quality, and increased depression compared to group B. A statistically significant negative linear correlation was found between VO2max and glycated hemoglobin, and a significant positive linear correlation was found between glycated hemoglobin and duration of diabetes, poor quality of sleep, and depression for all subjects, which was insignificant in the groups. Conclusions: A long duration of diabetes and an increased glycemic status may influence cardiovascular fitness, sleep quality, and life quality, leading to depression and fatigue.
Interventional Therapies for Acute Pulmonary Embolism: Current Status and Principles for the Development of Novel Evidence: A Scientific Statement From the American Heart Association
Authors: Giri Jay , Sista Akhilesh K. , Weinberg Ido , Kearon Clive , Kumbhani Dharam J. , Desai Nimesh D. , Piazza Gregory , Gladwin Mark T. , Chatterjee Saurav , Kobayashi Taisei , Kabrhel Christopher , Barnes Geoffrey D. ,   On behalf of the American Heart Association Council on Peripheral Vascular Disease; Council on Arteriosclerosis, Thrombosis and Vascular Biology; Council on Cardiopulmonary, Critical Care, Perioperative and Resuscitation; and Council on Cardiovascular Surgery and Anesthesia
Published: October 2019

Pulmonary embolism (PE) represents the third leading cause of cardiovascular mortality. The technological landscape for management of acute intermediate- and high-risk PE is rapidly evolving. Two interventional devices using pharmacomechanical means to recanalize the pulmonary arteries have recently been cleared by the US Food and Drug Administration for marketing, and several others are in various stages of development. The purpose of this document is to clarify the current state of endovascular interventional therapy for acute PE and to provide considerations for evidence development for new devices that will define which patients with PE would derive the greatest net benefit from their use in various clinical settings. First, definitions and limitations of commonly used risk stratification tools for PE are reviewed. An adjudication of risks and benefits of available interventional therapies for PE follows. Next, considerations for optimal future evidence development in this field are presented in the context of the current US regulatory framework. Finally, the document concludes with a discussion of the pros and cons of the rapidly expanding PE response team model of care delivery.
Impact of Body Mass Index on the Outcomes of Catheter Ablation of Atrial Fibrillation: A European Observational Multicenter Study
Authors: Providência Rui , Adragão Pedro , de Asmundis Carlo , Chun Julian , Chierchia Gianbattista , Defaye Pascal , Anselme Frédéric , Creta Antonio , Lambiase Pier D. , Schmidt Boris , Chen Shaojie , Cavaco Diogo , Hunter Ross J. , Carmo João , Combes Stephane , Honarbakhsh Shohreh , Combes Nicolas , Sousa Maria João , Jebberi Zeynab , Albenque Jean‐Paul , Boveda Serge
Published: October 2019

Background

Outcomes of catheter ablation of atrial fibrillation (
AF
) are variable and the predictors of success require further elucidation since the identification of correctable risk factors could help to optimize therapy. We aimed to assess the impact of body mass index (
BMI
) in the overall safety and efficacy of catheter ablation of
AF
, with emphasis on the use of cryoballoon ablation and novel oral anticoagulants.

Methods and Results

There were 2497 consecutive patients undergoing catheter ablation of
AF
in 7 European high volume centers were stratified according to
BMI
(normal weight <25 kg/m
2
, pre‐obese 25–30 kg/m
2
, obesity 30–35 kg/m
2
, and morbid obesity ≥35 kg/m
2
) and comparisons of procedural outcomes evaluated. Pre‐obese and obese patients presented more comorbidities (hypertension, diabetes mellitus, and sleep apnea), and had higher rates of non‐paroxysmal
AF
ablation procedures. The rate of atrial 12‐month arrhythmia relapse increased alongside with
BMI
(35.2%, 35.7%, 43.6%, and 48.0%
P
<0.001). During a median follow‐up of 18.8 months (interquartile range 11–28), after adjusting for all baseline differences,
BMI
was an independent predictor of relapse (hazard ratio=1.01 per kg/m
2
; 95% CI 1.01–1.02;
P
=0.002), adding incremental predictive value to obstructive sleep apnea.
BMI
was not a predictor for any of the reported complications. Using novel oral anticoagulants and cryoballoon ablation was safe and efficacy was comparable with vitamin‐K antagonists and radiofrequency ablation.

Conclusions

Obese patients present with a more adverse comorbidity profile, more advanced forms of
AF
, and have lower chances of being free from
AF
relapse after ablation. Use of novel oral anticoagulants and cryoballoon ablation may be an option in this patient group.
Endothelial Function Assessed by Digital Volume Plethysmography Predicts the Development and Progression of Type 2 Diabetes Mellitus
Authors: Hahad Omar , Wild Philipp S. , Prochaska Jürgen H. , Schulz Andreas , Hermanns Iris , Lackner Karl J. , Pfeiffer Norbert , Schmidtmann Irene , Beutel Manfred , Gori Tommaso , Deanfield John E. , Münzel Thomas
Published: October 2019

Background

Endothelial dysfunction is a consequence of type 2 diabetes mellitus, but it is unclear whether endothelial dysfunction of conductance versus resistance vessels may also precede type 2 diabetes mellitus development.

Methods and Results

In a population‐based cohort of 15 010 individuals from the GHS (Gutenberg Health Study) (aged 35–74 years at enrollment in 2007–2012), we identified 1610 cases of incident pre–diabetes mellitus and 386 cases of incident type 2 diabetes mellitus by hemoglobin A
1c
(HbA
1c
) and/or medical history between 2012 and 2017. Endothelial function of conductance and resistance vessels was measured by flow‐mediated dilation and digital volume plethysmography–derived reactive hyperemia index, respectively. Multivariable regression modeling was used to estimate β coefficients of HbA
1c
levels at follow‐up and relative risks of incident (pre–)diabetes mellitus. Reactive hyperemia index was independently associated with HbA
1c
after multivariable adjustment for baseline HbA
1c
, sex, age, socioeconomic status, arterial hypertension, waist/height ratio, pack‐years of smoking, non–high‐density lipoprotein/high‐density lipoprotein ratio, physical activity, family history of myocardial infarction/stroke, prevalent cardiovascular disease, medication use, and C‐reactive protein (β=−0.020;
P
=0.0029). The adjusted relative risk per SD decline in reactive hyperemia index was 1.08 (95% CI, 1.02–1.15;
P
=0.012) for incident pre–diabetes mellitus and 1.16 (95% CI, 1.01–1.34;
P
=0.041) for incident type 2 diabetes mellitus. Flow‐mediated dilation independently increased the relative risk for developing pre–diabetes mellitus by 8% (95% CI, 1.02–1.14;
P
=0.012), but it was not independently associated with incident type 2 diabetes mellitus (relative risk, 1.01; 95% CI, 0.86–1.19;
P
=0.92) and with HbA
1c
(β=−0.003;
P
=0.59).

Conclusions

Endothelial dysfunction of resistance rather than conductance vessels may precede the development of (pre–)diabetes mellitus. Assessment of endothelial function by digital volume plethysmography may help to identify subjects at risk for development of type 2 diabetes mellitus.
The Play’s the Thing: Toys in Ancient Jewish Society—Visualizing through the Words of the Rabbis
Authors: Schwartz Joshua
Published: October 2019

Everyone plays and that, of course, includes children. In an ideal world, there would be literary traditions, archaeological remains and artistic renditions, which would enable the reconstruction of toys. Unfortunately, the situation does not exist for ancient Jewish society. For the most part, there are depictions in rabbinic literature and it is those toy traditions which I examine.

The study begins with those toys explicitly connected to halakhic issues, firstly with those traditions in which the toy is essential to the law and afterwards to those in which the toy is tangential to the law. The study then deals with those toys mentioned in a nonlegal rabbinic framework. Finally, I discuss toys that were popular in the Greco-Roman world but not mentioned in rabbinic literature. I seek to determine whether descriptions of toys in rabbinic literature and set within the broader Greco-Roman world are sufficient for visualization.
Enhancing the Efficiency of Dye Sensitized Solar Cells by Using Anatase and Brookite Mixed Phases of TiO2
Authors: Khan M. I. , Shahnawaz  , Imran Shahid , Yousaf Muhammad Waqas , Wahab A. , Adil F. , Majeed Shahbaz , Khan M. Fiaz , Aziz Tariq
Published: October 2019

The phases of TiO2 have an important role in the efficiency of dye sensitized solar cells (DSSCs). In this research, the effects of anatase and mixed phases (brookite and anatase) of TiO2 on the efficiency of DSSCs have been reported. 2% Cu doped TiO2
(Cu:TiO2) thin films are prepared by sol–gel dip coating technique. These films are annealed at the temperatures of "350 °C, 450 °C, 550 °C and 650 °C." XRD showed that at 550 °C and 650 °C, films have mixed phases of TiO2. Also, it showed
that grain size is increased by increasing temperature. No extra phases of Cu like CuO etc. were observed in XRD graphs, which confirmed that Cu is completely dissolved into TiO2. UV-Vis results showed that all the films have more than 80% transmittance in the visible region. The
optical band gap energy (Eg) of films at "350 °C, 450 °C, 550 °C and 650 °C" is 3.96, 3.81, 3.75 and 3.64 eV, respectively. The electrical resistivity of these thin films by four point probe technique is calculated as 121.8 × 102 Ω-m,
95.69 × 102 Ω-m, 86.65 × 102 Ω-m and 76.3 × 102Ω-m respectively. Solar simulator results showed that the current density (Jsc) of mixed phase is higher than single phase, causing higher efficiency. The maximum
Jsc 5.12 mAcm–2 is achieved at 650 °C (mixed phase), resulting in higher efficiency of 2.35% which is more than 100 times the efficiency of anatase phase which has 1.18%. This work will provide a way to enhance the efficiency of DSSCs by using mixed phases
of TiO2. In future, if 1-D structure of these mixed phases is used in DSSCs then efficiency of DSSCs will improve definitely (or positively).
Analysis of Temperature Sensors Based on Ternary One Dimensional Photonic Crystals with Double Defects
Authors: El-Ghany S. E.-S. Abd
Published: October 2019

Based on the transfer matrix method (TMM), the interaction of electromagnetic waves in ultraviolet (Uv), visible and Infrared (IR) spectra with ternary one-dimensional photonic crystals with different double defects, has been theoretically studied. The multilayer system has been taken
as temperature dependent. The numerical results showed that the number of photonic band gap (PBG) was increased by increasing the degree of temperature. The variation of temperature, the thickness of the second layer and both the type and the thickness of the second defect caused shifting
of the photonic ban gaps to higher wavelengths which can be exploited in the design of temperature sensors.
Optimal Design and Performance Study of Optical Fiber Raman Amplifier with Flat Gain
Authors: Li Hongsheng
Published: October 2019

Optical fiber communication is favored by many communication manufacturers because of its low interference, large capacity, long distance and low consumption. Extending the transmission distance of optical fiber communication system will result in attenuation loss. Therefore, it is
necessary to improve the incident power of the initial optical fiber, but it will be affected by Raman scattering effect, thus reducing the performance of the overall optical fiber communication system. In order to overcome the above problems, Raman amplifier is used to pump high-power short-wavelength
light wave and amplify long-wavelength and low-power signals, but the flattening of signal gain needs to be considered. In this study, the working principle of Raman amplifier is introduced, the Raman pump module is optimized, the system architecture of the module is studied, and the module
circuit is designed. It mainly covers the structure design, driving circuit design and auxiliary circuit design of the module. In the experimental process, based on the transmission coupling equation of the fiber Raman amplifier, the distribution of pump and signal power on the fiber is calculated
by numerical analysis. By optimizing the pump module, the gain flatness of the amplification system is optimized, and the signal gain of the whole fiber communication system is reduced by more than 80%. It proves that the optimal design of fiber Raman amplifier proposed in this study is effective
and can achieve the overall stability of signal reception in the application of optical fiber communication system.
The Effect of Weather on Crime in a Torrid Urban Zone
Authors: Trujillo Juan C. , Howley Peter
Published: October 2019

This study investigates the relationship between weather and crime in Barranquilla, Colombia, a city in the Torrid Zone, which in contrast to more commonly studied temperate zones is hot and humid year-round. Our analysis is based on daily variations in four weather variables (temperature, relative humidity, precipitation, and wind speed) and two indicators of criminal activity, namely, homicides and interpersonal violence. To help identify statistical links, we add controls for temporal variables. Using count data models in the estimations, we do not find any statistically significant relationship between weather patterns and homicides. However, we find that weather can be an important predictor of interpersonal violence in this area. These findings draw attention to the importance of considering weather factors when designing a long-run urban security policy in one of the world’s most vulnerable regions to climate change.
Power system education and research applications using free and open-source, graphical and multiplatform PSP-UFU software
Authors: Oliveira Thales L , Guimarães Geraldo C , Silva Leonardo RC , Rezende Jaqueline O
Published: October 2019

This article presents a new free and open-source computer platform that is capable of performing power flow simulations, balanced and unbalanced short-circuits, besides transitory and dynamic stability studies with user-defined controls. The software, called Power Systems Platform from the Federal University of Uberlândia (PSP-UFU), has as its goal to aid in the areas of research and education. Through an interface aligned with the CAD tool, the construction of any electric network and control system is permitted by the directing of visual elements. Standard software architecture was used in the development of the platform, as well as standardisation and documentation, which are necessary practices for an understanding into the source code and software development by third parties. The software possesses an excellent computational performance and a friendly and intuitive interface, which all go on to make it ideal for educational applications in electric power systems.