bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigating the quantitative and qualitative status of effluent in the wastewater treatment plant in Iran Central Iron Ore
Authors: Mehralian Mohammad , Gholamrezapour Ebrahim , Fatahi Hamed , Izadian Mehdi , Khashij Maryam
Published: July 2020

The aim of present study was to investigate the quality of the produced effluent from different units of the Iran Central Iron Ore in Bafq city and comparison of effluent with the standards. This study presents the physicochemical and biological parameters data of effluent of three Sequencing batch reactors (SBR) with a capacity of 160 m3∙d−1. Most common parameters include pH, total suspended solids (TSS), total nitrogen (TN), total phosphorus (TP), biochemical oxygen demand (BOD5), chemical oxygen demand (COD), heavy metals, and total coliforms and fecal coliforms as biological indicators. Then, for each SBR system, the average of each parameter was determined, and results were compared with the standard recommended by the Iranian Environmental Protection Agency. Based on the results, some of the parameters, including BOD5, COD, and TSS in the wastewater treatment plant (WWTP) effluent, are higher than the permitted amount for discharge to the surface water. Considering the BOD5, COD, and TSS concentration in WWTPs, the treated wastewater is only suitable for agricultural and irrigation use. Therefore, wastewater produced by Iran Central Iron Ore Co. will need additional treatment to achieve standard quality of water before discharge in surface water and adsorbent well.
Baicalin prevents the up‐regulation of TRPV1 in dorsal root ganglion and attenuates chronic neuropathic pain
Authors: Wang Zheyin , Ling Diyang , Wu Chenxiang , Han Jian , Zhao Yan
Published: July 2020

Background

Neuropathic pain is a major public health problem because it has a considerable impact on life quality of patients. TRP channels from dorsal root ganglion (DRG) play a crucial role in facilitating pain transmission at peripheral and spinal sites. Baicalin has neuroprotective effects and improves the pathological and behavioural outcomes of various types of nerve injury. The present study aims to examine the analgesic effects of baicalin on chronic neuropathic pain.

Methods

Neuropathic pain animal model was created by chronic constriction injury of the sciatic nerve (CCI). Behavioural tests were performed by von Frey and hot plate tests. mRNA and protein expression levels were examined by quantitative RT‐PCR and western blot.

Results

Consecutive intraperitoneal administration of baicalin for 16 days reduced the mechanical and thermal nociceptive responses induced by CCI surgery in a dose‐dependent manner. The mRNA expression levels of Trpv1 and Trpa1 were significantly increased in the DRG of CCI rats. Moreover baicalin administration reversed TRPV1 expression and phosphorylation of ERK in DRG neurons after peripheral nerve injury.

Conclusions

Our results suggested that baicalin may ameliorate neuropathic pain by suppressing TRPV1 up‐regulation and ERK phosphorylation in DRG of neuropathic pain rats. Baicalin has a significant analgesic effect on alleviating neuropathic pain and thus may serve as a therapeutic approach for neuropathic pain.
On the Carbonate Formation in Thermally Stressed Hydroxysodalite – Some Facts to Notice for SOD Application in Separation Processes
Authors: Peschke Irma , Hildebrand Hagen , Pioch Robert , Buhl Josef‐Christian
Published: July 2020

Basic sodalite (hydroxysodalite) was synthesized from two Si‐Al sources: (1) kaolin to obtain |Na7.5(OH)1.5(H2O)3.5|[AlSiO4]6 sodalites (SOD) with small crystals (< 0.5 μm) and (2) a mixture of cristobalite and corundum (CC) to obtain larger microcrystals (1–5 μm) with ideal composition |Na8(OH)2(H2O)2|[AlSiO4]6. Both SOD were exposed to thermal stress by long‐time heating at 773 K under open conditions, in N2 and CO2 atmosphere and in presence of a NaOH‐Na2CO3 melt. The crystals obtained from kaolin were dehydrated and developed remarkable degrees of carbonate cage fillings already under open conditions. The large microcrystals obtained from CC exhibit this effect only at very low scale even after long‐time heating in CO2 atmosphere. Whereas heating in presence of the melt showed no effect, investigations in CO2 clearly indicate an intra‐cage reaction between CO2 and the enclathrated [Na4OH]3+ ions as the carbonate generating mechanism instead of destruction of hydroxysodalite followed by recrystallization. A model is proposed, in which cage fillings [Na3□]3+ with a vacancy in the Na tetrahedron known from dehydrated hydrosodalites |Na6|[AlSiO4]6 are required to induce the intra‐cage reaction of hydroxysodalite. As those fillings only occur in a noticeable number in dehydrated hydroxysodalite obtained from kaolin, the large extent of the carbonate formation inside this sample becomes obvious. The results are significant for future improvement of hydroxysodalite membranes.
Highly Active Heterogeneous PdCl2/MOF Catalyst for Suzuki–Miyaura Cross‐Coupling Reactions of Aryl Chloride
Authors: Gong Xue‐Fang , Zhang Ling‐Yan , Zhang Hui‐Xin , Cui Yu‐Meng , Jin Fen‐Chun , Liu Yu , Zhai Yu‐Feng , Li Jin‐Heng , Liu Gui‐Yan , Zeng Yong‐Fei
Published: July 2020

The exploration of highly efficient Pd/MOF heterogeneous catalyst system for the Suzuki–Miyaura cross‐coupling (SMC) reactions of aryl chlorides is still challenging. Herein, a PdCl2/UiO‐67‐bpydc was successfully synthesized by immobilizing a low amount of PdCl2 onto the zirconium‐based MOF (UiO‐67‐bpydc). PdCl2/UiO‐67‐bpydc showed excellent catalytic performance and good recycle ability for the SMC reaction of aryl chlorides under an ambient condition. Furthermore, PdCl2/UiO‐67‐bpydc retains the high catalytic activity even after five cycles, and exhibited excellent substrate size selectivity.
Gesundheitliche Auswirkungen von Umgebungslärm im urbanen Raum
Authors: Wothge Jördis , Niemann Hildegard
Published: July 2020

Umgebungslärm ist eine große Belastung für die Menschen in Deutschland, insbesondere im urbanen Raum. Häufig sind mehrere Schallquellenarten für die Belastung verantwortlich. Die andauernde Belastung kann verschiedene und weitreichende gesundheitliche Auswirkungen haben wie Lärmbelästigung, Schlafstörungen, ischämische Herzerkrankungen und Depressionen. Zusätzlichen Belastungen entstehen z. B. durch Feinstaub oder Luftschadstoffe. Um den Herausforderungen im urbanen Raum zu begegnen, lassen sich verschiedene Maßnahmen und Instrumente beschreiben und diskutieren. Der vorliegende Beitrag gibt einen Überblick über wichtige gesundheitliche Folgen einer langfristigen Geräuschbelastung, thematisiert die verbundenen Herausforderungen im städtischen Raum und zeigt Möglichkeiten zur Lärmminderung auf.
Organic metamorphism as a key for reconstructing tectonic processes: a case study from the Austroalpine unit (Eastern Alps)
Authors: Rantitsch Gerd , Iglseder Christoph , Schuster Ralf , Hollinetz Marianne Sophie , Huet Benjamin , Werdenich Manuel
Published: July 2020

At the northwestern margin of the Gurktal Alps (Eastern Alps), Eoalpine (Cretaceous) thrusting of carbonaceous material (CM) bearing metasediments formed a very low- to low-grade metamorphic nappe stack above higher-grade metamorphic basement nappes. Sedimentary burial as well as progressive metamorphism transformed the enclosed CM to anthracite, metaanthracite and semigraphite. In a kinematically well-constrained section at the northwestern frontal margin of the nappe stack, this transformation has been investigated by vitrinite reflectance measurements and Raman spectroscopy of carbonaceous materials (RSCM). Automated, interactive fitting of Raman spectra estimates the metamorphic peak temperatures in a complete section through the upper part of the Upper Austroalpine unit. A RSCM trend indicates a temperature profile of ca. 250–600 °C. The top part of the gradient is reconstructed by one-dimensional thermal modeling. The certainty of ca. ± 25 °C at a confidence level of 0.9 resembles the data variability within a sample location. Due to the large calibration range, the method is able to reconstruct a thermal crustal profile in space and time. The study highlights the versatility of RSCM, which characterizes almost 250 Ma of a complex and polyphase tectonic history. RSCM data characterize the Variscan metamorphic grade in nappes now imbricated in the Eoalpine nappe stack. They additionally constrain a numerical model which emphasizes the significance of an increased thermal gradient in a continental margin towards the western Neotethyan ocean during Permo-Triassic lithospheric extension. It finally characterizes the Eoalpine metamorphic gradient during nappe stacking and a significant metamorphic jump related to exhumation and normal faulting.
Self-assembled mono- and bilayers on gold electrodes to assess antioxidants—a comparative study
Authors: Ravandeh Mehdi , Thal Dana , Kahlert Heike , Wende Kristian , Lalk Michael
Published: July 2020

Oxidative stress is considered as an imbalance of reactive species over antioxidants, leading to diseases and cell death. Various methods have been developed to determine the antioxidant potential of natural or synthetic compounds based on the ability to scavenge free radicals. However, most of them lack biological relevance. Here, a gold-based self-assembled monolayer (SAM) was compared with a gold-supported lipid bilayer as models for the mammalian cell membrane to evaluate the free radical scavenging activity of different antioxidants. The oxidative damage induced by reactive species was verified by cyclic and differential pulse voltammetry and measured by the increase of electrochemical peak current of a redox probe. Trolox, caffeic acid (CA), epigallocatechin gallate (EGCG), ascorbic acid (AA), and ferulic acid (FA) were used as model antioxidants. The change in the decrease of the electrochemical signal reflecting oxidative membrane damage confirms the expected protective role. Both model systems showed similar efficacies of each antioxidant, the achieved order of radical scavenging potential is as follows: Trolox > CA > EGCG > AA > FA. The results showed that the electrochemical assay with SAM-modified electrodes is a stable and powerful tool to estimate qualitatively the antioxidative activity of a compound with respect to cell membrane protection against biologically relevant reactive species.
Why is renal impairment associated with poorer cancer specific survival in breast cancer patients?: a comparison with patients with other comorbidities
Authors: Evans Andy , Petty Russell , Macaskill Jane
Published: July 2020

Background

Our aim is to assess whether the poor breast cancer specific survival (BCSS) seen in women with breast cancer and impaired renal function can be explained by associations with other prognostic factors.

Methods

The study group was a consecutive series of patients undergoing breast ultrasound (US) who had invasive breast cancer (n = 1171). All women had their US diameter and mean stiffness (kPa) at shear wave elastography (SWE) recorded. The core biopsy grade and receptor status were noted. Core biopsy of abnormal axillary nodes and the patient referral source was also noted. Survival including cause of death was ascertained. Comorbidities at diagnosis were recorded. Patients were divided into those with a GFR<60 (“renal group”), those with other comorbidities and those with none. BCSS was assessed using Kaplan–Meier survival curves and Cox proportional hazards regression.

Results

One thousand, one hundred and forty-one patients constituted the study group. 107 (9%) patients had impaired renal function, 182 (16%) had other comorbidities while 852 (75%) had no comorbidities. Mean follow-up was 5.8 years. 109 breast cancer and 122 non-breast cancer deaths occurred. BCSS in the renal group was significantly worse than the other groups. Women with renal comorbidity were older, more likely to present symptomatically, have a pre-operative diagnosis of axillary metastases, and have larger and stiffer cancers. Cox proportional hazards regression showed that renal impairment maintained independent significance.

Conclusion

The poor BCSS in women with impaired renal function is partially explained by advanced tumour stage at presentation. However, impaired renal function maintains an independent prognostic effect.
Recent advances in the biosynthesis of RiPPs from multicore-containing precursor peptides
Authors: Rubin Garret M , Ding Yousong
Published: July 2020

Ribosomally synthesized and post-translationally modified peptides (RiPPs) compose a large structurally and functionally diverse family of natural products. The biosynthesis system of RiPPs typically involves a precursor peptide comprising of a leader and core motif and nearby processing enzymes that recognize the leader and act on the core for producing modified peptides. Interest in RiPPs has increased substantially in recent years as improvements in genome mining techniques have dramatically improved access to these peptides and biochemical and engineering studies have supported their applications. A less understood, intriguing feature in the RiPPs biosynthesis is the precursor peptides of multiple RiPPs families produced by bacteria, fungi and plants carrying multiple core motifs, which we term “multicore”. Herein, we present the prevalence of the multicore systems, their biosynthesis and engineering for applications.
Sustainable Peeling of Kapok Tree (Ceiba pentandra) Bark by the Chimpanzees (Pan troglodytes verus) of Comoé National Park, Ivory Coast
Authors: Lapuente Juan , Arandjelovic Mimi , Kühl Hjalmar , Dieguez Paula , Boesch Christophe , Linsenmair K. Eduard
Published: July 2020

Primates often consume either bark or cambium (inner bark) as a fallback food to complete their diet during periods of food scarcity. Wild chimpanzees exhibit great behavioral diversity across Africa, as studies of new populations frequently reveal. Since 2014, we have been using a combination of camera traps and indirect signs to study the ecology and behavior of wild chimpanzees (Pan troglodytes verus) in Comoé National Park, Ivory Coast, to document and understand the behavioral adaptations that help them to survive in a savanna–forest mosaic landscape. We found that Comoé chimpanzees peel the bark of the buttresses of kapok tree (Ceiba pentandra) trees to eat the cambium underneath. Individuals of all sex/age classes across at least six neighboring communities peeled the bark, but only during the late rainy season and beginning of the dry season, when cambium may represent an important fallback food. Baboons (Papio anubis) also target the same trees but mainly eat the bark itself. Most of the bark-peeling wounds onCeibatrees healed completely within 2 years, seemingly without any permanent damage. We recorded chimpanzees visiting trees in early stages of wound recovery but leaving them unpeeled. Only 6% of peeled trees (N= 53) were reexploited after a year, suggesting that chimpanzees waited for the rest of the trees to regrow the bark fully before peeling them again, thus using them sustainably. Many human groups of hunter-gatherers and herders exploited cambium sustainably in the past. The observation that similar sustainable bark-peeling behavior evolved in both chimpanzees and humans suggests that it has an important adaptive value in harsh environments when other food sources become seasonally scarce, by avoiding the depletion of the resource and keeping it available for periods of scarcity.
Classifying Chimpanzee (Pan troglodytes) Landscapes Across Large-Scale Environmental Gradients in Africa
Authors: van Leeuwen Kelly L. , Hill Ross A. , Korstjens Amanda H.
Published: July 2020

Primates are sometimes categorized in terms of their habitat. Although such categorization can be oversimplistic, there are scientific benefits from the clarity and consistency that habitat categorization can bring. Chimpanzees (Pan troglodytes) inhabit various environments, but researchers often refer to “forest” or “savanna” chimpanzees. Despite the wide use of this forest–savanna distinction, clear definitions of these landscapes for chimpanzees, based on environmental variables at study sites or determined in relation to existing bioclimatic classifications, are lacking. The robustness of the forest–savanna distinction thus remains to be assessed. We review 43 chimpanzee study sites to assess how the landscape classifications of researchers fit with the environmental characteristics of study sites and with three bioclimatic classifications. We use scatterplots and principal components analysis to assess the distribution of chimpanzee field sites along gradients of environmental variables (temperature, rainfall, precipitation seasonality, forest cover, and satellite-derived Hansen tree cover). This revealed an environmental continuum of chimpanzee study sites from savanna to dense forest, with a rarely acknowledged forest mosaic category in between, but with no natural separation into these three classes and inconsistencies with the bioclimatic classifications assessed. The current forest–savanna dichotomy therefore masks a progression of environmental adaptation for chimpanzees, and we propose that recognizing an additional, intermediate “forest mosaic” category is more meaningful than focusing on the ends of this environmental gradient only. Future studies should acknowledge this habitat continuum, place their study sites on the forest–savanna gradient, and include detailed environmental data to support further attempts at quantification.
„Webcam child sexual abuse“
Authors: de Tribolet-Hardy Fanny , Hill Andreas , Habermeyer Elmar
Published: July 2020

Die forensische Psychiatrie sieht sich mit einem neuen Phänomen der Internetsexualdelinquenz konfrontiert, dem „webcam child sexual abuse“ (WCSA), der mittels des Internets erfolgenden Anstiftung zur sexuellen Ausbeutung von Minderjährigen. Der Begriff umfasst jegliche Form sexueller Ausbeutung von Minderjährigen per Internet-Livestream, wobei das Spektrum der übertragenen Handlungen vom Posieren bis hin zu sexuell-sadistischen Übergriffen reicht. Während Schätzungen des Kinderhilfswerkes Terre des Hommes seit 2009 auf eine hohe Prävalenz solcher Handlungen verweisen, stieg die Zahl der Verurteilungen wegen WCSA erst in den letzten Jahren an. Die Anonymität des Internets und das weitgehende Fehlen von Datenspuren erschweren nicht nur die Überführung der Täter, sondern bergen auch Herausforderungen für die forensisch-psychiatrische Begutachtung. Anhand von WCSA-Fällen in der hiesigen Gutachtenstelle erfolgen Überlegungen zur kriminologischen Einordnung der Tathandlungen sowie zu Herausforderungen im Rahmen des Begutachtungsprozesses. Mithilfe einer idealtypischen Kasuistik werden Hypothesen zur Fallkonzeption gebildet und daraus Empfehlungen für die diagnostische Einordnung, Beurteilung der Einsichts- und Steuerungsfähigkeit, Prognose und Behandlung abgeleitet.
Phase boundary engineering of metal-organic-framework-derived carbonaceous nickel selenides for sodium-ion batteries
Authors: Lu Shiyao , Wu Hu , Hou Jingwei , Liu Limin , Li Jiao , Harris Chris J. , Lao Cheng-Yen , Guo Yuzheng , Xi Kai , Ding Shujiang , Gao Guoxin , Cheetham Anthony K. , Kumar R. Vasant
Published: July 2020

Sodium-ion batteries (SIBs) are promising power sources due to the low cost and abundance of battery-grade sodium resources, while practical SIBs suffer from intrinsically sluggish diffusion kinetics and severe volume changes of electrode materials. Metal-organic framework (MOFs) derived carbonaceous metal compound offer promising applications in electrode materials due to their tailorable composition, nanostructure, chemical and physical properties. Here, we fabricated hierarchical MOF-derived carbonaceous nickel selenides with bi-phase composition for enhanced sodium storage capability. As MOF formation time increases, the pyrolyzed and selenized products gradually transform from a single-phase Ni3Se4 into bi-phase NiSex then single-phase NiSe2, with concomitant morphological evolution from solid spheres into hierarchical urchin-like yolk-shell structures. As SIBs anodes, bi-phase NiSex@C/CNT-10h (10 h of hydrothermal synthesis time) exhibits a high specific capacity of 387.1 mAh/g at 0.1 A/g, long cycling stability of 306.3 mAh/g at a moderately high current density of 1 A/g after 2,000 cycles. Computational simulation further proves the lattice mismatch at the phase boundary facilitates more interstitial space for sodium storage. Our understanding of the phase boundary engineering of transformed MOFs and their morphological evolution is conducive to fabricate novel composites/hybrids for applications in batteries, catalysis, sensors, and environmental remediation.
Tunable colors and conductivity by electroless growth of Cu/Cu2O particles on sol-gel modified cellulose
Authors: Landsiedel Justus , Root Waleri , Schramm Christian , Menzel Alexander , Witzleben Steffen , Bechtold Thomas , Pham Tung
Published: July 2020

Development of colored surfaces by formation of nano-structured aggregates is a widely used strategy in nature to color lightweight structures (e.g. butterflies) without the use of dye pigments. The deposition of nanoscale particles mimics nature in it’s approach coloring surfaces. This work presents sol-gel modification of cellulose surfaces used to form a template for growth of Cu/Cu2O core-shell particles with defined size-distributions. Besides improving the adhesion of the deposited particulate material, the sol-gel matrix serves as a template for the control of particle sizes of the Cu/Cu2O structures, and as a consequence of particle size variation the surface color is tunable. As an example, red color was achieved with an average particle size of 35 nm, and shifts gradually to blue appearance when particles have grown to 80 nm on the sol-gel modified fabric. The copper concentration on representative fabrics is kept low to avoid modifying the textile characteristics and were all in the range of 150–170 mg per g of cellulose material. As a result of copper deposition on the surface of the material, the cellulose fabric also became electrically conductive. Remarkably, the electrical conductivity was found to be dependent on the average particle sizes of the deposits and thus related to the change in observed color. The generation of color by growth of nano-sized particles on sol-gel templates provides a highly promising approach to stain surfaces by physical effects without use of synthetic colorants, which opens a new strategy to improve environmental profile of coloration.
Towards Understanding and Arguing with Classifiers: Recent Progress
Authors: Shao Xiaoting , Rienstra Tjitze , Thimm Matthias , Kersting Kristian
Published: July 2020

Machine learning and argumentation can potentially greatly benefit from each other. Combining deep classifiers with knowledge expressed in the form of rules and constraints allows one to leverage different forms of abstractions within argumentation mining. Argumentation for machine learning can yield argumentation-based learning methods where the machine and the user argue about the learned model with the common goal of providing results of maximum utility to the user. Unfortunately, both directions are currently rather challenging. For instance, combining deep neural models with logic typically only yields deterministic results, while combining probabilistic models with logic often results in intractable inference. Therefore, we review a novel deep but tractable model for conditional probability distributions that can harness the expressive power of universal function approximators such as neural networks while still maintaining a wide range of tractable inference routines. While this new model has shown appealing performance in classification tasks, humans cannot easily understand the reasons for its decision. Therefore, we also review our recent efforts on how to “argue” with deep models. On synthetic and real data we illustrate how “arguing” with a deep model about its explanations can actually help to revise the model, if it is right for the wrong reasons.
DNA sequencing using nanopores and kinetic proofreading
Authors: Ling Xinsheng Sean
Published: July 2020

We discuss the feasibility of using a nanopore sandwich device to implement the principle of kinetic proofreading to discriminate incorrect hybridizing oligonucleotides on a target DNA or RNA. We propose a method of sequencing DNA or RNA using this approach. The design parameters for such a DNA sequencer are estimated from the Hopfield‐Ninio theory of kinetic proofreading and Schrödinger’s first‐passage‐time distribution function.
Distillation of Best Practices from Refactoring FLASH for Exascale
Authors: Dubey Anshu , O’Neal Jared , Weide Klaus , Chawdhary Saurabh
Published: July 2020

FLASH is a multiphysics software package that was created in 1998 by combining three preexisting packages and has undergone three major revisions. Software design and engineering practices were integrated early in the development and maintenance processes of FLASH, and these processes have evolved strongly at each of the revisions. As high-performance computing enters the age of exascale, challenges along the orthogonal axes of node-level hardware and solver heterogeneity force developers of complex multiphysics software to consider a software architecture overhaul. Because of the nature and scope of necessary changes, an effort to refactor and grow the architecture of the FLASH code has been launched as a separate software project. For this project to succeed, its development team must evaluate, improve, and modernize software processes and policies to meet the unique challenges posed by the exascale era. We describe here our experiences, lessons we have learned, and the methods that we have developed as part of this ongoing project. Within the context of the challenges posed by exascale, we review the FLASH design approach as well as some of the main software engineering processes and tools that have been implemented or updated throughout the lifetime of FLASH. Modernization applied to these processes and tools is also detailed. Reviewing and reevaluating the FLASH experience of establishing and updating software design and engineering practices have been helpful in understanding the needs of the project as it transitions to exascale and in planning the transition. We find that our historical design methodology is still important and relevant. We also believe that using a mixture of plan-based and agile methods is still the best for our project and is in accord with the guidance found in the literature. We present a section on inferences and lessons learned related to software design and engineering practices.
Use of the Certificate for Pharmaceutical Products (CPP) in 18 Maturing Pharmaceutical Markets: Comparing Agency Guidelines with Company Practice
Authors: Rodier Céline , Bujar Magda , McAuslane Neil , Patel Prisha , Liberti Lawrence
Published: July 2020

Background

The certificate of pharmaceutical product (CPP) was implemented to accelerate the availability of new drugs in developing countries by providing evidence of the quality of products and reducing the time to market through reliance on a prior trusted analysis. However, the CPP format, issuing process and use have not been revised since 1997 and there are significant differences among countries in regard to requirements for CPP timing, terminology, and format. We sought to determine current CPP practices versus national regulatory guidelines and to inform recommendations for the efficient use of the CPP based on the needs of the modern regulatory environment.

Methods

We conducted a comparative analysis of company practice versus agency guidelines across 18 maturing pharmaceutical markets using data from the Cortellis for Regulatory Intelligence® (CRI) and the Centre for Innovation in Regulatory Science (CIRS) Emerging Markets Regulatory Review Times (EMaRReT) databases and regulatory authorities’ websites.

Results

Of the studied 18 countries, 16 require the CPP for submission of new registrations; many accept alternative documentation but most still require legalization of the CPP and many are not compliant with the complex CPP format. Additional complicating factors include language requirements and varying local guidelines for CPP submission timing and validity dates.

Conclusions

With the implementation of a number of suggested improvements, the CPP can continue to serve an important role in streamlining regulatory efficiency and provide confidence in new medicines, ensuring a more efficient and effective approval process and expediting patient access to safe and effective medicines worldwide.
‘That is why we raise children’: African American fathers' race‐related concerns for their adolescents and parenting strategies
Authors: Cooper Shauna M. , Burnett Marketa , Johnson Maria S. , Brooks Jasmin , Shaheed Janae , McBride Margarett
Published: July 2020

Introduction

The current study highlights the voices and perspectives of African American fathers, with specific emphasis on their race‐related concerns for their adolescents as well as how these concerns guide their parenting strategies.

Method

Twenty‐four African American fathers participated in 1.5–3 h long focus group interviews. All fathers (M = 42.24 years, SD = 6.93) resided in a mid‐sized city in the Southeastern United States. All participants were either biological fathers (n = 20) or non‐biological (n = 4) fathers. Fathers were residential (76%) and non‐residential (24%), with at least one adolescent child (M = 14.32 years, SD = 5.80; Range: 10–16 years). Fifty‐eight percent of fathers (n = 14) had both male and female children, 29% had only female children (n = 7) and 13% had only male children (n = 3). After codebook development and refinement, key themes were explored using a theoretical thematic analysis.

Results

In response to race‐related and other social risks for African American adolescents, fathers articulated a number of parenting motivations and intentions: 1) fathers' own racial experiences; 2) negative media images of Black youth and families (e.g. media influences, negative stereotypes, and portrayals of Black fathers); 3) preserving families through community support; 4) developing awareness of discrimination and coping strategies; 5) cultivating positive personal and cultural identities; and 6) achievement as necessity. Also, gender emerged as a critical lens for African American fathers’ concerns and parenting strategies.

Conclusion

Overall, our investigation highlights African American fathers’ own meaning‐making around concerns for their adolescents as well as how they shape parenting processes.
A Novel Penile Splint as Early Traction Therapy After Grafting Techniques for Peyronie's Disease
Authors: Fernández-Pascual Esaú , Manfredi Celeste , Cocci Andrea , Quintana Franco Luis Miguel , Egui Rojo María Alejandra , Carballido Rodríguez Joaquín , Martínez-Salamanca Juan Ignacio
Published: July 2020

Background

Some studies showed encouraging results on the efficacy and safety of penile traction therapy after Peyronie's disease (PD) surgery. The early traction therapy (ETT) could be an effective and safe approach to minimize penile shortening in patients undergoing PD surgery.

Aim

To evaluate the feasibility, efficacy, and safety of a novel penile splint as ETT in patients with PD undergoing grafting techniques.

Methods

Patients with PD underwent plaque incision and grafting technique; at the end of the procedure, a novel penile splint (ETT) was applied to all patient. The device consisted of 2 10CH intubating stylets, self-adapted to each patient, that kept the penis stretched with the aid of non-absorbable sutures. The total expense for the materials needed to build each penile splint was less than 15 euros. This active traction was maintained for 1–3 weeks; then, we removed the stitches leaving the device on-site for a passive traction. Within 3–4 weeks from surgery, the penile splint was replaced by a standard penile traction device.

Outcomes

The main outcomes evaluated at 6 months included stretched penile length (SPL), penile curvature, International Index of Erectile Function-erectile function (IIEF-EF) domain, patient satisfaction, and time to first satisfactory sexual intercourse.

Results

A total of 46 patients were enrolled. The median preoperative IIEF-EF, penile curvature, and SPL were 27 points, 70°, and 13 cm, respectively. The median follow-up was 15 months. The median postoperative IIEF-EF was 25 points (P < .001). The median residual penile curvature was 10° (P < .001). The median postoperative SPL was 13 cm (P = .269). 8 patients (17.4%) lost 1 cm of SPL; no shortening greater than 1 cm was recorded. The median time to first satisfactory sexual intercourse and patient satisfaction score was 6 weeks and 9 points, respectively.

Clinical Implications

Our results could pave the way for a new line of research, which in turn could lead to an improvement in the postoperative management of the patient undergoing surgery for PD.

Strength & Limitations

This is the first study evaluating the ETT after PD surgery. The main limitation of this study is the lack of a randomized control group. Other weaknesses are the small sample size and the short follow-up time.

Conclusion

Our novel penile splint is inexpensive, easy to assemble, and adaptable to the patient. ETT using this novel device, followed by standard traction therapy, seems to be feasible, effective, and safe.
Are We Overstating the Risk of Priapism with Oral Phosphodiesterase Type 5 Inhibitors?
Authors: Rezaee Michael E. , Gross Martin S.
Published: July 2020

Background

Priapism is an adverse drug reaction (ADR) associated with phosphodiesterase type 5 inhibitors (PDE5is) in the treatment of erectile dysfunction.

Aim

The purpose of this study was to identify the true data about PDE5i-associated priapism to properly counsel patients.

Methods

We queried the U.S. Food and Drug Administration (FDA) Adverse Reporting System Public Dashboard to identify cases of drug-induced priapism among medications commonly associated with priapism. Next, a systematic review and analysis of publications describing cases of drug-induced priapism were carried out.

Outcomes

The main outome of this study is incidence of PDE5i-induced priapism.

Results

We found 411 cases of drug-induced priapism secondary to Viagra, Cialis, or Levitra reported to the Food and Drug Administration since 1998. Compared with PDE5is, drug-induced priapism was 2.6 (n = 1,065) and 2.0 times (n = 817) more commonly reported for second-generation antipsychotics and the antidepressant/sleep aid trazodone, respectively. A total of 240 manuscripts describing cases of drug-induced priapism in patients with non-sickle cell disease were identified. PDE5i-induced priapism accounted for only 2.9% (n = 7) of drug-induced priapism cases. Second-generation antipsychotics (33.8%), a group of “other” medications (11.3%), and alpha-adrenergic antagonists (8.8%) accounted for the greatest percentage of published drug-induced priapism cases.

Clinical Implications

Extensive counseling about priapism as an ADR for PDE5i for the routine treatment of erectile dysfunction is likely unnecessary.

Strengths & Limitations

The study used national-level data to identify drug-induced priapism cases. Reported and published cases of drug-induced priapism may reflect more severe and atypical cases of this ADR, which may have underestimated our results.

Conclusion

PDE5i-induced priapism is a rare event. Drug-induced priapism should be attributed to a wider spectrum of medications that can cause this condition.
The radiobiology of HPV-positive and HPV-negative head and neck squamous cell carcinoma
Authors: Zhou Chumin , Parsons Jason L.
Published: July 2020

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide, with reported incidences of ~800 000 cases each year. One of the critical determinants in patient response to radiotherapy, particularly for oropharyngeal cancers, is human papillomavirus (HPV) status where HPV-positive patients display improved survival rates and outcomes particularly because of increased responsiveness to radiotherapy. The increased radiosensitivity of HPV-positive HNSCC has been largely linked with defects in the signalling and repair of DNA double-strand breaks. Therefore, strategies to further radiosensitise HPV-positive HNSCC, but also radioresistant HPV-negative HNSCC, have focussed on targeting key DNA repair proteins including PARP, DNA-Pk, ATM and ATR. However, inhibitors against CHK1 and WEE1 involved in cell-cycle checkpoint activation have also been investigated as targets for radiosensitisation in HNSCC. These studies, largely conducted using established HNSCC cell lines in vitro, have demonstrated variability in the response dependent on the specific inhibitors and cell models utilised. However, promising results are evident targeting specifically PARP, DNA-Pk, ATR and CHK1 in synergising with radiation in HNSCC cell killing. Nevertheless, these preclinical studies require further expansion and investigation for translational opportunities for the effective treatment of HNSCC in combination with radiotherapy.
Enabling the engine of workplace thriving through servant leadership: The moderating role of core self-evaluations
Authors: Usman Muhammad , Liu Yuxin , Li Haihong , Zhang Jianwei , Ghani Usman , Gul Habib
Published: July 2020

Grounding our research in social exchange theory and the conservation of resources perspective, we hypothesized a model that examines the effects of servant leadership (SL) on employees' workplace thriving via agentic work behaviors. To clarify the effects, employee core self-evaluations (CSEs) were investigated to determine boundary conditions on the relationship between SL and thriving. Data were collected at three points in time from 260 professionals across diverse functional backgrounds and industries. The analysis results confirmed an indirect effect from SL to workplace thriving via agentic work behaviors. Importantly, the moderation results demonstrated that the relationship between SL and workplace thriving is stronger when individuals have high CSEs. Implications for theory and practice are discussed.
Effect of newborn screening for critical CHD on healthcare utilisation
Authors: Sakai-Bizmark Rie , Kumamaru Hiraku , Webber Eliza J. , Estevez Dennys , Mena Laurie A. , Marr Emily H. , Chang Ruey-Kang R.
Published: July 2020

Objective:

To evaluate the impact of state-mandated policies for pulse oximetry screening on healthcare utilisation, with a focus on use of echocardiograms.

Data sources/study setting:

Healthcare Cost and Utilisation Project, Statewide Inpatient Databases from 2008 to 2014 from six states.

Methods:

We defined pre- and post-mandate cohorts based on dates when pulse oximetry became mandated in each state. Linear segmented regression models for interrupted time series assessed associations between implementation of the screening and changes in rate of newborns with Critical CHD-negative echocardiogram results. We also evaluated the changes in rate of newborns who underwent echocardiogram but were not diagnosed with any health issues that could cause hypoxemia.

Results:

We identified 5967 critical CHD-negative echocardiograms (2847 and 3120 in the pre- and post-mandate periods, respectively). Our models detected a statistically significant increasing trend in rate of critical CHD-negative echocardiograms in the pre-mandate period (Incidence Rate Ratio: 1.08, p = 0.02), but did not detect any statistical differences in changes between pre- and post-mandate periods (Incidence Rate Ratio: 0.93, p = 0.14). Among non-Whites, an increasing trend of Critical CHD-negative echocardiogram during the pre-mandate period was detected (Incidence Rate Ratio 1.12, p < 0.01) and was attenuated during the post-mandate period (Incidence Rate Ratio 0.89, p = 0.02). Similar results were observed in the sensitivity analyses among both Whites and non-Whites.

Conclusions:

Results suggest that mandatory state screening policies are associated with reductions in false-positive screening rates for hypoxemic conditions, with reductions primarily attributed to trends among non-Whites.
Standing Alone? Towards a More Unified View of Party–Group Relations in Contemporary Democracies
Authors: Lisi Marco , Oliveira Rui
Published: July 2020

This article focuses on the relationship between political parties and interest groups in contemporary democracies. Although this is a key topic for assessing the evolution of representative political systems and the quality of democracies, the theoretical and empirical studies have not developed a cumulative body of knowledge. As well as the lack of an integrated perspective, we argue that the literature on this topic has remained conceptually fuzzy and has failed to elaborate a common approach to examine how parties and interest organisations interact. Although some researchers point to a weakening of relations between parties and interest groups, the most current data point not to disappearance but to a change in the way both political actors interact. This article contributes to updating the research on the topic and also sheds light on why the literature has remained segmented. The study shows that the variety of conceptualisations, approaches and typologies has led to incongruent – and often non-comparable – results. The final section identifies a number of research gaps and suggest new topics and approaches that can unify this object of study in the near future.
Estimating energy expenditure of head-hauling water and grain grinding from heart rate monitor measurements in northern Mozambique
Authors: Russel Kory C , Buman Matthew P , Davis Jennifer , Haskell William L
Published: July 2020

Objective:

Even though sub-Saharan African women spend millions of person-hours per day fetching water and pounding grain, to date, few studies have rigorously assessed the energy expenditure costs of such domestic activities. As a result, most analyses that consider head-hauling water or hand pounding of grain with a mortar and pestle (pilão use) employ energy expenditure values derived from limited research. The current paper compares estimated energy expenditure values from heart rate monitorsv. indirect calorimetry in order to understand some of the limitations with using such monitors to measure domestic activities.

Design:

This confirmation study estimates the metabolic equivalent of task (MET) value for head-hauling water and hand-pounding grain using both indirect calorimetry and heart rate monitors under laboratory conditions.

Setting:

The study was conducted in Nampula, Mozambique.

Participants:

Forty university students in Nampula city who recurrently engaged in water-fetching activities.

Results:

Including all participants, the mean MET value for head hauling 20 litres (20·5 kg, including container) of water (2·7 km/h, 0 % slope) was 4·3 (sd0·9) and 3·7 (sd1·2) for pilão use. Estimated energy expenditure predictions from a mixed model were found to correlate with observed energy expenditure (r20·68,r0·82). Re-estimating the model with pilão use data excluded improved the fit substantially (r20·83,r0·91).

Conclusions:

The current study finds that heart rate monitors are suitable instruments for providing accurate quantification of energy expenditure for some domestic activities, such as head-hauling water, but are not appropriate for quantifying expenditures of other activities, such as hand-pounding grain.
Simultaneous Localization and Quantitation of Progesterone Receptor Immunoreactivity in Human Breast Carcinomas.
Authors: Roth KA
Published: July 2020

The presence of estrogen and progesterone receptors on human breast carcinomas correlates with both response to hormonal therapy and survival. Quantitation of receptor activity is typically performed by radioreceptor assay on fresh frozen tumor tissue obtained at the time of surgical resection. Estrogen and progesterone receptor reactivity can also be detected immunohistochemically on frozen sections of breast cancer and in appropriately fixed paraffin embedded tissues. Several studies have shown that semi-quantitative visual determination and quantitative image analysis assessment of estrogen and progesterone receptor immunoreactivity on fixed tissue sections is highly correlated with biochemical measurements of receptor in frozen samples. We recently developed a procedure for the simultaneous localization and quantitation of antigens in fixed tissue samples that does not involve antigen extraction, radioactive materials, or image analysis. In this procedure, which we term a “Midwestern assay”, fixed tissue sections are used with antigen-specific enzyme-linked antibodies to generate soluble reaction products which are spectrophotometrically quantitatable, as in an ELISA, and deposited reaction products which are microscopically localizable, as in enzyme-based immunohistochemistry.
Morphological and Histochemical Changes in Macrophage Activity After Novel Anti-Neoplastic Platinum Agents
Authors: Muenchen H J , Aggarwal SK , Misra HK , Andrulis P J
Published: July 2020

Poly-[(trans-1,2-diaminocyclohexane) platinumj-carboxyamylose (“poly-plat”), 5-sulfosalicylato-trans-(1,2-diaminocyclohexane) platinum (SSP), and 4-hydroxy-∝-sulfonylphenylacetato (trans 1,2-diaminocyclohexane) platinum (II) (SAP) are second generation analogs of cisplatin (CDDP) with higher efficacy and potency than cisplatin. This is particularly true of “poly-plat” which contains 1/5 the platinum of CDDP. In order to understand the mechanism of action of these compounds, isolated murine peritoneal macrophages in culture medium were treated with “poly-plat”, SSP, or SAP (5 μg/ml) for 2 h. Drug containing medium was then replaced with fresh medium and the cells were allowed to incubate at 37° C (5% CO2) for 24 h. Supernatants were collected at 0.5, 1, 2, and 24 h post-treatment for immunocytochemical analysis. Confocal microscopy studies demonstrated an increase in the number of lysosomes in the treated macrophages, but only “poly-plat” and SSP treated macrophages were stimulated to form cytoplasmic extensions at 2 h and 24 h.
Insights About Brain Tumors Gained Through Immunohistochemistry and in Situ Hybridization of Nuclear and Phenotypic Markers
Authors: Bailey GW , Dimlich RVW , Alexander KB , McCarthy JJ , Pretlow TP , McKeever PE
Published: July 2020

Immunohistochemistry (IHC) has provided major insights about the classification of brain tumors by identifying cellular markers of phenotype, and about tumor growth potential with nuclear markers of proliferation. Newer in situ hybridization shows promise in tumor classification and prognostication.

Fig. 1 shows the sensitive and reliable avidin-biotin conjugate (ABC) method of localizing glial fibrillary acidic protein (GFAP). GFAP is the most specific marker of gliomas, tumors of brain cells, available today. The ABC method can be used to find any antigen for which a primary antibody is available. A molecular bridge then links this primary antibody bound to tissue with a label that can be seen, a substrate of the horseradish peroxidase (HRP) enzyme like diaminobenzidine (DAB) that produces a brown, insoluble reaction product at the site of the antigen. IHC for GFAP has revealed that brain tumors previously thought to be sarcomas are actually malignant gliomas (Fig. 2).