bluuebunny/crossref_metadata_2025 huggingface dataset:
Enhancing the Catalytic Activity of Zeolitic Imidazolate Framework‐8‐Derived N‐Doped Carbon with Incorporated CeO2 Nanoparticles in the Oxygen Reduction Reaction
Authors: Yu Yue , Gao Li , Liu Xianchun , Wang Yuanhong , Xing Shuangxi
Published: May 2017

Incorporation of CeO2 nanoparticles into the cavity of zeolitic imidazolate framework‐8 (ZIF‐8) was followed by high‐temperature pyrolysis to generate CeO2@N‐doped carbon materials. Introduction of the CeO2 nanoparticles greatly enhanced the catalytic activity of the ZIF‐8‐derived carbon materials in the oxygen reduction reaction (ORR) owing to the presence of Ce3+ and oxygen vacancies with high content of chemisorbed oxygen in CeO2 and the well‐maintained skeleton of the original ZIF‐8 with uniform mesoporous structure. The material treated at 900 °C (CeO2@N‐C‐900) showed excellent ORR catalytic activity in both acidic and alkaline electrolyte. The ORR onset and half‐wave potentials of CeO2@N‐C‐900 were 1.003 and 0.908 V versus RHE, respectively, in 0.1 m KOH aqueous solution, which are comparable to those of Pt/C catalysts. Furthermore, it exhibited much better stability and methanol crossover tolerance than Pt/C, indicative of its good potential for applications in energy conversion.
Halogen‐Bonding‐Mediated and Controlled Cationic Polymerization of Isobutyl Vinyl Ether: Expanding the Catalytic Scope of 2‐Iodoimidazolium Salts
Authors: Takagi Koji , Yamauchi Koji , Murakata Hiroto
Published: May 2017

Metal‐free initiating systems for living cationic polymerizations are desirable from the viewpoint of environmentally benign polymer synthesis. We describe here the development of a halogen‐bonding‐mediated and controlled cationic polymerization of isobutyl vinyl ether (IBVE) using 2‐iodoimidazolium salts as an organocatalyst. Due to the ionic nature of the catalysts, the polymerization should be performed in CH2Cl2. The HCl‐adduct of IBVE was the most suitable initiator, and the polymerization was carried out at −10 °C under the catalyst concentration of 10 mm to suppress alcohol elimination from the polymer chain. The addition of a small amount of nBu4NCl (0.02 equivalent) was effective to accomplish the controlled cationic polymerization and obtain polyIBVE, having the molecular weight distribution below 1.3.
Trump, Brexit und Alternative Fakten
Authors: Böck Barbara
Published: May 2017

No abstract.
An MRI scanner‐independent radiofrequency dosimeter for the estimation of RF power deposition with a human torso phantom
Authors: Seo Youngseob
Published: May 2017

An assessment of radiofrequency (RF) power deposition independent of the information provided by MRI scanners is thus desirable. We developed a novel scanner‐independent RF dosimeter based on measurements of the resistance of a thermistor that dissipates the RF power during scanning. With the RF dosimeter, the RF power deposition for four MRI sequences with specific absorption rate (SAR) values (0.1‐3.3 W/kg) was measured on five different scanners and the correlation between the RF dosimeter reading and the SAR levels calculated by the scanners was investigated. The novel RF dosimeter showed a linear relationship between the RF power deposition and the scanner‐reported whole‐body averaged SAR for each scanner. However, there was a variability in the reading among different scanners. The RF dosimeter readings were 9.7 and 9.5 mW on GE 1.5 T (SAR=2.6 W/kg), 3.6 and 3.7 mW on Philips 1.5 T (SAR=3.3 W/kg), 9.5 and 8.6 mW on Siemens 3 T (SAR=3.0 W/kg), and 4.7 and 3.9 mW on Philips 3 T (SAR=2.6 W/kg), respectively. The scanner‐independent RF dosimeter developed in this study can play a significant role in checking the accuracy of scanners’ SAR values as a standardized method for measuring the RF power deposition for MR safety.
Sacituzumab govitecan (IMMU‐132), an anti‐Trop‐2‐SN‐38 antibody‐drug conjugate for the treatment of diverse epithelial cancers: Safety and pharmacokinetics
Authors: Ocean Allyson J. , Starodub Alexander N. , Bardia Aditya , Vahdat Linda T. , Isakoff Steven J. , Guarino Michael , Messersmith Wells A. , Picozzi Vincent J. , Mayer Ingrid A. , Wegener William A. , Maliakal Pius , Govindan Serengulam V. , Sharkey Robert M. , Goldenberg David M.
Published: May 2017

BACKGROUND

Sacituzumab govitecan (IMMU‐132), an antitrophoblastic cell‐surface antigen (anti‐Trop‐2) humanized antibody‐SN‐38 conjugate, had encouraging efficacy in the phase 1 clinical trial. This report further examines the pharmacokinetics and safety of multiple cycles of IMMU‐132 at doses of 8 or 10 mg/kg in patients with diverse advanced epithelial cancers.

METHODS

Patients who had multiple prior therapies received IMMU‐132 on days 1 and 8 of 21‐day treatment cycles. Trop‐2 staining of archived tumor specimens, clearance of IMMU‐132 and its constituents (ie, immunoglobulin G [IgG], SN‐38 [a camptothecin, the active component of irinotecan], and glucuronidated SN‐38 [SN‐38G]), antibody responses, and uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) levels were determined. Safety was assessed according to Common Terminology Criteria for Adverse Events version 4.0, and responses were assessed using Response Evaluation Criteria in Solid Tumors, version 1.1.

RESULTS

Patients with diverse metastatic cancers who received IMMU‐132 at 8 mg/kg (n = 81) and 10 mg/kg (n = 97) were examined. Trop‐2 was positive in 93% of the available specimens. IMMU‐132 cleared with a half‐life of approximately 11 to 14 hours, reflecting the release of SN‐38 from the conjugate; IgG cleared more slowly (half‐life, approximately 103‐114 hours). Most SN‐38 in the serum (>95%) was bound to IgG. SN‐38G concentrations were lower than SN‐38 concentrations. Dose‐limiting neutropenia after the first cycle was not correlated with SN‐38 in serum or with UGT1A1 genotype. No antibody responses were detected. Objective responses were observed in several indications, including metastatic triple‐negative breast cancer, confirming that 10 mg/kg produced an encouraging overall response.

CONCLUSIONS

Sacituzumab govitecan has a predictable pharmacokinetic profile and manageable toxicity at doses of 8 and 10 mg/kg. With objective responses and a good therapeutic index at 10 mg/kg, this dose was chosen for future development. Cancer 2017;123:3843–3854. © 2017 American Cancer Society
Analytics for citizens: A linked open data model for statistical data exploration
Authors: Diamantini Claudia , Potena Domenico , Storti Emanuele
Published: May 2017

A growing number of public institutions all over the world have recently started to make government statistical data available in open formats, thus enhancing transparency and accountability, stimulating innovation, and promoting civic awareness and engagement. Integration issues related to fragmentation and heterogeneity of these datasets can be partially addressed by referring to the Linked Data approach, which also enables easier access and consumption by users. However, the lack of an explicit representation of how statistical indicators are calculated still hinders their interpretation, and hence the development of applications and services especially useful for citizens, who do not have full knowledge and control over the underlying data and analysis models. In the present work, we discuss an approach to ease the interaction of communities of citizens with statistical Linked Open Data. We define a model and a set of services allowing people to recognize the mathematical structure of statistical indicators, improving in this way user awareness of the meaning of indicators and their mutual relations. Through such services, it is possible to enable interactive browsing of indicator formulas and novel typologies of data exploration, including dynamic computation of indicators not explicitly stored and comparison of different Linked Data resources.
Epoxy Matrices Modified by Green Additives for Recyclable Materials
Authors: Henriksen Martin L. , Ravnsbæk Jens B. , Bjerring Morten , Vosegaard Thomas , Daasbjerg Kim , Hinge Mogens
Published: May 2017

Epoxy‐based thermosets are one of the most popular matrix materials in many industries, and significant environmental benefits can be obtained by developing a recyclable variant of this widely utilized material. Incorporation of a bio‐based disulfide additive within a commercial epoxy system leads to a cross‐linked material that can be fractionated under mild and environmentally benign conditions. The material has been analyzed by FTIR and solid‐state NMR. Furthermore, modified epoxy matrices with low additive concentrations are demonstrated to have similar mechanical and thermal properties compared to commercially available benchmarks. Thus, additive formulation and fractionation based on green chemistry principles have been demonstrated, and a recyclable epoxy matrix has been developed.
Bottom‐Up Construction of Porous Organic Frameworks with Built‐In TEMPO as a Cathode for Lithium–Sulfur Batteries
Authors: Zhou Baolong , Hu Xiang , Zeng Guang , Li Shiwu , Wen Zhenhai , Chen Long
Published: May 2017

Two redox‐active porous organic frameworks (POFs) with a built‐in radical moiety (TEMPO) and hierarchical porous structures were synthesized through a facile bottom‐up strategy and studied as cathode materials for lithium–sulfur (Li−S) batteries. The sulfur loading in these two POFs reached 61 %, benefitting from their large pore volumes. Owing to the highly dense docking sites of TEMPO, sulfur could be covalently immobilized within the porous networks and efficiently inhibit the shuttle effect, thereby significantly improving the cycling performance. The composites TPE‐TEMPO‐POF‐S (TPE=tetraphenylethene) deliver a capacity in excess of 470 mAh g−1 after 200 cycles with a coulombic efficiency of around 100 % at a current rate of 0.1 C. Furthermore, TEMPO‐POFs with sulfur embedded showed excellent rate capability with limited capacity loss at rates of 0.1–1 C.
Dynamic changes and prognostic value of pulmonary congestion by lung ultrasound in acute and chronic heart failure: a systematic review
Authors: Platz Elke , Merz Allison A. , Jhund Pardeep S. , Vazir Ali , Campbell Ross , McMurray John J.
Published: May 2017

Aims

Pulmonary congestion is an important finding in patients with heart failure (HF) that can be quantified by lung ultrasound (LUS). We conducted a systematic review to describe dynamic changes in LUS findings of pulmonary congestion (B‐lines) in HF and to examine the prognostic utility of B‐lines in HF.

Methods and results

We searched online databases for studies conducted in patients with chronic or acute HF that used LUS to assess dynamic changes or the prognostic value of pulmonary congestion. We included studies in adult populations, published in English, and conducted in ≥25 patients. Of 1327 identified studies, 13 (25–290 patients) met the inclusion criteria: six reported on dynamic changes in LUS findings (438 patients) and seven on the prognostic value of B‐lines in HF (953 patients). In acute HF, B‐line number changed within as few as 3 h of HF treatment. In acute HF, ≥15 B‐lines on 28‐zone LUS at discharge identified patients at a more than five‐fold risk for HF readmission or death. Similarly, in ambulatory patients with chronic HF, ≥3 B‐lines on five‐ or eight‐zone LUS marked those at a nearly four‐fold risk for 6‐month HF hospitalization or death.

Conclusions

Lung ultrasound findings change rapidly in response to HF therapy. This technique may represent a useful and non‐invasive method to track dynamic changes in pulmonary congestion. Furthermore, residual congestion at the time of discharge in acute HF or in ambulatory patients with chronic HF may identify those at high risk for adverse events.
Air‐Tolerant 1‐Amino‐1,3‐diphosphacyclobutane‐2,4‐diyls Featuring Strong Electron‐Donating Properties and Small HOMO–LUMO Gaps
Authors: Ito Shigekazu , Ueta Yasuhiro , Ngo Trang Thi Thu , Koshino Kota , Mikami Koichi
Published: May 2017

The sterically encumbered 1‐amino‐1,3‐diphosphacyclobuten‐4‐yl anion, prepared from 1‐(2,4,6‐tri‐tert‐butylphenyl)‐2‐phosphaethyne and lithium diisopropylamide (0.5 equiv.), was characterized spectroscopically and afforded air‐tolerant amino‐substituted 1,3‐diphosphacyclobutane‐2,4‐diyls by SN2‐type alkylation and arylation reactions with benzyne. The photoabsorption and electrochemical parameters of the P‐heterocyclic singlet open‐shell compounds revealed that they had higher electron‐donating character than the relevant hydrocarbon‐substituted P‐heterocycles in addition to a reduction between the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) levels. The structures of the amino‐substituted 1,3‐diphosphacyclobutane‐2,4‐diyls were unambiguously determined by X‐ray crystallography, and the metric parameters were compatible with the physical properties. The successful synthesis and full characterization of the amino‐substituted phosphorus congener of cyclobutane‐1,3‐diyl will be helpful to develop functional materials based on open‐shell neutral and ionized phosphorus heterocycles.
2,2′:6′,2′′‐Terpyridine Analogues: Structural, Electrochemical, and Photophysical Properties of 2,6‐Di(thiazol‐2‐yl)pyridine Derivatives
Authors: Maroń Anna , Kula Slawomir , Szlapa‐Kula Agata , Świtlicka Anna , Machura Barbara , Krompiec Stanisław , Małecki Jan Grzegorz , Kruszyński Rafał , Chrobok Anna , Schab‐Balcerzak Ewa , Kotowicz Sonia , Siwy Mariola , Smolarek Karolina , Maćkowski Sebastian , Janeczek Henryk , Libera Marcin
Published: May 2017

Several 2,6‐di(thiazol‐2‐yl)pyridine (dtpy) derivatives substituted at the 4‐position were synthesized, and their structural, photophysical, and electrochemical properties were investigated. The studies proved the attractiveness of this new class of compound as building blocks for materials science, coordination chemistry, and supramolecular chemistry and also revealed the possible tuning of their thermal, photophysical, electrochemical, and electroluminescence properties through the modification of the structure of the substituent. The thermal, photophysical, and electrochemical behavior of the compounds was examined by differential scanning calorimetry (DSC) and for selected compounds by thermogravimetric analysis (TGA), UV/Vis spectroscopy, photoluminescence (PL) spectroscopy, and cyclic voltammetry (CV). Additionally, their selected properties were investigated theoretically by density functional theory (DFT) calculations. The electroluminescence abilities of the synthesized compounds were preliminary tested in host–guest light‐emitting diodes.
A Benzoquinone Imine Assisted Ring‐Opening/Ring‐Closing Strategy of the RCOCHN1N2 System: Dinitrogen Extrusion Reaction to Benzimidazoles
Authors: Kumar Atul , Ahmed Qazi Naveed
Published: May 2017

A mild, three‐component dinitrogen extrusion reaction proceeding at room temperature to give different 1,2‐disubstituted benzimidazoles from 2‐oxoaldehydes, 4‐azidophenol, and benzotriazoles was successfully developed. Mechanistically, this transformation occurs through the benzoquinone imine assisted ring opening/ring closing of a highly unstable RCOCHN1N2 system.
Hydrophilic interaction anion exchange for separation of multiply modified neutral and anionic Dictyostelium N‐glycans
Authors: Hykollari Alba , Malzl Daniel , Yan Shi , Wilson Iain B. H. , Paschinger Katharina
Published: May 2017

The unusual nature of the N‐glycans of the cellular slime mould Dictyostelium discoideum has been revealed by a number of studies, primarily based on examination of radiolabeled glycopeptides but more recently also by MS. The complexity of the N‐glycomes of even glycosylation mutants is compounded by the occurrence of anionic modifications, which also present an analytical challenge. In this study, we have employed hydrophilic interaction anion exchange (HIAX) HPLC in combination with MALDI‐TOF MS/MS to explore the anionic N‐glycome of the M31 (modA) strain, which lacks endoplasmic reticulum α‐glucosidase II, an enzyme conserved in most eukaryotes including Homo sapiens. Prefractionation with HIAX chromatography enabled the identification of N‐glycans with unusual oligo‐α1,2‐mannose extensions as well as others with up to four anionic modifications. Due to the use of hydrofluoric acid treatment, we were able to discriminate isobaric glycans differing in the presence of sulphate or phosphate on intersected structures as opposed to those carrying GlcNAc‐phosphodiesters. The latter represent biosynthetic intermediates during the pathway leading to formation of the methylphosphorylated mannose epitope, which may have a similar function in intracellular targeting of hydrolases as the mannose‐6‐phosphate modification of lysosomal enzymes in mammals. In conclusion, HIAX in combination with MS is a highly sensitive approach for both fine separation and definition of neutral and anionic N‐glycan structures.
Sustainable Energy‐Storage Materials from Lignin–Graphene Nanocomposite‐Derived Porous Carbon Film
Authors: Tran Chau D. , Ho Hoi Chun , Keum Jong K. , Chen Jihua , Gallego Nidia C. , Naskar Amit K.
Published: May 2017

A simple, green approach to fabricating porous free‐standing carbon films is presented. An alkaline solution of low‐cost, renewable lignin and graphene oxide (GO) is cast, followed by simultaneous carbonization and activation. Lignin, which is the least valued product from several biomass processing industries, is an efficient source of carbon when used as an intercalating agent to separate graphene sheets derived from homogeneous GO/lignin nanocomposite films prepared from an aqueous alkaline (KOH) solution. After thermal treatment the GO/lignin films show complete dispersion of reduced GO sheets within amorphous lignin‐derived carbon. The presence of KOH in the film produces activated carbon. These activated carbon films display a specific surface area of up to 1744 m2 g−1 and consist of a balance of pore volumes with pore sizes below and above 1 nm. A two‐electrode supercapacitor composed of these films in an aqueous electrolyte exhibits near‐ideal capacitive behavior at an ultrahigh scan rate of 1 V s−1, while maintaining an excellent specific capacitance of 162 F g−1. Such outstanding performance of renewable carbon as a supercapacitor, in addition to the ease of electrode fabrication from a precursor containing 85 % lignin, offers a novel method for valorization of lignin‐rich byproduct streams from biomass processing industries.
Advancing the adverse outcome pathway framework—An international horizon scanning approach
Authors: LaLone Carlie A. , Ankley Gerald T. , Belanger Scott E. , Embry Michelle R. , Hodges Geoff , Knapen Dries , Munn Sharon , Perkins Edward J. , Rudd Murray A. , Villeneuve Daniel L. , Whelan Maurice , Willett Catherine , Zhang Xiaowei , Hecker Markus
Published: May 2017

Our ability to conduct whole-organism toxicity tests to understand chemical safety has been outpaced by the synthesis of new chemicals for a wide variety of commercial applications. As a result, scientists and risk assessors are turning to mechanistically based studies to increase efficiencies in chemical risk assessment and making greater use of in vitro and in silico methods to evaluate potential environmental and human health hazards. In this context, the adverse outcome pathway (AOP) framework has gained traction in regulatory science because it offers an efficient and effective means for capturing available knowledge describing the linkage between mechanistic data and the apical toxicity end points required for regulatory assessments. A number of international activities have focused on AOP development and various applications to regulatory decision-making. These initiatives have prompted dialogue between research scientists and regulatory communities to consider how best to use the AOP framework. Although expert-facilitated discussions and AOP development have been critical in moving the science of AOPs forward, it was recognized that a survey of the broader scientific and regulatory communities would aid in identifying current limitations while guiding future initiatives for the AOP framework. To that end, a global horizon scanning exercise was conducted to solicit questions concerning the challenges or limitations that must be addressed to realize the full potential of the AOP framework in research and regulatory decision-making. The questions received fell into several broad topical areas: AOP networks, quantitative AOPs, collaboration on and communication of AOP knowledge, AOP discovery and development, chemical and cross-species extrapolation, exposure/toxicokinetics considerations, and AOP applications. Expert ranking was then used to prioritize questions for each category, where 4 broad themes emerged that could help inform and guide future AOP research and regulatory initiatives. In addition, frequently asked questions were identified and addressed by experts in the field. Answers to frequently asked questions will aid in addressing common misperceptions and will allow for clarification of AOP topics. The need for this type of clarification was highlighted with surprising frequency by our question submitters, indicating that improvements are needed in communicating the AOP framework among the scientific and regulatory communities. Overall, horizon scanning engaged the global scientific community to help identify key questions surrounding the AOP framework and guide the direction of future initiatives. Environ Toxicol Chem 2017;36:1411–1421. © 2017 SETAC
Improvement of the weighted essentially nonoscillatory scheme based on the interaction of smoothness indicators
Authors: Chai Delin , Sun Zhongguo , Huang Zhu , Xi Guang
Published: May 2017

The weighted essentially nonoscillatory scheme is improved by introducing new smoothness indicators that evaluate the interactions among the classical smoothness indicators suggested by Jiang and Shu. The effect of the key parameters in the new smoothness indicators on the scheme is systematically investigated. The improved scheme has smaller dissipation with larger weight assignment to the discontinuous stencils and higher numerical accuracy with weights closer to the ideal weights. To verify the theory, benchmark problems governed by the linear transport equation, the 1‐dimensional nonlinear Burgers equation, and the Euler equations are conducted and analyzed, respectively. Better computational performances both on numerical resolution and accuracy are shown in the comparisons with other classical weighted essentially nonoscillatory schemes.
Evidence for decreased interaction and improved carotenoid bioavailability by sequential delivery of a supplement
Authors: Salter‐Venzon Dawna , Kazlova Valentina , Izzy Ford Samantha , Intra Janjira , Klosner Allison E. , Gellenbeck Kevin W.
Published: May 2017

Despite the notable health benefits of carotenoids for human health, the majority of human diets worldwide are repeatedly shown to be inadequate in intake of carotenoid‐rich fruits and vegetables, according to current health recommendations. To address this deficit, strategies designed to increase dietary intakes and subsequent plasma levels of carotenoids are warranted. When mixed carotenoids are delivered into the intestinal tract simultaneously, competition occurs for micelle formation and absorption, affecting carotenoid bioavailability. Previously, we tested the in vitro viability of a carotenoid mix designed to deliver individual carotenoids sequentially spaced from one another over the 6 hr transit time of the human upper gastrointestinal system. We hypothesized that temporally and spatially separating the individual carotenoids would reduce competition for micelle formation, improve uptake, and maximize efficacy. Here, we test this hypothesis in a double‐blind, repeated‐measure, cross‐over human study with 12 subjects by comparing the change of plasma carotenoid levels for 8 hr after oral doses of a sequentially spaced carotenoid mix, to a matched mix without sequential spacing. We find the carotenoid change from baseline, measured as area under the curve, is increased following consumption of the sequentially spaced mix compared to concomitant carotenoids delivery. These results demonstrate reduced interaction and regulation between the sequentially spaced carotenoids, suggesting improved bioavailability from a novel sequentially spaced carotenoid mix.
From the Foundation Up
Authors: Callahan Daniel
Published: May 2017

In 2019, The Hastings Center will celebrate its fiftieth anniversary. It is more than a bit staggering to think how far we have come since 1969. When I floated the idea of a center on bioethics to my friend and neighbor, psychiatrist Willard Gaylin, at a Christmas party in 1968—even before the word “bioethics” was used—I had only the fuzziest idea of where that would take us. Neither Will nor I had run anything, nor did we know how to raise money to support an organization. We would and did learn how, but much of what we did in those early years was made up on the fly. We not only had to invent an organization but no less to invent a field of research and education on issues still little noticed by the public or academics. Out of curiosity, I recently googled “bioethics.” I was astonished at what I found and by the sheer quantity of what is going on.
How to Rethink the Fourteen‐Day Rule
Authors: Chan Sarah
Published: May 2017

Recently, attention has been drawn to the basic principles governing the use of human embryos in research: specifically, the so‐called fourteen‐day rule. This rule stipulates that human embryos should not be allowed to grow in vitro past fourteen days of development. For years, the fourteen‐day limit was largely theoretical, since culture techniques were not sufficient to maintain embryos up to this point. Yet in the past year, research has suggested that growing embryos beyond fourteen days might be feasible and scientifically valuable. At the same time, work with pluripotent stem cells, including human PSCs, has shown that under certain conditions, they can form structures that recapitulate developmental features of the postimplantation embryo. This raises the possibility that PSCs could generate embryo‐like structures in vitro, even “synthetic embryos,” that might provoke moral concern but would not fall under most current embryo research policies. In countries that permit embryo research, the fourteen‐day rule has long been the linchpin of an effective policy compromise between what remain deeply divided moral positions on the human embryo's status. It has also, particularly in the United Kingdom, been influential in establishing a bioethics public‐policy process. Any moves to change the rule must consider not just the implications for the use of embryos but also the potential impact of this model of bioethical governance of science.
Reconciling Patient Safety and Epistemic Humility: An Ethical Use of Opioid Treatment Plans
Authors: Ho Anita
Published: May 2017

In this issue of the Hastings Center Report, Joshua Rager and Peter Schwartz suggest using opioid treatment agreements as public health monitoring tools to inform patients about “the requirements entailed by undergoing opioid therapy,” rather than as contractual agreements to alter patients’ individual behavior or to benefit them directly. Because Rager and Schwartz's argument presents suspected OTA violations as a justification to stop providing opioids yet does not highlight the broader epistemic and systemic context within which clinicians prescribe these medications, their proposal may perpetuate a climate of distrust and stigmatization without correcting systemic factors that may have placed patients and others at risk in the first place. Given the context of epistemic uncertainty regarding opioid safety and efficacy, insufficient training for opioid prescribers, and inadequate patient education, I propose replacing OTAs, which have a narrow focus on patient behaviors, with opioid treatment plans, which would promote mutual, collaborative, and shared decision‐making on the most appropriate pain management program. An OTP can be ethically justified as a tool to prevent and treat iatrogenic addiction under a specific paradigm—one that adopts a default position of professional epistemic humility and holds all collaborative parties accountable in chronic pain management.
Opioid Treatment Agreements Repurposed—But Who Monitors the Monitors?
Authors: Payne Richard
Published: May 2017

In this issue of the Hastings Center Report, Joshua Rager and Peter Schwartz reframe the justification for the use of opioid treatment agreements. Instead of documents used to define the roles and responsibilities of doctors and patients to one another in the course of opioid treatment for chronic pain and to describe the risks and benefits of therapy for the individual, OTAs are now proposed for use as “surveillance and monitoring” instruments. As such, they are specifically meant to disclose the risks of opioid therapy and to describe the other processes and tools used to monitor abuse and diversion of medications. Given the crisis of the opioid overdose and death epidemic, along with this repurposing of OTAs as disclosure documents primarily, Rager and Schwartz argue that patient consent is not needed (although desired) and that OTAs should be universally applied in clinical practices. We can all agree on the big picture goal of limiting the number of opioid prescriptions in order to minimize the tragedy of opioid overdose deaths. We disagree, though, about the acceptable level of collateral damage to people in pain who fall victim to fighting the war against the so‐called opioid epidemic.
Research with Pregnant Women: New Insights on Legal Decision‐Making
Authors: Mastroianni Anna C. , Henry Leslie Meltzer , Robinson David , Bailey Theodore , Faden Ruth R. , Little Margaret O. , Lyerly Anne Drapkin
Published: May 2017

U.S. researchers and scholars often point to two legal factors as significant obstacles to the inclusion of pregnant women in clinical research: the Department of Health and Human Services’ regulatory limitations specific to pregnant women's research participation and the fear of liability for potential harm to children born following a pregnant woman's research participation. This article offers a more nuanced view of the potential legal complexities that can impede research with pregnant women than has previously been reflected in the literature. It reveals new insights into the role of legal professionals throughout the research pathway, from product conception to market, and it highlights a variety of legal factors influencing decision‐making that may slow or halt research involving pregnant women. Our conclusion is that closing the evidence gap created by the underrepresentation and exclusion of pregnant women in research will require targeted attention to the role of legal professionals and the legal factors that influence their decisions.
Flu, Floods, and Fire: Ethical Public Health Preparedness
Authors: Phelan Alexandra L. , Gostin Lawrence O.
Published: May 2017

Even as public health ethics was developing as a field, major incidents such as 9/11 and the SARS epidemic propelled discourse around public health emergency preparedness and response. Policy and practice shifted to a multidisciplinary approach, recognizing the broad range of potential threats to public health, including biological, physical, radiological, and chemical threats. This propelled the development of surveillance systems to detect incidents, laboratory capacities to rapidly test for potential threats, and therapeutic and social countermeasures to prepare for and respond to a range of hazards. In bringing public health ethics and emergency preparedness together, Emergency Ethics: Public Health Preparedness and Response adds depth and complexity to both fields. As global threats continue to emerge, the book, edited by Bruce Jennings, John D. Arras, Drue H. Barrett, and Barbara A. Ellis, will offer a vital compass.
Somatostatin depresses the excitability of subicular bursting cells: Roles of inward rectifier K+ channels, KCNQ channels and Epac
Authors: Hu Binqi , Cilz Nicholas I. , Lei Saobo
Published: May 2017

The hippocampus is a crucial component for cognitive and emotional processing. The subiculum provides much of the output for this structure but the modulation and function of this region is surprisingly under‐studied. The neuromodulator somatostatin (SST) interacts with five subtypes of SST receptors (sst1 to sst5) and each of these SST receptor subtypes is coupled to Gi proteins resulting in inhibition of adenylyl cyclase (AC) and decreased level of intracellular cAMP. SST modulates many physiological functions including cognition, emotion, autonomic responses and locomotion. Whereas SST has been shown to depress neuronal excitability in the subiculum, the underlying cellular and molecular mechanisms have not yet been determined. Here, we show that SST hyperpolarized two classes of subicular neurons with a calculated EC50 of 0.1 μM. Application of SST (1 μM) induced outward holding currents by primarily activating K+ channels including the G‐protein‐activated inwardly‐rectifying potassium channels (GIRK) and KCNQ (M) channels, although inhibition of cation channels in some cells may also be implicated. SST‐elicited hyperpolarization was mediated by activation of sst2 receptors and required the function of G proteins. The SST‐induced hyperpolarization resulted from decreased activity of AC and reduced levels of cAMP but did not require the activity of either PKA or PKC. Inhibition of Epac2, a guanine nucleotide exchange factor, partially blocked SST‐mediated hyperpolarization of subicular neurons. Furthermore, application of SST resulted in a robust depression of subicular action potential firing and the SST‐induced hyperpolarization was responsible for its inhibitory action on LTP at the CA1‐subicilum synapses. Our results provide a novel cellular and molecular mechanism that may explain the roles of SST in modulation of subicular function and be relevant to SST‐related physiological functions.
Substance‐related psychopathology and aggressiveness in a nightlife holiday resort: Results from a pilot study in a psychiatric inpatient unit in Ibiza
Authors: Martinotti Giovanni , Cinosi Eduardo , Santacroce Rita , Papanti Duccio , Pasquini Anna , Mancini Valerio , Corbo Mariangela , Fiori Federica , Sarchione Fabiola , Marchetti Daniela , Verrocchio Maria Cristina , Di Giannantonio Massimo , Torrens Marta , Schifano Fabrizio , Morlan Coarasa Maria Jose , Merino del Villar Cristina
Published: May 2017

Objectives

We aimed to describe a sample of subjects admitted to a psychiatric unit after the intake of psychoactive substances for recreational purposes.

Methods

Between June and September 2015, 49 subjects were included. Sociodemographic characteristics and psychopathological aspects were investigated, and urine samples for further analysis were collected. Three subgroups (cannabinoids, stimulants, and depressors users) were identified, according to the structured interview regarding substance use and urinalysis.

Results

Level of aggressiveness was found to be significantly higher (p < .05) in the cannabinoids subgroup. Self‐reported symptom severity was comparable among groups, but trends could be identified: SCL‐90 results showed a prevalence of anxiety symptoms among depressors users, hostility or aggression in the tetrahydrocannabinol subgroup, and psychoticism in the stimulants subgroup.

Conclusions

The use of psychoactive substances was be characterised by poly‐use of both traditional and novel substances. The presence of aggressiveness emerged as a main feature associated with the use of cannabis and other cannabinoids. Binge drinking and sleep deprivation also represented a relevant component in almost all the evaluated subjects.
Combining density forecasts using focused scoring rules
Authors: Opschoor Anne , van Dijk Dick , van der Wel Michel
Published: May 2017

We investigate the added value of combining density forecasts focused on a specific region of support. We develop forecast combination schemes that assign weights to individual predictive densities based on the censored likelihood scoring rule and the continuous ranked probability scoring rule (CRPS) and compare these to weighting schemes based on the log score and the equally weighted scheme. We apply this approach in the context of measuring downside risk in equity markets using recently developed volatility models, including HEAVY, realized GARCH and GAS models, applied to daily returns on the S&P 500, DJIA, FTSE and Nikkei indexes from 2000 until 2013. The results show that combined density forecasts based on optimizing the censored likelihood scoring rule significantly outperform pooling based on equal weights, optimizing the CRPS or log scoring rule. In addition, 99% Value‐at‐Risk estimates improve when weights are based on the censored likelihood scoring rule.
Hydroxychloroquine affects bone resorption both in vitro and in vivo
Authors: Both Tim , Zillikens M. Carola , Schreuders‐Koedam Marijke , Vis Marijn , Lam Wai‐Kwan , Weel Angelique E. A. M. , van Leeuwen Johannes P. T. M. , van Hagen P. Martin , van der Eerden Bram C. J. , van Daele Paul L. A.
Published: May 2017

We recently showed that patients with primary Sjögren syndrome (pSS) have significantly higher bone mineral density (BMD) compared to healthy controls. The majority of those patients (69%) was using hydroxychloroquine (HCQ), which may have favorable effects on BMD. The aim of the study was to evaluate whether HCQ modulates osteoclast function. Osteoclasts were cultured from PBMC‐sorted monocytes for 14 days and treated with different HCQ doses (controls 1 and 5 μg/ml). TRAP staining and resorption assays were performed to evaluate osteoclast differentiation and activity, respectively. Staining with an acidification marker (acridine orange) was performed to evaluate intracellular pH at multiple timepoints. Additionally, a fluorescent cholesterol uptake assay was performed to evaluate cholesterol trafficking. Serum bone resorption marker β‐CTx was evaluated in rheumatoid arthritis patients. HCQ inhibits the formation of multinuclear osteoclasts and leads to decreased bone resorption. Continuous HCQ treatment significantly decreases intracellular pH and significantly enhanced cholesterol uptake in mature osteoclasts along with increased expression of the lowdensity lipoprotein receptor. Serum β‐CTx was significantly decreased after 6 months of HCQ treatment. In agreement with our clinical data, we demonstrate that HCQ suppresses bone resorption in vitro and decreases the resorption marker β‐CTx in vivo. We also showed that HCQ decreases the intracellular pH in mature osteoclasts and stimulates cholesterol uptake, suggesting that HCQ induces osteoclastic lysosomal membrane permeabilization (LMP) leading to decreased resorption without changes in apoptosis. We hypothesize that skeletal health of patients with increased risk of osteoporosis and fractures may benefit from HCQ by preventing BMD loss.
Comparison of manual and automatic processing of biological samples for electron microscopy
Authors: Yang Rui , Wang Shuai , Wang Jianli , Luo Xi , Zhao Wenchao , Zhang Qing , Nan Zhangjie , Yang Liu , Wang Shaohui
Published: May 2017

The ultrastructure of a sample can be observed by electron microscopy (EM), which has become an indispensable research tool in morphological studies. However, EM sample preparation techniques are complicated and time‐consuming, with a high labor cost. The current study was conducted to compare the conventional manual and automated methods for sample processing and post‐staining for electron microscopy. Automated sample processing reduces OsO4 contamination, improves the efficiency of sample preparation and is easy to use. Therefore, the results of their study provide a practical and feasible method for the preparation of biological samples for electron microscopy.
Wind waves climatology of the Southeast Pacific Ocean
Authors: Aguirre Catalina , Rutllant José A. , Falvey Mark
Published: May 2017

The climatology of wind waves over the Southeast Pacific is analysed using a 32‐year hindcast from the WaveWatch III model, complemented by satellite‐derived significant wave height (SWH) and buoy measurements for validation. Using partitioned spectral data, a regional climatology of wind sea and swell parameters was constructed. In general, the simulated SWH shows a good agreement with satellite and in situ SWH measurements, although the model appears to have a spatially uniform bias of approximately 0.3 m. The spatial pattern of SWH is clearly influenced by the meridional variation of mean surface wind speed, where the stronger winds over the Southern Ocean play a significant role generating higher waves at higher latitudes. Nevertheless, regional features are observed in the annual variability of SWH, which are associated with the existence of atmospheric coastal low‐level jets off the coast of Peru and central Chile. In particular, the seasonal variation of these synoptic scale jets shows a direct relationship with the annual variability of SWH and with the probability of occurrence of wind sea conditions. Off the coast of Peru at approximately 15°S the coastal low‐level jet is strongest during austral winter, increasing the wind sea SWH. In contrast, off central Chile, there is an important increase of wind sea SWH during summer. The seasonal variation of the wind sea component leads to a contrasting seasonal variation of the total SWH at these locations: off Peru the coastal jet amplifies the annual variability of SWH, while off Central Chile the annual variability of SWH is suppressed by the presence of the coastal jet. Although the general conclusions of this research are considered to be robust, we discuss the limitations of the spectral partitioning method used to distinguish wind sea and swell‐sea states.
Evaluation of satellite rainfall climatology using CMORPH, PERSIANN‐CDR, PERSIANN, TRMM, MSWEP over Iran
Authors: Alijanian Mohammadali , Rakhshandehroo Gholam Reza , Mishra Ashok K. , Dehghani Maryam
Published: May 2017

In situ rainfall data observed by gauges is the most important data in water resources management. However, these data have some limitations both spatially and temporally. With the advancements in satellite rainfall products, it is now possible to evaluate whether these products can capture the climatology of known rainfall characteristics. In this study, five satellite rainfall estimates (SREs) were evaluated against gauge data based on different rainfall regimes over Iran. The evaluated SREs are Climate Prediction Center Morphing Technique, Precipitation Estimation from Remotely Sensed Information using Artificial Neural Networks (PERSIANN) and Tropical Rainfall Measuring Mission (TRMM), PERSIANN Climate Data Record (PERSIANN‐CDR) and the most recently available Multi‐Source Weighted‐Ensemble Precipitation (MSWEP) data. The performance of these five SREs is evaluated with respect to gauge data (total: 958 stations) in eight different climatic zones at daily, monthly, and wet/dry spells during a ten‐year period (2003–2012). Performance of SREs was evaluated using metrics of comparison based on correlation coefficient (CC), root mean square error, and relative error. The study shows that MSWEP has the highest CC (0.72) followed by TRMM (0.46) and PERSIANN‐CDR (0.43) at daily time scale. The performance of SREs varies with respect to climatic regimes, for example, the best correlation was observed in the south, the shore of Persian Gulf with ‘very hot and humid’ climate with CC values of 0.72, 0.70, and 0.82 for MSWEP, TRMM and PERSIANN‐CDR, respectively. Further, the performance of SREs was evaluated using the categorical statistics to capture the rainfall pattern based on different groups (e.g. light, moderate and heavy rainfall events). Results show that MSWEP, PERSIANN‐CDR, and TRMM performed well to distinguish rain from no‐rain condition, whereas for higher rainfall rates, PERSIANN‐CDR outperforms the other SREs.
Improving ENSO prediction in CFSv2 with an analogue‐based correction method
Authors: Liu Ying , Ren Hong‐Li
Published: May 2017

This study focuses on improving the El Niño–Southern Oscillation (ENSO) prediction in Climate Forecast System version 2 (CFSv2) of the National Centers for Environmental Prediction through the development and application of an analogue‐based correction method. We show that errors in sea surface temperature (SST) forecasts in CFSv2 in the tropical Pacific are strongly correlated with the observed SST anomaly index in the Niño3.4 region at the forecast initiation time, indicating that SST forecast errors in CFSv2 is similar in cases in which the corresponding initial SST states are also similar. Therefore, the analogue‐based correction method is developed, in which SST forecast errors in CFSv2 can be corrected empirically using historical forecast errors, which are calculated by the same model, initiated from states that are analogues of the present initial state. Results show that the corrected SST anomaly forecasts have improved skills, as measured by the temporal correlation coefficient and root‐mean‐square error, compared with uncorrected forecasts. This is true for several different Niño SST indices, at most of lead months, and for most of initiation calendar months. Particular improvement is found for forecasts of the SST anomaly indices that are specially used to depict the two different ENSO flavours/types. With regard to the Niño3.4 index, the analogue‐based correction method also predicted the 2014/2016 El Niño event relatively successfully. The results indicate that the analogue‐based correction method provides an effective means of empirically improving ENSO prediction in CFSv2.
Comparative study of five current reanalyses in characterizing total cloud fraction and top‐of‐the‐atmosphere cloud radiative effects over the Asian monsoon region
Authors: Li Jiandong , Mao Jiangyu , Wang Fang
Published: May 2017

This study evaluates total cloud fraction (TCF) and top‐of‐the‐atmosphere cloud radiative effects (CREs) in five widely used reanalyses (CFSR, ERA‐Interim, JRA55, MERRA2, and NCEP1) using satellite‐based observations for the period 2001–2014, with the emphasis on the Asian monsoon region (AMR) including East Asia (EA) and South Asia (SA). The results indicate that despite certain biases, most reanalyses (especially CFSR and ERA‐Interim) broadly capture global spatial patterns of TCF and CREs, with pattern correlations with the observations being greater than 0.7, and also generally reproduce the pronounced contrast of the winter and summer means over EA and SA. In contrast, biases and differences in TCF and CREs in reanalyses are significantly larger over the AMR, particularly in summer. Over EA, the reanalyses underestimate annual and winter mean TCF, shortwave CRE (SWCRE), and net CRE (NCRE), with negative biases of 0–40%. Over SA, the reanalyses broadly reproduce the observed annual cycles of each CRE component, but most of them have considerable biases in magnitude, with an overestimation of NCRE by up to 90%, and an unrealistic ratio of longwave (LWCRE) to SWCRE. Such an unrealistic relationship between LWCRE and SWCRE in some reanalyses may produce an unrealistic annual mean state, annual cycle, and inter‐annual variation of NCRE over SA. Comparatively, ERA‐Interim and JRA55 give better performance in the annual cycle and inter‐annual variations of CREs over EA. The inter‐annual biases of TCF and NCRE in CFSR are substantially larger over SA while its TCF reproducibility over EA is the best of the reanalyses. The examination of TCF in MERRA2 with the satellite simulator shows that larger TCF biases occur over the AMR region relative to original satellite and MERRA2 products. It requires more quantitative comparison among reanalyzed and satellite‐retrieved cloud properties to identify and improve cloud parameterization.