bluuebunny/crossref_metadata_2025 huggingface dataset:
Syntheses of biodegradable polymer networks based on polycaprolactone and glutamic acid
Authors: Park Soo Yong , Kim Soo‐Yeon , Kim Taeyoon , Ahn Heejoon , Chung Ildoo
Published: December 2018

Biodegradable trifunctional oligomer was synthesized from polycaprolactone and glutamic acid and characterized by Fourier‐transform infrared (FTIR) and proton nuclear magnetic resonance (1H NMR) spectroscopies. Injectable and in situ crosslinkable polymer networks were fabricated by the copolymerization of oligomer with triethylene glycol dimethacrylate (TEGDMA) and used to evaluate the initial compressive strengths, viscosities, shrinkages, thermal stabilities, and biodegradabilities in the forms of polymer network neat resin and their composites with β‐tricalcium phosphate. The initial compressive strengths (CS) values of neat resins ranged from 9.54 to 187.6 MPa. Both neat resins and composites had polymerization shrinkage ranging from 0% to 11.7%, which increased with increasing of TEGDMA contents in resin. Moreover, in polymer composite resins, shrinkage values decreased with increasing filler level from 0% to 4.6%, and exothermic evolution values decreased from 33.5°C to 29.7°C as increasing filler level. The composite with the formulation of (polycaprolactone)‐glutamate triacrylate (PCLGTA)/TEGDMA (25/75) and powder/liquid (P/L) ratio of 1.0 exhibited the highest exothermal and lowest shrinkage values. The increase of oligomer in the formulation led to an increase in viscosity.
Neutrophils in the initiation and resolution of acute pulmonary inflammation: understanding biological function and therapeutic potential
Authors: Potey Philippe MD , Rossi Adriano G , Lucas Christopher D , Dorward David A
Published: December 2018

Acute respiratory distress syndrome (ARDS) is the often fatal sequelae of a broad range of precipitating conditions. Despite decades of intensive research and clinical trials there remain no therapies in routine clinical practice that target the dysregulated and overwhelming inflammatory response that characterises ARDS. Neutrophils play a central role in the initiation, propagation and resolution of this complex inflammatory environment by migrating into the lung and executing a variety of pro‐inflammatory functions. These include degranulation with liberation of bactericidal proteins, release of cytokines and reactive oxygen species as well as production of neutrophil extracellular traps. Although these functions are advantageous in clearing bacterial infection, the consequence of associated tissue damage, the contribution to worsening acute inflammation and prolonged neutrophil lifespan at sites of inflammation are deleterious. In this review, the importance of the neutrophil will be considered, together with discussion of recent advances in understanding neutrophil function and the factors that influence them throughout the phases of inflammation in ARDS. From a better understanding of neutrophils in this context, potential therapeutic targets are identified and discussed. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
Autophagy, cancer stem cells and drug resistance
Authors: Smith Alexandra G , Macleod Kay F
Published: December 2018

Autophagy is a cellular survival mechanism that is induced by cancer therapy, among other stresses, and frequently contributes to cancer cell survival during long periods of dormancy and the eventual outgrowth of metastatic disease. Autophagy degrades large cellular structures that, once broken down, contribute to cellular survival through the recycling of their constituent metabolites. However, the extent to which this fuel function of autophagy is key to its role in promoting stemness, dormancy and drug resistance remains to be determined. Other roles for autophagy in determining cell fate more directly through targeted degradation of key transcription factors, such as p53 and FoxO3A, or by enforcing a reversible quiescent growth arrest, are discussed in this review. This review also highlights the need to parse out the roles of different forms of selective autophagy in stemness, CD44 expression and dormancy that, for example, are increasingly being attributed explicitly to mitophagy. The clinical relevance of this work and how an increased understanding of functions of autophagy in stemness, dormancy and drug resistance could be manipulated for increased therapeutic benefit, including eliminating minimal residual disease and preventing metastasis, are discussed. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
New tools for pathology: a user's review of a highly multiplexed method for in situ analysis of protein and RNA expression in tissue
Authors: Decalf Jérémie , Albert Matthew L , Ziai James
Published: December 2018

Tumor cell heterogeneity and tumor cell–stromal interactions are being explored as determinants of disease progression and treatment resistance in solid tumor and hematological malignancies. As such, tools simultaneously capable of highly multiplexed profiling of tissues' protein and RNA content, as well as interrogation of rare or single cells, are required to precisely characterize constituent tumor cell populations, infiltrating lymphocytes and stromal elements. Access to spatial relationships will enable more precise characterization of tumors, support patient stratification and may help to identify novel drug targets. Multiple platforms are being developed to address these critical unmet needs. The NanoString digital spatial profiling (DSP) platform enables highly multiplexed, spatial assessment of protein and/or RNA targets in tissues by detecting oligonucleotide barcodes conjugated via a photocleavable linker to primary antibodies or nucleic acid probes. Although this platform enables high‐dimensional spatial interrogation of tissue protein and RNA expression, a detailed understanding of its composition, function and chemistry is advisable to guide experimental design and data interpretation. The purpose of this review is to provide an independent, comprehensive description of the DSP technology, including an overview of NanoString's capture and antibody barcode conjugation chemistries, experimental workflow, data output and analysis methods. The DSP technology will be discussed in the context of other highly multiplexed immunohistochemistry methods, including imaging mass cytometry and multiplexed ion beam imaging, to inform potential users of the advantages and limitations of each. Additional issues such as preanalytical variability, sampling and specimen adequacy will be considered with respect to the platforms to inform potential experimental design. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
The role of oxygen doping on elemental intermixing at the PVD‐CdS/Cu (InGa)Se2 heterojunction
Authors: He Xiaoqing , Ercius Peter , Varley Joel , Bailey Jeff , Zapalac Geordie , Nagle Tim , Poplavskyy Dmitry , Mackie Neil , Bayman Atiye , Lordi Vincenzo , Rockett Angus
Published: December 2018

Elemental intermixing at the CdS/CuIn1−xGaxSe2 (CIGS) heterojunction in thin‐film photovoltaic devices plays a crucial role in carrier separation and thus device efficiency. Using scanning transmission electron microcopy in combination with energy dispersive X‐ray mapping, we find that by controlling the oxygen in the sputtering gas during physical vapor deposition (PVD) of the CdS, we can tailor the degree of elemental intermixing. More oxygen suppresses Cu migration from the CIGS into the CdS, while facilitating Zn doping in the CdS from the ZnO transparent contact. Very high oxygen levels induce nanocrystallinity in the CdS, while moderate or no oxygen content can promote complete CdS epitaxy on the CIGS grains. Regions of cubic Cu2S phase were observed in the Cu‐rich CdCuS when no oxygen is included in the CdS deposition process. In the process‐of‐record sample (moderate O2) that exhibits the highest solar conversion efficiency, we observe a ~26‐nm‐thick Cu‐deficient CIGS surface counter‐doped with the highest Cd concentration among all of the samples. Cd movement into the CIGS was found to be less than 10 nm deep for samples with either high or zero O2. The results are consistent with the expectation that Cd doping of the CIGS surface and lack of Zn diffusion into the buffer both enhance device performance.
High‐Strain Shape Memory Behavior of PLA–PEG Multiblock Copolymers and Its Microstructural Origin
Authors: Koosomsuan Wasin , Yamaguchi Masayuki , Phinyocheep Pranee , Sirisinha Kalyanee
Published: December 2018

Shape memory properties of two thermoplastic multiblock copolymers composed of poly(lactic acid) (PLA) and poly(ethylene glycol) (PEG) having different PEG‐segment lengths of 6 and 11 kDa were studied. The performance as a shape memory polymer at high strain level (600%) and its interrelations with shape‐programming conditions, molecular orientation, and microstructural changes are elucidated. A significant contribution of strain‐induced crystallization of PLA segments to the improvement of temporary shape fixation was evidenced upon increasing draw ratio and/or shape‐holding duration as well as programming temperature (within certain range) without largely sacrificing the shape recoverability. Series of microstructural characterizations reveal the occurrence of fibrillar‐to‐lamellar transformation upon shape recovery (at 60 °C) of the samples programmed at 40 °C, generating shish–kebab crystalline morphology. Such phenomenon is responsible for the high‐strain shape memory effect of these materials. The unprecedented formation of shish–kebab structure at such relatively low temperature (instead of the melting temperature range) in solid state observed in these copolymers as well as their high‐strain shape memory functionality would bestow the promising future for their practicability in diverse areas. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2019, 57, 241–256
Coffee diterpenes kahweol acetate and cafestol synergistically inhibit the proliferation and migration of prostate cancer cells
Authors: Iwamoto Hiroaki , Izumi Kouji , Natsagdorj Ariunbold , Naito Renato , Makino Tomoyuki , Kadomoto Suguru , Hiratsuka Kaoru , Shigehara Kazuyoshi , Kadono Yoshifumi , Narimoto Kazutaka , Saito Yohei , Nakagawa‐Goto Kyoko , Mizokami Atsushi
Published: December 2018

Background

Coffee inhibits the progression of prostate cancer; however, the direct mechanism through which coffee acts on prostate cancer cells remains unclear. This study aimed to identify the key compounds of coffee that possess anti‐cancer effects and to investigate their mechanisms of action.

Methods

The anti‐proliferation and anti‐migration effects of six potentially active types of coffee compounds, including kahweol acetate, cafestol, caffeine, caffeic acid, chlorogenic acid, and trigonelline hydrochloride, were evaluated using LNCaP, LNCaP‐SF, PC‐3, and DU145 human prostate cancer cells. The synergistic effects of these compounds were also investigated. Apoptosis‐related and epithelial‐mesenchymal transition‐related proteins, androgen receptor in whole cell and in nucleus, and chemokines were assessed. A xenograft study of SCID mice was performed to examine the in vivo effect of coffee compounds.

Results

Among the evaluated compounds, only kahweol acetate and cafestol inhibited the proliferation and migration of prostate cancer cells in a dose‐dependent manner. The combination treatment involving kahweol acetate and cafestol synergistically inhibited proliferation and migration (combination index <1) with the induction of apoptosis, the inhibition of epithelial‐mesenchymal transition, and decrease in androgen receptor, resulting in the reduction of nuclear androgen receptor in androgen receptor‐positive cells. Moreover, kahweol acetate and cafestol downregulated CCR2 and CCR5 without an increase in their ligands, CCL2 and CCL5. The xenograft study showed that oral administration of kahweol acetate and cafestol significantly inhibited tumor growth.

Conclusion

Kahweol acetate and cafestol synergistically inhibit the progression of prostate cancer. These coffee compounds may be novel therapeutic candidates for prostate cancer.
Robust control of systems with sector nonlinearities via convex optimization: A data‐driven approach
Authors: Nicoletti Achille , Karimi Alireza
Published: December 2018

In this paper, a new data‐driven method for designing robust controllers is proposed for systems with sector‐bounded nonlinearities and multimodel uncertainties. The results from the circle criterion are used to generate necessary and sufficient convex constraints that guarantee the stability of the closed‐loop system. The main feature of the proposed approach is that only the frequency response data of the linear part of the system is used for guaranteeing the stability of the closed‐loop nonlinear system. Additionally, a convex optimization problem is formulated to ensure
performance with respect to the fundamental component of a sector‐bounded nonlinearity. The case study illustrates how the proposed method can be used to control uncertain systems that are subject to sector‐bounded nonlinearities.
Hydrogen Peroxide Responsive Iron–Based Nanoplatform for Multimodal Imaging–Guided Cancer Therapy
Authors: Wang Peng , Shi Yunhao , Zhang Shichao , Huang Xiaoyu , Zhang Jiaojiao , Zhang Yewei , Si Weili , Dong Xiaochen
Published: December 2018

Cancer multimodal phototherapy triggered by hydrogen peroxide has attracted widespread attention as a dominating strategy to increase phototherapeutic efficiency. Herein, a hydrogen peroxide responsive iron oxide nanoplatform, with the diameter of about 50 nm, is fabricated to intracellularly trigger the Fenton reaction and achieve synergistic photodynamic therapy and photothermal therapy. The nanoplatform based on iron oxide nanoparticles is decorated with indocyanine green (ICG, photosensitizer) and hyaluronic acid (HA, targeting molecular) through electrostatic interaction, thus the as‐prepared nanoplatform (IONPs‐ICG‐HA) exhibits excellent active targeting ability and biocompatibility. More importantly, it can effectively utilize the intratumoral overproduced hydrogen peroxide to generate reactive oxygen species for cancer cell killing via intracellular Fenton reactions. In vitro and in vivo experiments reveal that the IONPs‐ICG‐HA nanocomposites realize effective photoacoustic/photothermal/fluorescence imaging–guided phototherapy, leading to promising hydrogen peroxide responsive cancer theranostics.
Plasmonic Gold Nanovesicles for Biomedical Applications
Authors: Huang Yan , Huang Peng , Lin Jing
Published: December 2018

Gold nanoparticles (GNPs), with tunable optical properties, bioinertness, and surface multivalent effect, have been widely explored for biomedical applications. As one classical type of GNPs‐based assemblies, plasmonic gold nanovesicles (GVs), with a hollow cavity, “solid skeleton” composed of GNPs cores and a “soft body” composed of functional polymers, have attracted considerable attention due to their tunable localized surface plasmon resonance, strong surface‐enhanced Raman scattering properties, and high photothermal conversion efficiency. This review summarizes recent advances in biomedical applications for plasmonic GVs. Firstly, the synthesis methods of GVs are mainly including self‐assembly and in situ gold growth methods. Secondly, the classification of GVs is described according to the morphology of GNPs cores. Thirdly, different biomedical applications of GVs are elaborated, including in vitro diagnosis, in vivo imaging, and in vivo therapy. Finally, the challenges and perspectives of GVs are discussed.
A Journey towards Salivary Fluoride Level Detection by Suitable Low Cost Chemosensor: From Molecule to Product
Authors: Ghosh Pritam , Banerjee Priyabrata
Published: December 2018

Fluoride is a ubiquitous anion and essential for us owing to its ability to protect human body from several health related issues. The safe limit of Fluoride ion for human body is 1.5 ppm, above it the ion becomes toxic and can cause dental‐skeletal fluorosis or urolithiasis. Several countries are facing such health hazard owing to the naturally abundant excess fluoride in ground water. As a consequence, habitants of such fluoride enriched zone needs to monitor the concentration of fluoride in their body by periodic analysis. In this regard, development of a chemosensor which can detect fluoride from human body fluid at easy‐instant‐economic way is an obvious mandate. For the first time, our group has developed a sensor kit and sensor station device as a deliverable product for individual and batch scale detection of salivary fluoride level by colorimetric method. The sensor station is the first device made by interfacing chemical output with electronics and the encrypted signal in digital version could be used as a level of fluoride in saliva. Our journey towards the development of suitable chemosensor for recognition of fluoride from human body fluid is summarized in this account.
Predictive modelling and analytics for diabetes using a machine learning approach
Authors: Kaur Harleen , Kumari Vinita
Published: December 2018

Diabetes is a major metabolic disorder which can affect entire body system adversely. Undiagnosed diabetes can increase the risk of cardiac stroke, diabetic nephropathy and other disorders. All over the world millions of people are affected by this disease. Early detection of diabetes is very important to maintain a healthy life. This disease is a reason of global concern as the cases of diabetes are rising rapidly. Machine learning (ML) is a computational method for automatic learning from experience and improves the performance to make more accurate predictions. In the current research we have utilized machine learning technique in Pima Indian diabetes dataset to develop trends and detect patterns with risk factors using R data manipulation tool. To classify the patients into diabetic and non-diabetic we have developed and analyzed five different predictive models using R data manipulation tool. For this purpose we used supervised machine learning algorithms namely linear kernel support vector machine (SVM-linear), radial basis function (RBF) kernel support vector machine, k-nearest neighbour (k-NN), artificial neural network (ANN) and multifactor dimensionality reduction (MDR).
Absence Causation for Causal Dispositionalists
Authors: CLARKE RANDOLPH
Published: December 2018

Several theories of causation rule out causation of or by lacks, omissions, or absences of things. They thereby conflict with much of what we think and say about what causes what. This article proposes a modification of one kind of theory, causal dispositionalism, so that it accepts absence causation while retaining a fundamental commitment of dispositionalism.
Navigating the Western Academy: An Aboriginal Man's PhD Perspective
Authors: Kelly Steven
Published: December 2018

This paper discusses the PhD research process from my perspective as an Aboriginal man. The paper illuminates how I navigated my way through a Western academic system using an Aboriginal framework. I give insights into the dynamics at play in both academic and traditional ways of knowing, being and doing. As an Aboriginal researcher, I was intent, as many Aboriginal scholars are, on doing research that was inclusive, respectful, culturally appropriate and satisfactory to both partners. The paper is not designed as a ‘one size fits all’, but may be used as a signpost for those who choose to do research with Aboriginal people or for insights into the experiences of an Aboriginal Higher Degree by Research student and researcher.
Same words, different worlds: Exploring differences in researcher and participant understandings of promise and obligation in the psychological contract
Authors: Ma Guoxin , Blenkinsopp John , Armstrong Steve
Published: December 2018

This paper addresses longstanding questions about how promise and obligation, two of the key conceptual building blocks for psychological contract research, are conceptualized and operationalized: How do employees understand these concepts? Would their understandings be congruent with the researchers’ and how would this knowledge inform future psychological contract research? Drawing on interviews with 61 Chinese workers from diverse backgrounds, our results suggest the concepts have distinct meanings for participants in terms of three criteria (defining characteristics, key features and manifestations in employment). We argue that promise and obligation are likely to serve different functions in employment relationship and have different meanings for researchers versus participants, and accordingly we highlight the challenges of using them to conceptualize and operationalize psychological contracts in China and beyond.
Fat-soluble vitamins from diet in relation to risk of type 2 diabetes mellitus in Japanese population
Authors: Eshak Ehab S. , Iso Hiroyasu , Muraki Isao , Tamakoshi Akiko
Published: December 2018

The role of fat-soluble vitamins in the pathology of type 2 diabetes needs further research. Possible protective effects could be expected for vitamins A and E via their antioxidant properties, vitamin K via its modulating effects on cytokines and insulin resistance and vitamin D via the enhancement of insulin sensitivity. However, the evidence on association between fat-soluble vitamins from diet and risk of diabetes is limited. Therefore, among 19 168 healthy Japanese of both sexes aged 40–79 years, we used the logistic regression analyses to examine the prospective association between FFQ-estimated dietary fat-soluble vitamins (A, K, E and D) and the risk of type 2 diabetes incident over a 5-year period. During this 5-year period, 494 new cases of diabetes were self-reported. Vitamins K and E from diet were associated with lowered risk of incident diabetes, whereas no associations with dietary intake of vitamin A or D were observed. The multivariable OR in the highest v. lowest quartiles of intakes were 0·71 (95 % CI 0·54, 0·93, Ptrend=0·01) for vitamin K and 0·72 (95 % CI 0·55, 0·95, Ptrend=0·02) for vitamin E. Mutual adjustment for dietary intake of these vitamins did not change the association. There were no interactions with sex, age, smoking status, BMI or having a family history of diabetes, P were >0·10. In conclusion, higher dietary intake of fat-soluble vitamins K and E, but not vitamin A or D, were associated with lowered risk of type 2 diabetes among Japanese population.
Modelling appropriate use of trypanocides to restrict wide-spread multi-drug resistance during chemotherapy of animal African trypanosomiasis
Authors: Wangwe Ibrahim I. , Wamwenje Sarah A. , Mirieri Caroline , Masila Nicodemus M. , Wambua Lillian , Kulohoma Benard W.
Published: December 2018

Trypanocide resistance remains a huge challenge in the management of animal African trypanosomiasis. Paucity of data on the prevalence of multi-drug resistant trypanosomes has greatly hindered optimal veterinary management practices. We use mathematical model predictions to highlight appropriate drug regimens that impede trypanocide resistance development in cattle. We demonstrate that using drugs in decreasing resistance order results in a negligible increase in number of cattle with resistant infection, in contrast to a more pronounced increase from trypanocide use in increasing resistance order. We demonstrate that the lowest levels of trypanocide resistance are achieved with combination therapy. We also show that increasing the number of cattle treated leads to a progressive reduction in the number of cattle with drug resistant infections for treatments of up to 80% of the cattle population for the combination treatment strategy. Our findings provide an initial evidence-based framework on some essential practices that promote optimal use of the handful of trypanocides. We anticipate that our modest forecasts will improve therapeutic outcomes by appropriately informing on the best choice, and combination of drugs that minimize treatment failure rates.
Cellular immunity in the insectGalleria mellonellaagainst insect non-parasitic nematodes
Authors: Ono Masaya , Yoshiga Toyoshi
Published: December 2018

Immunity to microbial infections is well understood; however, information regarding the immunity to parasitic multicellular organisms remains lacking. To understand innate host cellular immunity to nematodes, we compared the cellular response of the greater wax moth (Galleria mellonella) larvae against the non-parasitic, bacterial-feeding nematodeCaenorhabditis elegansand pathogenic nematodeHeterorhabditis bacteriophora. When intact first-instar or dauer larvae ofC. eleganswere injected into aG. mellonellalarva, most of the nematodes were alive and not confined by the surrounding reaction by insect haemocytes (encapsulation), similarly as the pathogenic nematode, whereas most of the heat-killed nematodes of both species were severely encapsulated by 24 h after inoculation. Other non-parasitic nematodes were also not encapsulated. Surprisingly,C. elegansinjected into the insect haemocoel grew and propagated in the live insect, resulting in death of the host insect. Our results suggest thatC. eleganshas some basic mechanisms to evade immunity ofG. mellonenllaand grow in the haemocoel.
Are family warmth and positive remarks related to outcomes in psychosis? A systematic review
Authors: Butler Rebecca , Berry Katherine , Varese Filippo , Bucci Sandra
Published: December 2018

Background

Affective attitudes and behaviours manifested within the family environment have been characterised as expressed emotion (EE). High EE environments have been robustly shown to put psychosis patients at a greater risk of relapse compared with low EE exposure. Positive EE dimensions (warmth; positive remarks) have received far less attention than negative EE dimensions such that EE has become synonymous with a negative family atmosphere; the predictive value of positive EE dimensions is largely ignored. A systematic review examining the relationship between positive family EE and outcomes in psychosis is needed.

Methods

A systematic search was conducted. Studies reporting bias and study quality were assessed.

Results

A total of 2368 studies were identified. Of these, 27 met eligibility criteria reporting outcomes including relapse, symptomatology, social functioning and life satisfaction. Relapse was the most commonly measured outcome. Stronger evidence emerged for the association between EE warmth and outcomes compared with EE positive remarks, with effects mostly evident in the early phase of psychosis. Evidence for protective effects of warmth on relapse was found up to 9 months follow-up. No effects were evident between positive remarks and relapse. Studies assessing symptom outcomes showed inconsistent findings. Evidence for an association with social functioning was evident, primarily in at risk mental states. Warmth and positive remarks predicted life satisfaction.

Conclusions

The positive aspects of EE require further investigation with longitudinal research designs. Clinical interventions should focus not only on reducing negative aspects of EE but also foster warmth within families in the context of psychosis.
The Rise of Safe Havens for Threatened Cultural Heritage
Authors: Paumgartner Nikolaus Thaddäus , Zingg Raphael
Published: December 2018

In light of the recent rise of destruction and looting of cultural property, a need for formalized heritage protection has arisen. Increasingly popular in the debate has become the instrument of international assistance known as “safe havens.” These temporary refuges for at-risk cultural goods in a third country have recently been implemented by Switzerland, France, the United States, and the Association of Art Museum Directors. We assess the contributions and shortcomings of these four regimes using a comparative approach. Mainly, we find that, despite variations in their scope and structure, none of the models accounts entirely for today’s major difficulties in protecting endangered cultural properties. We draw recommendations for future safe haven states against the backdrop of the existing models and hope to see the instrument used in practice as a way to safely isolate cultural property from destructive conflicts.
CAPTIVE REPRESENTATIONS AND SOCIAL DISCOURSE AT IZAPA AND IN LATE FORMATIVE SOUTHEASTERN MESOAMERICA
Authors: Guernsey Julia
Published: December 2018

This paper takes Izapa Stela 21, with its vivid portrayal of captive sacrifice, as the point of departure for an analysis of the ways in which acts of aggression were portrayed in Late Formative monuments from a region that includes the Pacific slope and adjacent highlands of Mexico and Guatemala. It considers the social significance of themes of captive sacrifice and violence, and their role within a larger iconographic system designed to accommodate the mutually reinforcing ideas of ideology and coercive power. While clearly laden with implications of political control, subjugation, deference, and fealty, the imagery also alludes to agricultural fertility, the arrival of rain, and broader notions of social order.
IZAPA'S INDUSTRIAL HINTERLAND: THE EASTERN SOCONUSCO MANGROVE ZONE DURING ARCHAIC AND FORMATIVE TIMES
Authors: Neff Hector , Burger Paul H. , Culleton Brendan J. , Kennett Douglas J. , Jones John G.
Published: December 2018

Archaeological survey and excavations in the mangrove-estuary zone south of Izapa have generated an understanding of how the environment and human exploitation patterns changed during the Archaic and Formative periods. Archaic-period archaeological remains are not present, but the sedimentary record shows that Archaic people were clearing the coastal-plain forest for agricultural purposes. This activity augmented delivery of sediments to the littoral zone, which expanded the mangrove forest and created a productive environment that could be colonized by Early Formative villagers by around 1600 calb.c.Population growth during the Early Formative created conditions that favored emergence of specialized pyro-industries, especially salt production, by around 1000 calb.c.Production intensity increased thereafter, especially during the Late Formative period, coincident with the apogee of Izapa. Salt production became more episodic during the Terminal Formative period, when interior populations were declining to a nadir after cala.d.250.
Why We Should Defend Gene Editing as Eugenics
Authors: AGAR NICHOLAS
Published: December 2018

This paper considers the relevance of the concept of “eugenics,”—a term associated with some of the most egregious crimes of the twentieth century—to the possibility of editing human genomes. The author identifies some uses of gene editing as eugenics but proposes that this identification does not suffice to condemn them. He proposes that we should distinguish between “morally wrong” practices, which should be condemned, and “morally problematic” practices that call for solutions, and he suggests that eugenic uses of gene editing fall into this latter category. Although when we choose the characteristics of future people we are engaging in morally dangerous acts, some interventions in human heredity should nevertheless be acknowledged as morally good. These morally good eugenic interventions include some uses of preimplantation genetic diagnosis. The author argues that we should think about eugenic interventions in the same way that we think about morally problematic interventions in public health. When we recognize some uses of gene editing as eugenics, we make the dangers of selecting or modifying human genetic material explicit.
Gene Doping—in Animals? Ethical Issues at the Intersection of Animal Use, Gene Editing, and Sports Ethics
Authors: NEUHAUS CAROLYN P. , PARENT BRENDAN
Published: December 2018

Gene editors such as CRISPR could be used to create stronger, faster, or more resilient nonhuman animals. This is of keen interest to people who breed, train, race, and profit off the millions of animals used in sport that contribute billions of dollars to legal and illegal economies across the globe. People have tried for millennia to perfect sport animals; CRISPR proposes to do in one generation what might have taken decades previously. Moreover, gene editing may facilitate enhancing animals’ capacities beyond their typical limits. This paper describes the state of animal use and engineering for sport, examines the moral status of animals, and analyzes current and future ethical issues at the intersection of animal use, gene editing, and sports. We argue that animal sport enthusiasts and animal welfarists alike should be concerned about the inevitable use of CRISPR in sport animals. Though in principle CRISPR could be used to improve sport animals’ well-being, we think it is unlikely in practice to do so.
Genome Editing for Involuntary Moral Enhancement
Authors: RAKIĆ VOJIN
Published: December 2018

During the previous years, voluntary moral bioenhancement (VMBE) has been contrasted to compulsory moral bioenhancement (CMBE). In this paper a third possible type of moral bioenhancement is discussed: genome editing for moral enhancement of the unborn that is neither voluntary nor compulsory, but involuntary. Involuntary moral bioenhancement (IMBE) might engineer people who will be more moral than they otherwise would have been. The possibilities of genome editing aimed at moral enhancement of our offspring is assessed. It is argued that genome editing might have the potential to engineer our offspring in three domains: to be more empathetic, to be less violently aggressive, and to have a higher potential for complex moral reflection. Genome editing is discussed in these three domains, and a proposal made that a combination of VMBE and IMBE might be the best option humans have to become better.
Continued Access to Investigational Medicinal Products for Clinical Trial Participants—An Industry Approach
Authors: KELMAN ARIELLA , KANG ANNA , CRAWFORD BRIAN
Published: December 2018

In the conduct of clinical trials for pharmaceutical research, access to investigational medicines following clinical trials is often necessary for the continued health and well-being of the trial participants; it is an ethical obligation under some circumstances, as outlined in the Declaration of Helsinki 2013 Article 34. This obligation becomes particularly important in lower-income countries, where access to medical care may be limited. Although there is agreement among global research and bioethics communities that continued access should be provided with prospectively defined parameters and procedures, the process is complex, as many responsible parties and complicated logistics are involved. Roche Pharmaceuticals developed and publicly posted the company’s policy regarding continued access to investigational medicines in 2013. This article provides insights on the policy, including the parameters that determine when continued access is and is not considered to be appropriate, along with an example from an active clinical development program. It also describes how multiple stakeholders, including those in academia, industry, government, and patient advocacy, have worked together to assess approaches to continued access. Continued access plans should be transparent and agreed to by research participants, investigators, and governments prior to the study and reassessed based on clinical trial evidence of safety and efficacy and availability of adequate treatments, along with relevant international laws and customs. Conducting responsible continued access programs requires close partnerships with investigators, health authorities, and third-party research partners.
Healthy Volunteers for Clinical Trials in Resource-Poor Settings: National Registries Can Address Ethical and Safety Concerns
Authors: BOMPART FRANCOIS
Published: December 2018

Healthy volunteers (HVs) who participate in clinical trials are a vulnerable group that deserves specific protection. We assessed the number and types of studies that involve HVs around the world and outline the methodological barriers to their analysis. We found that tens of thousands of HVs are involved every year in clinical trials in a large variety of countries and that the overwhelming majority of studies are not “first-in-human” but pharmacokinetic studies. The two cornerstones for both ethical and safe participation of HVs in clinical trials are properly obtained informed consent and a minimization of exposure to risk, in particular by avoiding concealed participation in multiple trials. To minimize the risk of exploitation of HVs and their exposure to risk, we propose ways to ensure genuine informed consent, and advocate setting up national healthy volunteer registries as established in France and the U.K.
Advance Directives and Code Status Information Exchange: A Consensus Proposal for a Minimum Set of Attributes
Authors: LEHMANN CHRISTOPH U. , PETERSEN CAROLYN , BHATIA HARESH , BERNER ETA S. , GOODMAN KENNETH W.
Published: December 2018

Documentation of code status and advance directives for end-of-life (EOL) care improves care and quality of life, decreases cost of care, and increases the likelihood of an experience desired by the patient and his/her family. However, the use of advance directives and code status remains low and only a few organizations maintain code status in electronic form. Members of the American Medical Informatics Association’s Ethics Committee identified a need for a patient’s EOL care wishes to be documented correctly and communicated easily through the electronic health record (EHR) using a minimum data set for the storage and exchange of code status information. After conducting an environmental scan that produced multiple resources, Ethics Committee members used multiple conference calls and a shared document to arrive at consensus on the proposed minimum data set. Ethics Committee members developed a minimum required data set with links to the HL7 C_CDA Advance Directives Module. Data categories include information on the organization obtaining the code status information, the patient, any supporting documentation, and finally the desired code status information including mandatory, optional, and conditional elements. The “minimum set of attributes” to exchange advance directive / code status data described in this manuscript enables communication of patient wishes across multiple providers and health care settings. The data elements described serve as a starting point for a dialog among informatics professionals, physicians experienced in EOL care, and EHR vendors, with the goal of developing standards for incorporating this functionality into the EHR systems.
Cardiac Networks United: an integrated paediatric and congenital cardiovascular research and improvement network
Authors: Gaies Michael , Anderson Jeffrey , Kipps Alaina , Lorts Angela , Madsen Nicolas , Marino Bradley , Costello John M. , Brown David , Jacobs Jeffrey P. , Kasnic David , Lihn Stacey , Lannon Carole , Margolis Peter , Pearson Gail D. , Kaltman Jonathan , Charpie John R. , Redington Andrew N. , Pasquali Sara K. ,   on behalf of the Cardiac Networks United Executive Committee and Advisory Board
Published: December 2018

Optimising short- and long-term outcomes for children and patients with CHD depends on continued scientific discovery and translation to clinical improvements in a coordinated effort by multiple stakeholders. Several challenges remain for clinicians, researchers, administrators, patients, and families seeking continuous scientific and clinical advancements in the field. We describe a new integrated research and improvement network – Cardiac Networks United – that seeks to build upon the experience and success achieved to-date to create a new infrastructure for research and quality improvement that will serve the needs of the paediatric and congenital heart community in the future. Existing gaps in data integration and barriers to improvement are described, along with the mission and vision, organisational structure, and early objectives of Cardiac Networks United. Finally, representatives of key stakeholder groups – heart centre executives, research leaders, learning health system experts, and parent advocates – offer their perspectives on the need for this new collaborative effort.
A General Framework for Global Retrievals of Trace Gases From IASI: Application to Methanol, Formic Acid, and PAN
Authors: Franco B. , Clarisse L. , Stavrakou T. , Müller J.‐F , Van Damme M. , Whitburn S. , Hadji‐Lazaro J. , Hurtmans D. , Taraborrelli D. , Clerbaux C. , Coheur P.‐F
Published: December 2018

Retrieving concentrations of minor atmospheric trace gases from satellite observations is challenging due to their weak spectral signature. Here we present a new version of the ANNI (Artificial Neural Network for Infrared Atmospheric Sounding Interferometer, IASI) retrieval framework, which relies on a hyperspectral range index (HRI) for the quantification of the gas spectral signature and on an artificial feedforward neural network to convert the HRI into a gas total column. We detail the different steps of the retrieval method, especially where they differ from previous work, and apply the retrieval to three important volatile organic compounds: methanol (CH3OH), formic acid (HCOOH), and peroxyacetyl nitrate (PAN). The comparison of the retrieved columns with those from an optimal estimation inversion retrieval shows an overall excellent agreement: differences occur mainly when the sensitivity to the target gas is low and are consistent with the conceptual differences between the two approaches. We present retrieval examples over selected regions, comparison with previously developed products, and the global seasonal distributions including the first global distributions of PAN on a daily basis. The ANNI retrieval has been carried out on the whole time series of IASI observations (2007–2018), so that currently over 10 years of twice‐daily global CH3OH, HCOOH, and PAN total column distributions have been produced. This unique data set opens avenues for tackling important questions related to sources, transport, and transformation of volatile organic compounds in the global atmosphere.
Groundwater‐River Water Exchange Enhances Growing Season Evapotranspiration and Carbon Uptake in a Semiarid Riparian Ecosystem
Authors: Missik Justine E. C. , Liu Heping , Gao Zhongming , Huang Maoyi , Chen Xingyuan , Arntzen Evan , Mcfarland Douglas P. , Ren Huiying , Titzler P. Scott , Thomle Jonathan N. , Goldman Amy
Published: December 2018

Semiarid ecosystems play a critical role in determining the interannual variability of the global terrestrial carbon sink. Water availability is a critical driver of productivity in semiarid ecosystems, which often alternate between carbon sink/source functioning during wet/dry years. In this study, we investigate how groundwater availability resulting from groundwater‐river water exchange influences net ecosystem exchange of CO2 (NEE), evapotranspiration (ET), and the surface energy balance at two semiarid ecosystems along the Columbia River in central Washington, USA. We examined 1 year of eddy covariance measurements from an upland sagebrush ecosystem primarily fed by rainfall without groundwater access and a riparian grassland ecosystem with groundwater access during the dry season due to lateral groundwater‐river water exchange. The two sites had distinct seasonal patterns of NEE and ET, driven by differences in water availability. While NEE at the upland sagebrush site was strongly constrained by water availability during the dry months, access to groundwater allowed the riparian site to maintain high NEE magnitude and ET during the same dry months. The riparian site had larger annual gross primary productivity than the upland site (612 vs. 424 gC/m2), which was offset by higher ecosystem respiration (558 vs. 363 gC/m2). Thus, the magnitude of the annual NEE at the upland site was larger than that at the riparian site (−62 vs. −54 gC/m2). Our results demonstrate that groundwater access determined by connectivity between groundwater and surface water can be a critical driver of carbon uptake and ET in semiarid ecosystems.
Are Slope Streaks Indicative of Global‐Scale Aqueous Processes on Contemporary Mars?
Authors: Bhardwaj Anshuman , Sam Lydia , Martín‐Torres F. Javier , Zorzano María‐Paz
Published: December 2018

Slope streaks are prevalent and intriguing dark albedo surface features on contemporary Mars. Slope streaks are readily observed in the equatorial and subequatorial dusty regolith regions with low thermal inertia. They gradually fade over decadal timescales. The proposed mechanisms for their formation vary widely based on several physicochemical and geomorphological explanations. The scientific community is divided in proposing both dry and wet mechanisms for the formation of slope streaks. Here we perform a systematic evaluation of the literature for these wet and dry mechanisms. We discuss the probable constraints on the various proposed mechanisms and provide perspectives on the plausible process driving global‐scale slope streak formation on contemporary Mars. Although per our understanding, a thorough consideration of the global distribution of slope streaks, their morphology and topography, flow characteristics, physicochemical and atmospheric coincidences, and terrestrial analogies weighs more in favor of several wet mechanisms, we acknowledge that such wet mechanisms cannot explain all the reported morphological and terrain variations of slope streaks. Thus, we suggest that explanations considering both dry and wet processes can more holistically describe all the observed morphological variations among slope streaks. We further acknowledge the constraints on the resolutions of remote sensing data and on our understanding of the Martian mineralogy, climate, and atmosphere and recommend continuous investigations in this direction using future remote sensing acquisitions and simulations. In this regard, finding more wet and dry terrestrial analogs for Martian slope streaks and studying them at high spatiotemporal resolutions can greatly improve our understanding.
A Historically Based Review of Empirical Work on Color and Psychological Functioning: Content, Methods, and Recommendations for Future Research
Authors: Elliot Andrew J.
Published: December 2018

Empirical work on color and psychological functioning has a long history, dating back to the 19th century. This early research focused on five different areas: Arousal, physical strength, preference, time perception, and attention. In the present paper, I overview the relations observed in this early research, and detail methodological weaknesses therein. I then trace subsequent 20th and 21st century developments in these research areas, in terms of both content and methods. Finally, I extend the review to cover the full breadth of research in this domain of inquiry, and provide guidelines for interpreting existing work and conducting future work. Thus, this historically based review tells us much about research on color and psychological functioning, including where it started, where it has been, where it is, and where it can go.