Recent studies show that racism still exists in the American medical profession, the fact of which legitimizes the historically long-legacy of mistrust towards medical profession and health authorities among African Americans. Thus, it was suspected that the participation of black patients in end-of-life care has always been significantly low stemmed primarily from their mistrust of the medical profession. On the other hand, much research finds that there are other reasons than the mistrust which makes African Americans feel reluctant to the (...) end-of-life care, such as cultural-religious difference and genuine misunderstanding of the services. If so, two crucial questions are raised. One is how pervasive or significant the mistrust is, compared to the other factors, when they opt out of the end-of-life care. The other is if there is a remedy or solution to the seemingly broken relationship. While no studies available answer these questions, we have conducted an experiment to explore them. The research was performed at two Philadelphia hospitals of Mercy Health System, and the result shows that Black patients’ mistrust is not too great to overcome and that education can remove the epistemic obstacles as well as overcome the mistrust. (shrink)

For many, Thomas Beauchamp and James Childress have elaborated moral reasoning by using the four principles whereby all substantive problems of medical ethics (and of ethics more generally) can be properly analysed and cogent philosophical solutions for the problems can be found. It seems that their ‘principlism’ gets updated, with better features being added during the course of the six editions of Principles of Biomedical Ethics. Nonetheless, Beauchamp and Childress seem to have been losing their way when it comes to (...) the common-morality justification, which is the epistemological (and perhaps metaphysical) backbone of their method, and this is shown more vividly in their most recent (2009) edition of Principles of Biomedical Ethics. The author points out what he calls the problem of ‘thick in status, thin in content’ in principlism. The problem exists because principlism cannot adequately explain how the prescriptive sense of common morality it supports is consistent with the existence of what Beauchamp and Childress call the ‘legitimate moral diversity in the world’. Because of this problem, first, the practical end that principlism allegedly accomplishes (ie, providing practical moral guidelines in a relatively ‘thick’ content, based on common morality) is frustrated, and, second, principlism makes itself the method of common morality de jure and of moral pluralism de facto. (shrink)

Addressing the question of how medicine should engage with people who consider their clinical disease condition to be importantly constitutive of their identity, this article focuses on one group—advocates for the fat acceptance (FA) or body positivity movement in American society. Drawing on philosophical analysis, I try to show that FA and physician communities represent different traditions within the larger culture and that whether obesity should be considered a disease is a culture battle. I argue that diseases (medical) and illnesses (...) (cultural) are 2 different designations of clinical symptoms and that both disease and illness designations can change over time or be uncertain. (shrink)

The number of police departments carrying Narcan keeps increasing at a fast pace throughout the U.S., as it is considered an effective measure to fight the opioid epidemic. However, there have been strong oppositions to the idea of the police Narcan use. Still, in 2018, the nation is debating about it. Though not clearly visible to the public, there are important ethical arguments against the police Narcan use which necessarily involve understanding of the ethical roles and responsibilities of police as (...) the law enforcement agency and apprehension of the moral status of a non-therapeutic opioid use. The authors of the paper investigate, primarily, the existing ethical controversies surrounding the police Narcan use while touching upon the issue of the decriminalizing drug policy in the U.S. The authors conclude that the police can carry and administer Narcan without self-contradiction and that the policymakers’ investigation on the drug decriminalization policy should begin with the understanding of the “common morality” of the American public, the ethical view shared and practiced by the greatest number of people. (shrink)

The 2017 story of Charlie Gard is revisited. Upon the British High Court’s ruling in favor of the physicians that the infant should be allowed to die without the experimental treatment, the view of the public as well as the opinions of bioethicists and Catholic bishops are divided, interestingly along with a cultural line. American bioethicists and Catholic bishops tend to believe that the parents should have the final say while British/European bioethicists and Catholic bishops in general side with the (...) court’s decision. The paper explores the place of culture in bioethical reasoning between the UK/Europe and the US while claiming that cultural differences are more important than geopolitical or religious differences to understand the bioethical positions of a group. In addition, the authors introduce a decision-making program for handicapped neonates which is developed by the American Jesuit Bioethicist, Richard McCormick, and modified further by the contemporary American Jesuit Bioethicist, Peter A. Clark, in an attempt to see if the program’s normatizing categories can contribute to the culture-laden ethical discussions on Charlie’s case. However, it is admitted that the McCormick-Clark device is borne out of the American and Catholic theological context. (shrink)

Starting January 1, 2017, the Oregon Health Authority (OHA, henceforth) made a sweeping decision that no elective surgery is to be performed for Medicaid recipients who smoke tobacco. The authors of this paper investigate the administrative procedures behind the OHA’s decision, explore some possible ethical arguments for and against the decision, and render our ethical verdict about the ban and our suggestion for the OHA. Meanwhile, since this issue involves the problems of smoking-related addiction, the agent’s autonomy which may be (...) understood in the light of moral freedom and rationality/irrationality, and our society’s perception about obesity and cigarette smoking; the paper engages in a deeper philosophical debate about the problems beyond the legal purview of the ban. (shrink)

It seems certain that one day we will allow the genetic technology which will enhance our offspring. A highly effective new tool, called CRISPR, which allows for carving out genes, is already being used to edit the genomes of animals. In July 2017, the FDA legalized that germline drugs for therapeutic purposes could be sold in the market. It is a high time, now, that we need engage in discussions about the ethics of germline intervention. To contribute to the discussion (...) by showing our thought and to educate the public, we write this paper. (shrink)

Ebola is a deadly disease with no cure; there is no vaccine developed yet. Many died during the 2014 outbreak in West Africa, and many healthcare professionals went to the virus infected area to treat the patients while placing their lives in danger. Not every medical professional placed in the field is a fully trained specialist, and sometimes one or two under-trained doctors are in charge of the entire clinic with some nurses and operating technicians. When unexpected outbreaks of the (...) virus occur in the places, the doctor(s) would encounter medical and ethical dilemmas. Should they leave or stay? In fact, this dilemma is not confined to the Ebola pandemic but relevant to all similar cases. In this paper, three authors, a medical resident, a clinical bioethicist, and a theoretical bioethicist respond to the dilemma. (shrink)

The Deaf culture in the United States is a unique culture that is not widely understood. To members of the Deaf community in the United States, deafness is not viewed as a disease or pathology to be treated or cured; instead it is seen as a difference in human experience. Members of this community do not hide their deafness; instead they take great pride in their Deaf identity. The Deaf culture in the United States is very communitarian not individualistic. Mary (...) Beth and Dominic are a married couple in their late 20s who are genetically deaf. They are active members in the Deaf community and work as advocates for individuals who are deaf, family members of Deaf people and sign language interpreters who identify with the Deaf culture. Mary Beth and Dominic approach the fertility clinic with a request that they only want a child with the genetic gene for deafness. They would want the embryos that do not have the gene to be destroyed. This would entail creating a child who would have the gene for deafness. Medically and ethically, should the fertility clinic agree to the couple’s request? The authors argue that the couple's request should be denied and provide reasons for it from the perspectives of foundational and clinical ethics. (shrink)

Investigating an actual case that occurred in a New York state hospital where an Orthodox Jewish patient’s legal proxy demands that the clinicians and hospital administrators should provide aggressive treatment with all available technological resources for the seemingly brain-dead patient with a medically futile condition. The authors argue that a health care policy or regulation should be developed to limit patient’s access to technology in critical care. Otherwise, we will be allowing society to issue a carte blanche to religious autonomy (...) by technology abuse. It is argued that religious autonomy should be restricted when its demand exhibits apparent logical absurdity and/or goes against the common survival of the entire population. (shrink)

As the Zika virus pandemic continues to bring worry and fear to health officials and medical scientists, Centers for Disease Control and Prevention (CDC) and World Health Organization (WHO) have recommended that residents of the Zika-infected countries, e.g., Brazil, and those who have traveled to the area should delay having babies which may involve artificial contraceptive, particularly condom. This preventive policy, however, is seemingly at odds with the Roman Catholic Church’s position on the contraceptive. As least since the promulgation of (...) Paul VI’s 1968 encyclical, Humanae Vitae, the Church has explicitly condemned artificial birth control as intrinsic evil. However, the current pontiff, Pope Francis, during his recent visit to Latin America, remarked that the use of artificial contraception may not be in contradiction to the teaching of Humanae Vitae while drawing a parallel between the current Zika Crisis and the 1960’s Belgian Congo Nun Controversy. The pope mentioned that the traditional ethical principle of the lesser of two evils may be the doctrine that justified the exceptions. The authors of this paper attempt to expand the theological rationale of the pope’s suggestion. In so doing, the authors rely on casuistical reasoning as an analytic tool that compares the Belgian Congo Nun case and the given Zika case, and suggest that the former is highly similar to, if not the same as, the latter in terms of normative moral feature. That is, in both cases the use of artificial contraception is theologically justified in reference to the criteria that the doctrine of the lesser of two evils requires. The authors wish that the paper would provide a solid theological-ethical ground based on which condom-use as the most immediate and effective preventive measure can be recommended in numerous Catholic hospitals as well as among Catholic communities in the world, particularly the most Zika-affected and largest Catholic community in the world, Brazil – 123 million present Brazilian citizens are reported to be Roman Catholic. (shrink)

The paper attempts to set a guideline to contemporary common morality debate. The author points out what he sees as two common problems that occur in the field of comparative cultural studies related to a common morality debate. The first problem is that the advocates and opponents of common morality, consciously or unconsciously, define the moral terms in question in a way that their respective meanings would naturally lead to the outcomes that each party desires. The second problem is that (...) the examples each party chooses as the empirical evidences may not be as simple and clear-cut as the researchers think they are, mainly because the situational contexts where the examples are located between two different cultures vastly differ. To prevent these mistakes, the author emphasizes that we should pay attention to a subtle distinction between "thick" and "thin" construed from the levels of "theoretical status" and of "material content". With the conceptual distinctions in mind, the author shows how different cultures (i.e., Western individualist society and East Asian neo-Confucian society) see the moral principles like autonomy and beneficence in different lexical orders. (shrink)

Ethics in Public Health and Population Health.

This paper is a study about Philadelphia’s comprehensive user engagement sites (CUESs) as the authors address and examine issues related to the upcoming implementation of a CUES while seeking solutions for its disputed questions and plans. Beginning with the federal drug schedules, the authors visit some of the medical and public health issues vis-à-vis safe injection facilities (SIFs). Insite, a successful Canadian SIF, has been thoroughly researched as it represents a paradigm for which a Philadelphia CUES can expand upon. Also, (...) the existing criticisms against SIFs are revisited while critically unpackaged and responded to in favor of the establishment. In the main section, the authors propose the layout and services of the upcoming CUES, much of which would be in congruent to Vancouver’s Insite. On the other hand, the CUES would be distinct from Insite, as the authors emphasize, in that it will offer an information center run by individuals in recovery and place additional emphasis on early education for young healthcare professionals by providing them a platform to work at the site. The paper will also briefly investigate the implementation of a CUES site under an ethical scope of the Harm Reduction Theory. Lastly, the authors recommend some strategic plans that the Philadelphia City government may consider employing at this crucial stage. (shrink)

It is reported that medical students both in the U.S. and Poland have experience of interacting with pharmaceutical company representatives (pharma reps) during their school years. Studies have warned that the interaction typically initiated by the pharma reps’ general gift-giving eventually leads to the quid pro quo relationship between the pharma company and the future doctors, the result of which is that the doctors will prescribe their patients drugs in favor of the pharma company. Built upon the existing finding, this (...) research engages in analysis with three foci. The first is to compare attitudinal differences of the American and Polish medical students as they interact with pharma reps. Second, it investigates the role of the different economic and cultural elements (respectively in the U.S. and Poland) in the students’ attitudinal differences. Last, it suggests that the medical schools in both countries should have strict policies and effective education curriculum to help their students better prepare to interact ethically with pharma reps. Since there has been no direct comparative cultural analysis of this kind which is known in a published literature or report, the authors believe that the paper will serve as a catalyst for further research in the area. (shrink)

Interest in subjective values and decision responses are investigated empirically, including statistically testing the predictive relationships between subjective values, other independent variables such as level and area of executive responsibility, and decision responses.

A study of 513 executives researched decisions involving ethics, relationships and results. Analyzing personal values, organization role and level, career stage, gender and sex role with decisions in ten scenarios produced conclusions about both the role of gender, subjective values, and the other study variables and about situational relativity, gender stereotypes, career stages, and future research opportunities.

A cross-sectional study to ascertain what the Singapore population would regard as material risk in the anaesthesia consent-taking process and identify demographic factors that predict patient preferences in medical decision-making to tailor a more patient-centered informed consent. A survey was performed involving patients 21 years old and above who attended the pre-operative evaluation clinic over a 1-month period in Singapore General Hospital. Questionnaires were administered to assess patients’ perception of material risks, by trained interviewers. Patients’ demographics were obtained. Mann–Whitney U (...) test and Kruskal-Wallis one-way analysis of variance was used. Statistical significance was taken at p < 0.05. Four hundred fourteen patients were eligible of which 26 refused to participate and 24 were excluded due to language barrier. 364 patients were recruited. A higher level of education, being employed and younger age group are factors identified in patients who wanted greater participation in medical decisions. Gender, marital status, type of surgery, and previous surgical history did not affect their level of participation. The complications most patients knew about were Nausea, Drowsiness and Surgical Wound Pain. Patients ranked Heart Attack, Death and Stroke as the most significant risks that they wanted to be informed about in greater detail. Most patients wanted to make a joint decision with the anaesthetist, instead of letting the doctor decide or deciding for themselves. Discussion with the anaesthetist is the preferred medium of communication compared to reading a pamphlet or watching a video. Age and educational level can influence medical decision-making. Despite the digital age, most patients still prefer a clinic consult instead of audio-visual multimedia for pre-operative anaesthetic counselling. The local population appears to place greater importance on rare but serious complications compared to common complications. This illustrates the need to contextualize information provided during informed consent to strengthen the doctor-patient relationship. (shrink)

Federal regulations in the United States have shaped Institutional Review Boards to focus on protecting individual human subjects. Health services research studies focusing on healthcare institutions such as hospitals or clinics do not have individual human subjects. Since U.S. federal regulations are silent on what type of review, if any, these studies require, different IRBs may approach similar studies differently, resulting in undesirable variation in the review of studies focusing on healthcare institutions. Further, although these studies do not focus on (...) individual human subjects, they may pose risks to participating institutions, as well as individuals who work at those institutions, if identifying information becomes public. (shrink)

Although considerable research indicates that mental energy is an important factor in many domains, including athletic performance (Cook & Davis, 2006), athletic mental energy (AME) has never been conceptualized and measured. Therefore, the aim of this study was to conceptualize and develop a reliable and valid instrument to assess athletic mental energy. In Study 1, a focus group interview established the initial framework of athletic mental energy. Study 2 used a survey to collect athletes’ experiences of athletic mental energy and (...) develop a scale draft titled “Athletic Mental Energy Scale (AMES).” In Study 3, we examined the psychometric properties and the underlying structure of AMES via item analysis, internal consistency, and exploratory factor analysis (EFA). In Study 4, we used confirmatory factor analysis (CFA) to examine AMES’s factorial validity; and examined concurrent and discriminant validity by examining correlations with athletes’ life stress, positive state of mind, and burnout. In study 5, we examined the measurement invariance of the 6-factor, 18-item AMES with Taiwanese and Malaysian samples. Study 6 examined the predictive validity by comparing AMES scores of successful and unsuccessful martial artists. Across these phases, results showed a 6-factor, 18-item AMES had adequate content validity, factorial structure, nomological validity, discriminant validity, predictive validity, measurement invariance, and reliability. We suggest future studies may use AMES to examine its relationships with athletes’ cognition, affect, and performance. The application of AMES in sport psychology was also discussed. (shrink)

© The Author 2016. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists.Lignin poses a major challenge in the processing of plant biomass for agro-industrial applications. For bioengineering purposes, there is a pressing interest in identifying and characterizing the enzymes responsible for the biosynthesis of lignin. Hydroxycinnamoyl-CoA:shikimate hydroxycinnamoyl transferase is a key metabolic entry point for the synthesis of the most important lignin monomers: coniferyl and sinapyl alcohols. In this study, we investigated the substrate promiscuity of (...) HCT from a bryophyte and from five representatives of vascular plants using a yeast expression system. We demonstrate for these HCTs a conserved capacity to acylate with p-coumaroyl-CoA several phenolic compounds in addition to the canonical acceptor shikimate normally used during lignin biosynthesis. Using either recombinant HCT from switchgrass or an Arabidopsis stem protein extract, we show evidence of the inhibitory effect of these phenolics on the synthesis of p-coumaroyl shikimate in vitro, which presumably occurs via a mechanism of competitive inhibition. A structural study of PvHCT2a confirmed the binding of a non-canonical acceptor in a similar manner to shikimate in the active site of the enzyme. Finally, we exploited in Arabidopsis the substrate flexibility of HCT to reduce lignin content and improve biomass saccharification by engineering transgenic lines that overproduce one of the HCT non-canonical acceptors. Our results demonstrate conservation of HCT substrate promiscuity and provide support for a new strategy for lignin reduction in the effort to improve the quality of plant biomass for forage and cellulosic biofuels. (shrink)

© 2015 Elsevier Inc. β-adrenergic signaling pathways mediate key aspects of cardiac function. Its dysregulation is associated with a range of cardiac diseases, including dilated cardiomyopathy. Previously, we established an iPSC model of familial DCM from patients with a mutation in TNNT2, a sarcomeric protein. Here, we found that the β-adrenergic agonist isoproterenol induced mature β-adrenergic signaling in iPSC-derived cardiomyocytes but that this pathway was blunted in DCM iPSC-CMs. Although expression levels of several β-adrenergic signaling components were unaltered between control (...) and DCM iPSC-CMs, we found that phosphodiesterases 2A and PDE3A were upregulated in DCM iPSC-CMs and that PDE2A was also upregulated in DCM patient tissue. We further discovered increased nuclear localization of mutant TNNT2 and epigenetic modifications of PDE genes in both DCM iPSC-CMs and patient tissue. Notably, pharmacologic inhibition of PDE2A and PDE3A restored cAMP levels and ameliorated the impaired β-adrenergic signaling of DCM iPSC-CMs, suggesting therapeutic potential. In this paper, Wu etal. profiled the β-adrenergic signaling properties in human iPSC-CMs and demonstrated novel epigenetic mechanisms that underlie the compromised β-adrenergic signaling in DCM, a common cause of heart failure and cardiac transplantation. These results enhance our understanding of DCM pathogenesis and may uncover new therapeutic targets. (shrink)

Elephants show a rich social organization and display a number of unusual traits. In this paper, we analyse reports collected over a thirty-five year period, describing behaviour that has the potential to reveal signs of empathic understanding. These include coalition formation, the offering of protection and comfort to others, retrieving and 'babysitting' calves, aiding individuals that would otherwise have difficulty in moving, and removing foreign objects attached to others. These records demonstrate that an elephant is capable of diagnosing animacy and (...) goal directedness, and is able to understand the physical competence, emotional state and intentions of others, when they differ from its own. We argue that an empathic understanding of others is the simplest explanation of these abilities, and discuss reasons why elephants appear to show empathy more than other non-primate species. (shrink)

Drug Safety Communications are used by the Food and Drug Administration to inform health care providers, patients, caregivers, and the general public about safety issues related to FDA-approved drugs. To assess patient knowledge of the messaging contained in DSCs related to the sleep aids zolpidem and eszopiclone, we conducted a large, cross-sectional patient survey of 1,982 commercially insured patients selected by stratified random sampling from the Optum Research Database who had filled at least two prescriptions for either zolpidem or eszopiclone (...) between July 1, 2012 and June 30, 2013. Among the 594 respondents, two-thirds reported hearing generally about drug safety information prior to starting a new drug, with the remaining one-third “rarely” or “never” hearing such information. Providers and pharmacists were primary sources of drug safety information. Two-thirds of zolpidem users and half of eszopiclone users reported having heard about the related DSC messages, ability to accurately identify the major factual messages was limited. Respondents reacted to new drug safety information about their sleep aids by reporting that they would want to learn about alternative ways to help them sleep and seek out more information about the safety of their specific sleeping pill. Opportunities may exist for the FDA to work with providers and pharmacies to help ensure the DSC information is more widely received and is more fully understood by those taking the affected medications. (shrink)

Objectives: To evaluate ROP screening rates in a population-based cohort; and to identify characteristics of patients that were missed. Study design: We used the California Perinatal Quality Care Collaborative data from 2005-2007 for a cross-sectional study. Using eligibility criteria, screening rates were calculated for each hospital. Multivariable regression was used to assess associations between patient clinical and sociodemographic factors and the odds of missing screening. Results: Overall rates of missed ROP screening decreased from 18.6% in 2005 to 12.8% in 2007. (...) Higher gestational age, higher birth weight, and singleton birth were associated with higher probability of missing screening. Level II neonatal intensive care units and neonatal intensive care units with lower volume were more likely to miss screenings. Conclusion: Although ROP screening rates improved over time, larger and older infants are at risk for not receiving screening. Furthermore, large variations in screening rates exist among hospitals in California. Identification of gaps in quality of care creates an opportunity to improve ROP screening rates and prevent impaired vision in this vulnerable population. Copyright © 2012 Mosby Inc. (shrink)

Exaggerated contraction of airway smooth muscle is the major cause of symptoms in asthma, but the mechanisms that prevent exaggerated contraction are incompletely understood. Here, we showed that integrin α 9β 1on airway smooth muscle localizes the polyamine catabolizing enzyme spermidine/spermine N 1-acetyltransferase in close proximity to the lipid kinase PIP5K1γ. As PIP5K1γ is the major source of PIP2 in airway smooth muscle and its activity is regulated by higher-order polyamines, this interaction inhibited IP3-dependent airway smooth muscle contraction. Mice lacking (...) integrin α 9β 1 in smooth muscle had increased airway responsiveness in vivo, and loss or inhibition of integrin α 9β 1 increased in vitro airway narrowing and airway smooth muscle contraction in murine and human airways. Contraction was enhanced in control airways by the higher-order polyamine spermine or by cell-permeable PIP2, but these interventions had no effect on airways lacking integrin α 9β 1 or treated with integrin α 9β 1-blocking antibodies. Enhancement of SSAT activity or knockdown of PIP5K1γ inhibited airway contraction, but only in the presence of functional integrin α 9β 1. Therefore, integrin α 9β 1 appears to serve as a brake on airway smooth muscle contraction by recruiting SSAT, which facilitates local catabolism of polyamines and thereby inhibits PIP5K1γ. Targeting key components of this pathway could thus lead to new treatment strategies for asthma. (shrink)

© 2016 American Chemical Society.Hydrostatic pressure applied using diamond anvil cells has been widely explored to modulate physical properties of materials by tuning their lattice degree of freedom. Independently, electrical field is able to tune the electronic degree of freedom of functional materials via, for example, the field-effect transistor configuration. Combining these two orthogonal approaches would allow discovery of new physical properties and phases going beyond the known phase space. Such experiments are, however, technically challenging and have not been demonstrated. (...) Herein, we report a feasible strategy to prepare and measure FETs in a DAC by lithographically patterning the nanodevices onto the diamond culet. Multiple-terminal FETs were fabricated in the DAC using few-layer MoS2 and BN as the channel semiconductor and dielectric layer, respectively. It is found that the mobility, conductance, carrier concentration, and contact conductance of MoS2 can all be significantly enhanced with pressure. We expect that the approach could enable unprecedented ways to explore new phases and properties of materials under coupled mechano-electrostatic modulation. (shrink)

Attention Restoration Theory proposes that exposure to natural environments helps to restore attention. For sustained attention—the ongoing application of focus to a task, the effect appears to be modest, and the underlying mechanisms of attention restoration remain unclear. Exposure to nature may improve attention performance through many means: modulation of alertness and one’s connection to nature were investigated here, in two separate studies. In both studies, participants performed the Sustained Attention to Response Task before and immediately after viewing a meadow, (...) ocean, or urban image for 40 s, and then completed the Perceived Restorativeness Scale. In Study 1, an eye-tracker recorded the participants’ tonic pupil diameter during the SARTs, providing a measure of alertness. In Study 2, the effects of connectedness to nature on SART performance and perceived restoration were studied. In both studies, the image viewed was not associated with participants’ sustained attention performance; both nature images were perceived as equally restorative, and more restorative than the urban image. The image viewed was not associated with changes in alertness. Connectedness to nature was not associated with sustained attention performance, but it did moderate the relation between viewing the natural images and perceived restorativeness; participants reporting a higher connection to nature also reported feeling more restored after viewing the nature, but not the urban, images. Dissociation was found between the physiological and behavioral measures and the perceived restorativeness of the images. The results suggest that restoration associated with nature exposure is not associated with modulation of alertness but is associated with connectedness with nature. (shrink)

Drug discovery and development to date has relied on animal models, which are useful but are often expensive, slow, and fail to mimic human physiology. The discovery of human induced pluripotent stem cells has led to the emergence of a new paradigm of drug screening using human and disease-specific organ-like cultures in a dish. Although classical static culture systems are useful for initial screening and toxicity testing, they lack the organization of differentiated iPS cells into microphysiological, organ-like structures deemed necessary (...) for high-content analysis of candidate drugs. One promising approach to produce these organ-like structures is the use of advanced microfluidic systems, which can simulate tissue structure and function at a micron level, and can provide high-throughput testing of different compounds for therapeutic and diagnostic applications. Here, we provide a brief outline on the different approaches, which have been used to engineer in vitro tissue constructs of iPS cell-based myocardium and liver functions on chip. Combining these techniques with iPS cell biology has the potential of reducing the dependence on animal studies for drug toxicity and efficacy screening. (shrink)

© 2015. American Geophysical Union. All Rights Reserved. Anthropogenic water management can change surface energy budgets and the water cycle. In this study, we focused on impacts of Asian low-latitude irrigation on regional and global climates during boreal wintertime. A state-of-the-art Earth system model is used to simulate the land-air interaction processes affected by irrigation and the consequent responses in atmospheric circulation. Perturbed experiments show that wet soil moisture anomalies at low latitudes can reduce the surface temperature on a continental (...) scale through atmospheric feedback. The intensity of prevailing monsoon circulation becomes stronger because of larger land-sea thermal contrast. Furthermore, anomalous upper level convergence over South Asia and midlatitude climatic changes indicate tropical-extratropical teleconnections. The wintertime Aleutian low is deepened and an anomalous warm surface temperature is found in North America. Previous studies have noted this warming but left it unexplained, and we provide plausible mechanisms for these remote impacts coming from the irrigation over Asian low-latitude regions. Key Points Model simulation without considering irrigation underestimates ET over Indo-Gangetic Plain Irrigation at Asian low latitudes has the potential to induce PNA teleconnection Irrigation results in interhemispheric thermal gradient, thereby modifying Pacific subtropical jet. (shrink)

In the management and business ethics literatures, stakeholder engagement has been demonstrated to lead to more ethical management practices. However, there may be limits on the extent to which stakeholder engagement can, as currently conceptualized, resolve some of the more difficult ethical challenges faced by managers. In this paper we argue that stakeholder engagement, when seen as a way of reducing five types of knowledge problems—risk, ambiguity, complexity, equivocality, and a priori irreducible uncertainty—can aid managers in resolving such ethical challenges. (...) Using a practical illustration of the ethical challenges surrounding the development and application of genetic modification technologies, we demonstrate how stakeholder engagement enables managers to better address these knowledge problems, thereby to manage more ethically. In this way, we suggest that stakeholder engagement has an even more crucial role to play in business ethics research and practice. (shrink)

© 2015 Wu et al. Pancreatic cancer has an extremely high mortality rate due to its aggressive metastatic nature. Resolving the underlying mechanisms will be crucial for treatment. Here, we found that overexpression of IL-17B receptor strongly correlated with postoperative metastasis and inversely correlated with progression-free survival in pancreatic cancer patients. Consistently, results from ex vivo experiments further validated that IL-17RB and its ligand, IL-17B, plays an essential role in pancreatic cancer metastasis and malignancy. Signals from IL-17B-IL-17RB activated CCL20/CXCL1/IL-8/TFF1 chemokine (...) expressions via the ERK1/2 pathway to promote cancer cell invasion, macrophage and endothelial cell recruitment at primary sites, and cancer cell survival at distant organs. Treatment with a newly derived monoclonal antibody against IL-17RB blocked tumor metastasis and promoted survival in a mouse xenograft model. These findings not only illustrate a key mechanism underlying the highly aggressive characteristics of pancreatic cancer but also provide a practical approach to tackle this disease. (shrink)