Cyclin-dependent kinase 5 has been implicated in Alzheimer's disease pathogenesis. Here, we demonstrate that overexpression of p25, an activator of cdk5, led to increased levels of BACE1 mRNA and protein in vitro and in vivo. A p25/cdk5 responsive region containing multiple sites for signal transducer and activator of transcription was identified in the BACE1 promoter. STAT3 interacts with the BACE1 promoter, and p25-overexpressing mice had elevated levels of pSTAT3 and BACE1, whereas cdk5-deficient mice had reduced levels. Furthermore, mice with a (...) targeted mutation in the STAT3 cdk5 responsive site had lower levels of BACE1. Increased BACE levels in p25 overexpressing mice correlated with enhanced amyloidogenic processing that could be reversed by a cdk5 inhibitor. These data demonstrate a pathway by which p25/cdk5 increases the amyloidogenic processing of APP through STAT3-mediated transcriptional control of BACE1 that could have implications for AD pathogenesis. (shrink)

Using the corpus of JSTOR articles, we investigate the role of gender in collaboration patterns across the scholarly landscape by analyzing gender-based homophily--the tendency for researchers to co-author with individuals of the same gender. For a nuanced analysis of gender homophily, we develop methodology necessitated by the fact that the data comprises heterogeneous sub-disciplines and that not all authorships are exchangeable. In particular, we distinguish three components of gender homophily in collaborations: a structural component that is due to demographics and (...) non-gendered authorship norms of a scholarly community, a compositional component which is driven by varying gender representation across sub-disciplines, and a behavioral component which we define as the remainder of observed homophily after its structural and compositional components have been taken into account. Using minimal modeling assumptions, we measure and test for behavioral homophily. We find that significant behavioral homophily can be detected across the JSTOR corpus and show that this finding is robust to missing gender indicators in our data. In a secondary analysis, we show that the proportion of female representation in a field is positively associated with significant behavioral homophily. (shrink)

Survival after solid-organ transplantation has improved significantly, and many contemporary transplant recipients are of childbearing potential. There are limited data to guide decision-making surrounding pregnancy after transplantation, variations in clinical practice, and significant knowledge gaps, all of which raise significant ethical issues. Post-transplant pregnancy is associated with an increased risk of maternal and fetal complications. Shared decision-making is a central aspect of patient counselling but is complicated by significant knowledge gaps. Stakeholder interests can be in conflict; exploring these tensions can (...) help patients to evaluate their options and inform their deliberations. We argue that uniform, evidence-based recommendations for pregnancy after solid organ transplantation are needed. Conducting research, including patient-engaged studies, in this area should be priority for the transplant community. (shrink)

Objective: The objectives of this study are to understand the current functions, structure and operation of hospital ethics committees (HECs) in Shanghai and to facilitate their improvement. Methods: (1) A questionnaire survey, (2) interviews with secretaries and (3) on-site document reviews of HECs in Shanghai were used in the study, which surveyed 33 hospitals. Results: In Shanghai, 57.56% of the surveyed hospitals established HECs from 1998 to 2005. Most HECs used bioethical review of research involving human subjects as well as (...) bioethical review or consultation regarding medical care services and administrative decision- making. Of the surveyed HECs, 14.3% did not provide any formal bioethical training to the HECs’ members and many HECs had no standard operating procedures. Some HECs had no clear definition of what was “conflict of interest” that should be considered by the HECs, while 44.4% of the HECs did not perform continuing review. Discussion: After the issues of related national regulations, more and more hospitals established HECs in Shanghai, but the functions of HECs need to be further developed and formal training on bioethics should be provided to HEC members. To assure the independence and good performance of HECs, the conflict of interest procedure, the standard operating procedures and bioethical review should be improved. Conclusion: HECs in Shanghai had developed in the preceding 10 years and they played great roles in protecting the rights and welfare of human subjects and patients; some areas need improvement. (shrink)

We present the logic K/2 which is a logic with classical implication and only the left part of classical negation.We show that it is possible to define a classical negation into K/2 and that the classical proposition logic K can be translated into this apparently weaker logic.We use concepts from model-theory in order to characterized rigorously this translation and to understand this paradox. Finally we point out that K/2 appears, following Haack's distinction, both as a deviation and an extension of (...) K. (shrink)

~Et moi,.... si j'avait su comment en revenir, One service mathematics has rendered the je n'y serais point alle.' human race. It has put common sense back Jules Verne where it belongs, on the topmost shelf next to the dusty canister labelled 'discarded non· The series is divergent; therefore we may be sense'. Eric T. Bell able to do something with it. O. Heaviside Mathematics is a tool for thought. A highly necessary tool in a world where both feedback and (...) non­ linearities abound. Similarly, all kinds of parts of mathematics serve as tools for other parts and for other sciences. Applying a simple rewriting rule to the quote on the right above one finds such statements as: 'One service topology has rendered mathematical physics...'; 'One service logic has rendered com­ puter science...'; 'One service category theory has rendered mathematics...'. All arguably true. And all statements obtainable this way form part of the raison d'etre of this series. (shrink)

This paper is aimed at a critical assessment of the moral framework of the current Chinese health system from a Confucian perspective, by focusing on the debate between the individual directed approach and the family-oriented approach to a health care system. Concerned with the nature and status of the family in communal life, the paper deals with the following questions: to cope with the frailties of material life (including susceptibility to disease), what good is presupposed by human existence and flourishing; (...) why it is the family that serves as the primary locus of bearing and realizing this unique good; and what kind of society might possess the structures necessary to achieve the good thus conceived. All these questions lead to a revision of the theory of justice required in health care, in favor of family health saving accounts as an important institutional guarantee. (shrink)

Memory exhibits episodic superposition, an analog of the quantum superposition of physical states: Before a cue for a presented or unpresented item is administered on a memory test, the item has the simultaneous potential to occupy all members of a mutually exclusive set of episodic states, though it occupies only one of those states after the cue is administered. This phenomenon can be modeled with a nonadditive probability model called overdistribution (OD), which implements fuzzy-trace theory's distinction between verbatim and gist (...) representations. We show that it can also be modeled based on quantum probability theory. A quantum episodic memory (QEM) model is developed, which is derived from quantum probability theory but also implements the process conceptions of global matching memory models. OD and QEM have different strengths, and the current challenge is to identify contrasting empirical predictions that can be used to pit them against each other. (shrink)

The common liberal understanding of reproductive autonomy – characterized by free choice and a principle of non-interference – serves as a useful way to analyse the normative appeal of having certain choices open to people in the reproductive realm, especially for issues like abortion rights. However, this liberal reading of reproductive autonomy only offers us a limited ethical understanding of what is at stake in many kinds of reproductive choices, particularly when it comes to different uses of reproductive technologies and (...) third-party reproduction. This is because the liberal framework does not fully capture who benefits from which reproductive options, the extent of the risks and harms involved in various reproductive interventions, and the reasons for why people are driven to make certain reproductive choices. (shrink)

Literature on testimonial injustice and ways that perpetrators might combat it have flourished since Miranda Fricker’s ground-breaking work on testimonial injustice. Less attention has been given, however, to the role of bystanders. In this paper, I examine the accountability that bystanders may have for their omissions to redress testimonial injustice. I argue that bystander accountability applies in cases where it is opportune for bystanders to intervene, and if they are also sufficiently equipped and able to redress the testimonial injustice. Moreover, (...) I recommend that we move beyond virtue responsibilism for ameliorative thinking about testimonial injustice. (shrink)

Durante los días 16 al 23 de agosto se ha celebrado en la ciudad austriaca de Kirchberg am Wechsel un Congreso Internacional sobre Filosofía de la Matemática. La organización corría a cargo de la renovada Österreichische Ludwig Wittgenstein Geellschaft, que preside Rudolf Haller y cuenta con Jaakko Hintikka como principal scholar. El Congreso ha servido para reunir un buen número de especialistas en esta materia, entre los que figuran M. Dummett, H. Field, I. Grattan-Guinness, P. Maddy, Ch. Parsons, St. Shapiro (...) y H. Wang. Respecto del proyecto inicial sólo hubo una ausencia relevante: el profesor Crispin Wright, conocido especialmente en esta disciplina por su libro sobre la concepción fregeana del número como objeto y su estudio acerca del pensamiento wittgensteiniano sobre los fundamentos de la Matemática. (shrink)

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)