Improving introspection to inform free will regarding the choice by healthy individuals to use or not use cognitive enhancing drugs

A commentary in Nature entitled "Towards responsible use of cognitive-enhancing drugs by the healthy" (Greely et al 2008 Nature 456: 702–705) offers an opportunity to move toward a humane societal appreciation of mind-altering drugs. Using cognitive enhancing drugs as an exemplar, this article presents a series of hypotheses concerning how an individual might learn optimal use. The essence of the proposal is that individuals can cultivate sensitivity to the effects of ever-smaller amounts of psychoactive drugs thereby making harm less likely and benign effects more probable. Four interrelated hypotheses are presented and briefly discussed. 1. Humans can learn to discriminate ever-smaller doses of at least some mind-altering drugs; a learning program can be designed or discovered that will have this outcome. 2. The skill to discriminate drugs and dose can be generalized, i.e. if learned with one drug a second one is easier and so on. 3. Cultivating this skill/knack would be beneficial in leading to choices informed by a more accurate sense of mind-body interactions. 4. From a philosophical point of view learning the effects of ever-smaller doses of psychoactive agents offers a novel path into and to transcend the objective/subjective barrier and the mind/body problem

The Risk of Paradoxical Embolism (RoPE) Study: Developing risk models for application to ongoing randomized trials of percutaneous patent foramen ovale closure for cryptogenic stroke

<p>Abstract</p> <p>Background</p> <p>Despite the diffusion into practice of percutaneous closure of a patent foramen ovale (PFO) in patients with cryptogenic stroke (CS), the benefits have not been demonstrated, and remain unclear. For any individual presenting with a PFO in the setting of CS, it is not clear whether the PFO is pathogenically-related to the index event or an incidental finding. Further, the overall rate of stroke recurrence is low in patients with CS and PFO. How patient-specific factors affect the likelihood that a discovered PFO is related to an index stroke or affect the risk of recurrence is not well understood. These probabilities are likely to be important determinants of the benefits of PFO closure in CS.</p> <p>Design/Methods</p> <p>The goal of the Risk of Paradoxical Embolism (RoPE) Study is to develop and test a set of predictive models that can identify those patients most likely to benefit from preventive treatments for PFO-related stroke recurrence, such as PFO closure. To do this, we will construct a database of patients with CS, both with and without PFO, by combining existing cohort studies. We will use this pooled database to identify patient characteristics associated with the presence (versus the absence) of a PFO, and to use this "PFO propensity" to estimate the patient-specific probability that a PFO was pathogenically related to the index stroke (Model #1). We will also develop, among patients with both a CS and a PFO, a predictive model to estimate patient-specific stroke recurrence risk based on clinical, radiographic and echocardiographic characteristics. (Model #2). We will then combine Models #1 and #2 into a composite index that can rank patients with CS and PFO by their conditional probability that their PFO was pathogenically related to the index stroke <it>and </it>the risk of stroke recurrence. Finally, we will apply this composite index to completed clinical trials (currently on-going) testing endovascular PFO closure against medical therapy, to stratify patients from low-expected-benefit to high-expected-benefit.</p

Signal and noise in bridging PCR

BACKGROUND: In a variant of the standard PCR reaction termed bridging, or jumping, PCR the primer-bound sequences are originally on separate template molecules. Bridging can occur if, and only if, the templates contain a region of sequence similarity. A 3' end of synthesis in one round of synthesis that terminates in this region of similarity can prime on the other. In principle, Bridging PCR (BPCR) can detect a subpopulation of one template that terminates synthesis in the region of sequence shared by the other template. This study considers the sensitivity and noise of BPCR as a quantitative assay for backbone interruptions. Bridging synthesis is also important to some methods for computing with DNA. RESULTS: In this study, BPCR was tested over a 328 base pair segment of the E. coli lac operon and a signal to noise ratio (S/N) of approximately 10 was obtained under normal PCR conditions with Taq polymerase. With special precautions in the case of Taq or by using the Stoffel fragment the S/N was improved to 100, i.e. 1 part of cut input DNA yielded the same output as 100 parts of intact input DNA. CONCLUSIONS: In the E. coli lac operator region studied here, depending on details of protocol, between 3 and 30% per kilobase of final PCR product resulted from bridging. Other systems are expected to differ in the proportion of product that is bridged consequent to PCR protocol and the sequence analyzed. In many cases physical bridging during PCR will have no informational consequence because the bridged templates are of identical sequence, but in a number of special cases bridging creates, or, destroys, information

Bedingungsloses Grundeinkommen als Antwort auf die Krise der Erwerbsarbeit

Die vorliegende Arbeit soll einen Beitrag zur Diskussion rund um das bedingungslose Grundeinkommen (BGE) leisten und unter Berücksichtigung möglicher Einwände seine Chancen aufzeigen. Dabei wird besonderes Augenmerk auf die Darstellung der Krise der Erwerbsarbeit gelegt. Diese Krise ist vor allem dadurch entstanden, dass unsere Gesellschaft noch nicht gelernt hat, mit den veränderten Arbeitsbedingungen umzugehen. Die Gesellschaften sind potentiell wohlhabend, Not und materieller Mangel durch fehlende Produktionsmöglichkeiten müssten eigentlich nicht mehr existieren. Der Umfang der produzierten Güter und erbrachten Dienstleistungen wächst, gleichzeitig werden für diese Wertschöpfung aber weniger Leute gebraucht. Dadurch breiten sich mit Einkommenseinbußen verbundene Arbeitslosigkeit und atypische Beschäftigungsformen, welche oft Niedriglohnjobs sind, aus. Häufig kommt es zusätzlich zu einer Stigmatisierung der von Arbeitslosigkeit und Prekarisierung Betroffenen. Das BGE stellt vor diesem Hintergrund eine Alternative dar. Vielen erscheint es nun sinnvoll und gerecht, jedem Mitglied einer Gesellschaft ein bedingungsloses Grundeinkommen in existenzsichernder Höhe, unabhängig von Arbeit, Einkommen oder Lebenssituation, zukommen zu lassen. In meiner Arbeit werde ich mögliche Auswirkungen eines BGE diskutieren, sowie der Frage nachgehen, ob es eine gerechte Idee ist. Außerdem wird auf die Finanzierung des BGE eingegangen und dabei ein spezielles Modell näher beleuchtet. Den Abschluss meiner Arbeit bildet eine empirische Fallstudie, in welcher der Bekanntheitsgrad sowie Auswirkungen eines BGE in drei unterschiedlichen gesellschaftlichen Gruppen untersucht werden

Robots as vectors for marine invasions: best practices for minimizing transmission of invasive species via observation-class ROVs.

Remotely operated vehicles (ROVs) present a potential risk for the transmission of invasive species. This is particularly the case for small, low-cost microROVs that can be easily transported among ecosystems and, if not properly cleaned and treated, may introduce novel species into new regions. Here we present a set of 5 best-practice guidelines to reduce the risk of marine invasive species introduction for microROV operators. These guidelines include: educating ROV users about the causes and potential harm of species invasion; visually inspecting ROVs prior to and at the conclusion of each dive; rinsing ROVs in sterile freshwater following each dive; washing ROVs in a mild bleach (or other sanitizing agent) solution before moving between discrete geographic regions or ecosystems; and minimizing transport between ecosystems. We also provide a checklist that microROV users can incorporate into their pre- and post-dive maintenance routine

Quantification of Cell Movement Reveals Distinct Edge Motility Types During Cell Spreading

Actin-based motility is central to cellular processes such as migration, bacterial engulfment, and cancer metastasis, and requires precise spatial and temporal regulation of the cytoskeleton. We studied one such process, fibroblast spreading, which involves three temporal phases: early, middle, and late spreading, distinguished by differences in cell area growth. In these studies, aided by improved algorithms for analyzing edge movement, we observed that each phase was dominated by a single, kinematically and biochemically distinct cytoskeletal organization, or motility type. Specifically, early spreading was dominated by periodic blebbing; continuous protrusion occurred predominantly during middle spreading; and periodic contractions were prevalent in late spreading. Further characterization revealed that each motility type exhibited a distinct distribution of the actin-related protein VASP, while inhibition of actin polymerization by cytochalasin D treatment revealed different dependences on barbed-end polymerization. Through this detailed characterization and graded perturbation of the system, we observed that although each temporal phase of spreading was dominated by a single motility type, in general cells exhibited a variety of motility types in neighboring spatial domains of the plasma membrane edge. These observations support a model in which global signals bias local cytoskeletal biochemistry in favor of a particular motility type