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Background Placebo or sham controls are the standard against which the benefits and harms of many active interventions are measured. Whilst the components and the method of their delivery have been shown to affect study outcomes, placebo and sham controls are rarely reported and often not matched to those of the active comparator. This can influence how beneficial or harmful the active intervention appears to be. Without adequate descriptions of placebo or sham controls, it is difficult to interpret results about the benefits and harms of active interventions within placebo-controlled trials. To overcome this problem, we developed a checklist and guide for reporting placebo or sham interventions. Methods and findings We developed an initial list of items for the checklist by surveying experts in placebo research (n = 14). Because of the diverse contexts in which placebo or sham treatments are used in clinical research, we consulted experts in trials of drugs, surgery, physiotherapy, acupuncture, and psychological interventions. We then used a multistage online Delphi process with 53 participants to determine which items were deemed to be essential. We next convened a group of experts and stakeholders (n = 16). Our main output was a modification of the existing Template for Intervention Description and Replication (TIDieR) checklist; this allows the key features of both active interventions and placebo or sham controls to be concisely summarised by researchers. The main differences between TIDieR-Placebo and the original TIDieR are the explicit requirement to describe the setting (i.e., features of the physical environment that go beyond geographic location), the need to report whether blinding was successful (when this was measured), and the need to present the description of placebo components alongside those of the active comparator. Conclusions We encourage TIDieR-Placebo to be used alongside TIDieR to assist the reporting of placebo or sham components and the trials in which they are used.

Background. Human immunodeficiency virus (HIV), which causes AIDS, is most often spread through unprotected sex (vaginal, oral, or anal) with an infected partner. Individuals can reduce their risk of becoming infected with HIV by abstaining from sex or delaying first sex, by being faithful to one partner or having few partners, and by always using a male or female condom. Various HIV prevention programs targeted at young people encourage these protective sexual behaviors. Abstinence-only programs (for example, Project Reality in the US) present no sex before marriage as the only means of reducing the risk of catching HIV. Abstinence-plus programs (for example, the UK Apause program) also promote sexual abstinence as the safest behavior choice to prevent HIV infection. However, recognizing that not everyone will remain abstinent, and that in many locations same-sex couples are not permitted to marry, abstinence-plus programs also encourage young people who do become sexually active to use condoms and other safer-sex strategies. Safer-sex programs, a third approach, teach people how to protect themselves from pregnancy and infections and might recommend delaying first sex until they are physically and emotionally ready, but do not promote sexual abstinence over safer-sex strategies such as condom use. Why Was This Study Done? There is considerable controversy, particularly in the US, about the relative merits of abstinence-based programs for HIV prevention. Abstinence-only programs, which the US government supports, have been criticized because they provide no information to protect participants who do become sexually active. Critics of abstinence-plus programs contend that teaching young people about safer sex undermines the abstinence message, confuses participants, and may encourage them to become sexually active. Conversely, some people worry that the promotion of abstinence might undermine the safer-sex messages of abstinence-plus programs. Little has been done, however, to look methodically at how these programs change sexual behavior. In this study, the researchers have systematically reviewed studies of abstinence-plus interventions for HIV prevention in high-income countries to get an idea of their effect on sexual behavior. What Did the Researchers Do and Find? In an extensive search for existing abstinence-plus studies, the researchers identified 39 trials done in high-income countries that compared the effects on sexual behavior of various abstinence-plus programs with the effects of no intervention or of other interventions designed to prevent HIV infection. All the trials met strict preset criteria (for example, trial participants had to have an unknown or negative HIV status), and all studies meeting the criteria turned out to involve young people in the US, Canada, or the Bahamas, nearly 40,000 participants in total. In 23 of the trials, the abstinence-plus program studied was found to improve at least one self-reported protective sexual behavior (for example, it increased abstinence or condom use) when compared to the other interventions in the trial; none of the trials reported a significant negative effect on any behavioral outcome. Limited evidence from a few trials indicated that some abstinence-plus programs reduced pregnancy rates, providing a biological indicator of program effectiveness. Conversely, there were no indications of adverse biological outcomes such as an increased occurrence of sexually transmitted diseases in any of the trials. What Do These Findings Mean? These findings indicate that some abstinence-plus programs reduce HIV risk behavior among young people in North America. Importantly, the findings do not uncover evidence of any abstinence-plus program causing harm. That is, fears that these programs might encourage young people to become sexually active earlier or confuse them about the use of condoms for HIV prevention seem unfounded. These findings may not apply to all abstinence-plus programs in high-income countries, do not include low-income countries, do not specifically address nonheterosexual risk behavior, and are subject to limited reliability in self-reporting of sexual activity by young people. Nonetheless, this analysis provides support for the use of abstinence-plus programs, particularly in light of another systematic review by the same authors (A systematic review of abstinence-only programs for prevention of HIV infection, published in the British Medical Journal), which found that abstinence-only programs did not reduce pregnancy, sexually transmitted diseases, or sexual behaviors that increase HIV risk. Abstinence-plus programs, these findings suggest, represent a reasonable strategy for HIV prevention among young people in high-income countries.

La educación superior en América del Sur se enfrenta a varios desafíos que afectan su calidad y accesibilidad. Los principales problemas incluyen la falta de financiamiento adecuado, la falta de acceso a recursos educativos de alta calidad, la baja retención estudiantil y la falta de relevancia de los programas de estudio para las necesidades del mercado laboral. Para abordar estos desafíos, se han implementado varias soluciones. Algunas soluciones incluyen la creación de sistemas de becas y préstamos para estudiantes de bajos ingresos, la promoción de la colaboración entre universidades y empresas para desarrollar programas de estudio más relevantes y la implementación de tecnología educativa para mejorar la accesibilidad a recursos educativos de alta calidad. Además, también se están promoviendo políticas que fomentan la diversidad y la inclusión en las instituciones de educación superior, lo que ayuda a mejorar la equidad y la justicia social. Estas políticas incluyen la implementación de cuotas para grupos minoritarios y la creación de programas de tutoría y apoyo para estudiantes de bajos ingresos. En resumen, aunque la educación superior en América del Sur enfrenta desafíos significativos, hay soluciones en marcha para mejorar su calidad y accesibilidad. La implementación de estas soluciones debería ayudar a mejorar la equidad y la justicia social, así como también mejorar la calidad de vida y las oportunidades económicas de los estudiantes de la región.

Diabetes Mellitus (DM) is a chronic disease that is associated with high morbidity and mortality rates, especially concerning its acute and chronic complications and is characterized by an increase in the concentration of glucose in the bloodstream due to a deficiency of insulin secretion or action. High drug costs, increased hospitalizations, increased number of medical appointments, lost productivity, and premature deaths are associated with diabetic patients. DM is a disease that must be treated correctly so that its complications are avoided and that there is no loss of quality of life for the patient.

A classical result of K. L. Chung and W. Feller deals with the partial sums S k S_k arising in a fair coin-tossing game. If N n N_n is the number of “positive” terms among S 1 S_1 , S 2 S_2 , …, S n S_n then the quantity P ( N 2 n = 2 r ) P(N_{2n} = 2r) takes an elegant form. We lift the restriction on an even number of tosses and give a simple expression for P ( N 2 n + 1 = r ) P(N_{2n+1} = r) , r = 0 r = 0 , 1 1 , 2 2 , …, 2 n + 1 2n+1 . We get to this ansatz by adaptating the Feynman–Kac methodology.

Nomophobia is the rising social phenomenon consisting of an irrational fear of being left without a mobile phone. Although the name refers to the absence of a mobile phone, it emphasizes smartphones and mobile data connectivity. This review will aim to establish a connection between the exaggerated use of smartphones, social media, and other online services with the stressful and challenging routines of medical students and medical professionals. Furthermore, this study will try to determine whether or not a connection exists between elevated anxiety levels, procrastination of academic duties, and overall underachievement with nomophobia behavior among said students and professionals. A chronological and systematic literature review was performed, including scientific findings published no earlier than 2017, and excluding older publications.

Cannabidiol (CBD) is a medication made from the cannabis plant, Cannabis sativa, which acts on the central nervous system, helping to treat psychiatric or neurodegenerative diseases, such as schizophrenia, Parkinson's disease, epilepsy or anxiety. CBD can generate feelings of calmness, inhibiting the absorption of anandamide, an endocannabinoid that helps maintain homeostasis. It is also indicated for the relief of symptoms such as pain, inflammation, depression and anxiety. Studies still show that cannabidiol has the potential to prevent and inhibit SARS-CoV-2 infection.

This research assesses the risks and benefits of herbal medicine in an overview of scientific evidence in the field of medicine. Objective: to study and assess the risks and benefits of herbal medicine in an overview of scientific evidence in the field of medicine; promoting the health of the population through information and guidance about different diseases and how to use herbal pharmacological preparations for their treatment, with a more dynamic approach and based on the social context, promoting an improvement in the quality of life. Methodology: Production of a scientific article, using a qualitative approach and explanatory investigation of bibliographic research. Carried out in a participatory manner, through group research, bringing journals, articles, books and theses to medical students to build knowledge about the diseases dealt with and treatment by herbal preparations, thus allowing greater assimilation of the topics discussed. The VHL databases were used: LILACS, MEDLINE, MEDCARIB, PAHO-IRIS, WHOLIS. This work is a review article of several types of research on the topic of phytotherapy that reached the state of the art and was here described, transcribed and evaluated in our final considerations. Results: There was an understanding that medical qualification in herbal medicine is of vital importance for the cure and/or treatment of various pathologies. The insertion of phytotherapy in public health services would also be a condition of professional and scientific help in this area, which is so popular and often encourages patients to self-medicate. Final Considerations: The activity allows the application of academic knowledge in promoting community health and favours the creation of new knowledge for medical professionals and the historical recognition of herbal medicine already used by our ancestors, leading to an appreciation of this knowledge now put to evidence for prevention and health promotion.

Dear reader, we are writing this piece as a collaborative collage based on our experience of our ongoing PhD journey in a “top” business school, on self-compassion and the inner saboteur, all saturated by the unpredictable developments of the COVID-19 pandemic. Contrary to the linear argumentation of academic writing, collage writing works by opening up “new possibilities for understanding” what is written (Herrmann, 2020, p. 298). This introduction is where we manage your expectations, by letting you know that what follows below does not replicate the structure or the form of a conventionally organized paper.

From micro to planetary scales, spatial heterogeneity-patchiness-is ubiquitous in ecosystems, defining the environments in which organisms move and interact. However, most large-scale models still use spatially averaged 'mean fields' to represent natural populations, while fine-scale spatially explicit models are mostly restricted to particular organisms or systems. In a conceptual paper, Grünbaum (2012, Interface Focus 2: 150-155) introduced a heuristic, based on three dimensionless ratios quantifying movement, reproduction and resource consumption, to characterise patchy ecological interactions and identify when mean-field assumptions are justifiable. We calculated these dimensionless numbers for 33 interactions between consumers and their resource patches in terrestrial, aquatic and aerial environments. Consumers ranged in size from bacteria to whales, and patches lasted from minutes to millennia, with separation scales from mm to hundreds of km. No interactions could be accurately represented by naive mean-field models, though 19 (58%) could be partially simplified by averaging out movement, reproductive or consumption dynamics. Clustering interactions by their non-dimensional ratios revealed several unexpected dynamic similarities. For example, bacterial Pseudoalteromonas exploit nutrient plumes similarly to Mongolian gazelles grazing on ephemeral steppe vegetation. We argue that dimensional analysis is valuable for characterising ecological patchiness and can link widely different systems into a single quantitative framework.

We present a statistical approach for the discovery of relationships between mathematical entities that is based on linear regression and deep learning with fully connected artificial neural networks. The strategy is applied to computational knot data and empirical connections between combinatorial and hyperbolic knot invariants are revealed., 17 pages, 1 figure

This paper concerns local yet systematic problems of contrastive underdetermination of model choice in cognitive neuroscience debates about the so-called two visual systems hypothesis. The underdetermination problem is systematically generated by the way certain assumptions about the representationalist nature of computation are translated into experimental practice. The problem is that behavioural data underdetermine the choice between competing representational models. In this paper, I diagnose how these assumptions generate underdetermination problems in the choice between competing functional models of perception– action. Using the tools of philosophy of science, I describe the type of underdetermination and sketch a possible cure.

When a person decides to do something in the future, she forms an intention and her intention persists. Philosophers have thought about the rational requirement that an agent’s intention persists until its execution. But philosophers have neglected to think about the causal memory mechanisms that could enable this kind of persistence and its role in rational long-term agency. Our aim of this paper is to fill this gap by arguing that memory for intention is a specific kind of memory. We do this by evaluating and rejecting standard declarative accounts of memory for intention and arguing for the plausibility of an alternative model of memory for intention. We argue for the alternative by spelling out a number of computational principles that could enable retaining and retrieving intentions from long-term memory. These principles could explain a number of core features of intentions.

In this paper, we propose a new mathematical model of retrieval of intentions from long-term memory. We model retrieval as a stochastic race between a plurality of potentially relevant intentions stored in long-term memory. Psychological theories are dominated by two opposing conceptions of the role of memory in temporally extended agency – as when a person has to remember to make a phone call in the afternoon because, in the morning, she promised she would do so. According to the Working Memory conception, remembering to make the phone call is explained in terms of the construction and maintenance of intentions in working-memory. According to the Long-Term Memory conception, we should explain the episode in terms of an ability to store intentions in long-term memory. The two conceptions predict different processing profiles. The aim of this paper is to present a new mathematical model of the type of memory mechanism that could realise the long-term memory representations of intentions necessary for the Long-Term Memory conception. We present and illustrate the formal model and propose a new type of experimental paradigm that could allow us to test which of the two conceptions provides the best explanation of the role of memory in temporally extended agency.

The singular value decomposition going with many problems in medical imaging, non-destructive testing, geophysics, etc. is of central importance. The singular functions are characterized as the eigenfunctions of a compact, selfadjoint integral operator with (as in the case of limited angle tomography) a certain number of significantly nonzero eigenvalues. A stable reconstruction algorithm should aim at finding the projection of the unknown object on the linear span of the singular functions going with only these eigenvalues. If this linear span is not satisfactory for the spatial resolution that one wants to achieve, one needs to measure over a larger range of angles and compute the new singular value decomposition from scratch. Unfortunately the effective numerical determination of the eigenfunctions of these integral operators, i.e. the singular functions in question, is a very ill-posed problem. The best known remedy to this problem goes back the work of Slepian, Landau and Pollak, Bell Labs 1960-1965. They found a mathematical miracle: one can produce a differential operator that shares these eigenfunctions and has a very spread out spectrum, resulting in a numerically stable problem. The search for other situations where this (albeit exceptional) miracle holds is the motivation of this paper. We show that the master symmetries of the Korteweg-de Vries equation give a way to extend the remarkable result of David Slepian in connection with the Bessel integral kernel and the existence of a differential operator that commutes with it. The original result of Slepian has already played an important role in signal processing as well as in Random matrix theory.

This chapter focuses on an unexpected windfall of the investigation: the linking of breaks to hostile sibling figures in a child’s mind. It explores core themes in child psychotherapy with children who have suffered early abuse and neglect. The chapter investigates possible links between breaks in the time structure of therapy and such core themes. The chapter examines development of a transparent and systematic methodology for the psychoanalytic case study by application of a rigorous qualitative research method. A main finding of the study was a characteristic pattern of subjective core themes running as a red thread through all Samantha’s relationships, not only inside the therapy, but also in early infancy and her daily life concurrent to therapy. The specific pattern of core themes probably reflects the fact that Samantha early in her life had suffered severe neglect and maltreatment.

War and torture related trauma shatter the conditions for ordinary family life and parental care. Later on, the reverberations of past assaults and loss intrude upon current relationships, undermining the parental couple and ordinary, benign adult authority. Sadly, some children are secondarily traumatised because of disturbed relationships and sometimes domestic violence exerted by their traumatised parents or siblings. This article presents case material, the aim of which is twofold: firstly to exemplify a possible, quite concrete entanglement between the ongoing traumatic processes and images in the mind of the traumatised parents and the symptoms of the children. Secondly, to show that during the period of assessment for child psychotherapy a prolonged, flexible approach combining the individual assessment of the child with family intervention and/or sibling work may be necessary. During such preparatory work the state of the family needs special consideration, since an invisible collapse of parental role responsibilities and care structures may render the child psychologically homeless.

Milner and Goodale's Two Visual Systems Hypothesis (TVSH) is regarded as common ground in recent discussions of visual consciousness. A central part of TVSH is a functional model of vision and action (a functional perception-action model, PAM for short). In this paper, I provide a brief overview of these current discussions and argue that PAM is ambiguous between a strong and a weak version. I argue that, given a standard way of individuating computational mechanisms, the available evidence cannot be used to distinguish between these versions. This not only has consequences for philosophical theories of the role of visual consciousness but also has implications for the role of experimental evidence in model testing in cognitive neuroscience.

BACKGROUND: Previous studies have suggested that blockade of the renin-angiotensin system may prevent diabetes in people with cardiovascular disease or hypertension. METHODS: In a double-blind, randomized clinical trial with a 2-by-2 factorial design, we randomly assigned 5269 participants without cardiovascular disease but with impaired fasting glucose levels (after an 8-hour fast) or impaired glucose tolerance to receive ramipril (up to 15 mg per day) or placebo (and rosiglitazone or placebo) and followed them for a median of 3 years. We studied the effects of ramipril on the development of diabetes or death, whichever came first (the primary outcome), and on secondary outcomes, including regression to normoglycemia. RESULTS: The incidence of the primary outcome did not differ significantly between the ramipril group (18.1%) and the placebo group (19.5%; hazard ratio for the ramipril group, 0.91; 95% confidence interval [CI], 0.81 to 1.03; P=0.15). Participants receiving ramipril were more likely to have regression to normoglycemia than those receiving placebo (hazard ratio, 1.16; 95% CI, 1.07 to 1.27; P=0.001). At the end of the study, the median fasting plasma glucose level was not significantly lower in the ramipril group (102.7 mg per deciliter [5.70 mmol per liter]) than in the placebo group (103.4 mg per deciliter [5.74 mmol per liter], P=0.07), though plasma glucose levels 2 hours after an oral glucose load were significantly lower in the ramipril group (135.1 mg per deciliter [7.50 mmol per liter] vs. 140.5 mg per deciliter [7.80 mmol per liter], P=0.01). CONCLUSIONS: Among persons with impaired fasting glucose levels or impaired glucose tolerance, the use of ramipril for 3 years does not significantly reduce the incidence of diabetes or death but does significantly increase regression to normoglycemia. (ClinicalTrials.gov number, NCT00095654 [ClinicalTrials.gov].).

I argue against the view that an agent’s knowledge of her own current action cannot in any way rely on perception for its justification. Instead, I argue that when it comes to an agent’s knowledge of her own object-oriented intentional action, the agent’s belief about what she is doing is partly justified by her perception of the object of action. I proceed by first proposing an account of such actions according to which the agent’s knowledge is partly justified by her perception. I then discuss several of objections to my proposal. The most important objection is that I have only managed to show that perception plays an enabling role and not a justificatory role for the agent’s knowledge of her own intentional action

Psychologists and philosophers are often tempted to make general claims about the importance of certain experimental results for our commonsense notions of intentional agency, moral responsibility, and free will. It is a strong intuition that if the agent does not intentionally control her own behavior, her behavior will not be an expression of agency, she will not be morally responsible for its consequences, and she will not be acting as a free agent. It therefore seems natural that the interest centers on the notion of intentional control. If it can be experimentally shown that agents do as a matter of fact not control their own actions, even though they think they do, it will have far reaching consequences for our moral psychology. In this paper I look at recent eliminative arguments allegedly demonstrating that our commonsense notion of intentional control is incompatible with experimental data in support of the dual visual stream theory.

I present an account of how agents can know what they are doing when they intentionally execute object-oriented actions. When an agent executes an object-oriented intentional action, she uses perception in such a way that it can fulfil a justificatory role for her knowledge of her own action and it can fulfil this justificatory role without being inferentially linked to the cognitive states that it justifies. I argue for this proposal by meeting two challenges: in an agent's knowledge of her action perception can only play an enabling role (and no justificatory role) for the agent's knowledge and if perception has a justificatory role, then the agent's knowledge must be inferential.

A dominant view in contemporary cognitive neuroscience is that low-level, comparator-based mechanisms of motor control produce a distinctive experience often called the feeling of agency (the FoA-hypothesis). An opposing view is that comparator-based motor control is largely non-conscious and not associated with any particular type of distinctive phenomenology (the simple hypothesis). In this paper, I critically evaluate the nature of the empirical evidence researchers commonly take to support FoA-hypothesis. The aim of this paper is not only to scrutinize the FoA-hypothesis and data supposed to support it; it is equally to argue that experimentalists supporting the FoA-hypothesis fail to establish that the experimental outcomes are more probable given the FoA-hypothesis than given the simpler hypothesis.

OBJECTIVE—Impaired glucose tolerance (IGT) and/or impaired fasting glucose (IFG) are risk factors for diabetes, cardiovascular disease (CVD), and kidney disease. We determined the effects of ramipril and rosiglitazone on combined and individual CVD and renal outcomes in people with IGT and/or IFG in the Diabetes REduction Assessment With ramipril and rosiglitazone Medication (DREAM) trial. RESEARCH DESIGN AND METHODS—A total of 5,269 people aged ≥30 years, with IGT and/or IFG without known CVD or renal insufficiency, were randomized to 15 mg/day ramipril versus placebo and 8 mg/day rosiglitazone versus placebo. A composite cardiorenal outcome and its CVD and renal components were assessed during the 3-year follow-up. RESULTS—Compared with placebo, neither ramipril (15.7% [412 of 2,623] vs. 16.0% [424 of 2,646]; hazard ratio [HR] 0.98 [95% CI 0.84–1.13]; P = 0.75) nor rosiglitazone (15.0% [394 of 2,635] vs. 16.8% [442 of 2,634]; 0.87 [0.75–1.01]; P = 0.07) reduced the risk of the cardiorenal composite outcome. Ramipril had no impact on the CVD and renal components. Rosiglitazone increased heart failure (0.53 vs. 0.08%; HR 7.04 [95% CI 1.60–31.0]; P = 0.01) but reduced the risk of the renal component (0.80 [0.68–0.93]; P = 0.005); prevention of diabetes was independently associated with prevention of the renal component (P < 0.001). CONCLUSIONS—Ramipril did not alter the cardiorenal outcome or its components. Rosiglitazone, which reduced diabetes, also reduced the development of renal disease but not the cardiorenal outcome and increased the risk of heart failure.

New Volitionalism is a name for certain widespread conception of the nature of intentional action. Some of the standard arguments for New Volitionalism, the so-called arguments from total failure, have even acquired the status of basic assumptions for many other kinds of philosophers. It is therefore of singular interest to investigate some of the most important arguments from total failure. This is what I propose to do in this paper. My aim is not be to demonstrate that these arguments are inconsistent or that total failure and naked tryings are metaphysically impossible. Rather, my aim is be to build a case against the possibility of naked, independently existing tryings, by questioning how well we understand the scenarios invoked in their favour. Thus, rather than attempting to present a definitive metaphysical refutation of New Volitionalism, I attempt to diminish or demolish its underlying motivation.

This article is about how to describe an agent’s awareness of her bodily movements when she is aware of executing an action for a reason. Against current orthodoxy, I want to defend the claim that the agent’s experience of moving has an epistemic place in the agent’s awareness of her own intentional action. In “The problem,” I describe why this should be thought to be problematic. In “Motives for denying epistemic role,” I state some of the main motives for denying that bodily awareness has any epistemic role to play in the content of the agent’s awareness of her own action. In “Kinaesthetic awareness and control,” I sketch how I think the experience of moving and the bodily sense of agency or control are best described. On this background, I move on to present, in “Arguments for epistemic role,” three arguments in favour of the claim that normally the experience of moving is epistemically important to one’s awareness of acting intentionally. In the final “Concluding remarks,” I round off by raising some of the worries that motivated the denial of my claim in the first place.

Aims/hypothesis Diabetes is a rapidly rising independent risk factor for atherosclerosis and serious illness. This risk can be reduced by lifestyle changes and/or various drugs. Novel therapies to prevent diabetes, as well as new risk factors for diabetes, atherosclerosis and obesity require testing and identification. Methods People with impaired fasting glucose or impaired glucose tolerance were randomised to ramipril (15 mg/day) or placebo and rosiglitazone (8 mg/day) or placebo with a 2x2 factorial design. They are assessed semi-annually for the primary outcome (diabetes or death). Diabetes is diagnosed if two consecutive plasma glucose levels exceed diagnostic thresholds (i.e. fasting >/=7.0 mmol/l or 2-h >/=11.1 mmol/l) within a 3-month period. Assuming an annual primary outcome incidence of 5%, there is more than 90% power to detect a 22% reduction. Approximately 20% of participants are having annual carotid ultrasounds to assess the effects on atherosclerosis. Patients screened but not randomised are being followed prospectively to identify determinants of obesity, diabetes and related disorders. Results A total of 24,872 individuals in 21 countries were screened over 2 years and are eligible for follow-up. Of these, 5269 were randomised: 1835 (35%) had isolated impaired glucose tolerance, 739 (14%) had isolated impaired fasting glucose, and 2692 (51%) had both disorders. Annual carotid ultrasounds are currently being performed in 1406 randomised individuals. Conclusions/interpretation The DREAM trial and related studies will determine if ramipril or rosiglitazone reduces the number of cases of diabetes and atherosclerosis, and will identify novel risk factors for diabetes.

The cross-cultural survey presented here examines the attitudes towards business ethics of Finnish and American business students from the Southern states. The findings indicate that the differences between the attitudes of these groups are small and essentially linked to the strength of their position. Both see deliberation on moral issues as part of a business manager's job and believe that managers should participate in the solving of social problems. Both Finns and Americans make a distinction between acting legally and ethically, and both endorse cultural relativism.

ims: Impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and diabetes arise due to insufficient insulin secretion and are risk factors for cardiovascular (CV) events. Thus, targeting normal fasting glucose levels with insulin may reduce CV events. Previous studies suggest that omega-3 fatty acid supplements may reduce CV death ; however, their effect in high- risk dysglycemic individuals is not known. Methods: People aged > or = 50 years with evidence of CV disease and with IFG, IGT, newly detected or established diabetes (on 0 or 1 oral agent), and a local glycated hemoglobin < 150% of the upper limit of normal for that assay were recruited and allocated to (a) either 1 daily injection of insulin glargine with the dose titrated to achieve a fasting plasma glucose < or = 5.3 mmol/L (95 mg/dL), or standard glycemic care ; and (b) either omega-3-acid ethyl esters 90 (1 g consisting of EPA 465 mg and DHA 375 mg) or identical placebo, according to a 2 x 2 factorial design. The 2 different primary outcomes for the insulin and omega-3 fatty acid arms are CV events and CV death, respectively. Results: A total of 12, 612 (mean age 64, 35% women) people in 40 countries were randomized during a 2-year period ending December 2005. Eighty-two percent had established diabetes, 6% had new diabetes, and 12% had IGT or IFG ; the mean fasting plasma glucose was 7.3 mmol/L (131 mg/dL). Conclusions: The ORIGIN trial will determine whether or not either or both of these interventions can reduce CV events.

In this article, I argue that the representation of simple, bodily action has the function of endowing the narrative sequence with a visualizing power. It makes the narrated scenes or situations ready for visualization by the reader or listener. By virtue of this visualizing power or disposition, these narrated actions disrupt the theoretical divisions, on the one hand, between the narrated story and the narrating discourse, and on the other hand, between plot-narratology and discourse-narratology. As narrated actions, they seem to belong to the domain of plot-narratology, but insofar as they serve an important visualizing function, these narrated actions have a communicative function and, as such, they can be said to belong to the domain of discourse-narratology. In the first part of the article, I argue that a certain type of plot-narratology, due to its retrospective epistemology and abstract definition of action, is unable to conceive of this visualizing function. In the second part, I argue that discourse-narratology fares no better since the visualizing function is independent of voice and focalization. In the final part, I sketch a possible account of the visualizing function of simple actions in narratives.

In dibutyryl-cAMP-differentiated HL-60 cells, histamine H1 and formyl peptide receptors mediate increases in the cytosolic Ca2+ concentration ([Ca2+]i) via pertussis toxin-sensitive G proteins of the Gi family. We compared the effects of 2-(3-chlorophenyl)-histamine (CPH) [2-[2-(3-chlorophenyl)-1H-imidazol-4-yl] ethanamine], one of the most potent and selective H1 receptor agonists presently available, with those of histamine and N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP) in these cells. CPH increased [Ca2+]i through Ca2+ mobilization and Ca2+ influx. Unlike histamine-induced rises in [Ca2+]i, those induced by CPH were not desensitized in a homologous manner, and there was no cross-desensitization between CPH and histamine. Like fMLP, CPH activated phospholipases C and D, tyrosine phosphorylation, superoxide anion formation, and azurophilic granule release. The effects of CPH on [Ca2+]i, phospholipase D, and superoxide anion formation were inhibited by pertussis toxin. CPH and fMLP stimulated high affinity GTP hydrolysis by Gi proteins in HL-60 membranes. They also enhanced binding of guanosine-5'-O-(3-thio)triphosphate and GTP azidoanilide to, and cholera toxin-catalyzed ADP-ribosylation of, Gi protein alpha subunits. Histamine receptor antagonists did not inhibit the stimulatory effects of CPH, and CPH did not reduce fMLP binding in HL-60 membranes. Our data suggest that CPH activates Gi proteins in HL-60 cells through a receptor agonist-like mechanism that is, however, independent of known histamine receptor subtypes and formyl peptide receptors. CPH may be an agonist at an as yet unknown histamine receptor subtype or, by analogy with other cationic-amphiphilic substances, may activate G proteins directly. Future studies will have to take into consideration the fact that CPH, in addition to activating H1 receptors, may show other, most unexpected, stimulatory effects on G protein-mediated signal transduction processes.

In the spirit of Felix Klein's “Erlangen Program” a methodical approach is developed to three levels of classification of geometric objects. These three levels are successive refinements of the classification by the crystallographic (symmetry) groups. The approach provides a systematic framework for most kinds of previously classified objects, such as dot patterns (= lattice complexes), circle or ellipse patterns (= circle packings, ellipse packings), tilings (tessellations) with equivalent tiles (or edges, or vertices), and many others.