On non-supersymmetric conformal manifolds: field theory and holography

We discuss the constraints that a conformal field theory should enjoy to admit exactly marginal deformations, i.e. to be part of a conformal manifold. In particular, using tools from conformal perturbation theory, we derive a sum rule from which one can extract restrictions on the spectrum of low spin operators and on the behavior of OPE coefficients involving nearly marginal operators. We then consider conformal field theories admitting a gravity dual description, and as such a large-$N$ expansion. We discuss the relation between conformal perturbation theory and loop expansion in the bulk, and show how such connection could help in the search for conformal manifolds beyond the planar limit. Our results do not rely on supersymmetry, and therefore apply also outside the realm of superconformal field theories

Participatory Workshops are Not Enough to Prevent Policy Implementation Failures: An Example of a Policy Development Process Concerning the Drug Interferon-beta for Multiple Sclerosis

A possible explanation for policy implementation failure is that the views of the policy’s target groups are insufficiently taken into account during policy development. It has been argued that involving these groups in an interactive process of policy development could improve this. We analysed a project in which several target populations participated in workshops aimed to optimise the utilisation of an expensive novel drug (interferon beta) for patients with Multiple Sclerosis. All participants seemed to agree on the appropriateness of establishing a central registry of Multiple Sclerosis patients and developing guidelines. Nevertheless, these policy measures were not implemented. Possible explanations include (1) the subject no longer had high priority when the costs appeared lower than expected, (2) the organisers had paid insufficient attention to the perceived problems of parties involved, and (3) changes within the socio-political context. The workshops in which representatives of the policy’s target populations participated did not provide enough interactivity to prevent policy implementation failure

Historical literacy and consciousness

A ideia de literacia histórica - enquanto conjunto de competências de interpretação e compreensão do passado - surge associada à proposta de desenvolvimento da consciência histórica, tal como defende Peter Lee. Esta necessidade de orientação temporal exige identificações múltiplas, a várias escalas (do local ao global), e a consideração de pontos de vista diversificados, apresentados quer por historiadores quer por outras fontes para a História. Assumindo a relevância desta problemática para a formação da consciência histórica, é pertinente interrogarmo-nos acerca de como desenvolvem os alunos universitários (futuros professores de História) as suas competências de literacia histórica. No âmbito da disciplina de Metodologia do Ensino da História, no 4º ano da Licenciatura em Ensino de História (Universidade do Minho), explorararam-se as seguintes questões de investigação: 1) Que critérios utilizam os futuros professores de História quando decidem entre versões históricas diferentes? 2) Como é que estes futuros professores fundamentam os seus argumentos a favor ou contra uma determinada versão? Aos dezoito alunos do curso participantes neste estudo, foi proposta uma tarefa de avaliação de dois textos históricos, um de Luís de Albuquerque, historiador português, outro de Sanjay Subrahmanyam, historiador indiano, sobre a primeira viagem marítima dos portugueses à Índia (com suporte em várias fontes, nomeadamente um excerto do diário de viagem de Gama). Conjugando-se as dimensões de interpretação substantiva das mensagens com a de uso de critérios históricos, os dados sugeriram uma categorização global constituída por cinco níveis de ideias. Os padrões mais observados ligam-se a noções de viés (a validade histórica depende de uma maior ou menor neutralidade) ou de influência do contexto de produção nos historiadores. A aceitação da validade de versões diferentes, enquanto algo genuíno no conhecimento histórico, emergiu entre alguns poucos alunos universitários. Esta tipologia coincide com os níveis de idéias observados em adolescentes e crianças portuguesas, em estudos anteriores, embora os níveis mais elaborados apareçam mais frequentemente entre os alunos universitários.The idea of historical literacy - as a set of competences of historical interpretation and understanding - is emerging as linked to the proposal of developing historical consciousness, as Peter Lee argues. This need for temporal orientation demands multiple identifications at several scales (from the local up to the global scale) as well as the consideration of diversified points of view, given either by historians or many other sources of history. Assuming the relevance of this issue, it is pertinent to question about the way university students (preservice history teachers) are developing their own competences of historical literacy. In the context of the Methodology of History Teaching subject, at year 4 of the Teaching of History Graduate Course (University of Minho), the following research questions were explored: 1) What criteria do the preservice history teachers employ when deciding about different historical versions? 2) How those preservice history teachers support their arguments for or against a given version? An assessment task of two historical texts, one written by Luís de Albuquerque, Portuguese historian, another by Sanjay Subrahmanyam, Indian historian, was accomplished by the 18 participants of this study. The historical texts focussed on the first Portuguese maritime voyage to India (and they were grounded on several evidence, namely an excerpt of the Gama trip log). Combining the dimensions of substantive interpretation of messages and use of historical criteria, data suggested a global categorization with five levels of ideas. The most observed patterns are related to notions of bias (historical validity depends on neutrality) or notions of influence of the historical production context). The recognition of validity of different versions as a genuine element of the historical knowledge emerged just among a few university students. Such a tipology matches with the levels of ideas observed among Portuguese children and adolescents in former studies, although the most elaborate levels appear more frequently among the university students

Paradigms in multiple sclerosis: time for a change, time for a unifying concept

It has recently been suggested that, rather than being an autoimmune disease, multiple sclerosis (MS) is an example of a neurocristopathy, a pathological process resulting from a faulty development of the neural crest. Whilst several characteristics of the disease suggest a neurocristopathy, other aetiological factors require consideration, including hygiene-related factors that alter the immune responses to common pathogens resulting in an eclipse of immune reactivity that could protect against MS, the possible role of human endogenous retroviruses (HERVs) in pathogenesis and autoimmune phenomena, HLA polymorphism, vitamin D levels before and after birth and immune repair mechanisms. A postulated aetiological factor in MS, associated with altered vitamin D metabolism and abnormal HERV expression, is a long-lasting disturbed redox regulation in the biosynthesis of a melanoma-like melanin pigment. Although intensive further studies on melanin pigments in nerve tissue in MS are required, the known properties of a pathological form of such pigments in melanoma could explain a number of observations in MS, including the impact of light, UV-light, and vitamin D, and could explain the clinical manifestations of MS on the basis of an oscillating process of oxidative charge and discharge of the pigments and a threshold phenomenon with a change of the quasi-catalytic function of the pigment from destroying reactive oxygen radicals or species to transforming them to more harmful long-persisting highly reactive species. Taken together with the consequences of an adaptive process in partly demyelinated neurons, resulting in an increase in number of mitochondria, and the impact of stressful life events, these conditions are necessary and sufficient to explain the disease process of MS with its spatial (plaques) and temporal (attacks and remissions) characteristics. This suggested unifying concept of the pathogenesis of MS may open perspectives for prevention, diagnosis and therapy. In particular, prevention may be achieved by vaccinating against Epstein-Barr virus in early childhood

Medroxyprogesterone improves nocturnal breathing in postmenopausal women with chronic obstructive pulmonary disease

BACKGROUND: Progestins as respiratory stimulants in chronic obstructive pulmonary disease (COPD) have been investigated in males and during wakefulness. However, sleep and gender may influence therapeutic responses. We investigated the effects of a 2-week medroxyprogesterone acetate (MPA) therapy on sleep and nocturnal breathing in postmenopausal women. METHODS: A single-blind placebo-controlled trial was performed in 15 postmenopausal women with moderate to severe COPD. A 12-week trial included 2-week treatment periods with placebo and MPA (60 mg/d/14 days). All patients underwent a polysomnography with monitoring of SaO(2 )and transcutaneous PCO(2 )(tcCO(2)) at baseline, with placebo, with medroxyprogesterone acetate (MPA 60 mg/d/14 days), and three and six weeks after cessation of MPA. RESULTS: Thirteen patients completed the trial. At baseline, the average ± SD of SaO(2 )mean was 90.6 ± 3.2 % and the median of SaO(2 )nadir 84.8 % (interquartile range, IQR 6.1). MPA improved them by 1.7 ± 1.6 %-units (95 % confidence interval (CI) 0.56, 2.8) and by 3.9 %-units (IQR 4.9; 95% CI 0.24, 10.2), respectively. The average of tcCO(2 )median was 6.0 ± 0.9 kPa and decreased with MPA by 0.9 ± 0.5 kPa (95% CI -1.3, -0.54). MPA improved SaO(2 )nadir and tcCO(2 )median also during REM sleep. Three weeks after cessation of MPA, the SaO(2 )mean remained 1.4 ± 1.8 %-units higher than at baseline, the difference being not significant (95% CI -0.03, 2.8). SaO(2 )nadir was 2.7 %-units (IQR 4.9; 95% CI 0.06, 18.7) higher than at baseline. Increases in SaO(2 )mean and SaO(2 )nadir during sleep with MPA were inversely associated with baseline SaO(2 )mean (r = -0.70, p = 0.032) and baseline SaO(2 )nadir (r = -0.77, p = 0.008), respectively. Treatment response in SaO(2 )mean, SaO(2 )nadir and tcCO(2 )levels did not associate with pack-years smoked, age, BMI, spirometric results or sleep variables. CONCLUSION: MPA-induced respiratory improvement in postmenopausal women seems to be consistent and prolonged. The improvement was greater in patients with lower baseline SaO(2 )values. Long-term studies in females are warranted

Cortical injury in multiple sclerosis; the role of the immune system

The easily identifiable, ubiquitous demyelination and neuronal damage that occurs within the cerebral white matter of patients with multiple sclerosis (MS) has been the subject of extensive study. Accordingly, MS has historically been described as a disease of the white matter. Recently, the cerebral cortex (gray matter) of patients with MS has been recognized as an additional and major site of disease pathogenesis. This acknowledgement of cortical tissue damage is due, in part, to more powerful MRI that allows detection of such injury and to focused neuropathology-based investigations. Cortical tissue damage has been associated with inflammation that is less pronounced to that which is associated with damage in the white matter. There is, however, emerging evidence that suggests cortical damage can be closely associated with robust inflammation not only in the parenchyma, but also in the neighboring meninges. This manuscript will highlight the current knowledge of inflammation associated with cortical tissue injury. Historical literature along with contemporary work that focuses on both the absence and presence of inflammation in the cerebral cortex and in the cerebral meninges will be reviewed

Lipid rafts are essential for release of phosphatidylserine-exposing extracellular vesicles from platelets.

Platelets protect the vascular system during damage or inflammation, but platelet activation can result in pathological thrombosis. Activated platelets release a variety of extracellular vesicles (EVs). EVs shed from the plasma membrane often expose phosphatidylserine (PS). These EVs are pro-thrombotic and increased in number in many cardiovascular and metabolic diseases. The mechanisms by which PS-exposing EVs are shed from activated platelets are not well characterised. Cholesterol-rich lipid rafts provide a platform for coordinating signalling through receptors and Ca2+ channels in platelets. We show that cholesterol depletion with methyl-β-cyclodextrin or sequestration with filipin prevented the Ca2+-triggered release of PS-exposing EVs. Although calpain activity was required for release of PS-exposing, calpain-dependent cleavage of talin was not affected by cholesterol depletion. P2Y12 and TPα, receptors for ADP and thromboxane A2, respectively, have been reported to be in platelet lipid rafts. However, the P2Y12 antagonist, AR-C69931MX, or the cyclooxygenase inhibitor, aspirin, had no effect on A23187-induced release of PS-exposing EVs. Together, these data show that lipid rafts are required for release of PS-exposing EVs from platelets.Isaac Newton Trust/ Wellcome Trust ISSF/University of Cambridge Joint Research Grant British Heart Foundation grant SP/15/7/3156

The effects of Δ9-tetrahydrocannabinol on the dopamine system

Δ(9)-tetrahydrocannabinol (THC), the main psychoactive ingredient in cannabis, is a pressing concern to global mental health. Patterns of use are changing drastically due to legalisation, availability of synthetic analogues (‘spice’), cannavaping and aggrandizements in the purported therapeutic effects of cannabis. Many of THC’s reinforcing effects are mediated by the dopamine system. Due to complex cannabinoid-dopamine interactions there is conflicting evidence from human and animal research fields. Acute THC causes increased dopamine release and neuron activity, whilst long-term use is associated with blunting of the dopamine system. Future research must examine the long-term and developmental dopaminergic effects of the drug