Matching the (DR4)-R-6 interaction at two-loops

The coefficient of the $D^6 {\cal R}^4$ interaction in the low energy expansion of the two-loop four-graviton amplitude in type II superstring theory is known to be proportional to the integral of the Zhang-Kawazumi (ZK) invariant over the moduli space of genus-two Riemann surfaces. We demonstrate that the ZK invariant is an eigenfunction with eigenvalue 5 of the Laplace-Beltrami operator in the interior of moduli space. Exploiting this result, we evaluate the integral of the ZK invariant explicitly, finding agreement with the value of the two-loop $D^6 {\cal R}^4$ interaction predicted on the basis of S-duality and supersymmetry. A review of the current understanding of the $D^{2p} {\cal R}^4$ interactions in type II superstring theory compactified on a torus $T^d$ with $p \leq 3$ and $d \leq 4$ is included.Comment: 40 pages, various typos and coefficients corrected in version

Security policy refinement using data integration: a position paper.

In spite of the wide adoption of policy-based approaches for security management, and many existing treatments of policy verification and analysis, relatively little attention has been paid to policy refinement: the problem of deriving lower-level, runnable policies from higher-level policies, policy goals, and specifications. In this paper we present our initial ideas on this task, using and adapting concepts from data integration. We take a view of policies as governing the performance of an action on a target by a subject, possibly with certain conditions. Transformation rules are applied to these components of a policy in a structured way, in order to translate the policy into more refined terms; the transformation rules we use are similar to those of global-as-view database schema mappings, or to extensions thereof. We illustrate our ideas with an example. Copyright 2009 ACM

La rappresentazione del rapporto tra utenti e sistema sanitario: I modelli culturali dei medici di medicina generale - The representation of the relationship between users and healthcare system: Cultural models of general practitioners

The present research study explores the emotional and symbolic representation of the Italian healthcare system and specifically of general medical services reported by a group of Italian general practitioners. General medicine is recently affected by a structural change which could be sustained also by a cultural revolution, however this revolution seems to be oriented to expected values without a clear methodology which promotes and accompanies this cultural change. The present study deals with the lack of practices due to these unrealized expected values and assumes that for intervening it is necessary knowing the existing culture before thinking to change it. Interviews to 36 general practitioners were analyzed by Emotional Text Analysis (AET). Results highlight a factorial space characterized by five clusters. According to respondents’ perspective, healthcare problems refer to two large issues characterized by powerlessness of general practitioners to intervene. On the one hand, there is health emergency, dealt with by first aid and emergency medicine. On the other hand, there is chronicity, especially affecting the elderly, which is dealt with by other workers (nurses, private family assistants, social workers) who care patients at home and replace physicians. The general practitioners’ work is difficult because of many different reasons; but the central theme is the lack of absolute power – based on morality and consciousness – which leads to the perception of catastrophic consequences for medical profession and the physician-patient relationship. Often, general practitioners are in their offices and are not able to go to patients’ home, therefore they cannot create care relationships based on trust and dependence which allow useful and trustworthy interventions. In sum, the core theme emerging from data refers to the general practitioners’ perceived lack of personal and trust-based relationships with patients

Mandatory vaccinations in European countries, undocumented information, false news and the impact on vaccination uptake: the position of the Italian pediatric society.

BACKGROUND: High rates of vaccination coverage are important in preventing infectious diseases. Enforcing mandatory vaccinations is one of the strategies that some Countries adopted to protect the community when vaccination coverage is not satisfactory. In Italy, in 2017 vaccination against diphtheria, tetanus, pertussis, hepatitis B, poliovirus, Haemophilus influenzae type b, measles, mumps, rubella and varicella became compulsory in childhood. In order to contrast vaccination policies, anti-vaccination campaigns contribute to the spread of fake news. Among them, there is the false information that Italy is the only one country with mandatory vaccination policy. Aim of our study is confronting vaccination policies in children under 18 months against among different European countries for the following vaccines: diphtheria, tetanus, pertussis, hepatitis B, poliovirus, Haemophilus influenzae type b, measles, mumps, rubella and varicella. METHODS: Information on policies of mandatory or recommended vaccinations of the European Countries were gathered by ECDC and compared to the Italian one. RESULTS: European Countries recommend or contemplate compulsory vaccines. Among them, eleven Countries (35.4%) have mandatory vaccinations for at least one out of diphtheria, tetanus, pertussis, hepatitis B, poliovirus, Haemophilus influenzae type b, measles, mumps, rubella and varicella vaccine. CONCLUSION: Not only in Italy, vaccination against diphtheria, tetanus, pertussis, hepatitis B, poliovirus, Haemophilus influenzae type b, measles, mumps, rubella and varicella is mandatory in children under 18 months. Other European countries adopted compulsory policies in order to prevent the spread of infectious diseases and to protect the community

The preclinical discovery and development of brivaracetam for the treatment of focal epilepsy.

INTRODUCTION: Brivaracetam (BRV) is a new AED currently licensed for the adjunctive treatment of adult patients with focal epilepsies. It is a ligand of the ubiquitous synaptic vesicle glycoprotein 2A (SV2A). Areas covered: This paper covers the preclinical and subsequent clinical development of BRV focusing on the discovery of the SV2A protein as the main target for levetiracetam (LEV) and the main similarities and differences between LEV and BRV in terms of pharmacodynamic and pharmacokinetic properties. Phase II and Phase III studies are also presented and data from post-marketing phase IV studies are discussed. Expert opinion: The preclinical development of BRV is quite unique and has raised several doubts on current methodologies adopted for AED development, reinforcing the need for new approaches. The preclinical and clinical profile suggest that BRV is potentially an ideal compound in the emergency setting given the rapid onset of action associated with being water soluble and, therefore, available in intravenous formulation. In addition, data from Phase III studies have already suggested that BRV may be effective not only in focal epilepsies but also in generalised syndromes. Further data from special populations such as children and women of child bearing age are urgently needed

5-FU targets rpL3 to induce mitochondrial apoptosis via cystathionine-b-synthase in colon cancer cells lacking p53

Recent findings revealed in cancer cells novel stress response pathways, which in response to many chemotherapeutic drugs causing nucleolar stress, will function independently from tumor protein p53 (p53) and still lead to cell cycle arrest and/or apoptosis. Since it is known that most cancers lack functional p53, it is of great interest to explore these emerging molecular mechanisms. Here, we demonstrate that nucleolar stress induced by 5-fluorouracil (5-FU) in colon cancer cells devoid of p53 leads to the activation of ribosomal protein L3 (rpL3) as proapoptotic factor. rpL3, as ribosome-free form, is a negative regulator of cystathionine-β-synthase (CBS) expression at transcriptional level through a molecular mechanism involving Sp1. The rpL3-CBS association affects CBS stability and, in addition, can trigger CBS translocation into mitochondria. Consequently apoptosis will be induced through the mitochondrial apoptotic cell death pathway characterized by an increased ratio of Bax to Bcl-2, cytochrome c release and subsequent caspase activation. It is noteworthy that silencing of CBS is associated to a strong increase of 5-FU-mediated inhibition of cell migration and proliferation. These data reveal a novel mechanism to accomplish p53-independent apoptosis and suggest a potential therapeutic approach aimed at upregulating rpL3 for treating cancers lacking p53

Chemical and physical properties of bulk aerosols within four sectors observed during TRACE-P

Chemical and physical aerosol data collected on the DC-8 during TRACE-P were grouped into four sectors based on back trajectories. The four sectors represent long-range transport from the west (WSW), regional circulation over the western Pacific and Southeast Asia (SE Asia), polluted transport from northern Asia with substantial sea salt at low altitudes (NNW) and a substantial amount of dust (Channel). WSW has generally low mixing ratios at both middle and high altitudes, with the bulk of the aerosol mass due to non-sea-salt water-soluble inorganic species. Low altitude SE Asia also has low mean mixing ratios in general, with the majority of the aerosol mass comprised of non-sea-salts, however, soot is also relatively important in this region. NNW had the highest mean sea salt mixing ratios, with the aerosol mass at low altitudes (\u3c2 km) evenly divided between sea salts, non-sea-salts, and dust. The highest mean mixing ratios of water-soluble ions and soot were observed at the lowest altitudes (\u3c2 km) in the Channel sector. The bulk of the aerosol mass exported from Asia emanates from Channel at both low and midaltitudes, due to the prevalence of dust compared to other sectors. Number densities show enhanced fine particles for Channel and NNW, while their volume distributions are enhanced due to sea salt and dust. Low-altitude Channel exhibits the highest condensation nuclei (CN) number densities along with enhanced scattering coefficients, compared to the other sectors. At midaltitudes (2–7 km), low mean CN number densities coupled with a high proportion of nonvolatile particles (≥65%) observed in polluted sectors (Channel and NNW) are attributed to wet scavenging which removes hygroscopic CN particles. Low single scatter albedo in SE Asia reflects enhanced soot