In Vitro and In Vivo Activity of a Palladacycle Complex on Leishmania (Leishmania) amazonensis

Leishmaniasis is an important public health problem with an estimated annual incidence of 1.5 million of new human cases of cutaneous leishmaniasis and 500,000 of visceral leishmaniasis. Treatment of the diseases is limited by toxicity and parasite resistance to the drugs currently in use, validating the need to develop new leishmanicidal compounds. We evaluated the killing by the palladacycle complex DPPE 1.2 of Leishmania (Leishmania) amazonensis, an agent of human cutaneous leishmaniasis in the Amazon region, Brazil. DPPE 1.2 destroyed promastigotes of L. (L.) amazonensis in vitro at nanomolar concentrations, whereas intracellular amastigotes were killed at drug concentrations 10-fold less toxic than those displayed to macrophages. L. (L.) amazonensis-infected BALB/c mice treated by intralesional injection of DPPE 1.2 exhibited a significant decrease of foot lesion sizes and a 97% reduction of parasite burdens when compared to untreated controls. Additional experiments indicated the inhibition of the cathepsin B activity of L. (L.) amazonensis amastigotes by DPPE 1.2. Further studies are needed to explore the potential of DPPE 1.2 as an additional option for the chemotherapy of leishmaniasis

Clinical Manifestations Associated with Neurocysticercosis: A Systematic Review

Neurocysticercosis is an infection of the brain with the flatworm Taenia solium which is normally transmitted between humans and pigs. Sometimes, humans can infect other humans and the larva of the parasite can go the brain, causing the disease neurocysticercosis. There has never been a systematic review of what clinical signs are found among people with neurocysticercosis. We conducted a thorough review of the literature to answer this question. We reviewed 1569 and 21 were of a sufficient quality to be included in the final analysis. Among neurocysticercosis patients who are seeking care in neurology clinics, about 79% have seizures/epilepsy, 38% severe headaches, 16% focal deficits and 12% signs of increased intracranial pressure. Several other symptoms were also reported in less than 10% of patients. People with neurocysticercosis who seek care in neurology clinics show a whole range of manifestations. Clinicians should be encouraged to consider neurocysticercosis in their differential diagnosis when a patient presented with one of the symptoms described in this review. This would ultimately improve the estimates of the frequency of symptoms associated with neurocysticercosis

Adapting evidence-informed complex population health interventions for new contexts : a systematic review of guidance

Background Adapting interventions that have worked elsewhere can save resources associated with developing new interventions for each specific context. While a developing body of evidence shows benefits of adapted interventions compared with interventions transported without adaptation, there are also examples of interventions which have been extensively adapted, yet have not worked in the new context. Decisions on when, to what extent, and how to adapt interventions therefore are not straightforward, particularly when conceptualising intervention effects as contingent upon contextual interactions in complex systems. No guidance currently addresses these questions comprehensively. To inform development of an overarching guidance on adaptation of complex population health interventions, this systematic review synthesises the content of the existing guidance papers. Methods We searched for papers published between January 2000 and October 2018 in 7 bibliographic databases. We used citation tracking and contacted authors and experts to locate further papers. We double screened all the identified records. We extracted data into the following categories: descriptive information, key concepts and definitions, rationale for adaptation, aspects of adaptation, process of adaptation, evaluating and reporting adapted interventions. Data extraction was conducted independently by two reviewers, and retrieved data were synthesised thematically within pre-specified and emergent categories. Results We retrieved 6694 unique records. Thirty-eight papers were included in the review representing 35 sources of guidance. Most papers were developed in the USA in the context of implementing evidence-informed interventions among different population groups within the country, such as minority populations. We found much agreement on how the papers defined key concepts, aims, and procedures of adaptation, including involvement of key stakeholders, but also identified gaps in scope, conceptualisation, and operationalisation in several categories. Conclusions Our review found limitations that should be addressed in future guidance on adaptation. Specifically, future guidance needs to be reflective of adaptations in the context of transferring interventions across countries, including macro- (e.g. national-) level interventions, better theorise the role of intervention mechanisms and contextual interactions in the replicability of effects and accordingly conceptualise key concepts, such as fidelity to intervention functions, and finally, suggest evidence-informed strategies for adaptation re-evaluation and reporting

HE-LHC: The High-Energy Large Hadron Collider: Future Circular Collider Conceptual Design Report Volume 4

In response to the 2013 Update of the European Strategy for Particle Physics (EPPSU), the Future Circular Collider (FCC) study was launched as a world-wide international collaboration hosted by CERN. The FCC study covered an energy-frontier hadron collider (FCC-hh), a highest-luminosity high-energy lepton collider (FCC-ee), the corresponding 100 km tunnel infrastructure, as well as the physics opportunities of these two colliders, and a high-energy LHC, based on FCC-hh technology. This document constitutes the third volume of the FCC Conceptual Design Report, devoted to the hadron collider FCC-hh. It summarizes the FCC-hh physics discovery opportunities, presents the FCC-hh accelerator design, performance reach, and staged operation plan, discusses the underlying technologies, the civil engineering and technical infrastructure, and also sketches a possible implementation. Combining ingredients from the Large Hadron Collider (LHC), the high-luminosity LHC upgrade and adding novel technologies and approaches, the FCC-hh design aims at significantly extending the energy frontier to 100 TeV. Its unprecedented centre-of-mass collision energy will make the FCC-hh a unique instrument to explore physics beyond the Standard Model, offering great direct sensitivity to new physics and discoveries

FCC-ee: The Lepton Collider: Future Circular Collider Conceptual Design Report Volume 2

In response to the 2013 Update of the European Strategy for Particle Physics, the Future Circular Collider (FCC) study was launched, as an international collaboration hosted by CERN. This study covers a highest-luminosity high-energy lepton collider (FCC-ee) and an energy-frontier hadron collider (FCC-hh), which could, successively, be installed in the same 100 km tunnel. The scientific capabilities of the integrated FCC programme would serve the worldwide community throughout the 21st century. The FCC study also investigates an LHC energy upgrade, using FCC-hh technology. This document constitutes the second volume of the FCC Conceptual Design Report, devoted to the electron-positron collider FCC-ee. After summarizing the physics discovery opportunities, it presents the accelerator design, performance reach, a staged operation scenario, the underlying technologies, civil engineering, technical infrastructure, and an implementation plan. FCC-ee can be built with today’s technology. Most of the FCC-ee infrastructure could be reused for FCC-hh. Combining concepts from past and present lepton colliders and adding a few novel elements, the FCC-ee design promises outstandingly high luminosity. This will make the FCC-ee a unique precision instrument to study the heaviest known particles (Z, W and H bosons and the top quark), offering great direct and indirect sensitivity to new physics