The impact and control of malignant catarrhal fever in Tanzania

Malignant Catarrhal Fever (MCF), an often-lethal infectious disease, presents as a variable complex of lesions in susceptible ungulate species. The disease is caused by a -herpesvirus following transmission from an inapparent carrier host. Two major epidemiological forms exist: wildebeest-associated MCF (WA-MCF), in which the virus is transmitted to susceptible species by wildebeest calves less than approximately four months of age, and sheepassociated MCF (SA-MCF) in which the virus is spread by sheep (primarily adolescents). Due to the lack of an in-vitro propagation system for the causative agent of the more economically significant SA-MCF, and with the expectation that cross-protective immunity may be provided, vaccine development has focused on the more easily propagated alcelaphine herpesvirus-1 (AlHV-1) that causes WA-MCF. In 2008 a direct viral challenge trial showed that a novel vaccine, employing an attenuated AlHV-1 (atAlHV-1) `C5000 virus strain, protected British Friesian-Holstein (FH) cattle against an intranasal challenge with virulent AlHV-1 `C5000 virus. For cattle keeping people living near wildebeest calving areas in sub-Saharan Africa an effective vaccine would have value as it would release them from the costly annual disease avoidance strategy of having to move their herds away from the oncoming wildebeest. On the other hand, an effective vaccine will release herd owners from the need to avoid MCF, allowing them to graze their cattle alongside wildebeest on the highly nutritious pastures of the calving areas. As such conservationists have raised concerns that the development of a vaccine might lead to detrimental grazing competition. The principle objective of this study was to test the novel vaccine on Tanzanian shorthorn zebu cross cattle (SZC).We did this firstly using a natural challenge field trial (Chapter Two) which demonstrated that immunisation with the atAlHV-1 vaccine was well tolerated and induced an oro-nasopharyngeal AlHV-1-specific and -neutralising antibody response. This resulted in an immunity in SZC cattle that was partially protective and reduced naturally transmitted infection by 56%. We also demonstrated that non-fatal infections occurred with a much higher frequency than previously thought. Because the calculated efficacy of the vaccine was less than that seen in British FH cattle we wanted to determine whether host factors, particular to SZC cattle, had impacted the outcomes of the field trial. To do this we repeated the 2008 direct viral challenge trial using SZC cattle (Chapter Four). During this trial we also investigated whether the recombinant bacterial flagellin monomer (FliC), when used as an adjuvant, might improve the vaccine’s efficacy. The findings from this trial indicated that direct challenge with pathogenic AlHV-1 is effective at inducing MCF in SZC cattle and that FliC is not an appropriate adjuvant for this vaccine. Furthermore, with less control group cattle dying of MCF than expected we speculate that SZC cattle may have a degree of resistance to MCF that affords them protection from infection and developing fatal disease. In Chapter Three we investigated aspects of the epidemiology of MCF, specifically whether wildebeest placenta, long implicated by Maasai cattle owners as a source of MCF, might play a role in viral transmission. Additionally, through comparative sequence analysis, at two specific genes (A9.5 and ORF50) of wild-type and atAlHV-1, we investigated whether the `C5000 strain, the source of which was taken from Africa more than 40 years ago, was appropriate for vaccine development. The detection of AlHV-1 virus in approximately 50% of placentae indicated that infection can occur in-utero and that this tissue might play a role in disease transmission. And, despite describing three new alleles of the A9.5 gene (supporting previous evidence that this gene is polymorphic and encodes a secretory protein with interleukin-4 as the major homologue), the observation that the most frequently detected haplotypes, in both wild-type and attenuated AlHV-1, were identical suggests that AlHV-1 has a slow molecular clock and that the attenuated strain was appropriate for vaccine development. In Chapter Five we present the first quantitative assessment of the annual MCF avoidance costs that Maasai pastoralists incur. In particular we estimated that as a result of MCF avoidance 64% of the total daily milk yield during the MCF season was not available to be used by the 81% of the family unit remaining at the permanent boma. This represents an upper-bound loss of approximately 8% of a household0s annual income. Despite these considerable losses we concluded that, given an incidence of fatal MCF in cattle living in wildebeest calving areas of 5% to 10%, if herd owners were to stop trying to avoid MCF by allowing their cattle to graze alongside wildebeest, any gains made through increased availability of milk, improved body condition and reduced energy demands would be offset by an increase in MCF-incidence. With the development of an effective vaccine, however, this alternative strategy might become optimal. The overall conclusion we draw therefore is that, despite the substantial costs incurred each year avoiding MCF, the partial protection afforded by the novel vaccine strategy is not sufficient to warrant a wholesale change in disease avoidance strategy. Nonetheless, even the partial protection provided by this vaccine could be of value to protect animals that cannot be moved, for example where some of the herd remain at the boma to provide milk or where land-use changes make traditional disease avoidance difficult. Furthermore, the vaccine may offer a feasible solution to some of the current land-use challenges and conflicts, providing a degree of protection to valuable livestock where avoidance strategies are not possible, but with less risk of precipitating the potentially damaging environmental consequences, such as overgrazing of highly nutritious seasonal pastures, that might result if herd owners decide they no longer need to avoid wildebeest.

Pluralismo y derechos fundamentales en el estado social de derecho: la situación de las poblaciones indígenas en Colombia en 2014

Este es un estudio sobre la garantía y aplicabilidad de los derechos humanos de las poblaciones indígenas colombianas durante los primeros cuatro años de mandato de la administración Santos. La investigación busca explicar la manera en que las adversas condiciones socio económicas que caracterizan el desarrollo de las poblaciones indígenas, denotan la incapacidad del Estado Social de Derecho para garantizar la protección y aplicabilidad de los derechos fundamentales de estas comunidades. Las disposiciones constitucionales han tenido un desarrollo truncado debido a las escasas medidas proferidas por diferentes gobiernos frente a las necesidades de estos grupos en particular. En razón de lo anterior, el estudio se inscribe dentro del marco teórico referente al neo constitucionalismo debido al alto valor explicativo que ofrecen los postulados de Gustavo Zagrebelsky y Luigi Ferrajoli en relación al fenómeno que se pretende analizar. Se concluye que frente a la persistencia de los factores que afectan el desarrollo de las poblaciones indígenas, el reconocimiento constitucional debe ser complementado por una efectiva normatividad que asegure la aplicabilidad de los derechos fundamentales por parte de las administraciones políticas: no debe existir un desfase entre las nociones de principio y la ley.

Changes in fish assemblage structure after implementation of Marine Protected Areas in the south western coast of Portugal.

Marine Protected Areas (MPAs) are increasingly being recommended as management tools for biodiversity conservation and fisheries. With the purpose of protecting the region's biodiversity and prevent the over exploitation of marine resources, in February 2011 the no-take MPAs of Ilha do Pessegueiro and Cabo Sard~ao were implemented within the “Parque Natural do Sudoeste Alentejano e Costa Vicentina “(PNSACV) Marine Park, south western coast of Portugal. As such, commercial and recreational fishing became prohibited in these areas. In order to evaluate the effects of these no-take MPAs, the structure of their fish assemblages and of adjacent control areas without fishing restrictions were studied between 2011 (immediately after implementation) and 2013 (two years after implementation). A total of 4 sampling campaigns were conducted (summer 2011, winter 2012, summer 2013 and winter 2013) using trammel nets and bottom trawl. Ichthyofaunal assemblages from the no-take MPAs (treatment) were compared with adjacent areas (controls) and changes evaluated as a function of time since protection. Results revealed significant increase in fish abundance after the implementation of the no-take MPAs. Furthermore, significant differences in the structure of fish assemblages (abundance and fish size) between protected and neighbouring areas were rapidly observed upon the implementation of the no-take MPAs. In addition, specimens of larger size occurred more frequently within Ilha do Pessegueiro no-take MPA in the last year of the study. Overall, despite the young age of these no-take MPAs, changes on the structure of their fish assemblages were already evident after only two years of protection, indicating that management measures such as MPA designation may play an important role to promote fisheries sustainable exploitation as well as to protect species with conservation interest.

Synthesis, Modification and Characterization of Polymeric Membranes for CO2 Separation

This doctorate focused on the development of dense polymeric membranes for carbon capture, mostly in post combustion applications, and for natural gas sweetening. The work was supported by the European Project NANOMEMC2 funded under H2020 program. Different materials have been investigated, that rely on two main transport mechanisms: the solution-diffusion and the facilitated transport. In both cases, proper nano-fillers have been added to the matrix, in order to boost the mechanical and permselective properties of the membranes. Facilitated transport membranes were based on the use of was polyvinylamine (PVAm), as main matrix with fixed-site carriers, and L-Arginine as mobile carrier; the filler, used mostly as reinforcer, was carboxymethylated nanocellulose (cNFC). Humid test showed interesting results, and especially the blend made of PVAm/cNFC/Arg in weight ratio 27,5/27,5/45 crossed the Robeson CO2/N2 upper bound, representing current state of the art membranes, with a CO2 permeability of 271 Barrer and CO2/N2 selectivity of 70. Solution diffusion membranes were based on Pebax®2533 matrix which was added with three different graphene oxide (GO)-based materials, namely pristine GO, Porous Graphene Oxide (PGO) and a GO functionalized with polyetheramine (PEAGO). All of them provided a modest but clear increment of permeability of the Pebax matrix, from plus 2% (GO) to plus 8% (PGO), with no change in selectivity. The gas tested with this type of composites were CO2 and N2, for Post combustion capture applications. Pebax®2533 was also chemically modified, obtaining the product called “Benzoyl-P2533”, that was fully characterized, and tested in term of permeation using five gas: CO2, N2, CH4, O2, and He. Modified material showed an increment of the overall permeability of the material of a fair 10% for all gases tested, apart from helium, that increased of almost 50%.

Surgery after biological therapy in locally advanced NSCLC with molecular driver: feasibility and effectiveness of a new multidisciplinary approach

Introduction: Surgical outcomes after biological therapy have not been investigated yet and no information about timing, postoperative complications and survival have been recorded. Methods: This is a prospective study which compares a group of stage IIIA and IIIB NSCLC patients treated with biological therapy with patients undergoing standard induction chemotherapy. Data reported are preliminary results on the safety and effectiveness of surgery after target therapy. Results: We compared 22 patients treated with standard chemotherapy (Group 1) and 6 patients who received target therapy (Group 2). No differences were observed with an important bias due to the limited number of cases. The median time of resection was 159.8 ± 62.8 for group 1 and 201 ± 57.8 for group 2 (p=0.194). Complete resection was obtained in all Group 1-cases. Post-operative complication rate was 22% vs 16% (p=1). Pathologists reported necrosis >50% in 13% in group 1, Fibrosis >50% was presents respectively in 27% and 33% of patients (p=1). Residual vital tumor was >50% in 77% of patients undergone CT and in 66% of patients undergone TT (p=0.622). A total of 6 (31%) patients in the CT-group developed recurrence, 3 in the TT- group (64.2%), p was 0.634. No difference was observed both in terms of OS (P=0.29, Figure 3) and in term of DFS (P=0.106, Figure 4). Discussion: There is no consensus in the use of target therapy for advanced tumor in association with surgery. EGFR-tyrosine kinase inhibitors showed higher and more rapid response and our study wants to demonstrate that surgery after target therapy gives full access to the advantage of definitive local treatment. In our series, despite fibrosis, radical surgery has been achieved in all patients operated. The intraoperative blood loss, operation time, postoperative hospital stay and postoperative complication rate seems to be similar.

Security enhancements and flaws of emerging communication technologies

The multi-faced evolution of network technologies ranges from big data centers to specialized network infrastructures and protocols for mission-critical operations. For instance, technologies such as Software Defined Networking (SDN) revolutionized the world of static configuration of the network - i.e., by removing the distributed and proprietary configuration of the switched networks - centralizing the control plane. While this disruptive approach is interesting from different points of view, it can introduce new unforeseen vulnerabilities classes. One topic of particular interest in the last years is industrial network security, an interest which started to rise in 2016 with the introduction of the Industry 4.0 (I4.0) movement. Networks that were basically isolated by design are now connected to the internet to collect, archive, and analyze data. While this approach got a lot of momentum due to the predictive maintenance capabilities, these network technologies can be exploited in various ways from a cybersecurity perspective. Some of these technologies lack security measures and can introduce new families of vulnerabilities. On the other side, these networks can be used to enable accurate monitoring, formal verification, or defenses that were not practical before. This thesis explores these two fields: by introducing monitoring, protections, and detection mechanisms where the new network technologies make it feasible; and by demonstrating attacks on practical scenarios related to emerging network infrastructures not protected sufficiently. The goal of this thesis is to highlight this lack of protection in terms of attacks on and possible defenses enabled by emerging technologies. We will pursue this goal by analyzing the aforementioned technologies and by presenting three years of contribution to this field. In conclusion, we will recapitulate the research questions and give answers to them.

Epilepsies Associated With Hippocampal Sclerosis.

Hippocampal sclerosis (HS) is considered the most frequent neuropathological finding in patients with mesial temporal lobe epilepsy (MTLE). Hippocampal specimens of pharmacoresistant MTLE patients that underwent epilepsy surgery for seizure control reveal the characteristic pattern of segmental neuronal cell loss and concomitant astrogliosis. However, classification issues of hippocampal lesion patterns have been a matter of intense debate. International consensus classification has only recently provided significant progress for comparisons of neurosurgical and clinic-pathological series between different centers. The respective four-tiered classification system of the International League Against Epilepsy subdivides HS into three types and includes a term of gliosis only, no-HS. Future studies will be necessary to investigate whether each of these subtypes of HS may be related to different etiological factors or with postoperative memory and seizure outcome. Molecular studies have provided potential deeper insights into the pathogenesis of HS and MTLE on the basis of epilepsy-surgical hippocampal specimens and corresponding animal models. These include channelopathies, activation of NMDA receptors, and other conditions related to Ca(2+) influx into neurons, the imbalance of Ca(2+)-binding proteins, acquired channelopathies that increase neuronal excitability, paraneoplastic and non-paraneoplastic inflammatory events, and epigenetic regulation promoting or facilitating hippocampal epileptogenesis. Genetic predisposition for HS is clearly suggested by the high incidence of family history in patients with HS, and by familial MTLE with HS. So far, it is clear that HS is multifactorial and there is no individual pathogenic factor either necessary or sufficient to generate this intriguing histopathological condition. The obvious variety of pathogenetic combinations underlying HS may explain the multitude of clinical presentations, different responses to clinical and surgical treatment. We believe that the stratification of neuropathological patterns can help to characterize specific clinic-pathological entities and predict the postsurgical seizure control in an improved fashion.

Avaliação subjetiva da qualidade de vida em individuos de meia idade submetidos a treinamento fisico

Universidade Estadual de Campinas . Faculdade de Educação Física

As patentes nas universidades: análise dos depósitos das universidades públicas paulistas (1995-2006)

Este artigo analisou os depósitos das universidades públicas paulistas no Instituto Nacional de Propriedade Industrial (Inpi) no período de 1995-2006, perfazendo 672 registros. Foram consideradas as seguintes: Universidade Estadual de Campinas, Universidade de São Paulo, Universidade Estadual Paulista, Universidade Federal de São Carlos e Universidade Federal de São Paulo. Com os resultados obtidos verificou-se um avanço, mesmo que instável, do número de depósitos de patentes advindas das universidades e o adiantamento da Unicamp em relação às demais na quantidade de patentes depositadas, responsável por 60% do total de registros. Como conclusão vale destacar que o fortalecimento das políticas internas das universidades relacionadas à propriedade industrial acarretará maior índice de proteção das invenções acadêmicas, garantindo os direitos sobre a invenção, incentivando a realização de novas pesquisas e, através de mecanismos efetivos, viabilizando a transferência da tecnologia produzida nas universidades para o setor produtivo.

O óbito e sua investigação: reflexões sobre alguns aspectos relevantes

O artigo aborda questões relativas ao óbito e sua investigação como elementos importantes para a Epidemiologia e a Saúde Pública. Ressalta aspectos ligados à melhoria da sua qualidade e da vigilância, bem como da pesquisa científica/epidemiológica nessa área, vistos sob a óptica da legislação e das normas éticas existentes no Brasil. Discute o problema relativo, a saber, "a quem pertence a informação em saúde e quais os limites de sua utilização", tratando, inclusive, da possibilidade do uso de bancos de dados identificados. Conclui sugerindo meios hábeis, como "Termo de Responsabilidade e Confidencialidade" por parte do pesquisador, para que a pesquisa científica/epidemiológica possa ter continuidade no país, com agilidade e oportunidade.

Matemal Concepts and Expectations regarding a Preterm Infant

The objective of the present study was: (a) to identify the concerns, verbally expressed, of 50 mothers regarding their preterm infants (PT) and then compare their verbal expression with those of 25 mothers of full-term infants (FT): and (b) to correlate the mothers` verbal expressions with maternal and infant variables. The following instruments were used to compose and characterize the sample: Structure Clinical Interview for DSM III-R Non-Patient (SCID/NP), State-Trait Anxiety Inventory (STAI), Beck Depression Inventory (BDI), and medical charts. Results showed that there was no difference between groups in term of mothers` expectations and conceptualizations, both groups exhibited predominantly positive expectations and concepts. In comparison with FT mothers, PT mothers verbally expressed more feelings and reactions predominantly negative or conflicting in relation to infant birth. Higher levels of maternal anxiety and depression in the PT Group were correlated with more verbal expressions about negative or conflicting emotions. In addition, lower birth weight, higher neonatal risk and longer length of stay in intensive care nursery of the infants were related with more negative or conflicting concepts by the mothers.

A DNA vaccine candidate encoding the structural prM/E proteins elicits a strong immune response and protects mice against dengue-4 virus infection

A DNA vaccine expressing dengue-4 virus premembrane (prM) and envelope (E) genes was produced by inserting these genes into a mammalian expression plasmid (pCI). Following a thorough screening, including confirmation of protein expression in vitro, a recombinant clone expressing these genes was selected and used to immunize BALB/c mice. After 3 immunizations all the animals produced detectable levels of neutralizing antibodies against dengue-4 virus. The cytokines levels and T cell proliferation, detected ex vivo from the spleen of the immunized mice, showed that our construction induced substantial immune stimulation after three doses. Even though the antibody levels, induced by our DNA vaccine, were lower than those obtained in mice immunized with dengue-4 virus the levels of protection were high with this vaccine. This observation is further supported by the fact that 80% of the vaccine immunized group was protected against lethal challenge. In conclusion, we developed a DNA vaccine employing the genes of the prM and E proteins from dengue-4 virus that protects mice against this virus. (C) 2010 Elsevier Ltd. All rights reserved.

Lipids, Mitochondria and Cell Death: Implications in Neuro-oncology

Polyunsaturated fatty acids (PUFAs) are known to inhibit cell proliferation of many tumour types both in vitro and in vivo. Their capacity to interfere with cell proliferation has been linked to their induction of reactive oxygen species (ROS) production in tumour tissues leading to cell death through apoptosis. However, the exact mechanisms of action of PUFAs are far from clear, particularly in brain tumours. The loss of bound hexokinase from the mitochondrial voltage-dependent anion channel has been directly related to loss of protection from apoptosis, and PUFAs can induce this loss of bound hexokinase in tumour cells. Tumour cells overexpressing Akt activity, including gliomas, are sensitised to ROS damage by the Akt protein and may be good targets for chemotherapeutic agents, which produce ROS, such as PUFAs. Cardiolipin peroxidation may be an initial event in the release of cytochrome c from the mitochondria, and enriching cardiolipin with PUFA acyl chains may lead to increased peroxidation and therefore an increase in apoptosis. A better understanding of the metabolism of fatty acids and eicosanoids in primary brain tumours such as gliomas and their influence on energy balance will be fundamental to the possible targeting of mitochondria in tumour treatment.

Further studies on an intermediate host murine model showing that a primary Echinococcus granulosus infection is protective against subsequent oncospheral challenge

We describe the use of a murine model to evaluate resistance against subsequent challenge following a primary infection with oncospheres of Echinococcus granulosus. Mice (Kunming strain) were infected with hatched oncospheres of Echinococcus granulosus; 21 days later a second challenge was given by a different route of infection. A primary infection by intraperitoneal (i.p.) injection stimulated 100 and 90.5% protection in terms of reduced cyst numbers against a secondary infection given subcutaneously (s.c.) or intravenously (i.v.) respectively. A primary infection given s.c. followed by i.p. or i.v. challenge resulted in 84.0 and 100% protection, respectively. Intravenous infection followed by i.p. or s.c. challenge resulted in 98.5 and 69.4% protection, respectively. With the i.v. route of infection, almost all resultant cysts were present in the lungs. The data show that a primary infection with oncospheres can induce total or a high degree of protection against a subsequent challenge and confirms that natural (concomitant) immunity can be stimulated in the intermediate host as the result of a primary infection. This may explain the decline in hydatid infection in sheep older than 2 years in hyper-endemic areas such as those found in Xingjiang, China. These older sheep may have been earlier infected and have subsequently self-cured, with the primary infection stimulating an immune response that protects the intermediate host animals from further infection. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.

Cellular responses to Schistosoma japonicum cathepsin D aspartic protease

Lymphocyte proliferation and cytokine production were measured in groups of mice vaccinated (but not subsequently challenge infected) with recombinant forms of Schistosoma japonicum cathepsin D aspartic protease, rSjASP1 (expressed in bacteria; enzymatically inactive) and rSjASP2 (expressed in insect cells; enzymatically active). Both forms of the schistosome enzyme induced significant proliferation of splenocytes recovered from vaccinated mice, and expression of interferon (IFN)-gamma, interleukin (IL)-4 and IL-10 mRNA in these cells was detected using reverse transcriptase-polymerase chain reaction. Secretion of IFN-gamma, IL-4 and IL-10 by splenocytes from vaccinated mice was confirmed and quantified using enzyme-linked immunosorbent assay. IFN-gamma was the most abundant cytokine produced, followed by IL-4 and IL-10 in rank order. These findings indicated that vaccination of mice with the schistosome protease induces a mixed Th1/Th2 cytokine response, which may explain the modest level of protection after challenge infection in cathepsin d-vaccinated mice, reported previously.