Chimpanzees and supporting models in the study of malaria pre-erythrocytic stages

Chimpanzees are being used in the study of immune response to Plasmodium falciparum malaria pre-erythrocytic stages (MPES). Responses induced by immunisation with recombinant/synthetic antigens and by irradiated sporozoites are being evaluated in a model system that is phylogenetically close to humans and that is amenable to limited manipulation not possible in humans. The value of chimpanzees for the in-depth study of immunological mechanisms at work in MPES-induced protection are discussed. A total number of 7 chimpanzees have been used to evaluate the immune response to recombinant antigens, and 5 have been challenged with large numbers of sporozoites, followed by surgical liver-wedge resection, in order to generate infected liver tissue for histological and immunological studies. As a complementary model, SCID mice carrying live, transplanted human and primate hepatocytes have been inoculated with sporozoites and infection of transplanted cells has been monitored by histological and immunological methods. In ongoing experiments chimpanzees are being immunised with MPES-derived lipopeptides that have been shown to overcome MHC restriction in mice, and with irradiated sporozoites.

Timing of Palaeozoic magmatism in the Maggia and Sambuco nappes and paleogeographic implications (Central Lepontine Alps)

Magmatic rocks from the pre-Mesozoic basements of the Sambuco and Maggia nappes have been dated by U-Pb zircon ages with the LA-ICPMS technique. Several magmatic events have been identified in the Sambuco nappe. The mafic banded calc-alkaline suite of Scheggia is dated at 540 Ma, an age comparable to that of mafic rocks in the Austroalpine Silvretta nappe. The Sasso Nero peraluminous augengneiss has an age of 480-470 Ma, like many other ``older orthogneisses'' in Alpine basement units. It hosts a large proportion of inherited zircons, which were dated around 630 Ma, a Panafrican age indicating the Gondwanan affiliation of the Sambuco basement. The calc-alkaline Matorello pluton yielded ages around 300 Ma, similar to numerous Late Carboniferous intrusions in other basement units of the Lower Penninic (Monte Leone, Antigorio, Verampio) and Helvetic domains (Gotthard and other External Crystalline Massifs). Associated lamprophyric dykes are slightly younger (300-290 Ma), like similar dykes sampled in gneiss blocks included in the sedimentary cover of the underlying Antigorio nappe (290-285 Ma). The Cocco granodiorite and Ruscada leucogranite, both intruding the basement of the neighbouring Maggia nappe, yielded ages of ca. 300-310 Ma, identical within errors to the age of the Matorello pluton. They are significantly older than former age determinations. This age coincidence, coupled with remarkable petrologic similarities between the Cocco and Matorello granodiorites, strongly suggests paleogeographic proximity of the Sambuco and Maggia nappes in Late Carboniferous times. In recent publications these two nappes have been interpreted as belonging to distinct Mesozoic paleogeographic domains: ``European'' for Sambuco and ``Brian double dagger onnais'' for Maggia, separated by the ``Valais'' oceanic basin. In this case, the similarity of the Matorello and Cocco intrusions would demonstrate the absence of any significant transcurrent movement between these two continental domains. Alternatively, according to a more traditional view, Sambuco and Maggia might belong to a single large Alpine tectonic unit.

A gene-rich, transcriptionally active environment and the pre-deposition of repressive marks are predictive of susceptibility to KRAB/KAP1-mediated silencing.

AbstractBACKGROUND: KRAB-ZFPs (Krüppel-associated box domain-zinc finger proteins) are vertebrate-restricted transcriptional repressors encoded in the hundreds by the mouse and human genomes. They act via an essential cofactor, KAP1, which recruits effectors responsible for the formation of facultative heterochromatin. We have recently shown that KRAB/KAP1 can mediate long-range transcriptional repression through heterochromatin spreading, but also demonstrated that this process is at times countered by endogenous influences.METHOD: To investigate this issue further we used an ectopic KRAB-based repressor. This system allowed us to tether KRAB/KAP1 to hundreds of euchromatic sites within genes, and to record its impact on gene expression. We then correlated this KRAB/KAP1-mediated transcriptional effect to pre-existing genomic and chromatin structures to identify specific characteristics making a gene susceptible to repression.RESULTS: We found that genes that were susceptible to KRAB/KAP1-mediated silencing carried higher levels of repressive histone marks both at the promoter and over the transcribed region than genes that were insensitive. In parallel, we found a high enrichment in euchromatic marks within both the close and more distant environment of these genes.CONCLUSION: Together, these data indicate that high levels of gene activity in the genomic environment and the pre-deposition of repressive histone marks within a gene increase its susceptibility to KRAB/KAP1-mediated repression.

Activity of 9-acridanone-hydrazone drugs detected at the pre-postural phase, in the experimental schistosomiasis mansoni

The compound Ro-15.5458/000, derivative in the class of 9-acridanone-hydrazones, was found to be effective against Schistosoma mansoni in mice, killing almost all the skin schistosomules (24 hr after infection), when administered at the dose of 100 mg/kg. In experiments carried out with Cebus monkeys, the drug was shown to be fully effective at 25 mg/kg, 7 days after infection. These data, associated with the good results obtained earlier at the post-postural phase of schistosomiasis, allow the inference that this promising compound may be important in the set of antischistosomal drugs, depending on further toxicological and clinical tests.

Perioperative nutrition is still a surgical orphan: results of a Swiss-Austrian survey.

Background/Objectives:There is strong evidence for the beneficial effects of perioperative nutrition in patients undergoing major surgery. We aimed to evaluate implementation of current guidelines in Switzerland and Austria.Subjects/Methods:A survey was conducted in 173 Swiss and Austrian surgical departments. We inquired about nutritional screening, perioperative nutrition and estimated clinical significance.Results:The overall response rate was 55%, having 69% (54/78) responders in Switzerland and 44% (42/95) in Austria. Most centres were aware of reduced complications (80%) and shorter hospital stay (59%). However, only 20% of them implemented routine nutritional screening. Non-compliance was because of financial (49%) and logistic restrictions (33%). Screening was mainly performed in the outpatient's clinic (52%) or during admission (54%). The nutritional risk score was applied by 14% only; instead, various clinical (78%) and laboratory parameters (56%) were used. Indication for perioperative nutrition was based on preoperative screening in 49%. Although 23% used preoperative nutrition, 68% applied nutritional support pre- and postoperatively. Preoperative nutritional treatment ranged from 3 days (33%), to 5 (31%) and even 7 days (20%).Conclusions:Although malnutrition is a well-recognised risk factor for poor post-operative outcome, surgeons remain reluctant to implement routine screening and nutritional support according to evidence-based guidelines.

Genetic differentiation in two European tree frog (Hyla arborea) metapopulations in contrasted landscapes of Western Switzerland

The survival of threatened species as the European tree frog (Hyla arborea) is strongly dependent on the genetic variability within populations, as well as gene flow between them. In Switzerland, only two sectors in its western part still harbour metapopulations. The first is characterised by a very heterogeneous and urbanized landscape, while the second is characterised by a uninterrupted array of suitable habitats. In this study, six microsatellite loci were used to establish levels of genetic differentiation among the populations from the two different locations. The results show that the metapopulations have: (i) weak levels of genetic differentiation (FST within metapopulation ≈ 0.04), (ii) no difference in levels of genetic structuring between them, (iii) significant (p = 0.019) differences in terms of genetic diversity (Hs) and observed heterozygozity (Ho), the metapopulation located in a disturbed landscape showing lower values. Our results suggest that even if the dispersal of H. arborea among contiguous ponds seems to be efficient in areas of heterogeneous landscape, a loss of genetic diversity can occur.

Cross-country polarisation in CO2 emissions per capita in the European Union: changes and explanatory factors

In this study, we analyse the degree of polarisation-a concept fundamentally different from that of inequality-in the international distribution of CO2 emissions per capita in the European Union. It is analytically relevant to examine the degree of instability inherent to a distribution and, in the analysed case, the likelihood that the distribution and its evolution will increase or decrease the chances of reaching an agreement. Two approaches were used to measure polarisation: the endogenous approach, in which countries are grouped according to their similarity in terms of emissions, and the exogenous approach, in which countries are grouped geographically. Our findings indicate a clear decrease in polarisation since the mid-1990s, which can essentially be explained by the fact that the different groups of countries have converged (i.e. antagonism among the CO2 emitters has decreased) as the contribution of energy intensity to between-group differences has decreased. This lower degree of polarisation in CO2 distribution suggests a situation more conducive to the possibility of reaching EU-wide agreements on the mitigation of CO2 emissions.

Explanatory factors of CO2 per capita emission inequality in the European Union

The design of European mitigation policies requires a detailed examination of the factors explaining the unequal emissions in the different countries. This research analyzes the evolution of inequality in CO2 per capita emissions in the European Union (EU-27) in the 1990-2006 period and its explanatory factors. For this purpose, we decompose the Theil index of inequality into the contributions of the different Kaya factors. The decomposition is also applied to the inequality between and within groups of countries (North Europe, South Europe, and East Europe). The analysis shows an important reduction in inequality, to a large extent due to the smaller differences between groups and because of the lower contribution of the energy intensity factor. The importance of the GDP per capita factor increases and becomes the main explanatory factor. However, within the different groups of countries the carbonization index appears to be the most relevant factor in explaining inequalities.

Value of allogeneic versus autologous stem cell transplantation and chemotherapy in patients with myelodysplastic syndromes and secondary acute myeloid leukemia. Final results of a prospective randomized European Intergroup Trial.

BACKGROUND: Allogeneic stem cell transplantation is usually considered the only curative treatment option for patients with advanced or transformed myelodysplastic syndromes in complete remission, but post-remission chemotherapy and autologous stem cell transplantation are potential alternatives, especially in patients over 45 years old. DESIGN AND METHODS: We evaluated, after intensive anti-leukemic remission-induction chemotherapy, the impact of the availability of an HLA-identical sibling donor on an intention-to treat basis. Additionally, all patients without a sibling donor in complete remission after the first consolidation course were randomized to either autologous peripheral blood stem cell transplantation or a second consolidation course consisting of high-dose cytarabine. RESULTS: The 4-year survival of the 341 evaluable patients was 28%. After achieving complete remission, the 4-year survival rates of patients under 55 years old with or without a donor were 54% and 41%, respectively, with an adjusted hazard ratio of 0.81 (95% confidence interval [95% CI], 0.49-1.35) for survival and of 0.67 (95% CI, 0.42-1.06) for disease-free survival. In patients with intermediate/high risk cytogenetic abnormalities the hazard ratio in multivariate analysis was 0.58 (99% CI, 0.22-1.50) (P=0.14) for survival and 0.46 (99% CI, 0.22-1.50) for disease-free survival (P=0.03). In contrast, in patients with low risk cytogenetic characteristics the hazard ratio for survival was 1.17 (99% CI, 0.40-3.42) and that for disease-free survival was 1.02 (99% CI, 0.40-2.56). The 4-year survival of the 65 patients randomized to autologous peripheral blood stem cell transplantation or a second consolidation course of high-dose cytarabine was 37% and 27%, respectively. The hazard ratio in multivariate analysis was 1.22 (95% CI, 0.65-2.27) for survival and 1.02 (95% CI, 0.56-1.85) for disease-free survival. CONCLUSIONS: Patients with a donor and candidates for allogeneic stem cell transplantation in first complete remission may have a better disease-free survival than those without a donor in case of myelodysplastic syndromes with intermediate/high-risk cytogenetics. Autologous peripheral blood stem cell transplantation does not provide longer survival than intensive chemotherapy.

The effects of nutrition, puberty and dancing on bone density in adolescent ballet dancers.

Ballet dancers have on average a low bone mineral content (BMC), with elevated fracture-risk, low body mass index (BMI) for age (body mass index, kg/m2), low energy intake, and delayed puberty. This study aims at a better understanding of the interactions of these factors, especially with regard to nutrition. During a competition for pre-professional dancers we examined 127 female participants (60 Asians, 67 Caucasians). They averaged 16.7 years of age, started dancing at 5.8 years, and danced 22 hours/week. Assessments were made for BMI, BMC (DXA), and bone mineral apparent density (BMAD) at the lumbar spine and femoral neck, pubertal stage (Tanner score), and nutritional status (EAT-40 questionnaire and a qualitative three-day dietary record). BMI for age was found to be normal in only 42.5% of the dancers, while 15.7% had a more or less severe degree of thinness (12.6% Grade2 and 3.1% Grade 3 thinness). Menarche was late (13.9 years, range 11 to 16.8 years). Food intake, evaluated by number of consumed food portions, was below the recommendations for a normally active population in all food groups except animal proteins, where the intake was more than twice the recommended amount. In this population, with low BMI and intense exercise, BMC was low and associated with nutritional factors; dairy products had a positive and non-dairy proteins a negative influence. A positive correlation between BMAD and years since menarche confirmed the importance of exposure to estrogens and the negative impact of delayed puberty. Because of this and the probable negative influence of a high intake of non-dairy proteins, such as meat, fish, and eggs, and the positive association with a high dairy intake, ballet schools should promote balanced diets and normal weight and should recognize and help dancers avoid eating disorders and delayed puberty caused by extensive dancing and inadequate nutrition.

European Society of Hypertension practice guidelines for ambulatory blood pressure monitoring.

Given the increasing use of ambulatory blood pressure monitoring (ABPM) in both clinical practice and hypertension research, a group of scientists, participating in the European Society of Hypertension Working Group on blood pressure monitoring and cardiovascular variability, in year 2013 published a comprehensive position paper dealing with all aspects of the technique, based on the available scientific evidence for ABPM. The present work represents an updated schematic summary of the most important aspects related to the use of ABPM in daily practice, and is aimed at providing recommendations for proper use of this technique in a clinical setting by both specialists and practicing physicians. The present article details the requirements and the methodological issues to be addressed for using ABPM in clinical practice, The clinical indications for ABPM suggested by the available studies, among which white-coat phenomena, masked hypertension, and nocturnal hypertension, are outlined in detail, and the place of home measurement of blood pressure in relation to ABPM is discussed. The role of ABPM in pharmacological, epidemiological, and clinical research is also briefly mentioned. Finally, the implementation of ABPM in practice is considered in relation to the situation of different countries with regard to the reimbursement and the availability of ABPM in primary care practices, hospital clinics, and pharmacies.

The Role of the European Union in the Processes to Ban Cluster Munitions

At the end of 2008 the Convention on Cluster Munitions (CCM) that outlawed almost all types of cluster munitions was signed. It was the product of the so-called Oslo process, which had been set up two years earlier as a reaction to the failure to add a new protocol banning cluster munitions to the Convention on Certain Conventional Weapons (CCW). The position of the EU in these two processes was ambivalent: on the one hand it belonged to the strongest proponents for a new protocol within the CCW, but on the other hand the member states were in general not able to act jointly in the Oslo Process. According to this working paper especially the aspect of national security and the related relationship to the United States influenced the stances of many member states and complicated the formation of a common European position. There were common normative values of the EU detected, which played a role in the CCW, but they were only secondary to other interests of the member states.

Entrevistant infants pre-escolars víctimes d’abús sexual i/o maltractament familiar : Eficàcia dels models d’entrevista forense

Entrevistant infants pre-escolars víctimes d’abús sexual i/o maltractament familiar: eficàcia dels models d’entrevista forense Entrevistar infants en edat preescolar que han viscut una situació traumàtica és una tasca complexa que dins l’avaluació psicològica forense necessita d’un protocol perfectament delimitat, clar i temporalitzat. Per això, s’han seleccionat 3 protocols d’entrevista: el Protocol de Menors (PM) de Bull i Birch, el model del National Institute for Children Development (NICHD) de Michel Lamb, a partir del qual es va desenvolupar l’EASI (Evaluación del Abuso Sexual Infantojuvenil) i l’Entrevista Cognitiva (EC) de Fisher i Geiselman. La hipòtesi de partida vol comprovar si els anteriors models permeten obtenir volums informatius diferents en infants preescolars. Conseqüentment, els objectius han estat determinar quin dels models d’entrevista permet obtenir un volum informatiu amb més precisions i menys errors, dissenyar un model d’entrevista propi i consensuar aquest model. En el treball s’afegeixen esquemes pràctics que facilitin l’obertura, desenvolupament i tancament de l’entrevista forense. La metodologia ha reproduït el binomi infant - esdeveniment traumàtic, mitjançant la visualització i l’explicació d’un fet emocionalment significatiu amb facilitat per identificar-se: l’accident en bicicleta d’un infant que cau, es fa mal, sagna i el seu pare el cura. A partir d’aquí, hem entrevistat 135 infants de P3, P4 i P5, mitjançant els 3 models d’entrevista referits, enfrontant-los a una demanda específica: recordar i narrar aquest esdeveniment. S’ha conclòs que el nivell de record correcte, quan s’utilitza un model d’entrevista adequat amb els infants en edat preescolar, oscil•la entre el 70-90%, fet que permet defensar la confiança en els records dels infants. Es constata que el percentatge d’emissions incorrectes dels infants en edat preescolar és mínim, al voltant d’un 5-6%. L’estudi remarca la necessitat d’establir perfectament les regles de l’entrevista i, per últim, en destaca la ineficàcia de les tècniques de memòria de l’entrevista cognitiva en els infants de P3 i P4. En els de P5 es comencen a veure beneficis gràcies a la tècnica de la reinstauració contextual (RC), estant les altres tècniques fora de la comprensió i utilització dels infants d’aquestes edats. Interviewing preschoolers victims of sexual abuse and/or domestic abuse: Effectiveness of forensic interviews models 135 preschool children were interviewed with 3 different interview models in order to remember a significant emotional event. Authors conclude that the correct recall of children ranging from 70-90% and the percentage of error messages is 5-6%. It is necessary to fully establish the rules of the interview. The present research highlights the effectiveness of the cognitive interview techniques in children from P3 and P4. Entrevistando niños preescolares víctimas de abuso sexual y/o maltrato familiar: eficacia de los modelos de entrevista forense Se han entrevistado 135 niños preescolares con 3 modelos de entrevista diferentes para recordar un hecho emocionalmente significativo. Se concluye que el recuerdo correcto de los niños oscila entre el 70-90% y el porcentaje de errores de mensajes es del 5-6%. El estudio remarca la necesidad de establecer perfectamente las reglas de la entrevista y se destaca la ineficacia de las técnicas de la entrevista cognitiva en los niños de P3 y P4.