Systems Genetics of Metabolism: The Use of the BXD Murine Reference Panel for Multiscalar Integration of Traits.

Metabolic homeostasis is achieved by complex molecular and cellular networks that differ significantly among individuals and are difficult to model with genetically engineered lines of mice optimized to study single gene function. Here, we systematically acquired metabolic phenotypes by using the EUMODIC EMPReSS protocols across a large panel of isogenic but diverse strains of mice (BXD type) to study the genetic control of metabolism. We generated and analyzed 140 classical phenotypes and deposited these in an open-access web service for systems genetics (www.genenetwork.org). Heritability, influence of sex, and genetic modifiers of traits were examined singly and jointly by using quantitative-trait locus (QTL) and expression QTL-mapping methods. Traits and networks were linked to loci encompassing both known variants and novel candidate genes, including alkaline phosphatase (ALPL), here linked to hypophosphatasia. The assembled and curated phenotypes provide key resources and exemplars that can be used to dissect complex metabolic traits and disorders.

Dynamic Modelling of Material Flows and Sustainable Resource Use: Case Studies in Regional Metabolism and Space Life Support Systems

Sustainable resource use is one of the most important environmental issues of our times. It is closely related to discussions on the 'peaking' of various natural resources serving as energy sources, agricultural nutrients, or metals indispensable in high-technology applications. Although the peaking theory remains controversial, it is commonly recognized that a more sustainable use of resources would alleviate negative environmental impacts related to resource use. In this thesis, sustainable resource use is analysed from a practical standpoint, through several different case studies. Four of these case studies relate to resource metabolism in the Canton of Geneva in Switzerland: the aim was to model the evolution of chosen resource stocks and flows in the coming decades. The studied resources were copper (a bulk metal), phosphorus (a vital agricultural nutrient), and wood (a renewable resource). In addition, the case of lithium (a critical metal) was analysed briefly in a qualitative manner and in an electric mobility perspective. In addition to the Geneva case studies, this thesis includes a case study on the sustainability of space life support systems. Space life support systems are systems whose aim is to provide the crew of a spacecraft with the necessary metabolic consumables over the course of a mission. Sustainability was again analysed from a resource use perspective. In this case study, the functioning of two different types of life support systems, ARES and BIORAT, were evaluated and compared; these systems represent, respectively, physico-chemical and biological life support systems. Space life support systems could in fact be used as a kind of 'laboratory of sustainability' given that they represent closed and relatively simple systems compared to complex and open terrestrial systems such as the Canton of Geneva. The chosen analysis method used in the Geneva case studies was dynamic material flow analysis: dynamic material flow models were constructed for the resources copper, phosphorus, and wood. Besides a baseline scenario, various alternative scenarios (notably involving increased recycling) were also examined. In the case of space life support systems, the methodology of material flow analysis was also employed, but as the data available on the dynamic behaviour of the systems was insufficient, only static simulations could be performed. The results of the case studies in the Canton of Geneva show the following: were resource use to follow population growth, resource consumption would be multiplied by nearly 1.2 by 2030 and by 1.5 by 2080. A complete transition to electric mobility would be expected to only slightly (+5%) increase the copper consumption per capita while the lithium demand in cars would increase 350 fold. For example, phosphorus imports could be decreased by recycling sewage sludge or human urine; however, the health and environmental impacts of these options have yet to be studied. Increasing the wood production in the Canton would not significantly decrease the dependence on wood imports as the Canton's production represents only 5% of total consumption. In the comparison of space life support systems ARES and BIORAT, BIORAT outperforms ARES in resource use but not in energy use. However, as the systems are dimensioned very differently, it remains questionable whether they can be compared outright. In conclusion, the use of dynamic material flow analysis can provide useful information for policy makers and strategic decision-making; however, uncertainty in reference data greatly influences the precision of the results. Space life support systems constitute an extreme case of resource-using systems; nevertheless, it is not clear how their example could be of immediate use to terrestrial systems.

Deaths rates in public hospitals of eastern cape province of South Africa.

BACKGROUND: South Africa (SA) is experiencing a rapid epidemiologic transition as a consequence of political, economic and social changes. In this study we described, based on hospital data, the mortality patterns of Non communicable Diseases (NCD), Communicable Diseases (CD), the NCD/CD ratios, and the trends of deaths. METHODS: We conducted a cross-sectional survey of all deaths occurring in several public hospitals in the Eastern Cape Province of SA between 2002 and 2006. Causes of deaths were coded according to the ICD 10 Edition. RESULTS: A total of 107380 admissions responded to the inclusion criteria between 2002 and 2006. The crude death rate was 4.3% (n=4566) with a mean age of 46±21 years and a sex ratio of 3.1 men (n=3453): 1 woman (n=1113). Out of all deaths, there were 62.9% NCD (n=2872) vs. 37.1% CD (n=1694) with NCD/CD ratio of 1.7. The ratio NCD/CD deaths in men was 1.3 (n=1951/1502) vs. NCD/CD deaths in women of 1.9 (n=735/378). The peak of deaths was observed in winter season. The majority of NCD deaths were at age of 30-64 years, whereas the highest rate of CD deaths was at age< 30 years. The trend of deaths including the majority of NCD, increased from 2002 to 2006. There was a tendency of increase in tuberculosis deaths, but a tendency of decrease in HIV/AIDS deaths was from 2002 to 2006. CONCLUSION: Non-communicable diseases are the leading causes of deaths in rural Eastern Cape province of SA facing Post-epidemiologic transition stages. We recommend overarching priority actions for the response to the Non-communicable Diseases: policy change, prevention, treatment, international cooperation, research, monitoring, accountability, and re-orientation of health systems.

Family interactions in IVF families: change over the transition to parenthood

Objective: This article presents a study of the change over time in the family interactions of couples who conceived through in-vitro fertilisation (IVF). Background: Observational methods are rarely used to study family interactions in families who used assisted reproductive techniques, but these methods are crucial for taking account of the communication that occurs in interactions with infants. Methods: Thirty-one couples expecting their first child were seen during the fifth month of pregnancy and when the child was nine months old. Family interactions were recorded in pre- and postnatal versions of the Lausanne Trilogue Play situation. Measures of marital satisfaction and parent-to-foetus/baby attachment or 'bonding' were also used to assess family relational dynamics. Results: Results showed that family alliance, marital satisfaction and parental attachment scores in the IVF sample were all similar to or higher than those in the reference sample during pregnancy. However, at nine months postnatally, the family alliance scores were lower. While marital satisfaction decreased over the period and parent-baby attachment increased, the family alliance scores were unstable, as no association was observed between the pre- and postnatal scores. In addition, neither prenatal marital satisfaction nor parent-foetus attachment predicted the postnatal family alliance. Conclusion: The change in the family alliance over the transition to parenthood appears to be specific to our IVF sample. Given that postnatal family functioning could not be predicted by prenatal family functioning, our observational data underline the importance of offering postnatal support to these families.

Ground-state order and spin-lattice coupling in tetrahedral spin systems Cu2Te2O5X2 (X = Br or Cl)

High-resolution ac susceptibility and thermal conductivity measurement on Cu2Te2O5X2 (X=Br,Cl) single crystals are reported. For Br-sample, sample dependence prevents one from distinguishing between possibilities of magnetically ordered and spin-singlet ground states. In Cl-sample a three-dimensional transition at 18.5 K is accompanied by almost isotropic behavior of susceptibility and almost switching behavior of thermal conductivity. Thermal conductivity studies suggest the presence of a tremendous spin-lattice coupling characterizing Cl- but not Br-sample. Below the transition Cl-sample is in a complex magnetic state involving AF order but also the elements consistent with the presence of a gap in the excitation spectrum.

Organic geochemistry across the Permian-Triassic transition at the Idrijca Valley, Western Slovenia

Bulk and molecular stable C isotopic compositions and biomarker distributions provide evidence for a diverse community of algal and bacterial organisms in the sedimentary organic matter of a carbonate section throughout the Permian-Triassic (P/Tr) transition at the Idrijca Valley, Western Slovenia. The input of algae and bacteria in all the Upper Permian and Lower Scythian samples is represented by the predominance of C-15-C-22 n-alkanes, odd C-number alkylcyclohexanes, C-27 steranes and substantial contents Of C-21-C-30 acyclic isoprenoids. The occurrence of odd long-chain n-alkanes (C-22-C-30) and C29 steranes in all the samples indicate a contribution of continental material. The decrease of C-org and C-carb contents, increase of Rock-Eval oxygen indices, and C-13-enrichment of the kerogen suggest a decrease in anoxia of the uppermost Permian bottom water. The predominance of odd C-number alkylcycloalkanes, C-27 steranes, and C-17 n-alkanes with delta(13)C values similar to-30parts per thousand, and C-13-enrichment of the kerogens in the lowermost Scythian samples are evidence of greater algal productivity. This increased productivity was probably sustained by a high nutrient availability and changes of dissolved CO2 speciation associated to the earliest Triassic transgression. A decrease Of Corg content in the uppermost Scythian samples, associated to a C-13-depletetion in the carbonates (up to 4parts per thousand) and individual n-alkanes (up to 3.4parts per thousand) compared to the Upper Permian samples, indicate lowering of the primary productivity (algae, cyanobacteria) and/or higher degradation of the organic matter. (C) 2003 Elsevier Ltd. All rights reserved.

Challenge of transition in the socio-professional insertion of youngsters with neurodisabilities.

Objective: To evaluate the activities of patients with neurodisabilities and assess their insertion problems in the professional world. Methods: It is based on medical records of 267 patients (224 with neurodevelopmental diseases and 43 with neuromuscular diseases), aged 16-25 years, followed in the transition clinic of young adults in the neurorehabilitation services of a tertiary center. Results: Nearly half of them (46.8%) were in a protected environment, 37.08% studied and only 3.4% worked. Their studies are much longer and they are less in university than Swiss people of same age. The competitiveness criteria are no mental retardation and to be completely independent. Finally, 29.2% reported work problems, the foremost being the lack of adaptation in the workplace. Conclusion: These results highlight the need to increase the integration of young adults with neuromotor disorders in the labor market.

ENFIN--A European network for integrative systems biology.

Integration of biological data of various types and the development of adapted bioinformatics tools represent critical objectives to enable research at the systems level. The European Network of Excellence ENFIN is engaged in developing an adapted infrastructure to connect databases, and platforms to enable both the generation of new bioinformatics tools and the experimental validation of computational predictions. With the aim of bridging the gap existing between standard wet laboratories and bioinformatics, the ENFIN Network runs integrative research projects to bring the latest computational techniques to bear directly on questions dedicated to systems biology in the wet laboratory environment. The Network maintains internally close collaboration between experimental and computational research, enabling a permanent cycling of experimental validation and improvement of computational prediction methods. The computational work includes the development of a database infrastructure (EnCORE), bioinformatics analysis methods and a novel platform for protein function analysis FuncNet.

Bond strength tests of dental adhesive systems and their correlation with clinical results : a meta-analysis

OBJECTIVE: To evaluate the variability of bond strength test results of adhesive systems (AS) and to correlate the results with clinical parameters of clinical studies investigating cervical restorations. MATERIALS AND METHODS: Regarding the clinical studies, the internal database which had previously been used for a meta-analysis on cervical restorations was updated with clinical studies published between 2008 and 2012 by searching the PubMed and SCOPUS databases. PubMed and the International Association for Dental Research abstracts online were searched for laboratory studies on microtensile, macrotensile and macroshear bond strength tests. The inclusion criteria were (1) dentin, (2) testing of at least four adhesive systems, (3) same diameter of composite and (4) 24h of water storage prior to testing. The clinical outcome variables were retention loss, marginal discoloration, detectable margins, and a clinical index comprising the three parameters by weighing them. Linear mixed models which included a random study effect were calculated for both, the laboratory and the clinical studies. The variability was assessed by calculating a ratio of variances, dividing the variance among the estimated bonding effects obtained in the linear mixed models by the sum of all variance components estimated in these models. RESULTS: Thirty-two laboratory studies fulfilled the inclusion criteria comprising 183 experiments. Of those, 86 used the microtensile test evaluating 22 adhesive systems (AS). Twenty-seven used the macrotensile test with 17 AS, and 70 used the macroshear test with 24 AS. For 28 AS the results from clinical studies were available. Microtensile and macrotensile (Spearman rho=0.66, p=0.007) were moderately correlated and also microtensile and macroshear (Spearman rho=0.51, p=0.03) but not macroshear and macrotensile (Spearman rho=0.34, p=0.22). The effect of the adhesive system was significant for microtensile and macroshear (p<0.001) but not for macrotensile. The effect of the adhesive system could explain 36% of the variability of the microtensile test, 27% of the macrotensile and 33% of the macroshear test. For the clinical trials, about 49% of the variability of retained restorations could be explained by the adhesive system. With respect to the correlation between bond strength tests and clinical parameters, only a moderate correlation between micro- and macrotensile test results and marginal discoloration was demonstrated. However, no correlation between these tests and a retention loss or marginal integrity was shown. The correlation improved when more studies were included compared to assessing only one study. SIGNIFICANCE: The high variability of bond strength test results highlights the need to establish individual acceptance levels for a given test institute. The weak correlation of bond-strength test results with clinical parameters leads to the conclusion that one should not rely solely on bond strength tests to predict the clinical performance of an adhesive system but one should conduct other laboratory tests like tests on the marginal adaptation of fillings in extracted teeth and the retention loss of restorations in non-retentive cavities after artificial aging.

A systems view of risk factors for knee osteoarthritis reveals insights into the pathogenesis of the disease.

Early detection of osteoarthritis (OA) remains a critical yet unsolved multifaceted problem. To address the multifaceted nature of OA a systems model was developed to consolidate a number of observations on the biological, mechanical and structural components of OA and identify features common to the primary risk factors for OA (aging, obesity and joint trauma) that are present prior to the development of clinical OA. This analysis supports a unified view of the pathogenesis of OA such that the risk for developing OA emerges when one of the components of the disease (e.g., mechanical) becomes abnormal, and it is the interaction with the other components (e.g., biological and/or structural) that influences the ultimate convergence to cartilage breakdown and progression to clinical OA. The model, applied in a stimulus-response format, demonstrated that a mechanical stimulus at baseline can enhance the sensitivity of a biomarker to predict cartilage thinning in a 5 year follow-up in patients with knee OA. The systems approach provides new insight into the pathogenesis of the disease and offers the basis for developing multidisciplinary studies to address early detection and treatment at a stage in the disease where disease modification has the greatest potential for a successful outcome.

Elevated hypertension risk for African-origin populations in biracial societies : Modeling the Epidemiologic Transition Study.

OBJECTIVES: Blood pressures in persons of African descent exceed those of other racial/ethnic groups in the United States. Whether this trait is attributable to the genetic factors in African-origin populations, or a result of inadequately measured environmental exposures, such as racial discrimination, is not known. To study this question, we conducted a multisite comparative study of communities in the African diaspora, drawn from metropolitan Chicago, Kingston, Jamaica, rural Ghana, Cape Town, South Africa, and the Seychelles. METHODS: At each site, 500 participants between the age of 25 and 49 years, with approximately equal sex balance, were enrolled for a longitudinal study of energy expenditure and weight gain. In this study, we describe the patterns of blood pressure and hypertension observed at baseline among the sites. RESULTS: Mean SBP and DBP were very similar in the United States and South Africa in both men and women, although among women, the prevalence of hypertension was higher in the United States (24 vs. 17%, respectively). After adjustment for multiple covariates, relative to participants in the United States, SBP was significantly higher among the South Africans by 9.7 mmHg (P < 0.05) and significantly lower for each of the other sites: for example, Jamaica: -7.9 mmHg (P = 0.06), Ghana: -12.8 mmHg (P < 0.01) and Seychelles: -11.1 mmHg (P = 0.01). CONCLUSION: These data are consistent with prior findings of a blood pressure gradient in societies of the African diaspora and confirm that African-origin populations with lower social status in multiracial societies, such as the United States and South Africa, experience more hypertension than anticipated based on anthropometric and measurable socioeconomic risk factors.