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.

Two Unusual Cases of Sudden Death in Children

We report two unusual cases of sudden unexpected death in children. Histopathologic examination showed intimal fibroplasias, a variant of fibromuscular dysplasia of the right coronary artery associated in both cases with fatty infiltration of the right ventricular myocardium. The significance of this particular combination of two lesions known to induce a sudden death in young people is discussed.

The effect of non-medical factors on variations in the performance of colonoscopy among different health care settings

BACKGROUND: Previous published studies have shown significant variations in colonoscopy performance, even when medical factors are taken into account. This study aimed to examine the role of nonmedical factors (ie, embodied in health care system design) as possible contributors to variations in colonoscopy performance. METHODS: Patient data from a multicenter observational study conducted between 2000 and 2002 in 21 centers in 11 western countries were used. Variability was captured through 2 performance outcomes (diagnostic yield and colonoscopy withdrawal time), jointly studied as dependent variables, using a multilevel 2-equation system. RESULTS: Results showed that open-access systems and high-volume colonoscopy centers were independently associated with a higher likelihood of detecting significant lesions and longer withdrawal durations. Fee for service (FFS) payment was associated with shorter withdrawal durations, and so had an indirect negative impact on the diagnostic yield. Teaching centers exhibited lower detection rates and longer withdrawal times. CONCLUSIONS: Our results suggest that gatekeeping colonoscopy is likely to miss patients with significant lesions and that developing specialized colonoscopy units is important to improve performance. Results also suggest that FFS may result in a lower quality of care in colonoscopy practice and highlight the fact that longer withdrawal times do not necessarily indicate higher quality in teaching centers.

Paleohydrological Reconstruction from Late Holocene Records in Interdune Lakes (N'Guigmi, Northern Bank of the Lake Chad, Niger)

An old erg covers the northern part of the Lake Chad basin. This dune landform allowed the formation of many inter- dune ponds of various sizes. Still present in certain zones where the groundwater level is high (e.g. Kanem, southern Manga), these ponds formed in the past a vast network of lacustrine microsystems, as shown by the nature and the dis- tribution of their deposits. In the Manga, these interdune deposits represent the main sedimentary records of the Holo- cene environmental succession. Their paleobiological (pollens, diatoms, ostracods) and geochemical (δ18O, δ13C, Sr/ Ca) contents are often the basis for paleoenvironmental reconstruction. On the other hand, their sedimentological char- acters are rarely exploited. This study of palustro-lacustrine deposits of the Holocene N'Guigmi lake (northern bank of the Lake Chad; Niger) is based on the relationships between the sedimentological features and the climato-hydrological fluctuations. The mineralogical parameters (e.g. calcium carbonate content, clay mineralogy) and the nature of autoch- thonous mineralization (i.e. amorphous silica, clays, calcium carbonates) can be interpreted using a straightforward hy- dro-sedimentary model. Established to explain the geochemical dynamics of Lake Chad, this model is based on a bio- geochemical cycle of the main elements (i.e. silicium, calcium) directly controlled by the local hydrological balance (i.e. rainfall/evaporation ratio). All these results show that a detailed study of sedimentological features can provide impor- tant paleohydrological informations about the regional aridification since ca 6500 14C BP.

Posterior Sub-Tenon Triamcinolone Injection for Chronic Macular Oedema Associated With Non-Ischemic Branch or Central Retinal Vein Occlusion

Aims: To evaluate the effectiveness and safety of Posterior Sub-Tenon (PST) Triamcinolone Acetonide (TA) injection for persistent macular oedema associated with non-ischemic Central Retinal Vein Occlusion (CRVO) or Branch Retinal Vein Occlusion (BRVO) in non-vitrectomized eye. Methods: Fourteen consecutive eyes of 14 patients characterized by macular oedema lasting more than 3 months and with a visual acuity of less than 20/40 were enrolled. Six eyes presented with BRVO, 8 eyes with CRVO. PST injection of 40 mg TA was performed in topical anaesthesia. All patients were phakic, and followed for at least 6 months. Snellen visual acuity converted to LogMAR units and anatomic responses were evaluated before, and at 1, 3, 6, and 12 (if required) months after injections and re-injection considered. Results: In the BRVO group, mean foveal thickness was 548.2±49.50 μm preoperatively, and 452.8±56.2 μm and 280.8±62.5 μm at 1 and 12 month follow-up, respectively. Statistical analysis showed significant differences between preoperative and postoperative measurements (P<.05, paired t test) 3 months after injections. Improvement of visual acuity by at least 0.2 LogMAR was seen in 3(50%) of the 6 eyes. No re-injection was needed. In the CRVO group, mean foveal thickness was 543.7±34.4 μm preoperatively, and 283.0±29.0 μm and 234.8±23.6 μm at 1 and 12 month follow-up, respectively. Statistical analysis showed significant differences between preoperative and postoperative measurements (P<.05, paired t test). Improvement of visual acuity by at least 0.2 LogMAR was seen in 7 eyes (88%). Mean number of re-injection was of 2.1±0.3. Intraocular pressure elevation of 22 mm Hg or higher was found in 2/14 eyes (14%). Cataract progression was noted in 5/14 eyes (36%). Conclusions: PST injection of TA appears to be as safe and effective treatment for chronic macular oedema associated due to both non-ischemic BRVO or CRVO, with a better efficacy in BRVO.

Cost evaluation of cardiovascular magnetic resonance versus coronary angiography for the diagnostic work-up of coronary artery disease: Application of the European Cardiovascular Magnetic Resonance registry data to the German, United Kingdom, Swiss, and United States health care systems.

ABSTRACT: BACKGROUND: Cardiovascular magnetic resonance (CMR) has favorable characteristics for diagnostic evaluation and risk stratification of patients with known or suspected CAD. CMR utilization in CAD detection is growing fast. However, data on its cost-effectiveness are scarce. The goal of this study is to compare the costs of two strategies for detection of significant coronary artery stenoses in patients with suspected coronary artery disease (CAD): 1) Performing CMR first to assess myocardial ischemia and/or infarct scar before referring positive patients (defined as presence of ischemia and/or infarct scar to coronary angiography (CXA) versus 2) a hypothetical CXA performed in all patients as a single test to detect CAD. METHODS: A subgroup of the European CMR pilot registry was used including 2,717 consecutive patients who underwent stress-CMR. From these patients, 21% were positive for CAD (ischemia and/or infarct scar), 73% negative, and 6% uncertain and underwent additional testing. The diagnostic costs were evaluated using invoicing costs of each test performed. Costs analysis was performed from a health care payer perspective in German, United Kingdom, Swiss, and United States health care settings. RESULTS: In the public sectors of the German, United Kingdom, and Swiss health care systems, cost savings from the CMR-driven strategy were 50%, 25% and 23%, respectively, versus outpatient CXA. If CXA was carried out as an inpatient procedure, cost savings were 46%, 50% and 48%, respectively. In the United States context, cost savings were 51% when compared with inpatient CXA, but higher for CMR by 8% versus outpatient CXA. CONCLUSION: This analysis suggests that from an economic perspective, the use of CMR should be encouraged as a management option for patients with suspected CAD.

Female genital mutilation and its prevention: a challenge for paediatricians.

Female genital mutilation (FGM) is defined as an injury of the external female genitalia for cultural or non-therapeutic reasons. FGM is mainly performed in sub-Saharan and Eastern Africa. The western health care systems are confronted with migrants from this cultural background. The aim is to offer information on how to approach this subject. The degree of FGM can vary from excision of the prepuce and clitoris to infibulation. Infections, urinary retention, pain, lesions of neighbouring organs, bleeding, psychological trauma and even death are possible acute complications. The different long-term complications include the risk of reduced fertility and difficulties during labour, which are key arguments against FGM in the migrant community. Paediatricians often have questions on how to approach the subject. With an open, neutral approach and basic knowledge, discussions with parents are constructive. Talking about the newborn, delivery or traditions may be a good starting point. Once they feel accepted, they speak surprisingly openly. FGM is performed out of love for their daughters. We have to be aware of their arguments and fears, but we should also stress the parents' responsibility in taking a health risk for their daughters. It is important to know the family's opinion on FGM. Some may need support, especially against community pressure. As FGM is often performed on newborns or at 4-9 years of age, paediatricians should have an active role in the prevention of FGM, especially as they have repeated close contact with those concerned and medical consequences are the main arguments against FGM.

Migration of sharks into freshwater systems during the Miocene and implications for Alpine paleoelevation

Trace-element and isotopic compositions of fossilized shark teeth sampled from Miocene marine sediments of the north Alpine Molasse Basin, the Vienna Basin, and the Pannonian Basin generally show evidence of formation in a marine environment under conditions geochemically equivalent to the open ocean. In contrast, two of eight shark teeth from the Swiss Upper Marine Molasse locality of La Moliere have extremely low delta O-18 values (10.3% and 11.3%) and low Sr-87/Sr-86 ratios (0.707840 and 0.707812) compared to other teeth from this locality (21.1%,22.4%o and 0.708421-0.708630). The rare earth element (REE) abundances and patterns from La Moliere not only differ between dentine and enameloid of the same tooth, but also between different teeth, supporting variable conditions of diagenesis at this site. However, the REE patterns of enameloid from the ``exotic'' teeth analyzed for O and Sr isotopic compositions are similar to those of teeth that have O and Sr isotopic compositions typical of a marine setting at this site. Collectively, this suggests that the two ``exotic'' teeth were formed while the sharks frequented a freshwater environment with very low O-18-content and Sr isotopic composition controlled by Mesozoic calcareous rocks. This is consistent with a paleogeography of high-elevation (similar to 2300 m) Miocene Alps adjacent to a marginal sea.

Progesterone down-regulates the open probability of the amiloride-sensitive epithelial sodium channel via a Nedd4-2-dependent mechanism.

Activation of the mitogen-activated protein (MAP) kinase cascade by progesterone in Xenopus oocytes leads to a marked down-regulation of activity of the amiloride-sensitive epithelial sodium channel (ENaC). Here we have studied the signaling pathways involved in progesterone effect on ENaC activity. We demonstrate that: (i) the truncation of the C termini of the alphabetagammaENaC subunits results in the loss of the progesterone effect on ENaC; (ii) the effect of progesterone was also suppressed by mutating conserved tyrosine residues in the Pro-X-X-Tyr (PY) motif of the C termini of the beta and gamma ENaC subunits (beta(Y618A) and gamma(Y628A)); (iii) the down-regulation of ENaC activity by progesterone was also suppressed by co-expression ENaC subunits with a catalytically inactive mutant of Nedd4-2, a ubiquitin ligase that has been previously demonstrated to decrease ENaC cell-surface expression via a ubiquitin-dependent internalization/degradation mechanism; (iv) the effect of progesterone was significantly reduced by suppression of consensus sites (beta(T613A) and gamma(T623A)) for ENaC phosphorylation by the extracellular-regulated kinase (ERK), a MAP kinase previously shown to facilitate the binding of Nedd4 ubiquitin ligases to ENaC; (v) the quantification of cell-surface-expressed ENaC subunits revealed that progesterone decreases ENaC open probability (whole cell P(o), wcP(o)) and not its cell-surface expression. Collectively, these results demonstrate that the binding of active Nedd4-2 to ENaC is a crucial step in the mechanism of ENaC inhibition by progesterone. Upon activation of ERK, the effect of Nedd4-2 on ENaC open probability can become more important than its effect on ENaC cell-surface expression.

Tight open knots.

The tightest open conformations of a few prime knots (3(1), 4(1), 5(1), 5(2), and 6(3)) found with the use of the SONO algorithm are presented and discussed. The conformations are obtained from the tightest closed conformations of the knots by cutting and opening them at different locations. The length of the rope engaged in each of the open conformations is calculated. The curvature and torsion profiles of the unique tightest conformations of the 3(1) and 4(1) open knots are presented and discussed. In particular, symmetry properties of the knots reflected within their curvature and torsion profiles are analysed. Connections with the physics of polymers are discussed.

Density-dependent pollen limitation and reproductive assurance in a wind-pollinated herb with contrasting sexual systems

1. Wind pollination is thought to have evolved in response to selection for mechanisms to promote pollination success, when animal pollinators become scarce or unreliable. We might thus expect wind-pollinated plants to be less prone to pollen limitation than their insect-pollinated counterparts. Yet, if pollen loads on stigmas of wind-pollinated species decline with distance from pollen donors, seed set might nevertheless be pollen-limited in populations of plants that cannot self-fertilize their progeny, but not in self-compatible hermaphroditic populations.2. Here, we test this hypothesis by comparing pollen limitation between dioecious and hermaphroditic (monoecious) populations of the wind-pollinated herb Mercurialis annua.3. In natural populations, seed set was pollen-limited in low-density patches of dioecious, but not hermaphroditic, M. annua, a finding consistent with patterns of distance-dependent seed set by females in an experimental array. Nevertheless, seed set was incomplete in both dioecious and hermaphroditic populations, even at high local densities. Further, both factors limited the seed set of females and hermaphrodites, after we manipulated pollen and resource availability in a common garden experiment.4. Synthesis. Our results are consistent with the idea that pollen limitation plays a role in the evolution of combined vs. separate sexes in M. annua. Taken together, they point to the potential importance of pollen transfer between flowers on the same plant (geitonogamy) by wind as a mechanism of reproductive assurance and to the dual roles played by pollen and resource availability in limiting seed set. Thus, seed set can be pollen-limited in sparse populations of a wind-pollinated species, where mates are rare or absent, having potentially important demographic and evolutionary implications.

Comparative study and identification of potent eukaryotic transcriptional repressors in gene switch systems.

In mammalian cells, proper gene regulation is achieved by the complex interplay of transcription factors that activate or repress gene expression by binding to the regulatory regions of target promoters. While transcriptional activators have been extensively characterised and classified into functional groups, relatively little is known about the comparative strength and cell type-specificity of transcriptional repressors. Here, we have compared the ability of a series of eukaryotic repression domains to silence basal and activated transcription. A series of the most potent repression domains was further tested in the context of a gene therapy gene-switch system in various cell types. The results indicate that the analysed repression domains exert varying silencing activities in different promoter contexts. Furthermore, their potential for gene silencing varies also depending on the cellular context. When multimerised within one chimeric repressor protein, particular combinations of repressor domains were found to display synergistic repressing effects and efficient repression in a panel of cell lines. This approach thus allowed the identification of transcriptional repressors that are both potent and versatile in terms of cellular specificity as a basis for gene switch systems.