Systemic conditions and treatments as risks for implant therapy

PURPOSE: To evaluate whether systemic diseases with/without systemic medication increase the risk of implant failure and therefore diminish success and survival rates of dental implants. MATERIALS AND METHODS: A MEDLINE search was undertaken to find human studies reporting implant survival in subjects treated with osseointegrated dental implants who were diagnosed with at least one of 12 systemic diseases. RESULTS: For most conditions, no studies comparing patients with and without the condition in a controlled setting were found. For most systemic diseases there are only case reports or case series demonstrating that implant placement, integration, and function are possible in affected patients. For diabetes, heterogeneity of the material and the method of reporting data precluded a formal meta-analysis. No unequivocal tendency for subjects with diabetes to have higher failure rates emerged. The data from papers reporting on osteoporotic patients were also heterogeneous. The evidence for an association between osteoporosis and implant failure was low. Nevertheless, some reports now tend to focus on the medication used in osteoporotic patients, with oral bisphosphonates considered a potential risk factor for osteonecrosis of the jaws, rather than osteoporosis as a risk factor for implant success and survival on its own. CONCLUSIONS: The level of evidence indicative of absolute and relative contraindications for implant therapy due to systemic diseases is low. Studies comparing patients with and without the condition in a controlled setting are sparse. Especially for patients with manifest osteoporosis under an oral regime of bisphosphonates, prospective controlled studies are urgently needed.

Integrated data acquisition and processing to determine metabolite contents, relaxation times, and macromolecule baseline in single examinations of individual subjects

Absolute quantitation of clinical (1)H-MR spectra is virtually always incomplete for single subjects because the separate determination of spectrum, baseline, and transverse and longitudinal relaxation times in single subjects is prohibitively long. Integrated Processing and Acquisition of Data (IPAD) based on a combined 2-dimensional experimental and fitting strategy is suggested to substantially improve the information content from a given measurement time. A series of localized saturation-recovery spectra was recorded and combined with 2-dimensional prior-knowledge fitting to simultaneously determine metabolite T(1) (from analysis of the saturation-recovery time course), metabolite T(2) (from lineshape analysis based on metabolite and water peak shapes), macromolecular baseline (based on T(1) differences and analysis of the saturation-recovery time course), and metabolite concentrations (using prior knowledge fitting and conventional procedures of absolute standardization). The procedure was tested on metabolite solutions and applied in 25 subjects (15-78 years old). Metabolite content was comparable to previously found values. Interindividual variation was larger than intraindividual variation in repeated spectra for metabolite content as well as for some relaxation times. Relaxation times were different for various metabolite groups. Parts of the interindividual variation could be explained by significant age dependence of relaxation times.

Prevalence and risk-factor analysis of Shiga toxigenic Escherichia coli in faecal samples of organically and conventionally farmed dairy cattle

Cattle are a natural reservoir for Shiga toxigenic Escherichia coli (STEC), however, no data are available on the prevalence and their possible association with organic or conventional farming practices. We have therefore studied the prevalence of STEC and specifically O157:H7 in Swiss dairy cattle by collecting faeces from approximately 500 cows from 60 farms with organic production (OP) and 60 farms with integrated (conventional) production (IP). IP farms were matched to OP farms and were comparable in terms of community, agricultural zone, and number of cows per farm. E. coli were grown overnight in an enrichment medium, followed by DNA isolation and PCR analysis using specific TaqMan assays. STEC were detected in all farms and O157:H7 were present in 25% of OP farms and 17% of IP farms. STEC were detected in 58% and O157:H7 were evidenced in 4.6% of individual faeces. Multivariate statistical analyses of over 250 parameters revealed several risk-factors for the presence of STEC and O157:H7. Risk-factors were mainly related to the potential of cross-contamination of feeds and cross-infection of cows, and age of the animals. In general, no significant differences between the two farm types concerning prevalence or risk for carrying STEC or O157:H7 were observed. Because the incidence of human disease caused by STEC in Switzerland is low, the risk that people to get infected appears to be small despite a relatively high prevalence in cattle. Nevertheless, control and prevention practices are indicated to avoid contamination of animal products.

Suspended sediment pulse effects in rainbow trout (Oncorhynchus mykiss) - relating apical and systemic responses

To provide an integrated perspective on mineral particle effects in salmonids, juvenile rainbow trout (Oncorhynchus mykiss) were exposed to daily mica particle pulses for 8 and 24 days. On day 8, increased immature erythrocyte proportions indicated a previous stress response. This response was absent on day 24, on which condition factor as well as plasma protein and aspartate aminotransferase activity decreased. The latter two related negatively to the hepato-somatic index, suggesting metabolic adaptations. The hepato-somatic index increased on days 8 and 24, while spleen-somatic index increased on day 24. No histopathological damage occurred in gills, liver, spleen, or kidney. However, splenic melano-macrophages increased on both days, and hyaline degenerations of kidney tubular cells were apparent on day 24. Overall, particle pulses affected rainbow trout more via turbidity rather than by physical damage. We conclude that (i) rainbow trout may adapt to sediment pulses as early as 8 days of exposure and (ii) particle pulses over 24 days can cause structural and metabolic changes in rainbow trout, even when gill damage is absent and apical effects on condition are moderate.

Skin and mucosa care in systemic sclerosis - patients' and family caregivers' experiences and expectations of a specific education programme: a qualitative study

BACKGROUND Skin and mucosal manifestations such as skin thickening, pruritus, reduced microvascular circulation, digital lesions, appearance-related changes, and dryness of the eyes and mucosa are common in systemic sclerosis (SSc). A specific skin and mucosa care education programme for patients and their family caregivers should increase their self-efficacy and improve coping strategies. AIMS The aims of this qualitative study were to explore the participants' experiences of both everyday life with skin and mucosal manifestations and the programme itself, while identifying unmet needs for programme development. METHODS Narrative interviews were conducted with eight SSc patients and two family caregivers of individuals with SSc. Using qualitative content analysis techniques, the transcribed interviews were systematically summarized and categories inductively developed. RESULTS The findings illustrated participants' experiences of skin and mucosal symptoms and revealed them to be experts in finding the right therapy mix alone (before diagnosis) and also in collaboration with health professionals (after diagnosis). Participants emphasized that the programme gave them useful education on skin and mucosa care. They described how they had to cope alone with the lack of information on pathophysiology, people's reactions, and the impact on their family and working lives. Nevertheless, participants said that they maintained a positive attitude by not dwelling on future disabilities. CONCLUSIONS Patients and family caregivers benefited from the individualized and SSc-specific education on skin and mucosa care. Future improvements to the programme should focus on imparting understandable information on SSc pathophysiology, dealing with disfigurement and seeking reliable disease information, as well as facilitating peer support.

Proteomic analysis of the Theileria annulata schizont

The apicomplexan parasite, Theileria annulata, is the causative agent of tropical theileriosis, a devastating lymphoproliferative disease of cattle. The schizont stage transforms bovine leukocytes and provides an intriguing model to study host/pathogen interactions. The genome of T. annulata has been sequenced and transcriptomic data are rapidly accumulating. In contrast, little is known about the proteome of the schizont, the pathogenic, transforming life cycle stage of the parasite. Using one-dimensional (1-D) gel LC-MS/MS, a proteomic analysis of purified T. annulata schizonts was carried out. In whole parasite lysates, 645 proteins were identified. Proteins with transmembrane domains (TMDs) were under-represented and no proteins with more than four TMDs could be detected. To tackle this problem, Triton X-114 treatment was applied, which facilitates the extraction of membrane proteins, followed by 1-D gel LC-MS/MS. This resulted in the identification of an additional 153 proteins. Half of those had one or more TMD and 30 proteins with more than four TMDs were identified. This demonstrates that Triton X-114 treatment can provide a valuable additional tool for the identification of new membrane proteins in proteomic studies. With two exceptions, all proteins involved in glycolysis and the citric acid cycle were identified. For at least 29% of identified proteins, the corresponding transcripts were not present in the existing expressed sequence tag databases. The proteomics data were integrated into the publicly accessible database resource at EuPathDB (www.eupathdb.org) so that mass spectrometry-based protein expression evidence for T. annulata can be queried alongside transcriptional and other genomics data available for these parasites.

Monitoring Programmes, Multiple Stress Analysis and Decision Support for River Basin Management

The identification of plausible causes for water body status deterioration will be much easier if it can build on available, reliable, extensive and comprehensive biogeochemical monitoring data (preferably aggregated in a database). A plausible identification of such causes is a prerequisite for well-informed decisions on which mitigation or remediation measures to take. In this chapter, first a rationale for an extended monitoring programme is provided; it is then compared to the one required by the Water Framework Directive (WFD). This proposal includes a list of relevant parameters that are needed for an integrated, a priori status assessment. Secondly, a few sophisticated statistical tools are described that subsequently allow for the estiation of the magnitude of impairment as well as the likely relative importance of different stressors in a multiple stressed environment. The advantages and restrictions of these rather complicated analytical methods are discussed. Finally, the use of Decision Support Systems (DSS) is advocated with regard to the specific WFD implementation requirements.

Adult-onset mastocytosis in the skin is highly suggestive of systemic mastocytosis

Adult-onset urticaria pigmentosa/mastocytosis in the skin almost always persists throughout life. The prevalence of systemic mastocytosis in such patients is not precisely known. Bone marrow biopsies from 59 patients with mastocytosis in the skin and all available skin biopsies (n=27) were subjected to a meticulous cytological, histological, immunohistochemical, and molecular analysis for the presence of WHO-defined diagnostic criteria for systemic mastocytosis: compact mast cell infiltrates (major criterion); atypical mast cell morphology, KIT D816V, abnormal expression of CD25 by mast cells, and serum tryptase levels >20 ng/ml (minor criteria). Systemic mastocytosis is diagnosed when the major diagnostic criterion plus one minor criterion or at least three minor criteria are fulfilled. Systemic mastocytosis was confirmed in 57 patients (97%) by the diagnosis of compact mast cell infiltrates plus at least one minor diagnostic criterion (n=42, 71%) or at least three minor diagnostic criteria (n=15, 25%). In two patients, only two minor diagnostic criteria were detectable, insufficient for the diagnosis of systemic mastocytosis. By the use of highly sensitive molecular methods, including the analysis of microdissected mast cells, KIT D816V was found in all 58 bone marrow biopsies investigated for it but only in 74% (20/27) of the skin biopsies. It is important to state that even in cases with insufficient diagnostic criteria for systemic mastocytosis, KIT D816V-positive mast cells were detected in the bone marrow. This study demonstrates, for the first time, that almost all patients with adult-onset mastocytosis in the skin, in fact, have systemic mastocytosis with cutaneous involvement.

Water quality and health in a Sahelian semi-arid urban context: an integrated geographical approach in Nouakchott, Mauritania

Access to sufficient quantities of safe drinking water is a human right. Moreover, access to clean water is of public health relevance, particularly in semi-arid and Sahelian cities due to the risks of water contamination and transmission of water-borne diseases. We conducted a study in Nouakchott, the capital of Mauritania, to deepen the understanding of diarrhoeal incidence in space and time. We used an integrated geographical approach, combining socio-environmental, microbiological and epidemiological data from various sources, including spatially explicit surveys, laboratory analysis of water samples and reported diarrhoeal episodes. A geospatial technique was applied to determine the environmental and microbiological risk factors that govern diarrhoeal transmission. Statistical and cartographic analyses revealed concentration of unimproved sources of drinking water in the most densely populated areas of the city, coupled with a daily water allocation below the recommended standard of 20 l per person. Bacteriological analysis indicated that 93% of the non-piped water sources supplied at water points were contaminated with 10-80 coliform bacteria per 100 ml. Diarrhoea was the second most important disease reported at health centres, accounting for 12.8% of health care service consultations on average. Diarrhoeal episodes were concentrated in municipalities with the largest number of contaminated water sources. Environmental factors (e.g. lack of improved water sources) and bacteriological aspects (e.g. water contamination with coliform bacteria) are the main drivers explaining the spatio-temporal distribution of diarrhoea. We conclude that integrating environmental, microbiological and epidemiological variables with statistical regression models facilitates risk profiling of diarrhoeal diseases. Modes of water supply and water contamination were the main drivers of diarrhoea in this semi-arid urban context of Nouakchott, and hence require a strategy to improve water quality at the various levels of the supply chain.

Integrated reconstruction of Holocene millennial-scale environmental changes in Tierra del Fuego, southernmost South America

This study presents new paleoenvironmental data obtained from sedimentary cores from Lago Fagnano, an elon- gated lake located at 54°S in southernmost South America. Data from palynomorphs (pollen, spores and algae) and associated palynofacies as well as from diatom taxa retrieved from these cores compared with other regional proxies contribute to evaluate the similarities and differences in the climate patterns based on different proxies from southernmost Patagonia. The pollen analysis reveals that a grass steppe environment existed during the early Holocene (11,300–~8000 cal a BP) followed by a major vegetation change characterized by development of forest-steppe ecotone communities between ~8000 and ~6500 cal a BP, under more humid conditions. Between ~ 6500 and ~ 4000 cal a BP, expansion and colonization by Nothofagus forests reflect an increase in effec- tive moisture levels, while openness in the forest communities characterizes the region after ~ 1100 cal a BP. The palynological organic matter combined with the algal content reflects hydrological changes occurring in the lake and its nutrient status, probably in close relation with past climate oscillations. All these past ecological changes are closely related to oscillations in precipitation and temperature as a response to the variations in the latitudinal position and/or strength of the Southern Westerlies wind belt during the Holocene.

Carbon dioxide and climate impulse response functions for the computation of greenhouse gas metrics: a multi-model analysis

The responses of carbon dioxide (CO2) and other climate variables to an emission pulse of CO2 into the atmosphere are often used to compute the Global Warming Potential (GWP) and Global Temperature change Potential (GTP), to characterize the response timescales of Earth System models, and to build reduced-form models. In this carbon cycle-climate model intercomparison project, which spans the full model hierarchy, we quantify responses to emission pulses of different magnitudes injected under different conditions. The CO2 response shows the known rapid decline in the first few decades followed by a millennium-scale tail. For a 100 Gt-C emission pulse added to a constant CO2 concentration of 389 ppm, 25 ± 9% is still found in the atmosphere after 1000 yr; the ocean has absorbed 59 ± 12% and the land the remainder (16 ± 14%). The response in global mean surface air temperature is an increase by 0.20 ± 0.12 °C within the first twenty years; thereafter and until year 1000, temperature decreases only slightly, whereas ocean heat content and sea level continue to rise. Our best estimate for the Absolute Global Warming Potential, given by the time-integrated response in CO2 at year 100 multiplied by its radiative efficiency, is 92.5 × 10−15 yr W m−2 per kg-CO2. This value very likely (5 to 95% confidence) lies within the range of (68 to 117) × 10−15 yr W m−2 per kg-CO2. Estimates for time-integrated response in CO2 published in the IPCC First, Second, and Fourth Assessment and our multi-model best estimate all agree within 15% during the first 100 yr. The integrated CO2 response, normalized by the pulse size, is lower for pre-industrial conditions, compared to present day, and lower for smaller pulses than larger pulses. In contrast, the response in temperature, sea level and ocean heat content is less sensitive to these choices. Although, choices in pulse size, background concentration, and model lead to uncertainties, the most important and subjective choice to determine AGWP of CO2 and GWP is the time horizon.

Characterisation of flash floods in small ungauged mountain basins of Central Spain using an integrated approach

One of the main problems of flood hazard assessment in ungauged or poorly gauged basins is the lack of runoff data. In an attempt to overcome this problem we have combined archival records, dendrogeomorphic time series and instrumental data (daily rainfall and discharge) from four ungauged and poorly gauged mountain basins in Central Spain with the aim of reconstructing and compiling information on 41 flash flood events since the end of the 19th century. Estimation of historical discharge and the incorporation of uncertainty for the at-site and regional flood frequency analysis were performed with an empirical rainfall–runoff assessment as well as stochastic and Bayesian Markov Chain Monte Carlo (MCMC) approaches. Results for each of the ungauged basins include flood frequency, severity, seasonality and triggers (synoptic meteorological situations). The reconstructed data series clearly demonstrates how uncertainty can be reduced by including historical information, but also points to the considerable influence of different approaches on quantile estimation. This uncertainty should be taken into account when these data are used for flood risk management.

Performance analysis of a miniature turbine generator for intracorporeal energy harvesting

Replacement intervals of implantable medical devices are commonly dictated by battery life. Therefore, intracorporeal energy harvesting has the potential to reduce the number of surgical interventions by extending the life cycle of active devices. Given the accumulated experience with intravascular devices such as stents, heart valves, and cardiac assist devices, the idea to harvest a small fraction of the hydraulic energy available in the cardiovascular circulation is revisited. The aim of this article is to explore the technical feasibility of harvesting 1 mW electric power using a miniature hydrodynamic turbine powered by about 1% of the cardiac output flow in a peripheral artery. To this end, numerical modelling of the fluid mechanics and experimental verification of the overall performance of a 1:1 scale friction turbine are performed in vitro. The numerical flow model is validated for a range of turbine configurations and flow conditions (up to 250 mL/min) in terms of hydromechanic efficiency; up to 15% could be achieved with the nonoptimized configurations of the study. Although this article does not entail the clinical feasibility of intravascular turbines in terms of hemocompatibility and impact on the circulatory system, the numerical model does provide first estimates of the mechanical shear forces relevant to blood trauma and platelet activation. It is concluded that the time-integrated shear stress exposure is significantly lower than in cardiac assist devices due to lower flow velocities and predominantly laminar flow.

Life-threatening adverse events following therapeutic opioid administration in adults: Is pharmacogenetic analysis useful?

BACKGROUND Systemic approaches are needed to understand how variations in the genes associated with opioid pharmacokinetics and response can be used to predict patient outcome. The application of pharmacogenetic analysis to two cases of life-threatening opioid-induced respiratory depression is presented. The usefulness of genotyping in the context of these cases is discussed. METHODS A panel of 20 functional candidate polymorphisms in genes involved in the opioid biotransformation pathway (CYP2D6, UGT2B7, ABCB1, OPRM1, COMT) were genotyped in these two patients using commercially available genotyping assays. RESULTS In case 1, the patient experienced adverse outcomes when administered codeine and morphine, but not hydromorphone. Genetic test results suggested that this differential response may be due to an inherent propensity to generate active metabolites from both codeine and morphine. These active metabolites are not generated with hydromorphone. In case 2, the patient experienced severe respiratory depression during postoperative recovery following standard doses of morphine. The patient was found to carry genetic variations that result in decreased morphine efflux transporter activity at the blood-brain barrier and increased sensitivity to opioids. CONCLUSIONS Knowledge of the relative contribution of pharmacogenetic biomarkers and their influence on opioid response are continually evolving. Pharmacogenetic analysis, together with clinical history, has the potential to provide mechanistic insight into severe respiratory depressive events in patients who receive opioids at therapeutic doses.

Stakeholder analysis combined with social network analysis provides fine-grained insights into water infrastructure planning processes

Environmental policy and decision-making are characterized by complex interactions between different actors and sectors. As a rule, a stakeholder analysis is performed to understand those involved, but it has been criticized for lacking quality and consistency. This lack is remedied here by a formal social network analysis that investigates collaborative and multi-level governance settings in a rigorous way. We examine the added value of combining both elements. Our case study examines infrastructure planning in the Swiss water sector. Water supply and wastewater infrastructures are planned far into the future, usually on the basis of projections of past boundary conditions. They affect many actors, including the population, and are expensive. In view of increasing future dynamics and climate change, a more participatory and long-term planning approach is required. Our specific aims are to investigate fragmentation in water infrastructure planning, to understand how actors from different decision levels and sectors are represented, and which interests they follow. We conducted 27 semi-structured interviews with local stakeholders, but also cantonal and national actors. The network analysis confirmed our hypothesis of strong fragmentation: we found little collaboration between the water supply and wastewater sector (confirming horizontal fragmentation), and few ties between local, cantonal, and national actors (confirming vertical fragmentation). Infrastructure planning is clearly dominated by engineers and local authorities. Little importance is placed on longer-term strategic objectives and integrated catchment planning, but this was perceived as more important in a second analysis going beyond typical questions of stakeholder analysis. We conclude that linking a stakeholder analysis, comprising rarely asked questions, with a rigorous social network analysis is very fruitful and generates complementary results. This combination gave us deeper insight into the socio-political-engineering world of water infrastructure planning that is of vital importance to our well-being.