GIS-based approach for optimization of onshore wind park infrastructure alignment in Finland

Wind power is a rapidly developing, low-emission form of energy production. In Fin-land, the official objective is to increase wind power capacity from the current 1 005 MW up to 3 500–4 000 MW by 2025. By the end of April 2015, the total capacity of all wind power project being planned in Finland had surpassed 11 000 MW. As the amount of projects in Finland is record high, an increasing amount of infrastructure is also being planned and constructed. Traditionally, these planning operations are conducted using manual and labor-intensive work methods that are prone to subjectivity. This study introduces a GIS-based methodology for determining optimal paths to sup-port the planning of onshore wind park infrastructure alignment in Nordanå-Lövböle wind park located on the island of Kemiönsaari in Southwest Finland. The presented methodology utilizes a least-cost path (LCP) algorithm for searching of optimal paths within a high resolution real-world terrain dataset derived from airborne lidar scannings. In addition, planning data is used to provide a realistic planning framework for the anal-ysis. In order to produce realistic results, the physiographic and planning datasets are standardized and weighted according to qualitative suitability assessments by utilizing methods and practices offered by multi-criteria evaluation (MCE). The results are pre-sented as scenarios to correspond various different planning objectives. Finally, the methodology is documented by using tools of Business Process Management (BPM). The results show that the presented methodology can be effectively used to search and identify extensive, 20 to 35 kilometers long networks of paths that correspond to certain optimization objectives in the study area. The utilization of high-resolution terrain data produces a more objective and more detailed path alignment plan. This study demon-strates that the presented methodology can be practically applied to support a wind power infrastructure alignment planning process. The six-phase structure of the method-ology allows straightforward incorporation of different optimization objectives. The methodology responds well to combining quantitative and qualitative data. Additional-ly, the careful documentation presents an example of how the methodology can be eval-uated and developed as a business process. This thesis also shows that more emphasis on the research of algorithm-based, more objective methods for the planning of infrastruc-ture alignment is desirable, as technological development has only recently started to realize the potential of these computational methods.

Asymmetrinen hybridikatalyysi orgaanisessa syntetiikassa

Lääke- ja kemianteollisuuden pyrkimykset kohti haitallisten liuottimien käytön vähentämistä sekä erityisesti tarve tuottaa enantiomeerisesti puhtaita ja biologisesti aktiivisia yhdisteitä luovat tarpeen vesiliuoksissa tehokkaasti toimiville stereoselektiivisille katalyyteille. Hybridikatalyysitutkimuksen pyrkimyksenä on yhdistää siirtymämetallikatalyyttien synteettinen monipuolisuus sekä entsyymien stereoselektiiviset ja reaktionopeutta kasvattavat ominaisuudet. Hybridikatalyyteissä stereokemiallisesti aktiivinen biopolymeerirakenne liitetään katalyyttisesti aktiiviseen siirtymämetalli-ioniin. Tutkielman kirjallisuusosassa käsitellään peptidi- ja DNA-pohjaisten keinotekoisten metalloentsyymien ja metallopeptidien viimeaikaista kehitystä. Huomiota kiinnitetään erityisesti täysin keinotekoisiin metallopeptideihin, sekä katalyytteihin, joissa DNA:n erilaisia mikrorakenteita on käytetty hybridikatalyytin biopolymeerirunkona asymmetrisessä katalyysissa. Kokeellisen osan tavoitteena oli tarkastella bipyridyylipohjaisen DNA-katalyytin toimivuutta hybridikatalyytin biopolymeerirunkona ja stereoselektiivisyyden lähteenä kuparikatalysoidussa Diels-Alderin reaktiossa. Erityisesti kiinnitettiin huomiota siihen, miten kolmannen oligonukleotidijuosteen lisääminen kaksoiskierteeseen vaikuttaa katalyytin stereoselektiivisyyteen. Bipyridyyliligandin lisäksi selvitettiin kolmen erilaisen DNA:han tunnetusti sitoutuvan aminoglykosidin potentiaalia DNA-pohjaisten hybridikatalyyttien kupariligandeina.

A importância das interacções medicamento-alimento no controlo da terapêutica com Varfarina

Os anticoagulantes orais, nomeadamente a varfarina, inibem a acção da vitamina K, essencial para a síntese hepática de vários factores de coagulação (II, VII, IX e X), assim como das proteínas anticoagulantes C e S. O tratamento oral com varfarina necessita de procedimentos estandardizados para o controlo e seguimento. Esta necessidade de monitorização é justificada por várias razões, entre as quais: grande variabilidade individual no que diz respeito à resposta terapêutica; medicamento com margem terapêutica estreita; elevada frequência de interacções com medicamentos e com alimentos. Os alimentos são indispensáveis à sobrevivência humana, permitindo a integridade estrutural e funcional do organismo. Quando essa integridade é alterada torna-se necessário o recurso a terapia medicamentosa, com o intuito de repor essa mesma integridade. As interacções alimento-medicamento, nutriente-medicamento e medicamento-álcool são muitas vezes desprezadas, contudo deveriam ser consideradas aquando da avaliação da eficácia dos fármacos. Embora as consequências destas interacções sejam raramente graves e fatais, não são raras as vezes em que surgem reacções adversas e respostas farmacológicas diferentes das teoricamente esperadas. Com este trabalho pretendeu-se rever as possíveis interacções existentes entre os alimentos e a varfarina, avaliando o possível impacto clínico dos alimentos na eficácia terapêutica da varfarina. Para cumprir os objectivos supra citados, este trabalho foi dividido em duas partes. A primeira parte resulta de uma revisão bibliográfica, na qual são abordadas as interacções entre a varfarina e diferentes tipos de alimentos, classificados de acordo com a sua composição (alimentos com alto, moderado e baixo teor de vitamina K; com alto teor de vitamina E; hiperproteicos; hipoproteicos; alcalinizantes; acidificantes). Foram ainda abordadas as interacções entre a varfarina e alimentos específicos como o leite de soja, óleo de peixe, manga, alho, sumo de mirtilo, sumo de uva, papaia, hipericão e sumo de toranja e as bebidas alcoólicas. A segunda parte do presente trabalho compreende um estudo que pretendeu analisar a influência da alimentação no controlo do INR, em doentes a fazer terapêutica oral com varfarina, através de um questionário efectuado a 22 indivíduos. O tratamento estatístico dos dados recolhidos efectuou-se com recurso a estatística descritiva, e as hipóteses foram testadas com recurso a estatística correlacional, nomeadamente a Correlação de Spearman. Com o presente trabalho concluiu-se que consumos mais altos de alimentos ricos em vitamina K davam origem a mais valores de INR subterapêuticos. Um consumo baixo a moderado de alimentos alcalinizantes e acidificantes foi aquele que permitiu manter um maior número de valores de INR dentro do intervalo terapêutico. Concluiu-se também que ao aumentarmos o consumo de álcool contribuímos para mais valores de INR subterapêuticos.

Senescence rates are determined by ranking on the fast-slow life-history continuum

Comparative analyses of survival senescence by using life tables have identified generalizations including the observation that mammals senesce faster than similar-sized birds. These generalizations have been challenged because of limitations of life-table approaches and the growing appreciation that senescence is more than an increasing probability of death. Without using life tables, we examine senescence rates in annual individual fitness using 20 individual-based data sets of terrestrial vertebrates with contrasting life histories and body size. We find that senescence is widespread in the wild and equally likely to occur in survival and reproduction. Additionally, mammals senesce faster than birds because they have a faster life history for a given body size. By allowing us to disentangle the effects of two major fitness components our methods allow an assessment of the robustness of the prevalent life-table approach. Focusing on one aspect of life history - survival or recruitment - can provide reliable information on overall senescence.

Impact of polydextrose on the faecal microbiota: a double-blind, crossover, placebo-controlled feeding study in healthy human subjects

In this placebo-controlled, double-blind, crossover human feeding study, the effects of polydextrose (PDX; 8 g/d) on the colonic microbial composition, immune parameters, bowel habits and quality of life were investigated. PDX is a complex glucose oligomer used as a sugar replacer. The main goal of the present study was to identify the microbial groups affected by PDX fermentation in the colon. PDX was shown to significantly increase the known butyrate producer Ruminococcus intestinalis and bacteria of the Clostridium clusters I, II and IV. Of the other microbial groups investigated, decreases in the faecal Lactobacillus–Enterococcus group were demonstrated. Denaturing gel gradient electrophoresis analysis showed that bacterial profiles between PDX and placebo treatments were significantly different. PDX was shown to be slowly degraded in the colon, and the fermentation significantly reduced the genotoxicity of the faecal water. PDX also affected bowel habits of the subjects, as less abdominal discomfort was recorded and there was a trend for less hard and more formed stools during PDX consumption. Furthermore, reduced snacking was observed upon PDX consumption. This study demonstrated the impact of PDX on the

Causal relationship between obesity and vitamin D status: bi-directional mendelian randomization analysis of multiple cohorts

BACKGROUND: Obesity is associated with vitamin D deficiency, and both are areas of active public health concern. We explored the causality and direction of the relationship between body mass index (BMI) and 25-hydroxyvitamin D [25(OH)D] using genetic markers as instrumental variables (IVs) in bi-directional Mendelian randomization (MR) analysis. METHODS AND FINDINGS: We used information from 21 adult cohorts (up to 42,024 participants) with 12 BMI-related SNPs (combined in an allelic score) to produce an instrument for BMI and four SNPs associated with 25(OH)D (combined in two allelic scores, separately for genes encoding its synthesis or metabolism) as an instrument for vitamin D. Regression estimates for the IVs (allele scores) were generated within-study and pooled by meta-analysis to generate summary effects. Associations between vitamin D scores and BMI were confirmed in the Genetic Investigation of Anthropometric Traits (GIANT) consortium (n = 123,864). Each 1 kg/m(2) higher BMI was associated with 1.15% lower 25(OH)D (p = 6.52×10⁻²⁷). The BMI allele score was associated both with BMI (p = 6.30×10⁻⁶²) and 25(OH)D (-0.06% [95% CI -0.10 to -0.02], p = 0.004) in the cohorts that underwent meta-analysis. The two vitamin D allele scores were strongly associated with 25(OH)D (p≤8.07×10⁻⁵⁷ for both scores) but not with BMI (synthesis score, p = 0.88; metabolism score, p = 0.08) in the meta-analysis. A 10% higher genetically instrumented BMI was associated with 4.2% lower 25(OH)D concentrations (IV ratio: -4.2 [95% CI -7.1 to -1.3], p = 0.005). No association was seen for genetically instrumented 25(OH)D with BMI, a finding that was confirmed using data from the GIANT consortium (p≥0.57 for both vitamin D scores). CONCLUSIONS: On the basis of a bi-directional genetic approach that limits confounding, our study suggests that a higher BMI leads to lower 25(OH)D, while any effects of lower 25(OH)D increasing BMI are likely to be small. Population level interventions to reduce BMI are expected to decrease the prevalence of vitamin D deficiency.

A genome-wide association meta-analysis identifies new childhood obesity loci

Multiple genetic variants have been associated with adult obesity and a few with severe obesity in childhood; however, less progress has been made in establishing genetic influences on common early-onset obesity. We performed a North American, Australian and European collaborative meta-analysis of 14 studies consisting of 5,530 cases (≥95th percentile of body mass index (BMI)) and 8,318 controls (<50th percentile of BMI) of European ancestry. Taking forward the eight newly discovered signals yielding association with P < 5 × 10(-6) in nine independent data sets (2,818 cases and 4,083 controls), we observed two loci that yielded genome-wide significant combined P values near OLFM4 at 13q14 (rs9568856; P = 1.82 × 10(-9); odds ratio (OR) = 1.22) and within HOXB5 at 17q21 (rs9299; P = 3.54 × 10(-9); OR = 1.14). Both loci continued to show association when two extreme childhood obesity cohorts were included (2,214 cases and 2,674 controls). These two loci also yielded directionally consistent associations in a previous meta-analysis of adult BMI(1).

Association of vitamin D status with arterial blood pressure and hypertension risk: a mendelian randomisation study

BACKGROUND: Low plasma 25-hydroxyvitamin D (25[OH]D) concentration is associated with high arterial blood pressure and hypertension risk, but whether this association is causal is unknown. We used a mendelian randomisation approach to test whether 25(OH)D concentration is causally associated with blood pressure and hypertension risk. METHODS: In this mendelian randomisation study, we generated an allele score (25[OH]D synthesis score) based on variants of genes that affect 25(OH)D synthesis or substrate availability (CYP2R1 and DHCR7), which we used as a proxy for 25(OH)D concentration. We meta-analysed data for up to 108 173 individuals from 35 studies in the D-CarDia collaboration to investigate associations between the allele score and blood pressure measurements. We complemented these analyses with previously published summary statistics from the International Consortium on Blood Pressure (ICBP), the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, and the Global Blood Pressure Genetics (Global BPGen) consortium. FINDINGS: In phenotypic analyses (up to n=49 363), increased 25(OH)D concentration was associated with decreased systolic blood pressure (β per 10% increase, -0·12 mm Hg, 95% CI -0·20 to -0·04; p=0·003) and reduced odds of hypertension (odds ratio [OR] 0·98, 95% CI 0·97-0·99; p=0·0003), but not with decreased diastolic blood pressure (β per 10% increase, -0·02 mm Hg, -0·08 to 0·03; p=0·37). In meta-analyses in which we combined data from D-CarDia and the ICBP (n=146 581, after exclusion of overlapping studies), each 25(OH)D-increasing allele of the synthesis score was associated with a change of -0·10 mm Hg in systolic blood pressure (-0·21 to -0·0001; p=0·0498) and a change of -0·08 mm Hg in diastolic blood pressure (-0·15 to -0·02; p=0·01). When D-CarDia and consortia data for hypertension were meta-analysed together (n=142 255), the synthesis score was associated with a reduced odds of hypertension (OR per allele, 0·98, 0·96-0·99; p=0·001). In instrumental variable analysis, each 10% increase in genetically instrumented 25(OH)D concentration was associated with a change of -0·29 mm Hg in diastolic blood pressure (-0·52 to -0·07; p=0·01), a change of -0·37 mm Hg in systolic blood pressure (-0·73 to 0·003; p=0·052), and an 8·1% decreased odds of hypertension (OR 0·92, 0·87-0·97; p=0·002). INTERPRETATION: Increased plasma concentrations of 25(OH)D might reduce the risk of hypertension. This finding warrants further investigation in an independent, similarly powered study.

Blockade of ActRIIB signaling triggers muscle fatigability and metabolic myopathy

Myostatin regulates skeletal muscle size via the activin receptor IIB (ActRIIB). However, its effect on muscle energy metabolism and energy dependent muscle function remains largely unexplored. This question needs to be solved urgently since various therapies for neuromuscular diseases based on blockade of ActRIIB signaling are being developed. Here we show in mice that four months of pharmacological abrogation of ActRIIB signaling by treatment with soluble ActRIIB-Fc triggers extreme muscle fatigability. This is associated with elevated serum lactate levels and a severe metabolic myopathy in the mdx mouse, an animal model of Duchenne muscular dystrophy. Blockade of ActRIIB signaling down-regulates Porin, a crucial ADP/ATP shuttle between cytosol and mitochondrial matrix leading to a consecutive deficiency of oxidative phosphorylation as measured by in vivo Phophorus Magnetic Resonance Spectroscopy (31P-MRS). Further, ActRIIB blockade reduces muscle capillarization, which further compounds the metabolic stress. We show that ActRIIB regulates key determinants of muscle metabolism, such as Pparβ, Pgc1α, and Pdk4 thereby optimizing different components of muscle energy metabolism. In conclusion, ActRIIB signaling endows skeletal muscle with high oxidative capacity and low fatigability. The severe metabolic side effects following ActRIIB blockade caution against deploying this strategy, at least in isolation, for treatment of neuromuscular disorders.

Seasonal patterns of viral and bacterial infections among children hospitalized with community-acquired pneumonia in a tropical region

Community-acquired pneumonia (CAP) is a common cause of morbidity among children. Evidence on seasonality, especially on the frequency of viral and bacterial causative agents is scarce; such information may be useful in an era of changing climate conditions worldwide. To analyze the frequency of distinct infections, meteorological indicators and seasons in children hospitalized for CAP in Salvador, Brazil, nasopharyngeal aspirate and blood were collected from 184 patients aged < 5 y over a 21-month period. Fourteen microbes were investigated and 144 (78%) cases had the aetiology established. Significant differences were found in air temperature between spring and summer (p = 0.02) or winter (p < 0.001), summer and fall (p = 0.007) or winter (p < 0.001), fall and winter (p = 0.002), and on precipitation between spring and fall (p = 0.01). Correlations were found between: overall viral infections and relative humidity (p = 0.006; r = 0.6) or precipitation (p = 0.03; r = 0.5), parainfluenza and precipitation (p = 0.02; r = -0.5), respiratory syncytial virus (RSV) and air temperature (p = 0.048; r = -0.4) or precipitation (p = 0.045; r = 0.4), adenovirus and precipitation (p = 0.02; r = 0.5), pneumococcus and air temperature (p = 0.04; r = -0.4), and Chlamydia trachomatis and relative humidity (p = 0.02; r = -0.5). The frequency of parainfluenza infection was highest during spring (32.1%; p = 0.005) and that of RSV infection was highest in the fall (36.4%; p < 0.001). Correlations at regular strength were found between several microbes and meteorological indicators. Parainfluenza and RSV presented marked seasonal patterns.

Procalcitonin is useful in identifying bacteraemia among children with pneumonia

Empirical antibiotic use is prescribed in managing children with pneumonia worldwide. We assessed the usefulness of procalcitonin (PCT) and interferon-alpha (IFN-alpha) in differentiating viral from bacterial pneumonia. Among 159 hospitalized children, pneumonia was diagnosed based on clinical complaints plus pulmonary infiltrate. Aetiology was investigated for 9 viruses and 4 atypical and 3 typical bacteria. PCT and IFN-alpha were measured in the serum sample collected on admission. Eight patients had bacteraemic infections, 38 had non-bacteraemic typical infections, and 19 patients had atypical bacterial infections. Viral and unknown aetiology was established in 57 (36%) and 34 (21%) cases, respectively. Three patients with bacterial infection without collected blood culture were excluded. IFN-alpha (IU/ml) was detectable in 20 (13%) cases. The difference among median PCT values of the bacteraemic (4.22; 1.56-7.56), non-bacteraemic typical bacterial (1.47; 0.24-4.07), atypical bacterial (0.18; 0.06-1.03) and only viral (0.65; 0.11-2.22) subgroups was significant (p = 0.02). PCT was >= 2 ng/ml in 52 (33%) cases. The presence of IFN-alpha was associated with PCT <2 ng/ml (90% vs. 64%, p = 0.02). The negative predictive value (95% confidence interval) of PCT >= 2 ng/ml was 95% (89-100%), 89% (78-100%), 93% (85-100%) for differentiation of bacteraemic from viral, atypical bacterial and non-bacteraemic typical bacterial infection, respectively, and 58% (49-68%) for differentiation between bacterial and viral infection. PCT may be useful in identifying bacteraemia among children hospitalized with community-acquired pneumonia. IFN-alpha was uncommonly detected.

Sole infection by human metapneumovirus among children with radiographically diagnosed community-acquired pneumonia in a tropical region

Background Limited information is available on the role of human metapneumovirus (HMPV) as the unique pathogen among children hospitalized for community-acquired pneumonia (CAP) in a tropical region. Objective We aimed to describe HMPV infection among children with CAP investigating bacterial and viral co-infections. Patients and methods A prospective study was carried out in Salvador, North-East Brazil. Overall, 268 children aged <5 years hospitalized for CAP were enrolled. Human metapneumovirus RNA was detected in nasopharyngeal aspirates (NPA) by reverse transcription polymerase chain reaction. Sixteen other bacterial and viral pathogens were investigated by an expanded panel of laboratory methods. Chest X-ray taken on admission was read by an independent paediatric radiologist unaware of clinical information or the established aetiology. Results Human metapneumovirus RNA was detected in NPAs of 11 (4.1%) children, of which 4 (36%) had sole HMPV infection. The disease was significantly shorter among patients with sole HMPV infection in comparison with patients with mixed infection (4 +/- 1 versus 7 +/- 2 days, P = 0.03). Three of those four patients had alveolar infiltrates. Conclusion Sole HMPV infection was detected in children with CAP in Salvador, North-East Brazil. HMPV may play a role in the childhood CAP burden.

The role of respiratory viral infections among children hospitalized for community-acquired pneumonia in a developing country

We report an investigation for 16 bacteria and viruses among 184 children hospitalized with pneumonia in Salvador, Brazil. Etiology was established in 144 (78%) cases. Viral, bacterial, and mixed infections were found in 110 (60%), 77 (42%), and 52 (28%) patients, respectively. Rhinovirus (21%) and Streptococcus pneumoniae (21%) were the most common pathogens. Our results demonstrate the importance of viral and pneumococcal infections among those patients.