Effectiveness of proactive video therapy for problematic alcohol use on treatment initiation, compliance, and alcohol intake: a randomised controlled trial in Denmark.

BACKGROUND: Few people with problematic alcohol use reach treatment and dropout is frequent. Therapy for problematic alcohol use delivered via video conference (e-alcohol therapy) might overcome treatment barriers. In this randomised study, we tested whether proactive e-alcohol therapy outperformed face-to-face alcohol therapy (standard care) regarding treatment initiation, compliance, and weekly alcohol intake at 3-month and 12-month follow-up. METHODS: In this two-arm randomised controlled trial, we recruited individuals who had problematic alcohol use, defined as a score of 8 or more on the Alcohol Use Disorders Identification Test; were 18 years or older; and had access to a personal computer, smartphone, or tablet with internet access in Denmark through online advertisements. Participants were assigned to receive alcohol therapy delivered either face-to-face or via video conference. The number, frequency, and duration of therapy sessions were individualised in both groups. Data analysis was conducted using masked data. Primary analyses were based on an intention-to-treat sample. The study is registered with ClinicalTrials.gov (NCT03116282). FINDINGS: Between Jan 22, 2018, and June 29, 2020, 816 individuals signed up for the trial and 502 (63%) were assessed for eligibility. We randomly assigned 379 to proactive e-alcohol therapy (n=187) or standard care (n=192), of which, 170 (48%) participants were female and 186 (52%) were male. In the intervention group, more participants initiated treatment (155 [88%] of 177 vs 96 [54%] of 179; odds ratio [OR] 6·3; 95% CI 2·8 to 13·8; p<0·0001 at 3 months; 151 [85%] of 177 vs 115 [64%] of 179; OR 3·2; 95% CI 1·6 to 6·2; p=0·0007 at 12 months) and complied with treatment (130 [73%] of 177 vs 74 [41%] of 179; OR 4·0; 95% CI 2·2 to 7·2; p<0·0001 at 3 months; 140 [79%] of 177 vs 95 [53%] of 179; OR 3·4; 95% CI 1·8 to 6·3; p=0·0002 at 12 months). Weekly alcohol intake was significantly lower in the intervention group only after 3 months (13·0 standard drinks per week vs 21·3 standard drinks per week; adjusted difference -6·7; 95% CI -12·3 to -1·0; p=0·019). INTERPRETATION: Proactive e-alcohol therapy was associated with increased treatment initiation and compliance and is promising as an easily accessible and effective alcohol treatment for individuals with problematic alcohol use. FUNDING: TrygFonden.

Characterization of Deformational Isomerization Potential and Interconversion Dynamics with Ultrafast X-ray Solution Scattering.

Dimeric complexes composed of d8 square planar metal centers and rigid bridging ligands provide model systems to understand the interplay between attractive dispersion forces and steric strain in order to assist the development of reliable methods to model metal dimer complexes more broadly. [Ir2 (dimen)4]2+ (dimen = para-diisocyanomenthane) presents a unique case study for such phenomena, as distortions of the optimal structure of a ligand with limited conformational flexibility counteract the attractive dispersive forces from the metal and ligand to yield a complex with two ground state deformational isomers. Here, we use ultrafast X-ray solution scattering (XSS) and optical transient absorption spectroscopy (OTAS) to reveal the nature of the equilibrium distribution and the exchange rate between the deformational isomers. The two ground state isomers have spectrally distinct electronic excitations that enable the selective excitation of one isomer or the other using a femtosecond duration pulse of visible light. We then track the dynamics of the nonequilibrium depletion of the electronic ground state population─often termed the ground state hole─with ultrafast XSS and OTAS, revealing a restoration of the ground state equilibrium in 2.3 ps. This combined experimental and theoretical study provides a critical test of various density functional approximations in the description of bridged d8-d8 metal complexes. The results show that density functional theory calculations can reproduce the primary experimental observations if dispersion interactions are added, and a hybrid functional, which includes exact exchange, is used.

Modern approaches to improving phase contrast electron microscopy.

Although defocus can be used to generate partial phase contrast in transmission electron microscope images, cryo-electron microscopy (cryo-EM) can be further improved by the development of phase plates which increase contrast by applying a phase shift to the unscattered part of the electron beam. Many approaches have been investigated, including the ponderomotive interaction between light and electrons. We review the recent successes achieved with this method in high-resolution, single-particle cryo-EM. We also review the status of using pulsed or near-field enhanced laser light as alternatives, along with approaches that use scanning transmission electron microscopy (STEM) with a segmented detector rather than a phase plate.

Novel details on the dissociation of casein micelle suspensions as a function of pH and temperature.

Membrane filtration is a widespread process for fractionation and recombination of milk components. Although the dissociation of micellar caseins has been studied in detail in skim milk, it is important to better understand the dissociation dynamics occurring between the colloidal and noncolloidal fractions in systems of modified composition. This research aimed at understanding the dissociation of casein proteins in micellar fractions depleted of whey proteins. Casein micelle dispersions were tested at neutral pH and pH 6 (using glucono-δ-lactone as acidulant), after incubation at 4°C or 22°C, and compared with skim milk. The ionic composition of the serum phase was measured using inductively coupled plasma-mass spectrometry, and the protein distribution analyzed using reversed phase-HPLC coupled with mass spectrometry. When incubated at 22°C, there were no differences in casein micelle dissociation between skim milk and whey protein-depleted micelles (∼2.6% dissociated casein). No additional dissociation occurred by lowering the pH from 6.8 to 6 at 22°C, albeit there were more soluble ions at low pH (71% Ca and 65% P). At 4°C, there was an increased amount of ß-casein found in the serum phase (23-33% of total ß-casein). In addition, there was an uneven dissociation behavior of the various genetic ß-casein variants, whereof A2 was more readily released with cooling. In skim milk, approximately 22%, 18%, and 14% of κ-, αS2, and αS1-caseins, respectively, were dissociated from the micellar phase upon cooling and acidification to pH 6.0. This was in contrast to whey protein-depleted casein suspensions, in which only 6%, 5%, and 3% of κ-, αS2, and αS1-caseins, respectively, had dissociated. The results suggested that the whey proteins in the serum phase play a role in the equilibrium between colloidal and soluble caseins in milk. This is of great relevance in processes such as cold membrane fractionation, where more attention should be given to the protein composition in the serum phase, especially when concentration is combined with fractionation of the serum proteins.

Multiple paternally inherited chloroplast capture events associated with Taxus speciation in the Hengduan Mountains.

Mountainous regions provide a multitude of habitats and opportunities for complex speciation scenarios. Hybridization leading to chloroplast capture, which can be revealed by incongruent phylogenetic trees, is one possible outcome. Four allopatric Taxus lineages (three species and an undescribed lineage) from the Hengduan Mountains, southwest China, exhibit conflicting phylogenetic relationships between nuclear and chloroplast phylogenies. Here, we use multi-omic data at the population level to investigate their historical speciation processes. Population genomic analysis based on ddRAD-seq data revealed limited contemporary inter-specific gene flow involving only populations located close to another species. In a historical context, chloroplast and nuclear data (transcriptome) consistently showed conflicting phylogenetic relationships for T. florinii and the Emei type lineage. ILS and chloroplast recombination were excluded as possible causes, and transcriptome and ddRAD-seq data revealed an absence of the mosaic nuclear genomes that characterize hybrid origin scenarios. Therefore, T. florinii appears to have originated when a lineage of T. florinii captured the T. chinensis plastid type, whereas plastid introgression in the opposite direction generated the Emei Type. All four species have distinct ecological niche based on community investigations and ecological niche analyses. We propose that the origins of both species represent very rare examples of chloroplast capture events despite the paternal cpDNA inheritance of gymnosperms. Specifically, allopatrically and/or ecologically diverged parental species experienced a rare secondary contact, subsequent hybridization and reciprocal chloroplast capture, generating two new lineages, each of which acquired a unique ecological niche. These events might have been triggered by orogenic activities of the Hengduan Mountains and an intensification of the Asian monsoon in the late Miocene, and may represent a scenario more common in these mountains than presently known.

Overcoming resolution loss due to thermal magnetic field fluctuations from phase plates in transmission electron microscopy.

We identify thermal magnetic field fluctuations, caused by thermal electron motion ("Johnson noise") in electrically conductive materials, as a potential resolution limit in transmission electron microscopy with a phase plate. Specifically, resolution loss can occur if the electron diffraction pattern is magnified to extend phase contrast to lower spatial frequencies, and if conductive materials are placed too close to the electron beam. While our initial implementation of a laser phase plate (LPP) was significantly affected by these factors, a redesign eliminated the problem and brought the performance close to the expected level. The resolution now appears to be limited by residual Johnson noise arising from the electron beam liner tube in the region of the LPP, together with the chromatic aberration of the relay optics. These two factors can be addressed during future development of the LPP.

Overcoming resolution loss due to thermal magnetic field fluctuations from phase plates in transmission electron microscopy.

We identify thermal magnetic field fluctuations, caused by thermal electron motion ("Johnson noise") in electrically conductive materials, as a potential resolution limit in transmission electron microscopy with a phase plate. Specifically, resolution loss can occur if the electron diffraction pattern is magnified to extend phase contrast to lower spatial frequencies, and if conductive materials are placed too close to the electron beam. While our initial implementation of a laser phase plate (LPP) was significantly affected by these factors, a redesign eliminated the problem and brought the performance close to the expected level. The resolution now appears to be limited by residual Johnson noise arising from the electron beam liner tube in the region of the LPP, together with the chromatic aberration of the relay optics. These two factors can be addressed during future development of the LPP.

Supporting the routine use of evidence during the policy-making process: a WHO Checklist

This WHO checklist is for any organization or person supporting the routine use of evidence in the process of policy-making. Evidence-informed policy-making (EIPM) is essential for achieving the Sustainable Development Goals (SDGs) and universal health coverage (UHC). Its importance is emphasized in WHO's Thirteenth General Programme of Work 2019­2023 (GPW13). This checklist was developed by the WHO Secretariat of Evidence-Informed Policy Network (EVIPNet) to assist its Member countries in institutionalizing EIPM. Government agencies (i.e. the staff of the Ministry of Health), knowledge intermediaries and researchers focused on strengthening EIPM will find in this checklist some key steps and tools to help their work. While the health sector is a key target group for EVIPNet, this tool can be applied by stakeholders from different social sectors. The focus of this tool is to present the domains and processes through which government bodies can institutionalize the use of evidence. It can be used by people and organizations supporting governments, from the inside or the outside, to reflect on its path towards evidence-informed policy-making (EIPM). Given the general paucity of texts that offer guidance in understanding the institutionalization of EIPM, this tool is largely based on two recent systematic reviews/critical interpretive syntheses, one of which was developed specifically for the Checklist. These summarize the available evidence on this subject.

Inhibition of P2X7 receptors by Lu AF27139 diminishes colonic hypersensitivity and CNS prostanoid levels in a rat model of visceral pain.

Visceral pain is a prominent feature of various gastrointestinal diseases. The P2X7 receptor is expressed by multiple cell types including dorsal root ganglion satellite glial cells, macrophages, and spinal microglia, all of which have been implicated in nociceptive sensitization. We have used the selective and CNS penetrant P2X7 receptor antagonist Lu AF27139 to explore this receptor's role in distinct rat models of inflammatory and visceral hypersensitivity. Rats injected with CFA in the hindpaw displayed a marked reduction in hindpaw mechanical threshold, which was dose-dependently reversed by Lu AF27139 (3-30 mg/kg, p.o.). In rats injected with TNBS in the proximal colon, the colorectal distension threshold measured distally was significantly lower than sham treated rats at 7 days post-injection (P < 0.001), indicative of a marked central sensitization. Colonic hypersensitivity was also reversed by Lu AF27139 (10-100 mg/kg) and by the κ-opioid receptor agonist U-50,488H (3 mg/kg, s.c.). Moreover, both Lu AF27139 and U-50,488H prevented a TNBS-induced increase in spinal and brain levels of PGE2 and LTB4, as well as an increase in brain levels of PGF2α and TXB2. Lu AF27139 was well tolerated as revealed by a lack of significant effect on rotarod motor function and coordination at all doses tested up to 300 mg/kg. Thus, P2X7 receptor antagonism is efficacious in a rat model of visceral pain, via a mechanism which potentially involves attenuation of microglial function within spinal and/or supraspinal pain circuits, albeit a peripheral site of action cannot be excluded.

Differential expressions of anthocyanin synthesis genes underlie flower color divergence in a sympatric Rhododendron sanguineum complex.

BACKGROUND: The Rhododendron sanguineum complex is endemic to alpine mountains of northwest Yunnan and southeast Tibet of China. Varieties in this complex exhibit distinct flower colors even at the bud stage. However, the underlying molecular regulations for the flower color variation have not been well characterized. Here, we investigated this via measuring flower reflectance profiles and comparative transcriptome analyses on three coexisting varieties of the R. sanguineum complex, with yellow flush pink, bright crimson, and deep blackish crimson flowers respectively. We compared the expression levels of differentially-expressed-genes (DEGs) of the anthocyanin / flavonoid biosynthesis pathway using RNA-seq and qRT-PCR data. We performed clustering analysis based on transcriptome-derived Single Nucleotide Polymorphisms (SNPs) data, and finally analyzed the promoter architecture of DEGs. RESULTS: Reflectance spectra of the three color morphs varied distinctively in the range between 400 and 700 nm, with distinct differences in saturation, brightness, hue, and saturation/hue ratio, an indirect measurement of anthocyanin content. We identified 15,164 orthogroups that were shared among the three varieties. The SNP clustering analysis indicated that the varieties were not monophyletic. A total of 40 paralogous genes encoding 12 enzymes contributed to the flower color polymorphism. These anthocyanin biosynthesis-related genes were associated with synthesis, modification and transportation properties (RsCHS, RsCHI, RsF3H, RsF3'H, RsFLS, RsANS, RsAT, RsOMT, RsGST), as well as genes involved in catabolism and degradation (RsBGLU, RsPER, RsCAD). Variations in sequence and cis-acting elements of these genes might correlate with the anthocyanin accumulation, thus may contribute to the divergence of flower color in the R. sanguineum complex. CONCLUSIONS: Our results suggested that the varieties are very closely related and flower color variations in the R. sanguineum complex correlate tightly with the differential expression levels of genes involved in the anabolic and catabolic synthesis network of anthocyanin. Our study provides a scenario involving intricate relationships between genetic mechanisms for floral coloration accompanied by gene flow among the varieties that may represent an early case of pollinator-mediated incipient sympatric speciation.

Genome-wide DNA methylation analysis along the progression of gastric marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type.

Extra-nodal marginal zone B-cell lymphoma (MZBL) of mucosa-associated lymphoid tissue is an indolent lymphoma mostly affecting the gastrointestinal tract. The lymphoma initially has small-cell morphology (SC-MZBL) and often arises in the background of Helicobacter pylori-induced gastritis. In some cases, a clonal malignant progression to large-cell morphology (LC-MZBL) is observed. Here, we studied the DNA methylation profile of 30 gastric MZBLs along their progression. Genome-wide DNA methylation profiling, identified 7698 significantly differentially methylated loci during gastric MZBL progression (σ/σmax ≥0·4, q ≤ 0·001). LC-MZBL showed hypermethylation in comparison to SC-MZBL with an enrichment of regions involved in transcriptional regulation. In conclusion, our present data show that the morphological distinction between SC- and LC-MZBL is reflected by characteristic DNA methylation profiles.

Evidence, policy, impact: WHO guide for evidence-informed decision-making

Strengthening the use of research evidence to advance health impact - To improve health and well-being and accelerate the achievement of the Triple Billion targets, we need better evidence for better decisions. There are moral, socioeconomic and political arguments to increase the use of research in decision- and policy-making. By leveraging the best available evidence, we can improve the effectiveness, efficiency and equity of health policies and interventions, enhance the effective use of scarce public resources, and increase the transparency and accountability of policies and interventions. The importance of evidence-informed approaches, both in policy formulation and implementation, has long been recognized by the World Health Organization (WHO) and its Member States. With the General Programme of Work (GPW)13 and the creation of the Science Division, our Organization has reinforced its science- and evidence-based mandate. The COVID-19 pandemic additionally stressed the importance of the expeditious use of the best available scientific evidence to guide governments and practitioners in their emergency response. To achieve even better results in future, we need to further optimize our work across the evidence ecosystem and ensure that decision-makers are equipped to navigate a plethora of partially overlapping evidence and guidance of variable quality. A well-functioning evidence ecosystem with structures, capacity and incentives in place will ensure that evidence is available and accessible to all, and routinely used to inform decision-making. This ecosystem is also essential to increase countries' resilience to public health emergencies and will equip them to lead evidence-informed efforts to mount their own responses when emergencies strike. The "evidence ecosystem for impact" framework proposed in this guidance aims to provide a conceptual structure to promote a more comprehensive, integrated approach across the Organization and with Member States and partners to create synergistic effects at the country level. Our vision for this guide is for it to serve as a matrix to capture WHO's methods and tools linked to promoting better informed decision-making in countries and globally. By doing so, it will allow greater awareness and uptake of existing tools/practices and promote collaboration between areas within the Organization and with partners. (Dr Soumya Swaminathan, WHO Chief Scientist)

Movements and behaviour of blue whales satellite tagged in an Australian upwelling system.

Knowledge about the movement ecology of endangered species is needed to identify biologically important areas and the spatio-temporal scale of potential human impacts on species. Blue whales (Balaenoptera musculus) are endangered due to twentieth century whaling and currently threatened by human activities. In Australia, they feed in the Great Southern Australian Coastal Upwelling System (GSACUS) during the austral summer. We investigate their movements, occupancy, behaviour, and environmental drivers to inform conservation management. Thirteen whales were satellite tagged, biopsy sampled and photo-identified in 2015. All were genetically confirmed to be of the pygmy subspecies (B. m. brevicauda). In the GSACUS, whales spent most of their time over the continental shelf and likely foraging in association with several seascape variables (sea surface temperature variability, depth, wind speed, sea surface height anomaly, and chlorophyll a). When whales left the region, they migrated west and then north along the Australian coast until they reached West Timor and Indonesia, where their movements indicated breeding or foraging behaviour. These results highlight the importance of the GSACUS as a foraging ground for pygmy blue whales inhabiting the eastern Indian Ocean and indicate the whales' migratory route to proposed breeding grounds off Indonesia. Information about the spatio-temporal scale of potential human impacts can now be used to protect this little-known subspecies of blue whale.

Self-Persuasion Increases Healthy Eating Intention Depending on Cultural Background.

Unhealthy eating behavior has become a global health risk and thus needs to be influenced. Previous research has found that self-persuasion is more effective than direct persuasion in changing attitudes and behavioral intentions, but the influence of the cultural backgrounds of those being persuaded remains unclear. We conducted two studies to investigate the effectiveness of self-persuasion and direct persuasion techniques in promoting healthy eating intention among different ethnicities in the Netherlands. Native Dutch, Moroccan-Dutch, and Turkish-Dutch participated both online and offline. Participants saw a poster with either a self-persuasion message ("Why would you choose healthier food?") or a direct persuasion message ("Choose healthier food!"), and were then asked to report their intention to eat healthily in the upcoming month. Significant cultural differences were found between native Dutch and Moroccan-Dutch in Study 1, and between the native Dutch and Turkish-Dutch who participated offline in Study 2. Accordingly, cultural background was found to moderate the relationship between persuasion and healthy eating intention among these groups. These results provided preliminary evidence for the moderation effect of persuasion on healthy eating intention: Self-persuasion appears to be more effective for people with an individualistic background, and direct persuasion appears to be more effective for people with a collectivistic background.

Amylopectin Chain Length Dynamics and Activity Signatures of Key Carbon Metabolic Enzymes Highlight Early Maturation as Culprit for Yield Reduction of Barley Endosperm Starch after Heat Stress.

Abiotic environmental stresses have a negative impact on the yield and quality of crops. Understanding these stresses is an essential enabler for mitigating breeding strategies and it becomes more important as the frequency of extreme weather conditions increases due to climate change. This study analyses the response of barley (Hordeum vulgare L.) to a heat wave during grain filling in three distinct stages: the heat wave itself, the return to a normal temperature regime, and the process of maturation and desiccation. The properties and structure of the starch produced were followed throughout the maturational stages. Furthermore, the key enzymes involved in the carbohydrate supply to the grain were monitored. We observed differences in starch structure with well-separated effects because of heat stress and during senescence. Heat stress produced marked effects on sucrolytic enzymes in source and sink tissues. Early cessation of plant development as an indirect consequence of the heat wave was identified as the major contributor to final yield loss from the stress, highlighting the importance for functional stay-green traits for the development of heat-resistant cereals.

Biosorption and proteomic analysis of an encapsulated endophytic heavy-metal resistant Pestalotiopsis sp

Aims@#A study on biosorption ability using encapsulated endophytic fungi has been carried out to investigate its biosorption potential in removing heavy metals. Biosorption has emerged as an alternative bioremediation process to remove and sequester heavy metal ions from polluted water. An endophytic Pestalotiopsis sp. (isolated from Nypa fruticans) was found to be able to resist copper (Cu), chromium (Cr), lead (Pb) and zinc (Zn) up to 1,000 ppm and thus the aim of this study was to investigate the biosorption ability using encapsulated live and dead Pestalotiopsis sp. biomass (at pH 4-6) to remove heavy metals. Additionally, a proteomic study was conducted to investigate down- and up-regulation expression levels of proteins under the treatment of the heavy metals. @*Methodology and results@#Encapsulated live fungal biomass displayed higher efficiency in removing chromium at pH 5 and 6, while both encapsulated live and dead biomass were able to remove lead at pH 4 and 5 and copper at pH 5. Five (5) proteins of interest were identified via MALDI-ToF analysis. Among the proteins identified, multidrug resistance protein (MRP homolog) was up-regulated in the presence of lead. @*Conclusion, significance and impact of study@#The data obtained in this study provides an initial understanding of the biosorptive and defensive mechanisms of Pestalotiopsis sp. under heavy metal stress.

Risk factors associated with the recent cholera outbreak in Yemen: a case-control study / 한국역학회지

OBJECTIVES@#The cholera outbreak in Yemen has become the largest in the recent history of cholera records, having reached more than 1.4 million cases since it started in late 2016. This study aimed to identify risk factors for cholera in this outbreak.@*METHODS@#A case-control study was conducted in Aden in 2018 to investigate risk factors for cholera in this still-ongoing outbreak. In total, 59 cholera cases and 118 community controls were studied.@*RESULTS@#The following risk factors were associated with being a cholera case in the bivariate analysis: a history of travelling and having had visitors from outside Aden Province; eating outside the house; not washing fruit, vegetables, and khat (a local herbal stimulant) before consumption; using common-source water; and not using chlorine or soap in the household. In the multivariate analysis, not washing khat and the use of common-source water remained significant risk factors for being a cholera case.@*CONCLUSIONS@#Behavioural factors and unsafe water appear to be the major risk factors in the recent cholera outbreak in Yemen. In order to reduce the risk of cholera, hygiene practices for washing khat and vegetables and the use and accessibility of safe drinking water should be promoted at the community level.

First Human Case of Metacestode Infection Caused by Versteria sp. in a Kidney Transplant Recipient.

Cestodes are emerging agents of severe opportunistic infections among immunocompromised patients. We describe the first case of human infection, with the recently-proposed genus Versteria causing an invasive, tumor-like hepatic infection with regional and distant extension in a 53-year-old female kidney transplant recipient from Atlantic Canada.

Isotopic composition of nitrogen species in groundwater under agricultural areas: A review.

This work reviews applications of stable isotope analysis to the studies of transport and transformation of N species in groundwater under agricultural areas. It summarizes evidence regarding factors affecting the isotopic composition of NO3-, NH4+ and N2O in subsurface, and discusses the use of 11B, 18O, 13C, 34S, 87Sr/86Sr isotopes to support the analysis of δ15N values. The isotopic composition of NO3-, NH4+ and N2O varies depending on their sources and dynamics of N cycle processes. The reported δ15N-NO3- values for sources of NO3- are: soil organic N - +3‰-+8‰, mineral fertilizers - -8‰-+7‰; manure/household waste - +5‰ to +35‰. For NH4+ sources, the isotopic signature ranges are: organic matter - +2.4-+4.1‰, rainwater - -13.4-+2.3‰, mineral fertilizers - -7.4-+5.1‰, household waste - +5-+9‰; animal manure - +8-+11‰. For N2O, isotopic composition depends on isotopic signatures of substrate pools and reaction rates. δ15N values of NO3- are influenced by fractionation effects occurring during denitrification (ɛ=5-40‰), nitrification (ɛ=5-35‰) and DNRA (ɛ not reported). The isotopic signature of NH4+ is also affected by nitrification and DNRA as well as mineralization (ɛ=1‰), sorption (ɛ=1-8‰), anammox (ɛ=4.3-7.4‰) and volatilization (ɛ=25‰). As for the N2O, production of N2O leads to its depletion in 15N, whereas consumption - to enrichment in 15N. The magnitude of fractionation effects occurring during the considered processes depends on temperature, pH, DO, C/NO3- ratio, size of the substrate pool, availability of electron donors, water content in subsoil, residence time, land use, hydrogeology. While previous studies have accumulated rich data on isotopic composition of NO3- in groundwater, evidence remains scarce in the cases of NH4+ and N2O. Further research is required to consider variability of δ15N-NH4+ and δ15N-N2O in groundwater across agricultural ecosystems.

Whither systems medicine?

New technologies to generate, store and retrieve medical and research data are inducing a rapid change in clinical and translational research and health care. Systems medicine is the interdisciplinary approach wherein physicians and clinical investigators team up with experts from biology, biostatistics, informatics, mathematics and computational modeling to develop methods to use new and stored data to the benefit of the patient. We here provide a critical assessment of the opportunities and challenges arising out of systems approaches in medicine and from this provide a definition of what systems medicine entails. Based on our analysis of current developments in medicine and healthcare and associated research needs, we emphasize the role of systems medicine as a multilevel and multidisciplinary methodological framework for informed data acquisition and interdisciplinary data analysis to extract previously inaccessible knowledge for the benefit of patients.