Using ocean models to predict spatial and temporal variation in marine carbon isotopes

Natural-abundance stable isotope ratios provide a wealth of ecological information relating to food web structure, trophic level, and location. The correct interpretation of stable isotope data requires an understanding of spatial and temporal variation in the isotopic compositions at the base of the food web. In marine pelagic environments, accurate interpretation of stable isotope data is hampered by a lack of reliable, spatio-temporally distributed measurements of baseline isotopic compositions. In this study, we present a relatively simple, process-based carbon isotope model that predicts the spatio-temporal distributions of the carbon isotope composition of phytoplankton (here expressed as δ13CPLK) across the global ocean at one degree and monthly resolution. The model is driven by output from a coupled physics-biogeochemistry model, NEMO-MEDUSA, and operates offline; it could also be coupled to alternative underlying ocean model systems. Model validation is challenged by the same lack of spatio-temporally explicit data that motivates model development, but predictions from our model successfully reproduce major spatial patterns in carbon isotope values observed in zooplankton, and are consistent with simulations from alternative models. Model predictions represent an initial hypothesis of spatial and temporal variation in carbon isotopic baselines in ocean areas where a few data are currently available, and provide the best currently available tool to estimate spatial and temporal variation in baseline isotopic compositions at ocean basin to global scales

Molecular imaging: novel tools in visualizing rheumatoid arthritis

Molecular imaging is a rapidly emerging field in biomedical research, aiming at the visualization, characterization and quantification of molecular and cellular processes non-invasively within intact living organisms. To sense biological processes such as gene expression, angiogenesis, apoptosis or cell trafficking in vivo, imaging reporter agents that interact specifically with molecular targets and appropriate imaging systems are currently under development. In rheumatoid arthritis, these novel tools will be used to evaluate physiological and pathophysiological processes, to facilitate diagnosis and monitor therapeutic regimens, to enable reliable prognosis and to support the development of new therapies. In this review, we summarize the basic principles of molecular imaging, such as the development of molecular imaging agents, the actual capabilities of different imaging modalities and the most recent advances in molecular imaging, demonstrating the potential of this technology. With regard to their applicability in rheumatic diseases, we discuss potential molecular targets, current experimental approaches and the future prospects for molecular imaging in rheumatoid arthriti

The hysteroscopic view of infertility: the mid-secretory endometrium and treatment success towards pregnancy

The purpose of this study was the analysis of a correlation, in infertile patients, between the quality of the endometrium based on its vascularisation and the chances of conception. Hysteroscopy was carried out to determine the quality of the endometrial surface using the Sakumoto-Masamoto classification ("good” vs. "poor” endometrium) in the secretory phase of the menstrual cycle. The results were set in relation to the outcome of the subsequent infertility treatment, i.e. the establishment of a pregnancy within the study period (4years). In 108 (67%) of the 162 followed-up patients, the endometrium was endoscopically classified as "good”, while in 54 (33%) the result was "poor”. The overall pregnancy rate was 37% (60 patients); 47 of all pregnancies (78%) occurred in women with a "good” endometrium while 13 (22%) had a "poor” classification. This positive association between the establishment of a pregnancy in the follow-up and a "good" classification of the endometrial vasculature in the group with a "good" endometrium was significant (P = 0.0165, Fisher's exact test). This study confirms the usefulness of endometrial evaluation by hysteroscopy as a diagnostic instrument for providing a prognosis of the chance for the patients to become pregnan

Spectroscopic and redox properties of amine-unctionalized K_2[Os-^(II)(bpy)(CN)_4] complexes

We report the first examples of amine-functionalized K_2[Os^(II)(bpy)(CN)_4] (bpy = 2,2'-bipyridine) complexes. The tetracyanoosmate complexes were prepared by UV irradiation (λ = 254 nm) of K_4[Os^(II)(CN)_6] and primary amine-functionalized bpy ligands in acidic aqueous media. The aqueous solution pH dependences of the spectroscopic and redox properties of 4,4'- and 5,5'-substituted complexes have been investigated. The pendant amine functional groups and coordinated cyanide ligands are basic sites that can be sequentially protonated, thereby allowing systematic tuning of electrochemical and optical spectroscopic properties

Effect of embryo culture media on birthweight and length in singleton term infants after IVF-ICSI.

QUESTIONS UNDER STUDY: To investigate if two distinct, commercially available embryo culture media have a different effect on birthweight and length of singleton term infants conceived after IVF-ICSI. METHODS: University hospital based cohort study. Between 1 January 2000 and 31 December 2004, patients conceiving through IVF-ICSI at the University Hospital, Lausanne have been allocated to two distinct embryo culture media. Only term singleton pregnancies were analysed (n = 525). Data analysis was performed according to two commercially available culture media: Vitrolife (n = 352) versus Cook (n = 173). Analysis was performed through linear regression adjusted for confounders. Media were considered equivalent if the 95% confidence interval lay between -150 g/+150 g. RESULTS: Length, gestational age and distribution of birthweight percentiles did not differ between groups (for both genders). Analysis of the whole cohort, adjusted for a subset of confounders, resulted in a statistically not different mean birthweight between the two groups (Vitrolife +37 g vs Cook, 95%CI: -46 g to 119 g) suggesting equivalence. Adjustment for an enlarged number of confounders in a subsample of patients (n = 258) also revealed no relevant mean birthweight difference of +71 g (95%CI: -45 g to 187 g) in favour of Vitrolife; however, lacking power to prove equivalence. CONCLUSIONS: Our data suggest that significant differences in birthweight due to these two distinct, commercially available embryo culture media are unlikely

Gene expression in cultured endometrium from women with different outcomes following IVF

Estradiol and progesterone are crucial for the acquisition of receptivity and the change in transcriptional activity of target genes in the implantation window. The aim of this study was to differentiate the regulation of genes in the endometrium of patients with recurrent implantation failure (IF) versus those who became pregnant after in vitro fertilization (IVF) treatment. Moreover, the effect of embryo-derived factors on endometrial transcriptional activity was studied. Nine women with known IVF outcome (IF, M, miscarriage, OP, ongoing pregnancy) and undergoing hysteroscopy with endometrial biopsy were enrolled. Biopsies were taken during the midluteal phase. After culture in the presence of embryo-conditioned IVF media, total RNA was extracted and submitted to reverse transcription, target cDNA synthesis, biotin labelling, fragmentation and hybridization using the Affymetrix Human Genome U133A 2.0 Chip. Differential expression of selected genes was re-analysed by quantitative PCR, in which the results were calculated as threshold cycle differences between the groups and normalized to Glyceraldehyde phosphate dehydrogenase and β-actin. Differences were seen for several genes from endometrial tissue between the IF and the pregnancy groups, and when comparing OP with M, 1875 up- and 1807 down-regulated genes were returned. Real-time PCR analysis confirmed up-regulation for somatostatin, PLAP-2, mucin 4 and CD163, and down-regulation of glycodelin, IL-24, CD69, leukaemia inhibitory factor and prolactin receptor between Op and M. When the different embryo-conditioned media were compared, no significant differential regulation could be demonstrated. Although microarray profiling may currently not be sensitive enough for studying the effects of embryo-derived factors on the endometrium, the observed differences in gene expression between M and OP suggest that it will become an interesting tool for the identification of fertility-relevant markers produced by the endometriu

The inter-rater reliability of the diagnosis of surgical site infection in the context of a clinical trial.

ObjectivesThe diagnosis of surgical site infection following endoprosthetic reconstruction for bone tumours is frequently a subjective diagnosis. Large clinical trials use blinded Central Adjudication Committees (CACs) to minimise the variability and bias associated with assessing a clinical outcome. The aim of this study was to determine the level of inter-rater and intra-rater agreement in the diagnosis of surgical site infection in the context of a clinical trial.Materials and methodsThe Prophylactic Antibiotic Regimens in Tumour Surgery (PARITY) trial CAC adjudicated 29 non-PARITY cases of lower extremity endoprosthetic reconstruction. The CAC members classified each case according to the Centers for Disease Control (CDC) criteria for surgical site infection (superficial, deep, or organ space). Combinatorial analysis was used to calculate the smallest CAC panel size required to maximise agreement. A final meeting was held to establish a consensus.ResultsFull or near consensus was reached in 20 of the 29 cases. The Fleiss kappa value was calculated as 0.44 (95% confidence interval (CI) 0.35 to 0.53), or moderate agreement. The greatest statistical agreement was observed in the outcome of no infection, 0.61 (95% CI 0.49 to 0.72, substantial agreement). Panelists reached a full consensus in 12 of 29 cases and near consensus in five of 29 cases when CDC criteria were used (superficial, deep or organ space). A stable maximum Fleiss kappa of 0.46 (95% CI 0.50 to 0.35) at CAC sizes greater than three members was obtained.ConclusionsThere is substantial agreement among the members of the PARITY CAC regarding the presence or absence of surgical site infection. Agreement on the level of infection, however, is more challenging. Additional clinical information routinely collected by the prospective PARITY trial may improve the discriminatory capacity of the CAC in the parent study for the diagnosis of infection.Cite this article: J. Nuttall, N. Evaniew, P. Thornley, A. Griffin, B. Deheshi, T. O'Shea, J. Wunder, P. Ferguson, R. L. Randall, R. Turcotte, P. Schneider, P. McKay, M. Bhandari, M. Ghert. The inter-rater reliability of the diagnosis of surgical site infection in the context of a clinical trial. Bone Joint Res 2016;5:347-352. DOI: 10.1302/2046-3758.58.BJR-2016-0036.R1

Albumin-coupled methotrexate (MTX-HSA) is a new anti-arthritic drug which acts synergistically to MTX

Objective. To evaluate the anti-arthritic effects of the new inflammation-targeted drug MTX-HSA and to investigate whether peripheral blood mononuclear cells (PBMC) are potential target cells for albumin-mediated drug delivery. Methods. The murine model of collagen-induced arthritis (CIA) was used to measure the anti-arthritic effect of MTX, MTX-HSA or a combination of both (n = 30 to 35 per group). In addition, the uptake of fluorescence-labelled albumin (AFLc-HSA) in PBMC of 14 patients with RA was measured by fluorescence-activated cell sorting (FACS). Results. In equivalent doses of 7.5 mg/kg intravenously (IV) twice a week, MTX-HSA is significantly (P<0.02) superior to MTX in inhibiting the development of CIA and reducing the joint count as well as the number of affected paws. When given in lower doses as combination therapy, both drugs act synergistically (P<0.03). A mean of 96, 72 and 64% of the CD14-, CD16- and CD20-positive cells from peripheral blood of rheumatoid arthritis (RA) patients showed an uptake of albumin after incubation with AFLc-HSA in vitro. This finding was not significantly different in comparison to healthy controls. In contrast, the number of CD3-positive cells taking up albumin is increased significantly in RA patients in comparison to controls (26.3 ± 12.9% s.d. vs 11.6 ± 7.3% s.d.; P = 0.005). Conclusion. The data show that the effectiveness of MTX-HSA in CIA is superior to MTX and that both drugs act synergistically. In addition, albumin appears to be taken up by peripheral blood cells, suggesting that they might be one of the potential target cells of this novel anti-arthritic treatment approac

A Policy Maker’s Guide to Designing Payments for Ecosystem Services

Over the past five years, there has been increasing interest around the globe in payment schemes for the provision of ecosystem services, such as water purification, carbon sequestration, flood control, etc. Written for an Asian Development Bank project in China, this report provides a user-friendly guide to designing payments for the provision of ecosystem services. Part I explains the different types of ecosystem services, different ways of assessing their value, and why they are traditionally under-protected by law and policy. This is followed by an analysis of when payments for services are a preferable approach to other policy instruments. Part II explains the design issues underlying payments for services. These include identification of the service as well as potential buyers and sellers, the level of service needed, payment timing, payment type, and risk allocation. Part II contains a detailed analysis of the different types of payment mechanisms, ranging from general subsidy and certification to mitigation and offset payments. Part III explores the challenges to designing a payment scheme. These include the ability to monitor service provision, secure property rights, perverse incentives, supporting institutions, and poverty alleviation