Bringing results to fruition through publication: An analysis of a peer-reviewed, open access and context-focused journal's editorial practice

When it comes to helping to shape sustainable development, research is most useful when it bridges the science–implementation/management gap and when it brings development specialists and researchers into a dialogue (Hurni et al. 2004); can a peer-reviewed journal contribute to this aim? In the classical system for validation and dissemination of scientific knowledge, journals focus on knowledge exchange within the academic community and do not specifically address a ‘life-world audience’. Within a North-South context, another knowledge divide is added: the peer review process excludes a large proportion of scientists from the South from participating in the production of scientific knowledge (Karlsson et al. 2007). Mountain Research and Development (MRD) is a journal whose mission is based on an editorial strategy to build the bridge between research and development and ensure that authors from the global South have access to knowledge production, ultimately with a view to supporting sustainable development in mountains. In doing so, MRD faces a number of challenges that we would like to discuss with the td-net community, after having presented our experience and strategy as editors of this journal. MRD was launched in 1981 by mountain researchers who wanted mountains to be included in the 1992 Rio process. In the late 1990s, MRD realized that the journal needed to go beyond addressing only the scientific community. It therefore launched a new section addressing a broader audience in 2000, with the aim of disseminating insights into, and recommendations for, the implementation of sustainable development in mountains. In 2006, we conducted a survey among MRD’s authors, reviewers, and readers (Wymann et al. 2007): respondents confirmed that MRD had succeeded in bridging the gap between research and development. But we realized that MRD could become an even more efficient tool for sustainability if development knowledge were validated: in 2009, we began submitting ‘development’ papers (‘transformation knowledge’) to external peer review of a kind different from the scientific-only peer review (for ‘systems knowledge’). At the same time, the journal became open access in order to increase the permeability between science and society, and ensure greater access for readers and authors in the South. We are currently rethinking our review process for development papers, with a view to creating more space for communication between science and society, and enhancing the co-production of knowledge (Roux 2008). Hopefully, these efforts will also contribute to the urgent debate on the ‘publication culture’ needed in transdisciplinary research (Kueffer et al. 2007).

Analysis of functional and anatomic success following endonasal dacryocystorhinostomy

The aim of this study was to assess the concomitant perioperative procedures, the causes of nasolacrimal duct obstruction, the success rate, and the complications associated with endonasal dacryocystorhinostomy (ENDCR).

LC-MS/MS method for simultaneous analysis of uracil, 5,6-dihydrouracil, 5-fluorouracil and 5-fluoro-5,6-dihydrouracil in human plasma for therapeutic drug monitoring and toxicity prediction in cancer patients

The chemotherapeutic drug 5-fluorouracil (5-FU) is widely used for treating solid tumors. Response to 5-FU treatment is variable with 10-30% of patients experiencing serious toxicity partly explained by reduced activity of dihydropyrimidine dehydrogenase (DPD). DPD converts endogenous uracil (U) into 5,6-dihydrouracil (UH(2) ), and analogously, 5-FU into 5-fluoro-5,6-dihydrouracil (5-FUH(2) ). Combined quantification of U and UH(2) with 5-FU and 5-FUH(2) may provide a pre-therapeutic assessment of DPD activity and further guide drug dosing during therapy. Here, we report the development of a liquid chromatography-tandem mass spectrometry assay for simultaneous quantification of U, UH(2) , 5-FU and 5-FUH(2) in human plasma. Samples were prepared by liquid-liquid extraction with 10:1 ethyl acetate-2-propanol (v/v). The evaporated samples were reconstituted in 0.1% formic acid and 10 μL aliquots were injected into the HPLC system. Analyte separation was achieved on an Atlantis dC(18) column with a mobile phase consisting of 1.0 mm ammonium acetate, 0.5 mm formic acid and 3.3% methanol. Positively ionized analytes were detected by multiple reaction monitoring. The analytical response was linear in the range 0.01-10 μm for U, 0.1-10 μm for UH(2) , 0.1-75 μm for 5-FU and 0.75-75 μm for 5-FUH(2) , covering the expected concentration ranges in plasma. The method was validated following the FDA guidelines and applied to clinical samples obtained from ten 5-FU-treated colorectal cancer patients. The present method merges the analysis of 5-FU pharmacokinetics and DPD activity into a single assay representing a valuable tool to improve the efficacy and safety of 5-FU-based chemotherapy.

Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47

Genome-wide association studies and candidate gene studies in ulcerative colitis have identified 18 susceptibility loci. We conducted a meta-analysis of six ulcerative colitis genome-wide association study datasets, comprising 6,687 cases and 19,718 controls, and followed up the top association signals in 9,628 cases and 12,917 controls. We identified 29 additional risk loci (P < 5 × 10(-8)), increasing the number of ulcerative colitis-associated loci to 47. After annotating associated regions using GRAIL, expression quantitative trait loci data and correlations with non-synonymous SNPs, we identified many candidate genes that provide potentially important insights into disease pathogenesis, including IL1R2, IL8RA-IL8RB, IL7R, IL12B, DAP, PRDM1, JAK2, IRF5, GNA12 and LSP1. The total number of confirmed inflammatory bowel disease risk loci is now 99, including a minimum of 28 shared association signals between Crohn's disease and ulcerative colitis.

A Longitudinal Analysis of the Relations Among Stress, Depressive Symptoms, Leisure Satisfaction, and Endothelial Function in Caregivers

Stress and depressive symptoms have been associated with impaired endothelial function as measured by brachial artery flow-mediated dilation (FMD), possibly through repeated and heightened activation of the sympathetic nervous system. Behavioral correlates of depression, such as satisfaction with leisure activities (i.e., leisure satisfaction), may also be associated with endothelial function via their association with depressive symptoms. This study examined the longitudinal associations between stress, depressive symptoms, leisure satisfaction, and endothelial function as measured by FMD.

Sensitive and rapid detection of ganciclovir resistance by PCR based MALDI-TOF analysis

Cytomegalovirus (CMV) infection is associated with significant morbidity and mortality in transplant recipients. Resistance against ganciclovir is increasingly observed. According to current guidelines, direct drug resistance testing is not always performed due to high costs and work effort, even when resistance is suspected.

Characterisation and optimisation of the new Prompt Gamma-ray Activation Analysis (PGAA) facility at FRM II

At the research reactor Forschungs-Neutronenquelle Heinz Maier-Leibnitz (FRM II) a new Prompt Gamma-ray Activation Analysis (PGAA) facility was installed. The instrument was originally built and operating at the spallation source at the Paul Scherrer Institute in Switzerland. After a careful re-design in 2004–2006, the new PGAA instrument was ready for operation at FRM II. In this paper the main characteristics and the current operation conditions of the facility are described. The neutron flux at the sample position can reach up 6.07×1010 [cm−2 s−1], thus the optimisation of some parameters, e.g. the beam background, was necessary in order to achieve a satisfactory analytical sensitivity for routine measurements. Once the optimal conditions were reached, detection limits and sensitivities for some elements, like for example H, B, C, Si, or Pb, were calculated and compared with other PGAA facilities. A standard reference material was also measured in order to show the reliability of the analysis under different conditions at this instrument.

Comparison of implant stability by means of resonance frequency analysis for flapless and conventionally inserted implants

Background: Resonance frequency analysis (RFA) is a noninvasive technique for the quantitative assessment of implant stability. Information on the implant stability quotient (ISQ) of transmucosally inserted implants is limited. Purpose: The aim of this investigation was to compare the ISQ of conventionally inserted implants by raising a muco-periostal flap with implants inserted using a flapless procedure. Materials and Methods: Forty elderly patients with complete edentulous maxilla were consecutively admitted for treatment with implant-supported prostheses. A computer tomography was obtained for the computer-assisted implant planning. One hundred ten implants were placed conventionally in 23 patients (flap-group) and 85 implants in 17 patients by means of the flapless method (flapless-group) using a stereolithographic template. RFA measurements were performed after implant placement (baseline) and after a healing time of 12 weeks (reentry). Results: All implants exhibited clinically and radiographically successful osseointegration. Bone level did not change significantly neither for genders nor type of surgical protocol. Mean ISQ values of the flapless-group were significantly higher at baseline (p < .001) and at reentry (p < .001) compared with the flap-group. The ISQ values were significantly lower at reentry compared with baseline for the flap-group (p = .028) but not for the flapless-group. This group showed a moderate, but insignificant increase. RFA measurements of males resulted in ISQ values that were thoroughly higher as compared with females at both time-points in both groups. Correlation between RFA and bone level was not found. Conclusions: The flapless procedure showed favorable conditions with regard to implant stability and crestal bone level. Some changes of the ISQ values that represent primary (mechanical) and secondary (bone remodeling) implant stability were observed in slight favor of the flapless method and male patients. In properly planned and well-selected cases, the minimal invasive transmucosal technique using a drill-guide is a safe procedure.

Design, conduct, and analysis of a multicenter, pharmacogenomic, biomarker study in matched patients with severe sepsis treated with or without drotrecogin Alfa (activated)

A genomic biomarker identifying patients likely to benefit from drotrecogin alfa (activated) (DAA) may be clinically useful as a companion diagnostic. This trial was designed to validate biomarkers (improved response polymorphisms (IRPs)). Each IRP (A and B) contains two single nucleotide polymorphisms that were associated with a differential DAA treatment effect.

Acute health problems in African refugees: ten years' experience in a Swiss emergency department

Over the last two decades, the total number of applications from Africans for asylum in the countries of the European Union has increased from 578,000 to more than 2.9 million. About 20 % (7,196/36,100) of the asylum seekers in Switzerland originate from Africa. The disease profile of African asylum seekers is remarkably different from that of the native population in the country of application. We have therefore conducted an analysis of African asylum seekers presenting themselves to our emergency department.

Using stress testing to guide primary prevention of coronary heart disease among intermediate-risk patients: a cost-effectiveness analysis

Noninvasive stress testing might guide the use of aspirin and statins for primary prevention of coronary heart disease, but it is unclear if such a strategy would be cost effective.

The role of adjuvant hormonal treatment after surgery for localized high-risk prostate cancer: results of a matched multiinstitutional analysis

Introduction. To assess the role of adjuvant androgen deprivation therapy (ADT) in high-risk prostate cancer patients (PCa) after surgery. Materials and Methods. The analysis case matched 172 high-risk PCa patients with positive section margins or non-organ confined disease and negative lymph nodes to receive adjuvant ADT (group 1, n = 86) or no adjuvant ADT (group 2, n = 86). Results. Only 11.6% of the patients died, 2.3% PCa related. Estimated 5-10-year clinical progression-free survival was 96.9% (94.3%) for group 1 and 73.7% (67.0%) for group 2, respectively. Subgroup analysis identified men with T2/T3a tumors at low-risk and T3b margins positive disease at higher risk for progression. Conclusion. Patients with T2/T3a tumors are at low-risk for metastatic disease and cancer-related death and do not need adjuvant ADT. We identified men with T3b margin positive disease at highest risk for clinical progression. These patients benefit from immediate adjuvant ADT.

Phylogenetic analysis of the gag region encoding the matrix protein of small ruminant lentiviruses: comparative analysis and molecular epidemiological applications

Little sequence information exists on the matrix-protein (MA) encoding region of small ruminant lentiviruses (SRLV). Fifty-two novel sequences were established and permitted a first phylogenetic analysis of this region of the SRLV genome. The variability of the MA encoding region is higher compared to the gag region encoding the capsid protein and surprisingly close to that reported for the env gene. In contrast to primate lentiviruses, the deduced amino acid sequences of the N- and C-terminal domains of MA are variable. This permitted to pinpoint a basic domain in the N-terminal domain that is conserved in all lentiviruses and likely to play an important functional role. Additionally, a seven amino acid insertion was detected in all MVV strains, which may be used to differentiate CAEV and MVV isolates. A molecular epidemiology analysis based on these sequences indicates that the Italian lentivirus strains are closely related to each other and to the CAEV-CO strain, a prototypic strain isolated three decades ago in the US. This suggests a common origin of the SRLV circulating in the monitored flocks, possibly related to the introduction of infected goats in a negative population. Finally, this study shows that the MA region is suitable for phylogenetic studies and may be applied to monitor SRLV eradication programs.

Equine insect bite hypersensitivity: immunoblot analysis of IgE and IgG subclass responses to Culicoides nubeculosus salivary gland extract

Insect bite hypersensitivity (IBH) is an allergic dermatitis of horses caused by IgE-mediated reactions to bites of Culicoides and sometimes Simulium spp. The allergens causing IBH are probably salivary gland proteins from these insects, but they have not yet been identified. The aim of our study was to identify the number and molecular weight of salivary gland extract (SGE) proteins derived from Culicoides nubeculosus which are able to bind IgE antibodies (ab) from the sera of IBH-affected horses. Additionally, we sought to investigate the IgG subclass (IgGa, IgGb and IgGT) reactivity to these proteins. Individual IgE and IgG subclass responses to proteins of C. nubeculosus SGE were evaluated by immunoblot in 42 IBH-affected and 26 healthy horses belonging to different groups (Icelandic horses born in Iceland, Icelandic horses and horses from different breeds born in mainland Europe). Additionally, the specific antibody response was studied before exposure to bites of Culicoides spp. and over a period of 3 years in a cohort of 10 Icelandic horses born in Iceland and imported to Switzerland. Ten IgE-binding protein bands with approximate molecular weights of 75, 66, 52, 48, 47, 32, 22/21, 19, 15, 13/12 kDa were found in the SGE. Five of these bands bound IgE from 50% or more of the horse sera. Thirty-nine of the 42 IBH-affected horses but only 2 of the 26 healthy horses showed IgE-binding to the SGE (p<0.000001). Similarly, more IBH-affected than healthy horses had IgGa ab binding to the Culicoides SGE (19/22 and 9/22, respectively, p<0.01). Sera of IBH-affected horses contained IgE, IgGa and IgGT but not IgGb ab against significantly more protein bands than the sera of the healthy horses. The cohort of 10 Icelandic horses confirmed these results and showed that Culicoides SGE specific IgE correlates with onset of IBH. IBH-affected horses that were born in Iceland had IgGa and IgGT ab (p< or =0.01) as well as IgE ab (p=0.06) against a significantly higher number of SGE proteins than IBH-affected horses born in mainland Europe. The present study shows that Culicoides SGE contains at least 10 potential allergens for IBH and that IBH-affected horses show a large variety of IgE-binding patterns in immunoblots. These findings are important for the future development of a specific immunotherapy with recombinant salivary gland allergens.

Enantioselective analysis of ketamine and its metabolites in equine plasma and urine by CE with multiple isomer sulfated beta-CD

CE with multiple isomer sulfated beta-CD as the chiral selector was assessed for the simultaneous analysis of the enantiomers of ketamine and metabolites in extracts of equine plasma and urine. Different lots of the commercial chiral selector provided significant changes in enantiomeric ketamine separability, a fact that can be related to the manufacturing variability. A mixture of two lots was found to provide high-resolution separations and interference-free detection of the enantiomers of ketamine, norketamine, dehydronorketamine, and an incompletely identified hydroxylated metabolite of norketamine in liquid/liquid extracts of the two body fluids. Ketamine, norketamine, and dehydronorketamine could be unambiguously identified via HPLC fractionation of urinary extracts and using LC-MS and LC-MS/MS with 1 mmu mass discrimination. The CE assay was used to characterize the stereoselectivity of the compounds' enantiomers in the samples of five ponies anesthetized with isoflurane in oxygen and treated with intravenous continuous infusion of racemic ketamine. The concentrations of the ketamine enantiomers in plasma are equal, whereas the urinary amount of R-ketamine is larger than that of S-ketamine. Plasma and urine contain higher S- than R-norketamine levels and the mean S-/R-enantiomer ratios of dehydronorketamine in plasma and urine are lower than unity and similar.