Biocides and pesticides are designed to control the occurrence of unwanted organisms. From their point of application, these substances can be mobilized and transported to surface waters posing a ...threat to the aquatic environment. Historically, agricultural pesticides have received substantially more attention than biocidal compounds from urban use, despite being used in similar quantities.
This study aims at improving our understanding of the influence of mixed urban and agricultural land use on the overall concentration dynamics of biocides and pesticides during rain events throughout the year. A comprehensive field study was conducted in a catchment within the Swiss plateau (25 km
2). Four surface water sampling sites represented varying combinations of urban and agricultural sources. Additionally, the urban drainage system was studied by sampling the only wastewater treatment plant (WWTP) in the catchment, a combined sewer overflow (CSO), and a storm sewer (SS). High temporal resolution sampling was carried out during rain events from March to November 2007.
The results, based on more than 600 samples analyzed for 23 substances, revealed distinct and complex concentration patterns for different compounds and sources. Five types of concentration patterns can be distinguished: a) compounds that showed elevated background concentrations throughout the year (e.g. diazinon >50 ng L
−1), indicating a constant household source; b) compounds that showed elevated concentrations driven by rain events throughout the year (e.g. diuron 100–300 ng L
−1), indicating a constant urban outdoor source such as facades; c) compounds with seasonal peak concentrations driven by rain events from urban and agricultural areas (e.g. mecoprop 1600 ng L
−1 and atrazine 2500 ng L
−1 respectively); d) compounds that showed unpredictably sharp peaks (e.g. atrazine 10,000 ng L
−1, diazinon 2500 ng L
−1), which were most probably due to improper handling or even disposal of products; and finally, e) compounds that were used in high amounts but were not detected in surface waters (e.g. isothiazolinones).
It can be safely concluded that in catchments of mixed land use, the contributions of biocide and pesticide inputs into surface waters from urban areas are at least as important as those from agricultural areas.
Abstract Objectives We aimed to provide a consensus statement by the International Rapid Eye Movement Sleep Behavior Disorder Study Group (IRBD-SG) on devising controlled active treatment studies in ...rapid eye movement sleep behavior disorder (RBD) and devising studies of neuroprotection against Parkinson disease (PD) and related neurodegeneration in RBD. Methods The consensus statement was generated during the fourth IRBD-SG symposium in Marburg, Germany in 2011. The IRBD-SG identified essential methodologic components for a randomized trial in RBD, including potential screening and diagnostic criteria, inclusion and exclusion criteria, primary and secondary outcomes for symptomatic therapy trials (particularly for melatonin and clonazepam), and potential primary and secondary outcomes for eventual trials with disease-modifying and neuroprotective agents. The latter trials are considered urgent, given the high conversion rate from idiopathic RBD (iRBD) to Parkinsonian disorders (i.e., PD, dementia with Lewy bodies DLB, multiple system atrophy MSA). Results Six inclusion criteria were identified for symptomatic therapy and neuroprotective trials: (1) diagnosis of RBD needs to satisfy the International Classification of Sleep Disorders, second edition, (ICSD-2) criteria; (2) minimum frequency of RBD episodes should preferably be ⩾2 times weekly to allow for assessment of change; (3) if the PD-RBD target population is included, it should be in the early stages of PD defined as Hoehn and Yahr stages 1–3 in Off (untreated); (4) iRBD patients with soft neurologic dysfunction and with operational criteria established by the consensus of study investigators; (5) patients with mild cognitive impairment (MCI); and (6) optimally treated comorbid OSA. Twenty-four exclusion criteria were identified. The primary outcome measure for RBD treatment trials was determined to be the Clinical Global Impression (CGI) efficacy index, consisting of a four-point scale with a four-point side-effect scale. Assessment of video-polysomnographic (vPSG) changes holds promise but is costly and needs further elaboration. Secondary outcome measures include sleep diaries; sleepiness scales; PD sleep scale 2 (PDSS-2); serial motor examinations; cognitive indices; mood and anxiety indices; assessment of frequency of falls, gait impairment, and apathy; fatigue severity scale; and actigraphy and customized bed alarm systems. Consensus also was established for evaluating the clinical and vPSG aspects of RBD. End points for neuroprotective trials in RBD, taking lessons from research in PD, should be focused on the ultimate goal of determining the performance of disease-modifying agents. To date no compound with convincing evidence of disease-modifying or neuroprotective efficacy has been identified in PD. Nevertheless, iRBD patients are considered ideal candidates for neuroprotective studies. Conclusions The IRBD-SG provides an important platform for developing multinational collaborative studies on RBD such as on environmental risk factors for iRBD, as recently reported in a peer-reviewed journal article, and on controlled active treatment studies for symptomatic and neuroprotective therapy that emerged during the 2011 consensus conference in Marburg, Germany, as described in our report.
Three different chemical oxidation processes were investigated in terms of their capability to degrade organic chemical components of real mature landfill-leachate in combination with biological ...treatment run in a Sequencing Batch Biofilter Granular Reactor (SBBGR). H2O2, H2O2 + UV and O3 were integrated with SBBGR and respective effluents were analyzed and compared with the effluent obtained from biological SBBGR treatment alone. In agreement with their respective oxidative power, conventional bulk parameters (residual COD, TOC, Ntot, TSS) determined from the resulting effluents evidenced the following efficacy ranking for degradation: SBBGR/O3 > SBBGR/UV + H2O2 > SBBGR/H2O2 > SBBGR. A more detailed characterization of the organic compounds was subsequently carried out for the four treated streams. For this, effluents were first subjected to a sample preparation step, allowing for a classification in terms of acidic, basic, strongly acidic and strongly basic compounds, and finally to analysis by liquid chromatography/high resolution mass spectrometry (LC/HR-MS). This classification, combined with further data post-processing (non-target screening, Venn Diagram, tri-dimensional plot and Principal Component Analysis), evidenced that the SBBGR/H2O2 process is comparable to the pure biological oxidation. In contrast, SBBGR/O3 and SBBGR/UV + H2O2 not only resulted in a very different residual composition as compared to SBBGR and SBBGR/H2O2, but also differ significantly from each other. In fact, and despite of the SBBGR/O3 being the most efficient process, this treatment remained chemically more similar to SBBGR/H2O2 than to SBBGR/UV + H2O2. This finding may be attributable to different mechanism of degradation involved with the use of UV radiation. Apart from these treatment differences, a series of recalcitrant compounds was determined in all of the four treatments and partly identified as hetero-poly-aromatic species (humic acids-like species).
Display omitted
•A comparative investigation among four oxidation treatments of leachate is reported.•UPLC-HRMS profiles were analyzed with PCA.•Exact masses of recalcitrant compounds after non-target screening were determined.•Classification of compounds was determined according to the four oxidation treatments.•The chemical nature of recalcitrant fractions was widely revealed.
Abstract
STUDY QUESTION
Is the presence or absence of certain vaginal bacteria associated with failure or success to become pregnant after an in vitro fertilization (IVF) or IVF with intracytoplasmic ...sperm injection (IVF-ICSI) treatment?
SUMMARY ANSWER
Microbiome profiling with the use of interspace profiling (IS-pro) technique enables stratification of the chance of becoming pregnant prior to the start of an IVF or IVF-ICSI treatment.
WHAT IS KNOWN ALREADY
Live-birth rates for an IVF or IVF-ICSI treatment vary between 25 and 35% per cycle and it is difficult to predict who will or will not get pregnant after embryo transfer (ET). Recently, it was suggested that the composition of the vaginal microbiota prior to treatment might predict pregnancy outcome. Analysis of the vaginal microbiome prior to treatment might, therefore, offer an opportunity to improve the success rate of IVF or IVF-ICSI.
STUDY DESIGN, SIZE, DURATION
In a prospective cohort study, 303 women (age, 20–42 years) undergoing IVF or IVF-ICSI treatment in the Netherlands were included between June 2015 and March 2016.
PARTICIPANTS/MATERIALS, SETTING, METHODS
Study subjects provided a vaginal sample before the start of the IVF or IVF-ICSI procedure. The vaginal microbiota composition was determined using the IS-pro technique. IS-pro is a eubacterial technique based on the detection and categorization of the length of the 16S–23S rRNA gene interspace region. Microbiome profiles were assigned to community state types based on the dominant bacterial species. The predictive accuracy of the microbiome profiles for IVF and IVF-ICSI outcome of fresh ET was evaluated by a combined prediction model based on a small number of bacterial species. From this cohort, a model was built to predict outcome of fertility treatment. This model was externally validated in a cohort of 50 women who were undergoing IVF or IVF-ICSI treatment between March 2018 and May 2018 in the Dutch division of the MVZ VivaNeo Kinderwunschzentrum Düsseldorf, Germany.
MAIN RESULTS AND THE ROLE OF CHANCE
In total, the vaginal microbiota of 192 women who underwent a fresh ET could be analysed. Women with a low percentage of Lactobacillus in their vaginal sample were less likely to have a successful embryo implantation. The prediction model identified a subgroup of women (17.7%, n = 34) who had a low chance to become pregnant following fresh ET. This failure was correctly predicted in 32 out of 34 women based on the vaginal microbiota composition, resulting in a predictive accuracy of 94% (sensitivity, 26%; specificity, 97%). Additionally, the degree of dominance of Lactobacillus crispatus was an important factor in predicting pregnancy. Women who had a favourable profile as well as <60% L. crispatus had a high chance of pregnancy: more than half of these women (50 out of 95) became pregnant. In the external validation cohort, none of the women who had a negative prediction (low chance of pregnancy) became pregnant.
LIMITATIONS, REASONS FOR CAUTION
Because our study uses a well-defined study population, the results will be limited to the IVF or IVF-ICSI population. Whether these results can be extrapolated to the general population trying to achieve pregnancy without ART cannot be determined from these data.
WIDER IMPLICATIONS OF THE FINDINGS
Our results indicate that vaginal microbiome profiling using the IS-pro technique enables stratification of the chance of becoming pregnant prior to the start of an IVF or IVF-ICSI treatment. Knowledge of their vaginal microbiota may enable couples to make a more balanced decision regarding timing and continuation of their IVF or IVF-ICSI treatment cycles.
STUDY FUNDING/COMPETING INTEREST(S)
This study was financed by NGI Pre-Seed 2014–2016, RedMedTech Discovery Fund 2014–2017, STW Valorisation grant 1 2014–2015, STW Take-off early phase trajectory 2015–2016 and Eurostars VALBIOME grant (reference number: 8884). The employer of W.J.S.S.C. has in collaboration with ARTPred acquired a MIND subsidy to cover part of the costs of this collaboration project. The following grants are received but not used to finance this study: grants from Innovatie Prestatie Contract, MIT Haalbaarheid, other from Dutch R&D tax credit WBSO, RedMedTech Discovery Fund, (J.D.d.J.). Grants from Ferring (J.S.E.L., K.F., C.B.L. and J.M.J.S.S.), Merck Serono (K.F. and C.B.L.), Dutch Heart Foundation (J.S.E.L.), Metagenics Inc. (J.S.E.L.), GoodLife (K.F.), Guerbet (C.B.L.). R.K. is employed by ARTPred B.V. during her PhD at Erasmus Medical Centre (MC). S.A.M. has a 100% University appointment. I.S.P.H.M.S., S.A.M. and A.E.B. are co-owners of IS-Diagnostics Ltd. J.D.d.J. is co-owner of ARTPred B.V., from which he reports personal fees. P.H.M.S. reports non-financial support from ARTPred B.V. P.H.M.S., J.D.d.J. and A.E.B. have obtained patents `Microbial population analysis’ (9506109) and `Microbial population analysis’ (20170159108), both licenced to ARTPred B.V. J.D.d.J. and A.E.B. report patent applications `Method and kit for predicting the outcome of an assisted reproductive technology procedure’ (392EPP0) and patent `Method and kit for altering the outcome of an assisted reproductive technology procedure’ by ARTPred. W.J.S.S.C. received personal consultancy and educational fees from Goodlife Fertility B.V. J.S.E.L. reports personal consultancy fees from ARTPred B.V., Titus Health B.V., Danone, Euroscreen and Roche during the conduct of the study. J.S.E.L. and N.G.M.B. are co-applicants on an Erasmus MC patent (New method and kit for prediction success of in vitro fertilization) licenced to ARTPred B.V. F.J.M.B. reports personal fees from Advisory Board Ferring, Advisory Board Merck Serono, Advisory Board Gedeon Richter and personal fees from Educational activities for Ferring, outside the submitted work. K.F. reports personal fees from Ferring (commercial sponsor) and personal fees from GoodLife (commercial sponsor). C.B.L. received speakers’ fee from Ferring. J.M.J.S.S. reports personal fees and other from Merck Serono and personal fees from Ferring, unrelated to the submitted paper. The other authors declare that they have no competing interests.
TRIAL REGISTRATION NUMBER
ISRCTN83157250. Registered 17 August 2018. Retrospectively registered.
16S rRNA gene sequencing is currently the most common way of determining the composition of microbiota. This technique has enabled many new discoveries to be made regarding the relevance of ...microbiota to the health and disease of the host. However, compared to other diagnostic techniques, 16S rRNA gene sequencing is fairly costly and labor intensive, leaving room for other techniques to improve on these aspects.
The current study aimed to compare the output of 16S rRNA gene sequencing to the output of the quick IS-pro analysis, using vaginal swab samples from 297 women of reproductive age. 16S rRNA gene sequencing and IS-pro analyses yielded very similar vaginal microbiome profiles, with a median Pearson's R
of 0.97, indicating a high level of similarity between both techniques.
We conclude that the results of 16S rRNA gene sequencing and IS-pro are highly comparable and that both can be used to accurately determine the vaginal microbiota composition, with the IS-pro analysis having the benefit of rapidity.
Although various single-concentration measurements of pharmaceuticals are available in the literature, detailed information on the variation over time of the concentration and the load in wastewater ...effluents and rivers and on the fate of these compounds in the aquatic environment are lacking. We measured the concentrations of six pharmaceuticals, carbamazepine, clofibric acid, diclofenac, ibuprofen, ketoprofen, and naproxen, in the effluents of three wastewater treatment plants (WWTPs), in two rivers and in the water column of Lake Greifensee (Switzerland) over a time period of three months. In WWTP effluents, the concentrations reached 0.95 μg/L for carbamazepine, 0.06 μg/L for clofibric acid, 0.99 μg/L for diclofenac, 1.3 μg/L for ibuprofen, 0.18 μg/L for ketoprofen, and 2.6 μg/L for naproxen. The relative importance in terms of loads was carbamazepine, followed by diclofenac, naproxen, ibuprofen, clofibric acid, and ketoprofen. An overall removal rate of all these pharmaceuticals was estimated in surface waters, under real-world conditions (in a lake), using field measurements and modeling. Carbamazepine and clofibric acid were fairly persistent. Phototransformation was identified as the main elimination process of diclofenac in the lake water during the study period. With a relatively high sorption coefficient to particles, ibuprofen might be eliminated by sedimentation. For ketoprofen and naproxen, biodegradation and phototransformation might be elimination processes. For the first time, quantitative data regarding removal rates were determined in surface waters under real-world conditions. All these findings are important data for a risk assessment of these compounds in surface waters.
Olfactory dysfunction is observed in several neurological disorders, including Huntington disease (HD), and correlates with global cognitive performance, depression and degeneration of olfactory ...regions in the brain. Despite clear evidence demonstrating olfactory dysfunction in HD patients, only limited details are available in murine models and the underlying mechanisms are unknown. In order to determine if alterations in the olfactory bulb (OB) are observed in HD we assessed OB weight or area from 3 to 12 months of age in the BACHD transgenic lines (TG5 and TG9). A significant decrease in the OB was observed at 6 and 12 months of age compared to WT. We also detected increased mRNA and protein expression of mutant huntingtin (mHTT) in the OB of TG5 compared to TG9 at specific ages. Despite the higher expression of mHTT in the TG5 OBs, there was increased nuclear accumulation of mHTT in the OB of TG9 compared to WT and TG5 rats. As we observed atrophy of the OB in the BACHD rats we assessed for caspase activation, a known mechanism underlying the cell death observed in HD. We characterized caspase-3, −6, −8 and − 9 mRNA and protein expression levels in the OB of the BACHD transgenic lines at 3, 6 and 12 months of age. Alterations in caspase mRNA and protein expression were detected in the TG5 and TG9 lines. However, the changes observed in the mRNA and protein levels are in some cases discordant, suggesting that the caspase protein modifications detected may be more attributable to post-translational modifications. The caspase activation studies support that cell death may be increased in the rodent HD OB and further our understanding of the olfactory dysfunction and the role of caspases in the pathogenesis of HD.
•Olfactory bulb atrophy observed early in BACHD rats and in specific layers.•Activation of caspases in the olfactory bulb observed early in BACHD rats.•Increased nuclear accumulation of HTT in TG9 vs. TG5 olfactory bulb despite lower mHTT expression.•Discordance in caspase RNA vs. protein expression highlights the importance of PTMs.
Over 10% of deceased donors in 2011 met PHS/CDC criteria for infectious risk donor (IRD), and discard rates are significantly higher for kidneys from these donors. We hypothesized that patient ...phenotypes exist for whom the survival benefit outweighs the infectious risk associated with IRDs. A patient‐oriented Markov decision process model was developed and validated, based on SRTR data and meta‐analyses of window period risks among persons with IRD behaviors. The Markov model allows patients to see, for their phenotype, their estimated survival after accepting versus declining an IRD offer, graphed over a 5‐year horizon. Estimated 5‐year survival differences associated with accepting IRDs ranged from −6.4% to +67.3% for a variety of patient phenotypes. Factors most predictive of the survival difference with IRD transplantation were age, PRA, previous transplant, and the expected time until the next non‐IRD deceased donor offer. This study suggests that survival benefit derived from IRD kidneys varies widely by patient phenotype. Furthermore, within the inherent limitations of model‐based prediction, this study demonstrates that it is possible to identify those predicted to benefit from IRD kidneys, and illustrates how estimated survival curves based on a clinical decision can be presented to better inform patient and provider decision‐making.
Using a novel patient‐perspective Markov model, this study informs the clinical decision of accepting kidneys from infectious risk donors. See editorial by Turgeon et al on page 1121.
Climate Change and the Integrity of Science Sills, Jennifer
Science (American Association for the Advancement of Science),
05/2010, Letnik:
328, Številka:
5979
Journal Article
Background and purpose
Although Parkinson's disease (PD) is characterized by typical motor manifestations, non‐motor symptoms (NMS) are an outstanding part of the disease. At present, several ...specific instruments for assessment of NMS are available. The objective of our study was to determine the performance of the Movement Disorder Society‐Unified Parkinson's Disease Rating Scale (MDS‐UPDRS): Part I – Non‐Motor Aspects of Experiences of Daily Living (nM‐EDL) compared with the Non‐Motor Symptoms Scale (NMSS).
Methods
To this purpose, 434 consecutive patients with PD were included in an international, observational, cross‐sectional study. The association between scores of both scales was determined by the Spearman rank correlation coefficient. Equations for transformation of total score of a scale to the other were constructed from weighted regression models and both, transformed and observed score, contrasted by means of the Lin's Concordance Correlation Coefficient (LCCC) and Bland–Altman plot.
Results
As a whole, the prevalence of the NMS according to each scale was quite similar, and most of the correlations between their corresponding components were high (rS > 0.60). The total score correlation of the MDS‐UPDRS Part I with the NMSS was high (rS = 0.81). Concerning the transformed scores, estimated scores only partially approach the observed ones (sharing about 60–64% of the variance) because residual variance increased with increasing magnitudes of the scores, i.e. the most severe patients (Bland–Altman plot; LCCC < 0.60 for severe patients).
Conclusions
(i) MDS‐UPDRS Part I (nM‐EDL) and NMSS showed a strong convergent validity; (ii) however, transformed scores using the equations from weighted regression models showed that for patients with the most severe NMS they are not concordant.
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