MiDAS 4: A global catalogue of full-length 16S rRNA gene sequences and taxonomy for studies of bacterial communities in wastewater treatment plants

Microbial communities are responsible for biological wastewater treatment, but our knowledge of their diversity and function is still poor. Here, we sequence more than 5 million high-quality, full-length 16S rRNA gene sequences from 740 wastewater treatment plants (WWTPs) across the world and use the sequences to construct the ‘MiDAS 4’ database. MiDAS 4 is an amplicon sequence variant resolved, full-length 16S rRNA gene reference database with a comprehensive taxonomy from domain to species level for all sequences. We use an independent dataset (269 WWTPs) to show that MiDAS 4, compared to commonly used universal reference databases, provides a better coverage for WWTP bacteria and an improved rate of genus and species level classification. Taking advantage of MiDAS 4, we carry out an amplicon-based, global-scale microbial community profiling of activated sludge plants using two common sets of primers targeting regions of the 16S rRNA gene, revealing how environmental conditions and biogeography shape the activated sludge microbiota. We also identify core and conditionally rare or abundant taxa, encompassing 966 genera and 1530 species that represent approximately 80% and 50% of the accumulated read abundance, respectively. Finally, we show that for well-studied functional guilds, such as nitrifiers or polyphosphate-accumulating organisms, the same genera are prevalent worldwide, with only a few abundant species in each genus

Event shapes and azimuthal correlations in Z plus jets events in pp collisions at root √s=7TeV^{√s=7 TeV}

is produced in association with jets in proton–proton collisions. The data collected with the CMS detector at the CERN LHC at $^{√s=7 TeV}$ correspond to an integrated luminosity of 5.0 fb$^{-1}$. The analysis provides a test of predictions from perturbative QCD for a process that represents a substantial background to many physics channels. Results are presented as a function of jet multiplicity, for inclusive Z boson production and for Z bosons with transverse momenta greater than 150 GeV, and compared to predictions from Monte Carlo event generators that include leading-order multiparton matrix-element (with up to four hard partons in the final state) and next-to-leading-order simulations of Z+1-jet events. The experimental results are corrected for detector effects, and can be compared directly with other QCD model

Medication-Related Problems in Liver Transplant Recipients in the Outpatient Setting: A Dutch Cohort Study

Background: After liver transplantation (LTx), adherence to immunosuppressive medication and avoidance of contra-indicated drugs is essential for long-term survival. This study aimed to investigate the prevalence, types and severity of medication-related problems (MRPs) and interventions initiated by a clinical pharmacist (CP) in a cohort of LTx recipients in the outpatient setting. Method: This study was a retrospective, observational study in LTx recipients that visited the outpatient clinic for an annual check-up. A 20-minutes consultation with a CP consisted of medication reconciliation and consultation about medication, adherence, and adverse drug reactions (ADRs). Discrepancies between actual and intended drug use, and MRPs were identified and the severity of MRPs was assessed. Potential interventions were discussed with the patient and the treating physician and evaluated after one year. Results: The CP counseled 64 LTx recipients and found 96 discrepancies in 37 patients. Most discrepancies (60.4%, n = 58) concerned missing medications. In total, 98 MRPs were identified in 53 patients (median 2; range 1-5 per patient), with a total of 113 interventions. Most frequent MRPs were: ADRs (22.4%, n = 22), nonadherence (19.3%, n = 19), unnecessary drugs (16.3%, n = 16) and undertreatment (12.2%, n = 12). Interventions most frequently proposed included optimization of dosage regimen (21.2%, n = 24), individualized recommendation regarding compliance (16.8%, n = 19) and drug discontinuation (12.4%, n = 14). After one year, 15 of the 19 patients (79%) experienced no longer compliance issues and 27 of the 29 patients (93%) used no drugs with indication issues anymore. Conclusion: The CP in an outpatient monitoring program for LTx recipients can signal relevant discrepancies and MRPs. This leads to interventions that are accepted by both the patients and the physicians, with a positive effect after one year

Cometary dust collected by MIDAS on board Rosetta. I. Dust particle catalog and statistics

We aim to catalog all dust particles collected and analyzed by MIDAS, together with their main statistical properties such as size, height, basic shape descriptors, and collection time. Furthermore, we aim to present the scientific results that can be extracted from the catalog (e.g., the size distribution and statistical characteristics of cometary dust particles). The existing MIDAS particle catalog has been greatly improved by a careful re-analysis of the AFM images, leading to the addition of more dust particles and a detailed description of the particle properties. The catalog documents all images of identified dust particles and includes a variety of derived information tabulated one record per particle. Furthermore, the best image of each particle was chosen for subsequent studies. Finally, we created dust coverage maps and clustering maps of the MIDAS collection targets and traced any possible fragmentation of collected particles with a detailed algorithm. The revised MIDAS catalog includes 3523 MIDAS particles in total, where 1857 particles are expected to be usable for further analysis (418 scans of particles before perihelion + 1439 scans of particles after perihelion, both after the removal of duplicates), ranging from about 40 nm to about 8 ${\mu}$m in size. The mean value of the equivalent radius derived from the 2D projection of the particles is 0.91 ${\pm}$ 0.79 ${\mu}$m. A slightly improved equivalent radius based on the particle's volume coincides in the range of uncertainties with a value of 0.56 ${\pm}$ 0.45 ${\mu}$m. We note that those sizes and all following MIDAS particle size distributions are expected to be influenced by the fragmentation of MIDAS particles upon impact on the collection targets. Furthermore, fitting the slope of the MIDAS particle size distribution with a power law of a r ${^b}$ yields an index b of ${\sim}$ -1.67 to -1.88.Comment: 28 pages, 5 figure, 2 online table

Evaluation of medication-related problems in liver transplant recipients with and without an outpatient medication consultation by a clinical pharmacist: a cohort study

Background: Transplant recipients undergo significant changes in their medication regimen during follow-up and are at an increased risk for medication-related problems (MRPs). Aim: This study aimed to compare the prevalence and types of MRPs and interventions in liver transplant recipients with and without an outpatient medication consultation by a clinical pharmacist as well as the satisfaction with information about medicines and medication adherence. Method: We performed a single-center, observational cohort study. A retro- and prospective cohort were used and subdivided in a group that did and did not receive a medication consultation. The prevalence and types of MRPs and interventions were identified and categorized. The satisfaction parameters were evaluated using validated questionnaires. Results: Included were 291 patients. In total, 368 MRPs were identified in 197 patients in the non-medication consultation cohort (median 1; range 1–3 per patient) and 248 MRPs in 94 patients in the medication consultation cohort (median 2; range 1–4 per patient). In the medication consultation cohort, significantly fewer MRPs as unnecessary drugs (17.3% versus 58.7%, p < 0.001), suboptimal therapy (2.4% versus 9.5%, p < 0.001), untreated indication (2.8% versus 6.8%, p = 0.040) and underdosed drugs (0.4% versus 6.3%, p < 0.001) were identified. In the non-medication consultation cohort significantly more patients used unnecessary drugs (72.1% versus 39.4%, p < 0.001) compared to the medication consultation cohort. Patients in both cohorts are satisfied with the information about medicines and reported a high medication adherence. Conclusion: Patients in the medication consultation cohort had significantly fewer MRPs and used significantly less unnecessary drugs. Including a clinical pharmacist to the post-transplant care has an added value

Recommendations for the safe use of direct oral anticoagulants in patients with cirrhosis based on a systematic review of pharmacokinetic, pharmacodynamic and safety data

Purpose: The popularity of direct oral anticoagulants (DOACs) is increasing among patients with cirrhosis. Cirrhosis has a major impact on the pharmacokinetics of drugs, potentially increasing adverse events. Safe use of drugs in cirrhosis requires a diligent risk-benefit analysis. The aim of this study is to develop practice recommendations for safe use of DOACs in cirrhosis based on a systematic review of pharmacokinetic, pharmacodynamic and safety data. Methods: We conducted a systematic literature search to identify studies on pharmacokinetics, pharmacodynamics and safety of DOACs in cirrhosis. Data were collected and presented in summary tables by severity of cirrhosis using the Child–Turcotte–Pugh (CTP) classification. A multidisciplinary expert panel evaluated the results and classified the DOACs according to safety. Results: Fifty four studies were included. All DOACs were classified as ‘no additional risks known’ for CTP A. For CTP B, apixaban, dabigatran and edoxaban were classified as ‘no additional risks known’. Apixaban and edoxaban showed fewer adverse events in patients with cirrhosis, while dabigatran may be less impacted by severity of cirrhosis based on its pharmacokinetic profile. Rivaroxaban was classified as ‘unsafe’ in CTP B and C based on significant pharmacokinetic alterations. Due to lack of data, apixaban, dabigatran and edoxaban were classified as ‘unknown’ for CTP C. Conclusion: DOACs can be used in patients with CTP A cirrhosis, and apixaban, dabigatran and edoxaban can also be used in CTP B. It is recommended to avoid rivaroxaban in CTP B and C. There is insufficient evidence to support safe use of other DOACs in CTP C cirrhosis.</p

Recommendations for the safe use of direct oral anticoagulants in patients with cirrhosis based on a systematic review of pharmacokinetic, pharmacodynamic and safety data

Purpose: The popularity of direct oral anticoagulants (DOACs) is increasing among patients with cirrhosis. Cirrhosis has a major impact on the pharmacokinetics of drugs, potentially increasing adverse events. Safe use of drugs in cirrhosis requires a diligent risk-benefit analysis. The aim of this study is to develop practice recommendations for safe use of DOACs in cirrhosis based on a systematic review of pharmacokinetic, pharmacodynamic and safety data. Methods: We conducted a systematic literature search to identify studies on pharmacokinetics, pharmacodynamics and safety of DOACs in cirrhosis. Data were collected and presented in summary tables by severity of cirrhosis using the Child–Turcotte–Pugh (CTP) classification. A multidisciplinary expert panel evaluated the results and classified the DOACs according to safety. Results: Fifty four studies were included. All DOACs were classified as ‘no additional risks known’ for CTP A. For CTP B, apixaban, dabigatran and edoxaban were classified as ‘no additional risks known’. Apixaban and edoxaban showed fewer adverse events in patients with cirrhosis, while dabigatran may be less impacted by severity of cirrhosis based on its pharmacokinetic profile. Rivaroxaban was classified as ‘unsafe’ in CTP B and C based on significant pharmacokinetic alterations. Due to lack of data, apixaban, dabigatran and edoxaban were classified as ‘unknown’ for CTP C. Conclusion: DOACs can be used in patients with CTP A cirrhosis, and apixaban, dabigatran and edoxaban can also be used in CTP B. It is recommended to avoid rivaroxaban in CTP B and C. There is insufficient evidence to support safe use of other DOACs in CTP C cirrhosis.</p