Fate of drugs during wastewater treatment

This is the post-print version of the final paper published in TrAC Trends in Analytical Chemistry. The published article is available from the link below. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. Copyright @ 2013 Elsevier B.V.Recent trends in the determination of pharmaceutical drugs in wastewaters focus on the development of rapid multi-residue methods. This review addresses recent analytical trends in drug determination in environmental matrices used to facilitate fate studies. Analytical requirements for further fate evaluation and tertiary process selection and optimization are also discussed.EPSRC, Northumbrian Water, Anglian Water, Severn Trent Water, Yorkshire Water, and United Utilities

Basement membrane components are key players in specialized extracellular matrices

More than three decades ago, basement membranes (BMs) were described as membrane-like structures capable of isolating a cell from and connecting a cell to its environment. Since this time, it has been revealed that BMs are specialized extracellular matrices (sECMs) with unique components that support important functions including differentiation, proliferation, migration, and chemotaxis of cells during development. The composition of these sECM is as unique as the tissues to which they are localized, opening the possibility that such matrices can fulfill distinct functions. Changes in BM composition play significant roles in facilitating the development of various diseases. Furthermore, tissues have to provide sECM for their stem cells during development and for their adult life. Here, we briefly review the latest research on these unique sECM and their components with a special emphasis on embryonic and adult stem cells and their niches

A cluster of multidrug-resistant Mycobacterium tuberculosis among patients arriving in Europe from the Horn of Africa: a molecular epidemiological study

SummaryBackground The risk of tuberculosis outbreaks among people fleeing hardship for refuge in Europe is heightened. We describe the cross-border European response to an outbreak of multidrug-resistant tuberculosis among patients from the Horn of Africa and Sudan. Methods On April 29 and May 30, 2016, the Swiss and German National Mycobacterial Reference Laboratories independently triggered an outbreak investigation after four patients were diagnosed with multidrug-resistant tuberculosis. In this molecular epidemiological study, we prospectively defined outbreak cases with 24-locus mycobacterial interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR) profiles; phenotypic resistance to isoniazid, rifampicin, ethambutol, pyrazinamide, and capreomycin; and corresponding drug resistance mutations. We whole-genome sequenced all Mycobacterium tuberculosis isolates and clustered them using a threshold of five single nucleotide polymorphisms (SNPs). We collated epidemiological data from host countries from the European Centre for Disease Prevention and Control. Findings Between Feb 12, 2016, and April 19, 2017, 29 patients were diagnosed with multidrug-resistant tuberculosis in seven European countries. All originated from the Horn of Africa or Sudan, with all isolates two SNPs or fewer apart. 22 (76%) patients reported their travel routes, with clear spatiotemporal overlap between routes. We identified a further 29 MIRU-VNTR-linked cases from the Horn of Africa that predated the outbreak, but all were more than five SNPs from the outbreak. However all 58 isolates shared a capreomycin resistance-associated tlyA mutation. Interpretation Our data suggest that source cases are linked to an M tuberculosis clone circulating in northern Somalia or Djibouti and that transmission probably occurred en route before arrival in Europe. We hypothesise that the shared mutation of tlyA is a drug resistance mutation and phylogenetic marker, the first of its kind in M tuberculosis sensu stricto. Funding The Swiss Federal Office of Public Health, the University of Zurich, the Wellcome Trust, National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC), the Medical Research Council, BELTA-TBnet, the European Union, the German Center for Infection Research, and Leibniz Science Campus Evolutionary Medicine of the Lung (EvoLUNG)

Phase 2 Neoadjuvant Treatment Intensification Trials in Rectal Cancer: A Systematic Review

Purpose: Multiple phase 2 trials of neoadjuvant treatment intensification in locally advanced rectal cancer have reported promising efficacy signals, but these have not translated into improved cancer outcomes in phase 3 trials. Improvements in phase 2 trial design are needed to reduce these false-positive signals. This systematic review evaluated the design of phase 2 trials of neoadjuvant long-course radiation or chemoradiation therapy treatment intensification in locally advanced rectal cancer. Methods and Materials: The PubMed, EMBASE, MEDLINE, and Cochrane Library databases were searched for published phase 2 trials of neoadjuvant treatment intensification from 2004 to 2016. Trial clinical design and outcomes were assessed, with statistical design and compliance rated using a previously published system. Multivariable meta-regression analysis of pathologic complete response (pCR) was conducted. Results: We identified 92 eligible trials. Patients with American Joint Committee on Cancer stage II and III equivalent disease were eligible in 87 trials (94.6%). In 43 trials (46.7%), local staging on magnetic resonance imaging was mandated. Only 12 trials (13.0%) were randomized, with 8 having a standard-treatment control arm. Just 51 trials (55.4%) described their statistical design, with 21 trials (22.8%) failing to report their sample size derivation. Most trials (n=84, 91.3%) defined a primary endpoint, but 15 different primary endpoints were used. All trials reported pCR rates. Only 38 trials (41.3%) adequately reported trial statistical design and compliance. Meta-analysis revealed a pooled pCR rate of 17.5% (95% confidence interval, 15.7%-19.4%) across treatment arms of neoadjuvant long-course radiation or chemoradiation therapy treatment intensification and substantial heterogeneity among the reported effect sizes (I2 = 55.3%, P<.001). Multivariable meta-regression analysis suggested increased pCR rates with higher radiation therapy doses (adjusted P=.025). Conclusions: Improvement in the design of future phase 2 rectal cancer trials is urgently required. A significant increase in randomized trials is essential to overcome selection bias and determine novel schedules suitable for phase 3 testing. This systematic review provides key recommendations to guide future treatment intensification trial design in rectal cancer

How Policies That Impact Migrants Amplify or Mitigate Stigma Process

How are stigma processes refl ected in policies that impact migrants? How might policies that impact migrants amplify and/or mitigate stigma processes for migrants? This chapter explores the role of policy narratives and frameworks (e.g., assimilation, integration, multiculturalism) in shaping specifi c policy types (e.g., targeted, universal, mainstream) that diff erentially conceptualize and aff ect the roles, rights, and opportunities of migrants in society. The complexity of the policy-making process is examined, including the specifi c policy context and political discourse, trade-off s leading to a mix of policy types, competing policies across jurisdictions (e.g., international, federal, regional), and diff erential implementation of policies. Throughout, policies are considered that can intentionally or unintentionally generate, amplify, and/or mitigate stigma processes. In addition, this chapter examines consequences of these policy-generated stigma experiences for both migrants and nonmigrants, the feedback processes from these stigma experiences to the demand for policy change, and strategies to improve policy making with specifi c consideration for stigma in the context of migration-generated diversity. Empirical gaps in the literature are noted and recommendations are made to address these knowledge gaps

2002-852.oct

ABSTRACT. Objective. To validate the western Tennessee River limits of the originally described rheumatoid arthritis (RA) catchment area and to assess the possibility that absence of tuberculosis allowed the original development of RA. The hypothesis that RA was related to tuberculosis was once a driving force in treatment approach. RA initially was very limited in geographic distribution, in contrast to tuberculosis. Classical tubercular lesions were not observed in the rheumatoid catchment area in ancient times. Similarities between clinical and radiologic manifestations of spondyloarthropathy (SpA) and adjuvant arthritis raised the possibility of a potential conditioning role for occurrence of nonrheumatoid erosive arthritis. Methods. Skeletal samples from ancient RA catchment and non-catchment areas were compared for frequency of tubercular-relatable pathologies

Micropollutant Biotransformation Kinetics Associate with WWTP Process Parameters and Microbial Community Characteristics

The objective of this work was to identify relevant wastewater treatment plant (WWTP) parameters and underlying microbial processes that influence the biotransformation of a diverse set of micropollutants. To do this, we determined biotransformation rate constants for ten organic micropollutants in batch reactors seeded with activated sludge from ten diverse WWTPs. The estimated biotransformation rate constants for each compound ranged between one and four orders of magnitude among the ten WWTPs. The biotransformation rate constants were tested for statistical associations with various WWTP process parameters, <i>amoA</i> transcript abundance, and acetylene-inhibited monooxygenase activity. We determined that (i) ammonia removal associates with oxidative micropollutant biotransformation reaction rates; (ii) archaeal but not bacterial <i>amoA</i> transcripts associate with both ammonia removal and oxidative micropollutant biotransformation reaction rates; and (iii) the activity of acetylene-inhibited monooxygenases (including ammonia monooxygenase) associates with ammonia removal and the biotransformation rate of isoproturon, but does not associate with all oxidative micropollutant biotransformations. In combination, these results lead to the conclusion that ammonia removal and <i>amoA</i> transcript abundance can potentially be predictors of oxidative micropollutant biotransformation reactions, but that the biochemical mechanism is not necessarily linked to ammonia monooxygenase activity