A Quantitative Chemicals' Mixture Risk Assessment Approach For Contaminants Of Emerging Concern Management In Drinking Water

Uncertainties on occurrence and hazard of mixtures of Contaminants of Emerging Concern (CECs) in drinking water (DW) challenge water utilities and decision makers in prioritizing these compounds in, respectively, interventions for the optimization of DW treatment and DW regulations. Continuous development of quantitative risk assessment procedures addressing adverse effects of CECs supports decision-making regarding mitigation actions in minimizing health risks. We propose a novel, quantitative chemical risk assessment (QCRA) approach for mixtures of CECs in DW. The risks are evaluated with the aid of the benchmark quotient probabilistic distribution and including uncertainties in both (i) exposure assessment using occurrence data of different DW sources and simulating DW treatment by granular activated carbon and (ii) hazard assessment steps. The QCRA was applied to compare risks deriving from the presence of alkylphenols mixtures in tap or bottled DW, and to evaluate how actual DW consumption habits affect health risks

The Dutch secret: how to provide safe drinking water without chlorine in the Netherlands

The Netherlands is one of the few countries where chlorine is not used at all, neither for primary disinfection nor to maintain a residual disinfectant in the distribution network. The Dutch approach that allows production and distribution of drinking water without the use of chlorine while not compromising microbial safety at the tap, can be summarized as follows: <br> 1. Use the best source available, in order of preference:<br>     – microbiologically safe groundwater,<br>     – surface water with soil passage such as artificial recharge or bank filtration,<br>     – direct treatment of surface water in a multiple barrier treatment;<br> 2. Use a preferred physical process treatment such as sedimentation, filtration and UV-disinfection. If absolutely necessary, also oxidation by means of ozone or peroxide can be used, but chlorine is avoided;<br> 3. Prevent ingress of contamination during distribution;<br> 4. Prevent microbial growth in the distribution system by production and distribution of biologically stable (biostable) water and the use of biostable materials;<br> 5. Monitor for timely detection of any failure of the system to prevent significant health consequences. <br><br> New developments in safe drinking water in the Netherlands include the adaptation of the Dutch drinking water decree, implementation of quantitative microbial risk assessment (QMRA) by water companies and research into source water quality, drinking water treatment efficacy, safe distribution and biostability of drinking water during distribution and <i>Legionella</i>. This paper summarizes how the Dutch water companies warrant the safety of the drinking water without chlorine

Vaginal cuff dehiscence in laparoscopic hysterectomy: influence of various suturing methods of the vaginal vault

Vaginal cuff dehiscence (VCD) is a severe adverse event and occurs more frequently after total laparoscopic hysterectomy (TLH) compared with abdominal and vaginal hysterectomy. The aim of this study is to compare the incidence of VCD after various suturing methods to close the vaginal vault. We conducted a retrospective cohort study. Patients who underwent TLH between January 2004 and May 2011 were enrolled. We compared the incidence of VCD after closure with transvaginal interrupted sutures versus laparoscopic interrupted sutures versus a laparoscopic single-layer running suture. The latter was either bidirectional barbed or a running vicryl suture with clips placed at each end commonly used in transanal endoscopic microsurgery. Three hundred thirty-one TLHs were included. In 75 (22.7 %), the vaginal vault was closed by transvaginal approach; in 90 (27.2 %), by laparoscopic interrupted sutures; and in 166 (50.2 %), by a laparoscopic running suture. Eight VCDs occurred: one (1.3 %) after transvaginal interrupted closure, three (3.3 %) after laparoscopic interrupted suturing and four (2.4 %) after a laparoscopic running suture was used (p = .707). With regard to the incidence of VCD, based on our data, neither a superiority of single-layer laparoscopic closure of the vaginal cuff with an unknotted running suture nor of the transvaginal and the laparoscopic interrupted suturing techniques could be demonstrated. We hypothesise that besides the suturing technique, other causes, such as the type and amount of coagulation used for colpotomy, may play a role in the increased risk of VCD after TLH

The Psychiatric Case Register Middle Netherlands

<p>Abstract</p> <p>Background</p> <p>The Psychiatric Case Register Middle Netherlands (PCR-MN) registers the mental healthcare consumption of over Dutch 760,000 inhabitants in the centre of the Netherlands. In 2010 the follow-up period was over ten years. In this paper we describe the content, aims and research potential of this case register.</p> <p>Description</p> <p>All mental healthcare institutions in the middle-western part of the province of Utrecht participate in the PCR-MN case register. All in- and out-patients treated in these institutions have been included in the database from the period 2000 to 2010. Diagnosis according to DSM-IV on axis I to IV, visits to in- and out-patient clinics and basic demographics are recorded. A major advantage of this register is the possibility to link patients anonymously from the PCR-MN cohort to other databases to analyze relationships with determinants and outcomes, such as somatic healthcare consumption, mortality, and demographics, which further increases the research potential</p> <p>Conclusions</p> <p>The PCR-MN database has a large potential for scientific research because of its size, duration of follow-up and ability to link with additional databases, and is accessible for academic researchers.</p

The clinical response to infliximab in rheumatoid arthritis is in part dependent on pretreatment tumour necrosis factor α expression in the synovium

Objective: To determine whether the heterogeneous clinical response to tumour necrosis factor (TNF)alpha blocking therapy in rheumatoid arthritis (RA) can be predicted by TNF alpha expression in the synovium before initiation of treatment. Methods: Prior to initiation of infliximab treatment, arthroscopic synovial tissue biopsies were obtained from 143 patients with active RA. At week 16, clinical response was evaluated using the 28-joint Disease Activity Score (DAS28). Immunohistochemistry was used to analyse the cell infiltrate as well as the expression of various cytokines, adhesion molecules and growth factors. Stained sections were evaluated by digital image analysis. Student t tests were used to compare responders (decrease in DAS28 >= 1.2) with non-responders (decrease in DAS28 <1.2) and multivariable regression was used to identify the independent predictors of clinical response. Results: Synovial tissue analysis confirmed our hypothesis that the baseline level of TNF alpha expression is a significant predictor of response to TNF alpha blocking therapy. TNF alpha expression in the intimal lining layer and synovial sublining were significantly higher in responders than in non-responders (p = 0.047 and p = 0.008, respectively). The numbers of macrophages, macrophage subsets and T cells (all able to produce TNF alpha) were also significantly higher in responders than in non-responders. The expression of interleukin (IL)1 beta, IL6, IL18, IL10, E-selectin, intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1, vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) was not associated with response to anti-TNF alpha treatment. Conclusion: The effects of TNF alpha blockade are in part dependent on synovial TNF alpha expression and infiltration by TNF alpha producing inflammatory cells. Clinical response cannot be predicted completely, indicating involvement of other as yet unknown mechanism

Activity of high-dose epirubicin combined with gemcitabine in advanced non-small-cell lung cancer: a multicenter phase I and II study

The aim of the study was to evaluate efficacy and tolerance of epirubicin and gemcitabine as first-line chemotherapy in patients with advanced non-small-cell lung cancer. A phase I study was performed with the combination of escalating doses of epirubicin intravenously on day 1 and a fixed dose of gemcitabine on days 1 and 8 of a 21-day cycle. Eighteen patients were included in the phase I part of the study before the maximum tolerated dose was found. Dose-limiting toxicity was febrile neutropenia. The phase II part of the study was continued with epirubicin 100 mg m−2on day 1 and gemcitabine 1125 mg m−2on days 1 and 8 of a 21-day cycle. Forty-three chemotherapy-naive patients were included. The median age of the patients was 60 years (range 26–75). Most patients (74%) were in stage IV. Granulocytopenia CTC grade 4 occurred in 32.5% and thrombocytopenia grade 4 in 11.6% of cycles. Febrile neutropenia occurred in six patients. Non-haematological toxicity was mainly mucositis CTC grade 2 and 3 in 35% of patients. The tumour response rate was 49% (95% confidence interval (CI) 35–63%). The median survival time for the patients was 42 weeks (95% CI 13–69). © 2000 Cancer Research Campaig

A new paediatric formulation of valaciclovir : development and bioequivalence assessment

Peer reviewedPostprin

Self-regulation of ice flow varies across the ablation area in South-West Greenland

The concept of a positive feedback between ice flow and enhanced melt rates in a warmer climate fuelled the debate regarding the temporal and spatial controls on seasonal ice acceleration. Here we combine melt, basal water pressure and ice velocity data. Using 20 years of data covering the whole ablation area, we show that there is not a strong positive correlation between annual ice velocities and melt rates. Annual velocities even slightly decreased with increasing melt. Results also indicate that melt variations are most important for velocity variations in the upper ablation zone up to the equilibrium line altitude. During the extreme melt in 2012, a large velocity response near the equilibrium line was observed, highlighting the possibility of meltwater to have an impact even high on the ice sheet. This may lead to an increase of the annual ice velocity in the region above S9 and requires further monitoring

UJI AKTIVITAS PROTEASE DAN KARAKTERISASI PH ACTINOMYCETES ISOLAT ATH-03 ASAL TAHURA POCUT MEURAH INTAN KABUPATEN ACEH BESAR

ABSTRAKKata kunci: Aktivitas Protease, Karakterisasi pH, Actinomycetes.Penelitian Uji Aktivitas Protease dan Karakterisasi pH Actinomycetes Isolat ATH-03 Asal Tahura Pocut Meurah Intan Kabupaten Aceh Besar telah dilaksanakan sejak tanggal 3 September sampai dengan 27 Desember 2012. Penelitian ini bertujuan untuk mengukur aktivitas protease dan mengetahui pH optimum aktivitas protease dari isolat Actinomycetes ATH-03. Metode penelitian yang digunakan adalah metode Eksperimen dengan Rancangan Acak Lengkap Non Faktorial dengan 6 kali perlakuan, 2 kali ulangan. Data yang diperoleh dianalisis secara deskriptif yang terkait dengan nilai indeks proteolitik sebagai dasar seleksi isolat Actinomycetes. Isolat Actinomycetes berasal dari koleksi Laboratorium Mikrobiologi Jurusan Biologi FMIPA Universitas Syiah Kuala. Delapan belas isolat Actinomycetes menunjukkan aktivitas pada Media NA yang mengandung susu skim 1%. Isolat ATH-03 dipilih dalam penelitian ini karena memiliki zona bening yang lebar dengan indeks proteolitik (IP) tertinggi 8,537 setelah inkubasi selama 48 jam pada Media NAS. Protease ekstraseluler dikarakterisasi menggunakan media NB yang mengandung susu skim 1% sebagai media produksi. Waktu optimum pemanenan ekstrak kasar protease isolat ATH-03 pada hari ke-7 dengan aktivitas sebesar 0,083 U/ml, kadar protein 0,003 mg/ml dan aktivitas spesifik mencapai 23,72 U/mg. Hasil karakterisasi pH ekstrak kasar enzim isolat ATH-03 menunjukkan aktivitas optimum pada pH 8 yaitu 0,067 U/ml, protease yang dihasilkan oleh isolat ini aktif pada kisaran pH netral.Banda Ace