Continuous-flow laboratory simulation of stream water quality changes downstream of an untreated wastewater discharge.

In regions of the world with poor provision of wastewater treatment, raw sewage is often discharged directly into surface waters. This paper describes an experimental evaluation of the fate of two organic chemicals under these conditions using an artificial channel cascade fed with a mix of settled sewage and river water at its upstream end and operated under continuous steady-state conditions. The experiments underpin an environmental risk assessment methodology based on the idea of an “impact zone” (IZ) – the zone downstream of wastewater emission in which water quality is severely impaired by high concentrations of unionised ammonia, nitrite and biochemical oxygen demand (BOD). Radiolabelled dodecane-6-benzene sulphonate (DOBS) and aniline hydrochloride were used as the model chemical and reference compound respectively. Rapid changes in 14C counts were observed with flow-time for both these materials. These changes were most likely to be due to complete mineralisation. A dissipation half-life of approximately 7.1 h was observed for the 14C label with DOBS. The end of the IZ was defined as the point at which the concentration of both unionised ammonia and nitrite fell below their respective predicted no-effect concentrations for salmonids. At these points in the cascade, approximately 83 and 90% of the initial concentration of 14C had been removed from the water column, respectively. A simple model of mineral nitrogen transformations based on Michaelis–Menten kinetics was fitted to observed concentrations of NH4, NO2 and NO3. The cascade is intended to provide a confirmatory methodology for assessing the ecological risks of chemicals under direct discharge co

Diagnostic approach to paediatric movement disorders:a clinical practice guide

Paediatric movement disorders (PMDs) comprise a large group of disorders (tics, myoclonus, tremor, dystonia, chorea, Parkinsonism, ataxia), often with mixed phenotypes. Determination of the underlying aetiology can be difficult given the broad differential diagnosis and the complexity of the genotype-phenotype relationships. This can make the diagnostic process time-consuming and difficult. In this overview, we present a diagnostic approach for PMDs, with emphasis on genetic causes. This approach can serve as a framework to lead the clinician through the diagnostic process in eight consecutive steps, including recognition of the different movement disorders, identification of a clinical syndrome, consideration of acquired causes, genetic testing including next-generation sequencing, post-sequencing phenotyping, and interpretation of test results. The aim of this approach is to increase the recognition and diagnostic yield in PMDs.</p

Trendanalyse zware metalen in diervoeder(grondstoffen)

In dit rapport wordt er met behulp van historische waarden inzicht gegeven in het verloop van de gehalten aan kwik, cadmium en lood in diervoeders en diervoedergrondstoffen in Nederland. Het is een vervolg op het rapport 2007.001 “Trendanalyse van gehalten aan aflatoxine B1 en dioxinen/dioxine-achtige PCB’s in diervoeders” dat in 2007 is verschenen. Dit onderzoek is ook verricht op verzoek van de VWA. De resultaten van deze analyses bieden mogelijkheden voor de VWA om tot een meer risico-gestuurde bemonstering in het Nationaal Plan Diervoeders te kome

Beleidsboodschappen Natuurverkenning 2010-2040

Het natuurbeleid bevindt zich in een overgangsfase. Zowel rijk als provincies, maatschappelijke organisaties en het bedrijfsleven zijn op zoek naar verbetering van het bestaande natuurbeleid en hun positie daarbinnen. Het gaat daarbij niet alleen om natuurbeleid in de strikte zin, maar onder meer ook om het landschaps-, ruimtelijk, energie- en voedselbeleid. Dit artikel draagt bouwstenen voor die zoektocht aan op basis van vier kijkrichtingen die zijn ontwikkeld in de Natuurverkenning 2010-2040

Clinical Pearls - how my patients taught me:The fainting lark symptom

BACKGROUND: Compulsive movements, complex tics and stereotypies are frequent, especially among patients with autism or psychomotor retardation. These movements can be difficult to characterize and can mimic other conditions like epileptic seizures or paroxysmal dystonia, particularly when abnormal breathing and cerebral hypoxia are induced. CASE PRESENTATION: We describe an 18-year-old patient with Asperger syndrome who presented with attacks of tonic posturing of the trunk and neck. The attacks consisted of self-induced stereotypic stretching of the neck combined with a compulsive Valsalva-like maneuver. This induced cerebral hypoperfusion and subsequently dysautonomia and some involuntary movements of the arms. CONCLUSION: This patient suffered from a complex tic with compulsive respiratory stereotypies. His symptoms contain aspects of a phenomenon described in early literature as 'the fainting lark'

Body composition is associated with tacrolimus pharmacokinetics in kidney transplant recipients

PURPOSE: A population pharmacokinetic (popPK) model may be used to improve tacrolimus dosing and minimize under- and overexposure in kidney transplant recipients. It is unknown how body composition parameters relate to tacrolimus pharmacokinetics and which parameter correlates best with tacrolimus exposure. The aims of this study were to investigate which body composition parameter has the best association with the pharmacokinetics of tacrolimus and to describe this relationship in a popPK model. METHODS: Body composition was assessed using bio-impedance spectroscopy (BIS). Pharmacokinetic analysis was performed using nonlinear mixed effects modeling (NONMEM). Lean tissue mass, adipose tissue mass, over-hydration, and phase angle were measured with BIS and then evaluated as covariates. The final popPK model was evaluated using goodness-of-fit plots, visual predictive checks, and a bootstrap analysis. RESULTS: In 46 kidney transplant recipients, 284 tacrolimus concentrations were measured. The base model without body composition parameters included age, plasma albumin, plasma creatinine, CYP3A4 and CYP3A5 genotypes, and hematocrit as covariates. After full forward inclusion and backward elimination, only the effect of the phase angle on clearance (dOFV =  − 13.406; p < 0.01) was included in the final model. Phase angle was positively correlated with tacrolimus clearance. The inter-individual variability decreased from 41.7% in the base model to 34.2% in the final model. The model was successfully validated. CONCLUSION: The phase angle is the bio-impedance spectroscopic parameter that correlates best with tacrolimus pharmacokinetics. Incorporation of the phase angle in a popPK model can improve the prediction of an individual’s tacrolimus dose requirement after transplantation. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00228-022-03323-0

Low-frequency oscillation suppression in dystonia:Implications for adaptive deep brain stimulation

Background: Low-frequency oscillations (LFO) detected in the internal globus pallidus of dystonia patients have been identified as a physiomarker for adaptive Deep Brain Stimulation (aDBS), since LFO correlate with dystonic symptoms and are rapidly suppressed by continuous DBS (cDBS). However, it is as yet unclear how LFO should be incorporated as feedback for aDBS. Objectives: to test the acute effects of aDBS, using the amplitude of short-lived LFO-bursts to titrate stimulation, to explore the immediate effects of cDBS on LFO-modulation and dystonic symptoms, and to investigate whether a difference in the resting-state LFO is present between DBS-naïve patients and patients with chronic DBS. Methods: seven patients were assessed during either DBS-implantation (n = 2) or battery replacement surgery (n = 5), and pseudorandomized in three conditions: no stimulation, cDBS, and aDBS. Additionally, resting-state LFP-recordings from patients undergoing battery replacement were compared to those obtained during DBS-implantation; LFP-recordings from a previous cohort of six dystonia patients undergoing DBS-implantation were incorporated into this analysis (total n = 8 newly implanted patients). Results: we corroborated that a mild LFO-suppression rapidly occurs during cDBS. However, no acute changes in clinical symptoms were observed after cDBS or aDBS. Remarkably, we observed that resting-state LFO were significantly lower in patients who had been effectively treated with chronic cDBS compared to those of newly implanted patients, even when stimulation was suspended. Conclusions: our results indicate that LFO-suppression in dystonia, similar to symptom response to cDBS, might be gradual, and remain after stimulation is suspended. Therefore, tracking gradual changes in LFO may be required for aDBS implementation

Crossing barriers:a multidisciplinary approach to children and adults with young-onset movement disorders

Abstract Background Diagnosis of less common young-onset movement disorders is often challenging, requiring a broad spectrum of skills of clinicians regarding phenotyping, normal and abnormal development and the wide range of possible acquired and genetic etiologies. This complexity often leads to considerable diagnostic delays, paralleled by uncertainty for patients and their families. Therefore, we hypothesized that these patients might benefit from a multidisciplinary approach. We report on the first 100 young-onset movement disorders patients who visited our multidisciplinary outpatient clinic. Methods Clinical data were obtained from the medical records of patients with disease-onset before age 18 years. We investigated whether the multidisciplinary team, consisting of a movement disorder specialist, pediatric neurologist, pediatrician for inborn errors of metabolism and clinical geneticist, revised the movement disorder classification, etiological diagnosis, and/or treatment. Results The 100 referred patients (56 males) had a mean age of 12.5 ± 6.3 years and mean disease duration of 9.2 ± 6.3 years. Movement disorder classification was revised in 58/100 patients. Particularly dystonia and myoclonus were recognized frequently and supported by neurophysiological testing in 24/29 patients. Etiological diagnoses were made in 24/71 (34%) formerly undiagnosed patients, predominantly in the genetic domain. Treatment strategy was adjusted in 60 patients, of whom 43 (72%) reported a subjective positive effect. Conclusions This exploratory study demonstrates that a dedicated tertiary multidisciplinary approach to complex young-onset movement disorders may facilitate phenotyping and improve recognition of rare disorders, with a high diagnostic yield and minimal diagnostic delay. Future studies are needed to investigate the cost-benefit ratio of a multidisciplinary approach in comparison to regular subspecialty care