Grootschalige concentratie- en depositiekaarten Nederland : Rapportage 2014

Nieuwe concentratie- en depositiekaarten voor NSL en PAS Het RIVM heeft kaarten opgesteld waarop staat aangegeven wat in 2013 in Nederland de concentraties in de lucht waren van onder andere stikstofdioxide en fijn stof. Ook is op een kaart aangegeven in welke mate stikstof op de bodem neerslaat. Daarnaast zijn toekomstberekeningen voor deze stoffen gemaakt voor de periode 2015- 2030. De kaarten worden gebruikt voor de monitoring van het Nationaal Samenwerkingsprogramma Luchtkwaliteit (NSL) en de Programmatische Aanpak Stikstof (PAS). Hiermee worden onder andere de effecten van ruimtelijke plannen getoetst Stikstofdioxideconcentraties voor 2015 veelal lager De gemeten concentraties stikstofdioxide waren in 2013 lager dan in 2012. De concentraties die voor 2015 zijn berekend, zijn op de meeste locaties lager dan vorig jaar was geraamd. Toch blijven er een aantal probleemgebieden bestaan waarin de verwachte concentraties hoger zijn dan vorig jaar geraamd, vooral in de regio's Rotterdam en Den Haag. Wat de verwachte overschrijdingen van de normen in 2015 betreft, zal dat in Amsterdam en Utrecht op minder locaties aan de orde zijn dan eerder was ingeschat, en in Rotterdam op meer locaties Drie oorzaken voor deze aangepaste verwachting zijn het belangrijkst. Als eerste is bij de ramingen een correctie aangebracht voor systematische verschillen tussen gemeten en berekende stikstofdioxideconcentraties. Ten tweede stoten de nieuwste modellen vrachtauto's minder stikstofoxiden uit dan eerder was ingeschat. Ten derde zijn effecten meegenomen van het SER-energieakkoord uit 2013. Hierin zijn afspraken gemaakt om energie te besparen bij huishoudens, industrie en landbouw en het aandeel alternatieve energiebronnen als wind- en zonne-energie te vergroten Roetconcentraties dalen naar verwachting verder Steeds meer dieselauto's hebben een filter, waarmee roet effectief wordt afgevangen. Op basis van het huidige beleid wordt geschat dat de roetconcentratie de komende jaren verder daalt, en in 2020 bijna zal zijn gehalveerd ten opzicht van het huidige niveau Daling stikstofdepositie onveranderd De neerslag van stikstof op de bodem in Nederland daalt naar verwachting de komende jaren in ongeveer dezelfde mate als vorig jaar was geraamd. Een dalende stikstofdepositie is een voorwaarde voor natuurbehoudNew maps of concentrations and depositions for NSL and PAS In this report, the National Institute for Public Health and the Environment (RIVM) presents the latest maps of air concentrations in the Netherlands for several substances, including nitrogen dioxide and particulate matter for 2013. It also presents the maps for the deposition of nitrogen compounds to the soil for that year. Calculations for the future (2015-2030) have also been made. The maps are being used in the national air quality collaboration programme (NSL) and for the programmatic approach to nitrogen (PAS) for monitoring new spatial planning projects Nitrogen dioxide concentrations mostly lower for 2015 The measured concentrations of nitrogen dioxide were in 2013 lower than in 2012. Concentrations calculated for 2015 are at most locations below last year's estimates. Yet, there remain a number of areas where the expected concentrations are higher than last year's estimates, especially in the vicinity of Rotterdam and The Hague. The limit value for the nitrogen dioxide concentration will probably be exceeded in fewer locations in Amsterdam and Utrecht than was estimated earlier and in more locations in Rotterdam in 2015 There are three main reasons for these adjusted expectations of future concentrations. First, a correction is applied to projections of nitrogen dioxide concentrations for systematic differences between measured and calculated concentrations. Second, the latest truck models emit less nitrogen oxides than was previously expected. Third, the effects of the SER energy agreement from 2013 have been taken into account. Arrangements have been made in the agreement to save energy in households, industry and agriculture, and to increase the share of alternative energy sources, such as, wind and solar energy Soot concentrations are expected to decrease further More and more diesel cars have a filter, which is effective in capturing soot. It is expected that, based on the current policies, the soot concentrations will continue to decrease in the coming years and will be reduced by almost 50 percent by 2020 compared to current levels Decrease in nitrogen deposition unchanged The deposition of nitrogen to the soil in the Netherlands is expected to decrease in the coming years by approximately the same amount as was estimated last year. A reduction in nitrogen deposition is a prerequisite for nature conservationMinisterie van I&

Unraveling the heterogeneity of sarcoma survivors’ health-related quality of life regarding primary sarcoma location: Results from the Survsarc study

Simple SummarySarcomas are a rare group of heterogenous tumors that can develop anywhere in the body. Currently, studies on health-related quality of life (HRQoL) focus on sarcomas of the arm and leg or have too small sample sizes to examine the heterogeneity between different sarcoma locations, leading to limited insight into HRQoL of survivors with specific sarcoma locations. The aim of this study was to assess differences in HRQoL and examine treatment-specific HRQoL issues per sarcoma location. We found, in a population of 1099 sarcoma survivors, different patterns of HRQoL according to primary sarcoma location and a high number of additional, unique treatment-specific HRQoL issues per location, which were not captured with the general HRQoL questionnaire used in cancer patients. This indicates that the currently used HRQoL measures are too generic to capture all sarcoma-related issues, emphasizing the necessity for a comprehensive sarcoma-specific HRQoL measurement strategy.Sarcoma patients experience physical and psychological symptoms, depending on age of onset, subtype, treatment, stage, and location of the sarcoma, which can adversely affect patients' health-related quality of life (HRQoL). This study aimed to unravel the heterogeneity of sarcoma survivors' HRQoL regarding primary sarcoma location. A cross-sectional study was conducted among Dutch sarcoma survivors (N = 1099) aged &gt;= 18, diagnosed 2-10 years ago. Primary sarcoma locations were head and neck, chest, abdominal including retroperitoneal, pelvis including urogenital organs, axial skeleton, extremities (upper and lower), breast, skin and other locations. The European Organization for Research and Treatment of Cancer-Quality of Life Questionnaire (EORTC QLQ)-C30 was used to measure HRQoL accompanied by treatment-specific HRQoL questions. Sociodemographic and clinical characteristics were collected from the Netherlands Cancer Registry. Axial skeleton sarcomas had the lowest functioning levels and highest symptoms compared to other locations. Skin sarcomas had the highest functioning levels and lowest symptoms on most scales. Bone sarcomas scored worse on several HRQoL domains compared to soft tissue sarcomas. High prevalence of treatment-specific HRQoL issues were found per location. In conclusion, sarcomas can present everywhere, which is reflected by different HRQoL outcomes according to primary sarcoma location. The currently used HRQoL measure lacks treatment-specific questions and is too generic to capture all sarcoma-related issues, emphasizing the necessity for a comprehensive sarcoma-specific HRQoL measurement strategy.</p

A detailed clinical and molecular survey of subjects with nonsyndromic USH2A retinopathy reveals an allelic hierarchy of disease-causing variants.

Defects in USH2A cause both isolated retinal disease and Usher syndrome (ie, retinal disease and deafness). To gain insights into isolated/nonsyndromic USH2A retinopathy, we screened USH2A in 186 probands with recessive retinal disease and no hearing complaint in childhood (discovery cohort) and in 84 probands with recessive retinal disease (replication cohort). Detailed phenotyping, including retinal imaging and audiological assessment, was performed in individuals with two likely disease-causing USH2A variants. Further genetic testing, including screening for a deep-intronic disease-causing variant and large deletions/duplications, was performed in those with one likely disease-causing change. Overall, 23 of 186 probands (discovery cohort) were found to harbour two likely disease-causing variants in USH2A. Some of these variants were predominantly associated with nonsyndromic retinal degeneration ('retinal disease-specific'); these included the common c.2276 G>T, p.(Cys759Phe) mutation and five additional variants: c.2802 T>G, p.(Cys934Trp); c.10073 G>A, p.(Cys3358Tyr); c.11156 G>A, p.(Arg3719His); c.12295-3 T>A; and c.12575 G>A, p.(Arg4192His). An allelic hierarchy was observed in the discovery cohort and confirmed in the replication cohort. In nonsyndromic USH2A disease, retinopathy was consistent with retinitis pigmentosa and the audiological phenotype was variable. USH2A retinopathy is a common cause of nonsyndromic recessive retinal degeneration and has a different mutational spectrum to that observed in Usher syndrome. The following model is proposed: the presence of at least one 'retinal disease-specific' USH2A allele in a patient with USH2A-related disease results in the preservation of normal hearing. Careful genotype-phenotype studies such as this will become increasingly important, especially now that high-throughput sequencing is widely used in the clinical setting.European Journal of Human Genetics advance online publication, 4 February 2015; doi:10.1038/ejhg.2014.283

Intravitreal antisense oligonucleotide sepofarsen in Leber congenital amaurosis type 10: a phase 1b/2 trial

CEP290-associated Leber congenital amaurosis type 10 (LCA10) is a retinal disease resulting in childhood blindness. Sepofarsen is an RNA antisense oligonucleotide targeting the c.2991+1655A>G variant in the CEP290 gene to treat LCA10. In this open-label, phase 1b/2 (NCT03140969), 12-month, multicenter, multiple-dose, dose-escalation trial, six adult patients and five pediatric patients received ≤4 doses of intravitreal sepofarsen into the worse-seeing eye. The primary objective was to evaluate sepofarsen safety and tolerability via the frequency and severity of ocular adverse events (AEs); secondary objectives were to evaluate pharmacokinetics and efficacy via changes in functional outcomes. Six patients received sepofarsen 160 µg/80 µg, and five patients received sepofarsen 320 µg/160 µg. Ten of 11 (90.9%) patients developed ocular AEs in the treated eye (5/6 with 160 µg/80 µg; 5/5 with 320 µg/160 µg) versus one of 11 (9.1%) in the untreated eye; most were mild in severity and dose dependent. Eight patients developed cataracts, of which six (75.0%) were categorized as serious (2/3 with 160 µg/80 µg; 4/5 with 320 µg/160 µg), as lens replacement was required. As the 160-µg/80-µg group showed a better benefit–risk profile, higher doses were discontinued or not initiated. Statistically significant improvements in visual acuity and retinal sensitivity were reported (post hoc analysis). The manageable safety profile and improvements reported in this trial support the continuation of sepofarsen development

Aboveground Herbivory Shapes the Biomass Distribution and Flux of Soil Invertebrates

Contains fulltext : 72659.pdf ( ) (Open Access)Background Living soil invertebrates provide a universal currency for quality that integrates physical and chemical variables with biogeography as the invertebrates reflect their habitat and most ecological changes occurring therein. The specific goal was the identification of “reference” states for soil sustainability and ecosystem functioning in grazed vs. ungrazed sites. Methodology/Principal Findings Bacterial cells were counted by fluorescent staining and combined direct microscopy and automatic image analysis; invertebrates (nematodes, mites, insects, oligochaetes) were sampled and their body size measured individually to allow allometric scaling. Numerical allometry analyses food webs by a direct comparison of weight averages of components and thus might characterize the detrital soil food webs of our 135 sites regardless of taxonomy. Sharp differences in the frequency distributions are shown. Overall higher biomasses of invertebrates occur in grasslands, and all larger soil organisms differed remarkably. Conclusions/Significance Strong statistical evidence supports a hypothesis explaining from an allometric perspective how the faunal biomass distribution and the energetic flux are affected by livestock, nutrient availability and land use. Our aim is to propose faunal biomass flux and biomass distribution as quantitative descriptors of soil community composition and function, and to illustrate the application of these allometric indicators to soil systems.7 p

Gender differences in the use of cardiovascular interventions in HIV-positive persons; the D:A:D Study

Peer reviewe

Progress in gene therapy for neurological disorders

Diseases of the nervous system have devastating effects and are widely distributed among the population, being especially prevalent in the elderly. These diseases are often caused by inherited genetic mutations that result in abnormal nervous system development, neurodegeneration, or impaired neuronal function. Other causes of neurological diseases include genetic and epigenetic changes induced by environmental insults, injury, disease-related events or inflammatory processes. Standard medical and surgical practice has not proved effective in curing or treating these diseases, and appropriate pharmaceuticals do not exist or are insufficient to slow disease progression. Gene therapy is emerging as a powerful approach with potential to treat and even cure some of the most common diseases of the nervous system. Gene therapy for neurological diseases has been made possible through progress in understanding the underlying disease mechanisms, particularly those involving sensory neurons, and also by improvement of gene vector design, therapeutic gene selection, and methods of delivery. Progress in the field has renewed our optimism for gene therapy as a treatment modality that can be used by neurologists, ophthalmologists and neurosurgeons. In this Review, we describe the promising gene therapy strategies that have the potential to treat patients with neurological diseases and discuss prospects for future development of gene therapy