Patient and physician satisfaction in an observational study with methyl aminolevulinate daylight-photodynamic therapy in the treatment of multiple actinic keratoses of the face and scalp in 6 European countries

BACKGROUND Guidelines recommend treating actinic keratoses (AKs) as they are recognized as precursors of invasive squamous cell carcinoma. OBJECTIVE The objective of this study was to collect real-world clinical data on the use of methyl aminolevulinate daylight photodynamic therapy (MAL DL-PDT) for the treatment of face and scalp AK in Europe. METHODS A prospective, multicenter, non-interventional study was conducted in six European countries in patients receiving a single treatment of MAL DL-PDT for face and/or scalp AK. Patient-reported outcomes were assessed by patient questionnaires at baseline and at 3 months after treatment, efficacy was assessed at 3 months using a 6-point global improvement scale, and adverse events (AE) were recorded at each visit. RESULTS Overall, 325 patients were enrolled from 52 investigational centres, 314 of whom attended the 3-month visit. Most patients had multiple lesions (58.4% had >10 lesions) with lesions mainly located on the scalp (60.0%) and/or forehead (54.2%). AKs were predominantly grade I (39.4%) or grade II (33.2%), and 10.5% of patients had grade III lesions. The proportions of patients and physicians that were overall satisfied to very satisfied with the MAL DL-PDT treatment were 80.4% and 90.3%, respectively. The vast majority of patients (90.0%) would consider using MAL DL-PDT again if needed. Physician-assessed efficacy at 3 months was at least much improved in 83.5% of patients, with 45.9% of patients requiring no retreatment. Related AEs were reported in 15% of patients. CONCLUSION Use of MAL DL-PDT for multiple face and/or scalp AKs resulted in high levels of patient and physician satisfaction in clinical practice in Europe, reflecting the good efficacy and high tolerability of this convenient procedure

Haemoglobin causes neuronal damage in vivo which is preventable by haptoglobin

After subarachnoid haemorrhage, prolonged exposure to toxic extracellular haemoglobin occurs in the brain. Here, we investigate the role of haemoglobin neurotoxicity in vivo and its prevention. In humans after subarachnoid haemorrhage, haemoglobin in cerebrospinal fluid was associated with neurofilament light chain, a marker of neuronal damage. Most haemoglobin was not complexed with haptoglobin, an endogenous haemoglobin scavenger present at very low concentration in the brain. Exogenously added haptoglobin bound most uncomplexed haemoglobin, in the first 2 weeks after human subarachnoid haemorrhage, indicating a wide therapeutic window. In mice, the behavioural, vascular, cellular and molecular changes seen after human subarachnoid haemorrhage were recapitulated by modelling a single aspect of subarachnoid haemorrhage: prolonged intrathecal exposure to haemoglobin. Haemoglobin-induced behavioural deficits and astrocytic, microglial and synaptic changes were attenuated by haptoglobin. Haptoglobin treatment did not attenuate large-vessel vasospasm, yet improved clinical outcome by restricting diffusion of haemoglobin into the parenchyma and reducing small-vessel vasospasm. In summary, haemoglobin toxicity is of clinical importance and preventable by haptoglobin, independent of large-vessel vasospasm

Nieuwe verwaarding algenbiomassa : literatuurstudie en praktische screening van enkele ontsluitingsmethoden

Om de eiwitten, oliën, koolhydraten, carotenoïden en andere nuttige stoffen aanwezig in algencellen los van elkaar te kunnen benutten, is het nodig om de celwanden van de algen open te breken, ofwel om de algen te ontsluiten. Uiteraard is het van belang om dit te doen op een manier die de te winnen componenten zo min mogelijk beschadigt. Dit rapport bestaat uit twee delen. Het eerste is een literatuurstudie waarin een aantal algensoorten wordt omschreven, met waar mogelijk nadruk op de celwandstructuur. Verder wordt een aantal methoden beschreven om de celwanden te openen of te verzwakken. In het tweede deel van het rapport worden een aantal uitgevoerde proeven beschreven waarbij algen zijn behandeld met enzymen, schoonmaakazijn, of ethanol

Rare genetic variation in UNC13A may modify survival in amyotrophic lateral sclerosis

Our objective was to identify whether rare genetic variation in amyotrophic lateral sclerosis (ALS) candidate survival genes modifies ALS survival. Candidate genes were selected based on evidence for modifying ALS survival. Each tail of the extreme 1.5% of survival was selected from the UK MND DNA Bank and all samples available underwent whole genome sequencing. A replication set from the Netherlands was used for validation. Sequences of candidate survival genes were extracted and variants passing quality control with a minor allele frequency ≤0.05 were selected for association testing. Analysis was by burden testing using SKAT. Candidate survival genes UNC13A, KIFAP3, and EPHA4 were tested for association in a UK sample comprising 25 short survivors and 25 long survivors. Results showed that only SNVs in UNC13A were associated with survival (p = 6.57 × 10−3). SNV rs10419420:G > A was found exclusively in long survivors (3/25) and rs4808092:G > A exclusively in short survivors (4/25). These findings were not replicated in a Dutch sample. In conclusion, population specific rare variants of UNC13A may modulate survival in ALS

Groen proceswater: zuivering brouwerijprocesafvalwater met microalgen : Resultaten onderzoek 2013

Afgelopen jaar is de pilot met het kweken van algen met afvalwater van de brouwerijlocatie Zoeterwoude geslaagd. Dit is gedaan in een samenwerkingsverband van Heineken Nederland BV, Algae Food & Fuel en WUR-Acrres. Dit is de eerste inline pilot in de wereld waarbij met LED verlichting op 1000 L schaal algen zijn gekweekt met brouwerijafvalwater als nutriëntenbron. De algenreactoren blijven groen, verbeteren de waterkwaliteit en verwijderen 99% van de opgeloste minerale stikstof (NH4). Hiermee is het eerste doel bereikt, namelijk een aantal weken de algenreactoren on site en inline met de afvalwaterzuivering mee te laten draaien, met een (vooral voor stikstof) goed verwijderingsrendement

Genome-Wide Association Study of Clinical Outcome After Aneurysmal Subarachnoid Haemorrhage: Protocol

Aneurysmal subarachnoid haemorrhage (aSAH) results in persistent clinical deficits which prevent survivors from returning to normal daily functioning. Only a small fraction of the variation in clinical outcome following aSAH is explained by known clinical, demographic and imaging variables; meaning additional unknown factors must play a key role in clinical outcome. There is a growing body of evidence that genetic variation is important in determining outcome following aSAH. Understanding genetic determinants of outcome will help to improve prognostic modelling, stratify patients in clinical trials and target novel strategies to treat this devastating disease. This protocol details a two-stage genome-wide association study to identify susceptibility loci for clinical outcome after aSAH using individual patient-level data from multiple international cohorts. Clinical outcome will be assessed using the modified Rankin Scale or Glasgow Outcome Scale at 1-24 months. The stage 1 discovery will involve meta-analysis of individual-level genotypes from different cohorts, controlling for key covariates. Based on statistical significance, supplemented by biological relevance, top single nucleotide polymorphisms will be selected for replication at stage 2. The study has national and local ethical approval. The results of this study will be rapidly communicated to clinicians, researchers and patients through open-access publication(s), presentation(s) at international conferences and via our patient and public network

Private trade and monopoly structures : the East India Companies and the commodity trade to Europe in the eighteenth century

Our research is about the trade in material goods from Asia to Europe over this period, and its impact on Europe’s consumer and industrial cultures. It entails a comparative study of Europe’s East India Companies and the private trade from Asia over the period. The commodities trade was heavily dependent on private trade. The historiography to date has left a blind spot in this area, concentrating instead on corruption and malfeasance. Taking a global history approach we investigate the trade in specific consumer goods in many qualities and varieties that linked merchant communities and stimulated information flows. We set out how private trade functioned alongside and in connection with the various European East India companies; we investigate how this changed over time, how it drew on the Company infrastructure, and how it took the risks and developed new and niche markets for specific Asian commodities that the Companies could not sustain