We are showing a significant enhancement in the temporal contrast by reducing the coherent noise of the 10 PW laser system at the Extreme Light Infrastructure - Nuclear Physics facility. The temporal contrast was improved by four orders of magnitude at 10 picoseconds and by more than one order of magnitude at 50 picoseconds before the main peak. This improvement of the picosecond contrast is critical for the experiments using thin solid targets.

Background: Currently there are no disease modifying treatment for Synucleinopathies including Parkinson’s disease Dementia (PDD). Carrying a mutation in the GBA gene (beta-glucocerebrosidase/ GCAse) is a leading risk factor for synucleinopathies. Raising activity GCAse lowers α-synuclein levels in cells and animal models. Ambroxol is a pharmacological chaperone for GCAse and can raise GCAse levels. Our goal is to test Ambroxol as a disease-modifying treatment in PDD. Methods: We randomized fifty-five individuals with PDD to Ambroxol 1050mg/day, 525mg/day, or placebo for 52 weeks. Primary outcome measures included safety, Alzheimer’s disease Assessment Scale-cognitive (ADAS-Cog) subscale and the Clinician’s Global Impression of Change (CGIC). Secondary outcomes included pharmacokinetics, cognitive and motor outcomes and and plasma and CSF biomarkers. Results: Ambroxol was well tolerated. There were 7 serious adverse events (SAEs) none deemed related to Ambroxol. GCase activity was increased in white blood cells by ~1.5 fold. There were no differences between groups on primary outcome measures. Patients receiving high dose Ambroxol appeared better on the Neuropsychiatric Inventory. GBA carriers appeared to improve on some cognitive tests. pTau 181 was reduced in CSF. Conclusions: Ambroxol was safe and well-tolerated in PDD. Ambroxol may improve biomarkers and cognitive outcomes in GBA1 mutation carrie.rs Ambroxol improved some biomarkerss. ClinicalTrials.gov NCT02914366

The Mössbauer effect of Fe57 was used to probe and characterize iron ions adsorbed on the interlayer surfaces of montmorillonite. Measurements were performed with Fe- and Ca-saturated mont-morillonites. At 210°K the intensity of the Fe2+ line was greatly reduced, apparently due to the melting of interlayer water. Neither the structural Fe2+ in Ca-montmorillonite nor the adsorbed Fe3+ in Fe-mont-morillonite were affected by the melting process. From the temperature dependence of the absorption intensity, the effective Debye temperature of all the iron species appears to be approximately the same (θD = 189 ± 5°K). This result allowed for an accurate determination of the population of Fe2+/Fe3+ in various samples.

Background: Saccade and pupil responses are potential neurodegenerative disease biomarkers due to overlap between oculomotor circuitry and disease-affected areas. Instruction-based tasks have previously been examined as biomarker sources, but are arduous for patients with limited cognitive abilities; additionally, few studies have evaluated multiple neurodegenerative pathologies concurrently. Methods: The Ontario Neurodegenerative Disease Research Initiative recruited individuals with Alzheimer’s disease (AD), mild cognitive impairment (MCI), amyotrophic lateral sclerosis (ALS), frontotemporal dementia, progressive supranuclear palsy, or Parkinson’s disease (PD). Patients (n=274, age 40-86) and healthy controls (n=101, age 55-86) viewed 10 minutes of frequently changing video clips without instruction while their eyes were tracked. We evaluated differences in saccade and pupil parameters (e.g. saccade frequency and amplitude, pupil size, responses to clip changes) between groups. Results: Preliminary data indicates low-level behavioural alterations in multiple disease cohorts: increased centre bias, lower overall saccade rate and reduced saccade amplitude. After clip changes, patient groups generally demonstrated lower saccade rate but higher microsaccade rate following clip change to varying degrees. Additionally, pupil responses were blunted (AD, MCI, ALS) or exaggerated (PD). Conclusions: This task may generate behavioural biomarkers even in cognitively impaired populations. Future work should explore the possible effects of factors such as medication and disease stage.

Background: Eye movements reveal neurodegenerative disease processes due to overlap between oculomotor circuitry and disease-affected areas. Characterizing oculomotor behaviour in context of cognitive function may enhance disease diagnosis and monitoring. We therefore aimed to quantify cognitive impairment in neurodegenerative disease using saccade behaviour and neuropsychology. Methods: The Ontario Neurodegenerative Disease Research Initiative recruited individuals with neurodegenerative disease: one of Alzheimer’s disease, mild cognitive impairment, amyotrophic lateral sclerosis, frontotemporal dementia, Parkinson’s disease, or cerebrovascular disease. Patients (n=450, age 40-87) and healthy controls (n=149, age 42-87) completed a randomly interleaved pro- and anti-saccade task (IPAST) while their eyes were tracked. We explored the relationships of saccade parameters (e.g. task errors, reaction times) to one another and to cognitive domain-specific neuropsychological test scores (e.g. executive function, memory). Results: Task performance worsened with cognitive impairment across multiple diseases. Subsets of saccade parameters were interrelated and also differentially related to neuropsychology-based cognitive domain scores (e.g. antisaccade errors and reaction time associated with executive function). Conclusions: IPAST detects global cognitive impairment across neurodegenerative diseases. Subsets of parameters associate with one another, suggesting disparate underlying circuitry, and with different cognitive domains. This may have implications for use of IPAST as a cognitive screening tool in neurodegenerative disease.

Temperature and intraspecific competition are important factors influencing the growth of all organisms, including parasites. The temperature increase is suggested to stimulate the development of parasites within poikilothermic hosts. However, at high parasite densities, this effect could be diminished, due to stronger intraspecific competition. Our study, for the first time, addressed the joint effects of warming and parasite abundances on parasite growth in poikilothermic hosts. The growth of the common fish parasite larvae (trematode Diplostomum pseudospathaceum) within the rainbow trout at different infection intensities and temperatures (15°C and 18°C) was experimentally investigated. The results showed that temperature was positively correlated with both parasite infection success and growth rates. The growth rates increased much more compared to those in many free-living poikilothermic animals. Atypically for a majority of parasites, D. pseudospathaceum larvae grow faster when abundant (Allee effect). The possible causes for this phenomenon (manipulation cost sharing, etc.) are discussed in this study. Importantly, limited evidence of the interaction between temperature and population density was found. It is likely that temperature did not change the magnitude of the Allee effect but affected its timing. The impact of these effects is supposed to become more pronounced in freshwater ecosystems under current climate changes.

Towards the end of her seminal work on the notion of representation Hanna Pitkin makes the following observation:

Creutzfeldt-Jakob disease (CJD) is a fatal neurological illness for which accurate diagnosis is paramount. Real-time quaking-induced conversion (RT-QuIC) is a prion-specific assay with high sensitivity and specificity for CJD. The Canadian endpoint quaking-induced conversion (EP-QuIC) test is similar, but unlike RT-QuIC there is little data regarding its diagnostic utility in clinical practice. In this exploratory predictive value analysis of EP-QuIC in CJD, the negative predictive value (NPV) and positive predictive value (PPV) was 100% and 83%, respectively, with one false-positive result identified. Re-testing this sample with an optimized EP-QuIC protocol eliminated this false-positive result, leading to a PPV of 100%.

Removal of parasite free-living stages by predators has previously been suggested an important factor controlling parasite transmission in aquatic habitats. Experimental studies of zooplankton predation on macroparasite larvae are, however, scarce. We tested whether trematode cercariae, which are often numerous in shallow waters, are suitable prey for syntopic zooplankters. Feeding rates and survival of freshwater cyclopoids (Megacyclops viridis, Macrocyclops distinctus), calanoids (Arctodiaptomus paulseni), cladocerans (Sida crystallina) and rotifers Asplanchna spp., fed with cercariae of Diplostomum pseudospathaceum, a common fish trematode, were studied. In additional long-term experiments, we studied reproduction of cyclopoids fed with cercariae. All tested zooplankton species consumed cercariae. The highest feeding rates were observed for cyclopoids (33 ± 12 cercariae ind−1 h−1), which actively reproduced (up to one egg clutch day−1) when fed ad libitum with cercariae. Their reproductive characteristics did not change significantly with time, indicating that cercariae supported cyclopoids’ dietary needs. Mortality of rotifers and cladocerans was high (25–28% individuals) when exposed to cercariae in contrast to cyclopoids and calanoids (<2%). Cercariae clogged the filtration apparatus of cladocerans and caused internal injuries in predatory rotifers, which ingested cercariae. Observed trophic links between common freshwater zooplankters and cercariae may significantly influence food webs and parasite transmission in lentic ecosystems.

Recent results suggest that bivalves can play an important role in restraining the spread of various aquatic infections. However, the ability of mussels to remove free-living stages of macroparasites and reduce their transmission is still understudied, especially for freshwater ecosystems. We investigated the influence of the common freshwater mussel (Anodonta anatina) on the transmission of a trematode (eye fluke, Diplostomum pseudospathaceum), which frequently infects fish in farms and natural habitats. In our experiments, mussels caused a significant decrease (P < 0·001) in the abundance of trematode free-living stages, from 6520 to 1770 cercariae L−1 on average (about 4-fold in 2 h). Individual clearance rates of mussels were 0·6‒3·7 L per hour (mean 1·9). These tests were followed by experimental infections of rainbow trout (Oncorhynchus mykiss) with different doses of D. pseudospathaceum cercariae in the presence or absence of mussels. Exposure of fish to cercariae in the presence of mussels significantly (P < 0·05) reduced the infection intensities in fish (by 30–40%) at all exposure doses. Our results indicate that freshwater bivalves can markedly reduce local cercariae densities and could be useful in mitigation of trematodoses harmful to fish farming.