Using Narrow Band Photometry to Detect Young Brown Dwarfs in IC348

We report the discovery of a population of young brown dwarf candidates in the open star cluster IC348 and the development of a new spectroscopic classification technique using narrow band photometry. Observations were made using FLITECAM, the First Light Camera for SOFIA, at the 3-m Shane Telescope at Lick Observatory. FLITECAM is a new 1-5 micron camera with an 8 arcmin field of view. Custom narrow band filters were developed to detect absorption features of water vapor (at 1.495 microns) and methane (at 1.66 microns) characteristic of brown dwarfs. These filters enable spectral classification of stars and brown dwarfs without spectroscopy. FLITECAM's narrow and broadband photometry was verified by examining the color-color and color-magnitude characteristics of stars whose spectral type and reddening was known from previous surveys. Using our narrow band filter photometry method, it was possible to identify an object measured with a signal-to-noise ratio of 20 or better to within +/-3 spectral class subtypes for late-type stars. With this technique, very deep images of the central region of IC348 (H ~ 20.0) have identified 18 sources as possible L or T dwarf candidates. Out of these 18, we expect that between 3 - 6 of these objects are statistically likely to be background stars, with the remainder being true low-mass members of the cluster. If confirmed as cluster members then these are very low-mass objects (~5 Mjupiter). We also describe how two additional narrow band filters can improve the contrast between M, L, and T dwarfs as well as provide a means to determine the reddening of an individual object.Comment: 43 pages, 17 figures. Accepted for publication in the Astrophysical Journal 27 June 200

Phenotypic heterogeneity and genetic modification of P102L inherited prion disease in an international series

The largest kindred with inherited prion disease P102L, historically Gerstmann-Sträussler-Scheinker syndrome, originates from central England, with émigrés now resident in various parts of the English-speaking world. We have collected data from 84 patients in the large UK kindred and numerous small unrelated pedigrees to investigate phenotypic heterogeneity and modifying factors. This collection represents by far the largest series of P102L patients so far reported. Microsatellite and genealogical analyses of eight separate European kindreds support multiple distinct mutational events at a cytosine-phosphate diester-guanidine dinucleotide mutation hot spot. All of the smaller P102L kindreds were linked to polymorphic human prion protein gene codon 129M and were not connected by genealogy or microsatellite haplotype background to the large kindred or each other. While many present with classical Gerstmann-Sträussler-Scheinker syndrome, a slowly progressive cerebellar ataxia with later onset cognitive impairment, there is remarkable heterogeneity. A subset of patients present with prominent cognitive and psychiatric features and some have met diagnostic criteria for sporadic Creutzfeldt-Jakob disease. We show that polymorphic human prion protein gene codon 129 modifies age at onset: the earliest eight clinical onsets were all MM homozygotes and overall age at onset was 7 years earlier for MM compared with MV heterozygotes (P = 0.02). Unexpectedly, apolipoprotein E4 carriers have a delayed age of onset by 10 years (P = 0.02). We found a preponderance of female patients compared with males (54 females versus 30 males, P = 0.01), which probably relates to ascertainment bias. However, these modifiers had no impact on a semi-quantitative pathological phenotype in 10 autopsied patients. These data allow an appreciation of the range of clinical phenotype, modern imaging and molecular investigation and should inform genetic counselling of at-risk individuals, with the identification of two genetic modifiers

Patterns of Resource Use by a Drosophilid (Diptera) Leaf Miner on a Native Crucifer

Distribution and damage of Scaptomyza nigrita Wheeler on its host (bittercress, Cardamine cordifolia A. Gray), a native perennial crucifer, were examined over two growing seasons in relation to leaf position. Concentrations of defensive compounds (glucosinolates) and of nutritive compounds (total nitrogen, free amino acids, soluble carbohydrates) were also examined. The fly-host plant relationship was studied in sun and shade habitats at two sites. Oviposition and leaf-mining damage were concentrated on the lower central leaves of a stem in both habitats. These mature leaves have lower glucosinolate concentrations than new leaves. Adult densities and larval feeding damage were consistently and significantly greater on plants in the sun than on those in the shade. Higher S. nigrita densities in the sun habitat and slightly higher soluble carbohydrate concentrations in sun leaves at the beginning of the growing season, rather than variation in defensive glucosinolate levels, are the most likely mechanisms determining higher levels of leaf mining on host plants in the sun habitat

\u3ci\u3eScaptomyza nigrita\u3c/i\u3e Wheeler (Diptera: Drosophilidae), a Leaf Miner of the Native Crucifer, \u3ci\u3eCardamine cordifolia\u3c/i\u3e A. Gray (Bittercress)

The biology of Scaptomyza nigrita on its host plant, a native crucifer (Bittercress) in the Rocky Mountains, is described. Development of each stage in the life history was studied both in the field and in the laboratory. This is the first documentation of a host for S. nigrita. We examined the activity of adult flies in two adjacent habitats, sun and adjacent willow shade. Adult flies were more abundant on bittercress plants in sun-exposed versus in shaded areas, and were most active from mid-day to late afternoon. Female flies were significantly larger than male flies, but there were no differences in size of adults between the two habitats. Larval damage to bittercress is generally much greater on plants in sunny areas than on those in the shade, possibly due to the increased activity of ovipositing flies in sun-exposed areas

Imaging and CSF analyses effectively distinguish CJD from its mimics

OBJECTIVE: To review clinical and investigation findings in patients referred to a specialist prion clinic who were suspected to have sporadic Creutzfeldt-Jakob disease (sCJD) and yet were found to have an alternative final diagnosis. METHODS: Review the clinical findings and investigations in 214 patients enrolled into the UK National Prion Monitoring Cohort Study between October 2008 and November 2015 who had postmortem confirmed sCJD and compare these features with 50 patients referred over the same period who had an alternative final diagnosis (CJD mimics). RESULTS: Patients with an alternative diagnosis and those with sCJD were of similar age, sex and frequency of dementia but CJD mimics had a longer clinical history. Myoclonus, rigidity and hallucinations were more frequent in patients with sCJD but these features were not helpful in classifying individual patients. Alzheimer's disease, dementia with Lewy bodies and genetic neurodegenerative disorders were alternative diagnoses in more than half of the CJD mimic cases, and 10% had an immune-mediated encephalopathy; lymphoma, hepatic encephalopathy and progressive multifocal leukoencephalopathy were seen more than once. Diffusion-weighted MRI was the most useful readily available test to classify cases correctly (92% CJD, 2% CJD mimics). The CSF cell count, 14-3-3 protein detection and S100B were of limited value. A positive CSF RT-QuIC test, introduced during the course of the study, was found in 89% of tested CJD cases and 0% CJD mimics. CONCLUSION: The combination of diffusion-weighted MRI analysis and CSF RT-QuIC allowed a perfect classification of sCJD versus its mimics in this study

Preclinical detection of infectivity and disease-specific PrP in blood throughout the incubation period of prion disease.

Variant Creutzfeldt-Jakob disease (vCJD) is a fatal neurodegenerative disorder characterised by accumulation of pathological isoforms of the prion protein, PrP. Although cases of clinical vCJD are rare, there is evidence there may be tens of thousands of infectious carriers in the United Kingdom alone. This raises concern about the potential for perpetuation of infection via medical procedures, in particular transfusion of contaminated blood products. Accurate biochemical detection of prion infection is crucial to mitigate risk and we have previously reported a blood assay for vCJD. This assay is sensitive for abnormal PrP conformers at the earliest stages of preclinical prion disease in mice and precedes the maximum infectious titre in blood. Not only does this support the possibility of screening asymptomatic individuals, it will also facilitate the elucidation of the complex relationship that exists between the ensemble of abnormal PrP conformers present in blood and the relationship to infectivity

Cognitive decline heralds onset of symptomatic inherited prion disease

The clinical effectiveness of any disease-modifying treatment for prion disease, as for other neurodegenerative disorders, will depend on early treatment before damage to neural tissue is irrevocable. Thus, there is a need to identify markers that predict disease onset in healthy at-risk individuals. Whilst imaging and neurophysiological biomarkers have shown limited use in this regard, we recently reported progressive neurophysiological changes in individuals with the inherited prion disease mutation P102L. We have also previously demonstrated a signature pattern of fronto-parietal dysfunction in mild prion disease. Here we address whether these cognitive features anticipate the onset of symptoms in a unique sample of patients with inherited prion disease. In the cross-sectional analysis, we analysed the performance of patients at three time points in the course of disease onset: prior to symptoms (n = 27), onset of subjective symptoms without positive clinical findings (n = 8) and symptomatic with positive clinical findings (n = 24). In the longitudinal analysis, we analysed data from 24 patients who were presymptomatic at the time of recruitment and were followed up over a period of up to 17 years, of whom 16 remained healthy and eight converted to become symptomatic. In the cross-sectional analysis, the key finding was that, relative to a group of 25 healthy non-gene carrier controls, patients with subjective symptoms but without positive clinical findings were impaired on a smaller but similar set of tests (Trail Making Test part A, Stroop test, Performance IQ, gesture repetition, figure recall) to those previously found to be impaired in mild prion disease. In the longitudinal analysis, Trail Making Test parts A and B, Stroop test and Performance IQ scores significantly discriminated between patients who remained presymptomatic and those who converted, even before the converters reached criteria for formal diagnosis. Notably, performance on the Stroop test significantly discriminated between presymptomatic patients and converters before the onset of clinical symptoms [area under the curve = 0.83 (95% confidence interval, 0.62–1.00), P = 0.009]. Thus, we report here, for the first time, neuropsychological abnormalities in healthy patients prior to either symptom onset or clinical diagnosis of inherited prion disease. This constitutes an important component of an evolving profile of clinical and biomarker abnormalities in this crucial group for preventive medicine