The epidemiology of Creutzfeldt-Jakob disease in Canada: a review of mortality data.

Creutzfeldt-Jakob disease (CJD), and particularly its transmissibility through blood and blood products, has become a focus of concern in Canada. The recent identification of new variant CJD led to a review of the Canadian mortality database to identify any clustering of CJD by age, sex, or geographic location

Is Creutzfeldt-Jakob disease transmitted in blood?

Creutzfeldt-Jakob disease (CJD) has been considered infectious since the mid-1960s, but its transmissibility through the transfusion of blood or blood products is controversial. The causative agent's novel undefined nature and resistance to standard decontamination, the absence of a screening test, and the recognition that even rare cases of transmission may be unacceptable have led to the revision of policies and procedures worldwide affecting all facets of blood product manufacturing from blood collection to transfusion. We reviewed current evidence that CJD is transmitted through blood

Microscale Mechanics of Plug-and-Play In Vitro Cytoskeleton Networks

This chapter describes recent techniques that have been developed to reconstitute and characterize well-controlled, tunable networks of actin and microtubules outside of cells. It describes optical tweezers microrheology techniques to characterize the linear and nonlinear mechanics of these plug-and-play in vitro networks from the molecular-level to mesoscopic scales. It also details fluorescence microscopy and single-molecule tracking methods to determine macromolecular transport properties and stress propagation through cytoskeleton networks. Throughout the chapter the intriguing results that this body of work has revealed are highlighted—including how the macromolecular constituents of cytoskeleton networks map to their signature responses to stress or strain; and the elegant couplings between network structure, macromolecular mobility, and stress response that cytoskeleton networks exhibit

UBE2QL1 is Disrupted by a Constitutional Translocation Associated with Renal Tumor Predisposition and is a Novel Candidate Renal Tumor Suppressor Gene

Investigation of rare familial forms of renal cell carcinoma (RCC) has led to the identification of genes such as VHL and MET that are also implicated in the pathogenesis of sporadic RCC. In order to identify a novel candidate renal tumor suppressor gene, we characterized the breakpoints of a constitutional balanced translocation, t(5;19)(p15.3;q12), associated with familial RCC and found that a previously uncharacterized gene UBE2QL1 was disrupted by the chromosome 5 breakpoint. UBE2QL1 mRNA expression was downregulated in 78.6% of sporadic RCC and, although no intragenic mutations were detected, gene deletions and promoter region hypermethylation were detected in 17.3% and 20.3%, respectively, of sporadic RCC. Reexpression of UBE2QL1 in a deficient RCC cell line suppressed anchorage-independent growth. UBE2QL1 shows homology to the E2 class of ubiquitin conjugating enzymes and we found that (1) UBE2QL1 possesses an active-site cysteine (C88) that is monoubiquitinated in vivo, and (2) UBE2QL1 interacts with FBXW7 (an F box protein providing substrate recognition to the SCF E3 ubiquitin ligase) and facilitates the degradation of the known FBXW7 targets, CCNE1 and mTOR. These findings suggest UBE2QL1 as a novel candidate renal tumor suppressor gen

Differentiating normal and problem gambling: a grounded theory approach.

A previous study (Ricketts &amp; Macaskill, 2003) delineated a theory of problem gambling based on the experiences of treatment seeking male gamblers and allowed predictions to be made regarding the processes that differentiate between normal and problem gamblers. These predictions are the focus of the present study, which also utilised a grounded theory approach, but with a sample of male high frequency normal gamblers. The findings suggest that there are common aspects of gambling associated with arousal and a sense of achievement. The use of gambling to manage negative emotional states differentiated normal and problem gambling. Perceived self-efficacy , emotion management skills and perceived likelihood of winning money back were intervening variables differentiating problem and normal gamblers.</p

Light ion isotope identification in space using a pixel detector based single layer telescope

Citation: Kroupa, M., Bahadori, A. A., Campbell-Ricketts, T., George, S. P., Stoffle, N., & Zeitlin, C. (2018). Light ion isotope identification in space using a pixel detector based single layer telescope. Applied Physics Letters, 113(17), 174101. https://doi.org/10.1063/1.5052907It is demonstrated that modern pixel detectors can be utilized as single-layer particle telescopes, offering details of a particle's stopping power evolution surpassing those provided by multi-layer, non-pixelated instruments. For particles that stop in the detector, this advantage arises from repeatably sampling the Bragg curve: we always know which part of the Bragg peak was measured. We can then create a dE/dx1 vs dE/dx2 plot where the stopping power at the beginning and the end of the track is compared. We are able to identify and analyze several fine-grained features on such plots, including several related to particles that stop inside the detector, termed “stopping.” Using data from an instrument aboard the International Space Station, we show that different isotopes of stopping hydrogen can be identified as their stopping powers differ. Other features of the dE/dx1 vs dE/dx2 plot not resolvable in multi-layer particle telescopes are also exhibited, such as nuclear interactions that occur within the sensor active volume

The 1996 Soft State Transitions of Cygnus X-1

We report continuous monitoring of Cygnus X-1 in the 1.3 to 200 keV band using ASM/RXTE and BATSE/CGRO for about 200 days from 1996 February 21 to 1996 early September. During this period Cygnus X-1 experienced a hard-to-soft and then a soft-to-hard state transition. The low-energy X-ray (1.3-12 keV) and high-energy X-ray (20-200 keV) fluxes are strongly anti-correlated during this period. During the state transitions flux variations of about a factor of 5 and 15 were seen in the 1.3-3.0 keV and 100-200 keV bands, respectively, while the average 4.8-12 keV flux remains almost unchanged. The net effect of this pivoting is that the total 1.3-200 keV luminosity remained unchanged to within about 15%. The bolometric luminosity in the soft state may be as high as 50-70% above the hard state luminosity, after color corrections for the luminosity below 1.3 keV. The blackbody component flux and temperature increase in the soft state is probably caused by a combination of the optically thick disk mass accretion rate increase and a decrease of the inner disk radius.Comment: 18 pages, 1 PostScript figure. Accepted for ApJ

Methylation profiling and evaluation of demethylating therapy in renal cell carcinoma.

BACKGROUND: Despite therapeutic advances in targeted therapy, metastatic renal cell carcinoma (RCC) remains incurable for the vast majority of patients. Key molecular events in the pathogenesis of RCC include inactivation of the VHL tumour suppressor gene (TSG), inactivation of chromosome 3p TSGs implicated in chromatin modification and remodelling and de novo tumour-specific promoter methylation of renal TSGs. In the light of these observations it can be proposed that, as in some haematological malignancies, demethylating agents such as azacitidine might be beneficial for the treatment of advanced RCC. RESULTS: Here we report that the treatment of RCC cell lines with azacitidine suppressed cell proliferation in all 15 lines tested. A marked response to azacitidine therapy (>50% reduction in colony formation assay) was detected in the three cell lines with VHL promoter methylation but some RCC cell lines without VHL TSG methylation also demonstrated a similar response suggesting that multiple methylated TSGs might determine the response to demethylating therapies. To identify novel candidate methylated TSGs implicated in RCC we undertook a combined analysis of copy number and CpG methylation array data. Candidate novel epigenetically inactivated TSGs were further prioritised by expression analysis of RCC cell lines pre and post-azacitidine therapy and comparative expression analysis of tumour/normal pairs. Thus, with subsequent investigation two candidate genes were found to be methylated in more than 25% of our series and in the TCGA methylation dataset for 199 RCC samples: RGS7 (25.6% and 35.2% of tumours respectively) and NEFM in (25.6% and 30.2%). In addition three candidate genes were methylated in >10% of both datasets (TMEM74 (15.4% and 14.6%), GCM2 (41.0% and 14.6%) and AEBP1 (30.8% and 13.1%)). Methylation of GCM2 (P = 0.0324), NEFM (P = 0.0024) and RGS7 (P = 0.0067) was associated with prognosis. CONCLUSIONS: These findings provide preclinical evidence that treatment with demethylating agents such as azacitidine might be useful for the treatment of advanced RCC and further insights into the role of epigenetic changes in the pathogenesis of RCC

Infrared Spectroscopy of Symbiotic Stars. IV. V2116 Ophiuchi/GX 1+4, The Neutron Star Symbiotic

We have computed, based on 17 infrared radial velocities, the first set of orbital elements for the M giant in the symbiotic binary V2116 Ophiuchi. The giant's companion is a neutron star, the bright X-ray source GX 1+4. We find an orbital period of 1161 days by far the longest of any known X-ray binary. The orbit has a modest eccentricity of 0.10 with an orbital circularization time of less than 10^6 years. The large mass function of the orbit significantly restricts the mass of the M giant. Adopting a neutron-star mass of 1.35M(Sun), the maximum mass of the M giant is 1.22M(Sun), making it the less massive star. Derived abundances indicate a slightly subsolar metallicity. Carbon and nitrogen are in the expected ratio resulting from the red-giant first dredge-up phase. The lack of O-17 suggests that the M-giant has a mass less than 1.3M(Sun), consistent with our maximum mass. The red giant radius is 103R(Sun), much smaller than the estimated Roche lobe radius. Thus, the mass loss of the red giant is via a stellar wind. Although the M giant companion to the neutron star has a mass similar to the late-type star in low-mass X-ray binaries, its near-solar abundances and apparent runaway velocity are not fully consistent with the properties of this class of stars.Comment: In press to The Astrophysical Journal (10 April 2006 issue). 23 page

Laboratory-based evaluation of legionellosis epidemiology in Ontario, Canada, 1978 to 2006

BACKGROUND: Legionellosis is a common cause of severe community acquired pneumonia and respiratory disease outbreaks. The Ontario Public Health Laboratory (OPHL) has conducted most testing for Legionella species in the Canadian province of Ontario since 1978, and represents a multi-decade repository of population-based data on legionellosis epidemiology. We sought to provide a laboratory-based review of the epidemiology of legionellosis in Ontario over the past 3 decades, with a focus on changing rates of disease and species associated with legionellosis during that time period. METHODS: We analyzed cases that were submitted and tested positive for legionellosis from 1978 to 2006 using Poisson regression models incorporating temporal, spatial, and demographic covariates. Predictors of infection with culture-confirmed L. pneumophila serogroup 1 (LP1) were evaluated with logistic regression models. Results: 1,401 cases of legionellosis tested positive from 1978 to 2006. As in other studies, we found a late summer to early autumn seasonality in disease occurrence with disease risk increasing with age and in males. In contrast to other studies, we found a decreasing trend in cases in the recent decade (IRR 0.93, 95% CI 0.91 to 0.95, P-value = 0.001); only 66% of culture-confirmed isolates were found to be LP1. CONCLUSION: Despite similarities with disease epidemiology in other regions, legionellosis appears to have declined in the past decade in Ontario, in contrast to trends observed in the United States and parts of Europe. Furthermore, a different range of Legionella species is responsible for illness, suggesting a distinctive legionellosis epidemiology in this North American region