Brucella ceti
has been recovered from a number species of cetaceans worldwide over the last 25 yr. Here we report, for the first time, the recovery of
B. ceti
from a Risso’s dolphin
Grampus griseus
...and a killer whale
Orcinus orca
. Recovery from an abdominal mass in the dolphin provides further evidence of the systemic pathogenic potential for
B. ceti
infection in cetaceans. The isolation of
B. ceti
ST23 (porpoise cluster) from a killer whale from a group known to eat other marine mammals raises the possibility of infection via ingestion. This report takes the number of cetacean species in UK coastal waters from which
B. ceti
has been isolated to 11 and highlights the value of routine, comprehensive and specific screening for significant pathogens such as
Brucella
sp. by strandings networks.
Fatal Brucella ceti infection with histological lesions specific to the central nervous system has been described in only 3 species of cetaceans: striped dolphins Stenella coeruleoalba, Atlantic ...white-sided dolphins Lagenorhynchus acutus and short-beaked common dolphins Delphinus delphis. This paper describes the first report of a B. ceti-associated meningoencephalitis in a long-finned pilot whale Globicephala melas, showing the increasing range of species susceptibility. Brucella was recovered in larger numbers from cerebrospinal fluid than from brain tissue and is the sample of choice for isolation.
Despite decades of research, the pathophysiology of bipolar disorder (BD) is still not well understood. Structural brain differences have been associated with BD, but results from neuroimaging ...studies have been inconsistent. To address this, we performed the largest study to date of cortical gray matter thickness and surface area measures from brain magnetic resonance imaging scans of 6503 individuals including 1837 unrelated adults with BD and 2582 unrelated healthy controls for group differences while also examining the effects of commonly prescribed medications, age of illness onset, history of psychosis, mood state, age and sex differences on cortical regions. In BD, cortical gray matter was thinner in frontal, temporal and parietal regions of both brain hemispheres. BD had the strongest effects on left pars opercularis (Cohen's d=-0.293; P=1.71 × 10
), left fusiform gyrus (d=-0.288; P=8.25 × 10
) and left rostral middle frontal cortex (d=-0.276; P=2.99 × 10
). Longer duration of illness (after accounting for age at the time of scanning) was associated with reduced cortical thickness in frontal, medial parietal and occipital regions. We found that several commonly prescribed medications, including lithium, antiepileptic and antipsychotic treatment showed significant associations with cortical thickness and surface area, even after accounting for patients who received multiple medications. We found evidence of reduced cortical surface area associated with a history of psychosis but no associations with mood state at the time of scanning. Our analysis revealed previously undetected associations and provides an extensive analysis of potential confounding variables in neuroimaging studies of BD.
High doses of ionizing radiation clearly produce deleterious consequences in humans, including, but not exclusively, cancer induction. At very low radiation doses the situation is much less clear, ...but the risks of low-dose radiation are of societal importance in relation to issues as varied as screening tests for cancer, the future of nuclear power, occupational radiation exposure, frequent-flyer risks, manned space exploration, and radiological terrorism. We review the difficulties involved in quantifying the risks of low-dose radiation and address two specific questions. First, what is the lowest dose of x- or γ-radiation for which good evidence exists of increased cancer risks in humans? The epidemiological data suggest that it is ≈10-50 mSv for an acute exposure and ≈50-100 mSv for a protracted exposure. Second, what is the most appropriate way to extrapolate such cancer risk estimates to still lower doses? Given that it is supported by experimentally grounded, quantifiable, biophysical arguments, a linear extrapolation of cancer risks from intermediate to very low doses currently appears to be the most appropriate methodology. This linearity assumption is not necessarily the most conservative approach, and it is likely that it will result in an underestimate of some radiation-induced cancer risks and an overestimate of others.
Far-ultraviolet to far-infrared images of the nearby galaxy NGC 5194 (M51a), from a combination of space-based (Spitzer, GALEX, and Hubble Space Telescope) and ground-based data, are used to ...investigate local and global star formation and the impact of dust extinction. The Spitzer data provide unprecedented spatial detail in the infrared, down to sizes 6500 pc at the distance of NGC 5194. The multiwavelength set is used to trace the relatively young stellar populations, the ionized gas, and the dust absorption and emission in H II-emitting knots, over 3 orders of magnitude in wavelength range. As is common in spiral galaxies, dust extinction is high in the center of the galaxy (A sub(V) 6 3.5 mag), but its mean value decreases steadily as a function of galactocentric distance, as derived from both gas emission and stellar continuum properties. In the IR/UV-UV color plane, the NGC 5194 H II knots show the same trend observed for normal star-forming galaxies, having a much larger dispersion (61 dex peak to peak) than starburst galaxies. We identify the dispersion as due to the UV emission predominantly tracing the evolved, nonionizing stellar population, up to ages 650-100 Myr. While in starbursts the UV light traces the current star formation rate (SFR), in NGC 5194 it traces a combination of current and recent past SFRs. Possibly, mechanical feedback from supernovae is less effective at removing dust and gas from the star formation volume in normal star-forming galaxies than in starbursts because of the typically lower SFR densities in the former. The application of the starburst opacity curve for recovering the intrinsic UV emission (and deriving SFRs) in local and distant galaxies appears therefore appropriate only for SFR densities 1 M sub( )yr super(-1) kpc super(-2). Unlike the UV emission, the monochromatic 24 km luminosity is an accurate local SFR tracer for the H II knots in NGC 5194, with a peak-to-peak dispersion of less than a factor of 3 relative to hydrogen emission line tracers; this suggests that the 24 km emission carriers are mainly heated by the young, ionizing stars. However, preliminary results show that the ratio of the 24 km emission to the SFR varies by a factor of a few from galaxy to galaxy; this variation needs to be understood and carefully quantified before the 24 km luminosity can be used as an SFR tracer for galaxy populations. While also correlated with star formation, the 8 km emission is not directly proportional to the number of ionizing photons; it is overluminous, by up to a factor of 62, relative to the galaxy's average in weakly ionized regions and is underluminous, by up to a factor of 63, in strongly ionized regions. This confirms earlier suggestions that the carriers of the 8 km emission are heated by more than one mechanism.
The Spitzer Infrared Nearby Galaxies Survey (SINGS) is carrying out a comprehensive multiwavelength survey on a sample of 75 nearby galaxies. The 1-850 km spectral energy distributions (SEDs) are ...presented using broadband imaging data from Spitzer, 2MASS, ISO, IRAS, and SCUBA. The infrared colors derived from the globally integrated Spitzer data are generally consistent with the previous generation of models that were developed using global data for normal star-forming galaxies, although significant deviations are observed. Spitzer's excellent sensitivity and resolution also allow a detailed investigation of the infrared SEDs for various locations within the three large, nearby galaxies NGC 3031 (M81), NGC 5194 (M51), and NGC 7331. A wide variety of spectral shapes is found within each galaxy, especially for NGC 3031, the closest of the three targets and thus the galaxy for which the smallest spatial scales can be explored. Strong correlations exist between the local star formation rate and the infrared colors f sub(u)(70 km)/f sub(u)(160 km) and f sub(u)(24 km)/f sub(u)(160 km), suggesting that the 24 and 70 km emission are useful tracers of the local star formation activity level. Preliminary evidence indicates that variations in the 24 km emission, and not variations in the emission from polycyclic aromatic hydrocarbons at 8 km, drive the variations in the f sub(u)(8.0 km)/f sub(u)(24 km) colors within NGC 3031, NGC 5194, and NGC 7331. If the galaxy-to-galaxy variations in SEDs seen in our sample are representative of the range present at high redshift, then extrapolations of total infrared luminosities and star formation rates from the observed 24 km flux will be uncertain at the factor of 5 level (total range). The corresponding uncertainties using the redshifted 8.0 km flux (e.g., observed 24 km flux for a z = 2 source) are factors of 10-20. Considerable caution should be used when interpreting such extrapolated infrared luminosities.
To determine the sensitivity and specificity of methods to detect anti-basal ganglia antibodies (ABGA) in Sydenham's chorea (SC).
SC is a delayed manifestation of group Abeta hemolytic streptococcal ...infection typically associated with rheumatic fever (RHF). SC is characterized by chorea and motor and neuropsychiatric symptoms. Patients with SC produce antibodies that cross-react with streptococcal, caudate, and subthalamic nuclei antigens detected using an immunofluorescent (IF) method with inconsistent reports of positivity.
The authors developed ELISA and Western immunoblotting (WB) methods to detect ABGA and compared these assays to IF. They investigated samples from patients with acute SC (n = 20), persistent SC (n = 16), control samples from RHF (n = 16), and healthy pediatric volunteers (n = 11).
ABGA ELISA had a sensitivity of 95% and specificity of 93% in acute SC. Both WB and IF had a sensitivity of 100% and specificity of 93%. In the persistent SC group, ABGA sensitivity dropped to 69% using WB and to 63% using IF. Three common basal ganglia antigens were identified by WB in both acute and persistent SC (40 kDa n = 15, 45 kDa n = 15, and 60 kDa n = 13). There was no antibody reactivity to cerebellum, cerebral cortex, or myelin antigen preparations in any group.
These results support the hypothesis that Syndenham's chorea is an autoantibody-mediated disorder. Western immunoblotting and immunofluorescence are the best methods for detecting anti-basal ganglia antibodies, and reactivity to basal ganglia antigens of 40, 45, and 60 kDa were commonly seen in both acute and persistent cases of SC.
Polygenic risk scores (PRS) for epithelial ovarian cancer (EOC) have the potential to improve risk stratification. Joint estimation of Single Nucleotide Polymorphism (SNP) effects in models could ...improve predictive performance over standard approaches of PRS construction. Here, we implemented computationally efficient, penalized, logistic regression models (lasso, elastic net, stepwise) to individual level genotype data and a Bayesian framework with continuous shrinkage, "select and shrink for summary statistics" (S4), to summary level data for epithelial non-mucinous ovarian cancer risk prediction. We developed the models in a dataset consisting of 23,564 non-mucinous EOC cases and 40,138 controls participating in the Ovarian Cancer Association Consortium (OCAC) and validated the best models in three populations of different ancestries: prospective data from 198,101 women of European ancestries; 7,669 women of East Asian ancestries; 1,072 women of African ancestries, and in 18,915 BRCA1 and 12,337 BRCA2 pathogenic variant carriers of European ancestries. In the external validation data, the model with the strongest association for non-mucinous EOC risk derived from the OCAC model development data was the S4 model (27,240 SNPs) with odds ratios (OR) of 1.38 (95% CI: 1.28-1.48, AUC: 0.588) per unit standard deviation, in women of European ancestries; 1.14 (95% CI: 1.08-1.19, AUC: 0.538) in women of East Asian ancestries; 1.38 (95% CI: 1.21-1.58, AUC: 0.593) in women of African ancestries; hazard ratios of 1.36 (95% CI: 1.29-1.43, AUC: 0.592) in BRCA1 pathogenic variant carriers and 1.49 (95% CI: 1.35-1.64, AUC: 0.624) in BRCA2 pathogenic variant carriers. Incorporation of the S4 PRS in risk prediction models for ovarian cancer may have clinical utility in ovarian cancer prevention programs.
An analysis of 460 phase 1 oncology trials in adults sponsored by the Cancer Therapy Evaluation Program at the National Cancer Institute between 1991 and 2002, including 11,935 participants, found an ...overall response rate of 10.6 percent and a toxicity-related death rate of 0.5 percent. Response rates and death rates varied among the different types of trials.
An analysis of 460 phase 1 oncology trials in adults found an overall response rate of 10.6 percent and a toxicity-related death rate of 0.5 percent. The decision of a patient with advanced, treatment-refractory cancer to participate in a phase 1 trial requires a careful weighing of the risks and benefits.
The ethical issues raised by phase 1 oncology trials have been debated for decades.
1
–
6
These trials enroll patients with advanced cancer whose disease is usually refractory to available treatment in order to evaluate the safety and toxicity of new therapeutic agents, to establish the pharmacokinetic properties of those agents, and to determine a safe dose for subsequent testing.
7
Published reviews report that a tumor response occurs in 4 to 6 percent of the participants in these trials and that about 0.5 percent of participants die as the result of toxicity.
8
–
16
Critics of such trials cite these data when . . .
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