An excess of massive stars in the local 30 Doradus starburst.

The 30 Doradus star-forming region in the Large Magellanic Cloud is a nearby analog of large star-formation events in the distant universe. We determined the recent formation history and the initial mass function (IMF) of massive stars in 30 Doradus on the basis of spectroscopic observations of 247 stars more massive than 15 solar masses ([Formula: see text]). The main episode of massive star formation began about 8 million years (My) ago, and the star-formation rate seems to have declined in the last 1 My. The IMF is densely sampled up to 200 [Formula: see text] and contains 32 ± 12% more stars above 30 [Formula: see text] than predicted by a standard Salpeter IMF. In the mass range of 15 to 200 [Formula: see text], the IMF power-law exponent is [Formula: see text], shallower than the Salpeter value of 2.35.

Effects of early life stress on depression, cognitive performance and brain morphology.

BACKGROUND: Childhood early life stress (ELS) increases risk of adulthood major depressive disorder (MDD) and is associated with altered brain structure and function. It is unclear whether specific ELSs affect depression risk, cognitive function and brain structure. METHOD: This cross-sectional study included 64 antidepressant-free depressed and 65 never-depressed individuals. Both groups reported a range of ELSs on the Early Life Stress Questionnaire, completed neuropsychological testing and 3T magnetic resonance imaging (MRI). Neuropsychological testing assessed domains of episodic memory, working memory, processing speed and executive function. MRI measures included cortical thickness and regional gray matter volumes, with a priori focus on the cingulate cortex, orbitofrontal cortex (OFC), amygdala, caudate and hippocampus. RESULTS: Of 19 ELSs, only emotional abuse, sexual abuse and severe family conflict independently predicted adulthood MDD diagnosis. The effect of total ELS score differed between groups. Greater ELS exposure was associated with slower processing speed and smaller OFC volumes in depressed subjects, but faster speed and larger volumes in non-depressed subjects. In contrast, exposure to ELSs predictive of depression had similar effects in both diagnostic groups. Individuals reporting predictive ELSs exhibited poorer processing speed and working memory performance, smaller volumes of the lateral OFC and caudate, and decreased cortical thickness in multiple areas including the insula bilaterally. Predictive ELS exposure was also associated with smaller left hippocampal volume in depressed subjects. CONCLUSIONS: Findings suggest an association between childhood trauma exposure and adulthood cognitive function and brain structure. These relationships appear to differ between individuals who do and do not develop depression.

The vascular depression hypothesis: mechanisms linking vascular disease with depression.

The 'Vascular Depression' hypothesis posits that cerebrovascular disease may predispose, precipitate or perpetuate some geriatric depressive syndromes. This hypothesis stimulated much research that has improved our understanding of the complex relationships between late-life depression (LLD), vascular risk factors, and cognition. Succinctly, there are well-established relationships between LLD, vascular risk factors and cerebral hyperintensities, the radiological hallmark of vascular depression. Cognitive dysfunction is common in LLD, particularly executive dysfunction, a finding predictive of poor antidepressant response. Over time, progression of hyperintensities and cognitive deficits predicts a poor course of depression and may reflect underlying worsening of vascular disease. This work laid the foundation for examining the mechanisms by which vascular disease influences brain circuits and influences the development and course of depression. We review data testing the vascular depression hypothesis with a focus on identifying potential underlying vascular mechanisms. We propose a disconnection hypothesis, wherein focal vascular damage and white matter lesion location is a crucial factor, influencing neural connectivity that contributes to clinical symptomatology. We also propose inflammatory and hypoperfusion hypotheses, concepts that link underlying vascular processes with adverse effects on brain function that influence the development of depression. Testing such hypotheses will not only inform the relationship between vascular disease and depression, but also provide guidance on the potential repurposing of pharmacological agents that may improve LLD outcomes.

Salmonella serotype diversity and seasonality in urban and rural streams.

AIMS: To investigate the prevalence, seasonality and genetic diversity of Salmonella enterica serotypes, particularly those of human and veterinary health significance, in urban and rural streams. METHODS AND RESULTS: Using a swab collection technique and multiple culture media for isolation, Salmonella were detected in 78.4% of water samples (November 2003 to July 2005) taken from urban and rural/agricultural streams in the Grand River watershed (Ontario, Canada). Among 235 isolates, there were 38 serotypes, with the predominant serotypes and phagetypes (PT) being Salmonella Typhimurium PT 104 and Salmonella Heidelberg PT 19. These are also the most common Salmonella serotypes found in humans and farm animals locally and across Canada, a trend not commonly reported. The urban stream had more frequent Salmonella occurrence, greater serotype diversity and greater genetic variability (based on pulsed field gel electrophoresis) of specific strains compared with the rural/agricultural streams. Distinct seasonality in serotypes of health significance was observed only in the rural/agricultural streams, which is likely a reflection of seasonal source inputs in these watersheds. Despite the lower occurrence of these strains in stream water in the colder months, laboratory studies did not support reduced survival of Salm. Typhimurium and Salm. Heidelberg at lower temperatures, although survival differences were observed with other serotypes. CONCLUSIONS: A diverse range of Salmonella serotypes and PT were obtained from both urban and rural/agricultural streams, with the predominant strains being those most frequently associated with human and veterinary disease in Canada. SIGNIFICANCE AND IMPACT OF THE STUDY: The ubiquitous nature of Salmonella in water and the predominance of serotypes/PT of human or veterinary health significance suggest that the aquatic environment is a reservoir for this bacterium and could be involved in the transport and dissemination of this pathogen between hosts.

Impact of BDNF Val66Met and 5-HTTLPR polymorphism variants on neural substrates related to sadness and executive function.

The brain-derived neurotrophic factor (BDNF) Val(66) Met allelic variation is linked to both the occurrence of mood disorders and antidepressant response. These findings are not universally observed, and the mechanism by which this variation results in increased risk for mood disorders is unclear. One possible explanation is an epistatic relationship with other neurotransmitter genes associated with depression risk, such as the serotonin-transporter-linked promotor region (5-HTTLPR). Further, it is unclear how the coexistence of the BDNF Met and 5-HTTLPR S variants affects the function of the affective and cognitive control systems. To address this question, we conducted a functional magnetic resonance imaging (fMRI) study in 38 older adults (20 healthy and 18 remitted from major depressive disorder). Subjects performed an emotional oddball task during the fMRI scan and provided blood samples for genotyping. Our analyses examined the relationship between genotypes and brain activation to sad distractors and attentional targets. We found that 5-HTTLPR S allele carriers exhibited stronger activation in the amygdala in response to sad distractors, whereas BDNF Met carriers exhibited increased activation to sad stimuli but decreased activation to attentional targets in the dorsolateral prefrontal and dorsomedial prefrontal cortices. In addition, subjects with both the S allele and Met allele genes exhibited increased activation to sad stimuli in the subgenual cingulate and posterior cingulate. Our results indicate that the Met allele alone or in combination with 5-HTTLPR S allele may increase reactivity to sad stimuli, which might represent a neural mechanism underlying increased depression vulnerability.

BDNF Val66Met genotype and 6-month remission rates in late-life depression.

Although not observed in younger adult cohorts, in older individuals the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism is associated with major depressive disorder (MDD) risk. It is further associated with subjective social support and magnetic resonance imaging (MRI) hyperintense lesions, clinical features independently related to MDD. We examined the relationship between this polymorphism and antidepressant remission rates in an elderly sample with MDD, while also testing for mediation effects of social support and hyperintensities. A total of 229 elderly Caucasian subjects with MDD completed baseline assessments, 1.5 T MRI, and BDNF genotyping. They received antidepressant medication under a structured treatment algorithm and were evaluated for remission at 3 and 6 months. At the 3-month evaluation, BDNF Val66Met genotype was not associated with remission (Wald's χ²=2.51, P=0.1131). When not controlling for multiple comparisons, Met66 allele carriers were more likely to be remitted at 6 months (χ²=4.32, P=0.0377) with an odds ratio of 1.82 (95% CI: 1.04, 3.22). This effect persisted after controlling for lesion volume and social support, neither of which mediated this relationship. Thus in this exploratory analysis, the Met66 allele may be associated with increased odds of remission in older subjects, but also with increased time to remission as there was no 3-month effect.

Angiotensin receptor gene polymorphisms and 2-year change in hyperintense lesion volume in men.

This longitudinal study examined the relationship between 2-year change in white matter hyperintense lesion (WML) volume and polymorphisms in genes coding for the angiotensin-II type 1 and type 2 receptors, AGTR1 A1166C and AGTR2 C3123A, respectively. 137 depressed and 94 non-depressed participants aged >or=60 years were enrolled. Standard clinical evaluations were performed on all participants and blood samples obtained for genotyping. 1.5-T MRI (magnetic resonance imaging) data were obtained at baseline and approximately 2 years later. These scans were processed using a semi-automated segmentation process, which allowed for the calculation of WML volume at each time point. Statistical models were tested for the relationship between change in WML volume and genotype, while also controlling for age, sex, diagnostic strata, baseline WML volume and comorbid cerebrovascular risk factors. In men, AGTR1 1166A allele homozygotes exhibited significantly less change in WML volume than 1166C carriers. We also found that men reporting hypertension (HTN) with the AGTR2 3123C allele exhibit less change in WML volume than hypertensive men with the 3123A allele, or men without HTN. There were no significant relationships between these polymorphisms and change in WML volume in women. No significant gene-gene or gene-depression interactions were observed. Our results parallel earlier observed gender differences of the relationship between other renin-angiotensin system polymorphisms and HTN. Further work is needed to determine whether these observed relationships are secondary to polymorphisms affecting response to antihypertensive medication, and whether antihypertensive medications can slow WML progression and lower the risk of morbidity associated with WMLs.

The COMT Val158Met polymorphism and cognition in depressed and nondepressed older adults.

OBJECTIVE: The objective of the current study was to examine the relationship between the COMT Val(158)Met polymorphism and neuropsychological performance in depressed and nondepressed older adults. METHODS: One hundred and twenty-six clinically depressed older adults and 105 nondepressed comparison participants were compared on neuropsychological performance and COMT Val(158)Met (Val/Val, Val/Met, Met/Met). RESULTS: Based on multivariate regression models, the COMT Val(158)Met polymorphism was not associated with cognitive performance among depressed or nondepressed individuals, nor did this polymorphism account for the fact that depressed individuals performed worse than nondepressed individuals on several neuropsychological tests that are typically affected by depression. There was also no difference in frequency of the COMT Val(158)Met alleles between depressed and nondepressed individuals. CONCLUSIONS: Although the current study found no association between COMT Val(158)Met polymorphism on a number of clinical neuropsychological tests that are typically found to be sensitive to depression, differential effects of the COMT Val(158)Met polymorphism on dopamine transmission in psychiatric and non-psychiatric populations may be further clarified by clinical research with neuroscience-based paradigms that segregate cognitive tasks into component processes with precise neural substrates, particularly with respect to the complex functions of the prefrontal cortex. Negative results can be important to narrowing down target processes and understanding the influence of clinical and demographic characteristics in studies of psychiatric genetics.

Geosmin and MIB events in a new reservoir in southern California.

Diamond Valley Lake is a large drinking water reservoir in western Riverside County, California near the city of Hemet. In almost 6 years since filling began in 1999, this reservoir has experienced five episodes involving either geosmin or 2-methylisoborneol (MIB). The first one was a short-lived but intense geosmin event in May 2000, associated with a planktonic cyanobacterium, Anabaena circinalis. Geosmin levels reached 750 ng/L at the surface. All the other episodes involved benthic proliferations in the littoral zone. In September 2002, an MIB-producing growth developed in a shallow area near the outlet tower, dominated by Oscillatoria cf. curviceps and O. limosa. A similar event occurred in October 2003. In March 2004, an extensive growth of cyanobacteria that included two geosmin producers developed at the east dam, but had minimal effect on geosmin levels in the water. Finally, there was a major MIB episode in October 2004, in which the primary causative organism was again Oscillatoria cf. curviceps. A band of benthic cyanobacteria developed all around the shoreline from 3-9 m deep, and surface MIB levels reached 63 ng/L. These events showed that a new reservoir in a mild climate can be colonised by benthic cyanobacteria that produce MIB and geosmin, within a relatively short time.

A guide to geosmin- and MIB-producing cyanobacteria in the United States.

A guide to confirmed geosmin- and MIB-producing cyanobacteria isolated in the United States is being prepared. This document will include 41 different species or morphologically distinct types from eight states and diverse aquatic sources isolated over a 22-year period. The organisms comprised by this guide demonstrate the importance of attached cyanobacteria as off-flavor agents, the strain specificity of MIB production, the existence of unicellular MIB producers, the occurrence of multiple geosmin and MIB producers in reservoirs, and the relationship of certain planktonic odor producers to species in other countries.

Guidelines for treatment of onychomycosis.

These guidelines for management of onychomycosis have been prepared for dermatologists on behalf of the British Association of Dermatologists. They present evidence-based guidance for treatment, with identification of the strength of evidence available at the time of preparation of the guidelines, and a brief overview of epidemiological aspects, diagnosis and investigation.

The use of benthic mesocosms for the assessment of sediment contamination.

The diagnostic capability of changes in the benthic macroinvertebrate community composition to determine the cause in contaminated sediments were addressed using box core mesocosms subjected to cadmium, atrazine and nutrient enrichment. Intact cores of lake sediment were collected from Lake Erie at four occasions during 1996 and were returned to laboratory where they were maintained and manipulated. The benthic community composition of the artificially polluted mesocosms was compared with field data, collected at the same time as the intact cores, and to untreated control boxes. Community composition was related to the measured environmental variables using multi-dimensional scaling (MDS) and principle axis correlation (PCC). Community responses to different treatments were both different and consistent, suggesting that the community structure of these mesocosms could be used to identify the primary source of impact.

Maintenance of intact sediment box cores as laboratory mesocosms.

Mesocosms consisting of physically and biologically intact segments of natural communities are an ideal compromise between single species tests and ecosystem experiments in the assessment of sediment contamination. Therefore, large intact sediment cores, as mesocosms with naturally co-adapted communities, would allow sediment contamination to be assessed using the replicability and statistical power of laboratory techniques, while retaining much of the ecological realism of field studies. This study investigates the collection and maintenance of such cores, collected from an unimpacted site in Lake Erie. It demonstrates that box cores containing relatively undisturbed freshwater sediments can be brought back to the laboratory and maintained for up to 8 weeks with little change in the resident benthic fauna. Feeding the systems is not required, nor is it deleterious to the indigenous fauna.

Evidence of white matter tract disruption in MRI hyperintensities.

BACKGROUND: Diffusion tensor imaging (DTI) of brain tissue measures the apparent diffusion coefficient (ADC), or isotropic diffusion, and anisotropy, or diffusion as influenced by tissue structure. We hypothesized that hyperintensities, when compared with normal tissue by DTI, would show evidence of damage through an increased ADC and decreased anisotropy. We also hypothesized that DTI changes in hyperintensities would be similar between depressed subjects and control subjects. METHODS: Fourteen depressed geriatric patients and nineteen control subjects received DTI. The ADC and aniso-tropy of normal tissue from standard regions were compared with hyperintensities from these regions. The Students' t test compared individual regions and averaged white matter results. RESULTS: Hyperintensities showed higher ADC and lower anisotropy than normal regions. Gray matter exhibited similar trends. There was no significant difference in diffusion characteristics of hyperintensities between subjects and control subjects. CONCLUSIONS: Hyperintensities damage the structure of brain tissue, and do so comparably in depressed subjects and control subjects.

Preventing experimental vertical transmission of scrapie by embryo transfer.

This study investigated whether the transmission of naturally occurring scrapie in sheep can be prevented using embryo transfer. Embryos were collected from 38 donor ewes in a Suffolk sheep flock with a high incidence of naturally occurring scrapie, treated with a sanitary procedure (embryo washing) recommended by the International Embryo Transfer Society and then transferred to 58 scrapie-free recipient ewes. Ninety-four offspring were produced. None of the offspring or the recipient ewes developed scrapie. Furthermore, offspring derived from embryos collected from donor ewes bred to the immunohistochemically positive ram did not develop scrapie. We conclude that scrapie was not transmitted to offspring via the embryo nor was the infective agent transmitted to recipient ewes during embryo transfer procedures.

Resistance of cattle to scrapie by the oral route.

Early epidemiological information indicated that bovine spongiform encephalopathy (BSE) originated from scrapie in sheep. The question arose if scrapie in North America would induce a BSE-like disease in cattle. Six years ago, we reported that brain tissue from sheep with scrapie caused a neurologic disease when injected directly into the brains of cattle, but the disease induced was different from BSE as it occurs in the United Kingdom and Europe. Here, we report that cattle fed raw brain or meat and bone meal and tallow prepared from sheep with scrapie remained normal for 8 years after exposure. This work indicates that cattle are highly resistant to North American scrapie by the oral route.

Pathogenicity of West Nile virus in chickens.

In the fall of 1999, West Nile virus (WNV) was isolated for the first time in the Western Hemisphere during an outbreak of neurologic disease in humans, horses, and wild and zoo birds in the northeastern United States. Chickens are a potential reservoir for WNV, and little is known about the pathogenicity of WNV in domestic chickens. Seven-week-old chickens derived from a specific-pathogen-free flock were inoculated subcutaneously with 1.8 x 10(3) 50% tissue culture infectious dose of a crow isolate of WNV in order to observe clinical signs and evaluate the viremic phase, gross and microscopic lesions, contact transmission, and immunologic response. There were no observable clinical signs in the WNV-inoculated chickens during the 21-day observation period. However, histopathologic examination of tissues revealed myocardial necrosis, nephritis, and pneumonitis at 5 and 10 days postinoculation (DPI); moderate to severe nonsuppurative encephalitis also was observed in brain tissue from one of four inoculated birds examined at 21 DPI. WNV was recovered from blood plasma for up to 8 DPI. Virus titers as high as 10(5)/ml in plasma were observed at 4 DPI. Fecal shedding of virus was detected in cloacal swabs on 4 and 5 DPI only. The WNV also was isolated from myocardium, spleen, kidney, lung, and intestine collected from chickens euthanatized at 3, 5, and 10 DPI. No virus was isolated from inoculated chickens after 10 DPI. Antibodies specific to WNV were detected in inoculated chickens as early as 5 DPI by the plaque reduction neutralization test and 7 DPI by the indirect fluorescent antibody test. Chickens placed in contact with inoculated chickens at 1 DPI lacked WNV-specific antibodies, and no WNV was isolated from their blood plasma or cloacal swabs throughout the 21 days of the experiment.