Wildfire in western U.S. federally managed for- ests has increased substantially in recent decades, with large (>1000 acre) fires in the decade through 2012 over five times as frequent (450 percent increase) and burned area over ten times as great (930 percent increase) as the 1970s and early 1980s. These changes are closely linked to increased tempera- tures and a greater frequency and intensity of drought. Pro- jected additional future warming implies that wildfire activ- ity may continue to increase in western forests. However, the interaction of changes in climate, fire and other disturbances, vegetation and land management may eventually transform some forest ecosystems and fire regimes, with changes in the spatial extent of forest and fire regime types. In particular, for- ests characterized by infrequent, high-severity stand replac- ing fire may be highly sensitive to warming. Increased wildfire combined with warming may transform these ecosystems such that fuel availability, rather than flammability, becomes the dominant constraint on fire activity. Climate will continue to warm for some time regardless of future greenhouse gas emis- sions, requiring adaptation to warmer temperatures. Changes in forest location, extent and type will result in substantial changes in ecosystem services.

We have prospectively followed over a 5-year period 434 volunteers who were at intake ambulatory, functional, presumably nondemented, and between 75 and 85 years of age. Fifty-six (an incidence of 3.53 per 100 person-years at risk) developed a progressive dementia: 32 met diagnostic criteria for Alzheimer's disease (AD) (an incidence of 2.0 per 100 person-years at risk), 15 had vascular or mixed dementia, and 9 had other disorders or remain undiagnosed. New cases of dementia were as common as myocardial infarction and twice as common as stroke. Risk factors for both dementia and AD were age (over 80) and gender (female); other reported risk factors such as family history, prior head injury, thyroid disease, maternal age, and smoking were not risk factors for AD in this elderly cohort. Prior stroke was the major risk factor for vascular or mixed dementia; diabetes and left ventricular hypertrophy but not a history of hypertension per se were also risk factors for vascular dementia. The major predictor of the development of AD was the mental status score on entry. The 58.5% of the cohort who made zero to two errors on a 33-item mental status test had a less than 0.6% per year chance of developing AD, whereas the 16% of the cohort with five to eight errors on this test developed AD at a rate of over 12% per year. Thus, it is possible to identify a large cohort of 80-year-olds who are at low risk for AD and a smaller cohort at very high risk.

Objectives

HIV-infected individuals bear increased cardiovascular risk even in the absence of traditional cardiovascular risk factors. In the general population, coronary artery calcium (CAC) scanning is of value for cardiovascular risk stratification, but whether a CAC score of zero implies a low noncalcified coronary plaque burden in HIV-infected persons is unknown.

Methods

We assessed the prevalence of noncalcified coronary plaque and compared noncalcified coronary plaque burden between HIV-infected and HIV-uninfected participants who had CAC scores of zero in the Multicenter AIDS Cohort Study (MACS) using coronary computed tomography (CT) angiography.

Results

HIV infection was associated with the presence of noncalcified coronary plaque among these men with CAC scores of zero. In a model adjusted only for age, race, centre, and pre- or post-2001 cohort, the prevalence ratio for the presence of noncalcified plaque was 1.27 (95% confidence interval 1.04-1.56; P = 0.02). After additionally adjusting for cardiovascular risk factors, HIV infection remained associated with the presence of noncalcified coronary plaque (prevalence ratio 1.31; 95% confidence interval 1.07-1.6; P = 0.01).

Conclusions

Among men with CAC scores of zero, HIV infection is associated with an increased prevalence of noncalcified coronary plaque independent of traditional cardiovascular risk factors. This finding suggests that CAC scanning may underestimate plaque burden in HIV-infected men.

Neuronal remodeling in human heart disease is not well understood. Stellate ganglia from patients with cardiomyopathy (CMY) and refractory ventricular arrhythmias undergoing cardiac sympathetic denervation (n = 8), and from organ donors with normal hearts (n = 8) collected at the time of organ procurement were compared. Clinical data on all subjects were reviewed. Electron microscopy (EM), histologic, and immunohistochemical assessments of neurotransmitter profiles, glial activation and distribution, and lipofuscin deposition, a marker of oxidative stress, were quantified. In CMY specimens, lipofuscin deposits were larger, and present in more neurons (26.3% ± 6.3% vs. 16.7% ± 7.6%, P < 0.043), than age-matched controls. EM analysis revealed extensive mitochondrial degeneration in CMY specimens. T cell (CD3+) infiltration was identified in 60% of the CMY samples, with one case having large inflammatory nodules, while none were identified in controls. Myeloperoxidase-immunoreactive neutrophils were also identified at parenchymal sites distinct from inflammatory foci in CMY ganglia, but not in controls. The adrenergic phenotype of pathologic samples revealed a decrease in tyrosine hydroxylase staining intensity compared with controls. Evaluation of cholinergic phenotype by staining for the vesicular acetylcholine transporter revealed a low but comparable number of cholinergic neurons in ganglia from both groups and demonstrated that preganglionic cholinergic innervation was maintained in CMY ganglia. S100 staining (a glial cell marker) demonstrated no differences in glial distribution and relationship to neurons; however, glial activation demonstrated by glial fibrillary acidic protein (GFAP) staining was substantially increased in pathologic specimens compared with controls. Stellate ganglia from patients with CMY and arrhythmias demonstrate inflammation, neurochemical remodeling, oxidative stress, and satellite glial cell activation. These changes likely contribute to excessive and dysfunctional efferent sympathetic tone, and provide a rationale for sympathectomy as a treatment for arrhythmias in this population. This work was made possible by support from NIH grants HL125730 to OAA, GM107949 to DBH, and HL084261 and OT2OD023848 to KS.

Written and verbal languages are neurobehavioral traits vital to the development of communication skills. Unfortunately, disorders involving these traits-specifically reading disability (RD) and language impairment (LI)-are common and prevent affected individuals from developing adequate communication skills, leaving them at risk for adverse academic, socioeconomic and psychiatric outcomes. Both RD and LI are complex traits that frequently co-occur, leading us to hypothesize that these disorders share genetic etiologies. To test this, we performed a genome-wide association study on individuals affected with both RD and LI in the Avon Longitudinal Study of Parents and Children. The strongest associations were seen with markers in ZNF385D (OR = 1.81, P = 5.45 × 10(-7) ) and COL4A2 (OR = 1.71, P = 7.59 × 10(-7) ). Markers within NDST4 showed the strongest associations with LI individually (OR = 1.827, P = 1.40 × 10(-7) ). We replicated association of ZNF385D using receptive vocabulary measures in the Pediatric Imaging Neurocognitive Genetics study (P = 0.00245). We then used diffusion tensor imaging fiber tract volume data on 16 fiber tracts to examine the implications of replicated markers. ZNF385D was a predictor of overall fiber tract volumes in both hemispheres, as well as global brain volume. Here, we present evidence for ZNF385D as a candidate gene for RD and LI. The implication of transcription factor ZNF385D in RD and LI underscores the importance of transcriptional regulation in the development of higher order neurocognitive traits. Further study is necessary to discern target genes of ZNF385D and how it functions within neural development of fluent language.