Utilization and Perception of Peer-Support After Lower Limb Loss in the United States: Potential Benefits on Mobility Outcomes.

OBJECTIVE: To examine participants' experiences with peer-support after lower limb loss (LLL) and the associations between the peer-support experience (perceived benefits and barriers) and mobility outcomes. DESIGN: Quantitative and qualitative descriptive study with a cross-sectional design. SETTING: National survey (distributed to 169 peer-support groups in 44 states in the US). PARTICIPANTS: The survey was completed by 82 individuals with a major lower limb amputation (53% female, 54% over 55 years of age; N=82). MAIN OUTCOME MEASURES: A 32-item survey to examine respondents' experiences in peer-support activities. Prosthetic mobility was measured using the Prosthetic Limb Users Survey of Mobility (PLUS-M). RESULTS: Two out of 3 respondents received some forms of peer-support after amputation. Among them 75% reported peer-support having a positive effect on their outlook on life, and 78% reported that information gained from peer-support was helpful. Companionship, altruistic acts, and gaining information on how to cope with amputation were the top themes of why respondents enjoyed the peer-support experience. Nearly all (94%) respondents would recommend peer-support to other people with LLL. Individuals who received peer-support exhibited a trend of greater mobility (55th vs 36th percentile on PLUS-M; P=.055). CONCLUSION: Individuals with LLL reported generally positive experiences regarding their engagement in peer-support activities. Peer-support groups are viewed as a helpful source for both information and emotional support, potentially benefiting functional and psychological recovery after amputation. Individuals who have received peer-support also exhibited greater mobility.

Retinal pathological features and proteome signatures of Alzheimer's disease.

Alzheimer's disease (AD) pathologies were discovered in the accessible neurosensory retina. However, their exact nature and topographical distribution, particularly in the early stages of functional impairment, and how they relate to disease progression in the brain remain largely unknown. To better understand the pathological features of AD in the retina, we conducted an extensive histopathological and biochemical investigation of postmortem retina and brain tissues from 86 human donors. Quantitative examination of superior and inferior temporal retinas from mild cognitive impairment (MCI) and AD patients compared to those with normal cognition (NC) revealed significant increases in amyloid ß-protein (Aß42) forms and novel intraneuronal Aß oligomers (AßOi), which were closely associated with exacerbated retinal macrogliosis, microgliosis, and tissue atrophy. These pathologies were unevenly distributed across retinal layers and geometrical areas, with the inner layers and peripheral subregions exhibiting most pronounced accumulations in the MCI and AD versus NC retinas. While microgliosis was increased in the retina of these patients, the proportion of microglial cells engaging in Aß uptake was reduced. Female AD patients exhibited higher levels of retinal microgliosis than males. Notably, retinal Aß42, S100 calcium-binding protein B+ macrogliosis, and atrophy correlated with severity of brain Aß pathology, tauopathy, and atrophy, and most retinal pathologies reflected Braak staging. All retinal biomarkers correlated with the cognitive scores, with retinal Aß42, far-peripheral AßOi and microgliosis displaying the strongest correlations. Proteomic analysis of AD retinas revealed activation of specific inflammatory and neurodegenerative processes and inhibition of oxidative phosphorylation/mitochondrial, and photoreceptor-related pathways. This study identifies and maps retinopathy in MCI and AD patients, demonstrating the quantitative relationship with brain pathology and cognition, and may lead to reliable retinal biomarkers for noninvasive retinal screening and monitoring of AD.

Retinal arterial Aß40 deposition is linked with tight junction loss and cerebral amyloid angiopathy in MCI and AD patients.

INTRODUCTION: Vascular amyloid beta (Aß) protein deposits were detected in retinas of mild cognitively impaired (MCI) and Alzheimer's disease (AD) patients. We tested the hypothesis that the retinal vascular tight junctions (TJs) were compromised and linked to disease status. METHODS: TJ components and Aß expression in capillaries and larger blood vessels were determined in post mortem retinas from 34 MCI or AD patients and 27 cognitively normal controls and correlated with neuropathology. RESULTS: Severe decreases in retinal vascular zonula occludens-1 (ZO-1) and claudin-5 correlating with abundant arteriolar Aß40 deposition were identified in MCI and AD patients. Retinal claudin-5 deficiency was closely associated with cerebral amyloid angiopathy, whereas ZO-1 defects correlated with cerebral pathology and cognitive deficits. DISCUSSION: We uncovered deficiencies in blood-retinal barrier markers for potential retinal imaging targets of AD screening and monitoring. Intense retinal arteriolar Aß40 deposition suggests a common pathogenic mechanism of failed Aß clearance via intramural periarterial drainage.

Exosomal tau with seeding activity is released from Alzheimer's disease synapses, and seeding potential is associated with amyloid beta.

Synaptic transfer of tau has long been hypothesized from the human pathology pattern and has been demonstrated in vitro and in vivo, but the precise mechanisms remain unclear. Extracellular vesicles such as exosomes have been suggested as a mechanism, but not all tau is exosomal. The present experiments use a novel flow cytometry assay to quantify depolarization of synaptosomes by KCl after loading with FM2-10, which induces a fluorescence reduction associated with synaptic vesicle release; the degree of reduction in cryopreserved human samples equaled that seen in fresh mouse synaptosomes. Depolarization induced the release of vesicles in the size range of exosomes, along with tetraspanin markers of extracellular vesicles. A number of tau peptides were released, including tau oligomers; released tau was primarily unphosphorylated and C-terminal truncated, with Aß release just above background. When exosomes were immunopurified from release supernatants, a prominent tau band showed a dark smeared appearance of SDS-stable oligomers along with the exosomal marker syntenin-1, and these exosomes induced aggregation in the HEK tau biosensor assay. However, the flow-through did not seed aggregation. Size exclusion chromatography of purified released exosomes shows faint signals from tau in the same fractions that show a CD63 band, an exosomal size signal, and seeding activity. Crude synaptosomes from control, tauopathy, and AD cases demonstrated lower seeding in tauopathy compared to AD that is correlated with the measured Aß42 level. These results show that AD synapses release exosomal tau that is C-terminal-truncated, oligomeric, and with seeding activity that is enhanced by Aß. Taken together with previous findings, these results are consistent with a direct prion-like heterotypic seeding of tau by Aß within synaptic terminals, with subsequent loading of aggregated tau onto exosomes that are released and competent for tau seeding activity.

Cerebral Amyloid Angiopathy-related Inflammation Presenting With a Cystic Lesion in Young-onset Alzheimer Disease.

We describe a patient with cerebral amyloid angiopathy-related inflammation (CAA-ri) presenting as Alzheimer disease (AD) with a mass lesion with symptom onset at age 59. He was found to have a nonenhancing lesion in the right temporal lobe on magnetic resonance imaging without evidence of hemorrhage. He underwent a biopsy which showed amyloid beta in blood vessel walls and a perivascular inflammatory infiltrate consistent with CAA-ri. Neurofibrillary tangles were present and a flortaucipir positron emission tomography showed bilateral signal highest in the lateral temporal and parietal cortices. A lumbar puncture showed tau, p-tau, and amyloid beta levels consistent with AD without evidence of inflammation. He was homozygous for the APOE ε4 allele. He died at age 67. A focus of CAA-ri can be present in the context of AD with a mass lesion and without evidence of hemorrhage, significant ischemic changes, or overt inflammation on cerebrospinal fluid examination.

Non-linguistic cognitive measures as predictors of functionally defined developmental language disorder in monolingual and bilingual children.

BACKGROUND & AIMS: Given that standardized language measures alone are inadequate for identifying functionally defined developmental language disorder (fDLD), this study investigated whether non-linguistic cognitive abilities (procedural learning, motor functions, executive attention, processing speed) can increase the prediction accuracy of fDLD in children in linguistically diverse settings. METHODS & PROCEDURES: We examined non-linguistic cognitive abilities in mono- and bilingual school-aged children (ages 8-12) with and without fDLD. Typically developing (TD) children (14 monolinguals, 12 bilinguals) and children with fDLD (28 monolinguals, 12 bilinguals) completed tasks measuring motor functions, procedural learning, executive attention and processing speed. Children were assigned as fDLD based on parental or professional concerns regarding children's daily language functioning. If no concerns were present, children were assigned as TD. Standardized English scores, non-verbal IQ scores and years of maternal education were also obtained. Likelihood ratios were used to examine how well each measure separated the fDLD versus TD groups. A binary logistic regression was used to test whether combined measures enhanced the prediction of identifying fDLD status. OUTCOMES & RESULTS: A combination of linguistic and non-linguistic measures provided the best distinction between fDLD and TD for both mono- and bilingual groups. For monolingual children, the combined measures include English language scores, functional motor abilities and processing speed, whereas for bilinguals, the combined measures include English language scores and procedural learning. CONCLUSIONS & IMPLICATIONS: A combination of non-linguistic and linguistic measures significantly improved the distinction between fDLD and TD for both mono- and bilingual groups. This study supports the possibility of using non-linguistic cognitive measures to identify fDLD in linguistically diverse settings. WHAT THIS PAPER ADDS: What is already known on the subject Given that standardized English language measures may fail to identify functional language disorder, we examined whether supplementing English language measures with non-linguistic cognitive tasks could resolve the problem. Our study is based on the hypothesis that non-linguistic cognitive abilities contribute to language processing and learning. This is further supported by previous findings that children with language disorder exhibit non-linguistic cognitive deficits. What this paper adds to existing knowledge The results indicated that a combination of linguistic and non-linguistic cognitive abilities increased the prediction of functional language disorder in both mono- and bilingual children. What are the potential or actual clinical implications of this work? This study supports the possibility of using non-linguistic cognitive measures to identify the risk of language disorder in linguistically diverse settings.

Impact of Patient Engagement on Tailored Education for Joint Replacement Population Using Technology.

Patient engagement and technology use for healthcare are important for optimal care. This study was designed to leverage technology in education among the adult joint population based on their engagement capacity and utilization of technology for care. A convenience sample of 80 patients undergoing joint replacement surgery and followed in the inpatient setting participated. Comparisons were made between an intervention group who completed the Person Engagement Index to measure their engagement capacity and received a technological educational plan based on their score versus those receiving the standard educational plan. The Person Engagement Index psychometrics were sound and indicated high engagement capacity. Overall, the groups did not differ in utilization, satisfaction, and education comprehension; however, the intervention group reported a higher unit mean for the extent they felt ready for discharge and instructions for care at home. Results of this study informed patients' engagement capacity and technology use for pre-/postoperative education for procedure expectations and self-management throughout the joint replacement process and recovery. Future research includes use of technology for engagement capacity and outcomes with other populations, collecting socio-demographic data to determine differences among groups and examining the patient and provider experience and satisfaction with using technology to enhance care and outcomes.

Apolipoprotein E/Amyloid-ß Complex Accumulates in Alzheimer Disease Cortical Synapses via Apolipoprotein E Receptors and Is Enhanced by APOE4.

Apolipoprotein E (apoE) colocalizes with amyloid-ß (Aß) in Alzheimer disease (AD) plaques and in synapses, and evidence suggests that direct interactions between apoE and Aß are important for apoE's effects in AD. The present work examines the hypothesis that apoE receptors mediate uptake of apoE/Aß complex into synaptic terminals. Western blot analysis shows multiple SDS-stable assemblies in synaptosomes from human AD cortex; apoE/Aß complex was markedly increased in AD compared with aged control samples. Complex formation between apoE and Aß was confirmed by coimmunoprecipitation experiments. The apoE receptors low-density lipoprotein receptor (LDLR) and LDLR-related protein 1 (LRP1) were quantified in synaptosomes using flow cytometry, revealing up-regulation of LRP1 in early- and late-stage AD. Dual-labeling flow cytometry analysis of LRP1- and LDLR positives indicate most (approximately 65%) of LDLR and LRP1 is associated with postsynaptic density-95 (PSD-95)-positive synaptosomes, indicating that remaining LRP1 and LDLR receptors are exclusively presynaptic. Flow cytometry analysis of Nile red labeling revealed a reduction in cholesterol esters in AD synaptosomes. Dual-labeling experiments showed apoE and Aß concentration into LDLR and LRP1-positive synaptosomes, along with free and esterified cholesterol. Synaptic Aß was increased by apoE4 in control and AD samples. These results are consistent with uptake of apoE/Aß complex and associated lipids into synaptic terminals, with subsequent Aß clearance in control synapses and accumulation in AD synapses.

Identification of early pericyte loss and vascular amyloidosis in Alzheimer's disease retina.

Pericyte loss and deficient vascular platelet-derived growth factor receptor-ß (PDGFRß) signaling are prominent features of the blood-brain barrier breakdown described in Alzheimer's disease (AD) that can predict cognitive decline yet have never been studied in the retina. Recent reports using noninvasive retinal amyloid imaging, optical coherence tomography angiography, and histological examinations support the existence of vascular-structural abnormalities and vascular amyloid ß-protein (Aß) deposits in retinas of AD patients. However, the cellular and molecular mechanisms of such retinal vascular pathology were not previously explored. Here, by modifying a method of enzymatically clearing non-vascular retinal tissue and fluorescent immunolabeling of the isolated blood vessel network, we identified substantial pericyte loss together with significant Aß deposition in retinal microvasculature and pericytes in AD. Evaluation of postmortem retinas from a cohort of 56 human donors revealed an early and progressive decrease in vascular PDGFRß in mild cognitive impairment (MCI) and AD compared to cognitively normal controls. Retinal PDGFRß loss significantly associated with increased retinal vascular Aß40 and Aß42 burden. Decreased vascular LRP-1 and early apoptosis of pericytes in AD retina were also detected. Mapping of PDGFRß and Aß40 levels in pre-defined retinal subregions indicated that certain geometrical and cellular layers are more susceptible to AD pathology. Further, correlations were identified between retinal vascular abnormalities and cerebral Aß burden, cerebral amyloid angiopathy (CAA), and clinical status. Overall, the identification of pericyte and PDGFRß loss accompanying increased vascular amyloidosis in Alzheimer's retina implies compromised blood-retinal barrier integrity and provides new targets for AD diagnosis and therapy.

Integrating Subjective and Objective Dimensions of Resilience in Fire-Prone Landscapes.

Resilience has become a common goal for science-based natural resource management, particularly in the context of changing climate and disturbance regimes. Integrating varying perspectives and definitions of resilience is a complex and often unrecognized challenge to applying resilience concepts to social-ecological systems (SESs) management. Using wildfire as an example, we develop a framework to expose and separate two important dimensions of resilience: the inherent properties that maintain structure, function, or states of an SES and the human perceptions of desirable or valued components of an SES. In doing so, the framework distinguishes between value-free and human-derived, value-explicit dimensions of resilience. Four archetypal scenarios highlight that ecological resilience and human values do not always align and that recognizing and anticipating potential misalignment is critical for developing effective management goals. Our framework clarifies existing resilience theory, connects literature across disciplines, and facilitates use of the resilience concept in research and land-management applications.

Weight Stigma and Hypothalamic-Pituitary-Adrenocortical Axis Reactivity in Individuals Who Are Overweight.

BACKGROUND: Stigmatized people exhibit blunted cortisol responses to many stressors. PURPOSE: To examine the cortisol responses of individuals who are overweight to a stigma-related stressor involving interviewing for a weight-discriminatory company. METHODS: We recruited 170 men and women (mean age = 35.01) from towns located within about a 30-min drive of the study center. Weight was assessed using body mass index (BMI) and self-perceptions about being overweight. Participants were exposed to a laboratory stressor, modeled after the Trier Social Stress Test. In the stigmatizing condition, participants gave a supposedly videotaped speech about what makes them a good candidate for a job at a company that was described as having a weight-discriminatory health insurance benefit. Participants in the nonstigmatizing condition made a supposedly audiotaped speech for a company whose health insurance benefit was not described. Cortisol reactivity was then assessed. RESULTS: Participants who rated themselves as overweight or who were overweight according to their BMI evidenced a blunted cortisol response in the weight-stigmatizing condition, whereas lean participants in the weight-stigmatizing condition showed the rise in cortisol levels that typically occurs following the Trier Social Stress Test. CONCLUSIONS: People who experience the chronic stress of being stigmatized due to their weight show blunted cortisol responses just as other chronically stressed people do.

Fine-scale spatial climate variation and drought mediate the likelihood of reburning.

In many forested ecosystems, it is increasingly recognized that the probability of burning is substantially reduced within the footprint of previously burned areas. This self-limiting effect of wildland fire is considered a fundamental emergent property of ecosystems and is partly responsible for structuring landscape heterogeneity (i.e., mosaics of different age classes), thereby reducing the likelihood of uncharacteristically large fires in regions with active fire regimes. However, the strength and longevity of this self-limiting phenomenon is not well understood in most fire-prone ecosystems. In this study, we quantify the self-limiting effect in terms of its strength and longevity for five fire-prone study areas in western North America and investigate how each measure varies along a spatial climatic gradient and according to temporal (i.e., annual) climatic variation. Results indicate that the longevity (i.e., number of years) of the self-limiting effect ranges between 15 yr in the warm and dry study area in the southwestern United States to 33 yr in the cold, northern study areas in located in northwestern Montana and the boreal forest of Canada. We also found that spatial climatic variation has a strong influence on wildland fire's self-limiting capacity. Specifically, the self-limiting effect within each study area was stronger and lasted longer in areas with low mean moisture deficit (i.e., wetter and cooler settings) compared to areas with high mean moisture deficit (warmer and drier settings). Last, our findings show that annual climatic variation influences wildland fire's self-limiting effect: drought conditions weakened the strength and longevity of the self-limiting effect in all study areas, albeit at varying magnitudes. Overall, our study provides support for the idea that wildland fire contributes to spatial heterogeneity in fuel ages that subsequently mediate future fire sizes and effects. However, our findings show that the strength and longevity of the self-limiting effect varies considerably according to spatial and temporal climatic variation, providing land and fire managers relevant information for effective planning and management of fire and highlighting that fire itself is an important factor contributing to fire-free intervals.

Synaptic Amyloid-ß Oligomers Precede p-Tau and Differentiate High Pathology Control Cases.

Amyloid-ß (Aß) and hyperphosphorylated tau (p-tau) aggregates form the two discrete pathologies of Alzheimer disease (AD), and oligomeric assemblies of each protein are localized to synapses. To determine the sequence by which pathology appears in synapses, Aß and p-tau were quantified across AD disease stages in parietal cortex. Nondemented cases with high levels of AD-related pathology were included to determine factors that confer protection from clinical symptoms. Flow cytometric analysis of synaptosome preparations was used to quantify Aß and p-tau in large populations of individual synaptic terminals. Soluble Aß oligomers were assayed by a single antibody sandwich enzyme-linked immunosorbent assay. Total in situ Aß was elevated in patients with early- and late-stage AD dementia, but not in high pathology nondemented controls compared with age-matched normal controls. However, soluble Aß oligomers were highest in early AD synapses, and this assay distinguished early AD cases from high pathology controls. Overall, synapse-associated p-tau did not increase until late-stage disease in human and transgenic rat cortex, and p-tau was elevated in individual Aß-positive synaptosomes in early AD. These results suggest that soluble oligomers in surviving neocortical synaptic terminals are associated with dementia onset and suggest an amyloid cascade hypothesis in which oligomeric Aß drives phosphorylated tau accumulation and synaptic spread. These results indicate that antiamyloid therapies will be less effective once p-tau pathology is developed.

Potential relocation of climatic environments suggests high rates of climate displacement within the North American protection network.

Ongoing climate change may undermine the effectiveness of protected area networks in preserving the set of biotic components and ecological processes they harbor, thereby jeopardizing their conservation capacity into the future. Metrics of climate change, particularly rates and spatial patterns of climatic alteration, can help assess potential threats. Here, we perform a continent-wide climate change vulnerability assessment whereby we compare the baseline climate of the protected area network in North America (Canada, United States, México-NAM) to the projected end-of-century climate (2071-2100). We estimated the projected pace at which climatic conditions may redistribute across NAM (i.e., climate velocity), and identified future nearest climate analogs to quantify patterns of climate relocation within, among, and outside protected areas. Also, we interpret climatic relocation patterns in terms of associated land-cover types. Our analysis suggests that the conservation capacity of the NAM protection network is likely to be severely compromised by a changing climate. The majority of protected areas (~80%) might be exposed to high rates of climate displacement that could promote important shifts in species abundance or distribution. A small fraction of protected areas (<10%) could be critical for future conservation plans, as they will host climates that represent analogs of conditions currently characterizing almost a fifth of the protected areas across NAM. However, the majority of nearest climatic analogs for protected areas are in nonprotected locations. Therefore, unprotected landscapes could pose additional threats, beyond climate forcing itself, as sensitive biota may have to migrate farther than what is prescribed by the climate velocity to reach a protected area destination. To mitigate future threats to the conservation capacity of the NAM protected area network, conservation plans will need to capitalize on opportunities provided by the existing availability of natural land-cover types outside the current network of NAM protected areas.

Good Publication Practice for Communicating Company-Sponsored Medical Research: GPP3.

This updated Good Publication Practice (GPP) guideline, known as GPP3, builds on earlier versions and provides recommendations for individuals and organizations that contribute to the publication of research results sponsored or supported by pharmaceutical, medical device, diagnostics, and biotechnology companies. The recommendations are designed to help individuals and organizations maintain ethical and transparent publication practices and comply with legal and regulatory requirements. These recommendations cover publications in peer-reviewed journals and presentations (oral or poster) at scientific congresses. The International Society for Medical Publication Professionals invited more than 3000 professionals worldwide to apply for a position on the steering committee, or as a reviewer, for this guideline. The GPP2 authors reviewed all applications (n = 241) and assembled an 18-member steering committee that represented 7 countries and a diversity of publication professions and institutions. From the 174 selected reviewers, 94 sent comments on the second draft, which steering committee members incorporated after discussion and consensus. The resulting guideline includes new sections (Principles of Good Publication Practice for Company-Sponsored Medical Research, Data Sharing, Studies That Should Be Published, and Plagiarism), expands guidance on the International Committee of Medical Journal Editors' authorship criteria and common authorship issues, improves clarity on appropriate author payment and reimbursement, and expands information on the role of medical writers. By following good publication practices (including GPP3), individuals and organizations will show integrity; accountability; and responsibility for accurate, complete, and transparent reporting in their publications and presentations.

Pre-synaptic C-terminal truncated tau is released from cortical synapses in Alzheimer's disease.

The microtubule-associated protein tau has primarily been associated with axonal location and function; however, recent work shows tau release from neurons and suggests an important role for tau in synaptic plasticity. In our study, we measured synaptic levels of total tau using synaptosomes prepared from cryopreserved human postmortem Alzheimer's disease (AD) and control samples. Flow cytometry data show that a majority of synaptic terminals are highly immunolabeled with the total tau antibody (HT7) in both AD and control samples. Immunoblots of synaptosomal fractions reveal increases in a 20 kDa tau fragment and in tau dimers in AD synapses, and terminal-specific antibodies show that in many synaptosome samples tau lacks a C-terminus. Flow cytometry experiments to quantify the extent of C-terminal truncation reveal that only 15-25% of synaptosomes are positive for intact C-terminal tau. Potassium-induced depolarization demonstrates release of tau and tau fragments from pre-synaptic terminals, with increased release from AD compared to control samples. This study indicates that tau is normally highly localized to synaptic terminals in cortex where it is well-positioned to affect synaptic plasticity. Tau cleavage may facilitate tau aggregation as well as tau secretion and propagation of tau pathology from the pre-synaptic compartment in AD. Results demonstrate the abundance of tau, mainly C-terminal truncated tau, in synaptic terminals in aged control and in Alzheimer's disease (AD) samples. Tau fragments and dimers/oligomers are prominent in AD synapses. Following depolarization, tau release is potentiated in AD nerve terminals compared to aged controls. We hypothesize (i) endosomal release of the different tau peptides from AD synapses, and (ii) together with phosphorylation, fragmentation of synaptic tau exacerbates tau aggregation, synaptic dysfunction, and the spread of tau pathology in AD. Aß = amyloid-beta.

Wildland fire as a self-regulating mechanism: the role of previous burns and weather in limiting fire progression.

Theory suggests that natural fire regimes can result in landscapes that are both self-regulating and resilient to fire. For example, because fires consume fuel, they may create barriers to the spread of future fires, thereby regulating fire size. Top-down controls such as weather, however, can weaken this effect. While empirical examples demonstrating this pattern-process feedback between vegetation and fire exist, they have been geographically limited or did not consider the influence of time between fires and weather. The availability of remotely sensed data identifying fire activity over the last four decades provides an opportunity to explicitly quantify-the ability of wildland fire to limit the progression of subsequent fire. Furthermore, advances in fire progression mapping now allow an evaluation of how daily weather as a top-down control modifies this effect. In this study, we evaluated the ability of wildland fire to create barriers that limit the spread of subsequent fire along a gradient representing time between fires in four large study areas in the western United States. Using fire progression maps in conjunction with weather station data, we also evaluated the influence of daily weather. Results indicate that wildland fire does limit subsequent fire spread in all four study areas, but this effect decays over time; wildland fire no longer limits subsequent fire spread 6-18 years after fire, depending on the study area. We also found that the ability of fire to regulate, subsequent fire progression was substantially reduced under extreme conditions compared to moderate weather conditions in all four study areas. This study increases understanding of the spatial feedbacks that can lead to self-regulating landscapes as well as the effects of top-down controls, such as weather, on these feedbacks. Our results will be useful to managers who seek to restore natural fire regimes or to exploit recent burns when managing fire.

Psychological symptoms are associated with both abstinence and risky sex among men with HIV.

Sexual abstinence is often deemed the "safest behavior" in HIV prevention, but is sometimes associated with psychological symptoms (e.g., depression) just as sexually risky behavior is. This study explored whether sexual abstinence and risky sexual behavior among men with HIV were associated with similar constellations of psychological symptoms. Prior research has not addressed this issue because abstinent people often are not included in the sample or, when data are analyzed, researchers combine abstinent people with sexually active people who practice safer sex. Past research also neglects the co-morbidity of psychological symptoms. A latent class analysis of the psychological symptoms (assessed with the Symptom Check List 90-R; Derogatis, 1994) of 140 men with HIV, mostly from rural New England, revealed three latent classes: men who were asymptomatic on all symptom domains (28.8 %), men who were symptomatic on all domains (34.1 %), and men who were symptomatic on internalizing domains (37.1 %), but were asymptomatic on the externalizing symptoms of hostility and paranoid ideation. Logistic regression showed that sexual behavior during the past 90 days of men in the all symptom class and the internalizing symptoms class was similar, with abstinence and risky sex predominating, and safer sex being relatively uncommon for both classes. The sexual behavior of men in the asymptomatic class differed, with safer sex being relatively more likely to occur compared to the symptomatic classes. These findings suggest that the psychological symptom profile of sexually abstinent people places them at risk for inconsistent condom use should they engage in sexual behavior.

Levels of soluble apolipoprotein E/amyloid-ß (Aß) complex are reduced and oligomeric Aß increased with APOE4 and Alzheimer disease in a transgenic mouse model and human samples.

Human apolipoprotein E (apoE) isoforms may differentially modulate amyloid-ß (Aß) levels. Evidence suggests physical interactions between apoE and Aß are partially responsible for these functional effects. However, the apoE/Aß complex is not a single static structure; rather, it is defined by detection methods. Thus, literature results are inconsistent and difficult to interpret. An ELISA was developed to measure soluble apoE/Aß in a single, quantitative method and was used to address the hypothesis that reduced levels of soluble apoE/Aß and an increase in soluble Aß, specifically oligomeric Aß (oAß), are associated with APOE4 and AD. Previously, soluble Aß42 and oAß levels were greater with APOE4 compared with APOE2/APOE3 in hippocampal homogenates from EFAD transgenic mice (expressing five familial AD mutations and human apoE isoforms). In this study, soluble apoE/Aß levels were lower in E4FAD mice compared with E2FAD and E3FAD mice, thus providing evidence that apoE/Aß levels isoform-specifically modulate soluble oAß clearance. Similar results were observed in soluble preparations of human cortical synaptosomes; apoE/Aß levels were lower in AD patients compared with controls and lower with APOE4 in the AD cohort. In human CSF, apoE/Aß levels were also lower in AD patients and with APOE4 in the AD cohort. Importantly, although total Aß42 levels decreased in AD patients compared with controls, oAß levels increased and were greater with APOE4 in the AD cohort. Overall, apoE isoform-specific formation of soluble apoE/Aß modulates oAß levels, suggesting a basis for APOE4-induced AD risk and a mechanistic approach to AD biomarkers.