Morphological variability or inter-observer bias? A methodological toolkit to improve data quality of multi-researcher datasets for the analysis of morphological variation.

OBJECTIVES: The investigation of morphological variation in animals is widely used in taxonomy, ecology, and evolution. Using large datasets for meta-analyses has dramatically increased, raising concerns about dataset compatibilities and biases introduced by contributions of multiple researchers. MATERIALS AND METHODS: We compiled morphological data on 13 variables for 3073 individual mouse lemurs (Cheirogaleidae, Microcebus spp.) from 25 taxa and 153 different sampling locations, measured by 48 different researchers. We introduced and applied a filtering pipeline and quantified improvements in data quality (Shapiro-Francia statistic, skewness, and excess kurtosis). The filtered dataset was then used to test for genus-wide sexual size dimorphism and the applicability of Rensch's, Allen's, and Bergmann's rules. RESULTS: Our pipeline reduced inter-observer bias (i.e., increased normality of data distributions). Inter-observer reliability of measurements was notably variable, highlighting the need to reduce data collection biases. Although subtle, we found a consistent pattern of sexual size dimorphism across Microcebus, with females being the larger (but not heavier) sex. Sexual size dimorphism was isometric, providing no support for Rensch's rule. Variations in tail length but not in ear size were consistent with the predictions of Allen's rule. Body mass and length followed a pattern contrary to predictions of Bergmann's rule. DISCUSSION: We highlighted the usefulness of large multi-researcher datasets for testing ecological hypotheses after correcting for inter-observer biases. Using genus-wide tests, we outlined generalizable patterns of morphological variability across all mouse lemurs. This new methodological toolkit aims to facilitate future large-scale morphological comparisons for a wide range of taxa and applications.

Diversification processes in Gerp's mouse lemur demonstrate the importance of rivers and altitude as biogeographic barriers in Madagascar's humid rainforests.

Madagascar exhibits exceptionally high levels of biodiversity and endemism. Models to explain the diversification and distribution of species in Madagascar stress the importance of historical variability in climate conditions which may have led to the formation of geographic barriers by changing water and habitat availability. The relative importance of these models for the diversification of the various forest-adapted taxa of Madagascar has yet to be understood. Here, we reconstructed the phylogeographic history of Gerp's mouse lemur (Microcebus gerpi) to identify relevant mechanisms and drivers of diversification in Madagascar's humid rainforests. We used restriction site associated DNA (RAD) markers and applied population genomic and coalescent-based techniques to estimate genetic diversity, population structure, gene flow and divergence times among M. gerpi populations and its two sister species M. jollyae and M. marohita. Genomic results were complemented with ecological niche models to better understand the relative barrier function of rivers and altitude. We show that M. gerpi diversified during the late Pleistocene. The inferred ecological niche, patterns of gene flow and genetic differentiation in M. gerpi suggest that the potential for rivers to act as biogeographic barriers depended on both size and elevation of headwaters. Populations on opposite sides of the largest river in the area with headwaters that extend far into the highlands show particularly high genetic differentiation, whereas rivers with lower elevation headwaters have weaker barrier functions, indicated by higher migration rates and admixture. We conclude that M. gerpi likely diversified through repeated cycles of dispersal punctuated by isolation to refugia as a result of paleoclimatic fluctuations during the Pleistocene. We argue that this diversification scenario serves as a model of diversification for other rainforest taxa that are similarly limited by geographic factors. In addition, we highlight conservation implications for this critically endangered species, which faces extreme habitat loss and fragmentation.

Activities of Energy Metabolism Enzymes in Atlantic Salmon Salmo salar L. Smolts and Parr Grown under Different Light Regimens.

Activities of enzymes of energy and carbohydrate metabolism in muscles and the liver were studied in Atlantic salmon Salmo salar L. smolts and parr grown under continuous or natural lighting and different feeding regimens in autumn followed by a short photoperiod in winter. Enzyme activities were found to differ between test and control salmon groups and between parr and smolts sampled at the end of the winter period. Smolts grown under continuous lighting and round-the-clock feeding differed from other groups by having higher cytochrome c oxidase (COX) activity and lower aldolase activity in muscles. Differences in aerobic metabolism in muscles between parr and smolts were found to be the same in all experimental groups, COX and aldolase activities being relatively higher in smolts. The pattern of changes in enzyme activities in the liver from parr to smolts differed between different experimental groups. Based on the results, the photoperiod was assumed to affect the activities of energy metabolism enzymes in salmon juveniles and may eventually affect the completion of smoltification.

Population genomic structure in Goodman's mouse lemur reveals long-standing separation of Madagascar's Central Highlands and eastern rainforests.

Madagascar's Central Highlands are largely composed of grasslands, interspersed with patches of forest. The historical perspective was that Madagascar's grasslands had anthropogenic origins, but emerging evidence suggests that grasslands were a component of the pre-human Central Highlands vegetation. Consequently, there is now vigorous debate regarding the extent to which these grasslands have expanded due to anthropogenic pressures. Here, we shed light on the temporal dynamics of Madagascar's vegetative composition by conducting a population genomic investigation of Goodman's mouse lemur (Microcebus lehilahytsara; Cheirogaleidae). These small-bodied primates occur both in Madagascar's eastern rainforests and in the Central Highlands, making them a valuable indicator species. Population divergences among forest-dwelling mammals will reflect changes to their habitat, including fragmentation, whereas patterns of post-divergence gene flow can reveal formerly wooded migration corridors. To explore these patterns, we used RADseq data to infer population genetic structure, demographic models of post-divergence gene flow, and population size change through time. The results offer evidence that open habitats are an ancient component of the Central Highlands, and that widespread forest fragmentation occurred naturally during a period of decreased precipitation near the last glacial maximum. Models of gene flow suggest that migration across the Central Highlands has been possible from the Pleistocene through the recent Holocene via riparian corridors. Though our findings support the hypothesis that Central Highland grasslands predate human arrival, we also find evidence for human-mediated population declines. This highlights the extent to which species imminently threatened by human-mediated deforestation may already be vulnerable from paleoclimatic conditions.

Blood caspase-8 concentrations and mortality among septic patients.

OBJECTIVE: No data are available on blood caspase-8 concentrations (the initiator caspase in the extrinsic apoptosis pathway) in septic patients. The present study thus describes the blood caspase-8 concentrations in survivors and non-survivors, and examines the possible association between blood caspase-8 concentrations and mortality in septic patients. DESIGN: A prospective observational study was carried out. SETTING: Three Spanish Intensive Care Units. PATIENTS: Septic patients. INTERVENTIONS: Serum caspase-8 concentrations were determined at the diagnosis of sepsis. MAIN VARIABLE OF INTEREST: Mortality after 30 days. RESULTS: Patients not surviving at day 30 (n=81) compared to surviving patients (n=140) showed higher serum caspase-8 levels (p<0.001). Multiple logistic regression analysis found an association between serum caspase-8 levels>43.5ng/ml and mortality (OR=3.306; 95%CI=1.619-6.753; p=0.001). The area under the curve (AUC) for mortality predicted by serum caspase-8 levels was 67% (95% CI=60-73%; p<0.001). CONCLUSIONS: The novel findings of our study were that blood caspase-8 concentrations are higher in non-survivors than in survivors, and that there is an association between blood caspase-8 concentrations and mortality in septic patients.

Blood caspase-8 concentrations and mortality among septic patients / Niveles sanguíneos de caspasa-8 y mortalidad de los pacientes sépticos

Objective: No data are available on blood caspase-8 concentrations (the initiator caspase in the extrinsic apoptosis pathway) in septic patients. The present study thus describes the blood caspase-8 concentrations in survivors and non-survivors, and examines the possible association between blood caspase-8 concentrations and mortality in septic patients.Design: A prospective observational study was carried out.Setting: Three Spanish Intensive Care Units.Patients: Septic patients.Interventions: Serum caspase-8 concentrations were determined at the diagnosis of sepsis.Main variable of interest: Mortality after 30 days.Results: Patients not surviving at day 30 (n=81) compared to surviving patients (n=140) showed higher serum caspase-8 levels (p<0.001). Multiple logistic regression analysis found an association between serum caspase-8 levels>43.5ng/ml and mortality (OR=3.306; 95%CI=1.619-6.753; p=0.001). The area under the curve (AUC) for mortality predicted by serum caspase-8 levels was 67% (95% CI=60-73%; p<0.001).Conclusions: The novel findings of our study were that blood caspase-8 concentrations are higher in non-survivors than in survivors, and that there is an association between blood caspase-8 concentrations and mortality in septic patients (AU)

Objetivo: No existen datos publicados sobre los niveles sanguíneos de caspasa-8 (la caspasa iniciadora en la vía extrínseca de apoptosis) en pacientes sépticos. Por lo tanto, los objetivos del estudio fueron describir los niveles sanguíneos de caspasa-8 en pacientes supervivientes y fallecidos y determinar si existe una asociación entre los niveles sanguíneos de caspasa-8 y la mortalidad de los pacientes sépticos.DiseñoEstudio observacional y prospectivo.ÁmbitoTres unidades de cuidados intensivos españolas.PacientesPacientes sépticos.IntervencionesSe determinaron las concentraciones séricas de caspasa-8 al diagnóstico de la sepsis.Variable de interés principalMortalidad a los 30 días.ResultadosEncontramos que los pacientes fallecidos en los primeros 30 días (n=81) comparados con los pacientes supervivientes (n=140) presentaban niveles séricos mayores de caspasa-8 (p<0,001). En el análisis de regresión logística múltiple encontramos una asociación entre los niveles séricos de caspasa-8>43,5ng/ml y la mortalidad (OR: 3,306; IC 95%: 1,619-6,753; p=0,001). El área bajo la curva para predecir la mortalidad por los niveles séricos de caspasa-8 fue del 67% (IC 95%: 60-73%; p<0,001).ConclusionesLos nuevos hallazgos de nuestro estudio fueron que los niveles séricos mayores de caspasa-8 eran superiores en los pacientes fallecidos en los primeros 30 días, y que existe una asociación entre los niveles séricos de caspasa-8 y la mortalidad (AU)

Cervical Injury Outcomes among Older Adults Admitted to an Inpatient Trauma Service.

OBJECTIVE: Older adults are an increasing proportion of patients admitted to trauma services. Trauma in older adults' results from many mechanisms of injury with the distribution of mechanisms of injury among older adults different than those of younger adults. The acute management of these injuries may determine the patients' ability to return to independent living. It is known that prolonged immobilization of older patients results in deterioration of their functional status and increases the likelihood of hospital acquired complications, notably pneumonia, delirium, and loss of ambulation. DESIGN/SETTING: We reviewed 213 patients aged 65 and older admitted to our trauma services who sustained cervical spine injuries that were either placed in c spine immobilization or were not to understand the outcomes associated with their mechanism of injury. RESULTS: The youngest patients (65-74 years) were proportionately more likely to have sustained high energy injuries associated with motor vehicle crashes (36%) with a mortality rate of 11.5%. The oldest age group (> 85 years) had a higher mortality rate from falls from standing injuries (31%). Patients discharged with a collar were more likely to return to independent living. In addition, 96% of the patients that died in the acute care setting were not in cervical collar immobilization. CONCLUSION: Patients under 85 years with a cervical spine injury should be placed in c-spine immobilization and aggressively managed with a multidisciplinary team approach. The older adult trauma population requires specialty care including rapid cervical spine evaluation and prescreening of functional status on admission. The NEXUS guideline should be enhanced for the older adult trauma population.

Cryptic Patterns of Speciation in Cryptic Primates: Microendemic Mouse Lemurs and the Multispecies Coalescent.

Mouse lemurs (Microcebus) are a radiation of morphologically cryptic primates distributed throughout Madagascar for which the number of recognized species has exploded in the past two decades. This taxonomic revision has prompted understandable concern that there has been substantial oversplitting in the mouse lemur clade. Here, we investigate mouse lemur diversity in a region in northeastern Madagascar with high levels of microendemism and predicted habitat loss. We analyzed RADseq data with multispecies coalescent (MSC) species delimitation methods for two pairs of sister lineages that include three named species and an undescribed lineage previously identified to have divergent mtDNA. Marked differences in effective population sizes, levels of gene flow, patterns of isolation-by-distance, and species delimitation results were found among the two pairs of lineages. Whereas all tests support the recognition of the presently undescribed lineage as a separate species, the species-level distinction of two previously described species, M. mittermeieri and M. lehilahytsara is not supported-a result that is particularly striking when using the genealogical discordance index (gdi). Nonsister lineages occur sympatrically in two of the localities sampled for this study, despite an estimated divergence time of less than 1 Ma. This suggests rapid evolution of reproductive isolation in the focal lineages and in the mouse lemur clade generally. The divergence time estimates reported here are based on the MSC calibrated with pedigree-based mutation rates and are considerably more recent than previously published fossil-calibrated relaxed-clock estimates. We discuss the possible explanations for this discrepancy, noting that there are theoretical justifications for preferring the MSC estimates in this case. [Cryptic species; effective population size; microendemism; multispecies coalescent; speciation; species delimitation.].

Blood caspase-8 concentrations and mortality among septic patients.

OBJECTIVE: No data are available on blood caspase-8 concentrations (the initiator caspase in the extrinsic apoptosis pathway) in septic patients. The present study thus describes the blood caspase-8 concentrations in survivors and non-survivors, and examines the possible association between blood caspase-8 concentrations and mortality in septic patients. DESIGN: A prospective observational study was carried out. SETTING: Three Spanish Intensive Care Units. PATIENTS: Septic patients. INTERVENTIONS: Serum caspase-8 concentrations were determined at the diagnosis of sepsis. MAIN VARIABLE OF INTEREST: Mortality after 30 days. RESULTS: Patients not surviving at day 30 (n=81) compared to surviving patients (n=140) showed higher serum caspase-8 levels (p<0.001). Multiple logistic regression analysis found an association between serum caspase-8 levels>43.5ng/ml and mortality (OR=3.306; 95%CI=1.619-6.753; p=0.001). The area under the curve (AUC) for mortality predicted by serum caspase-8 levels was 67% (95% CI=60-73%; p<0.001). CONCLUSIONS: The novel findings of our study were that blood caspase-8 concentrations are higher in non-survivors than in survivors, and that there is an association between blood caspase-8 concentrations and mortality in septic patients.

Comparative Genomic Analysis of the Pheromone Receptor Class 1 Family (V1R) Reveals Extreme Complexity in Mouse Lemurs (Genus, Microcebus) and a Chromosomal Hotspot across Mammals.

Sensory gene families are of special interest for both what they can tell us about molecular evolution and what they imply as mediators of social communication. The vomeronasal type-1 receptors (V1Rs) have often been hypothesized as playing a fundamental role in driving or maintaining species boundaries given their likely function as mediators of intraspecific mate choice, particularly in nocturnal mammals. Here, we employ a comparative genomic approach for revealing patterns of V1R evolution within primates, with a special focus on the small-bodied nocturnal mouse and dwarf lemurs of Madagascar (genera Microcebus and Cheirogaleus, respectively). By doubling the existing genomic resources for strepsirrhine primates (i.e. the lemurs and lorises), we find that the highly speciose and morphologically cryptic mouse lemurs have experienced an elaborate proliferation of V1Rs that we argue is functionally related to their capacity for rapid lineage diversification. Contrary to a previous study that found equivalent degrees of V1R diversity in diurnal and nocturnal lemurs, our study finds a strong correlation between nocturnality and V1R elaboration, with nocturnal lemurs showing elaborate V1R repertoires and diurnal lemurs showing less diverse repertoires. Recognized subfamilies among V1Rs show unique signatures of diversifying positive selection, as might be expected if they have each evolved to respond to specific stimuli. Furthermore, a detailed syntenic comparison of mouse lemurs with mouse (genus Mus) and other mammalian outgroups shows that orthologous mammalian subfamilies, predicted to be of ancient origin, tend to cluster in a densely populated region across syntenic chromosomes that we refer to as a V1R "hotspot."

Activity of Metabolic Enzymes in Farmed Rainbow Trout Oncorhynchus mykiss Walb. Affected by Bacterial Septicemia: The Effect of Food Additives.

The effect of food additive including antioxidant dihydroquercetin and polysaccharide arabinogalactan on the activity of metabolic enzymes in muscles and liver of artificially grown rainbow trout Oncorhynchus mykiss affected by bacterial infection was investigated. The results of the study indicated an increase in the resistance of trout to the action of bacterial infection with the enrichment of the diet with the studied bioactive components, apparently mediated, among other factors, by the activation of metabolic pathways of synthesis of energy and reducing equivalents.

Geogenetic patterns in mouse lemurs (genus Microcebus) reveal the ghosts of Madagascar's forests past.

Phylogeographic analysis can be described as the study of the geological and climatological processes that have produced contemporary geographic distributions of populations and species. Here, we attempt to understand how the dynamic process of landscape change on Madagascar has shaped the distribution of a targeted clade of mouse lemurs (genus Microcebus) and, conversely, how phylogenetic and population genetic patterns in these small primates can reciprocally advance our understanding of Madagascar's prehuman environment. The degree to which human activity has impacted the natural plant communities of Madagascar is of critical and enduring interest. Today, the eastern rainforests are separated from the dry deciduous forests of the west by a large expanse of presumed anthropogenic grassland savanna, dominated by the Family Poaceae, that blankets most of the Central Highlands. Although there is firm consensus that anthropogenic activities have transformed the original vegetation through agricultural and pastoral practices, the degree to which closed-canopy forest extended from the east to the west remains debated. Phylogenetic and population genetic patterns in a five-species clade of mouse lemurs suggest that longitudinal dispersal across the island was readily achieved throughout the Pleistocene, apparently ending at ∼55 ka. By examining patterns of both inter- and intraspecific genetic diversity in mouse lemur species found in the eastern, western, and Central Highland zones, we conclude that the natural environment of the Central Highlands would have been mosaic, consisting of a matrix of wooded savanna that formed a transitional zone between the extremes of humid eastern and dry western forest types.

Delimiting species without nuclear monophyly in Madagascar's mouse lemurs.

BACKGROUND: Speciation begins when populations become genetically separated through a substantial reduction in gene flow, and it is at this point that a genetically cohesive set of populations attain the sole property of species: the independent evolution of a population-level lineage. The comprehensive delimitation of species within biodiversity hotspots, regardless of their level of divergence, is important for understanding the factors that drive the diversification of biota and for identifying them as targets for conservation. However, delimiting recently diverged species is challenging due to insufficient time for the differential evolution of characters--including morphological differences, reproductive isolation, and gene tree monophyly--that are typically used as evidence for separately evolving lineages. METHODOLOGY: In this study, we assembled multiple lines of evidence from the analysis of mtDNA and nDNA sequence data for the delimitation of a high diversity of cryptically diverged population-level mouse lemur lineages across the island of Madagascar. Our study uses a multi-faceted approach that applies phylogenetic, population genetic, and genealogical analysis for recognizing lineage diversity and presents the most thoroughly sampled species delimitation of mouse lemur ever performed. CONCLUSIONS: The resolution of a large number of geographically defined clades in the mtDNA gene tree provides strong initial evidence for recognizing a high diversity of population-level lineages in mouse lemurs. We find additional support for lineage recognition in the striking concordance between mtDNA clades and patterns of nuclear population structure. Lineages identified using these two sources of evidence also exhibit patterns of population divergence according to genealogical exclusivity estimates. Mouse lemur lineage diversity is reflected in both a geographically fine-scaled pattern of population divergence within established and geographically widespread taxa, as well as newly resolved patterns of micro-endemism revealed through expanded field sampling into previously poorly and well-sampled regions.

MtDNA and nDNA corroborate existence of sympatric dwarf lemur species at Tsinjoarivo, eastern Madagascar.

Madagascar is a biodiversity hotspot, well known for its endemic primates, the lemurs. Numbers of recognized lemur species have increased drastically in some genera (e.g. Microcebus), while field-based studies revealed low species diversity in the dwarf lemurs (genus Cheirogaleus). Only three (C. medius, C. major, C. crossleyi) of seven described species have to date been identified in field-based studies. Blanco et al. (2009) reported two sympatric Cheirogaleus species at Tsinjoarivo based on morphological data, one of which they attributed to C. crossleyi and the other of which they described as C. sibreei-like, or possibly a new species. Based on comparative analyses of mtDNA (cytb) and nDNA (vWF, fiba, adora3), we confirm the presence of C. crossleyi and show that the C. sibreei-like individuals form a well-defined fourth clade, basal to the three recognized species. Whereas these molecular analyses demonstrate that a non-holotype museum specimen considered by Groves (2000) to belong to C. sibreei does not cluster with the C. sibreei-like individuals from Tsinjoarivo, morphometric analysis of one Tsinjoarivo individual, the C. sibreei holotype from Ankeramadinika, and samples of C. medius, C. major, and C. crossleyi strongly suggests that the fourth (and basal) clade is indeed C. sibreei. Tsinjoarivo therefore becomes the only known field site harboring C. sibreei today. Given ongoing forest loss and fragmentation at Tsinjoarivo we can surmise that this population, critical to our understanding of the evolution of the genus Cheirogaleus, is also critically endangered.

Species delimitation in lemurs: multiple genetic loci reveal low levels of species diversity in the genus Cheirogaleus.

BACKGROUND: Species are viewed as the fundamental unit in most subdisciplines of biology. To conservationists this unit represents the currency for global biodiversity assessments. Even though Madagascar belongs to one of the top eight biodiversity hotspots of the world, the taxonomy of its charismatic lemuriform primates is not stable. Within the last 25 years, the number of described lemur species has more than doubled, with many newly described species identified among the nocturnal and small-bodied cheirogaleids. Here, we characterize the diversity of the dwarf lemurs (genus Cheirogaleus) and assess the status of the seven described species, based on phylogenetic and population genetic analysis of mtDNA (cytb + cox2) and three nuclear markers (adora3, fiba and vWF). RESULTS: This study identified three distinct evolutionary lineages within the genus Cheirogaleus. Population genetic cluster analyses revealed a further layer of population divergence with six distinct genotypic clusters. CONCLUSION: Based on the general metapopulation lineage concept and multiple concordant data sets, we identify three exclusive groups of dwarf lemur populations that correspond to three of the seven named species: C. major, C. medius and C. crossleyi. These three species were found to be genealogically exclusive in both mtDNA and nDNA loci and are morphologically distinguishable. The molecular and morphometric data indicate that C. adipicaudatus and C. ravus are synonymous with C. medius and C. major, respectively. Cheirogaleus sibreei falls into the C. medius mtDNA clade, but in morphological analyses the membership is not clearly resolved. We do not have sufficient data to assess the status of C. minusculus. Although additional patterns of population differentiation are evident, there are no clear subdivisions that would warrant additional specific status. We propose that ecological and more geographic data should be collected to confirm these results.

Organization of the clinical activity of geriatric oncology: report of a SIOG (International Society of Geriatric Oncology) task force.

Management for elderly cancer patients world wide is far from being optimal and few older patients are entering clinical trials. A SIOG Task Force was therefore activated to analyze how the clinical activity of Geriatric Oncology is organized. A structured questionnaire was circulated among the SIOG Members. Fifty eight answers were received. All respondents identified Geriatric Oncology, as an area of specialization, however the organization of the clinical activity was variable. Comprehensive Geriatric Assessment (CGA) was performed in 60% of cases. A Geriatric Oncology Program (GOP) was identified in 21 centers, 85% located in Oncology and 15% in Geriatric Departments. In the majority of GOP scheduled case discussion conferences dedicated to elderly cancer patients took regular place, the composition of the multidisciplinary team involved in the GOP activity included Medical Oncologists, Geriatricians, Nurses, Pharmacists, Social Workers. Fellowships in Geriatric Oncology were present in almost half of GOPs. Over 60% of respondents were willing to recruit patients over 70 years in clinical trials, while the proportion of cases included was only 20%. Enrolment in clinical trials was perceived as more difficult by 52% and much more difficult in 12% of the respondents. In conclusion, a better organization of the clinical activity in Geriatric Oncology allows a better clinical practice and an optimal clinical research. The GOP which can be set up in the oncological as well as in the geriatric environment thought a multidisciplinary coordinator effort. Future plans should also concentrate on divisions, units or departments of Geriatric Oncology.

Benefit of a favorable cardiovascular risk-factor profile in middle age with respect to Medicare costs.

BACKGROUND: People without major risk factors for cardiovascular disease in middle age live longer than those with unfavorable risk-factor profiles. It is not known whether such low-risk status also results in lower expenditures for medical care at older ages. We used data from the Chicago Heart Association Detection Project in Industry to assess the relation of a low risk of cardiovascular disease in middle age to Medicare expenditures later in life. METHODS: We studied 7039 men and 6757 women who were 40 to 64 years of age when surveyed between 1967 and 1973 and who survived to have at least two years of Medicare coverage in 1984 through 1994. Men and women classified as being at low risk for cardiovascular disease were those who had the following characteristics at the time they were initially surveyed: serum cholesterol level, <200 mg per deciliter (5.2 mmol per liter); blood pressure, < or =120/80 mm Hg; no current smoking; an absence of electrocardiographic abnormalities; no history of diabetes; and no history of myocardial infarction. We compared Medicare costs for the 279 men (4.0 percent) and 298 women (4.4 percent) who had this low-risk profile with those for the rest of the study group, who were not at low risk. Health Care Financing Administration charges for services to Medicare beneficiaries were used to estimate average annual health care costs (total costs, those for cardiovascular diseases, and those for cancer). RESULTS: Average annual health care charges were much lower for persons at low risk - the total charges for the men at low risk were less than two thirds of the charges for the men not at low risk ($1,615 less); for the women at low risk, the charges were less than one half of those for the women not at low risk ($1,885 less). Charges related to cardiovascular disease were lower for the low-risk groups of men and women than for those not at low risk (by $979 and $556, respectively), and charges related to cancer were also lower (by $134 and $189). CONCLUSIONS: People with favorable cardiovascular risk profiles in middle age had lower average annual Medicare charges in older age. Having optimal status with respect to major cardiovascular risk factors may result not only in greater longevity but also in lower health care costs.

Displaying electroencephalographic dipole sources on magnetic resonance images.

A simple, inexpensive method of displaying electroencephalographic (EEG) dipole sources on magnetic resonance images (MRIs) is presented. It consists of measuring the head according to the 10-20 system but instead of placing electrodes, benzonatate capsules (Tessalon Perles) (100 mg) are affixed to the patient's scalp. MRI is obtained with the capsules in place. In addition to the routine images, thin-section (1.0-1.3-mm) scans in a three-dimensional volume are obtained and the coordinates for each electrode position ascertained. The capsules are then replaced by electrodes and a waking and sleep recording is performed with a digital EEG instrument. Phenomena of interest are then averaged and interfaced with a source analysis program. The three-dimensional electrode coordinates are placed in a file and used to establish the electrode cloud on the basis of which source analysis proceeds. The three-dimensional source locations are then superimposed on the MRIs. The method is useful in the workup of epilepsy patients, by relating focal epileptogenic activity to definable lesions, and it also allows more precise localization of normal EEG phenomena.

Dipole sources of the human alpha rhythm.

Dipole sources were investigated in 22 normal subjects with a variety of strategies available through the BESA program. When all the data were summed one regional source, located near the midline in the basal portions of the occipital lobe, explained 92% of the variance. Two regional sources, initially constrained for symmetry but subsequently freed from constraint placed them also in the occipital regions near the midline and reduced the residual variance to 4%. Pooled data obscure, however, the marked individual differences especially in regard to lateralization. In the individual case the major source was also always in one occipital area but its location, especially the degree of separation from the midline depended upon alpha distribution and the strategy used in the workup of the data. The orientation of the major components of the regional sources was usually in the posterior-anterior direction, fairly parallel to the midline and while the other one pointed to the upper convexity. Because of the considerable variability of the alpha rhythm in given subjects and even within the same individual a model which requires symmetry constraints is not optimal for all instances, even when constraints are lifted thereafter. The study demonstrated the feasibility of distinguishing predominantly mesial sources from those which are bihemipheric with more lateral origins but several different models may have to be used to reach the most realistic conclusions.

Source analysis of generalized spike-wave complexes.

Dipole source analysis was carried out in three adults and four children with 3 c/s generalized spike-wave (SW) discharges and absence seizures. Eighty-seven SW complexes were investigated. When one regional source was used the equivalent location was always near the baso-frontal area close to the midline. It explained on the average 89% of the variance in the adults and 82% in the children. When two regional sources were used and initially constrained for symmetry, the residual variance (RV) was reduced to 7% in the adults and 9% in the children. The sources remained in the frontal areas and were on the average 2 cm from the midline. When the mirror source was freed it remained contralateral in 76% of the complexes but moved ipsilaterally to various locations in the rest. To reduce the RV to between 2 and 3% one or two additional regional sources were required. These were located in the temporal or parietal areas in the adults and occasionally one occipital region in the children. The study showed that widespread and repetitive EEG events, like the generalized SW, can lend themselves to spatio-temporal multiple dipole modeling. More precise anatomic correlates may become possible with an expanded electrode array and the verification of their locations against the patient's MRI scan.