Application of two types of migration data to multiregional demographic projections.
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Age Factors↗
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Multiregional evaluation of the SimPlate heterotrophic plate count method compared to the standard plate count agar pour plate method in water.
A new SimPlate heterotrophic plate count (HPC) method (IDEXX Laboratories, Westbrook, Maine) was compared with the pour plate method at 35 degrees C for 48 h. Six laboratories tested a total of 632 water samples. The SimPlate HPC method was found to be equivalent to the pour plate method by regression analysis (r = 0. 95; y = 0.99X + 0.06).
Agar↗
Molecular hallmarks of excitatory and inhibitory neuronal resilience to Alzheimer's disease.
BACKGROUND: A significant proportion of individuals maintain cognition despite extensive Alzheimer's disease (AD) pathology, known as cognitive resilience. Understanding the molecular mechanisms that protect these individuals could reveal therapeutic targets for AD. METHODS: This study defines molecular and cellular signatures of cognitive resilience by integrating bulk RNA and single-cell transcriptomic data with genetics across multiple brain regions. We analyzed data from the Religious Order Study and the Rush Memory and Aging Project (ROSMAP), including bulk RNA sequencing (n = 631 individuals) and multiregional single-nucleus RNA sequencing (n = 48 individuals). Subjects were categorized into AD, resilient, and control based on β-amyloid and tau pathology, and cognitive status. We identified and prioritized protected cell populations using whole-genome sequencing-derived genetic variants, transcriptomic profiling, and cellular composition. RESULTS: Transcriptomics and polygenic risk analysis position resilience as an intermediate AD state. Only GFAP and KLF4 expression distinguished resilience from controls at tissue level, whereas differential expression of genes involved in nucleic acid metabolism and signaling differentiated AD and resilient brains. At the cellular level, resilience was characterized by broad downregulation of LINGO1 expression and reorganization of chaperone pathways, specifically downregulation of Hsp90 and upregulation of Hsp40, Hsp70, and Hsp110 families in excitatory neurons. MEF2C, ATP8B1, and RELN emerged as key markers of resilient neurons. Excitatory neuronal subtypes in the entorhinal cortex (ATP8B+ and MEF2Chigh) exhibited unique resilience signaling through activation of neurotrophin (BDNF-NTRK2, modulated by LINGO1) and angiopoietin (ANGPT2-TEK) pathways. MEF2C+ inhibitory neurons were over-represented in resilient brains, and the expression of genes associated with rare genetic variants revealed vulnerable somatostatin (SST) cortical interneurons that survive in AD resilience. The maintenance of excitatory-inhibitory balance emerges as a key characteristic of resilience. CONCLUSIONS: We have defined molecular and cellular hallmarks of cognitive resilience, an intermediate state in the AD continuum. Resilience mechanisms include preserved neuronal function, balanced network activity, and activation of neurotrophic survival signaling. Specific excitatory neuronal populations appear to play a central role in mediating cognitive resilience, while a subset of vulnerable interneurons likely provides compensation against AD-associated hyperexcitability. This study offers a framework to leverage natural protective mechanisms to mitigate neurodegeneration and preserve cognition in AD.
Humans↗
Community control and pricing patterns of nonprofit hospitals: An antitrust analysis.
Traditional control of nonprofit hospitals by the communities they serve has been offered as justification for restraining antitrust enforcement of mergers that involve nonprofit hospitals. The community is arguably a constraint on a nonprofit's inclination to exercise market power in the form of higher prices; however, community control is likely to be attenuated for hospitals that through merger or acquisition become members of hospital systems--particularly those that operate on a regional or multiregional basis. We report findings from a study in which we examined empirically the relationship between market concentration and pricing patterns for three types of nonprofit hospitals that are distinguishable based on degree of community control: an independent hospital, a member of a local hospital system, and a member of a nonlocal hospital system. Study results indicated that when conditions existed to create a more concentrated market, (1) all three types of nonprofit hospitals exercised market power in the form of higher prices, and (2) hospitals that were members of nonlocal systems were more aggressive in exercising market power than were either independent or local system hospitals. The results have important implications for antitrust enforcement policy.
Antitrust Laws↗
Frequency of HIV type 1 dual infection and HIV diversity: analysis of low- and high-risk populations in Mbeya Region, Tanzania.
HIV-1 diversity, frequency of recombinants, and dual infection were determined in two populations with different HIV risk behavior. A high-risk cohort of 600 female bar workers and a normal-risk population of 1,108 antenatal clinic attendees and blood donors were recruited. Behavioral data were assessed and blood for HIV- 1 diagnosis and genotyping was sampled. HIV-1 subtypes were defined through the multiregion hybridization assay (MHA(acd)). HIV-1 prevalence differed significantly among the two populations. The prevalence was 67.8% in the population of bar workers and 17% in the normal-risk population (antenatal care attendees and blood donors). Within the normal-risk population the HIV-1 prevalence was lowest in the group of volunteer blood donors. The frequency of HIV-1 infection in women was 1.7 times higher than in men. The overall subtype distribution was A (8.5%), C (40.8%), D (3.8%), AC (25.4%), AD (5.4%), CD (8.8%), and ACD (7.3%). In the high-risk population there was a higher percentage of HIV-1 recombinant strains (54% vs. 40%, p < 0.05) and a higher frequency of dual infections (19% vs. 9%, p < 0.02) compared to the normal-risk population. High-risk populations may play an important role in the evolution of HIV, as they can provide an opportunity for the virus to coinfect, recombine, and adapt to the host-specific genetic background.
Adolescent↗
Qualitative and quantitative imaging of the hippocampus in mesial temporal lobe epilepsy with hippocampal sclerosis.
MR imaging allows the in vivo detection of hippocampal sclerosis (HS) and has been instrumental in the delineation of the syndrome of mesial temporal lobe epilepsy with HS (mTLE-HS). MR features of HS include hippocampal atrophy with an increased T2 signal. Quantitative MR imaging accurately reflects the degree of hippocampal damage.Ictal single photon emission computed tomography (SPECT) in mTLE-HS shows typical perfusion patterns of ipsilateral temporal lobe hyperperfusion, and ipsilateral frontoparietal and contralateral cerebellar hypoperfusion. Interictal 18fluoro-2-deoxyglucose positron emission tomography (PET) shows multiregional hypometabolism, involving predominantly the ipsilateral temporal lobe. 11C-flumazenil PET shows hippocampal decreases in central benzodiazepine receptor density. Future strategies to study the etiology and pathogenesis of HS should include longitudinal MR imaging studies,MR studies in families with epilepsy and febrile seizures, stratification for genetic background, coregistration with SPECT and PET, partial volume correction and statistical parametric mapping analysis of SPECT and PET images.
Brain Mapping↗
Molecular Epidemiology of HIV Type 1 in Ecuador, Peru, Bolivia, Uruguay, and Argentina.
Surveillance for HIV infection among people at increased risk was conducted in five countries in South America. Seroprevalence studies were conducted in more than 36,000 people in Ecuador, Peru, Boliva, Uruguay, and Argentina, along with genetic analysis of the HIV-1 strains. In all countries, the prevalence of HIV-1 among men who have sex with men (MSM) was high (3-30%), whereas the prevalence among female commercial sex workers (FCSMs) was low (0.3-6%). By envelope heteroduplex mobility assay, subtype B predominated in MSM communities and in FCSWs in Ecuador, Bolivia, and Peru. A new genetic screening assay, the multiregion hybridization assay for subtypes B and F (MHA-bf), was developed to improve large-scale genetic screening in South America. MHA-bf can screen four regions of the genome for subtype B or subtype F, and thus can detect most recombinants. The sensitivity of MHA-bf when applied to a panel of pure subtypes and CRF12_BF was 100%, and 88% of unique recombinants were also detected as recombinant. Using MHA-bf, more than 80% of samples from Ecuador, Peru, and Bolivia were classified as pure subtype B, whereas in Uruguay and Argentina this proportion was only 30 to 40%. BF recombinants were the most prevalent form of HIV-1 in Uruguay and Argentina. Subtype B is the most common subtype in countries lacking injecting drug use (IDU) epidemics, whereas BF recombinants are more common in countries where extensive IDU epidemics have been documented, suggesting the ontogeny of recombinant strains in particular risk groups in South America.
DNA, Viral↗
Cladistic analysis of dental traits in recent humans using a fossil outgroup.
The relationships between a range of modern human samples are assessed from cladistic analyses of the published population frequencies of tooth crown characters, using new data on the Krapina Neanderthal sample as an outgroup. All of the most parsimonious trees show an early divergence of African and Australasian groups. This result is compared with an alternative dendrogram proposed by Turner (1992). Reconstruction of a hypothetical dental ancestor suggests that the similarities between the African and Australasian groups result from the retention of symplesiomorphous dental traits. Additionally, despite expectations from multiregional evolution, recent Europeans are dentally less like the Krapina Neanderthals than are Africans and Australians.
Africa↗
[Interprovincial migration among foreign-born Canadians, 1981-1986].
"This article analyzes the spatial distribution as well as interprovincial migration of foreign-born persons living in Canada, using data from the 1986 census. The focus is placed on differences observed in migratory behaviour between native-born Canadians and those born abroad. Net migration patterns as well as the propensity to migrate by place of origin and destination are presented for different population groups according to birthplace. Finally, multiregional life tables are used to evaluate the effect of these migratory differentials on the retentive force exerted by the various regions." (SUMMARY IN ENG AND SPA)
Americas↗
Multiregional demographic projections in practice: a metropolitan example.
"This paper examines options for local and regional projections which reflect both demographic interdependencies with jobs and housing at this area scale, and the inapplicability of traditional demographic projection methods to population or areal subdivisions. This context for local demographic projections requires constraints (for example, to job and housing forecasts or to higher area totals), the use of proxy or explanatory indicators to predict demographic rates or totals, and parameterization of demographic schedules, to facilitate comparison across numerous localities and to set future assumptions about demographic components. The traditional framework of self-contained projection by deterministic cohort survival is therefore widened to include regio-scientific and stochastic modelling concepts. The framework for empirical analysis is London [England] and its boroughs." (SUMMARY IN FRE AND GER)
Demography↗
Ganglioglioma and intractable epilepsy: clinical and neurophysiologic features and predictors of outcome after surgery.
PURPOSE: To review the clinical, neurophysiologic, and radiological data of patients with ganglioglioma who had undergone evaluation and surgery in our Epilepsy Program. METHODS: The medical and neurophysiologic records of 38 patients with intractable epilepsy and ganglioglioma were reviewed. Data underwent statistical analysis. RESULTS: There were 28 temporal and 10 extratemporal resections, with a mean age at seizure onset of 10.5 years and mean age at surgery of 22 years. Five tumor resections performed earlier were recorded. Twenty-nine patients had auras and 20 had secondarily generalized seizures. All 28 patients with temporal tumor had complex partial seizures. Preoperative MRI demonstrated the tumor in 36 of 36 patients: 17 of 29 demonstrated gadolinium enhancement, and 17 of 36 had mass effect. Scalp interictal sharp waves were present in 32 patients, and in 15 they were multiregional. In two patients, scalp EEG seizure onset was from the hemisphere contralateral to the tumor. Postoperatively, 79% of patients (30 of 38) were seizure-free (Engel's class I) at 6 months, 72% at 1 year (26 of 36), and 63% at 2 years (20 of 32). Excellent outcome was associated with a lower age at operation (p = 0.008), shorter duration of epilepsy (p = <0.01), absence of generalized seizures (p = <0.01), and no epileptiform discharges on a postoperative EEG (p = 0.01). CONCLUSIONS: Good surgical outcome is expected in patients with ganglioglioma despite years of medically resistant seizures. Good outcome may be achieved despite EEG findings that may conflict with tumor location, and is more likely when surgery is performed relatively soon after epilepsy onset.
Adult↗
Global patterns of human DNA sequence variation in a 10-kb region on chromosome 1.
Human DNA variation is currently a subject of intense research because of its importance for studying human origins, evolution, and demographic history and for association studies of complex diseases. A approximately 10-kb region on chromosome 1, which contains only four small exons (each <155 bp), was sequenced for 61 humans (20 Africans, 20 Asians, and 21 Europeans) and for 1 chimpanzee, 1 gorilla, and 1 orangutan. We found 52 polymorphic sites among the 122 human sequences and 382 variant sites among the human, chimpanzee, gorilla, and orangutan sequences. For the introns sequenced (8,991 bp), the nucleotide diversity (pi) was 0.058% among all sequences, 0.076% among the African sequences, 0.047% among the Asian sequences, and 0.045% among the European sequences. A compilation of data revealed that autosomal regions have, on average, the highest pi value (0.091%), X-linked regions have a somewhat lower pi value (0.079%), and Y-linked regions have a very low pi value (0.008%). The lower polymorphism in the present region may be due to a lower mutation rate and/or selection in the gene containing these introns or in genes linked to this region. The present region and two other 10-kb noncoding regions all show a strong excess of low-frequency variants, indicating a relatively recent population expansion. This region has a low mutation rate, which was estimated to be 0.74 x 10 per nucleotide per year. An average estimate of approximately 12,600 for the long-term effective population size was obtained using various methods; the estimate was not far from the commonly used value of 10,000. Fu and Li's tests rejected the assumption of an equilibrium neutral Wright-Fisher population, largely owing to the high proportion of low-frequency variants. The age of the most recent common ancestor of the sequences in our sample was estimated to be more than 1 Myr. Allowing for some unrealistic assumptions in the model, this estimate would still suggest an age of more than 500,000 years, providing further evidence for a genetic history of humans much more ancient than the emergence of modern humans. The fact that many unique variants exist in Europe and Asia also suggests a fairly long genetic history outside of Africa and argues against a complete replacement of all indigenous populations in Europe and Asia by a small Africa stock. Moreover, the ancient genetic history of humans indicates no severe bottleneck during the evolution of humans in the last half million years; otherwise, much of the ancient genetic history would have been lost during a severe bottleneck. We suggest that both the "Out of Africa" and the multiregional models are too simple to explain the evolution of modern humans.
Africa↗
Immigration and the regional demographics of the elderly population in the United States.
OBJECTIVES: This research examined the impacts of past international and interregional migration flows on regional elderly population growth and distribution patterns. METHODS: The authors used 1960, 1970, 1980, and 1990 Census data and multiregional demographic models to analyze changes in the sources of regional elderly population growth rates, age compositions, and spatial distributions over time. RESULTS: Past elderly interregional migration patterns have exhibited considerable stability and have contributed less than aging-in-place in shaping regional elderly population geographies. Also the effects of immigration on elderly dependency ratios have been very modest. DISCUSSION: Little evidence exists of any significant breaks with past trends in internal elderly migration patterns. Reconstruction of elderly population changes between 1950 and 1990 reveals that the driving force behind the changes was net aging-in-place and not net migration. Finally, analysis of the possible population rejuvenating effects of immigration suggests that although its impact has contributed to lower elderly-to-worker dependency ratios, its level over the past decades has been insufficient to counteract the much stronger countervailing impact of population aging.
Aged↗
Characterization of biological diversity through analysis of discrete cranial traits.
In the present study, the frequency distributions of 20 discrete cranial traits in 70 major human populations from around the world were analyzed. The principal-coordinate and neighbor-joining analyses of Smith's mean measure of divergence (MMD), based on trait frequencies, indicate that 1). the clustering pattern is similar to those based on classic genetic markers, DNA polymorphisms, and craniometrics; 2). significant interregional separation and intraregional diversity are present in Subsaharan Africans; 3). clinal relationships exist among regional groups; 4). intraregional discontinuity exists in some populations inhabiting peripheral or isolated areas. For example, the Ainu are the most distinct outliers of the East Asian populations. These patterns suggest that founder effects, genetic drift, isolation, and population structure are the primary causes of regional variation in discrete cranial traits. Our results are compatible with a single origin for modern humans as well as the multiregional model, similar to the results of Relethford and Harpending ([1994] Am. J. Phys. Anthropol. 95:249-270). The results presented here provide additional measures of the morphological variation and diversification of modern human populations.
Anthropology, Physical↗
Ecotoxicology and spatial modeling in population dynamics: an illustration with brown trout.
We developed a multiregion matrix population model to explore how the demography of a hypothetical brown trout population living in a river network varies in response to different spatial scenarios of cadmium contamination. Age structure, spatial distribution, and demographic and migration processes are taken into account in the model. Chronic or acute cadmium concentrations affect the demographic parameters at the scale of the river range. The outputs of the model constitute population-level end points (the asymptotic population growth rate, the stable age structure, and the asymptotic spatial distribution) that allow comparing the different spatial scenarios of contamination regarding the demographic response at the scale of the whole river network. An analysis of the sensitivity of these end points to lower order parameters enables us to link the local effects of cadmium to the global demographic behavior of the brown trout population. Such a link is of broad interest in the point of view of ecotoxicological management.
Animal Migration↗
Acute regional myocardial ischemia identified by 2-dimensional multiregion tissue Doppler imaging technique.
BACKGROUND AND OBJECTIVE: Tissue Doppler echocardiography (TDE) is a promising method for the assessment of regional myocardial function, but pulsed TDE does not provide quantitative data from multiple regions simultaneously. This feature is important for the objective assessment of regional differences in myocardial function. In the present study, we investigated a new off-line TDE method that provides quantitative pulsed velocity data from an unlimited number of regions selected within a 2-dimensional (2D) image. The goal of the study was to determine the ability of this new approach to quantify regional myocardial function during acute myocardial ischemia induced by balloon angioplasty. METHODS: Twenty-two patients undergoing angioplasty of the left anterior descending coronary artery (LAD) were studied. Left ventricular longitudinal wall motion was assessed by 2D TDE from the apical 4-chamber view before, during, and after angioplasty. Images were sampled at a rate of 69 +/- 15 frames/s, and the off-line analysis allowed simultaneous measurement of velocities in multiple myocardial segments. RESULTS: There were 3 major alterations in the systolic velocity pattern during LAD occlusion. Peak early systolic velocities along the apical septum were significantly reduced during LAD occlusion (2.8 +/- 1.2 cm/s to 0.6 +/- 1.7 cm/s, P <.001). Myocardial velocities in mid systole suggested paradoxical wall motion (1.0 +/- 1.2 cm/s to -0.8 +/- 0.9 cm/s, P <.001). When comparing the ischemic regions of the left ventricle with the nonischemic regions, each patient demonstrated lower myocardial systolic velocities in the ischemic region. Furthermore, during early diastole, the wall motion of the ischemic segments showed a postsystolic contraction pattern with velocities changing from -0.9 +/- 1.0 cm/s to 1.9 +/- 1.3 cm/s (P <.001). CONCLUSION: This new 2D TDE approach is able to quantify detailed myocardial velocity profiles from multiple regions simultaneously. Single-beat comparisons of ischemic and nonischemic regions might enhance the sensitivity for diagnosing ischemic heart disease. Reversed systolic wall motion during midsystole and marked positive velocity during early diastole might be new and important markers of myocardial wall ischemia.
Aged↗
Monitoring change in spatial patterns of disease: comparing univariate and multivariate cumulative sum approaches.
Prospective disease surveillance has gained increasing attention, particularly in light of recent concern for quick detection of bioterrorist events. Monitoring of health events has the potential for the detection of such events, but the benefits of surveillance extend much more broadly to the quick detection of change in public health. In this paper, univariate and multivariate cumulative sum methods for disease surveillance are compared. Although the univariate method has been previously used in the context of health surveillance, the multivariate method has not. The univariate approach consists of simultaneously and independently monitoring the disease rate in each region; the multivariate approach accounts explicitly for any covariation between regions. The univariate approaches are limited by their lack of ability to account for the spatial autocorrelation of regional data; the multivariate methods are limited by the difficulty in accurately specifying the multiregional covariance structure. The methods are illustrated using both simulated data and county-level data on breast cancer in the northeastern United States. When the degree of spatial autocorrelation is low, the univariate method is generally better at detecting changes in rates that occur in a small number of regions; the multivariate is better when change occurs in a large number of regions.
Breast Neoplasms↗
Multicentre trials: a US regulatory perspective.
Multicentre trials are very common in the field of drug development. In recent years, multicentre trials have taken on a multinational and multiregional aspect. We provide a conceptual framework for the use of multicentre trials in the context of drug development, from the perspective of drug regulation in the United States. In this paper, we review some regulatory history, milestones and standards as they relate to multicentre trials. Special attention is given to the similarities and differences in the approaches to multicentre trials in the following documents; Guideline for the Format and Content of the Clinical and Statistical Sections of New Drug Applications, International Conference on Harmonization, Draft Guideline on Statistical Principles for clinical trials and the Guidance for Industry Providing Clinical Evidence of Effectiveness for Human Drug and Biologic Products. The paper includes a consideration of some of the issues in the analysis of data from multicentre trials.
Drug Approval↗