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PubMed1999

A method to assess the functional impact of cerebral connections on target populations of neurons.

We describe an innovative and tested approach combining two individually potent techniques to visualize simultaneously the functional impact of multiple projections on target populations of neurons in the brain. The rationale is simple: silence a defined set of efferent projections from one cortical region using cooling deactivation and then measure the impact of the deactivation on activities in multiple target regions using 2-deoxyglucose (2DG). This is a straightforward and sound approach because 2DG uptake by neurons reflects levels of underlying neural activity. All distant modifications evoked by the silencing of the set of efferent projections are examined in anatomical tissue and simultaneously for the multiple target sites to provide a global view of the functional impacts of the set of projections on the targets. With this method, downward adjustments of 2DG uptake levels identify removals of net excitatory signals, whereas upward adjustments identify net removals of suppressive influences. Future possible uses and modifications of the technique, including optical imaging, are discussed. Overall, the technique has the potential to provide fundamental, new measures on cerebral network interactions that both complement and extend current static models of cerebral networks and electrophysiological measures of functional impacts on individual neurons.

Amino Acids↗
PubMed1982

A method for using epidemiologic data to estimate the potential impact of an intervention on the health status of a target population.

A general method is proposed for estimating the potential impact of a prevention program involving risk factor modification on the incidence of specific diseases in a target population. An evaluative framework for comparing alternative intervention strategies is also presented. On the basis of results from epidemiologic studies, the user must specify certain parameters regarding the distribution of the risk factor that is to be modified in the population, the magnitude of the association between the risk factor and disease, and the total risk of disease in the population. A quantitative measure, called the potential impact fraction, is derived to estimate the proportion of expected new cases that may be prevented under intervention programs of varying success. Estimates of this measure are then used to assess the potential efficacy, effectiveness, adequacy, and efficiency of planned intervention strategies. The method is illustrated with published data relating relative weight and coronary heart disease among middle-aged U.S. men, comparing different strategies of weight reduction. Key assumptions of the method and interpretation of results are discussed.

Adult↗
PubMed1983

A pilot control trial of schistosomiasis in central Liberia by mass chemotherapy of target populations, combined with focal application of molluscicide.

In an area of high transmission of Schistosoma haematobium and S. mansoni in Central Liberia, populations of five villages and intermediate host snails were surveyed for two years. In three of these villages focal application of molluscicide (niclosamide) in the main transmission sites was combined with mass chemotherapy of a target population representing 76 to 90% of the contamination index. In the two other villages, which served as control, the prevalence indexes remained stable or increased a little during the period of this study. A three dose metrifonate mass treatment was applied in one village with only S. haematobium infections. The compliance was very poor for the second and third dose but the quantity of eggs eliminated by the whole population present before and after mass treatment was reduced by 50%. No snails were found after molluscicide applications but as the incidence remained unchanged it is suspected that inhabitants have been reinfected by going to their fields. Concurrent metrifonate and niridazole mass treatment in one dose was applied in another village with only S. haematobium infections. Molluscicide applications reduced the snail population by 80% but did not affect the transmission. Prevalence indexes were almost the same before and after this intervention. In the last village, praziquantel (40 mg/kg in 1 dose) was used because both S. haematobium and S. mansoni infections were present. Molluscicide applications reduced the snail population by 99% and 87% for Bulinus globosus and Biomphalaria pfeifferi, respectively. This intervention stopped the transmission of S. haematobium for at least one year and reduced the prevalence from 21% to 4.6%. On the contrary for S. mansoni infections, the incidence remained very high (50%) and the prevalence was unchanged after one year follow-up. This could be explained by lower efficacy of praziquantel against S. mansoni (cure rate: 53%) and of molluscicide application against B. pfeifferi, which are highly susceptible to S. mansoni (infection rate 44%). The importance of migration in these villages is emphasized. Prevalence indexes were largely influenced by the arrival of newcomers who played a more important role in the maintenance of transmission after target mass chemotherapy than the infected persons excluded from this treatment. The costs per capita protected were 3.33 US $ for metrifonate, 1.53 for metrifonate and niridazole combined and 1.67 US$ for praziquantel. These figures do not include costs for parasitological examinations.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1997

Evaluation of tests for detection of antibodies to Aujeszky's disease (pseudorabies) virus glycoprotein E in the target population.

Receiver operating characteristic (ROC) curves assess the quality of tests over the entire range of test signals. We compared the ability of an ELISA to detect antibodies to Aujeszky's disease (pseudorabies) virus gE in colostrum (test A) and in a single droplet of whole blood (test B) with the results obtained in serum (gold standard) in the target population by constructing and analyzing such curves. The area under the ROC curve, which is a quantitative measure of test performance, proved to be significantly (p < 0.01) smaller in test A than in test B or the gold standard. No significant differences in the area under the ROC curve were observed between test B and the gold standard.

Animals↗
PubMed1996

[The practical theory of occupational health planning: Part One--The theoretical background of the target population setting and needs assessment procedures (OPST research report 2)].

The OPSS is an 8 stage program which was developed as a practical tool for occupational health services planning. This paper examines the theoretical aspects of the first two stages. The OPSS is a planning tool with a theoretical grounding in OHP (The practical theory of Occupational Health Planning). The target population setting has two functions. The first is to establish the physician's first-hypothesis to design a program. The other is deciding the group which has an occupational health problem in a company. The Needs Assessment helps to clarify the physician's hypothesis, which may be weak due to the limited knowledge of various demands of the employees and senior management. On the other hand, the risks and needs vary according to what kind of expert looks at a situation. To date, occupational physicians have been limited to their medical background in determining only risks and needs. However, understanding the various stakeholders in a particular environment means that any project will be more relevant to all concerned. Another limitation of the occupational physicians hypothesis can be the lack of objective data to support it. This makes it difficult to persuade senior management to sign on to a program. The Needs Assessment procedure with OHQ steps is useful in a number of ways. The Observation step allows for finding risks and needs from various situations in the company from the occupational physician's viewpoint (prehypothesis setting). Hearing is for understanding the subject's demands and finding common themes in the company (final hypothesis setting). Finally, the questionnaire step is for providing objectivity of these common themes and quantitative data for the next Priority Setting procedure. The BITOP (Budget, Information, Time, Order, key Person) has been proposed as a way to diagnose the structural and functional aspects of an organization's procedures. Budget tracks the financial flow through the organization, while Information identifies key information sources. Time helps to understand the reaction speeds of a company against environmental changes in the business community. Order looks at the flow of information from senior management through strategic gatekeepers. Understanding this flow helps the occupational physician to identify specific issues at various levels of the organization. Finally, key Person looks at the flow of information up through the organization, and identifies which key executives the occupational physician needs cooperation from in order for the project to be approved and successful. The above two procedures are essential tasks for insuring that an occupational physician can effectively implement a project that identifies what is necessary for the company and what the company wants to do, and works effectively within the organizational structure.

Health Planning↗
PubMed1996

The etiology of vision impairment in target population.

PURPOSE: research the etiology of vision impairment in target persons over 45 years old in Doumen county, Guangdong province. METHODS: Depending on the prevalences of the blindness among the person aged over 50 years, the theoretic sample rate is 1,000/4,8733 x 100% = 2.05%. The 8 districts were divided into 3 parts according to the local economic situation and the proportion of the population in the areas. In fact, the sampling rate is 932/10055 = 88.34%. RESULTS: We found that impairment < 0.3 accounted for 10.94%. The prevalence of bilateral blindness and low vision was 1.61% and 3.22%, respectively. Both prevalences of blindness and low vision were increased with age. The leading cuase of blindness was cataract (45.2%). The second was corneal opacity (16.7%). Prevalences of the low vision and the blindness were higher in females than in males (P < 0.005). CONCLUSIONS: Curable and preventable diseases were the leading cause for the blindness (70%). Prevalences of blindness and the low vision increase with age. We will continually follow up the population over 50 years of age in Doumen county.

Age Factors↗
PubMed1996

The numerical matching of source and target populations in the CNS: the inferior olive to Purkinje cell projection.

During a defined critical period of development, if the target of a neuronal population is removed, there is a massive decrease in the number of neurons that survive into adulthood. Previous studies have found that source neuron number is a strictly linear function of target size. The current work extends these observations to the inferior olive-->Purkinje cell projection. Three distinct model systems have been used: (i) lurcher<-->wild-type aggregation chimeras, (ii) staggerer<-->wild-type chimeras and (iii) naturally occurring polymorphisms in Purkinje cell number found in different inbred mouse strains. Total neuron numbers were counted in the inferior olive and plotted as a function of the number of Purkinje cells in the contralateral cerebellar cortex. In lurcher mutants and chimeras, the relationship between these values is well described by a straight line. This suggests that, like the granule-->Purkinje cell circuit, the olive-->Purkinje cell circuit uses a linear algorithm to achieve a numerical balance. The results from the two other model systems were not as clear cut. In the staggerer chimeras, we found only a rough correlation between neuron and target numbers and in the inbred strains there was no discernible relationship at all. These findings indicate that in the final analysis, there are multiple factors involved in the determination of the number of olive cells surviving into adulthood. The potential contribution of sustaining collaterals and afferent inputs is discussed as well as the possible existence of different subcircuits of olivocerebellar connections, each with its own numerical matching function.

Animals↗
PubMed1992

Prenatal cystic fibrosis carrier testing: designing an information leaflet to meet the specific needs of the target population.

A questionnaire was given to 180 patients in an antenatal clinic, who were eligible to enter a pilot trial of cystic fibrosis (CF) carrier testing, seeking their views on the information leaflet inviting them to participate; 161 patients (89%) entered the trial and 145 patients (81%) responded to the questionnaire, including 10 who did not enter the trial. Ninety-six percent of these found the leaflet easy to understand, and 97% of those partners who read the leaflet also found it easy to understand. Fifteen percent of patients thought the leaflet should give additional information. Most (92%) had heard of CF before reading the leaflet, television being the most common source of information. Although avoiding the birth of a child with CF was the reason most patients gave for wishing to be screened, almost as many were interested to know their carrier status. The decision to accept or decline testing was taken in conjunction with their partner by 63% of women. Of those who were screened, 59% stated that taking the test made them feel reassured, while 38% felt slightly apprehensive. It was concluded that, with a number of minor amendments, the leaflet met the specific needs of the target patient population.

Attitude to Health↗
PubMed2026

Targeted population genomics uncovers demographic history and genetic divergence in north American wild cranberry.

Wild populations of North American cranberry (Vaccinium macrocarpon Aiton) are reservoirs of genetic variation that may contribute to the improvement of breeding-relevant traits. However, the extent to which wild genetic variation is geographically structured and represented in elite germplasm remains unclear. We analysed 179 wild cranberry accessions from the upper Midwest and Eastern North America to estimate nucleotide diversity (&#x3c0;), population structure, and loci associated with genetic differentiation and environmental variables using a genome-informed targeted genotyping panel. Additionally, 14 demographic scenarios were evaluated using site-frequency-spectrum-based inference to identify historical events that could explain current genetic diversity. We observed extremely low nucleotide diversity within the targeted panel (&#x3c0; = 5 &#xd7; 10-6). Rare allele distributions strongly influenced &#x3c0; and Tajima's D values, suggesting constrained diversity in the genomic regions assayed that is not captured by heterozygosity-based estimates alone. However, we interpreted these results as conservative lower bounds on genome-wide neutral diversity because the targeted panel is enriched for genic and conserved regions. A clear separation between the Midwest and East populations was observed, with inbreeding coefficients ranging from -0.13 to 0.15. Furthermore, site frequency spectrum inference from the targeted panel supported a demographic scenario consistent with a significant population reduction &#x2248;15-14 thousand years ago (kya), followed by a divergence between the two regions &#x2248;12 kya, and an asymmetric gene flow &#x2248;1.3 kya. We detected 254 candidate loci showing regional allele-frequency differentiation. Several of these loci colocalized with candidate genes linked to stress response, development, and metabolic processes. To evaluate the representation of geographically differentiated wild alleles in a breeding context, we analysed Rutgers breeding materials (n&#x2009;=&#x2009;484) and found that this panel is enriched for common alleles in Eastern wild populations. These findings indicate regionally structured allele-frequency variation in wild cranberry, with potential relevance to environmental response and breeding. This study extends prior wild cranberry population-genetic research by providing targeted-panel estimates of diversity, comparisons of demographic models, and breeding insights on geographically differentiated alleles, while highlighting the importance of conserving wild cranberry germplasm for use in modern breeding programs.

Journal Article↗
PubMed2000

Isoform-specific localization of voltage-gated K+ channels to distinct lipid raft populations. Targeting of Kv1.5 to caveolae.

The precise subcellular localization of ion channels is often necessary to ensure rapid and efficient integration of both intracellular and extracellular signaling events. Recently, we have identified lipid raft association as a novel mechanism for the subcellular sorting of specific voltage-gated K(+) channels to regions of the membrane rich in signaling complexes. Here, we demonstrate isoform-specific targeting of voltage-gated K(+) (Kv) channels to distinct lipid raft populations with the finding that Kv1.5 specifically targets to caveolae. Multiple lines of evidence indicate that Kv1.5 and Kv2.1 exist in distinct raft domains: 1) channel/raft association shows differential sensitivity to increasing concentrations of Triton X-100; 2) unlike Kv2.1, Kv1.5 colocalizes with caveolin on the cell surface and redistributes with caveolin following microtubule disruption; and 3) immunoisolation of caveolae copurifies Kv1.5 channel. Both depletion of cellular cholesterol and inhibition of sphingolipid synthesis alter Kv1.5 channel function by inducing a hyperpolarizing shift in the voltage dependence of activation and inactivation. The differential targeting of Kv channel subtypes to caveolar and noncaveolar rafts within a single membrane represents a unique mechanism of compartmentalization, which may permit isoform-specific modulation of K(+) channel function.

Animals↗
PubMed2003

Involvement of MKK6 in TCRalphabeta(int)CD69lo: a target population for apoptotic cell death in thymocytes.

By analyzing real-time caspase activity and DNA fragmentation in live thymocytes, we found that apoptosis occurs predominantly in a TCRalphabeta(int)/hiCD69lo population. The number of caspase-active cells and DNA-fragmented cells in MKK6-deficient mice, which were originally generated in our laboratory by gene targeting, was decreased in the TCRalphabeta(int)CD69lo population but not in the TCRalphabetahiCD69lo population. The percentage of caspase-active cells in the H-Y-specific TCRint population was more clearly decreased in male MKK6-deficient H-Y TCR-transgenic mice. Furthermore, the absolute number of TCRhiCD4loCD8lo cells, which are developmentally next to TCRintCD4hiCD8hi cells, was increased in MKK6-deficient H-Y TCR-transgenic mice. Deletion of TCRalphabeta(int)CD4hiCD8hi cells by injecting antigenic lymphocytic chorio-meningitis virus (LCMV) peptide into LCMV-specific TCR-transgenic mice was incomplete in MKK6-deficient mice. Cellular death of TCRalphabeta(int) fetal thymocytes induced by adding an antigenic peptide into an in vitro fetal thymic organ culture system was also diminished in MKK6-deficient TCR-transgenic thymi. These results indicate that MKK6 plays a role in the developing thymocytes, especially in the population of TCRalphabeta(int)CD69lo cells, which possibly undergo negative selection.

Animals↗
PubMed1981

[Continuously do a good job in planned parenthood work and fulfill this year's population target].

It has been a year since the CCP Central Committee issued an open letter to all CCP and CYL members on population control. In the past year, CCP and CYL members and the broad masses of people in our province have actively responded to the CCP Central Committee's call--1 child/couple. Over 1.7 million couples of childbearing age have applied for only-child certificates. Our province has scored great achievements in planned parenthood work. However, we must realize that new situations and new questions have arisen in planned parenthood work. 1st, the peak period of population growth in our province is from the late 1950s to the 1960s. Children born in this period are now entering the childbearing age. There soon will be a new peak population growth period. 2nd, because of the enactment of the new marriage law, the number of those married in the first 1/2 of this year doubled that of previous years. Responsibility systems in rural areas have pomoted development of productive forces. This is very good, but this has also stimulated population growth because people mistakenly think that more children mean more labor forces and more income. They begin to think of having more chidlren--especially sons. Some localities have lost control of population growth. The birth rate in rural areas has begun to climb quickly. If no measures are adopted immediately, our province's population will swell enormously. All the achievements scored in the 1970s will probably be spoiled, and we likely will again commit a historical error. As far as our province is concerned, planned parenthood is imperative. In 1949, our province's per capita farmland was 3 mu. At the end of 1980, it was only 1.49 mu. If no measures are adopted and the population keeps growing, the consequences will be serious.

Asia↗
PubMed1997

The social construction of target populations and the transformation of prison-based AIDS policy: a descriptive case study.

When interpreting policy changes, it is important to understand the social construction of those whom the policy affects. Policy Design Perspective by Schneider and Ingram (1993) concentrates on the construction of "agents" and "targets" in an attempt to comprehend policy formation and transformation. The following descriptive case study uses this design to assess the evolution of one prison's AIDS policy. This institution's HIV/AIDS policy originally was quite restrictive in nature, but the changing perceptions of the agents and targets allowed a more humanistic approach to emerge in the handling of HIV-positive inmates.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Use of photosensitive, antibody directed liposomes to destroy target populations of cells in bone marrow: a potential purging method for autologous bone marrow transplantation.

Liposomes containing the photosensitive dye sulphonated aluminium phthalocyanine (AlSPc) were coupled to polyclonal sheep anti-mouse-Ig antibody and bound to cells coated with specific mouse monoclonal antibody. When illuminated with red light, the AlSPc in the liposomes was activated to produce singlet oxygen and the antibody and liposome targeted cells were destroyed. DW-BCL cells (an Epstein Barr virus immortalised B-cell line) were targeted with an anti-B-cell antibody (8A) and killed specifically, both alone and in the presence of bone marrow mononuclear cells (BM-cells), without phototoxic effects on the untargeted bone marrow CFU-GM progenitor cells. The presence of an excess of non-target cells did not interfere with antibody and liposome binding, or light access to target cells. Similar results were obtained with T-lymphocytes as target cells using anti-CD3 antibody. Specific targeting to the B-cells was demonstrated in the cell mixtures by use of fluorescent microscopy combined with a sensitive technique to detect low levels of AlSPc fluorescence, a cooled charge couple device (CCD) camera. This was also able to show low levels of non-specific background binding of AlSPc to BM-cells and a small population of cells that took up AlSPc in the absence of antibody. The latter were shown to be monocytes by flow cytometry.

Bone Marrow↗
PubMed1998

Prevalence of HIV infection and HIV risk behaviors associated with living place: on-the-street homeless drug users as a special target population for public health intervention.

The study described here examined the prevalence of HIV infection as a function of place of residence and high-risk behaviors in six subpopulations of out-of-treatment drug injectors and crack cocaine users who participated in the National Institute on Drug Abuse (NIDA) Cooperative Agreement project. The subpopulations were blacks, Hispanics, and non-Hispanic whites sampled separately by gender. The research asked three questions: (a) Is the HIV infection rate higher among the on-the-street homeless than among those in other places of residence? (b) Do high-risk drug-related behaviors differ by housing status? and (c) What are the joint effects of high-risk drug-related behaviors and housing status on the probability of HIV infection? Overall, on-the-street homeless had a significantly higher HIV+ rate (19.0%) than the study population as a whole (11.2%). Rates differed by gender and race, with exceptionally high HIV+ rates for on-the-street homeless Hispanic males (29%) and females (32%) and for on-the-street homeless black females (38%). Having used drug works previously used by a HIV-infected person was a strong predictor of HIV+ status, as was frequency of drug injections and crack use. Having multiple sex partners was also a significant risk behavior. Findings argue against considering on-the-street homelessness as equivalent to shelter dwelling or aggregated homelessness for purposes of the AIDS epidemic. On-the-street homeless drug users were at strong risk for acquisition and transmission of HIV infection and therefore in need of targeted-racially relevant, ethnically relevant, and gender-relevant-public health interventions to help prevent the spread of AIDS.

HIV Infections↗
PubMed1999

Bioequivalence of levothyroxine tablets administered to a target population in steady state.

Two parallel trials were carried out with levothyroxine sodium salt in 50 and 100 microg strengths, respectively, giving 100 microg day-1(50x2 microg day-1 or 100x1 microg day-1) in both trials in a repeated dose regimen. Twenty patients suffering from primary hypothyroidism under treatment with 100 microg day-1 of thyroxine sodium salt were enrolled in each trial. They were clinically and chemically euthyroid. Each trial lasted 114 days, with 57 days being devoted to the first treatment (test or reference) and 57 days to the other (reference or test), according to a two-period, two-sequence, two-formulation design in a steady state without wash-out. The test formulation was prepared with a technological improvement and is being produced to replace that at present on the market. Serum concentrations of free and total levothyroxine, and free and total levotriiodothyronine were assayed repeatedly during the treatment and in timed samples after the last dose of each formulation, using radioimmunoassays. Cmax and AUCss,tau were considered to be target parameters for bioequivalence which was assessed through 90% confidence intervals in the 0.80-1.25 range, as required by EU and US FDA operating guidelines. The results have shown that of these hormones, the free and total parent compound thyroxine is that which most clearly showed a peak after dosing, whereas its metabolite, free and total triiodothyronine, fluctuated around pre-dose concentrations. Bioequivalence was fully assessed with Cmax and AUCss,tau, with all four hormones tested and at both strengths administered. The two test formulations in 50 and 100 microg are thus bioequivalent with the two reference preparations. Tolerability was very good in all cases.

Adult↗