Quasi-extinction risk and population targets for the Eastern, migratory population of monarch butterflies (Danaus plexippus)

USGS Publications Warehouse

Semmens, Brice X.; Semmens, Darius J.; Thogmartin, Wayne E.; Wiederholt, Ruscena; Lopez-Hoffman, Laura; Diffendorfer, James E.; Pleasants, John M.; Oberhauser, Karen S.; Taylor, Orley R.

2016-01-01

The Eastern, migratory population of monarch butterflies (Danaus plexippus), an iconic North American insect, has declined by ~80% over the last decade. The monarch’s multi-generational migration between overwintering grounds in central Mexico and the summer breeding grounds in the northern U.S. and southern Canada is celebrated in all three countries and creates shared management responsibilities across North America. Here we present a novel Bayesian multivariate auto-regressive state-space model to assess quasi-extinction risk and aid in the establishment of a target population size for monarch conservation planning. We find that, given a range of plausible quasi-extinction thresholds, the population has a substantial probability of quasi-extinction, from 11–57% over 20 years, although uncertainty in these estimates is large. Exceptionally high population stochasticity, declining numbers, and a small current population size act in concert to drive this risk. An approximately 5-fold increase of the monarch population size (relative to the winter of 2014–15) is necessary to halve the current risk of quasi-extinction across all thresholds considered. Conserving the monarch migration thus requires active management to reverse population declines, and the establishment of an ambitious target population size goal to buffer against future environmentally driven variability.

Qualitative methods to ensure acceptability of behavioral and social interventions to the target population

PubMed Central

Ayala, Guadalupe X.; Elder, John P.

2013-01-01

This paper introduces qualitative methods for assessing the acceptability of an intervention. Acceptability refers to determining how well an intervention will be received by the target population and the extent to which the new intervention or its components might meet the needs of the target population and organizational setting. In this paper, we focus on two common qualitative methods for conducting acceptability research and their advantages and disadvantages: focus groups and interviews. We provide examples from our own research and other studies to demonstrate the use of these methods for conducting acceptability research and how one might adapt this approach for oral health research. Finally, we present emerging methods for conducting acceptability research, including the use of community-based participatory research, as well as the utility of conducting acceptability research for assessing the appropriateness of measures in intervention research. PMID:21656958

Estimating the Public Health Impact of Setting Targets at the European Level for the Reduction of Zoonotic Salmonella in Certain Poultry Populations

PubMed Central

Messens, Winy; Vivas-Alegre, Luis; Bashir, Saghir; Amore, Giusi; Romero-Barrios, Pablo; Hugas, Marta

2013-01-01

In the European Union (EU), targets are being set for the reduction of certain zoonotic Salmonella serovars in different animal populations, including poultry populations, within the framework of Regulation (EC) No. 2160/2003 on the control of zoonoses. For a three-year transitional period, the EU targets were to cover only Salmonella Enteritidis and S. Typhimurium (and in addition S. Hadar, S. Infantis and S. Virchow for breeding flocks of Gallus gallus). Before the end of that transitional period, the revision of the EU targets was to be considered, including the potentially addition of other serovars with public health significance to the permanent EU targets. This review article aims at providing an overview of the assessments carried out by the Scientific Panel on Biological Hazards of the European Food Safety Authority in the field of setting targets for Salmonella in poultry populations (breeding flocks of Gallus gallus, laying flocks of Gallus gallus, broiler flocks of Gallus gallus and flocks of breeding and fattening turkeys) and their impact in subsequent changes in EU legislation. PMID:24157508

Adolescent women as a key target population for community nutrition education programs in Indonesia.

PubMed

Savage, Amy; Februhartanty, Judhiastuty; Worsley, Anthony

2017-05-01

Adolescence is a critical life-stage that sets the foundation for health in adulthood. Adolescent women are a unique population and should be targeted as such for nutrition promotion activities. Using Indonesia as a case study, this qualitative study aimed to identify existing nutrition promotion programs aimed at adolescent girls, how best to target this population and effective recommendations to inform nutrition education program design for this important group. Semi-structured interviews and questionnaires were conducted with ten key informants working in public health in Indonesia. Interview transcripts were analysed and coded to identify key themes. No existing nutrition education programs targeting adolescent women in Indonesia were identified. Several strategies apply to nutrition programs for adolescent girls: 1) nutrition promotion messages that are relevant to the lifestyles and interests of adolescent women; 2) technology-based interventions show promise, however, they need to be appropriately targeted to sub-groups; 3) school remains an important setting; and 4) early marriage is an important issue affecting nutritional status and engagement of adolescent girls. The informants recommended that: 1) more research is needed about the underlying motivations for behaviour change among adolescent women and ways to effectively implement the identified engagement strategies; 2) adolescent girls should be included in program design to improve its suitability and uptake; and 3) government budget and policy support is crucial to success. Adolescent women are an important population group and more research is required to identify the optimal forms of engagement to improve nutrition programs for them.

Measuring and Reducing Off-Target Activities of Programmable Nucleases Including CRISPR-Cas9

PubMed Central

Koo, Taeyoung; Lee, Jungjoon; Kim, Jin-Soo

2015-01-01

Programmable nucleases, which include zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and RNA-guided engineered nucleases (RGENs) repurposed from the type II clustered, regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9) system are now widely used for genome editing in higher eukaryotic cells and whole organisms, revolutionising almost every discipline in biological research, medicine, and biotechnology. All of these nucleases, however, induce off-target mutations at sites homologous in sequence with on-target sites, limiting their utility in many applications including gene or cell therapy. In this review, we compare methods for detecting nuclease off-target mutations. We also review methods for profiling genome-wide off-target effects and discuss how to reduce or avoid off-target mutations. PMID:25985872

Should anti-tobacco media messages be culturally targeted for Indigenous populations? A systematic review and narrative synthesis.

PubMed

Gould, Gillian Sandra; McEwen, Andy; Watters, Tracey; Clough, Alan R; van der Zwan, Rick

2013-07-01

To summarise published empirical research on culturally targeted anti-tobacco media messages for Indigenous or First Nations people and examine the evidence for the effectiveness of targeted and non-targeted campaigns. Studies were sought describing mass media and new media interventions for tobacco control or smoking cessation in Indigenous or First Nations populations. Studies of any design were included reporting outcomes of media-based interventions including: cognitions, awareness, recall, intention to quit and quit rates. Then, 2 reviewers independently applied inclusion criteria, which were met by 21 (5.8%) of the studies found. One author extracted data with crosschecking by a second. Both independently assessed papers using Scottish Intercollegiate Guidelines Network (SIGN; quantitative studies) and Daly et al (qualitative studies). A total of 21 studies were found (4 level 1 randomised controlled trials (RCTs), 11 level 2 studies and 6 qualitative studies) and combined with narrative synthesis. Eight evaluated anti-tobacco TV or radio campaigns; two assessed US websites; three New Zealand studies examined mobile phone interventions; five evaluated print media; three evaluated a CD-ROM, a video and an edutainment intervention. Although Indigenous people had good recall of generic anti-tobacco messages, culturally targeted messages were preferred. New Zealand Maori may be less responsive to holistic targeted campaigns, despite their additional benefits, compared to generic fear campaigns. Culturally targeted internet or mobile phone messages appear to be as effective in American Indians and Maori as generic messages in the general population. There is little research comparing the effect of culturally targeted versus generic messages with similar message content in Indigenous people.

Are brief alcohol interventions targeting alcohol use efficacious in military and veteran populations? A meta-analysis.

PubMed

Doherty, A M; Mason, C; Fear, N T; Rona, R; Greenberg, N; Goodwin, L

2017-09-01

Rates of hazardous and harm-related drinking are higher in the military and veteran populations compared to the general population. Brief alcohol interventions (BAIs) targeting alcohol use appear to reduce harmful drinking in the general population. However, less is known about the efficacy of BAIs targeting alcohol in military and veteran populations. A systematic review and meta-analysis was conducted to assess the type and efficacy of BAIs used to reduce alcohol use in military and veteran populations conducted from 2000 onwards. The meta-analysis was conducted using a standardised outcome measure of change in average weekly drinks (AWDs) from baseline to follow-up. The search revealed 10 papers that met the search criteria, and that reported data on 11 interventions included in the systematic review. 8 papers (reporting on 9 different interventions) were included in the meta-analysis after 2 papers were excluded for which the relevant outcome data were not available. There was no overall effect of BAIs; a non-significant weekly drink reduction of 0.95 drinks was found (95% CI, -0.17 to 2.07). This lack of efficacy persisted regardless of military group (conscripts, serving or veterans) and method of delivery (i.e., face-to-face, web-based or written information). Furthermore, sensitivity analyses revealed this small drink reduction was driven mainly by a single study. Based on these findings, existing BAIs do not seem to be efficacious in reducing alcohol use in military populations, despite some encouraging results from one electronic intervention which was of extensive duration. Copyright © 2017 Elsevier B.V. All rights reserved.

Controlling range expansion in habitat networks by adaptively targeting source populations.

PubMed

Hock, Karlo; Wolff, Nicholas H; Beeden, Roger; Hoey, Jessica; Condie, Scott A; Anthony, Kenneth R N; Possingham, Hugh P; Mumby, Peter J

2016-08-01

Controlling the spread of invasive species, pests, and pathogens is often logistically limited to interventions that target specific locations at specific periods. However, in complex, highly connected systems, such as marine environments connected by ocean currents, populations spread dynamically in both space and time via transient connectivity links. This results in nondeterministic future distributions of species in which local populations emerge dynamically and concurrently over a large area. The challenge, therefore, is to choose intervention locations that will maximize the effectiveness of the control efforts. We propose a novel method to manage dynamic species invasions and outbreaks that identifies the intervention locations most likely to curtail population expansion by selectively targeting local populations most likely to expand their future range. Critically, at any point during the development of the invasion or outbreak, the method identifies the local intervention that maximizes the long-term benefit across the ecosystem by restricting species' potential to spread. In so doing, the method adaptively selects the intervention targets under dynamically changing circumstances. To illustrate the effectiveness of the method we applied it to controlling the spread of crown-of-thorns starfish (Acanthaster sp.) outbreaks across Australia's Great Barrier Reef. Application of our method resulted in an 18-fold relative improvement in management outcomes compared with a random targeting of reefs in putative starfish control scenarios. Although we focused on applying the method to reducing the spread of an unwanted species, it can also be used to facilitate the spread of desirable species through connectivity networks. For example, the method could be used to select those fragments of habitat most likely to rebuild a population if they were sufficiently well protected. © 2016 Society for Conservation Biology.

[Estimates of Target Population for Pneumococcal Vaccination in People over 50 years in Catalonia and Spain].

PubMed

Vila-Córcoles, Angel; Ochoa-Gondar, Olga; Satué, Eva; de Diego, Cinta; Vila-Rovira, Marc; Jariod, Manel

2017-03-15

Published data about prevalence of distinct risk condictions for pneumococcal disease is scarce. This study investigated the prevalence of distinct risk conditions for pneumococal disease in Catalonian adults and stimated the potential size of target population for pneumococcal vaccination in Catalonia and Spain. Cross-sectional population-based study that included 2,033,465 individuals older than 49 years-old assigned to the Catalonian Health Institute (Catalonia, Spain) at 01/01/2015. The Catalonian Health Institute Information System for the Development of Research in Primary Care (SIDIAP) was used to identify comorbidities and/or underlying conditions in each subject and establish potential target population for pneumococcal vaccination on the basis of their risk for suffering pneumococcal infections: 1) immunocompromised subjects; 2) immunocompetents subjects with any risk condition; 3) immunocompetents subjects without risk conditions. Of the 2,033,465 study subjects, 1,053,155 (51.8%) had no risk conditions, 649,014 (31.9%) had one risk condition and 331,296 (16.3%) had multiple risk conditions (11.4% in 50-64 years vs 21.2% in people older than 65 years, p smaller than 0.001; 21.8% in men vs 11.6% in women, p smaller than 0.001). Overall, 176,600 (8.7%) and 803,710 (39.5%) were classified in risk stratum 1 and 2, respectively. According to distinct risk strata considered, the target population for pneumococcal vaccination varied between 0.2-1.9 million in Catalonia and 1.5-2.3 million in Spain. In our setting, almost fifty percent of people ≥50 years have at least one risk condition to suffert pneumococcal disease. Adult population susceptible for pneumococal vaccination largely varies depending on the risk stratum considered as targeted people for pneumococcal vaccination.

Widespread occurrence of both metabolic and target-site herbicide resistance mechanisms in Lolium rigidum populations.

PubMed

Han, Heping; Yu, Qin; Owen, Mechelle J; Cawthray, Gregory R; Powles, Stephen B

2016-02-01

Lolium rigidum populations in Australia and globally have demonstrated rapid and widespread evolution of resistance to acetyl coenzyme A carboxylase (ACCase)-inhibiting and acetolactate synthase (ALS)-inhibiting herbicides. Thirty-three resistant L. rigidum populations, randomly collected from crop fields in a most recent resistance survey, were analysed for non-target-site diclofop metabolism and all known target-site ACCase gene resistance-endowing mutations. The HPLC profile of [(14) C]-diclofop-methyl in vivo metabolism revealed that 79% of these resistant L. rigidum populations showed enhanced capacity for diclofop acid metabolism (metabolic resistance). ACCase gene sequencing identified that 91% of the populations contain plants with ACCase resistance mutation(s). Importantly, 70% of the populations exhibit both non-target-site metabolic resistance and target-site ACCase mutations. This work demonstrates that metabolic herbicide resistance is commonly occurring in L. rigidum, and coevolution of both metabolic resistance and target-site resistance is an evolutionary reality. Metabolic herbicide resistance can potentially endow resistance to many herbicides and poses a threat to herbicide sustainability and thus crop production, calling for major research and management efforts. © 2015 Society of Chemical Industry.

Targeted population screening of late onset Pompe disease in unspecified myopathy patients for Korean population.

PubMed

Lee, Jung Hwan; Shin, Jin-Hong; Park, Hyung Jun; Kim, Sook Za; Jeon, Young Mi; Kim, Hye Kyoung; Kim, Dae-Seong; Choi, Young-Chul

2017-06-01

We performed targeted population screening of late onset Pompe disease (LOPD) in unspecified myopathy patients, because early diagnosis is difficult due to its heterogeneous clinical features. We prospectively enrolled 90 unrelated myopathic patients who had one or more signs out of five LOPD-like clinical findings (proximal weakness, axial weakness, lingual weakness, respiratory difficulty, idiopathic hyperCKemia). Acid alpha glucosidase activity was evaluated with dried blood spot and mixed leukocyte simultaneously. For a final diagnosis of LOPD, 16 patients with decreased enzyme activity were genotyped by GAA molecular analysis. We found two patients with LOPD (2.2%), and the remaining 14 patients had at least one G576S or E689K mutation, known as the pseudodeficiency allele. Acid alpha glucosidase activity of LOPD patients was significantly lower than that of patients with at least one pseudodeficiency allele (p = 0.017). This study is the first LOPD screening study for targeted Korean population, and more generally, an Asian population. Our findings suggest that for diagnosis of LOPD in Asian population, modified cutoff value of acid alpha glucosidase activity with dry blood spot considering that of patients having heterozygote pathogenic variants or pseudodeficiency alleles may reduce time and cost requirements and increase the comfort of patients. Copyright © 2017 Elsevier B.V. All rights reserved.

Uptake of atrial fibrillation screening aiming at stroke prevention: geo-mapping of target population and non-participation.

PubMed

Engdahl, Johan; Holmén, Anders; Rosenqvist, Mårten; Strömberg, Ulf

2013-08-03

In a screening study for silent atrial fibrillation (AF), which is a frequent source of cardiac emboli with ischemic stroke, the proportion of non-participants was considerable and their clinical profile differed from the participants' profile. We intended to geo-map the target population and non-participation in an attempt to understand factors related to screening uptake and, thereby, obtain useful information needed to intervene for improved uptake. In the municipality of Halmstad, Sweden, all residents born in 1934-1935 were invited to the screening study during April 2010 to February 2012. The total study group included 848 participants and 367 non-participants from 12 parishes. Geo-maps displaying participation, along with target-population-based geo-maps displaying proportion of immigrants and ischemic stroke incidence, were used. Smoothed non-participation ratios (SmNPR) varied from 0.81 to 1.24 across different parishes (SmNRP=1 corresponds to the expected participation based on the total study group). Among high risk individuals, the geographical variation was more pronounced (SmNPR range 0.75-1.51). Two parishes with higher share of immigrants and elevated population-based ischemic stroke incidence showed markedly lower participation, particularly among high-risk individuals. AF screening uptake varied evidently between parishes, particularly among high-risk individuals. Geo-mapping of target population and non-participation yielded useful information needed to intervene for improved screening uptake.

Social network targeting to maximise population behaviour change: a cluster randomised controlled trial.

PubMed

Kim, David A; Hwong, Alison R; Stafford, Derek; Hughes, D Alex; O'Malley, A James; Fowler, James H; Christakis, Nicholas A

2015-07-11

Information and behaviour can spread through interpersonal ties. By targeting influential individuals, health interventions that harness the distributive properties of social networks could be made more effective and efficient than those that do not. Our aim was to assess which targeting methods produce the greatest cascades or spillover effects and hence maximise population-level behaviour change. In this cluster randomised trial, participants were recruited from villages of the Department of Lempira, Honduras. We blocked villages on the basis of network size, socioeconomic status, and baseline rates of water purification, for delivery of two public health interventions: chlorine for water purification and multivitamins for micronutrient deficiencies. We then randomised villages, separately for each intervention, to one of three targeting methods, introducing the interventions to 5% samples composed of either: randomly selected villagers (n=9 villages for each intervention); villagers with the most social ties (n=9); or nominated friends of random villagers (n=9; the last strategy exploiting the so-called friendship paradox of social networks). Participants and data collectors were not aware of the targeting methods. Primary endpoints were the proportions of available products redeemed by the entire population under each targeting method. This trial is registered with ClinicalTrials.gov, number NCT01672580. Between Aug 4, and Aug 14, 2012, 32 villages in rural Honduras (25-541 participants each; total study population of 5773) received public health interventions. For each intervention, nine villages (each with 1-20 initial target individuals) were randomised, using a blocked design, to each of the three targeting methods. In nomination-targeted villages, 951 (74·3%) of 1280 available multivitamin tickets were redeemed compared with 940 (66·2%) of 1420 in randomly targeted villages and 744 (61·0%) of 1220 in indegree-targeted villages. All pairwise differences

Which population groups should be targeted for cardiovascular prevention? A modelling study based on the Norwegian Hordaland Health Study (HUSK).

PubMed

Brekke, Mette; Rekdal, Magne; Straand, Jørund

2007-06-01

To assess level of cardiovascular risk factors in a non-selected, middle-aged population. To estimate the proportion target for risk intervention according to present guidelines and according to different cut-off levels for two risk algorithms. Population survey, modelling study. The Norwegian Hordaland Health Study (HUSK) 1997-99. A total of 22 289 persons born in 1950-57. Own and relatives' cardiovascular morbidity, antihypertensive and lipid-lowering treatment, smoking, blood pressure, cholesterol. Framingham and Systematic Coronary Risk Evaluation (SCORE) algorithms. The European guidelines on CVD prevention in clinical practice were applied to estimate size of risk groups. Some 9.7% of men and 7.6% of women had CVD, diabetes mellitus, a high level of one specific risk factor, or received lipid-lowering or antihypertensive treatment. Applying a SCORE (60 years) cut-off level at 5% to the rest of the population selected 52.4% of men and 0.8% of women into a primary prevention group, while a cut-off level at 8% included 22.0% and 0.06% respectively. A cut-off level for the Framingham score (60 years) of 20% selected 43.6% of men and 4.7% of women, while a cut-off level of 25% selected 25.6% of men and 1.8% of women. The findings illustrate how choices regarding risk estimation highly affect the size of the target population. Modelling studies are important when preparing guidelines, to address implications for resource allocation and risk of medicalization. The population share to be targeted for primary prevention ought to be estimated, including the impact of various cut-off points for risk algorithms on the size of the risk population.

Comparative Analysis of State Fish Consumption Advisories Targeting Sensitive Populations

PubMed Central

Scherer, Alison C.; Tsuchiya, Ami; Younglove, Lisa R.; Burbacher, Thomas M.; Faustman, Elaine M.

2008-01-01

Objective Fish consumption advisories are issued to warn the public of possible toxicological threats from consuming certain fish species. Although developing fetuses and children are particularly susceptible to toxicants in fish, fish also contain valuable nutrients. Hence, formulating advice for sensitive populations poses challenges. We conducted a comparative analysis of advisory Web sites issued by states to assess health messages that sensitive populations might access. Data sources We evaluated state advisories accessed via the National Listing of Fish Advisories issued by the U.S. Environmental Protection Agency. Data extraction We created criteria to evaluate advisory attributes such as risk and benefit message clarity. Data synthesis All 48 state advisories issued at the time of this analysis targeted children, 90% (43) targeted pregnant women, and 58% (28) targeted women of childbearing age. Only six advisories addressed single contaminants, while the remainder based advice on 2–12 contaminants. Results revealed that advisories associated a dozen contaminants with specific adverse health effects. Beneficial health effects of any kind were specifically associated only with omega-3 fatty acids found in fish. Conclusions These findings highlight the complexity of assessing and communicating information about multiple contaminant exposure from fish consumption. Communication regarding potential health benefits conferred by specific fish nutrients was minimal and focused primarily on omega-3 fatty acids. This overview suggests some lessons learned and highlights a lack of both clarity and consistency in providing the breadth of information that sensitive populations such as pregnant women need to make public health decisions about fish consumption during pregnancy. PMID:19079708

Does targeting key-containers effectively reduce Aedes aegypti population density?

PubMed

Maciel-de-Freitas, Rafael; Lourenço-de-Oliveira, Ricardo

2011-08-01

The elimination of Aedes aegypti breeding sites has been broadly adopted worldwide to keep vector population density below a critical threshold. We observed the effectiveness of targeting the most productive containers on adult A. aegypti females density, which was evaluated weekly. Adult mosquitoes were collected weekly over 55 weeks and pupal surveys were done in intervals of 4 months to determine container productivity and guidelines for interventions. Pupal surveys indicated that water tanks (72% of pupae in first survey) and metal drums (30.7% of pupae in second survey) were the most productive container types. We observed a dramatic but short-term decrease in weekly adult female A. aegypti density after covering 733 water tanks with nylon net. A long-term decrease in female adult population density was achieved only when we covered both water tanks and metal drums. Overall, pupae abundance and pupae standing crop diminished after netting water tanks and metal drums. Pupae per person, per hectare and per house decreased gradually between the first and the third pupal surveys, suggesting that targeting the most productive container types (water tanks and metal drums) produced a reduction in adult population density and infestation levels. Overall, targeting the most productive container types caused the adult mosquito density to decrease over time, supporting the assumption that this intervention is an effective tool for dengue control. However, this effect was observed only when both water tanks and metal drums were covered, possibly due to the functional similarity between these container types, which are large, often shaded, perennial water storage containers. © 2011 Blackwell Publishing Ltd.

Assessing Methods for Generalizing Experimental Impact Estimates to Target Populations

ERIC Educational Resources Information Center

Kern, Holger L.; Stuart, Elizabeth A.; Hill, Jennifer; Green, Donald P.

2016-01-01

Randomized experiments are considered the gold standard for causal inference because they can provide unbiased estimates of treatment effects for the experimental participants. However, researchers and policymakers are often interested in using a specific experiment to inform decisions about other target populations. In education research,…

Identification of population substructure among Jews using STR markers and dependence on reference populations included.

PubMed

Listman, Jennifer B; Hasin, Deborah; Kranzler, Henry R; Malison, Robert T; Mutirangura, Apiwat; Sughondhabirom, Atapol; Aharonovich, Efrat; Spivak, Baruch; Gelernter, Joel

2010-06-14

Detecting population substructure is a critical issue for association studies of health behaviors and other traits. Whether inherent in the population or an artifact of marker choice, determining aspects of a population's genetic history as potential sources of substructure can aid in design of future genetic studies. Jewish populations, among which association studies are often conducted, have a known history of migrations. As a necessary step in understanding population structure to conduct valid association studies of health behaviors among Israeli Jews, we investigated genetic signatures of this history and quantified substructure to facilitate future investigations of these phenotypes in this population. Using 32 autosomal STR markers and the program STRUCTURE, we differentiated between Ashkenazi (AJ, N = 135) and non-Ashkenazi (NAJ, N = 226) Jewish populations in the form of Northern and Southern geographic genetic components (AJ north 73%, south 23%, NAJ north 33%, south 60%). The ability to detect substructure within these closely related populations using a small STR panel was contingent on including additional samples representing major continental populations in the analyses. Although clustering programs such as STRUCTURE are designed to assign proportions of ancestry to individuals without reference population information, when Jewish samples were analyzed in the absence of proxy parental populations, substructure within Jews was not detected. Generally, for samples with a given grandparental country of birth, STRUCTURE assignment values to Northern, Southern, African and Asian clusters agreed with mitochondrial DNA and Y-chromosomal data from previous studies as well as historical records of migration and intermarriage.

Identification of population substructure among Jews using STR markers and dependence on reference populations included

PubMed Central

2010-01-01

Background Detecting population substructure is a critical issue for association studies of health behaviors and other traits. Whether inherent in the population or an artifact of marker choice, determining aspects of a population's genetic history as potential sources of substructure can aid in design of future genetic studies. Jewish populations, among which association studies are often conducted, have a known history of migrations. As a necessary step in understanding population structure to conduct valid association studies of health behaviors among Israeli Jews, we investigated genetic signatures of this history and quantified substructure to facilitate future investigations of these phenotypes in this population. Results Using 32 autosomal STR markers and the program STRUCTURE, we differentiated between Ashkenazi (AJ, N = 135) and non-Ashkenazi (NAJ, N = 226) Jewish populations in the form of Northern and Southern geographic genetic components (AJ north 73%, south 23%, NAJ north 33%, south 60%). The ability to detect substructure within these closely related populations using a small STR panel was contingent on including additional samples representing major continental populations in the analyses. Conclusions Although clustering programs such as STRUCTURE are designed to assign proportions of ancestry to individuals without reference population information, when Jewish samples were analyzed in the absence of proxy parental populations, substructure within Jews was not detected. Generally, for samples with a given grandparental country of birth, STRUCTURE assignment values to Northern, Southern, African and Asian clusters agreed with mitochondrial DNA and Y-chromosomal data from previous studies as well as historical records of migration and intermarriage. PMID:20546593

Cryostat including heater to heat a target

DOEpatents

Pehl, Richard H.; Madden, Norman W.; Malone, Donald F.

1990-01-01

A cryostat is provided which comprises a vacuum vessel; a target disposed within the vacuum vessel; a heat sink disposed within the vacuum vesssel for absorbing heat from the detector; a cooling mechanism for cooling the heat sink; a cryoabsorption mechanism for cryoabsorbing residual gas within the vacuum vessel; and a heater for maintaining the target above a temperature at which the residual gas is cryoabsorbed in the course of cryoabsorption of the residual gas by the cryoabsorption mechanism.

Impact of Targeted Tuberculosis Vaccination Among a Mining Population in South Africa: A Model-Based Study.

PubMed

Shrestha, Sourya; Chihota, Violet; White, Richard G; Grant, Alison D; Churchyard, Gavin J; Dowdy, David W

2017-12-15

Optimizing the use of new tools, such as vaccines, may play a crucial role in reaching global targets for tuberculosis (TB) control. Some of the most promising candidate vaccines target adults, although high-coverage mass vaccinations may be logistically more challenging among this population than among children. Vaccine-delivery strategies that target high-risk groups or settings might yield proportionally greater impact than do those that target the general population. We developed an individual-based TB transmission model representing a hypothetical population consisting of people who worked in South African gold mines or lived in associated labor-sending communities. We simulated the implementation of a postinfection adult vaccine with 60% efficacy and a mean effect duration of 10 years. We then compared the impact of a mine-targeted vaccination strategy, in which miners were vaccinated while in the mines, with that of a community-targeted strategy, in which random individuals within the labor-sending communities were vaccinated. Mine-targeted vaccination averted an estimated 0.37 TB cases per vaccine dose compared with 0.25 for community-targeted vaccination, for a relative efficacy of 1.46 (95% range, 1.13-1.91). The added benefit of mine-targeted vaccination primarily reflected the disproportionate demographic burden of TB among the population of adult males as a whole. As novel vaccines for TB are developed, venue-based vaccine delivery that targets high-risk demographic groups may improve both vaccine feasibility and the impact on transmission. © The Author(s) 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Cryostat including heater to heat a target

DOEpatents

Pehl, R.H.; Madden, N.W.; Malone, D.F.

1990-09-11

A cryostat is provided which comprises a vacuum vessel; a target disposed within the vacuum vessel; a heat sink disposed within the vacuum vessel for absorbing heat from the detector; a cooling mechanism for cooling the heat sink; a cryoabsorption mechanism for cryoabsorbing residual gas within the vacuum vessel; and a heater for maintaining the target above a temperature at which the residual gas is cryoabsorbed in the course of cryoabsorption of the residual gas by the cryoabsorption mechanism. 2 figs.

Nonlinear dynamics support a linear population code in a retinal target-tracking circuit.

PubMed

Leonardo, Anthony; Meister, Markus

2013-10-23

A basic task faced by the visual system of many organisms is to accurately track the position of moving prey. The retina is the first stage in the processing of such stimuli; the nature of the transformation here, from photons to spike trains, constrains not only the ultimate fidelity of the tracking signal but also the ease with which it can be extracted by other brain regions. Here we demonstrate that a population of fast-OFF ganglion cells in the salamander retina, whose dynamics are governed by a nonlinear circuit, serve to compute the future position of the target over hundreds of milliseconds. The extrapolated position of the target is not found by stimulus reconstruction but is instead computed by a weighted sum of ganglion cell outputs, the population vector average (PVA). The magnitude of PVA extrapolation varies systematically with target size, speed, and acceleration, such that large targets are tracked most accurately at high speeds, and small targets at low speeds, just as is seen in the motion of real prey. Tracking precision reaches the resolution of single photoreceptors, and the PVA algorithm performs more robustly than several alternative algorithms. If the salamander brain uses the fast-OFF cell circuit for target extrapolation as we suggest, the circuit dynamics should leave a microstructure on the behavior that may be measured in future experiments. Our analysis highlights the utility of simple computations that, while not globally optimal, are efficiently implemented and have close to optimal performance over a limited but ethologically relevant range of stimuli.

Targeting Hispanic populations: future research and prevention strategies.

PubMed Central

Ramirez, A G; McAlister, A; Gallion, K J; Villarreal, R

1995-01-01

Minority populations face a wide variety of economic, institutional, and cultural barriers to health care. These barriers and low levels of education and income pose significant challenges for health professionals in developing cancer research and prevention-control strategies. It is suggested that specific segments of Hispanic populations fit the model of an underdeveloped country in the intermediate stage of epidemiological transition. Since noncommunicable diseases have not yet fully emerged in some of these Hispanic population segments, the opportunity exists to apply primordial prevention strategies. Such campaigns would focus on dissuading members of these populations from adopting negative health behaviors while promoting positive lifestyle choices. Optimal programs would increase cancer screening participation and discourage risk behaviors through community-oriented, population-based interventions. Future directions in prevention and control efforts for minority populations should include expanded health insurance coverage, improved access to health care, greater emphasis on minority recruitment in health care fields, focused epidemiologic and clinical research, and identification and replication of effective components within existing prevention-control programs. PMID:8741800

TAPIR, a web server for the prediction of plant microRNA targets, including target mimics.

PubMed

Bonnet, Eric; He, Ying; Billiau, Kenny; Van de Peer, Yves

2010-06-15

We present a new web server called TAPIR, designed for the prediction of plant microRNA targets. The server offers the possibility to search for plant miRNA targets using a fast and a precise algorithm. The precise option is much slower but guarantees to find less perfectly paired miRNA-target duplexes. Furthermore, the precise option allows the prediction of target mimics, which are characterized by a miRNA-target duplex having a large loop, making them undetectable by traditional tools. The TAPIR web server can be accessed at: http://bioinformatics.psb.ugent.be/webtools/tapir. Supplementary data are available at Bioinformatics online.

Comprehensive target populations for current active safety systems using national crash databases.

PubMed

Kusano, Kristofer D; Gabler, Hampton C

2014-01-01

The objective of active safety systems is to prevent or mitigate collisions. A critical component in the design of active safety systems is the identification of the target population for a proposed system. The target population for an active safety system is that set of crashes that a proposed system could prevent or mitigate. Target crashes have scenarios in which the sensors and algorithms would likely activate. For example, the rear-end crash scenario, where the front of one vehicle contacts another vehicle traveling in the same direction and in the same lane as the striking vehicle, is one scenario for which forward collision warning (FCW) would be most effective in mitigating or preventing. This article presents a novel set of precrash scenarios based on coded variables from NHTSA's nationally representative crash databases in the United States. Using 4 databases (National Automotive Sampling System-General Estimates System [NASS-GES], NASS Crashworthiness Data System [NASS-CDS], Fatality Analysis Reporting System [FARS], and National Motor Vehicle Crash Causation Survey [NMVCCS]) the scenarios developed in this study can be used to quantify the number of police-reported crashes, seriously injured occupants, and fatalities that are applicable to proposed active safety systems. In this article, we use the precrash scenarios to identify the target populations for FCW, pedestrian crash avoidance systems (PCAS), lane departure warning (LDW), and vehicle-to-vehicle (V2V) or vehicle-to-infrastructure (V2I) systems. Crash scenarios were derived using precrash variables (critical event, accident type, precrash movement) present in all 4 data sources. This study found that these active safety systems could potentially mitigate approximately 1 in 5 of all severity and serious injury crashes in the United States and 26 percent of fatal crashes. Annually, this corresponds to 1.2 million all severity, 14,353 serious injury (MAIS 3+), and 7412 fatal crashes. In addition

Inclusion of populations at risk of advanced melanoma in an opportunistic targeted screening project involving general practitioners

PubMed Central

Rat, Cédric; Quereux, Gaelle; Grimault, Charlotte; Fernandez, Jérémy; Poiraud, Mickael; Gaultier, Aurélie; Chaslerie, Anicet; Pivette, Jacques; Khammari, Amir; Dreno, Brigitte; Nguyen, Jean-Michel

2016-01-01

Objective The study objective was to measure the rates of inclusion of populations at risk of advanced melanoma in a pilot targeted screening project involving general practitioners. Design This cross-sectional database study compared the inclusion rates of patients who signed inclusion in a targeted screening project with those of patients who did not, during a period in which both groups of patients consulted investigators. Setting Data were extracted from the national healthcare insurance records in western France from 11 April to 30 October 2011. Patients Patients, older than 18, considered for the data extraction had consulted one of the 78 participating GPs during the study period, and were affiliated with the national healthcare insurance. Main outcome measures Inclusion in the screening was the main outcome measure. Patients at risk of advanced melanoma were characterized by male gender, age over 50, low income, rural residence, farmer, and presence of chronic disease. Results A total of 57,279 patients consulted GPs during the inclusion period and 2711 (4.73%) were included in the targeted screening. Populations at risk of advanced melanoma were less included: men (OR = 0.67; 95%CI [0.61–0.73]; p < 0.001), older than 50 (OR = 0.67; 95%CI [0.60–0.74]; p < 0.001), low income (OR = 0.65; 95%CI [0.55–0.77]; p < 0.001), farmer (OR = 0.23; 95%CI [0.17–0.30]; p < 0.001) and presence of a chronic disease (OR = 0.87; 95%CI [0.77–0.98]; p < 0.028). Conclusion This study demonstrated inequalities in the inclusion of patients in a melanoma screening. Patients at risk of advanced cancer were screened less often. Further studies should focus on GPs ability to identify and screen these patients. Key Points Advanced melanoma is more frequently diagnosed in men, older patients and socioeconomically disadvantaged populations, which leads to survival inequalities.• Despite the involvement of general practitioners, the

Novel medical therapeutics in glioblastomas, including targeted molecular therapies, current and future clinical trials.

PubMed

Quant, Eudocia C; Wen, Patrick Y

2010-08-01

The prognosis for glioblastoma is poor despite optimal therapy with surgery, radiation, and chemotherapy. New therapies that improve survival and quality of life are needed. Research has increased our understanding of the molecular pathways important for gliomagenesis and disease progression. Novel agents have been developed against these targets, including receptor tyrosine kinases, intracellular signaling molecules, epigenetic abnormalities, and tumor vasculature and microenvironment. This article reviews novel therapies for glioblastoma, with an emphasis on targeted agents. Copyright 2010 Elsevier Inc. All rights reserved.

Emission-line diagnostics of nearby H II regions including interacting binary populations

NASA Astrophysics Data System (ADS)

Xiao, Lin; Stanway, Elizabeth R.; Eldridge, J. J.

2018-06-01

We present numerical models of the nebular emission from H II regions around young stellar populations over a range of compositions and ages. The synthetic stellar populations include both single stars and interacting binary stars. We compare these models to the observed emission lines of 254 H II regions of 13 nearby spiral galaxies and 21 dwarf galaxies drawn from archival data. The models are created using the combination of the BPASS (Binary Population and Spectral Synthesis) code with the photoionization code CLOUDY to study the differences caused by the inclusion of interacting binary stars in the stellar population. We obtain agreement with the observed emission line ratios from the nearby star-forming regions and discuss the effect of binary-star evolution pathways on the nebular ionization of H II regions. We find that at population ages above 10 Myr, single-star models rapidly decrease in flux and ionization strength, while binary-star models still produce strong flux and high [O III]/H β ratios. Our models can reproduce the metallicity of H II regions from spiral galaxies, but we find higher metallicities than previously estimated for the H II regions from dwarf galaxies. Comparing the equivalent width of H β emission between models and observations, we find that accounting for ionizing photon leakage can affect age estimates for H II regions. When it is included, the typical age derived for H II regions is 5 Myr from single-star models, and up to 10 Myr with binary-star models. This is due to the existence of binary-star evolution pathways, which produce more hot Wolf-Rayet and helium stars at older ages. For future reference, we calculate new BPASS binary maximal starburst lines as a function of metallicity, and for the total model population, and present these in Appendix A.

Targeting populations at higher risk for malaria: a survey of national malaria elimination programmes in the Asia Pacific.

PubMed

Wen, Shawn; Harvard, Kelly E; Gueye, Cara Smith; Canavati, Sara E; Chancellor, Arna; Ahmed, Be-Nazir; Leaburi, John; Lek, Dysoley; Namgay, Rinzin; Surya, Asik; Thakur, Garib D; Whittaker, Maxine Anne; Gosling, Roly D

2016-05-10

Significant progress has been made in reducing the malaria burden in the Asia Pacific region, which is aggressively pursuing a 2030 regional elimination goal. Moving from malaria control to elimination requires National Malaria Control Programmes (NMCPs) to target interventions at populations at higher risk, who are often not reached by health services, highly mobile and difficult to test, treat, and track with routine measures, and if undiagnosed, can maintain parasite reservoirs and contribute to ongoing transmission. A qualitative, free-text questionnaire was developed and disseminated among 17 of the 18 partner countries of the Asia Pacific Malaria Elimination Network (APMEN). All 14 countries that responded to the survey identified key populations at higher risk of malaria in their respective countries. Thirteen countries engage in the dissemination of malaria-related Information, Education, and Communication (IEC) materials. Eight countries engage in diagnostic screening, including of mobile and migrant workers, military staff, and/or overseas workers. Ten countries reported distributing or recommending the use of long-lasting insecticide-treated nets (LLINs) among populations at higher risk with fewer countries engaging in other prevention measures such as indoor residual spraying (IRS) (two countries), spatial repellents (four countries), chemoprophylaxis (five countries), and mass drug administration (MDA) (three countries). Though not specifically tailored to populations at higher risk, 11 countries reported using mass blood surveys as a surveillance tool and ten countries map case data. Most NMCPs lack a monitoring and evaluation structure. Countries in the Asia Pacific have identified populations at higher risk and targeted interventions to these groups but there is limited information on the effectiveness of these interventions. Platforms like APMEN offer the opportunity for the sharing of protocols and lessons learned related to finding, targeting and

Is health literacy related to health behaviors and cell phone usage patterns among the text4baby target population?

PubMed

Poorman, Elisabeth; Gazmararian, Julie; Elon, Lisa; Parker, Ruth

2014-01-01

Text4baby provides educational text messages to pregnant and postpartum women and targets underserved women. The primary purpose of this study is to examine the health behaviors and cell phone usage patterns of a text4baby target population and the associations with health literacy. Pregnant and postpartum women were recruited from two Women, Infant and Children clinics in Atlanta. Women were asked about their demographics, selected pregnancy or postpartum health behaviors, and cell phone usage patterns. Health literacy skills were measured with the English version of the Newest Vital Sign. Multivariable logistic regression was used to examine health behaviors and cell usage patterns by health literacy classification, controlling for commonly accepted confounders. Four hundred sixty-eight women were recruited, and 445 completed the Newest Vital Sign. Of these, 22% had inadequate health literacy, 50% had intermediate health literacy, and 28% had adequate health literacy skills. Compared to adequate health literacy, limited literacy was independently associated with not taking a daily vitamin during pregnancy (OR 3.6, 95% CI: 1.6, 8.5) and never breastfeeding their infant (OR 1.4, 95% CI: 1.1, 1.8). The majority (69.4%) of respondents received nine or more text messages a day prior to enrollment, one in four participants (24.6%) had changed their number within the last six months, and 7.0% of study participants shared a cell phone. Controlling for potentially confounding factors, those with limited health literacy were more likely to share a cell phone than those with adequate health literacy (OR 2.57, 95% CI: 1.79, 3.69). Text4baby messages should be appropriate for low health literacy levels, especially as this population may have higher prevalence of targeted unhealthy behaviors. Text4baby and other mhealth programs targetting low health literacy populations should also be aware of the different ways that these populations use their cell phones, including: sharing

[Folic acid fortified foods available in Spain: types of products, level of fortification and target population groups].

PubMed

Samaniego Vaesken, M L; Alonso-Aperte, E; Varela-Moreiras, G

2009-01-01

Folic acid is a potentially relevant factor in the prevention of a number of pathologies (congenital abnormalities, cardiovascular disease, colorectal cancer and neurocognitive decline). This has led to the introduction of different strategies in order to increase folate intake: nutritional education, pharmacological supplementation and mandatory or voluntary fortification of staple foods with folic acid. In Spain there is a growing number of folic acid fortified products on a voluntary basis, but there is also a lack of reliable data to assess their impact on the population's dietary folate intakes. To gather a better knowledge of folic acid food fortification practices in Spain. A Food Composition Database was developed using data from a market study. Also, previously published data of unfortified staple foods from Food Composition Tables was reviewed. The Database included 260 folic acid fortified food items and it was periodically updated. Food groups included were primarily "Cereals and derivatives" (52%) followed by "Dairy products". Most of these foodstuffs lacked a target population for their consumption (37%) or were aimed at "Weight control" (28%) and "Children" (23%), but only 2% targeted women at a reproductive age. Number of unfortified foods included was 690. Fortification levels declared by manufacturers ranged between 15 and 430% of the Recommended Dietary Allowances (RDA) for folic acid per 100 g/ml, and simultaneous addition of B6 and B12 vitamins was observed in 75% of the products. Currently, Spain market offers a significant number of folic acid fortified products on a voluntary basis and at a level > or = 15% of the RDA per 100 g/ml or serving declared by manufacturers.

X-Ray Binary Populations in a Cosmological Context, Including NuSTAR Predictions

NASA Technical Reports Server (NTRS)

Cardiff, Ann Hornschemeier

2011-01-01

The new ultradeep 4 Ms Chandra Deep Field South has afforded the deepest view ever of X-ray binary populations. We report on the latest results on both LMXB and HMXB evolution out to redshifts of approximately four, including comparison with the latest theoretical models, using this deepest-ever view of the X-ray universe with Chandra. The upcoming NuSTAR mission will open up X-ray binary populations in the hard X-ray band, similar to the pioneering work of Fabbiano et al. in the Einstein era. We report on plans to study both Local Group and starburst galaxies as well as the implications those observations may have for X-ray binary populations in galaxies contributing to the Cosmic X-ray Background.

Population and Human Development: A Course Curriculum Including Lesson Plans, Activities, and Bibliography. Revised.

ERIC Educational Resources Information Center

Murphy, Elaine M.; Long, Alison T.

This course outline suggests materials and learning activities on the interrelated causes and consequences of population growth and other population matters. The document describes 15 class sessions which integrate information for sociology, anthropology, psychology, biology, animal behavior, and education. Topics include the history of human…

A Distribution-based Method for Assessing The Differences between Clinical Trial Target Populations and Patient Populations in Electronic Health Records

PubMed Central

Li, Y.; Ryan, P.; Zhang, Y.; Liu, F.; Gao, J.; Bigger, J.T.; Hripcsak, G.

2014-01-01

Summary Objective To improve the transparency of clinical trial generalizability and to illustrate the method using Type 2 diabetes as an example. Methods Our data included 1,761 diabetes clinical trials and the electronic health records (EHR) of 26,120 patients with Type 2 diabetes who visited Columbia University Medical Center of New-York Presbyterian Hospital. The two populations were compared using the Generalizability Index for Study Traits (GIST) on the earliest diagnosis age and the mean hemoglobin A1c (HbA1c) values. Results Greater than 70% of Type 2 diabetes studies allow patients with HbA1c measures between 7 and 10.5, but less than 40% of studies allow HbA1c<7 and fewer than 45% of studies allow HbA1c>10.5. In the real-world population, only 38% of patients had HbA1c between 7 and 10.5, with 12% having values above the range and 52% having HbA1c<7. The GIST for HbA1c was 0.51. Most studies adopted broad age value ranges, with the most common restrictions excluding patients >80 or <18 years. Most of the real-world population fell within this range, but 2% of patients were <18 at time of first diagnosis and 8% were >80. The GIST for age was 0.75. Conclusions We contribute a scalable method to profile and compare aggregated clinical trial target populations with EHR patient populations. We demonstrate that Type 2 diabetes studies are more generalizable with regard to age than they are with regard to HbA1c. We found that the generalizability of age increased from Phase 1 to Phase 3 while the generalizability of HbA1c decreased during those same phases. This method can generalize to other medical conditions and other continuous or binary variables. We envision the potential use of EHR data for examining the generalizability of clinical trials and for defining population-representative clinical trial eligibility criteria. PMID:25024761

A Data-Driven Evaluation of the Stop TB Global Partnership Strategy of Targeting Key Populations at Greater Risk for Tuberculosis

PubMed Central

Schnippel, Kathryn; Sharp, Alana

2016-01-01

Objective Identifying those infected with tuberculosis (TB) is an important component of any strategy for reducing TB transmission and population prevalence. The Stop TB Global Partnership recently launched an initiative with a focus on key populations at greater risk for TB infection or poor clinical outcomes, due to housing and working conditions, incarceration, low household income, malnutrition, co-morbidities, exposure to tobacco and silica dust, or barriers to accessing medical care. To achieve operational targets, the global health community needs effective, low cost, and large-scale strategies for identifying key populations. Using South Africa as a test case, we assess the feasibility and effectiveness of targeting active case finding to populations with TB risk factors identified from regularly collected sources of data. Our approach is applicable to all countries with TB testing and census data. It allows countries to tailor their outreach activities to the particular risk factors of greatest significance in their national context. Methods We use a national database of TB test results to estimate municipality-level TB infection prevalence, and link it to Census data to measure population risk factors for TB including rates of urban households, informal settlements, household income, unemployment, and mobile phone ownership. To examine the relationship between TB prevalence and risk factors, we perform linear regression analysis and plot the set of population characteristics against TB prevalence and TB testing rate by municipality. We overlay lines of best fit and smoothed curves of best fit from locally weighted scatter plot smoothing. Findings Higher TB prevalence is statistically significantly associated with more urban municipalities (slope coefficient β1 = 0.129, p < 0.0001, R2 = 0.133), lower mobile phone access (β1 = -0.053, p < 0.001, R2 = 0.089), lower unemployment rates (β1 = -0.020, p = 0.003, R2 = 0.048), and a lower proportion of low

A Data-Driven Evaluation of the Stop TB Global Partnership Strategy of Targeting Key Populations at Greater Risk for Tuberculosis.

PubMed

McLaren, Zoë M; Schnippel, Kathryn; Sharp, Alana

2016-01-01

Identifying those infected with tuberculosis (TB) is an important component of any strategy for reducing TB transmission and population prevalence. The Stop TB Global Partnership recently launched an initiative with a focus on key populations at greater risk for TB infection or poor clinical outcomes, due to housing and working conditions, incarceration, low household income, malnutrition, co-morbidities, exposure to tobacco and silica dust, or barriers to accessing medical care. To achieve operational targets, the global health community needs effective, low cost, and large-scale strategies for identifying key populations. Using South Africa as a test case, we assess the feasibility and effectiveness of targeting active case finding to populations with TB risk factors identified from regularly collected sources of data. Our approach is applicable to all countries with TB testing and census data. It allows countries to tailor their outreach activities to the particular risk factors of greatest significance in their national context. We use a national database of TB test results to estimate municipality-level TB infection prevalence, and link it to Census data to measure population risk factors for TB including rates of urban households, informal settlements, household income, unemployment, and mobile phone ownership. To examine the relationship between TB prevalence and risk factors, we perform linear regression analysis and plot the set of population characteristics against TB prevalence and TB testing rate by municipality. We overlay lines of best fit and smoothed curves of best fit from locally weighted scatter plot smoothing. Higher TB prevalence is statistically significantly associated with more urban municipalities (slope coefficient β1 = 0.129, p < 0.0001, R2 = 0.133), lower mobile phone access (β1 = -0.053, p < 0.001, R2 = 0.089), lower unemployment rates (β1 = -0.020, p = 0.003, R2 = 0.048), and a lower proportion of low-income households (β1 = -0

Estimated Prevalence of the Target Population for Brain-Computer Interface Neurotechnology in the Netherlands.

PubMed

Pels, Elmar G M; Aarnoutse, Erik J; Ramsey, Nick F; Vansteensel, Mariska J

2017-07-01

People who suffer from paralysis have difficulties participating in society. Particularly burdensome is the locked-in syndrome (LIS). LIS patients are not able to move and speak but are cognitively healthy. They rely on assistive technology to interact with the world and may benefit from neurotechnological advances. Optimal research and design of such aids requires a well-defined target population. However, the LIS population is poorly characterized and the number of patients in this condition is unknown. Here we estimated and described the LIS patient population in the Netherlands to define the target population for assistive (neuro)technology. We asked physicians in the Netherlands if they had patients suffering from severe paralysis and communication problems in their files. Physicians responding affirmatively were asked to fill out a questionnaire on the patients' status. We sent out 9570 letters to general practitioners (GPs), who reported 83 patients. After first screening, the GPs of 46 patients received the questionnaire. Based on the responses, 26 patients were classified as having LIS. Extrapolation of these numbers resulted in a prevalence of 0.73 patients per 100 000 inhabitants. Notable results from the questionnaire were the percentage of patients with neuromuscular disease (>50%) and living at home (>70%). We revealed an etiologically diverse group of LIS patients. The functioning and needs of these patients were, however, similar and many relied on assistive technology. By characterizing the LIS population, our study may contribute to optimal development of assistive (neuro)technology.

Many Mobile Health Apps Target High-Need, High-Cost Populations, But Gaps Remain.

PubMed

Singh, Karandeep; Drouin, Kaitlin; Newmark, Lisa P; Lee, JaeHo; Faxvaag, Arild; Rozenblum, Ronen; Pabo, Erika A; Landman, Adam; Klinger, Elissa; Bates, David W

2016-12-01

With rising smartphone ownership, mobile health applications (mHealth apps) have the potential to support high-need, high-cost populations in managing their health. While the number of available mHealth apps has grown substantially, no clear strategy has emerged on how providers should evaluate and recommend such apps to patients. Key stakeholders, including medical professional societies, insurers, and policy makers, have largely avoided formally recommending apps, which forces patients to obtain recommendations from other sources. To help stakeholders overcome barriers to reviewing and recommending apps, we evaluated 137 patient-facing mHealth apps-those intended for use by patients to manage their health-that were highly rated by consumers and recommended by experts and that targeted high-need, high-cost populations. We found that there is a wide variety of apps in the marketplace but that few apps address the needs of the patients who could benefit the most. We also found that consumers' ratings were poor indications of apps' clinical utility or usability and that most apps did not respond appropriately when a user entered potentially dangerous health information. Going forward, data privacy and security will continue to be major concerns in the dissemination of mHealth apps. Project HOPE—The People-to-People Health Foundation, Inc.

WE-H-BRA-03: Development of a Model to Include the Evolution of Resistant Tumor Subpopulations Into the Treatment Optimization Process for Schedules Involving Targeted Agents in Chemoradiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Grassberger, C; Paganetti, H

Purpose: To develop a model that includes the process of resistance development into the treatment optimization process for schedules that include targeted therapies. Further, to validate the approach using clinical data and to apply the model to assess the optimal induction period with targeted agents before curative treatment with chemo-radiation in stage III lung cancer. Methods: Growth of the tumor and its subpopulations is modeled by Gompertzian growth dynamics, resistance induction as a stochastic process. Chemotherapy induced cell kill is modeled by log-cell kill dynamics, targeted agents similarly but restricted to the sensitive population. Radiation induced cell kill is assumedmore » to follow the linear-quadratic model. The validation patient data consist of a cohort of lung cancer patients treated with tyrosine kinase inhibitors that had longitudinal imaging data available. Results: The resistance induction model was successfully validated using clinical trial data from 49 patients treated with targeted agents. The observed recurrence kinetics, with tumors progressing from 1.4–63 months, result in tumor growth equaling a median volume doubling time of 92 days [34–248] and a median fraction of pre-existing resistance of 0.035 [0–0.22], in agreement with previous clinical studies. The model revealed widely varying optimal time points for the use of curative therapy, reaching from ∼1m to >6m depending on the patient’s growth rate and amount of pre-existing resistance. This demonstrates the importance of patient-specific treatment schedules when targeted agents are incorporated into the treatment. Conclusion: We developed a model including evolutionary dynamics of resistant sub-populations with traditional chemotherapy and radiation cell kill models. Fitting to clinical data yielded patient specific growth rates and resistant fraction in agreement with previous studies. Further application of the model demonstrated how proper timing of chemo

Decoding Target Distance and Saccade Amplitude from Population Activity in the Macaque Lateral Intraparietal Area (LIP)

PubMed Central

Bremmer, Frank; Kaminiarz, Andre; Klingenhoefer, Steffen; Churan, Jan

2016-01-01

Primates perform saccadic eye movements in order to bring the image of an interesting target onto the fovea. Compared to stationary targets, saccades toward moving targets are computationally more demanding since the oculomotor system must use speed and direction information about the target as well as knowledge about its own processing latency to program an adequate, predictive saccade vector. In monkeys, different brain regions have been implicated in the control of voluntary saccades, among them the lateral intraparietal area (LIP). Here we asked, if activity in area LIP reflects the distance between fovea and saccade target, or the amplitude of an upcoming saccade, or both. We recorded single unit activity in area LIP of two macaque monkeys. First, we determined for each neuron its preferred saccade direction. Then, monkeys performed visually guided saccades along the preferred direction toward either stationary or moving targets in pseudo-randomized order. LIP population activity allowed to decode both, the distance between fovea and saccade target as well as the size of an upcoming saccade. Previous work has shown comparable results for saccade direction (Graf and Andersen, 2014a,b). Hence, LIP population activity allows to predict any two-dimensional saccade vector. Functional equivalents of macaque area LIP have been identified in humans. Accordingly, our results provide further support for the concept of activity from area LIP as neural basis for the control of an oculomotor brain-machine interface. PMID:27630547

Transfer of genetic therapy across human populations: molecular targets for increasing patient coverage in repeat expansion diseases

PubMed Central

Varela, Miguel A; Curtis, Helen J; Douglas, Andrew GL; Hammond, Suzan M; O'Loughlin, Aisling J; Sobrido, Maria J; Scholefield, Janine; Wood, Matthew JA

2016-01-01

Allele-specific gene therapy aims to silence expression of mutant alleles through targeting of disease-linked single-nucleotide polymorphisms (SNPs). However, SNP linkage to disease varies between populations, making such molecular therapies applicable only to a subset of patients. Moreover, not all SNPs have the molecular features necessary for potent gene silencing. Here we provide knowledge to allow the maximisation of patient coverage by building a comprehensive understanding of SNPs ranked according to their predicted suitability toward allele-specific silencing in 14 repeat expansion diseases: amyotrophic lateral sclerosis and frontotemporal dementia, dentatorubral-pallidoluysian atrophy, myotonic dystrophy 1, myotonic dystrophy 2, Huntington's disease and several spinocerebellar ataxias. Our systematic analysis of DNA sequence variation shows that most annotated SNPs are not suitable for potent allele-specific silencing across populations because of suboptimal sequence features and low variability (>97% in HD). We suggest maximising patient coverage by selecting SNPs with high heterozygosity across populations, and preferentially targeting SNPs that lead to purine:purine mismatches in wild-type alleles to obtain potent allele-specific silencing. We therefore provide fundamental knowledge on strategies for optimising patient coverage of therapeutics for microsatellite expansion disorders by linking analysis of population genetic variation to the selection of molecular targets. PMID:25990798

Transfer of genetic therapy across human populations: molecular targets for increasing patient coverage in repeat expansion diseases.

PubMed

Varela, Miguel A; Curtis, Helen J; Douglas, Andrew G L; Hammond, Suzan M; O'Loughlin, Aisling J; Sobrido, Maria J; Scholefield, Janine; Wood, Matthew J A

2016-02-01

Allele-specific gene therapy aims to silence expression of mutant alleles through targeting of disease-linked single-nucleotide polymorphisms (SNPs). However, SNP linkage to disease varies between populations, making such molecular therapies applicable only to a subset of patients. Moreover, not all SNPs have the molecular features necessary for potent gene silencing. Here we provide knowledge to allow the maximisation of patient coverage by building a comprehensive understanding of SNPs ranked according to their predicted suitability toward allele-specific silencing in 14 repeat expansion diseases: amyotrophic lateral sclerosis and frontotemporal dementia, dentatorubral-pallidoluysian atrophy, myotonic dystrophy 1, myotonic dystrophy 2, Huntington's disease and several spinocerebellar ataxias. Our systematic analysis of DNA sequence variation shows that most annotated SNPs are not suitable for potent allele-specific silencing across populations because of suboptimal sequence features and low variability (>97% in HD). We suggest maximising patient coverage by selecting SNPs with high heterozygosity across populations, and preferentially targeting SNPs that lead to purine:purine mismatches in wild-type alleles to obtain potent allele-specific silencing. We therefore provide fundamental knowledge on strategies for optimising patient coverage of therapeutics for microsatellite expansion disorders by linking analysis of population genetic variation to the selection of molecular targets.

Profiles of the Adult Education Target Population: Information from the 2000 Census. Revised

ERIC Educational Resources Information Center

Lasater, Beth; Elliott, Barbara

2005-01-01

This report presents national, regional, and state profiles of the target population for adult education, that is, those individuals aged 16 years and over, who have not attained a high school diploma or equivalent and are not currently enrolled in school. The tables contained in this report describe the following characteristics of the target…

Treating spondyloarthritis, including ankylosing spondylitis and psoriatic arthritis, to target: recommendations of an international task force

PubMed Central

Smolen, Josef S; Braun, Jürgen; Dougados, Maxime; Emery, Paul; FitzGerald, Oliver; Helliwell, Philip; Kavanaugh, Arthur; Kvien, Tore K; Landewé, Robert; Luger, Thomas; Mease, Philip; Olivieri, Ignazio; Reveille, John; Ritchlin, Christopher; Rudwaleit, Martin; Schoels, Monika; Sieper, Joachim; de Wit, Martinus; Baraliakos, Xenofon; Betteridge, Neil; Burgos-Vargas, Ruben; Collantes-Estevez, Eduardo; Deodhar, Atul; Elewaut, Dirk; Gossec, Laure; Jongkees, Merryn; Maccarone, Mara; Redlich, Kurt; van den Bosch, Filip; Wei, James Cheng-Chung; Winthrop, Kevin; van der Heijde, Désirée

2014-01-01

Background Therapeutic targets have been defined for diseases like diabetes, hypertension or rheumatoid arthritis and adhering to them has improved outcomes. Such targets are just emerging for spondyloarthritis (SpA). Objective To define the treatment target for SpA including ankylosing spondylitis and psoriatic arthritis (PsA) and develop recommendations for achieving the target, including a treat-to-target management strategy. Methods Based on results of a systematic literature review and expert opinion, a task force of expert physicians and patients developed recommendations which were broadly discussed and voted upon in a Delphi-like process. Level of evidence, grade and strength of the recommendations were derived by respective means. The commonalities between axial SpA, peripheral SpA and PsA were discussed in detail. Results Although the literature review did not reveal trials comparing a treat-to-target approach with another or no strategy, it provided indirect evidence regarding an optimised approach to therapy that facilitated the development of recommendations. The group agreed on 5 overarching principles and 11 recommendations; 9 of these recommendations related commonly to the whole spectrum of SpA and PsA, and only 2 were designed separately for axial SpA, peripheral SpA and PsA. The main treatment target, which should be based on a shared decision with the patient, was defined as remission, with the alternative target of low disease activity. Follow-up examinations at regular intervals that depend on the patient's status should safeguard the evolution of disease activity towards the targeted goal. Additional recommendations relate to extra-articular and extramusculoskeletal aspects and other important factors, such as comorbidity. While the level of evidence was generally quite low, the mean strength of recommendation was 9–10 (10: maximum agreement) for all recommendations. A research agenda was formulated. Conclusions The task force defined the

The ethics and regulatory landscape of including vulnerable populations in pragmatic clinical trials.

PubMed

Welch, Mary Jane; Lally, Rachel; Miller, Jennifer E; Pittman, Stephanie; Brodsky, Lynda; Caplan, Arthur L; Uhlenbrauck, Gina; Louzao, Darcy M; Fischer, James H; Wilfond, Benjamin

2015-10-01

Policies have been developed to protect vulnerable populations in clinical research, including the US federal research regulations (45 Code of Federal Regulations 46 Subparts B, C, and D). These policies generally recognize vulnerable populations to include pregnant women, fetuses, neonates, children, prisoners, persons with physical handicaps or mental disabilities, and disadvantaged persons. The aim has been to protect these populations from harm, often by creating regulatory and ethical checks that may limit their participation in many clinical trials. The recent increase in pragmatic clinical trials raises at least two questions about this approach. First, is exclusion itself a harm to vulnerable populations, as these groups may be denied access to understanding how health interventions work for them in clinical settings? Second, are groups considered vulnerable in traditional clinical trials also vulnerable in pragmatic clinical trials? We argue first that excluding vulnerable subjects from participation in pragmatic clinical trials can be harmful by preventing acquisition of data to meaningfully inform clinical decision-making in the future. Second, we argue that protections for vulnerable subjects in traditional clinical trial settings may not be translatable, feasible, or even ethical to apply in pragmatic clinical trials. We conclude by offering specific recommendations for appropriately protecting vulnerable research subjects in pragmatic clinical trials, focusing on pregnant women, fetuses, neonates, children, prisoners, persons with physical handicaps or mental disabilities, and disadvantaged persons. © The Author(s) 2015.

An Evaluation of Six Brief Interventions that Target Drug-Related Problems in Correctional Populations

ERIC Educational Resources Information Center

Joe, George W.; Knight, Kevin; Simpson, D. Dwayne; Flynn, Patrick M.; Morey, Janis T.; Bartholomew, Norma G.; Tindall, Michele Staton; Burdon, William M.; Hall, Elizabeth A.; Martin, Steve S.; O'Connell, Daniel J.

2012-01-01

Finding brief effective treatments for criminal justice populations is a major public need. The CJ-DATS Targeted Intervention for Corrections (TIC), which consists of six brief interventions (communication, anger, motivation, criminal thinking, social networks, and HIV/sexual health), was tested in separate federally-funded randomized control…

Targeting Environmental Quality to Improve Population Health ...

EPA Pesticide Factsheets

Key goals of health care reform are to stimulate innovative approaches to improve healthcare quality and clinical outcomes while holding down costs. To achieve these goals value-based payment places the needs of the patient first and encourages multi-stakeholder cooperation. Yet, the stakeholders are typically all within the healthcare system, e.g. the Accountable Care Organization or Patient-Centered Medical Home, leaving important contributors to the health of the population such as the public health and environmental health systems absent. And rarely is the quality of the environment regarded as a modifiable factor capable of imparting a health benefit. Underscoring this point, a PubMed search of the search terms “environmental quality” with “value-based payment”, “value-based healthcare” or “value-based reimbursement” returned no relevant articles, providing further evidence that the healthcare industry largely disregards the quality of the environment as a significant determinant of wellbeing and an actionable risk factor for clinical disease management and population health intervention. Yet, the quality of the environment is unequivocally related to indicators of population health including all-cause mortality. The EPA’s Environmental Quality Index (EQI) composed of five different domains (air, land use, water, built environment and social) has provided new estimates of the associations between environmental quality and health stat

Target-site mutations conferring resistance to glyphosate in feathertop Rhodes grass (Chloris virgata) populations in Australia.

PubMed

Ngo, The D; Krishnan, Mahima; Boutsalis, Peter; Gill, Gurjeet; Preston, Christopher

2018-05-01

Chloris virgata is a warm-season, C 4 , annual grass weed affecting field crops in northern Australia that has become an emerging weed in southern Australia. Four populations with suspected resistance to glyphosate were collected in South Australia, Queensland and New South Wales, Australia, and compared with one susceptible (S) population to confirm glyphosate resistance and elucidate possible mechanisms of resistance. Based on the rate of glyphosate required to kill 50% of treated plants (LD 50 ), glyphosate resistance (GR) was confirmed in four populations of C. virgata (V12, V14.2, V14.16 and V15). GR plants were 2-9.7-fold more resistant and accumulated less shikimate after glyphosate treatment than S plants. GR and S plants did not differ in glyphosate absorption and translocation. Target-site EPSPS mutations corresponding to Pro-106-Leu (V14.2) and Pro-106-Ser (V15, V14.16 and V12) substitutions were found in GR populations. The population with Pro-106-Leu substitution was 2.9-4.9-fold more resistant than the three other populations with Pro-106-Ser substitution. This report confirms glyphosate resistance in C. virgata and shows that target-site EPSPS mutations confer resistance to glyphosate in this species. The evolution of glyphosate resistance in C. virgata highlights the need to identify alternative control tactics. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

High water-stressed population estimated by world water resources assessment including human activities under SRES scenarios

NASA Astrophysics Data System (ADS)

Kiguchi, M.; Shen, Y.; Kanae, S.; Oki, T.

2009-04-01

In an argument of the reduction and the adaptation for the climate change, the evaluation of the influence by the climate change is important. When we argue in adaptation plan from a damage scale and balance with the cost, it is particularly important. Parry et al (2001) evaluated the risks in shortage of water, malaria, food, the risk of the coast flood by temperature function and clarified the level of critical climate change. According to their evaluation, the population to be affected by the shortage of water suddenly increases in the range where temperature increases from 1.5 to 2.0 degree in 2080s. They showed how much we need to reduce emissions in order to draw-down significantly the number at risk. This evaluation of critical climate change threats and targets of water shortage did not include the water withdrawal divided by water availability. Shen et al (2008a) estimated the water withdrawal of projection of future world water resources according to socio-economic driving factors predicted for scenarios A1b, A2, B1, and B2 of the Special Report on Emission Scenarios (SRES). However, these results were in function of not temperature but time. The assessment of the highly water-stressed population considered the socioeconomic development is necessary for a function of the temperature. Because of it is easy to understand to need to reduce emission. We present a multi-GCM analysis of the global and regional populations lived in highly water-stressed basin for a function of the temperature using the socioeconomic data and the outputs of GCMs. In scenario A2, the population increases gradually with warming. On the other hand, the future projection population in scenario A1b and B1 increase gradually until the temperature anomaly exceeds around from +1 to +1.5 degree. After that the population is almost constant. From Shen et al (2008b), we evaluated the HWSP and its ratio in the world with temperature function for scenarios A1B, A2, and B1 by the index of W

Transgene expression in target-defined neuron populations mediated by retrograde infection with adeno-associated viral vectors.

PubMed

Rothermel, Markus; Brunert, Daniela; Zabawa, Christine; Díaz-Quesada, Marta; Wachowiak, Matt

2013-09-18

Tools enabling the manipulation of well defined neuronal subpopulations are critical for probing complex neuronal networks. Cre recombinase (Cre) mouse driver lines in combination with the Cre-dependent expression of proteins using viral vectors--in particular, recombinant adeno-associated viral vectors (rAAVs)--have emerged as a widely used platform for achieving transgene expression in specified neural populations. However, the ability of rAAVs to further specify neuronal subsets on the basis of their anatomical connectivity has been reported as limited or inconsistent. Here, we systematically tested a variety of widely used neurotropic rAAVs for their ability to mediate retrograde gene transduction in the mouse brain. We tested pseudotyped rAAVs of several common serotypes (rAAV 2/1, 2/5, and 2/9) as well as constructs both with and without Cre-dependent expression switches. Many of the rAAVs tested--in particular, though not exclusively, Cre-dependent vectors--showed a robust capacity for retrograde infection and transgene expression. Retrograde expression was successful over distances as large as 6 mm and in multiple neuron types, including olfactory projection neurons, neocortical pyramidal cells projecting to distinct targets, and corticofugal and modulatory projection neurons. Retrograde infection using transgenes such as ChR2 allowed for optical control or optically assisted electrophysiological identification of neurons defined genetically as well as by their projection target. These results establish a widely accessible tool for achieving combinatorial specificity and stable, long-term transgene expression to isolate precisely defined neuron populations in the intact animal.

Transgene Expression in Target-Defined Neuron Populations Mediated by Retrograde Infection with Adeno-Associated Viral Vectors

PubMed Central

Rothermel, Markus; Brunert, Daniela; Zabawa, Christine; Díaz-Quesada, Marta

2013-01-01

Tools enabling the manipulation of well defined neuronal subpopulations are critical for probing complex neuronal networks. Cre recombinase (Cre) mouse driver lines in combination with the Cre-dependent expression of proteins using viral vectors—in particular, recombinant adeno-associated viral vectors (rAAVs)—have emerged as a widely used platform for achieving transgene expression in specified neural populations. However, the ability of rAAVs to further specify neuronal subsets on the basis of their anatomical connectivity has been reported as limited or inconsistent. Here, we systematically tested a variety of widely used neurotropic rAAVs for their ability to mediate retrograde gene transduction in the mouse brain. We tested pseudotyped rAAVs of several common serotypes (rAAV 2/1, 2/5, and 2/9) as well as constructs both with and without Cre-dependent expression switches. Many of the rAAVs tested—in particular, though not exclusively, Cre-dependent vectors—showed a robust capacity for retrograde infection and transgene expression. Retrograde expression was successful over distances as large as 6 mm and in multiple neuron types, including olfactory projection neurons, neocortical pyramidal cells projecting to distinct targets, and corticofugal and modulatory projection neurons. Retrograde infection using transgenes such as ChR2 allowed for optical control or optically assisted electrophysiological identification of neurons defined genetically as well as by their projection target. These results establish a widely accessible tool for achieving combinatorial specificity and stable, long-term transgene expression to isolate precisely defined neuron populations in the intact animal. PMID:24048849

Vaccination against meningococcus C. vaccinal coverage in the French target population.

PubMed

Stahl, J-P; Cohen, R; Denis, F; Gaudelus, J; Lery, T; Lepetit, H; Martinot, A

2013-02-01

Immunization against meningococcus C has been recommended in France since 2009 (infants from 12 to 24 months of age, and catch up vaccination up to 25 years of age). It has been reimbursed since January 2010. We had for aim to assess the vaccine coverage in 2011. The study population included mothers of children targeted by the recommendation. They were recruited using Internet data (quotas based on the French National Institute of Statistics (INSEE) data based on a census made in 2007) based on the Institut des Mamans panel and its partners. The mothers had completed a standardized questionnaire and reported all vaccinations mentioned in their child's health-record. We included 3000 mothers of children, 0 to 35 months of age, (1000 for each of the following age range: 0-11 months, 12-23 months, 24-35 months), and 2250 mothers of teenagers, 14 to 16 years of age. Vaccination was deemed "essential/useful" for respectively 90.2% (CI 95%: 89.2-91.3) and 87.8% (CI 95%: 86.4-89.2) of mothers. Vaccine coverage levels were 32.3% (12-23 months), 57.3% (24-35 months), and 21.3% (14-16 years). Two years after the Ministry of Health's decision to reimburse this vaccine, vaccine coverage levels were much lower than they should have been, to expect effectiveness of the vaccination policy. Only 21.3% of teenagers had been vaccinated, and 32.3% of infants during the second year of life. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Managing American Oystercatcher (Haematopus palliatus) population qrowth by targeting nesting season vital rates

USGS Publications Warehouse

Felton, Shilo K.; Hostetter, Nathan J.; Pollock, Kenneth H.; Simons, Theodore R.

2017-01-01

In populations of long-lived species, adult survival typically has a relatively high influence on population growth. From a management perspective, however, adult survival can be difficult to increase in some instances, so other component rates must be considered to reverse population declines. In North Carolina, USA, management to conserve the American Oystercatcher (Haematopus palliatus) targets component vital rates related to fecundity, specifically nest and chick survival. The effectiveness of such a management approach in North Carolina was assessed by creating a three-stage female-based deterministic matrix model. Isoclines were produced from the matrix model to evaluate minimum nest and chick survival rates necessary to reverse population decline, assuming all other vital rates remained stable at mean values. Assuming accurate vital rates, breeding populations within North Carolina appear to be declining. To reverse this decline, combined nest and chick survival would need to increase from 0.14 to ≤ 0.27, a rate that appears to be attainable based on historical estimates. Results are heavily dependent on assumptions of other vital rates, most notably adult survival, revealing the need for accurate estimates of all vital rates to inform management actions. This approach provides valuable insights for evaluating conservation goals for species of concern.

Sharing reference data and including cows in the reference population improve genomic predictions in Danish Jersey.

PubMed

Su, G; Ma, P; Nielsen, U S; Aamand, G P; Wiggans, G; Guldbrandtsen, B; Lund, M S

2016-06-01

Small reference populations limit the accuracy of genomic prediction in numerically small breeds, such like Danish Jersey. The objective of this study was to investigate two approaches to improve genomic prediction by increasing size of reference population in Danish Jersey. The first approach was to include North American Jersey bulls in Danish Jersey reference population. The second was to genotype cows and use them as reference animals. The validation of genomic prediction was carried out on bulls and cows, respectively. In validation on bulls, about 300 Danish bulls (depending on traits) born in 2005 and later were used as validation data, and the reference populations were: (1) about 1050 Danish bulls, (2) about 1050 Danish bulls and about 1150 US bulls. In validation on cows, about 3000 Danish cows from 87 young half-sib families were used as validation data, and the reference populations were: (1) about 1250 Danish bulls, (2) about 1250 Danish bulls and about 1150 US bulls, (3) about 1250 Danish bulls and about 4800 cows, (4) about 1250 Danish bulls, 1150 US bulls and 4800 Danish cows. Genomic best linear unbiased prediction model was used to predict breeding values. De-regressed proofs were used as response variables. In the validation on bulls for eight traits, the joint DK-US bull reference population led to higher reliability of genomic prediction than the DK bull reference population for six traits, but not for fertility and longevity. Averaged over the eight traits, the gain was 3 percentage points. In the validation on cows for six traits (fertility and longevity were not available), the gain from inclusion of US bull in reference population was 6.6 percentage points in average over the six traits, and the gain from inclusion of cows was 8.2 percentage points. However, the gains from cows and US bulls were not accumulative. The total gain of including both US bulls and Danish cows was 10.5 percentage points. The results indicate that sharing reference

Multilevel Interventions Targeting Obesity: Research Recommendations for Vulnerable Populations

PubMed Central

Stevens, June; Pratt, Charlotte; Boyington, Josephine; Nelson, Cheryl; Truesdale, Kimberly P.; Ward, Dianne S.; Lytle, Leslie; Sherwood, Nancy E.; Robinson, Thomas N.; Moore, Shirley; Barkin, Shari; Cheung, Ying Kuen; Murray, David M.

2017-01-01

Introduction The origins of obesity are complex and multifaceted. To be successful, an intervention aiming to prevent or treat obesity may need to address multiple layers of biological, social, and environmental influences. Methods NIH recognizes the importance of identifying effective strategies to combat obesity, particularly in high-risk and disadvantaged populations with heightened susceptibility to obesity and subsequent metabolic sequelae. To move this work forward, the National Heart, Lung, and Blood Institute, in collaboration with the NIH Office of Behavioral and Social Science Research and NIH Office of Disease Prevention convened a working group to inform research on multilevel obesity interventions in vulnerable populations. The working group reviewed relevant aspects of intervention planning, recruitment, retention, implementation, evaluation, and analysis, and then made recommendations. Results Recruitment and retention techniques used in multilevel research must be culturally appropriate and suited to both individuals and organizations. Adequate time and resources for preliminary work are essential. Collaborative projects can benefit from complementary areas of expertise and shared investigations rigorously pretesting specific aspects of approaches. Study designs need to accommodate the social and environmental levels under study, and include appropriate attention given to statistical power. Projects should monitor implementation in the multiple venues and include a priori estimation of the magnitude of change expected within and across levels. Conclusions The complexity and challenges of delivering interventions at several levels of the social—ecologic model require careful planning and implementation, but hold promise for successful reduction of obesity in vulnerable populations. PMID:28340973

Can a public health package on glaucoma reach its target population?

PubMed

Baker, H; Murdoch, I E

2004-05-01

A pilot study to assess how successful a newspaper advertisement and a radio interview about glaucoma are at reaching their target population. The health intervention comprised two components: an interview on local radio and an advertisement in the local paper. Our target population were residents aged 45 years and above in either Southall (West London) or the Isle of Wight (IOW). A questionnaire was developed to be carried out pre- and post-intervention. The data from both locations pre and post were coded and cleaned. Tests of significance were carried out to assess statistical significance for differences in proportion, with tests for trend used where appropriate. All statistical analyses were carried out using Stata7. Overall, the proportion who had heard of glaucoma increased from 54% before the intervention to 60% after (chi(2) = 3.7, P = 0.055). The proportion who had heard of the disease increased by 13% (chi(2) = 8.76, P = 0.003) in Southall and by 8% (chi(2) = 5.02, P = 0.025) on the IOW. The proportion reporting seeing the advert increased significantly in both areas with greater effect in Southall. Those reporting hearing the radio interview only increased in Southall. On the IOW, females were more knowledgeable and responded more positively to the intervention. This differed in Southall where males tended to be the positive responders. Conclusion In both areas a significant effect on those having heard of glaucoma was found. This could be attributed to both the advert and interview in Southall but would appear to be attributable to the newspaper advertisement alone on the IOW.

Fertility targets and policy options in Asia.

PubMed

Bulatao, R A

1984-11-01

The 3rd Asian and Pacific Population Conference in Colombo in 1982 recommended that countries review and modify existing demographic targets and goals for reducing birth and death rates in order to attain low levels as early as possible and to attain replacement level by the year 2000. The demographic goals of selected Asian countries (Bangladesh, Indonesia, Korea, Thailand, India, Pakistan, and the Philippines are assessed and compared to World Bank population projections. It also discusses the underlying rationale for setting fertility targets, and considers what government actions could make them more achievable. 6 stages for controlling population are distinguished: 1) collection and publication of reliable demographic data; 2) enunciation of an official policy to reduce population growth; 3) development of appropriate institutions to integrate demographic projections into economic plans; 4) promotion of family planning; 5) provision of incentives and disincentives, including elimination of all implicit and explicit subsidies for child bearing; and 6) restitution of birth quotas requiring permission for each child born. Principles to maintain and accelerate fertility declines to meet demographic targets include creating appropriate and equitable development policies, increasing the standard of family planning programs, confronting organizational problems, providing easier and more equal access to contraceptive methods, exploring innovative approaches to encourage smaller families and making a firm political commitment to population control. Rapid fertility decline will also require financial commitment. Willingness to spend the necessary amounts, and the capacity to spend them as well, will determine whether the countries of Asia enter the next century in control of their population.

Integrating Vocational & Academic Education. A Handbook Featuring Four Demonstration Sites Including Students from Special Populations.

ERIC Educational Resources Information Center

Tindall, Lloyd W.; And Others

This handbook describes the processes and techniques used to develop, implement, and evaluate four integrated vocational and academic learning programs in Wisconsin that included students from special populations. The handbook contains seven chapters. Chapter 1 presents an overview of the project, including the request for proposal process and…

HLA-targeted flow cytometric sorting of blood cells allows separation of pure and viable microchimeric cell populations.

PubMed

Drabbels, Jos J M; van de Keur, Carin; Kemps, Berit M; Mulder, Arend; Scherjon, Sicco A; Claas, Frans H J; Eikmans, Michael

2011-11-10

Microchimerism is defined by the presence of low levels of nonhost cells in a person. We developed a reliable method for separating viable microchimeric cells from the host environment. For flow cytometric cell sorting, HLA antigens were targeted with human monoclonal HLA antibodies (mAbs). Optimal separation of microchimeric cells (present at a proportion as low as 0.01% in artificial mixtures) was obtained with 2 different HLA mAbs, one targeting the chimeric cells and the other the background cells. To verify purity of separated cell populations, flow-sorted fractions of 1000 cells were processed for DNA analysis by HLA-allele-specific and Y-chromosome-directed real-time quantitative PCR assays. After sorting, PCR signals of chimeric DNA markers in the positive fractions were significantly enhanced compared with those in the presort samples, and they were similar to those in 100% chimeric control samples. Next, we demonstrate applicability of HLA-targeted FACS sorting after pregnancy by separating chimeric maternal cells from child umbilical cord mononuclear cells. Targeting allelic differences with anti-HLA mAbs with FACS sorting allows maximal enrichment of viable microchimeric cells from a background cell population. The current methodology enables reliable microchimeric cell detection and separation in clinical specimens.

Identifying water price and population criteria for meeting future urban water demand targets

NASA Astrophysics Data System (ADS)

Ashoori, Negin; Dzombak, David A.; Small, Mitchell J.

2017-12-01

Predictive models for urban water demand can help identify the set of factors that must be satisfied in order to meet future targets for water demand. Some of the explanatory variables used in such models, such as service area population and changing temperature and rainfall rates, are outside the immediate control of water planners and managers. Others, such as water pricing and the intensity of voluntary water conservation efforts, are subject to decisions and programs implemented by the water utility. In order to understand this relationship, a multiple regression model fit to 44 years of monthly demand data (1970-2014) for Los Angeles, California was applied to predict possible future demand through 2050 under alternative scenarios for the explanatory variables: population, price, voluntary conservation efforts, and temperature and precipitation outcomes predicted by four global climate models with two CO2 emission scenarios. Future residential water demand in Los Angeles is projected to be largely driven by price and population rather than climate change and conservation. A median projection for the year 2050 indicates that residential water demand in Los Angeles will increase by approximately 36 percent, to a level of 620 million m3 per year. The Monte Carlo simulations of the fitted model for water demand were then used to find the set of conditions in the future for which water demand is predicted to be above or below the Los Angeles Department of Water and Power 2035 goal to reduce residential water demand by 25%. Results indicate that increases in price can not ensure that the 2035 water demand target can be met when population increases. Los Angeles must rely on furthering their conservation initiatives and increasing their use of stormwater capture, recycled water, and expanding their groundwater storage. The forecasting approach developed in this study can be utilized by other cities to understand the future of water demand in water-stressed areas

Multilevel Interventions Targeting Obesity: Research Recommendations for Vulnerable Populations.

PubMed

Stevens, June; Pratt, Charlotte; Boyington, Josephine; Nelson, Cheryl; Truesdale, Kimberly P; Ward, Dianne S; Lytle, Leslie; Sherwood, Nancy E; Robinson, Thomas N; Moore, Shirley; Barkin, Shari; Cheung, Ying Kuen; Murray, David M

2017-01-01

The origins of obesity are complex and multifaceted. To be successful, an intervention aiming to prevent or treat obesity may need to address multiple layers of biological, social, and environmental influences. NIH recognizes the importance of identifying effective strategies to combat obesity, particularly in high-risk and disadvantaged populations with heightened susceptibility to obesity and subsequent metabolic sequelae. To move this work forward, the National Heart, Lung, and Blood Institute, in collaboration with the NIH Office of Behavioral and Social Science Research and NIH Office of Disease Prevention convened a working group to inform research on multilevel obesity interventions in vulnerable populations. The working group reviewed relevant aspects of intervention planning, recruitment, retention, implementation, evaluation, and analysis, and then made recommendations. Recruitment and retention techniques used in multilevel research must be culturally appropriate and suited to both individuals and organizations. Adequate time and resources for preliminary work are essential. Collaborative projects can benefit from complementary areas of expertise and shared investigations rigorously pretesting specific aspects of approaches. Study designs need to accommodate the social and environmental levels under study, and include appropriate attention given to statistical power. Projects should monitor implementation in the multiple venues and include a priori estimation of the magnitude of change expected within and across levels. The complexity and challenges of delivering interventions at several levels of the social-ecologic model require careful planning and implementation, but hold promise for successful reduction of obesity in vulnerable populations. Copyright © 2016. Published by Elsevier Inc.

Design of ligand-targeted nanoparticles for enhanced cancer targeting

NASA Astrophysics Data System (ADS)

Stefanick, Jared F.

Ligand-targeted nanoparticles are increasingly used as drug delivery vehicles for cancer therapy, yet have not consistently produced successful clinical outcomes. Although these inconsistencies may arise from differences in disease models and target receptors, nanoparticle design parameters can significantly influence therapeutic efficacy. By employing a multifaceted synthetic strategy to prepare peptide-targeted nanoparticles with high purity, reproducibility, and precisely controlled stoichiometry of functionalities, this work evaluates the roles of polyethylene glycol (PEG) coating, ethylene glycol (EG) peptide-linker length, peptide hydrophilicity, peptide density, and nanoparticle size on tumor targeting in a systematic manner. These parameters were analyzed in multiple disease models by targeting human epidermal growth factor receptor 2 (HER2) in breast cancer and very late antigen-4 (VLA-4) in multiple myeloma to demonstrate the widespread applicability of this approach. By increasing the hydrophilicity of the targeting peptide sequence and simultaneously optimizing the EG peptide-linker length, the in vitro cellular uptake of targeted liposomes was significantly enhanced. Specifically, including a short oligolysine chain adjacent to the targeting peptide sequence effectively increased cellular uptake ~80-fold using an EG6 peptide-linker compared to ~10-fold using an EG45 linker. In vivo, targeted liposomes prepared in a traditional manner lacking the oligolysine chain demonstrated similar biodistribution and tumor uptake to non-targeted liposomes. However, by including the oligolysine chain, targeted liposomes using an EG45 linker significantly improved tumor uptake ~8-fold over non-targeted liposomes, while the use of an EG6 linker decreased tumor accumulation and uptake, owing to differences in cellular uptake kinetics, clearance mechanisms, and binding site barrier effects. To further improve tumor targeting and enhance the selectivity of targeted

Targeting distinct myeloid cell populations in vivo using polymers, liposomes and microbubbles.

PubMed

Ergen, Can; Heymann, Felix; Al Rawashdeh, Wa'el; Gremse, Felix; Bartneck, Matthias; Panzer, Ulf; Pola, Robert; Pechar, Michal; Storm, Gert; Mohr, Nicole; Barz, Matthias; Zentel, Rudolf; Kiessling, Fabian; Trautwein, Christian; Lammers, Twan; Tacke, Frank

2017-01-01

Identifying intended or accidental cellular targets for drug delivery systems is highly relevant for evaluating therapeutic and toxic effects. However, limited knowledge exists on the distribution of nano- and micrometer-sized carrier systems at the cellular level in different organs. We hypothesized that clinically relevant carrier materials, differing in composition and size, are able to target distinct myeloid cell subsets that control inflammatory processes, such as macrophages, neutrophils, monocytes and dendritic cells. Therefore, we analyzed the biodistribution and in vivo cellular uptake of intravenously injected poly(N-(2-hydroxypropyl) methacrylamide) polymers, PEGylated liposomes and poly(butyl cyanoacrylate) microbubbles in mice, using whole-body imaging (computed tomography - fluorescence-mediated tomography), intra-organ imaging (intravital multi-photon microscopy) and cellular analysis (flow cytometry of blood, liver, spleen, lung and kidney). While the three carrier materials shared accumulation in tissue macrophages in liver and spleen, they notably differed in uptake by other myeloid subsets. Kupffer cells and splenic red pulp macrophages rapidly take up microbubbles. Liposomes efficiently reach dendritic cells in liver, lung and kidney. Polymers exhibit the longest circulation half-life and target endothelial cells in the liver, neutrophils and alveolar macrophages. The identification of such previously unrecognized target cell populations might open up new avenues for more efficient drug delivery. Copyright © 2016 Elsevier Ltd. All rights reserved.

The ethics and regulatory landscape of including vulnerable populations in pragmatic clinical trials

PubMed Central

Welch, Mary Jane; Lally, Rachel; Miller, Jennifer E; Pittman, Stephanie; Brodsky, Lynda; Caplan, Arthur L; Uhlenbrauck, Gina; Louzao, Darcy M; Fischer, James H; Wilfond, Benjamin

2015-01-01

Policies have been developed to protect vulnerable populations in clinical research, particularly the US federal research regulations (45 CFR 46 subparts B, C, and D). These policies generally recognize vulnerable populations to include pregnant women, fetuses, neonates, children, prisoners, persons with physical handicaps or mental disabilities, and disadvantaged persons. The aim has been to protect these populations from harm, often by creating regulatory and ethical checks that may limit their participation in many clinical trials. The recent increase in pragmatic clinical trials (PCTs) raises at least two questions about this approach. First, is exclusion itself a harm to vulnerable populations, as these groups may be denied access to understanding how health interventions work for them in clinical settings? Second, are groups considered vulnerable in traditional clinical trials also vulnerable in PCTs? We argue first, that excluding vulnerable subjects from participation in PCTs can be harmful by preventing acquisition of data to meaningfully inform clinical decision-making in the future. Second, we argue that protections for vulnerable subjects in traditional clinical trial settings may not be translatable, feasible, or even ethical to apply in PCTs. We conclude by offering specific recommendations for appropriately protecting vulnerable research subjects in PCTs, focusing on pregnant women, fetuses, neonates, children, prisoners, persons with physical handicaps or mental disabilities, and disadvantaged persons. PMID:26374681

Network analysis of translocated Takahe populations to identify disease surveillance targets.

PubMed

Grange, Zoë L; VAN Andel, Mary; French, Nigel P; Gartrell, Brett D

2014-04-01

network in 2011. Likewise, the wild Murchison Mountains population was consistently the sink of the network. Other nodes, such as the offshore islands and the wildlife hospital, varied in importance over time. Common network descriptors and measures of centrality identified key locations for targeting disease surveillance. The visual representation of movements of animals in a population that this technique provides can aid decision makers when they evaluate translocation proposals or attempt to control a disease outbreak. © 2014 Society for Conservation Biology.

Use and outcomes of targeted therapies in early and metastatic HER2-positive breast cancer in Australia: protocol detailing observations in a whole of population cohort

PubMed Central

Daniels, Benjamin; Lord, Sarah J; Kiely, Belinda E; Houssami, Nehmat; Haywood, Philip; Lu, Christine Y; Ward, Robyn L; Pearson, Sallie-Anne

2017-01-01

Background The management of human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC) has changed dramatically with the introduction and widespread use of HER2-targeted therapies. However, there is relatively limited real-world information on patterns of use, effectiveness and safety in whole of population cohorts. The research programme detailed in this protocol will generate evidence on the prescribing patterns, safety monitoring and outcomes of patients with BC treated with HER2-targeted therapies in Australia. Methods/design Our ongoing research programme will involve a series of retrospective cohort studies that include every patient accessing Commonwealth-funded HER2-targeted therapies for the treatment of early BC and advanced BC in Australia. At the time of writing, our cohorts consist of 11 406 patients with early BC and 5631 with advanced BC who accessed trastuzumab and lapatinib between 2001 and 2014. Pertuzumab and trastuzumab emtansine were publicly funded for metastatic BC in 2015, and future data updates will include patients accessing these medicines. We will use dispensing claims for cancer and other medicines, medical service claims and demographics data for each patient accessing HER2-targeted therapies to undertake this research. Ethics and dissemination Ethics approval has been granted by the Population Health Service Research Ethics Committee and data access approval has been granted by the Australian Department of Human Services (DHS) External Review Evaluation Committee. Our findings will be reported in peer-reviewed publications, conference presentations and policy forums. By providing detailed information on the use and outcomes associated with HER2-targeted therapies in a national cohort treated in routine clinical care, our research programme will better inform clinicians and patients about the real-world use of these treatments and will assist third-party payers to better understand the use and economic costs of these

Culturally Targeted Strategies for Diabetes Prevention in Minority Population.

PubMed

Lagisetty, Pooja A; Priyadarshini, Shubadra; Terrell, Stephanie; Hamati, Mary; Landgraf, Jessica; Chopra, Vineet; Heisler, Michele

2017-02-01

Purpose The purpose of this study is to (a) assess the effectiveness of culturally tailored diabetes prevention interventions in minority populations and (b) develop a novel framework to characterize 4 key domains of culturally tailored interventions. Prevention strategies specifically tailored to the culture of ethnic minority patients may help reduce the incidence of diabetes. Methods We searched PubMed, EMBASE, and CINAHL for English-language, randomized controlled trials (RCTs) or quasi-experimental (QE) trials testing culturally tailored interventions to prevent diabetes in minority populations. Two reviewers independently extracted data and assessed risk of bias. Inductive thematic analysis was used to develop a framework with 4 domains (FiLLM: Facilitating [ie, delivering] Interventions Through Language, Location, and Message). The framework was used to assess the overall effectiveness of culturally tailored interventions. Results Thirty-four trials met eligibility criteria. Twelve studies were RCTs, and 22 were QE trials. Twenty-five out of 34 studies (74%) that used cultural tailoring demonstrated significantly improved A1C, fasting glucose, and/or weight loss. Of the 25 successful interventions, 21 (84%) incorporated at least 3 culturally targeted domains. Seven studies used all 4 domains and were all successful. The least utilized domain was delivery (4/34) of the intervention's key educational message. Conclusions Culturally tailoring interventions across the 4 domains of facilitators, language, location, and messaging can be effective in improving risk factors for progression to diabetes among ethnic minority groups. Future studies should evaluate how specific tailoring approaches work compared to usual care as well as comparative effectiveness of each tailoring domain.

In silico target prediction for elucidating the mode of action of herbicides including prospective validation.

PubMed

Chiddarwar, Rucha K; Rohrer, Sebastian G; Wolf, Antje; Tresch, Stefan; Wollenhaupt, Sabrina; Bender, Andreas

2017-01-01

The rapid emergence of pesticide resistance has given rise to a demand for herbicides with new mode of action (MoA). In the agrochemical sector, with the availability of experimental high throughput screening (HTS) data, it is now possible to utilize in silico target prediction methods in the early discovery phase to suggest the MoA of a compound via data mining of bioactivity data. While having been established in the pharmaceutical context, in the agrochemical area this approach poses rather different challenges, as we have found in this work, partially due to different chemistry, but even more so due to different (usually smaller) amounts of data, and different ways of conducting HTS. With the aim to apply computational methods for facilitating herbicide target identification, 48,000 bioactivity data against 16 herbicide targets were processed to train Laplacian modified Naïve Bayesian (NB) classification models. The herbicide target prediction model ("HerbiMod") is an ensemble of 16 binary classification models which are evaluated by internal, external and prospective validation sets. In addition to the experimental inactives, 10,000 random agrochemical inactives were included in the training process, which showed to improve the overall balanced accuracy of our models up to 40%. For all the models, performance in terms of balanced accuracy of≥80% was achieved in five-fold cross validation. Ranking target predictions was addressed by means of z-scores which improved predictivity over using raw scores alone. An external testset of 247 compounds from ChEMBL and a prospective testset of 394 compounds from BASF SE tested against five well studied herbicide targets (ACC, ALS, HPPD, PDS and PROTOX) were used for further validation. Only 4% of the compounds in the external testset lied in the applicability domain and extrapolation (and correct prediction) was hence impossible, which on one hand was surprising, and on the other hand illustrated the utilization of

The quest for population-level cancer recurrence data; current deficiencies and targets for improvement.

PubMed

In, Haejin; Simon, Cassie A; Phillips, Jerri Linn; Posner, Mitchell C; Ko, Clifford Y; Winchester, David P

2015-05-01

Cancer recurrence is a critical outcome in cancer care. However, population-level recurrence information is currently unavailable. Tumor registries provide an opportunity to generate this information, but require major reform. Our objectives were to (1) determine causes for variability in collection of recurrence, and (2) identify targets for intervention. On-site interviews and observations of tumor registry follow-up procedures were conducted at Commission on Cancer (CoC) accredited hospitals. Information regarding registry resources (caseload, staffing, chart availability), follow-up methods and perceived causes for difficulty in obtaining recurrence information was obtained. Seven NCI/academic, 5 comprehensive community and 2 community centers agreed to participate. Hospitals were inconsistent in their investigation of cancer recurrence, resulting in underreporting of rates of recurrence. Hospital characteristics, registry staffing, staff qualifications and medical chart access influenced follow-up practices. Coding standards and definitions for recurrence were suboptimal, resulting in hospital variability of recurrence reporting. Finally, inability to identify cases lost to follow-up in collected data prevents accurate analysis of recurrence rates. Tumor registries collect varying degrees of recurrence information and provide the underpinnings to capture population-level cancer recurrence data. Targets for intervention are listed, and provide a roadmap to obtain this critical information in cancer care. © 2015 Wiley Periodicals, Inc.

Planar optical waveguide based sandwich assay sensors and processes for the detection of biological targets including protein markers, pathogens and cellular debris

DOEpatents

Martinez, Jennifer S [Santa Fe, NM; Swanson, Basil I [Los Alamos, NM; Grace, Karen M [Los Alamos, NM; Grace, Wynne K [Los Alamos, NM; Shreve, Andrew P [Santa Fe, NM

2009-06-02

An assay element is described including recognition ligands bound to a film on a single mode planar optical waveguide, the film from the group of a membrane, a polymerized bilayer membrane, and a self-assembled monolayer containing polyethylene glycol or polypropylene glycol groups therein and an assay process for detecting the presence of a biological target is described including injecting a biological target-containing sample into a sensor cell including the assay element, with the recognition ligands adapted for binding to selected biological targets, maintaining the sample within the sensor cell for time sufficient for binding to occur between selected biological targets within the sample and the recognition ligands, injecting a solution including a reporter ligand into the sensor cell; and, interrogating the sample within the sensor cell with excitation light from the waveguide, the excitation light provided by an evanescent field of the single mode penetrating into the biological target-containing sample to a distance of less than about 200 nanometers from the waveguide thereby exciting the fluorescent-label in any bound reporter ligand within a distance of less than about 200 nanometers from the waveguide and resulting in a detectable signal.

[Characteristics and cardiovascular events in a general population included in the RICARTO (RIesgo CARdiovascular TOledo) study: Data from the first 1,500 individuals included in the study].

PubMed

Rodríguez-Roca, G C; Segura-Fragoso, A; Villarín-Castro, A; Alonso-Moreno, F J; Rodríguez-Padial, L; Rodríguez-García, M L; Fernández-Conde, J A; Rojas-Martelo, G A; Menchén-Herreros, A; Escobar-Cervantes, C; Fernández-Martín, J; Artigao-Rodenas, L M; Carbayo-Herencia, J A; Hernández-Moreno, J

2018-04-01

The aim of this study was to assess cardiovascular risk (CVR) by investigating the prevalence of CVR factors (CVRF), target organ damage (TOD), and cardiovascular disease (CVD) in general population of the health area of Toledo, Spain. Epidemiological and observational study that analysed a sample from the general population aged 18years or older, randomly selected from a database of health cards stratified by age and gender. Clinical history, physical examination, and complementary tests were performed. Total blood and serum samples were frozen at -85°C to evaluate genetic studies in the future. Standard statistical analysis was performed. CVR was assessed by the SCORE scale calibrated for the Spanish population, and the Framingham Heart Study scale. A total of 1,500 individuals (mean age 49.1±15.8years, 55.6% women) were included. Prevalences: dyslipidaemia 56.9% (95% confidence interval [95% CI]: 54.3-59.4), hypertension 33.0% (95%CI: 30.6-35.4), diabetes mellitus 8.6% (95%CI: 7.17-10.1), smoking 24.2% (95%CI; 122.0-26.4), obesity 25.3% (95%CI; 23.1-27.5), and sedentary life-style 39.4% (95%CI; 36.9-41.8). No CVRF was reported in 21.1% of cases, and 18.6% had 3-5 CVRF. TOD: electrocardiographic left ventricular hypertrophy, 4.3%, peripheral artery disease, 10.1% (Doppler ultrasound), and 15.3% (oscillometric device), microalbuminuria, 4.3%, sub-clinical renal disease, 3.2%, and nephropathy in 3.8% (CKD-EPI). At least one CVD was reported in 9.2% of cases. A low CVR (SCORE) was present in 44.6% of individuals. Dyslipidaemia was found in 60% of individuals, 40% had a sedentary life-style, 30% with hypertension, 20% smoked, 20% obesity, and almost 10% with diabetes. More than a half of individuals have a moderate-high-very high risk. The prevalence of TOD and CVD are significant. Copyright © 2017 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.

Pneumococcal vaccine targeting strategy for older adults: customized risk profiling.

PubMed

Balicer, Ran D; Cohen, Chandra J; Leibowitz, Morton; Feldman, Becca S; Brufman, Ilan; Roberts, Craig; Hoshen, Moshe

2014-02-12

Current pneumococcal vaccine campaigns take a broad, primarily age-based approach to immunization targeting, overlooking many clinical and administrative considerations necessary in disease prevention and resource planning for specific patient populations. We aim to demonstrate the utility of a population-specific predictive model for hospital-treated pneumonia to direct effective vaccine targeting. Data was extracted for 1,053,435 members of an Israeli HMO, age 50 and older, during the study period 2008-2010. We developed and validated a logistic regression model to predict hospital-treated pneumonia using training and test samples, including a set of standard and population-specific risk factors. The model's predictive value was tested for prospectively identifying cases of pneumonia and invasive pneumococcal disease (IPD), and was compared to the existing international paradigm for patient immunization targeting. In a multivariate regression, age, co-morbidity burden and previous pneumonia events were most strongly positively associated with hospital-treated pneumonia. The model predicting hospital-treated pneumonia yielded a c-statistic of 0.80. Utilizing the predictive model, the top 17% highest-risk within the study validation population were targeted to detect 54% of those members who were subsequently treated for hospitalized pneumonia in the follow up period. The high-risk population identified through this model included 46% of the follow-up year's IPD cases, and 27% of community-treated pneumonia cases. These outcomes were compared with international guidelines for risk for pneumococcal diseases that accurately identified only 35% of hospitalized pneumonia, 41% of IPD cases and 21% of community-treated pneumonia. We demonstrate that a customized model for vaccine targeting performs better than international guidelines, and therefore, risk modeling may allow for more precise vaccine targeting and resource allocation than current national and international

GM biofortified crops: potential effects on targeting the micronutrient intake gap in human populations.

PubMed

De Steur, Hans; Mehta, Saurabh; Gellynck, Xavier; Finkelstein, Julia L

2017-04-01

Genetic engineering has been successfully applied to increase micronutrient content in staple crops. Nutrition evidence is key to ensure scale-up and successful implementation. Unlike conventional plant breeding efforts, research on the efficacy or effectiveness of GM biofortified crops on nutritional status in human populations is lacking. This review reports on the potential role of GM biofortified crops in closing the micronutrient gap - increasing the dietary intake of micronutrients in human populations. To date, one clinical trial in the United States reported a high bio-conversion rate of β-carotene in Golden Rice, and potential effects of GM biofortified crop consumption on dietary intake and nutritional outcomes are promising. However, further research needs to confirm the ex ante assessments in target regions. Copyright © 2017. Published by Elsevier Ltd.

Pediatric, Adolescent, and Young Adult Thyroid Carcinoma Harbors Frequent and Diverse Targetable Genomic Alterations, Including Kinase Fusions

PubMed Central

Schrock, Alexa B.; Anderson, Peter M.; Morris, John C.; Heilmann, Andreas M.; Holmes, Oliver; Wang, Kai; Johnson, Adrienne; Waguespack, Steven G.; Ou, Sai‐Hong Ignatius; Khan, Saad; Fung, Kar‐Ming; Stephens, Philip J.; Erlich, Rachel L.; Miller, Vincent A.; Ross, Jeffrey S.; Ali, Siraj M.

2017-01-01

Background. Thyroid carcinoma, which is rare in pediatric patients (age 0–18 years) but more common in adolescent and young adult (AYA) patients (age 15–39 years), carries the potential for morbidity and mortality. Methods. Hybrid‐capture‐based comprehensive genomic profiling (CGP) was performed prospectively on 512 consecutively submitted thyroid carcinomas, including 58 from pediatric and AYA (PAYA) patients, to identify genomic alterations (GAs), including base substitutions, insertions/deletions, copy number alterations, and rearrangements. This PAYA data series includes 41 patients with papillary thyroid carcinoma (PTC), 3 with anaplastic thyroid carcinoma (ATC), and 14 with medullary thyroid carcinoma (MTC). Results. GAs were detected in 93% (54/58) of PAYA cases, with a mean of 1.4 GAs per case. In addition to BRAF V600E mutations, detected in 46% (19/41) of PAYA PTC cases and in 1 of 3 AYA ATC cases, oncogenic fusions involving RET, NTRK1, NTRK3, and ALK were detected in 37% (15/41) of PAYA PTC and 33% (1/3) of AYA ATC cases. Ninety‐three percent (13/14) of MTC patients harbored RET alterations, including 3 novel insertions/deletions in exons 6 and 11. Two of these MTC patients with novel alterations in RET experienced clinical benefit from vandetanib treatment. Conclusion. CGP identified diverse clinically relevant GAs in PAYA patients with thyroid carcinoma, including 83% (34/41) of PTC cases harboring activating kinase mutations or activating kinase rearrangements. These genomic observations and index cases exhibiting clinical benefit from targeted therapy suggest that young patients with advanced thyroid carcinoma can benefit from CGP and rationally matched targeted therapy. Implications for Practice. The detection of diverse clinically relevant genomic alterations in the majority of pediatric, adolescent, and young adult patients with thyroid carcinoma in this study suggests that comprehensive genomic profiling may be beneficial for young

Empirical and targeted therapy of candidemia with fluconazole versus echinocandins: a propensity score-derived analysis of a population-based, multicentre prospective cohort.

PubMed

López-Cortés, L E; Almirante, B; Cuenca-Estrella, M; Garnacho-Montero, J; Padilla, B; Puig-Asensio, M; Ruiz-Camps, I; Rodríguez-Baño, J

2016-08-01

We compared the clinical efficacy of fluconazole and echinocandins in the treatment of candidemia in real practice. The CANDIPOP study is a prospective, population-based cohort study on candidemia carried out between May 2010 and April 2011 in 29 Spanish hospitals. Using strict inclusion criteria, we separately compared the impact of empirical and targeted therapy with fluconazole or echinocandins on 30-day mortality. Cox regression, including a propensity score (PS) for receiving echinocandins, stratified analysis on the PS quartiles and PS-based matched analyses, were performed. The empirical and targeted therapy cohorts comprised 316 and 421 cases, respectively; 30-day mortality was 18.7% with fluconazole and 33.9% with echinocandins (p 0.02) in the empirical therapy group and 19.8% with fluconazole and 27.7% with echinocandins (p 0.06) in the targeted therapy group. Multivariate Cox regression analysis including PS showed that empirical therapy with fluconazole was associated with better prognosis (adjusted hazard ratio 0.38; 95% confidence interval 0.17-0.81; p 0.01); no differences were found within each PS quartile or in cases matched according to PS. Targeted therapy with fluconazole did not show a significant association with mortality in the Cox regression analysis (adjusted hazard ratio 0.77; 95% confidence interval 0.41-1.46; p 0.63), in the PS quartiles or in PS-matched cases. The results were similar among patients with severe sepsis and septic shock. Empirical or targeted treatment with fluconazole was not associated with increased 30-day mortality compared to echinocandins among adults with candidemia. Copyright © 2016 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Considering the needs of English language learner populations: an examination of the population validity of reading intervention research.

PubMed

Moore, Brooke A; Klingner, Janette K

2014-01-01

This article synthesizes reading intervention research studies intended for use with struggling or at-risk students to determine which studies adequately address population validity, particularly in regard to the diverse reading needs of English language learners. An extensive search of the professional literature between 2001 and 2010 yielded a total of 67 reading intervention studies targeting at-risk elementary students. Findings revealed that many current research studies fail to adequately describe the sample, including the accessible and target populations, and to disaggregate their findings based on demographic characteristics. When population validity issues are not addressed, researchers cannot generalize findings to other populations of students, and it becomes unclear what intervention strategies work, especially with English language learner student populations. However, 25 studies did specifically recognize and address the needs of English language learners, indicating more researchers are taking into consideration the diverse needs of other struggling student populations. © Hammill Institute on Disabilities 2012.

Improving the quality of primary care by allocating performance-based targets, in a diverse insured population.

PubMed

Peled, Ronit; Porath, Avi; Wilf-Miron, Rachel

2016-11-21

Primary Care Health organizations, operating under universal coverage and a regulated package of benefits, compete mainly over quality of care. Monitoring, primary care clinical performance, has been repeatedly proven effective in improving the quality of care. In 2004, Maccabi Healthcare Services (MHS), the second largest Israeli HMO, launched its Performance Measurement System (PMS) based on clinical quality indicators. A unique module was built in the PMS to adjust for case mix while tailoring targets to the local units. This article presents the concept and formulas developed to adjust targets to the units' current performance, and analyze change in clinical indicators over a six year period, between sub-population groups. Six process and intermediate outcome indicators, representing screening for breast and colorectal cancer and care for patients with diabetes and cardiovascular disease, were selected and analyzed for change over time (2003-2009) in overall performance, as well as the difference between the lowest and the highest socio-economic ranks (SERs) and Arab and non-Arab members. MHS demonstrated a significant improvement in the selected indicators over the years. Performance of members from low SERs and Arabs improved to a greater extent, as compared to members from high ranks and non-Arabs, respectively. The performance measurement system, with its module for tailoring of units' targets, served as a managerial vehicle for bridging existing gaps by allocating more resources to lower performing units. This concept was proven effective in improving performance while reducing disparities between diverse population groups.

Choice of Target Population Weights in Rater Comparability Scoring and Equating. Research Report. ETS RR-13-03

ERIC Educational Resources Information Center

Puhan, Gautam

2013-01-01

The purpose of this study was to demonstrate that the choice of sample weights when defining the target population under poststratification equating can be a critical factor in determining the accuracy of the equating results under a unique equating scenario, known as "rater comparability scoring and equating." The nature of data…

Evaluating targeted interventions via meta-population models with multi-level mixing.

PubMed

Feng, Zhilan; Hill, Andrew N; Curns, Aaron T; Glasser, John W

2017-05-01

Among the several means by which heterogeneity can be modeled, Levins' (1969) meta-population approach preserves the most analytical tractability, a virtue to the extent that generality is desirable. When model populations are stratified, contacts among their respective sub-populations must be described. Using a simple meta-population model, Feng et al. (2015) showed that mixing among sub-populations, as well as heterogeneity in characteristics affecting sub-population reproduction numbers, must be considered when evaluating public health interventions to prevent or control infectious disease outbreaks. They employed the convex combination of preferential within- and proportional among-group contacts first described by Nold (1980) and subsequently generalized by Jacquez et al. (1988). As the utility of meta-population modeling depends on more realistic mixing functions, the authors added preferential contacts between parents and children and among co-workers (Glasser et al., 2012). Here they further generalize this function by including preferential contacts between grandparents and grandchildren, but omit workplace contacts. They also describe a general multi-level mixing scheme, provide three two-level examples, and apply two of them. In their first application, the authors describe age- and gender-specific patterns in face-to-face conversations (Mossong et al., 2008), proxies for contacts by which respiratory pathogens might be transmitted, that are consistent with everyday experience. This suggests that meta-population models with inter-generational mixing could be employed to evaluate prolonged school-closures, a proposed pandemic mitigation measure that could expose grandparents, and other elderly surrogate caregivers for working parents, to infectious children. In their second application, the authors use a meta-population SEIR model stratified by 7 age groups and 50 states plus the District of Columbia, to compare actual with optimal vaccination during the

New developments in pediatric venous thromboembolism and anticoagulation, including the target-specific oral anticoagulants.

PubMed

Lyle, Courtney A; Sidonio, Robert F; Goldenberg, Neil A

2015-02-01

Pediatric venous thromboembolism (VTE) can affect children of all ages, requiring considerable pharmacologic intervention and is often associated with significant morbidity. Current research efforts are directed toward the development of risk-stratified VTE prevention strategies employing pharmacologic thromboprophylaxis, the optimization of conventional anticoagulation, and the investigation of the safety and efficacy of target-specific oral anticoagulants (TSOACs) in children. Recent research has considerably improved the understanding of risk factors of hospital-acquired VTE and how these factors may be employed in risk-stratified paradigms for VTE prevention in children. Additional insight has been gained in the optimization of conventional anticoagulants in special populations such as neonates and children with inflammatory conditions, and in improving the overall safety and compliance with periprocedural anticoagulation and the use of home International Normalized Ratio monitoring. Furthermore, the use of TSOACs has been described in children and is the focus of numerous ongoing clinical trials that are evaluating the safety and efficacy of these agents in children with VTE. Identification of hospital-acquired VTE risk factors may inform pediatric VTE prevention strategies. Although initial use of TSOACs may be promising, investigation of safety and efficacy in children is still underway.

Targeted mutation screening panels expose systematic population bias in detection of cystic fibrosis risk.

PubMed

Lim, Regine M; Silver, Ari J; Silver, Maxwell J; Borroto, Carlos; Spurrier, Brett; Petrossian, Tanya C; Larson, Jessica L; Silver, Lee M

2016-02-01

Carrier screening for mutations contributing to cystic fibrosis (CF) is typically accomplished with panels composed of variants that are clinically validated primarily in patients of European descent. This approach has created a static genetic and phenotypic profile for CF. An opportunity now exists to reevaluate the disease profile of CFTR at a global population level. CFTR allele and genotype frequencies were obtained from a nonpatient cohort with more than 60,000 unrelated personal genomes collected by the Exome Aggregation Consortium. Likely disease-contributing mutations were identified with the use of public database annotations and computational tools. We identified 131 previously described and likely pathogenic variants and another 210 untested variants with a high probability of causing protein damage. None of the current genetic screening panels or existing CFTR mutation databases covered a majority of deleterious variants in any geographical population outside of Europe. Both clinical annotation and mutation coverage by commercially available targeted screening panels for CF are strongly biased toward detection of reproductive risk in persons of European descent. South and East Asian populations are severely underrepresented, in part because of a definition of disease that preferences the phenotype associated with European-typical CFTR alleles.

Identification of Homeotic Target Genes in Drosophila Melanogaster Including Nervy, a Proto-Oncogene Homologue

PubMed Central

Feinstein, P. G.; Kornfeld, K.; Hogness, D. S.; Mann, R. S.

1995-01-01

In Drosophila, the specific morphological characteristics of each segment are determined by the homeotic genes that regulate the expression of downstream target genes. We used a subtractive hybridization procedure to isolate activated target genes of the homeotic gene Ultrabithorax (Ubx). In addition, we constructed a set of mutant genotypes that measures the regulatory contribution of individual homeotic genes to a complex target gene expression pattern. Using these mutants, we demonstrate that homeotic genes can regulate target gene expression at the start of gastrulation, suggesting a previously unknown role for the homeotic genes at this early stage. We also show that, in abdominal segments, the levels of expression for two target genes increase in response to high levels of Ubx, demonstrating that the normal down-regulation of Ubx in these segments is functional. Finally, the DNA sequence of cDNAs for one of these genes predicts a protein that is similar to a human proto-oncogene involved in acute myeloid leukemias. These results illustrate potentially general rules about the homeotic control of target gene expression and suggest that subtractive hybridization can be used to isolate interesting homeotic target genes. PMID:7498738

Do selective immunisation against tuberculosis and hepatitis B reach the targeted populations? A nationwide register-based study evaluating the recommendations in the Norwegian Childhood Immunisation Programme.

PubMed

Feiring, Berit; Laake, Ida; Molden, Tor; Håberg, Siri E; Nøkleby, Hanne; Seterelv, Siri Schøyen; Magnus, Per; Trogstad, Lill

2016-04-12

Selective immunisation is an alternative to universal vaccination if children at increased risk of disease can be identified. Within the Norwegian Childhood Immunisation Programme, BCG vaccine against tuberculosis and vaccine against hepatitis B virus (HBV) are offered only to children with parents from countries with high burden of the respective disease. We wanted to study whether this selective immunisation policy reaches the targeted groups. The study population was identified through the Norwegian Central Population Registry and consisted of all children born in Norway 2007-2010 and residing in Norway until their second birthday, in total 240,484 children. Information on vaccinations from the Norwegian Immunisation Registry, and on parental country of birth from Statistics Norway, was linked to the population registry by personal identifiers. The coverage of BCG and HBV vaccine was compared with the coverage of vaccines in the universal programme. Among the study population, 16.1% and 15.9% belonged to the target groups for BCG and HBV vaccine, respectively. Among children in the BCG target group the BCG vaccine coverage was lower than the coverage of pertussis and measles vaccine (83.6% vs. 98.6% and 92.3%, respectively). Likewise, the HBV vaccine coverage was lower than the coverage of pertussis and measles vaccine in the HBV target group (90.0% vs. 98.6% and 92.3%, respectively). The coverage of the targeted vaccines was highest among children with parents from South Asia and Sub-Saharan Africa. The coverage of vaccines in the universal programme was similar in targeted and non-targeted groups. Children targeted by selective vaccination had lower coverage of the target vaccines than of vaccines in the universal programme, indicating that selective vaccination is challenging. Improved routines for identifying eligible children and delivering the target vaccines are needed. Universal vaccination of all children with these vaccines could be considered

Survival-related Selection Bias in Studies of Racial Health Disparities: The Importance of the Target Population and Study Design.

PubMed

Howe, Chanelle J; Robinson, Whitney R

2018-07-01

The impact of survival-related selection bias has not always been discussed in relevant studies of racial health disparities. Moreover, the analytic approaches most frequently employed in the epidemiologic literature to minimize selection bias are difficult to implement appropriately in racial disparities research. This difficulty stems from the fact that frequently employed analytic techniques require that common causes of survival and the outcome are accurately measured. Unfortunately, such common causes are often unmeasured or poorly measured in racial health disparities studies. In the absence of accurate measures of the aforementioned common causes, redefining the target population or changing the study design represents a useful approach for reducing the extent of survival-related selection bias. To help researchers recognize and minimize survival-related selection bias in racial health disparities studies, we illustrate the aforementioned selection bias and how redefining the target population or changing the study design can be useful.

Modeling to Support the Development of Habitat Targets for Piping Plovers on the Missouri River

DOE Office of Scientific and Technical Information (OSTI.GOV)

Buenau, Kate E.

2015-05-05

Report on modeling and analyses done in support of developing quantative sandbar habitat targets for piping plovers, including assessment of reference, historical, dams present but not operated, and habitat construction calibrated to meet population viability targets.

Difference in target definition using three different methods to include respiratory motion in radiotherapy of lung cancer.

PubMed

Sloth Møller, Ditte; Knap, Marianne Marquard; Nyeng, Tine Bisballe; Khalil, Azza Ahmed; Holt, Marianne Ingerslev; Kandi, Maria; Hoffmann, Lone

2017-11-01

Minimizing the planning target volume (PTV) while ensuring sufficient target coverage during the entire respiratory cycle is essential for free-breathing radiotherapy of lung cancer. Different methods are used to incorporate the respiratory motion into the PTV. Fifteen patients were analyzed. Respiration can be included in the target delineation process creating a respiratory GTV, denoted iGTV. Alternatively, the respiratory amplitude (A) can be measured based on the 4D-CT and A can be incorporated in the margin expansion. The GTV expanded by A yielded GTV + resp, which was compared to iGTV in terms of overlap. Three methods for PTV generation were compared. PTV del (delineated iGTV expanded to CTV plus PTV margin), PTV σ (GTV expanded to CTV and A was included as a random uncertainty in the CTV to PTV margin) and PTV ∑ (GTV expanded to CTV, succeeded by CTV linear expansion by A to CTV + resp, which was finally expanded to PTV ∑ ). Deformation of tumor and lymph nodes during respiration resulted in volume changes between the respiratory phases. The overlap between iGTV and GTV + resp showed that on average 7% of iGTV was outside the GTV + resp implying that GTV + resp did not capture the tumor during the full deformable respiration cycle. A comparison of the PTV volumes showed that PTV σ was smallest and PTV Σ largest for all patients. PTV σ was in mean 14% (31 cm 3 ) smaller than PTV del , while PTV del was 7% (20 cm 3 ) smaller than PTV Σ . PTV σ yields the smallest volumes but does not ensure coverage of tumor during the full respiratory motion due to tumor deformation. Incorporating the respiratory motion in the delineation (PTV del ) takes into account the entire respiratory cycle including deformation, but at the cost, however, of larger treatment volumes. PTV Σ should not be used, since it incorporates the disadvantages of both PTV del and PTV σ .

Impacts of transgenic poplar-cotton agro-ecosystems upon target pests and non-target insects under field conditions.

PubMed

Zhang, D J; Liu, J X; Lu, Z Y; Li, C L; Comada, E; Yang, M S

2015-07-27

Poplar-cotton agro-ecosystems are the main agricultural planting modes of cotton fields in China. With increasing acres devoted to transgenic insect-resistant poplar and transgenic insect-resistant cotton, studies examining the effects of transgenic plants on target and non-target insects become increasingly important. We systematically surveyed populations of both target pests and non-target insects for 4 different combinations of poplar-cotton eco-systems over 3 years. Transgenic Bt cotton strongly resisted the target insects Fall webworm moth [Hyphantria cunea (Drury)], Sylepta derogata Fabrieius, and American bollworm (Heliothis armigera), but no clear impact on non-target insect cotton aphids (Aphis gossypii). Importantly, intercrops containing transgenic Pb29 poplar significantly increased the inhibitory effects of Bt cotton on Fall webworm moth in ecosystem IV. Highly resistant Pb29 poplar reduced populations of the target pests Grnsonoma minutara Hubner and non-target insect poplar leaf aphid (Chaitophorus po-pulialbae), while Fall webworm moth populations were unaffected. We determined the effects of Bt toxin from transgenic poplar and cotton on target and non-target pests in different ecosystems of cotton-poplar intercrops and identified the synergistic effects of such combinations toward both target and non-target insects.

MaCH-Admix: Genotype Imputation for Admixed Populations

PubMed Central

Liu, Eric Yi; Li, Mingyao; Wang, Wei; Li, Yun

2012-01-01

Imputation in admixed populations is an important problem but challenging due to the complex linkage disequilibrium (LD) pattern. The emergence of large reference panels such as that from the 1,000 Genomes Project enables more accurate imputation in general, and in particular for admixed populations and for uncommon variants. To efficiently benefit from these large reference panels, one key issue to consider in modern genotype imputation framework is the selection of effective reference panels. In this work, we consider a number of methods for effective reference panel construction inside a hidden Markov model and specific to each target individual. These methods fall into two categories: identity-by-state (IBS) based and ancestry-weighted approach. We evaluated the performance on individuals from recently admixed populations. Our target samples include 8,421 African Americans and 3,587 Hispanic Americans from the Women’s Health Initiative, which allow assessment of imputation quality for uncommon variants. Our experiments include both large and small reference panels; large, medium, and small target samples; and in genome regions of varying levels of LD. We also include BEAGLE and IMPUTE2 for comparison. Experiment results with large reference panel suggest that our novel piecewise IBS method yields consistently higher imputation quality than other methods/software. The advantage is particularly noteworthy among uncommon variants where we observe up to 5.1% information gain with the difference being highly significant (Wilcoxon signed rank test P-value < 0.0001). Our work is the first that considers various sensible approaches for imputation in admixed populations and presents a comprehensive comparison. PMID:23074066

Non-target screening to trace ozonation transformation products in a wastewater treatment train including different post-treatments.

PubMed

Schollée, Jennifer E; Bourgin, Marc; von Gunten, Urs; McArdell, Christa S; Hollender, Juliane

2018-05-25

Ozonation and subsequent post-treatments are increasingly implemented in wastewater treatment plants (WWTPs) for enhanced micropollutant abatement. While this technology is effective, micropollutant oxidation leads to the formation of ozonation transformation products (OTPs). Target and suspect screening provide information about known parent compounds and known OTPs, but for a more comprehensive picture, non-target screening is needed. Here, sampling was conducted at a full-scale WWTP to investigate OTP formation at four ozone doses (2, 3, 4, and 5 mg/L, ranging from 0.3 to 1.0 gO 3 /gDOC) and subsequent changes during five post-treatment steps (i.e., sand filter, fixed bed bioreactor, moving bed bioreactor, and two granular activated carbon (GAC) filters, relatively fresh and pre-loaded). Samples were measured with online solid-phase extraction coupled to liquid chromatography high-resolution tandem mass spectrometry (LC-HRMS/MS) using electrospray ionization (ESI) in positive and negative modes. Existing non-target screening workflows were adapted to (1) examine the formation of potential OTPs at four ozone doses and (2) compare the removal of OTPs among five post-treatments. In (1), data processing included principal component analysis (PCA) and chemical knowledge on possible oxidation reactions to prioritize non-target features likely to be OTPs. Between 394 and 1328 unique potential OTPs were detected in positive ESI for the four ozone doses tested; between 12 and 324 unique potential OTPs were detected in negative ESI. At a specific ozone dose of 0.5 gO 3 /gDOC, 27 parent compounds were identified and were related to 69 non-target features selected as potential OTPs. Two OTPs were confirmed with reference standards (venlafaxine N-oxide and chlorothiazide); 34 other potential OTPs were in agreement with literature data and/or reaction mechanisms. In (2), hierarchical cluster analysis (HCA) was applied on profiles detected in positive ESI mode across the

Target-site resistance to pyrethroid insecticides in German populations of the cabbage stem flea beetle, Psylliodes chrysocephala L. (Coleoptera: Chrysomelidae).

PubMed

Zimmer, Christoph T; Müller, Andreas; Heimbach, Udo; Nauen, Ralf

2014-01-01

Cabbage stem flea beetle, Psylliodes chrysocephala L. (Coleoptera: Chrysomelidae) is a major pest of winter oilseed rape in several European countries particularly attacking young emerging plants in autumn. Over the last several decades, pyrethroid insecticides have been foliarly applied to control flea beetle outbreaks. Recent control failures in northern Germany suggested pyrethroid resistance development in cabbage stem flea beetles, which were confirmed by resistance monitoring bioassays using lambda-cyhalothrin in an adult vial test. The purpose of this study was to investigate the presence of polymorphisms in the para-type voltage-gated sodium channel gene of P. chrysocephala known to be involved in knock-down resistance (kdr). By using a degenerate primer approach we PCR amplified part of the para-type sodium channel gene and identified in resistant flea beetles a single nucleotide polymorphism resulting in an L1014F (kdr) mutation within domain IIS6 of the channel protein, known as one of the chief pyrethroid target-site resistance mechanisms in several other pest insects. Twenty populations including four archived museum samples collected between 1945 and 1958 were analyzed using a newly developed pyrosequencing diagnostic assay. The assay revealed a kdr allele frequency of 90-100% in those flea beetle populations expressing high-level cross-resistance in discriminating dose bioassays against different pyrethroids such as lambda-cyhalothrin, tau-fluvalinate, etofenprox and bifenthrin. The presence of target-site resistance to pyrethroids in cabbage stem flea beetle is extremely worrying considering the lack of effective alternative modes of action to control this pest in Germany and other European countries, and is likely to result in major control problems once it expands to other geographies. The striking fact that cabbage stem flea beetle is next to pollen beetle, Meligethes aeneus the second coleopteran pest in European winter oilseed rape resisting

Attentional bias to threat in the general population is contingent on target competition, not on attentional control settings.

PubMed

Wirth, Benedikt Emanuel; Wentura, Dirk

2018-04-01

Dot-probe studies usually find an attentional bias towards threatening stimuli only in anxious participants. Here, we investigated under what conditions such a bias occurs in unselected samples. According to contingent-capture theory, an irrelevant cue only captures attention if it matches an attentional control setting. Therefore, we first tested the hypothesis that an attentional control setting tuned to threat must be activated in (non-anxious) individuals. In Experiment 1, we used a dot-probe task with a manipulation of attentional control settings ('threat' - set vs. control set). Surprisingly, we found an (anxiety-independent) attentional bias to angry faces that was not moderated by attentional control settings. Since we presented two stimuli (i.e., a target and a distractor) on the target screen in Experiment 1 (a necessity to realise the test of contingent capture), but most dot-probe studies only employ a single target, we conducted Experiment 2 to test the hypothesis that attentional bias in the general population is contingent on target competition. Participants performed a dot-probe task, involving presentation of a stand-alone target or a target competing with a distractor. We found an (anxiety-independent) attentional bias towards angry faces in the latter but not the former condition. This suggests that attentional bias towards angry faces in unselected samples is not contingent on attentional control settings but on target competition.

A system dynamics optimization framework to achieve population desired of average weight target

NASA Astrophysics Data System (ADS)

Abidin, Norhaslinda Zainal; Zulkepli, Jafri Haji; Zaibidi, Nerda Zura

2017-11-01

Obesity is becoming a serious problem in Malaysia as it has been rated as the highest among Asian countries. The aim of the paper is to propose a system dynamics (SD) optimization framework to achieve population desired weight target based on the changes in physical activity behavior and its association to weight and obesity. The system dynamics approach of stocks and flows diagram was used to quantitatively model the impact of both behavior on the population's weight and obesity trends. This work seems to bring this idea together and highlighting the interdependence of the various aspects of eating and physical activity behavior on the complex of human weight regulation system. The model was used as an experimentation vehicle to investigate the impacts of changes in physical activity on weight and prevalence of obesity implications. This framework paper provides evidence on the usefulness of SD optimization as a strategic decision making approach to assist in decision making related to obesity prevention. SD applied in this research is relatively new in Malaysia and has a high potential to apply to any feedback models that address the behavior cause to obesity.

Targeted gene flow and rapid adaptation in an endangered marsupial.

PubMed

Kelly, Ella; Phillips, Ben L

2018-06-13

Targeted gene flow is an emerging conservation strategy. It involves translocating individuals with favorable genes to areas where they will have a conservation benefit. The applications for targeted gene flow are wide-ranging, but include pre-adapting natives to the arrival of invasive species. The endangered carnivorous marsupial, the northern quoll, has declined rapidly since the introduction of the cane toad, which fatally poisons quolls that attack them. There are, however, a few remaining toad-invaded quoll populations in which the quolls survive because they know not to eat cane toads. It is this "toad-smart" behavior that we hope to promote through targeted gene flow. For targeted gene flow to be feasible, however, toad-smarts must have a genetic basis. To assess this, we used a common garden experiment and found offspring from toad-exposed populations were substantially less likely to eat toads than those with toad-naïve parents. Hybrid offspring showed similar responses to quolls with two toad-exposed parents, indicating the trait may be dominant. Together, these results suggest a heritable trait and rapid adaptive response in small number of toad-impacted populations. Although questions remain about outbreeding depression, our results are encouraging for targeted gene flow: suggesting it should be possible to introduce toad-smart behavior into soon to be impacted quoll populations. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Culture-Independent Identification of Periodontitis-Associated Porphyromonas and Tannerella Populations by Targeted Molecular Analysis

PubMed Central

de Lillo, A.; Booth, V.; Kyriacou, L.; Weightman, A. J.; Wade, W. G.

2004-01-01

Periodontitis is the commonest bacterial disease of humans and is the major cause of adult tooth loss. About half of the oral microflora is unculturable; and 16S rRNA PCR, cloning, and sequencing techniques have demonstrated the high level of species richness of the oral microflora. In the present study, a PCR primer set specific for the genera Porphyromonas and Tannerella was designed and used to analyze the bacterial populations in subgingival plaque samples from inflamed shallow and deep sites in subjects with periodontitis and shallow sites in age- and sex-matched controls. A total of 308 clones were sequenced and found to belong to one of six Porphyromonas or Tannerella species or phylotypes, one of which, Porphyromonas P3, was novel. Tannerella forsythensis was found in significantly higher proportions in patients than in controls. Porphyromonas catoniae and Tannerella phylotype BU063 appeared to be associated with shallow sites. Targeted culture-independent molecular ecology studies have a valuable role to play in the identification of bacterial targets for further investigations of the pathogenesis of bacterial infections. PMID:15583276

SeedVicious: Analysis of microRNA target and near-target sites.

PubMed

Marco, Antonio

2018-01-01

Here I describe seedVicious, a versatile microRNA target site prediction software that can be easily fitted into annotation pipelines and run over custom datasets. SeedVicious finds microRNA canonical sites plus other, less efficient, target sites. Among other novel features, seedVicious can compute evolutionary gains/losses of target sites using maximum parsimony, and also detect near-target sites, which have one nucleotide different from a canonical site. Near-target sites are important to study population variation in microRNA regulation. Some analyses suggest that near-target sites may also be functional sites, although there is no conclusive evidence for that, and they may actually be target alleles segregating in a population. SeedVicious does not aim to outperform but to complement existing microRNA prediction tools. For instance, the precision of TargetScan is almost doubled (from 11% to ~20%) when we filter predictions by the distance between target sites using this program. Interestingly, two adjacent canonical target sites are more likely to be present in bona fide target transcripts than pairs of target sites at slightly longer distances. The software is written in Perl and runs on 64-bit Unix computers (Linux and MacOS X). Users with no computing experience can also run the program in a dedicated web-server by uploading custom data, or browse pre-computed predictions. SeedVicious and its associated web-server and database (SeedBank) are distributed under the GPL/GNU license.

Targeting the T-Lak cell originated protein kinase by OTS964 shrinks the size of power-law coded heterogeneous glioma stem cell populations

PubMed Central

Sugimori, Michiya; Hayakawa, Yumiko; Koh, Masaki; Hayashi, Tomohide; Tamura, Ryoi; Kuroda, Satoshi

2018-01-01

Glioblastoma resists chemoradiotherapy, then, recurs to be a fatal space-occupying lesion. The recurrence is caused by re-growing cell populations such as glioma stem cells (GSCs), suggesting that GSC populations should be targeted. This study addressed whether a novel anti-cancer drug, OTS964, an inhibitor for T-LAK cell originated protein kinase (TOPK), is effective in reducing the size of the heterogeneous GSC populations, a power-law coded heterogeneous GSC populations consisting of glioma sphere (GS) clones, by detailing quantitative growth properties. We found that OTS964 killed GS clones while suppressing the growth of surviving GS clones, thus identifying clone-eliminating and growth-disturbing efficacies of OTS964. The efficacies led to a significant size reduction in GS populations in a dose-dependent manner. The surviving GS clones reconstructed GS populations in the following generations; the recovery of GS populations fits a recurrence after the chemotherapy. The recovering GS clones resisted the clone-eliminating effect of OTS964 in sequential exposure during the growth recovery. However, surprisingly, the resistant properties of the recovered-GS clones had been plastically canceled during self-renewal, and then the GS clones had become re-sensitive to OTS964. Thus, OTS964 targets GSCs to eliminate them or suppress their growth, resulting in shrinkage of the power-law coded GSC populations. We propose a therapy focusing on long-term control in recurrence of glioblastoma via reducing the size of the GSC populations by OTS964. PMID:29423027

Targeting the T-Lak cell originated protein kinase by OTS964 shrinks the size of power-law coded heterogeneous glioma stem cell populations.

PubMed

Sugimori, Michiya; Hayakawa, Yumiko; Koh, Masaki; Hayashi, Tomohide; Tamura, Ryoi; Kuroda, Satoshi

2018-01-09

Glioblastoma resists chemoradiotherapy, then, recurs to be a fatal space-occupying lesion. The recurrence is caused by re-growing cell populations such as glioma stem cells (GSCs), suggesting that GSC populations should be targeted. This study addressed whether a novel anti-cancer drug, OTS964, an inhibitor for T-LAK cell originated protein kinase (TOPK), is effective in reducing the size of the heterogeneous GSC populations, a power-law coded heterogeneous GSC populations consisting of glioma sphere (GS) clones, by detailing quantitative growth properties. We found that OTS964 killed GS clones while suppressing the growth of surviving GS clones, thus identifying clone-eliminating and growth-disturbing efficacies of OTS964. The efficacies led to a significant size reduction in GS populations in a dose-dependent manner. The surviving GS clones reconstructed GS populations in the following generations; the recovery of GS populations fits a recurrence after the chemotherapy. The recovering GS clones resisted the clone-eliminating effect of OTS964 in sequential exposure during the growth recovery. However, surprisingly, the resistant properties of the recovered-GS clones had been plastically canceled during self-renewal, and then the GS clones had become re-sensitive to OTS964. Thus, OTS964 targets GSCs to eliminate them or suppress their growth, resulting in shrinkage of the power-law coded GSC populations. We propose a therapy focusing on long-term control in recurrence of glioblastoma via reducing the size of the GSC populations by OTS964.

Dispersion of Projectile and Target Debris Upon Penetration of Thin Targets

NASA Astrophysics Data System (ADS)

Gwynn, D.; Bernhard, R. P.; See, T. H.; Horz, F.

1996-03-01

We continue to conduct penetration experiments of thin foils to support the development of cosmic-dust flight instruments that utilize thin films for the measurement of particle trajectories, or for the potential soft capture of hypervelocity impactors for subsequent compositional analysis upon retrieval to Earth. Each experiment is equipped with a witness plate, mounted to the rear of the target and fabricated from soft Aluminum-1100, ~30 x 30 cm in size and ranging from 2 to 5 mm thick; these witness plates essentially simulate the rear wall of a capture cell onto which the projectile material will plate out, including material that is being dislodged from the penetrated foil itself. Using compositionally contrasting projectile and foil materials in the laboratory, such as soda-lime glass impactors and aluminum targets, one produces two distinct populations of craters on the witness plates.

An Evaluation of Six Brief Interventions that Target Drug-Related Problems in Correctional Populations

PubMed Central

JOE, GEORGE W.; KNIGHT, KEVIN; SIMPSON, D. DWAYNE; FLYNN, PATRICK M.; MOREY, JANIS T.; BARTHOLOMEW, NORMA G.; TINDALL, MICHELE STATON; BURDON, WILLIAM M.; HALL, ELIZABETH A.; MARTIN, STEVE S.; O’CONNELL, DANIEL J.

2012-01-01

Finding brief effective treatments for criminal justice populations is a major public need. The CJ-DATS Targeted Intervention for Corrections (TIC), which consists of six brief interventions (Communication, Anger, Motivation, Criminal Thinking, Social Networks, and HIV/Sexual Health), were tested in separate federally-funded randomized control studies. In total, 1,573 criminal justice-involved individuals from 20 correction facilities participated (78% males; 54% white). Multi-level repeated measures analyses found significant gains in knowledge, attitudes, and psychosocial functioning (criteria basic to Knowledge, Attitude, and Practices (KAP) and TCU Treatment Process Models). While improvements were less consistent in criminal thinking, overall evidence supported efficacy for the TIC interventions. PMID:22547911

An Evaluation of a Flight Deck Interval Management Algorithm Including Delayed Target Trajectories

NASA Technical Reports Server (NTRS)

Swieringa, Kurt A.; Underwood, Matthew C.; Barmore, Bryan; Leonard, Robert D.

2014-01-01

NASA's first Air Traffic Management (ATM) Technology Demonstration (ATD-1) was created to facilitate the transition of mature air traffic management technologies from the laboratory to operational use. The technologies selected for demonstration are the Traffic Management Advisor with Terminal Metering (TMA-TM), which provides precise timebased scheduling in the terminal airspace; Controller Managed Spacing (CMS), which provides controllers with decision support tools enabling precise schedule conformance; and Interval Management (IM), which consists of flight deck automation that enables aircraft to achieve or maintain precise in-trail spacing. During high demand operations, TMA-TM may produce a schedule and corresponding aircraft trajectories that include delay to ensure that a particular aircraft will be properly spaced from other aircraft at each schedule waypoint. These delayed trajectories are not communicated to the automation onboard the aircraft, forcing the IM aircraft to use the published speeds to estimate the target aircraft's estimated time of arrival. As a result, the aircraft performing IM operations may follow an aircraft whose TMA-TM generated trajectories have substantial speed deviations from the speeds expected by the spacing algorithm. Previous spacing algorithms were not designed to handle this magnitude of uncertainty. A simulation was conducted to examine a modified spacing algorithm with the ability to follow aircraft flying delayed trajectories. The simulation investigated the use of the new spacing algorithm with various delayed speed profiles and wind conditions, as well as several other variables designed to simulate real-life variability. The results and conclusions of this study indicate that the new spacing algorithm generally exhibits good performance; however, some types of target aircraft speed profiles can cause the spacing algorithm to command less than optimal speed control behavior.

Scaling-up HIV responses with key populations in West Africa.

PubMed

Wheeler, Tisha; Wolf, R Cameron; Kapesa, Laurent; Cheng Surdo, Alison; Dallabetta, Gina

2015-03-01

Despite decades of HIV responses in pockets of West and Central Africa (WCA), the HIV response with key populations remains an understudied area. Recently, there has been a proliferation of studies highlighting epidemiologic and behavioral data that challenge attitudes of complacency among donors and country governments uncomfortable in addressing key populations. The articles in this series highlight new studies that provide a better understanding of the epidemiologic and structural burden facing key populations in the WCA region and how to improve responses through more effective targeting. Key populations face pervasive structural barriers including institutional and sexual violence and an intersection of stigma, criminalization, and marginalization as sexual minorities. Despite decades of smaller interventions that have shown the importance of integrated services for key populations, there remains incongruent provision of outreach or testing or family planning pointing to sustained risk. There remains an incongruent resource provision for key populations where they shoulder the burden of HIV and their access to services alone could turn around HIV epidemics within the region. These proximal and distal determinants must be addressed in regional efforts, led by the community, and resourced for scale, targeting those most at risk for the acquisition and transmission of HIV. This special issue builds the knowledge base for the region focusing on interventions that remove barriers to service access including treatment uptake for those living with HIV. Better analysis and use of data for strategic planning are shown to lead to more effective targeting of prevention, care, and HIV treatment programs with key populations. These articles further demonstrate the immediate need for comprehensive action to address HIV among key populations throughout the WCA region.

Population pharmacokinetic-pharmacodynamic target attainment analysis of imipenem plasma and urine data in neonates and children.

PubMed

Yoshizawa, Kenichi; Ikawa, Kazuro; Ikeda, Kayo; Ohge, Hiroki; Morikawa, Norifumi

2013-11-01

Population pharmacokinetic (PK)-pharmacodynamic target attainment analysis of imipenem was performed to elucidate the PK properties in neonates and children and to rationalize and optimize dosing regimens. Population PK models were separately developed in neonates and children by simultaneously fitting plasma and urine data from 60 neonates and 39 children. The newly developed models were then used to estimate the probability of attaining the pharmacodynamic target (40% of the time above the minimum inhibitory concentration) against clinical isolates of common bacteria in pediatric patients. The data were best described by a 1-compartment model in neonates and a 2-compartment model in children, respectively. Renal clearance in children (0.187 L/h/kg) was double that of neonates (0.0783 L/h/kg), whereas the volume of distribution at steady-state was approximately 1.8-fold larger in neonates (0.466 L/kg) than in children (0.260 L/kg). Age was not a statistically significant covariate in the PK of both groups. Infusions (0.5 h) of 15 mg/kg every 8 h (45 mg/kg/day) and 25 mg/kg every 12 h (50 mg/kg/day) were shown to be sufficient against common bacterial isolates in both patient populations. However, 1.5-h infusions of 25 mg/kg every 8 h (75 mg/kg/day) in neonates and 25 mg/kg every 6 h (100 mg/kg/day) in children were required to be effective against Pseudomonas aeruginosa (minimum inhibitory concentration for 90% of the isolates=16 μg/mL). These results explain the changes in imipenem PK properties during the human growth process and provide guidance for tailoring dosing regimens in each pediatric age group.

Population-level impact of an accelerated HIV response plan to reach the UNAIDS 90-90-90 target in Côte d’Ivoire: Insights from mathematical modeling

PubMed Central

Diabaté, Souleymane; Alary, Michel; Diouf, Daouda; Abo, Kouamé; Boily, Marie-Claude

2017-01-01

Background National responses will need to be markedly accelerated to achieve the ambitious target of the Joint United Nations Programme on HIV/AIDS (UNAIDS). This target aims for 90% of HIV-positive individuals to be aware of their status, for 90% of those aware to receive antiretroviral therapy (ART), and for 90% of those on treatment to have a suppressed viral load by 2020, with each individual target reaching 95% by 2030. We aimed to estimate the impact of various treatment-as-prevention scenarios in Côte d’Ivoire, one of the countries with the highest HIV incidence in West Africa, with unmet HIV prevention and treatment needs, and where key populations are important to the broader HIV epidemic. Methods and findings An age-stratified dynamic model was developed and calibrated to epidemiological and programmatic data using a Bayesian framework. The model represents sexual and vertical HIV transmission in the general population, female sex workers (FSW), and men who have sex with men (MSM). We estimated the impact of scaling up interventions to reach the UNAIDS targets, as well as the impact of 8 other scenarios, on HIV transmission in adults and children, compared to our baseline scenario that maintains 2015 rates of testing, ART initiation, ART discontinuation, treatment failure, and levels of condom use. In 2015, we estimated that 52% (95% credible intervals: 46%–58%) of HIV-positive individuals were aware of their status, 72% (57%–82%) of those aware were on ART, and 77% (74%–79%) of those on ART were virologically suppressed. Reaching the UNAIDS targets on time would avert 50% (42%–60%) of new HIV infections over 2015–2030 compared to 30% (25%–36%) if the 90-90-90 target is reached in 2025. Attaining the UNAIDS targets in FSW, their clients, and MSM (but not in the rest of the population) would avert a similar fraction of new infections (30%; 21%–39%). A 25-percentage-point drop in condom use from the 2015 levels among FSW and MSM would

Population-level impact of an accelerated HIV response plan to reach the UNAIDS 90-90-90 target in Côte d'Ivoire: Insights from mathematical modeling.

PubMed

Maheu-Giroux, Mathieu; Vesga, Juan F; Diabaté, Souleymane; Alary, Michel; Baral, Stefan; Diouf, Daouda; Abo, Kouamé; Boily, Marie-Claude

2017-06-01

National responses will need to be markedly accelerated to achieve the ambitious target of the Joint United Nations Programme on HIV/AIDS (UNAIDS). This target aims for 90% of HIV-positive individuals to be aware of their status, for 90% of those aware to receive antiretroviral therapy (ART), and for 90% of those on treatment to have a suppressed viral load by 2020, with each individual target reaching 95% by 2030. We aimed to estimate the impact of various treatment-as-prevention scenarios in Côte d'Ivoire, one of the countries with the highest HIV incidence in West Africa, with unmet HIV prevention and treatment needs, and where key populations are important to the broader HIV epidemic. An age-stratified dynamic model was developed and calibrated to epidemiological and programmatic data using a Bayesian framework. The model represents sexual and vertical HIV transmission in the general population, female sex workers (FSW), and men who have sex with men (MSM). We estimated the impact of scaling up interventions to reach the UNAIDS targets, as well as the impact of 8 other scenarios, on HIV transmission in adults and children, compared to our baseline scenario that maintains 2015 rates of testing, ART initiation, ART discontinuation, treatment failure, and levels of condom use. In 2015, we estimated that 52% (95% credible intervals: 46%-58%) of HIV-positive individuals were aware of their status, 72% (57%-82%) of those aware were on ART, and 77% (74%-79%) of those on ART were virologically suppressed. Reaching the UNAIDS targets on time would avert 50% (42%-60%) of new HIV infections over 2015-2030 compared to 30% (25%-36%) if the 90-90-90 target is reached in 2025. Attaining the UNAIDS targets in FSW, their clients, and MSM (but not in the rest of the population) would avert a similar fraction of new infections (30%; 21%-39%). A 25-percentage-point drop in condom use from the 2015 levels among FSW and MSM would reduce the impact of reaching the UNAIDS targets

Multistate matrix population model to assess the contributions and impacts on population abundance of domestic cats in urban areas including owned cats, unowned cats, and cats in shelters

PubMed Central

Coe, Jason B.

2018-01-01

Concerns over cat homelessness, over-taxed animal shelters, public health risks, and environmental impacts has raised attention on urban-cat populations. To truly understand cat population dynamics, the collective population of owned cats, unowned cats, and cats in the shelter system must be considered simultaneously because each subpopulation contributes differently to the overall population of cats in a community (e.g., differences in neuter rates, differences in impacts on wildlife) and cats move among categories through human interventions (e.g., adoption, abandonment). To assess this complex socio-ecological system, we developed a multistate matrix model of cats in urban areas that include owned cats, unowned cats (free-roaming and feral), and cats that move through the shelter system. Our model requires three inputs—location, number of human dwellings, and urban area—to provide testable predictions of cat abundance for any city in North America. Model-predicted population size of unowned cats in seven Canadian cities were not significantly different than published estimates (p = 0.23). Model-predicted proportions of sterile feral cats did not match observed sterile cat proportions for six USA cities (p = 0.001). Using a case study from Guelph, Ontario, Canada, we compared model-predicted to empirical estimates of cat abundance in each subpopulation and used perturbation analysis to calculate relative sensitivity of vital rates to cat abundance to demonstrate how management or mismanagement in one portion of the population could have repercussions across all portions of the network. Our study provides a general framework to consider cat population abundance in urban areas and, with refinement that includes city-specific parameter estimates and modeling, could provide a better understanding of population dynamics of cats in our communities. PMID:29489854

Multistate matrix population model to assess the contributions and impacts on population abundance of domestic cats in urban areas including owned cats, unowned cats, and cats in shelters.

PubMed

Flockhart, D T Tyler; Coe, Jason B

2018-01-01

Concerns over cat homelessness, over-taxed animal shelters, public health risks, and environmental impacts has raised attention on urban-cat populations. To truly understand cat population dynamics, the collective population of owned cats, unowned cats, and cats in the shelter system must be considered simultaneously because each subpopulation contributes differently to the overall population of cats in a community (e.g., differences in neuter rates, differences in impacts on wildlife) and cats move among categories through human interventions (e.g., adoption, abandonment). To assess this complex socio-ecological system, we developed a multistate matrix model of cats in urban areas that include owned cats, unowned cats (free-roaming and feral), and cats that move through the shelter system. Our model requires three inputs-location, number of human dwellings, and urban area-to provide testable predictions of cat abundance for any city in North America. Model-predicted population size of unowned cats in seven Canadian cities were not significantly different than published estimates (p = 0.23). Model-predicted proportions of sterile feral cats did not match observed sterile cat proportions for six USA cities (p = 0.001). Using a case study from Guelph, Ontario, Canada, we compared model-predicted to empirical estimates of cat abundance in each subpopulation and used perturbation analysis to calculate relative sensitivity of vital rates to cat abundance to demonstrate how management or mismanagement in one portion of the population could have repercussions across all portions of the network. Our study provides a general framework to consider cat population abundance in urban areas and, with refinement that includes city-specific parameter estimates and modeling, could provide a better understanding of population dynamics of cats in our communities.

Population genomics of C. melanopterus using target gene capture data: demographic inferences and conservation perspectives

PubMed Central

Maisano Delser, Pierpaolo; Corrigan, Shannon; Hale, Matthew; Li, Chenhong; Veuille, Michel; Planes, Serge; Naylor, Gavin; Mona, Stefano

2016-01-01

Population genetics studies on non-model organisms typically involve sampling few markers from multiple individuals. Next-generation sequencing approaches open up the possibility of sampling many more markers from fewer individuals to address the same questions. Here, we applied a target gene capture method to deep sequence ~1000 independent autosomal regions of a non-model organism, the blacktip reef shark (Carcharhinus melanopterus). We devised a sampling scheme based on the predictions of theoretical studies of metapopulations to show that sampling few individuals, but many loci, can be extremely informative to reconstruct the evolutionary history of species. We collected data from a single deme (SID) from Northern Australia and from a scattered sampling representing various locations throughout the Indian Ocean (SCD). We explored the genealogical signature of population dynamics detected from both sampling schemes using an ABC algorithm. We then contrasted these results with those obtained by fitting the data to a non-equilibrium finite island model. Both approaches supported an Nm value ~40, consistent with philopatry in this species. Finally, we demonstrate through simulation that metapopulations exhibit greater resilience to recent changes in effective size compared to unstructured populations. We propose an empirical approach to detect recent bottlenecks based on our sampling scheme. PMID:27651217

Population genomics of C. melanopterus using target gene capture data: demographic inferences and conservation perspectives.

PubMed

Maisano Delser, Pierpaolo; Corrigan, Shannon; Hale, Matthew; Li, Chenhong; Veuille, Michel; Planes, Serge; Naylor, Gavin; Mona, Stefano

2016-09-21

Population genetics studies on non-model organisms typically involve sampling few markers from multiple individuals. Next-generation sequencing approaches open up the possibility of sampling many more markers from fewer individuals to address the same questions. Here, we applied a target gene capture method to deep sequence ~1000 independent autosomal regions of a non-model organism, the blacktip reef shark (Carcharhinus melanopterus). We devised a sampling scheme based on the predictions of theoretical studies of metapopulations to show that sampling few individuals, but many loci, can be extremely informative to reconstruct the evolutionary history of species. We collected data from a single deme (SID) from Northern Australia and from a scattered sampling representing various locations throughout the Indian Ocean (SCD). We explored the genealogical signature of population dynamics detected from both sampling schemes using an ABC algorithm. We then contrasted these results with those obtained by fitting the data to a non-equilibrium finite island model. Both approaches supported an Nm value ~40, consistent with philopatry in this species. Finally, we demonstrate through simulation that metapopulations exhibit greater resilience to recent changes in effective size compared to unstructured populations. We propose an empirical approach to detect recent bottlenecks based on our sampling scheme.

Use of surveillance data to identify target populations for Staphylococcus aureus vaccines and prevent surgical site infections: A pilot study

PubMed Central

Gustin, Marie-Paule; Giard, Marine; Bénet, Thomas; Vanhems, Philippe

2015-01-01

The development of anti-staphylococcal vaccines is nowadays a priority to prevent surgical site infections (SSI). The objective of the present study was to identify a potential target population by assessing surveillance data on surgery patients for possible anti-staphylococcal vaccine administration. Individuals at high risk of SSI by Staphylococcus aureus (SA) were targeted by the French SSI Surveillance Network in south-eastern France between 2008 and 2011. Among 238,470 patients, those undergoing primary total hip replacement appeared to be an interesting and healthy enough population for anti-staphylococcal vaccine testing. These male patients, subjected to multiple procedures and with American Society of Anesthesiologists score >2, had a probability of SA SSI about 21 times higher than females with no severe systemic disease and no multiple procedures. Our study indicates that surveillance data on SSI might be an interesting epidemiological source for planning vaccine trials to prevent nosocomial infections. PMID:25668663

Population targeting amid complex mental health programming: Are California's Full Service Partnerships reaching underserved children?

PubMed

Cordell, Katharan D; Snowden, Lonnie R

2017-01-01

California's Mental Health Services Act (MHSA) created Full Service Partnership programs (FSPs) targeting socially and economically vulnerable children with mental illness who are underserved by counties' public mental health treatment system. To determine whether FSPs reach a distinctive group of children, this study compares indicators of FSP-targeted underservice for FSP entrants (n = 15,598) versus everyone treated in the counties' public mental health systems (n = 282,178) and for FSP entrants versus entrants in the most intensive Medicaid delivered program in California, Therapeutic Behavioral Services (TBS, n = 11,993). Results identify that, despite first encountering mental health services systems at earlier ages, FSP clients had fewer months of treatment and were less likely to have been treated in the prior 6 months, except for crisis care, as compared to all other children served, after considering clinical severity and indicators of service need. FSP entrants also had more substance abuse and trauma-related problems. Although less seriously ill than TBS served children, FSP served children were significantly underserved. The results indicate that, amid overlapping policies and programs, carving out and reaching a distinctly underserved population can be achieved in practice, and that specialized programs, such as the FSP program, which target underserved children, have the potential to augment a system's ability to reach the underserved. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Low haemoglobin density for detecting iron deficiency across a large population, including pregnancy.

PubMed

Crispin, P; Sinclair, F; Andriolo, K

2016-08-01

Low haemoglobin density (LHD%) from Coulter counters has been suggested as a means to detect iron deficiency. Its performance in a broad population group, including pregnancy, has not been evaluated. A retrospective study of adult and paediatric (under 12 years old) patient samples referred for blood counts and iron studies between October 2013 and March 2015. Receiver operator characteristic (ROC) curves were constructed to evaluate the performance of LHD% adults, children, and in the antenatal subgroup. Using a strict definition for iron deficiency, compared with a selected normal cohort, LHD% had a ROC area under the curve (AUC) of 0.90 (0.89-0.91), but in an unselected cohort, the AUC fell to 0.74 (0.73-0.75) with a sensitivity of 74% and specificity of 60% at a cut-off value of 5.9%. In the paediatric cohort, the AUC was 0.79(0.73-0.85), giving a sensitivity and specificity of 75% and 68%, respectively. LHD% did not effectively identify iron deficiency in pregnancy with an AUC of 0.60 (0.54-0.65) and was no better than MCV at detecting iron deficiency. LHD% detects iron deficiency in adult and paediatric populations, but not in the antenatal setting, and does not appear superior to MCV. © 2016 John Wiley & Sons Ltd.

AN ARCGIS TOOL FOR CREATING POPULATIONS OF WATERSHEDS

EPA Science Inventory

For the Landscape Investigations for Pesticides Study in the Midwest, the goal is to sample a representative subset of watersheds selected statistically from a target population of watersheds within the glaciated corn belt. This area stretches from Ohio to Iowa and includes parts...

Modeling health gains and cost savings for ten dietary salt reduction targets.

PubMed

Wilson, Nick; Nghiem, Nhung; Eyles, Helen; Mhurchu, Cliona Ni; Shields, Emma; Cobiac, Linda J; Cleghorn, Christine L; Blakely, Tony

2016-04-26

Dietary salt reduction is included in the top five priority actions for non-communicable disease control internationally. We therefore aimed to identify health gain and cost impacts of achieving a national target for sodium reduction, along with component targets in different food groups. We used an established dietary sodium intervention model to study 10 interventions to achieve sodium reduction targets. The 2011 New Zealand (NZ) adult population (2.3 million aged 35+ years) was simulated over the remainder of their lifetime in a Markov model with a 3 % discount rate. Achieving an overall 35 % reduction in dietary salt intake via implementation of mandatory maximum levels of sodium in packaged foods along with reduced sodium from fast foods/restaurant food and discretionary intake (the "full target"), was estimated to gain 235,000 QALYs over the lifetime of the cohort (95 % uncertainty interval [UI]: 176,000 to 298,000). For specific target components the range was from 122,000 QALYs gained (for the packaged foods target) down to the snack foods target (6100 QALYs; and representing a 34-48 % sodium reduction in such products). All ten target interventions studied were cost-saving, with the greatest costs saved for the mandatory "full target" at NZ$1260 million (US$820 million). There were relatively greater health gains per adult for men and for Māori (indigenous population). This work provides modeling-level evidence that achieving dietary sodium reduction targets (including specific food category targets) could generate large health gains and cost savings for a national health sector. Demographic groups with the highest cardiovascular disease rates stand to gain most, assisting in reducing health inequalities between sex and ethnic groups.

BEAM ON TARGET MODEL Produces All Gamma Ray Burst Phenomena Including Afterglow

NASA Astrophysics Data System (ADS)

Greyber, H.

2000-12-01

While one must applaud the splendid research by L. Piro et al and L. Amati et al reported in SCIENCE recently, one must question, as M. Rees and S. Woolsey have done, their conclusion that a ``supranova model" is the only explanation for these new X-ray observations. In fact L. Piro was quoted as saying, ``Our data helps rule out the scenario where two neutron stars or black holes collide. We think GRBs result from something similar to a supernova explosion, but much more powerful." A relatively unknown physical model for GRBs, Greyber's Beam On Target model (BOT), dating back to the first CGRO observations, can plausibly explain the iron emission lines observed for GRB991216, and also the mass of the dense medium within a light-day of the GRB being roughly equivalent to at least one-tenth solar mass, as well as the initial shedding of material followed by the GRB event. When a galaxy forms under gravitational collapse in the presence of a primordial magnetic field, Mestel and Strittmatter demonstrated that, for finite Ohmic diffusion, a growing equatorial current loop is formed. Even if this stable ``Storage Ring" has only 10exp-9 of the total energy released during a typical galaxy's formation, the relativistic beam can possess 10exp58 ergs. The GRB ``fireball" occurs when a target star races across the powerful beam, blowing off target material as a hot, rapidly expanding plasma cloud, simulating an explosion. Since currents in space are known to be sometimes filamentary, sharp millisecond spikes can be expected in some GRBs. Proton and alpha particle nuclear reactions produce a gamma ray beam. Beam particles impinging on denser cloud material create an electromagnetic shower, producing X-ray, optical and radio radiation. Since the Storage Ring has an intense magnetic field around it, synchrotron radiation is expected. The beam, striking a highly evolved massive target star, produces the iron emission lines. H. D. Greyber, in ``After the Dark Ages:When Galaxies

Nucleic acid-based vaccines targeting respiratory syncytial virus: Delivering the goods.

PubMed

Smith, Trevor R F; Schultheis, Katherine; Broderick, Kate E

2017-11-02

Respiratory syncytial virus (RSV) is a massive medical burden on a global scale. Infants, children and the elderly represent the vulnerable populations. Currently there is no approved vaccine to protect against the disease. Vaccine development has been hindered by several factors including vaccine enhanced disease (VED) associated with formalin-inactivated RSV vaccines, inability of target populations to raise protective immune responses after vaccination or natural viral infection, and a lack of consensus concerning the most appropriate virus-associated target antigen. However, with recent advances in the molecular understanding of the virus, and design of highly characterized vaccines with enhanced immunogenicity there is new belief a RSV vaccine is possible. One promising approach is nucleic acid-based vaccinology. Both DNA and mRNA RSV vaccines are showing promising results in clinically relevant animal models, supporting their transition into humans. Here we will discuss this strategy to target RSV, and the ongoing studies to advance the nucleic acid vaccine platform as a viable option to protect vulnerable populations from this important disease.

Broad Resistance to ACCase Inhibiting Herbicides in a Ryegrass Population Is Due Only to a Cysteine to Arginine Mutation in the Target Enzyme

PubMed Central

Kaundun, Shiv Shankhar; Hutchings, Sarah-Jane; Dale, Richard Paul; McIndoe, Eddie

2012-01-01

Background The design of sustainable weed management strategies requires a good understanding of the mechanisms by which weeds evolve resistance to herbicides. Here we have conducted a study on the mechanism of resistance to ACCase inhibiting herbicides in a Lolium multiflorum population (RG3) from the UK. Methodology/Principal Findings Analysis of plant phenotypes and genotypes showed that all the RG3 plants (72%) that contained the cysteine to arginine mutation at ACCase codon position 2088 were resistant to ACCase inhibiting herbicides. Whole plant dose response tests on predetermined wild and mutant 2088 genotypes from RG3 and a standard sensitive population indicated that the C2088R mutation is the only factor conferring resistance to all ten ACCase herbicides tested. The associated resistance indices ranged from 13 for clethodim to over 358 for diclofop-methyl. Clethodim, the most potent herbicide was significantly affected even when applied on small mutant plants at the peri-emergence and one leaf stages. Conclusion/Significance This study establishes the clear and unambiguous importance of the C2088R target site mutation in conferring broad resistance to ten commonly used ACCase inhibiting herbicides. It also demonstrates that low levels “creeping”, multigenic, non target site resistance, is not always selected before single gene target site resistance appears in grass weed populations subjected to herbicide selection pressure. PMID:22768118

Exploiting social influence to magnify population-level behaviour change in maternal and child health: study protocol for a randomised controlled trial of network targeting algorithms in rural Honduras

PubMed Central

Shakya, Holly B; Stafford, Derek; Hughes, D Alex; Keegan, Thomas; Negron, Rennie; Broome, Jai; McKnight, Mark; Nicoll, Liza; Nelson, Jennifer; Iriarte, Emma; Ordonez, Maria; Airoldi, Edo; Fowler, James H; Christakis, Nicholas A

2017-01-01

Introduction Despite global progress on many measures of child health, rates of neonatal mortality remain high in the developing world. Evidence suggests that substantial improvements can be achieved with simple, low-cost interventions within family and community settings, particularly those designed to change knowledge and behaviour at the community level. Using social network analysis to identify structurally influential community members and then targeting them for intervention shows promise for the implementation of sustainable community-wide behaviour change. Methods and analysis We will use a detailed understanding of social network structure and function to identify novel ways of targeting influential individuals to foster cascades of behavioural change at a population level. Our work will involve experimental and observational analyses. We will map face-to-face social networks of 30 000 people in 176 villages in Western Honduras, and then conduct a randomised controlled trial of a friendship-based network-targeting algorithm with a set of well-established care interventions. We will also test whether the proportion of the population targeted affects the degree to which the intervention spreads throughout the network. We will test scalable methods of network targeting that would not, in the future, require the actual mapping of social networks but would still offer the prospect of rapidly identifying influential targets for public health interventions. Ethics and dissemination The Yale IRB and the Honduran Ministry of Health approved all data collection procedures (Protocol number 1506016012) and all participants will provide informed consent before enrolment. We will publish our findings in peer-reviewed journals as well as engage non-governmental organisations and other actors through venues for exchanging practical methods for behavioural health interventions, such as global health conferences. We will also develop a ‘toolkit’ for practitioners to

Exploiting social influence to magnify population-level behaviour change in maternal and child health: study protocol for a randomised controlled trial of network targeting algorithms in rural Honduras.

PubMed

Shakya, Holly B; Stafford, Derek; Hughes, D Alex; Keegan, Thomas; Negron, Rennie; Broome, Jai; McKnight, Mark; Nicoll, Liza; Nelson, Jennifer; Iriarte, Emma; Ordonez, Maria; Airoldi, Edo; Fowler, James H; Christakis, Nicholas A

2017-03-13

Despite global progress on many measures of child health, rates of neonatal mortality remain high in the developing world. Evidence suggests that substantial improvements can be achieved with simple, low-cost interventions within family and community settings, particularly those designed to change knowledge and behaviour at the community level. Using social network analysis to identify structurally influential community members and then targeting them for intervention shows promise for the implementation of sustainable community-wide behaviour change. We will use a detailed understanding of social network structure and function to identify novel ways of targeting influential individuals to foster cascades of behavioural change at a population level. Our work will involve experimental and observational analyses. We will map face-to-face social networks of 30 000 people in 176 villages in Western Honduras, and then conduct a randomised controlled trial of a friendship-based network-targeting algorithm with a set of well-established care interventions. We will also test whether the proportion of the population targeted affects the degree to which the intervention spreads throughout the network. We will test scalable methods of network targeting that would not, in the future, require the actual mapping of social networks but would still offer the prospect of rapidly identifying influential targets for public health interventions. The Yale IRB and the Honduran Ministry of Health approved all data collection procedures (Protocol number 1506016012) and all participants will provide informed consent before enrolment. We will publish our findings in peer-reviewed journals as well as engage non-governmental organisations and other actors through venues for exchanging practical methods for behavioural health interventions, such as global health conferences. We will also develop a 'toolkit' for practitioners to use in network-based intervention efforts, including public

Detecting population recovery using gametic disequilibrium-based effective population size estimates

Treesearch

David A. Tallmon; Robin S. Waples; Dave Gregovich; Michael K. Schwartz

2012-01-01

Recovering populations often must meet specific growth rate or abundance targets before their legal status can be changed from endangered or threatened. While the efficacy, power, and performance of population metrics to infer trends in declining populations has received considerable attention, how these same metrics perform when populations are increasing is less...

Pharmacological targets of breast cancer stem cells: a review.

PubMed

Pindiprolu, Sai Kiran S S; Krishnamurthy, Praveen T; Chintamaneni, Pavan Kumar

2018-05-01

Breast cancers contain small population of tumor-initiating cells called breast cancer stem cells (BCSCs), which are spared even after chemotherapy. Recently, BCSCs are implicated to be a cause of metastasis, tumor relapse, and therapy resistance in breast cancer. BCSCs have unique molecular mechanisms, which can be targeted to eliminate them. These include surface biomarkers, proteins involved in self-renewal pathways, drug efflux transporters, apoptotic/antiapoptotic proteins, autophagy, metabolism, and microenvironment regulation. The complex molecular mechanisms behind the survival of BCSCs and pharmacological targets for elimination of BCSCs are described in this review.

Targeted marketing and public health.

PubMed

Grier, Sonya A; Kumanyika, Shiriki

2010-01-01

Targeted marketing techniques, which identify consumers who share common needs or characteristics and position products or services to appeal to and reach these consumers, are now the core of all marketing and facilitate its effectiveness. However, targeted marketing, particularly of products with proven or potential adverse effects (e.g., tobacco, alcohol, entertainment violence, or unhealthful foods) to consumer segments defined as vulnerable raises complex concerns for public health. It is critical that practitioners, academics, and policy makers in marketing, public health, and other fields recognize and understand targeted marketing as a specific contextual influence on the health of children and adolescents and, for different reasons, ethnic minority populations and other populations who may benefit from public health protections. For beneficial products, such understanding can foster more socially productive targeting. For potentially harmful products, understanding the nature and scope of targeted marketing influences will support identification and implementation of corrective policies.

75 FR 29776 - Tobacco Product Advertising and Promotion to Youth and Racial and Ethnic Minority Populations...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-27

... designed to appeal to specific racial and ethnic minority populations in the United States. For the same... Tobacco products are responsible for more than 440,000 deaths each year. The rates of tobacco use and..., ``[t]argeting of various population groups--including * * * specific racial and ethnic populations...

Measuring populations to improve vaccination coverage

NASA Astrophysics Data System (ADS)

Bharti, Nita; Djibo, Ali; Tatem, Andrew J.; Grenfell, Bryan T.; Ferrari, Matthew J.

2016-10-01

In low-income settings, vaccination campaigns supplement routine immunization but often fail to achieve coverage goals due to uncertainty about target population size and distribution. Accurate, updated estimates of target populations are rare but critical; short-term fluctuations can greatly impact population size and susceptibility. We use satellite imagery to quantify population fluctuations and the coverage achieved by a measles outbreak response vaccination campaign in urban Niger and compare campaign estimates to measurements from a post-campaign survey. Vaccine coverage was overestimated because the campaign underestimated resident numbers and seasonal migration further increased the target population. We combine satellite-derived measurements of fluctuations in population distribution with high-resolution measles case reports to develop a dynamic model that illustrates the potential improvement in vaccination campaign coverage if planners account for predictable population fluctuations. Satellite imagery can improve retrospective estimates of vaccination campaign impact and future campaign planning by synchronizing interventions with predictable population fluxes.

Measuring populations to improve vaccination coverage

PubMed Central

Bharti, Nita; Djibo, Ali; Tatem, Andrew J.; Grenfell, Bryan T.; Ferrari, Matthew J.

2016-01-01

In low-income settings, vaccination campaigns supplement routine immunization but often fail to achieve coverage goals due to uncertainty about target population size and distribution. Accurate, updated estimates of target populations are rare but critical; short-term fluctuations can greatly impact population size and susceptibility. We use satellite imagery to quantify population fluctuations and the coverage achieved by a measles outbreak response vaccination campaign in urban Niger and compare campaign estimates to measurements from a post-campaign survey. Vaccine coverage was overestimated because the campaign underestimated resident numbers and seasonal migration further increased the target population. We combine satellite-derived measurements of fluctuations in population distribution with high-resolution measles case reports to develop a dynamic model that illustrates the potential improvement in vaccination campaign coverage if planners account for predictable population fluctuations. Satellite imagery can improve retrospective estimates of vaccination campaign impact and future campaign planning by synchronizing interventions with predictable population fluxes. PMID:27703191

SuperTarget goes quantitative: update on drug–target interactions

PubMed Central

Hecker, Nikolai; Ahmed, Jessica; von Eichborn, Joachim; Dunkel, Mathias; Macha, Karel; Eckert, Andreas; Gilson, Michael K.; Bourne, Philip E.; Preissner, Robert

2012-01-01

There are at least two good reasons for the on-going interest in drug–target interactions: first, drug-effects can only be fully understood by considering a complex network of interactions to multiple targets (so-called off-target effects) including metabolic and signaling pathways; second, it is crucial to consider drug-target-pathway relations for the identification of novel targets for drug development. To address this on-going need, we have developed a web-based data warehouse named SuperTarget, which integrates drug-related information associated with medical indications, adverse drug effects, drug metabolism, pathways and Gene Ontology (GO) terms for target proteins. At present, the updated database contains >6000 target proteins, which are annotated with >330 000 relations to 196 000 compounds (including approved drugs); the vast majority of interactions include binding affinities and pointers to the respective literature sources. The user interface provides tools for drug screening and target similarity inclusion. A query interface enables the user to pose complex queries, for example, to find drugs that target a certain pathway, interacting drugs that are metabolized by the same cytochrome P450 or drugs that target proteins within a certain affinity range. SuperTarget is available at http://bioinformatics.charite.de/supertarget. PMID:22067455

Site-specific selfish genes as tools for the control and genetic engineering of natural populations.

PubMed

Burt, Austin

2003-05-07

Site-specific selfish genes exploit host functions to copy themselves into a defined target DNA sequence, and include homing endonuclease genes, group II introns and some LINE-like transposable elements. If such genes can be engineered to target new host sequences, then they can be used to manipulate natural populations, even if the number of individuals released is a small fraction of the entire population. For example, a genetic load sufficient to eradicate a population can be imposed in fewer than 20 generations, if the target is an essential host gene, the knockout is recessive and the selfish gene has an appropriate promoter. There will be selection for resistance, but several strategies are available for reducing the likelihood of it evolving. These genes may also be used to genetically engineer natural populations, by means of population-wide gene knockouts, gene replacements and genetic transformations. By targeting sex-linked loci just prior to meiosis one may skew the population sex ratio, and by changing the promoter one may limit the spread of the gene to neighbouring populations. The proposed constructs are evolutionarily stable in the face of the mutations most likely to arise during their spread, and strategies are also available for reversing the manipulations.

Are Cultural Values and Beliefs Included in U.S. Based HIV Interventions?

PubMed Central

Wyatt, Gail E.; Williams, John K.; Gupta, Arpana; Malebranche, Dominique

2013-01-01

Objective To determine the extent to which current U.S. based HIV/AIDS prevention and risk reduction interventions address and include aspects of cultural beliefs in definitions, curricula, measures and related theories that may contradict current safer sex messages. Method A comprehensive literature review was conducted to determine which published HIV/AIDS prevention and risk reduction interventions incorporated aspects of cultural beliefs. Results This review of 166 HIV prevention and risk reduction interventions, published between 1988 and 2010, identified 34 interventions that varied in cultural definitions and the integration of cultural concepts. Conclusion HIV interventions need to move beyond targeting specific populations based upon race/ethnicity, gender, sexual, drug and/or risk behaviors and incorporate cultural beliefs and experiences pertinent to an individual’s risk. Theory based interventions that incorporate cultural beliefs within a contextual framework are needed if prevention and risk reduction messages are to reach targeted at risk populations. Implications for the lack of uniformity of cultural definitions, measures and related theories are discussed and recommendations are made to ensure that cultural beliefs are acknowledged for their potential conflict with safer sex skills and practices. PMID:21884721

The Case for Diabetes Population Health Improvement: Evidence-Based Programming for Population Outcomes in Diabetes.

PubMed

Golden, Sherita Hill; Maruthur, Nisa; Mathioudakis, Nestoras; Spanakis, Elias; Rubin, Daniel; Zilbermint, Mihail; Hill-Briggs, Felicia

2017-07-01

The goal of this review is to describe diabetes within a population health improvement framework and to review the evidence for a diabetes population health continuum of intervention approaches, including diabetes prevention and chronic and acute diabetes management, to improve clinical and economic outcomes. Recent studies have shown that compared to usual care, lifestyle interventions in prediabetes lower diabetes risk at the population-level and that group-based programs have low incremental medial cost effectiveness ratio for health systems. Effective outpatient interventions that improve diabetes control and process outcomes are multi-level, targeting the patient, provider, and healthcare system simultaneously and integrate community health workers as a liaison between the patient and community-based healthcare resources. A multi-faceted approach to diabetes management is also effective in the inpatient setting. Interventions shown to promote safe and effective glycemic control and use of evidence-based glucose management practices include provider reminder and clinical decision support systems, automated computer order entry, provider education, and organizational change. Future studies should examine the cost-effectiveness of multi-faceted outpatient and inpatient diabetes management programs to determine the best financial models for incorporating them into diabetes population health strategies.

Small D-type asteroids in the NEO population: new targets for space missions

NASA Astrophysics Data System (ADS)

Barucci, Maria Antonietta; Perna, D.; Popescu, M.; Fornasier, S.; Doressoundiram, A.; Lantz, C.; Merlin, F.; Fulchignoni, M.; Dotto, E.; Kanuchova, S.

2018-06-01

In the framework of the Near Earth Objects (NEOs) observational campaign carried out within the NEOShield-2 project, we identify nine new small D-type asteroids with estimated diameter less than 600 m. The link with meteorites for this class of asteroids is weak and the best fit obtained is with the Tagish Lake meteorite for seven of them. D-type asteroids are believed to contain the most pristine material of the Solar system and could have delivered the pre-biotic material to the Earth. Our results double the known sample of the D-types in the NEO population and triple the candidates of this class for a sample-return mission (at very low ΔV). Our finding increases considerably the number of targets for sample-return mission. A sample-return mission to a D-type asteroid will provide a major progress in understanding the early history of the Solar system and to investigate the origin of life on the Earth.

Rationale and design of a home-based trial using wearable sensors to detect asymptomatic atrial fibrillation in a targeted population: The mHealth Screening To Prevent Strokes (mSToPS) trial.

PubMed

Steinhubl, Steven R; Mehta, Rajesh R; Ebner, Gail S; Ballesteros, Marissa M; Waalen, Jill; Steinberg, Gregory; Van Crocker, Percy; Felicione, Elise; Carter, Chureen T; Edmonds, Shawn; Honcz, Joseph P; Miralles, Gines Diego; Talantov, Dimitri; Sarich, Troy C; Topol, Eric J

2016-05-01

Efficient methods for screening populations for undiagnosed atrial fibrillation (AF) are needed to reduce its associated mortality, morbidity, and costs. The use of digital technologies, including wearable sensors and large health record data sets allowing for targeted outreach toward individuals at increased risk for AF, might allow for unprecedented opportunities for effective, economical screening. The trial's primary objective is to determine, in a real-world setting, whether using wearable sensors in a risk-targeted screening population can diagnose asymptomatic AF more effectively than routine care. Additional key objectives include (1) exploring 2 rhythm-monitoring strategies-electrocardiogram-based and exploratory pulse wave-based-for detection of new AF, and (2) comparing long-term clinical and resource outcomes among groups. In all, 2,100 Aetna members will be randomized 1:1 to either immediate or delayed monitoring, in which a wearable patch will capture a single-lead electrocardiogram during the first and last 2 weeks of a 4-month period beginning immediately or 4 months after enrollment, respectively. An observational, risk factor-matched control group (n = 4,000) will be developed from members who did not receive an invitation to participate. The primary end point is the incidence of new AF in the immediate- vs delayed-monitoring arms at the end of the 4-month monitoring period. Additional efficacy and safety end points will be captured at 1 and 3 years. The results of this digital medicine trial might benefit a substantial proportion of the population by helping identify and refine screening methods for undiagnosed AF. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Threat Assessment and Targeted Violence at Institutions of Higher Education: Implications for Policy and Practice Including Unique Considerations for Community Colleges

ERIC Educational Resources Information Center

Bennett, Laura; Bates, Michael

2015-01-01

This article provides an overview of the research on targeted violence, including campus violence, and the implications for policy and practice at institutions of higher education. Unique challenges of threat assessment in the community college setting are explored, and an overview of an effective threat assessment policy and team at William…

Alcohol and Sexuality Research in the AIDS Era: Trends in Publication Activity, Target Populations and Research Design

PubMed Central

George, William H.

2009-01-01

Research addressing relationships between alcohol and human sexuality has proliferated, due in part to efforts to characterize alcohol's role in HIV risk behavior. This study provides a descriptive review of the alcohol–sexuality literature, using abstracts from 264 identified studies to estimate changes in publication activity, target populations, and the prevalence of HIV-related studies over time. We also examine methodological trends by estimating the prevalence of experimental vs. non-experimental studies. Findings show considerable increases in research activity and diversity of populations studied since the mid-1980's and highlight the emergence of HIV-related studies as a focal point of alcohol–sexuality research efforts. Results also demonstrate a substantial decline in the proportion of studies utilizing experimental methods, in part because of frequent use of non-experimental approaches in studies of alcohol and HIV risk behavior. We discuss implications and review the role of experiments in evaluating causal relationships between alcohol and sexual risk behavior. PMID:16897352

Alcohol and sexuality research in the AIDS era: trends in publication activity, target populations and research design.

PubMed

Hendershot, Christian S; George, William H

2007-03-01

Research addressing relationships between alcohol and human sexuality has proliferated, due in part to efforts to characterize alcohol's role in HIV risk behavior. This study provides a descriptive review of the alcohol-sexuality literature, using abstracts from 264 identified studies to estimate changes in publication activity, target populations, and the prevalence of HIV-related studies over time. We also examine methodological trends by estimating the prevalence of experimental vs. non-experimental studies. Findings show considerable increases in research activity and diversity of populations studied since the mid-1980's and highlight the emergence of HIV-related studies as a focal point of alcohol-sexuality research efforts. Results also demonstrate a substantial decline in the proportion of studies utilizing experimental methods, in part because of frequent use of non-experimental approaches in studies of alcohol and HIV risk behavior. We discuss implications and review the role of experiments in evaluating causal relationships between alcohol and sexual risk behavior.

Population and Human Development: A Course Curriculum Including Lesson Plans, Activities and Bibliography.

ERIC Educational Resources Information Center

Murphy, Elaine M.

This course outline suggests materials and learning activities on the interrelated causes and consequences of population growth and other population concerns. Designed to educate general college audiences, it is also intended for use as a preservice course for teachers. In addition, the course can be modified for high school students. The course…

Targeting interventions for ethnic minority and low-income populations.

PubMed

Kumanyika, Shiriki; Grier, Sonya

2006-01-01

Although rates of childhood obesity among the general population are alarmingly high, they are higher still in ethnic minority and low-income communities. The disparities pose a major challenge for policymakers and practitioners planning strategies for obesity prevention. In this article Shiriki Kumanyika and Sonya Grier summarize differences in childhood obesity prevalence by race and ethnicity and by socioeconomic status. They show how various environmental factors can have larger effects on disadvantaged and minority children than on their advantaged white peers-and thus contribute to disparities in obesity rates. The authors show, for example, that low-income and minority children watch more television than white, non-poor children and are potentially exposed to more commercials advertising high-calorie, low-nutrient food during an average hour of TV programming. They note that neighborhoods where low-income and minority children live typically have more fast-food restaurants and fewer vendors of healthful foods than do wealthier or predominantly white neighborhoods. They cite such obstacles to physical activity as unsafe streets, dilapidated parks, and lack of facilities. In the schools that low-income and minority children attend, however, they see opportunities to lead the way to effective obesity prevention. Finally, the authors examine several aspects of the home environment-breast-feeding, television viewing, and parental behaviors-that may contribute to childhood obesity but be amenable to change through targeted intervention. Kumanyika and Grier point out that policymakers aiming to prevent obesity can use many existing policy levers to reach ethnic minority and low-income children and families: Medicaid, the State Child Health Insurance Program, and federal nutrition "safety net" programs. Ultimately, winning the fight against childhood obesity in minority and low-income communities will depend on the nation's will to change the social and physical

Colon-targeted delivery of live bacterial cell biotherapeutics including microencapsulated live bacterial cells

PubMed Central

Prakash, Satya; Malgorzata Urbanska, Aleksandra

2008-01-01

There has been an ample interest in delivery of therapeutic molecules using live cells. Oral delivery has been stipulated as best way to deliver live cells to humans for therapy. Colon, in particular, is a part of gastrointestinal (GI) tract that has been proposed to be an oral targeted site. The main objective of these oral therapy procedures is to deliver live cells not only to treat diseases like colorectal cancer, inflammatory bowel disease, and other GI tract diseases like intestinal obstruction and gastritis, but also to deliver therapeutic molecules for overall therapy in various diseases such as renal failure, coronary heart disease, hypertension, and others. This review provides a comprehensive summary of recent advancement in colon targeted live bacterial cell biotherapeutics. Current status of bacterial cell therapy, principles of artificial cells and its potentials in oral delivery of live bacterial cell biotherapeutics for clinical applications as well as biotherapeutic future perspectives are also discussed in our review. PMID:19707368

Population and policy in Finland.

PubMed

Hulkko, J

1989-03-01

Finland, with a population of 4.9 million, currently has an overall fertility rate of 1.6. There is a small population growth, but this is due to a large reproductive age group, return migration of Finns from Sweden, and a decrease in mortality that has increased the proportion of old people in the population. The state has no official population policy. A recommendation of the Finnish Committee on the World Population Year 1974 that the government establish an agency for population policy has not been adopted. The coalition government now in power has a program, however, aimed at influencing population growth. The program includes proposals to reduce work hours for parents with small children, increase the age limit for participation in the child allowance system, and increase the number of municipal day care facilities. Concerning regional policy, the government wants a balanced development of the country's different regions. Subsidiary industries of agriculture and forestry are being encouraged to preserve population levels in sparse areas. Finland also supports a health policy emphasizing preventive and non-institutional aspects of health care, with targets of life expectancy set at 82 years for women and 75 years for men by the year 2000.

Target Selection for the SDSS-IV APOGEE-2 Survey

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zasowski, G.; Cohen, R. E.; Carlberg, J. K.

APOGEE-2 is a high-resolution, near-infrared spectroscopic survey observing ∼3 × 10{sup 5} stars across the entire sky. It is the successor to APOGEE and is part of the Sloan Digital Sky Survey IV (SDSS-IV). APOGEE-2 is expanding on APOGEE’s goals of addressing critical questions of stellar astrophysics, stellar populations, and Galactic chemodynamical evolution using (1) an enhanced set of target types and (2) a second spectrograph at Las Campanas Observatory in Chile. APOGEE-2 is targeting red giant branch and red clump stars, RR Lyrae, low-mass dwarf stars, young stellar objects, and numerous other Milky Way and Local Group sources across the entiremore » sky from both hemispheres. In this paper, we describe the APOGEE-2 observational design, target selection catalogs and algorithms, and the targeting-related documentation included in the SDSS data releases.« less

The Case for Diabetes Population Health Improvement: Evidence-Based Programming for Population Outcomes in Diabetes

PubMed Central

Maruthur, Nisa; Mathioudakis, Nestoras; Spanakis, Elias; Rubin, Daniel; Zilbermint, Mihail; Hill-Briggs, Felicia

2017-01-01

Purpose of Review The goal of this review is to describe diabetes within a population health improvement framework and to review the evidence for a diabetes population health continuum of intervention approaches, including diabetes prevention and chronic and acute diabetes management, to improve clinical and economic outcomes. Recent Findings Recent studies have shown that compared to usual care, lifestyle interventions in prediabetes lower diabetes risk at the population-level and that group-based programs have low incremental medial cost effectiveness ratio for health systems. Effective outpatient interventions that improve diabetes control and process outcomes are multi-level, targeting the patient, provider, and healthcare system simultaneously and integrate community health workers as a liaison between the patient and community-based healthcare resources. A multi-faceted approach to diabetes management is also effective in the inpatient setting. Interventions shown to promote safe and effective glycemic control and use of evidence-based glucose management practices include provider reminder and clinical decision support systems, automated computer order entry, provider education, and organizational change. Summary Future studies should examine the cost-effectiveness of multi-faceted outpatient and inpatient diabetes management programs to determine the best financial models for incorporating them into diabetes population health strategies. PMID:28567711

Are cultural values and beliefs included in U.S. based HIV interventions?

PubMed

Wyatt, Gail E; Williams, John K; Gupta, Arpana; Malebranche, Dominique

2012-11-01

To determine the extent to which current United States based human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) prevention and risk reduction interventions address and include aspects of cultural beliefs in definitions, curricula, measures and related theories that may contradict current safer sex messages. A comprehensive literature review was conducted to determine which published human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) prevention and risk reduction interventions incorporated aspects of cultural beliefs. This review of 166 human immunodeficiency virus (HIV) prevention and risk reduction interventions, published between 1988 and 2010, identified 34 interventions that varied in cultural definitions and the integration of cultural concepts. human immunodeficiency virus (HIV) interventions need to move beyond targeting specific populations based upon race/ethnicity, gender, sexual, drug and/or risk behaviors and incorporate cultural beliefs and experiences pertinent to an individual's risk. Theory based interventions that incorporate cultural beliefs within a contextual framework are needed if prevention and risk reduction messages are to reach targeted at risk populations. Implications for the lack of uniformity of cultural definitions, measures and related theories are discussed and recommendations are made to ensure that cultural beliefs are acknowledged for their potential conflict with safer sex skills and practices. Copyright © 2011. Published by Elsevier Inc.

An integrated molecular analysis of lung adenocarcinomas identifies potential therapeutic targets among TTF1-negative tumors including DNA repair proteins and Nrf2

PubMed Central

Cardnell, Robert J.G.; Behrens, Carmen; Diao, Lixia; Fan, YouHong; Tang, Ximing; Tong, Pan; John D., Minna; Mills, Gordon B.; Heymach, John V.; Wistuba, Ignacio I.; Wang, Jing; Byers., Lauren A.

2015-01-01

Purpose Thyroid transcription factor-1 (TTF1) immunohistochemistry (IHC) is used clinically to differentiate primary lung adenocarcinomas (LUAD) from squamous lung cancers and metastatic adenocarcinomas from other primary sites. However, a subset of LUAD (15-20%) does not express TTF1 and TTF1-negative patients have worse clinical outcomes. As there are no established targeted agents with activity in TTF1-negative LUAD, we performed an integrated molecular analysis to identify potential therapeutic targets. Experimental Design Using two clinical LUAD cohorts (274 tumors), one from our institution (PROSPECT) and the TCGA, we interrogated proteomic profiles (by reverse-phase protein array (RPPA)), gene expression, and mutational data. Drug response data from 74 cell lines were used to validate potential therapeutic agents. Results Strong correlations were observed between TTF1 IHC and TTF1 measurements by RPPA (Rho=0.57, p<0.001) and gene expression (NKX2-1, Rho=0.61, p<0.001). Established driver mutations (e.g. BRAF and EGFR) were associated with high TTF1 expression. In contrast, TTF1-negative LUAD had a higher frequency of inactivating KEAP1 mutations (p=0.001). Proteomic profiling identified increased expression of DNA repair proteins (e.g., Chk1 and the DNA repair score) and suppressed PI3K/MAPK signaling among TTF1-negative tumors, with differences in total proteins confirmed at the mRNA level. Cell line analysis showed drugs targeting DNA repair to be more active in TTF1-low cell lines. Conclusions Combined genomic and proteomic analyses demonstrated infrequent alteration of validated lung cancer targets (including the absence of BRAF mutations in TTF1-negative LUAD), but identified novel potential targets for TTF1-negative LUAD includingKEAP1/Nrf2 and DNA repair pathways. PMID:25878335

Markerless motion capture systems as training device in neurological rehabilitation: a systematic review of their use, application, target population and efficacy.

PubMed

Knippenberg, Els; Verbrugghe, Jonas; Lamers, Ilse; Palmaers, Steven; Timmermans, Annick; Spooren, Annemie

2017-06-24

Client-centred task-oriented training is important in neurological rehabilitation but is time consuming and costly in clinical practice. The use of technology, especially motion capture systems (MCS) which are low cost and easy to apply in clinical practice, may be used to support this kind of training, but knowledge and evidence of their use for training is scarce. The present review aims to investigate 1) which motion capture systems are used as training devices in neurological rehabilitation, 2) how they are applied, 3) in which target population, 4) what the content of the training and 5) efficacy of training with MCS is. A computerised systematic literature review was conducted in four databases (PubMed, Cinahl, Cochrane Database and IEEE). The following MeSH terms and key words were used: Motion, Movement, Detection, Capture, Kinect, Rehabilitation, Nervous System Diseases, Multiple Sclerosis, Stroke, Spinal Cord, Parkinson Disease, Cerebral Palsy and Traumatic Brain Injury. The Van Tulder's Quality assessment was used to score the methodological quality of the selected studies. The descriptive analysis is reported by MCS, target population, training parameters and training efficacy. Eighteen studies were selected (mean Van Tulder score = 8.06 ± 3.67). Based on methodological quality, six studies were selected for analysis of training efficacy. Most commonly used MCS was Microsoft Kinect, training was mostly conducted in upper limb stroke rehabilitation. Training programs varied in intensity, frequency and content. None of the studies reported an individualised training program based on client-centred approach. Motion capture systems are training devices with potential in neurological rehabilitation to increase the motivation during training and may assist improvement on one or more International Classification of Functioning, Disability and Health (ICF) levels. Although client-centred task-oriented training is important in neurological rehabilitation

World Population: Facts in Focus. World Population Data Sheet Workbook. Population Learning Series.

ERIC Educational Resources Information Center

Crews, Kimberly A.

This workbook teaches population analysis using world population statistics. To complete the four student activity sheets, the students refer to the included "1988 World Population Data Sheet" which lists nations' statistical data that includes population totals, projected population, birth and death rates, fertility levels, and the…

Influence of socioeconomic and demographic status on spirometry testing in patients initiating medication targeting obstructive lung disease: a population-based cohort study.

PubMed

Koefoed, Mette M; Søndergaard, Jens; Christensen, René dePont; Jarbøl, Dorte E

2013-06-14

Socioeconomic status is known to influence the prevalence, severity and mortality of obstructive lung diseases, but it is uncertain whether it affects the use of diagnostic spirometry in patients initiating treatment for these conditions. The objective of this paper was to examine a possible association between education, income, labour market affiliation, cohabitation status and having spirometry performed when initiating medication targeting obstructive pulmonary disease. We conducted a population-based cohort study. Danish national registers were linked, retrieving data on prescriptions, spirometry testing, socioeconomic and demographic variables in all first time users of medication targeting obstructive lung disease in 2008. A total of 37,734 persons were included and approximately half of the cohort had spirometry performed. Among medication users under 65 years of age, being unemployed was significantly associated with reduced odds of having spirometry performed, the strongest association was seen in men (OR = 0.82, CI = 0.73-0.91). Medium income was associated with increased odds of having spirometry performed in men (OR =1.18, CI = 1.06-1.30) and high educational level (>12 years) was associated with reduced odds of having spirometry performed in women (OR = 0.86, CI = 0.78-0.94). Cohabitation status was not associated with having spirometry performed. Among medication users over 65 years of age, living alone was associated with reduced odds of having spirometry performed among men (OR = 0.78, CI = 0.69-0.88). Social inequity in spirometry testing among patients initiating medication targeting obstructive lung disease was confirmed in this study. Increased focus on spirometry testing among elderly men living alone, among the unemployed and among women with higher education is required when initiating medication.

CIP2A is a candidate therapeutic target in clinically challenging prostate cancer cell populations.

PubMed

Khanna, Anchit; Rane, Jayant K; Kivinummi, Kati K; Urbanucci, Alfonso; Helenius, Merja A; Tolonen, Teemu T; Saramäki, Outi R; Latonen, Leena; Manni, Visa; Pimanda, John E; Maitland, Norman J; Westermarck, Jukka; Visakorpi, Tapio

2015-08-14

Residual androgen receptor (AR)-signaling and presence of cancer stem-like cells (SCs) are the two emerging paradigms for clinically challenging castration-resistant prostate cancer (CRPC). Therefore, identification of AR-target proteins that are also overexpressed in the cancer SC population would be an attractive therapeutic approach.Our analysis of over three hundred clinical samples and patient-derived prostate epithelial cultures (PPECs), revealed Cancerous inhibitor of protein phosphatase 2A (CIP2A) as one such target. CIP2A is significantly overexpressed in both hormone-naïve prostate cancer (HN-PC) and CRPC patients . CIP2A is also overexpressed, by 3- and 30-fold, in HN-PC and CRPC SCs respectively. In vivo binding of the AR to the intronic region of CIP2A and its functionality in the AR-moderate and AR-high expressing LNCaP cell-model systems is also demonstrated. Further, we show that AR positively regulates CIP2A expression, both at the mRNA and protein level. Finally, CIP2A depletion reduced cell viability and colony forming efficiency of AR-independent PPECs as well as AR-responsive LNCaP cells, in which anchorage-independent growth is also impaired.These findings identify CIP2A as a common denominator for AR-signaling and cancer SC functionality, highlighting its potential therapeutic significance in the most clinically challenging prostate pathology: castration-resistant prostate cancer.

Missing the target: including perspectives of women with overweight and obesity to inform stigma‐reduction strategies

PubMed Central

Himmelstein, M. S.; Gorin, A. A.; Suh, Y. J.

2017-01-01

Summary Objective Pervasive weight stigma and discrimination have led to ongoing calls for efforts to reduce this bias. Despite increasing research on stigma‐reduction strategies, perspectives of individuals who have experienced weight stigma have rarely been included to inform this research. The present study conducted a systematic examination of women with high body weight to assess their perspectives about a broad range of strategies to reduce weight‐based stigma. Methods Women with overweight or obesity (N = 461) completed an online survey in which they evaluated the importance, feasibility and potential impact of 35 stigma‐reduction strategies in diverse settings. Participants (91.5% who reported experiencing weight stigma) also completed self‐report measures assessing experienced and internalized weight stigma. Results Most participants assigned high importance to all stigma‐reduction strategies, with school‐based and healthcare approaches accruing the highest ratings. Adding weight stigma to existing anti‐harassment workplace training was rated as the most impactful and feasible strategy. The family environment was viewed as an important intervention target, regardless of participants' experienced or internalized stigma. Conclusion These findings underscore the importance of including people with stigmatized identities in stigma‐reduction research; their insights provide a necessary and valuable contribution that can inform ways to reduce weight‐based inequities and prioritize such efforts. PMID:28392929

Distinctions Among Circulating Antibody Secreting Cell Populations, Including B-1 Cells, in Human Adult Peripheral Blood1

PubMed Central

Quách, Tâm D.; Rodríguez-Zhurbenko, Nely; Hopkins, Thomas J.; Guo, Xiaoti; Vázquez, Ana María Hernández; Li, Wentian; Rothstein, Thomas L.

2015-01-01

Human antibody secreting cell (ASC) populations in circulation are not well studied. In addition to B-1 (CD20+CD27+CD38lo/intCD43+) cell and the conventional plasmablast (CD20-CD27hiCD38hi) cell populations, here we identified a novel B cell population termed 20+38hi B cells (CD20+CD27hiCD38hi) that spontaneously secretes antibody. At steady state, 20+38hi B cells are distinct from plasmablasts on the basis of CD20 expression, amount of antibody production, frequency of mutation, and diversity of B cell receptor repertoire. However, cytokine treatment of 20+38hi B cells induces loss of CD20 and acquisition of CD138, suggesting that 20+38hi B cells are precursors to plasmablasts, or pre-plasmablasts. We then evaluated similarities and differences between CD20+CD27+CD38lo/intCD43+ B-1 cells, CD20+CD27hiCD38hi 20+38hi B cells, CD20-CD27hiCD38hi plasmablasts, and CD20+CD27+CD38lo/intCD43- memory B cells. We found that B-1 cells differ from 20+38hi B cells and plasmablasts in numbers of ways, including antigen expression, morphological appearance, transcriptional profiling, antibody skewing, antibody repertoire, and secretory response to stimulation. In terms of gene expression, B-1 cells align more closely with memory B cells than with 20+38hi B cells or plasmablasts, but differ in that memory B cells do not express antibody secretion related genes. We found that, B-1 cell antibodies utilize Vh4-34, which is often associated with autoreactivity, 3 to 6-fold more often than other B cell populations. Along with selective production of IgM anti-PC, this data suggests that human B-1 cells might be preferentially selected for autoreactivity/natural-specificity. In sum, our results indicate that human healthy adult peripheral blood at steady state consists of 3 distinct ASC populations. PMID:26740107

The Drosophila genome nexus: a population genomic resource of 623 Drosophila melanogaster genomes, including 197 from a single ancestral range population.

PubMed

Lack, Justin B; Cardeno, Charis M; Crepeau, Marc W; Taylor, William; Corbett-Detig, Russell B; Stevens, Kristian A; Langley, Charles H; Pool, John E

2015-04-01

Hundreds of wild-derived Drosophila melanogaster genomes have been published, but rigorous comparisons across data sets are precluded by differences in alignment methodology. The most common approach to reference-based genome assembly is a single round of alignment followed by quality filtering and variant detection. We evaluated variations and extensions of this approach and settled on an assembly strategy that utilizes two alignment programs and incorporates both substitutions and short indels to construct an updated reference for a second round of mapping prior to final variant detection. Utilizing this approach, we reassembled published D. melanogaster population genomic data sets and added unpublished genomes from several sub-Saharan populations. Most notably, we present aligned data from phase 3 of the Drosophila Population Genomics Project (DPGP3), which provides 197 genomes from a single ancestral range population of D. melanogaster (from Zambia). The large sample size, high genetic diversity, and potentially simpler demographic history of the DPGP3 sample will make this a highly valuable resource for fundamental population genetic research. The complete set of assemblies described here, termed the Drosophila Genome Nexus, presently comprises 623 consistently aligned genomes and is publicly available in multiple formats with supporting documentation and bioinformatic tools. This resource will greatly facilitate population genomic analysis in this model species by reducing the methodological differences between data sets. Copyright © 2015 by the Genetics Society of America.

Targeting survival pathways in chronic myeloid leukaemia stem cells

PubMed Central

Sinclair, A; Latif, A L; Holyoake, T L

2013-01-01

Chronic myeloid leukaemia (CML) is a clonal myeloproliferative disorder characterized by the presence of a fusion oncogene BCR-ABL, which encodes a protein with constitutive TK activity. The implementation of tyrosine kinase inhibitors (TKIs) marked a major advance in CML therapy; however, there are problems with current treatment. For example, relapse occurs when these drugs are discontinued in the majority of patients who have achieved a complete molecular response on TKI and these agents are less effective in patients with mutations in the BCR-ABL kinase domain. Importantly, TKI can effectively target proliferating mature cells, but do not eradicate quiescent leukaemic stem cells (LSCs), therefore allowing disease persistence despite treatment. It is essential that alternative strategies are used to target the LSC population. BCR-ABL activation is responsible for the modulation of different signalling pathways, which allows the LSC fraction to evade cell death. Several pathways have been shown to be modulated by BCR-ABL, including PI3K/AKT/mTOR, JAK-STAT and autophagy signalling pathways. Targeting components of these survival pathways, alone or in combination with TKI, therefore represents an attractive potential therapeutic approach for targeting the LSC. However, many pathways are also active in normal stem cells. Therefore, potential targets must be validated to effectively eradicate CML stem cells while sparing normal counterparts. This review summarizes the main pathways modulated in CML stem cells, the recent developments and the use of novel drugs to target components in these pathways which may be used to target the LSC population. Linked Articles This article is part of a themed section on Emerging Therapeutic Aspects in Oncology. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2013.169.issue-8 PMID:23517124

Obesity Rates in Special Populations of Children and Potential Interventions

ERIC Educational Resources Information Center

Holcomb, Matthew J.; Pufpaff, Lisa A.; McIntosh, David E.

2009-01-01

Childhood obesity has become a problem of epidemic proportions in the United States, but much of the research has focused on prevention and intervention programs, which target the general population of school children. Overlooked in the literature are children with special needs (including autism, genetic disorders, Down syndrome, and Prader-Willi…

Future Freshwater Stress on Small Islands: Population, Aridity and Global Warming Targets

NASA Astrophysics Data System (ADS)

Karnauskas, K. B.; Schleussner, C. F.; Donnelly, J. P.; Anchukaitis, K. J.

2017-12-01

Small island developing states (SIDS) face multiple threats from anthropogenic climate change, including potential changes in freshwater resource availability. Future freshwater stress, including geographic and seasonal variability, has important implications for climate change adaptation scenarios for vulnerable human populations living on islands across the world ocean. Due to a mismatch in spatial scale between SIDS landforms and the horizontal resolution of global climate models (GCMs), SIDS are mostly unaccounted for in GCMs that are used to make future projections of global climate change and its regional impacts. Specific approaches are required to address this gap between broad-scale model projections and regional, policy-relevant outcomes. Here we apply a recently developed methodology to project future changes in aridity in combination with population projections associated with different shared socioeconomic pathways (SSPs) to evaluate overall changes in freshwater stress in SIDS at warming levels of 1.5°C and 2°C above pre-industrial levels. By accounting for evaporative demand a posteriori, we reveal a robust yet spatially variable tendency towards increasing aridity for 16 million people living on islands by mid-century. Although about half of the islands are projected to experience increased rainfall—predominantly in the deep tropics—projected changes in evaporation are more uniform, shifting the global distribution of changes in island freshwater balance towards greater aridity. In many cases, the magnitude of projected drying is comparable to the amplitude of the estimated observed interannual variability, with important consequences for extreme events. While we find that future population growth will dominate changes in projected freshwater stress especially towards the end of the century, projected changes in aridity are found to compound freshwater stress for the vast majority of SIDS. Particularly across the Caribbean region, a

[The dynamics of heath indicators of population of industrial town].

PubMed

Kalinkin, D E; Karpov, A B; Takhauov, R M; Samoĭlova, Iu A

2013-01-01

The article presents the results of analysis of dynamics of health indicators of population of industrial town (medical demographic indicators, disability, morbidity of social hygienically important diseases) during 1970-2010. The classified administrative territorial municipality of Seversk constructed near the Siberian chemical industrial center, the internationally first-rate complex of nuclear industry enterprises was used as a research base. It is demonstrated that dynamics of health indicators of studied population had such negative tendencies as rapid population ageing, population loss due to decrease of natality and increase of mortality (population of able-bodied age included), prevalence of cardio-vascular diseases, malignant neoplasms and external causes, chronization of diseases. The established tendencies are to be considered in management decision making targeted to support and promote population health in industrial towns.

Demographic and genetic status of an isolated population of bog turtles (Glyptemys muhlenbergii): Implications for managing small populations of long-lived animals

USGS Publications Warehouse

Pittman, Shannon E.; King, T.L.; Faurby, S.; Dorcas, M.E.

2011-01-01

In this study, we sought to determine the population stability and genetic diversity of one isolated population of the federally-threatened bog turtle (Glyptemys muhlenbergii) in North Carolina. Using capture-recapture data, we estimated adult survival and population growth rate from 1992 to 2007. We found that the population decreased from an estimated 36 adult turtles in 1994 to approximately 11 adult turtles in 2007. We found a constant adult survival of 0. 893 (SE = 0. 018, 95% confidence interval, 0. 853-0. 924) between 1992 and 2007. Using 18 microsatellite markers, we compared the genetic status of this population with five other bog turtle populations. The target population displayed allelic richness (4. 8 ?? 0. 5) and observed heterozygosity (0. 619 ?? 0. 064) within the range of the other bog turtle populations. Coalescent analysis of population growth rate, effective population size, and timing of population structuring event also indicated the genetics of the target population were comparable to the other populations studied. Estimates of effective population size were a proportion of the census size in all populations except the target population, in which the effective population size was larger than the census size (30 turtles vs. 11 turtles). We attribute the high genetic diversity in the target population to the presence of multiple generations of old turtles. This study illustrates that the demographic status of populations of long-lived species may not be reflected genetically if a decline occurred recently. Consequently, the genetic integrity of populations of long-lived animals experiencing rapid demographic bottlenecks may be preserved through conservation efforts effective in addressing demographic problems. ?? 2011 Springer Science+Business Media B.V.

The drug target genes show higher evolutionary conservation than non-target genes.

PubMed

Lv, Wenhua; Xu, Yongdeng; Guo, Yiying; Yu, Ziqi; Feng, Guanglong; Liu, Panpan; Luan, Meiwei; Zhu, Hongjie; Liu, Guiyou; Zhang, Mingming; Lv, Hongchao; Duan, Lian; Shang, Zhenwei; Li, Jin; Jiang, Yongshuai; Zhang, Ruijie

2016-01-26

Although evidence indicates that drug target genes share some common evolutionary features, there have been few studies analyzing evolutionary features of drug targets from an overall level. Therefore, we conducted an analysis which aimed to investigate the evolutionary characteristics of drug target genes. We compared the evolutionary conservation between human drug target genes and non-target genes by combining both the evolutionary features and network topological properties in human protein-protein interaction network. The evolution rate, conservation score and the percentage of orthologous genes of 21 species were included in our study. Meanwhile, four topological features including the average shortest path length, betweenness centrality, clustering coefficient and degree were considered for comparison analysis. Then we got four results as following: compared with non-drug target genes, 1) drug target genes had lower evolutionary rates; 2) drug target genes had higher conservation scores; 3) drug target genes had higher percentages of orthologous genes and 4) drug target genes had a tighter network structure including higher degrees, betweenness centrality, clustering coefficients and lower average shortest path lengths. These results demonstrate that drug target genes are more evolutionarily conserved than non-drug target genes. We hope that our study will provide valuable information for other researchers who are interested in evolutionary conservation of drug targets.

Serving some and serving all: how providers navigate the challenges of providing racially targeted health services.

PubMed

Zhou, Amy

2017-10-01

Racially targeted healthcare provides racial minorities with culturally and linguistically appropriate health services. This mandate, however, can conflict with the professional obligation of healthcare providers to serve patients based on their health needs. The dilemma between serving a particular population and serving all is heightened when the patients seeking care are racially diverse. This study examines how providers in a multi-racial context decide whom to include or exclude from health programs. This study draws on 12 months of ethnographic fieldwork at an Asian-specific HIV organization. Fieldwork included participant observation of HIV support groups, community outreach programs, and substance abuse recovery groups, as well as interviews with providers and clients. Providers managed the dilemma in different ways. While some programs in the organization focused on an Asian clientele, others de-emphasized race and served a predominantly Latino and African American clientele. Organizational structures shaped whether services were delivered according to racial categories. When funders examined client documents, providers prioritized finding Asian clients so that their documents reflected program goals to serve the Asian population. In contrast, when funders used qualitative methods, providers could construct an image of a program that targets Asians during evaluations while they included other racial minorities in their everyday practice. Program services were organized more broadly by health needs. Even within racially targeted programs, the meaning of race fluctuates and is contested. Patients' health needs cross cut racial boundaries, and in some circumstances, the boundaries of inclusion can expand beyond specific racial categories to include racial minorities and underserved populations more generally.

Demographic history and rare allele sharing among human populations.

PubMed

Gravel, Simon; Henn, Brenna M; Gutenkunst, Ryan N; Indap, Amit R; Marth, Gabor T; Clark, Andrew G; Yu, Fuli; Gibbs, Richard A; Bustamante, Carlos D

2011-07-19

High-throughput sequencing technology enables population-level surveys of human genomic variation. Here, we examine the joint allele frequency distributions across continental human populations and present an approach for combining complementary aspects of whole-genome, low-coverage data and targeted high-coverage data. We apply this approach to data generated by the pilot phase of the Thousand Genomes Project, including whole-genome 2-4× coverage data for 179 samples from HapMap European, Asian, and African panels as well as high-coverage target sequencing of the exons of 800 genes from 697 individuals in seven populations. We use the site frequency spectra obtained from these data to infer demographic parameters for an Out-of-Africa model for populations of African, European, and Asian descent and to predict, by a jackknife-based approach, the amount of genetic diversity that will be discovered as sample sizes are increased. We predict that the number of discovered nonsynonymous coding variants will reach 100,000 in each population after ∼1,000 sequenced chromosomes per population, whereas ∼2,500 chromosomes will be needed for the same number of synonymous variants. Beyond this point, the number of segregating sites in the European and Asian panel populations is expected to overcome that of the African panel because of faster recent population growth. Overall, we find that the majority of human genomic variable sites are rare and exhibit little sharing among diverged populations. Our results emphasize that replication of disease association for specific rare genetic variants across diverged populations must overcome both reduced statistical power because of rarity and higher population divergence.

Demographic history and rare allele sharing among human populations

PubMed Central

Gravel, Simon; Henn, Brenna M.; Gutenkunst, Ryan N.; Indap, Amit R.; Marth, Gabor T.; Clark, Andrew G.; Yu, Fuli; Gibbs, Richard A.; Bustamante, Carlos D.; Altshuler, David L.; Durbin, Richard M.; Abecasis, Gonçalo R.; Bentley, David R.; Chakravarti, Aravinda; Clark, Andrew G.; Collins, Francis S.; De La Vega, Francisco M.; Donnelly, Peter; Egholm, Michael; Flicek, Paul; Gabriel, Stacey B.; Gibbs, Richard A.; Knoppers, Bartha M.; Lander, Eric S.; Lehrach, Hans; Mardis, Elaine R.; McVean, Gil A.; Nickerson, Debbie A.; Peltonen, Leena; Schafer, Alan J.; Sherry, Stephen T.; Wang, Jun; Wilson, Richard K.; Gibbs, Richard A.; Deiros, David; Metzker, Mike; Muzny, Donna; Reid, Jeff; Wheeler, David; Wang, Jun; Li, Jingxiang; Jian, Min; Li, Guoqing; Li, Ruiqiang; Liang, Huiqing; Tian, Geng; Wang, Bo; Wang, Jian; Wang, Wei; Yang, Huanming; Zhang, Xiuqing; Zheng, Huisong; Lander, Eric S.; Altshuler, David L.; Ambrogio, Lauren; Bloom, Toby; Cibulskis, Kristian; Fennell, Tim J.; Gabriel, Stacey B.; Jaffe, David B.; Shefler, Erica; Sougnez, Carrie L.; Bentley, David R.; Gormley, Niall; Humphray, Sean; Kingsbury, Zoya; Koko-Gonzales, Paula; Stone, Jennifer; McKernan, Kevin J.; Costa, Gina L.; Ichikawa, Jeffry K.; Lee, Clarence C.; Sudbrak, Ralf; Lehrach, Hans; Borodina, Tatiana A.; Dahl, Andreas; Davydov, Alexey N.; Marquardt, Peter; Mertes, Florian; Nietfeld, Wilfiried; Rosenstiel, Philip; Schreiber, Stefan; Soldatov, Aleksey V.; Timmermann, Bernd; Tolzmann, Marius; Egholm, Michael; Affourtit, Jason; Ashworth, Dana; Attiya, Said; Bachorski, Melissa; Buglione, Eli; Burke, Adam; Caprio, Amanda; Celone, Christopher; Clark, Shauna; Conners, David; Desany, Brian; Gu, Lisa; Guccione, Lorri; Kao, Kalvin; Kebbel, Andrew; Knowlton, Jennifer; Labrecque, Matthew; McDade, Louise; Mealmaker, Craig; Minderman, Melissa; Nawrocki, Anne; Niazi, Faheem; Pareja, Kristen; Ramenani, Ravi; Riches, David; Song, Wanmin; Turcotte, Cynthia; Wang, Shally; Mardis, Elaine R.; Wilson, Richard K.; Dooling, David; Fulton, Lucinda; Fulton, Robert; Weinstock, George; Durbin, Richard M.; Burton, John; Carter, David M.; Churcher, Carol; Coffey, Alison; Cox, Anthony; Palotie, Aarno; Quail, Michael; Skelly, Tom; Stalker, James; Swerdlow, Harold P.; Turner, Daniel; De Witte, Anniek; Giles, Shane; Gibbs, Richard A.; Wheeler, David; Bainbridge, Matthew; Challis, Danny; Sabo, Aniko; Yu, Fuli; Yu, Jin; Wang, Jun; Fang, Xiaodong; Guo, Xiaosen; Li, Ruiqiang; Li, Yingrui; Luo, Ruibang; Tai, Shuaishuai; Wu, Honglong; Zheng, Hancheng; Zheng, Xiaole; Zhou, Yan; Li, Guoqing; Wang, Jian; Yang, Huanming; Marth, Gabor T.; Garrison, Erik P.; Huang, Weichun; Indap, Amit; Kural, Deniz; Lee, Wan-Ping; Leong, Wen Fung; Quinlan, Aaron R.; Stewart, Chip; Stromberg, Michael P.; Ward, Alistair N.; Wu, Jiantao; Lee, Charles; Mills, Ryan E.; Shi, Xinghua; Daly, Mark J.; DePristo, Mark A.; Altshuler, David L.; Ball, Aaron D.; Banks, Eric; Bloom, Toby; Browning, Brian L.; Cibulskis, Kristian; Fennell, Tim J.; Garimella, Kiran V.; Grossman, Sharon R.; Handsaker, Robert E.; Hanna, Matt; Hartl, Chris; Jaffe, David B.; Kernytsky, Andrew M.; Korn, Joshua M.; Li, Heng; Maguire, Jared R.; McCarroll, Steven A.; McKenna, Aaron; Nemesh, James C.; Philippakis, Anthony A.; Poplin, Ryan E.; Price, Alkes; Rivas, Manuel A.; Sabeti, Pardis C.; Schaffner, Stephen F.; Shefler, Erica; Shlyakhter, Ilya A.; Cooper, David N.; Ball, Edward V.; Mort, Matthew; Phillips, Andrew D.; Stenson, Peter D.; Sebat, Jonathan; Makarov, Vladimir; Ye, Kenny; Yoon, Seungtai C.; Bustamante, Carlos D.; Clark, Andrew G.; Boyko, Adam; Degenhardt, Jeremiah; Gravel, Simon; Gutenkunst, Ryan N.; Kaganovich, Mark; Keinan, Alon; Lacroute, Phil; Ma, Xin; Reynolds, Andy; Clarke, Laura; Flicek, Paul; Cunningham, Fiona; Herrero, Javier; Keenen, Stephen; Kulesha, Eugene; Leinonen, Rasko; McLaren, William M.; Radhakrishnan, Rajesh; Smith, Richard E.; Zalunin, Vadim; Zheng-Bradley, Xiangqun; Korbel, Jan O.; Stütz, Adrian M.; Humphray, Sean; Bauer, Markus; Cheetham, R. Keira; Cox, Tony; Eberle, Michael; James, Terena; Kahn, Scott; Murray, Lisa; Chakravarti, Aravinda; Ye, Kai; De La Vega, Francisco M.; Fu, Yutao; Hyland, Fiona C. L.; Manning, Jonathan M.; McLaughlin, Stephen F.; Peckham, Heather E.; Sakarya, Onur; Sun, Yongming A.; Tsung, Eric F.; Batzer, Mark A.; Konkel, Miriam K.; Walker, Jerilyn A.; Sudbrak, Ralf; Albrecht, Marcus W.; Amstislavskiy, Vyacheslav S.; Herwig, Ralf; Parkhomchuk, Dimitri V.; Sherry, Stephen T.; Agarwala, Richa; Khouri, Hoda M.; Morgulis, Aleksandr O.; Paschall, Justin E.; Phan, Lon D.; Rotmistrovsky, Kirill E.; Sanders, Robert D.; Shumway, Martin F.; Xiao, Chunlin; McVean, Gil A.; Auton, Adam; Iqbal, Zamin; Lunter, Gerton; Marchini, Jonathan L.; Moutsianas, Loukas; Myers, Simon; Tumian, Afidalina; Desany, Brian; Knight, James; Winer, Roger; Craig, David W.; Beckstrom-Sternberg, Steve M.; Christoforides, Alexis; Kurdoglu, Ahmet A.; Pearson, John V.; Sinari, Shripad A.; Tembe, Waibhav D.; Haussler, David; Hinrichs, Angie S.; Katzman, Sol J.; Kern, Andrew; Kuhn, Robert M.; Przeworski, Molly; Hernandez, Ryan D.; Howie, Bryan; Kelley, Joanna L.; Melton, S. Cord; Abecasis, Gonçalo R.; Li, Yun; Anderson, Paul; Blackwell, Tom; Chen, Wei; Cookson, William O.; Ding, Jun; Kang, Hyun Min; Lathrop, Mark; Liang, Liming; Moffatt, Miriam F.; Scheet, Paul; Sidore, Carlo; Snyder, Matthew; Zhan, Xiaowei; Zöllner, Sebastian; Awadalla, Philip; Casals, Ferran; Idaghdour, Youssef; Keebler, John; Stone, Eric A.; Zilversmit, Martine; Jorde, Lynn; Xing, Jinchuan; Eichler, Evan E.; Aksay, Gozde; Alkan, Can; Hajirasouliha, Iman; Hormozdiari, Fereydoun; Kidd, Jeffrey M.; Sahinalp, S. Cenk; Sudmant, Peter H.; Mardis, Elaine R.; Chen, Ken; Chinwalla, Asif; Ding, Li; Koboldt, Daniel C.; McLellan, Mike D.; Dooling, David; Weinstock, George; Wallis, John W.; Wendl, Michael C.; Zhang, Qunyuan; Durbin, Richard M.; Albers, Cornelis A.; Ayub, Qasim; Balasubramaniam, Senduran; Barrett, Jeffrey C.; Carter, David M.; Chen, Yuan; Conrad, Donald F.; Danecek, Petr; Dermitzakis, Emmanouil T.; Hu, Min; Huang, Ni; Hurles, Matt E.; Jin, Hanjun; Jostins, Luke; Keane, Thomas M.; Le, Si Quang; Lindsay, Sarah; Long, Quan; MacArthur, Daniel G.; Montgomery, Stephen B.; Parts, Leopold; Stalker, James; Tyler-Smith, Chris; Walter, Klaudia; Zhang, Yujun; Gerstein, Mark B.; Snyder, Michael; Abyzov, Alexej; Balasubramanian, Suganthi; Bjornson, Robert; Du, Jiang; Grubert, Fabian; Habegger, Lukas; Haraksingh, Rajini; Jee, Justin; Khurana, Ekta; Lam, Hugo Y. K.; Leng, Jing; Mu, Xinmeng Jasmine; Urban, Alexander E.; Zhang, Zhengdong; Li, Yingrui; Luo, Ruibang; Marth, Gabor T.; Garrison, Erik P.; Kural, Deniz; Quinlan, Aaron R.; Stewart, Chip; Stromberg, Michael P.; Ward, Alistair N.; Wu, Jiantao; Lee, Charles; Mills, Ryan E.; Shi, Xinghua; McCarroll, Steven A.; Banks, Eric; DePristo, Mark A.; Handsaker, Robert E.; Hartl, Chris; Korn, Joshua M.; Li, Heng; Nemesh, James C.; Sebat, Jonathan; Makarov, Vladimir; Ye, Kenny; Yoon, Seungtai C.; Degenhardt, Jeremiah; Kaganovich, Mark; Clarke, Laura; Smith, Richard E.; Zheng-Bradley, Xiangqun; Korbel, Jan O.; Humphray, Sean; Cheetham, R. Keira; Eberle, Michael; Kahn, Scott; Murray, Lisa; Ye, Kai; De La Vega, Francisco M.; Fu, Yutao; Peckham, Heather E.; Sun, Yongming A.; Batzer, Mark A.; Konkel, Miriam K.; Walker, Jerilyn A.; Xiao, Chunlin; Iqbal, Zamin; Desany, Brian; Blackwell, Tom; Snyder, Matthew; Xing, Jinchuan; Eichler, Evan E.; Aksay, Gozde; Alkan, Can; Hajirasouliha, Iman; Hormozdiari, Fereydoun; Kidd, Jeffrey M.; Chen, Ken; Chinwalla, Asif; Ding, Li; McLellan, Mike D.; Wallis, John W.; Hurles, Matt E.; Conrad, Donald F.; Walter, Klaudia; Zhang, Yujun; Gerstein, Mark B.; Snyder, Michael; Abyzov, Alexej; Du, Jiang; Grubert, Fabian; Haraksingh, Rajini; Jee, Justin; Khurana, Ekta; Lam, Hugo Y. K.; Leng, Jing; Mu, Xinmeng Jasmine; Urban, Alexander E.; Zhang, Zhengdong; Gibbs, Richard A.; Bainbridge, Matthew; Challis, Danny; Coafra, Cristian; Dinh, Huyen; Kovar, Christie; Lee, Sandy; Muzny, Donna; Nazareth, Lynne; Reid, Jeff; Sabo, Aniko; Yu, Fuli; Yu, Jin; Marth, Gabor T.; Garrison, Erik P.; Indap, Amit; Leong, Wen Fung; Quinlan, Aaron R.; Stewart, Chip; Ward, Alistair N.; Wu, Jiantao; Cibulskis, Kristian; Fennell, Tim J.; Gabriel, Stacey B.; Garimella, Kiran V.; Hartl, Chris; Shefler, Erica; Sougnez, Carrie L.; Wilkinson, Jane; Clark, Andrew G.; Gravel, Simon; Grubert, Fabian; Clarke, Laura; Flicek, Paul; Smith, Richard E.; Zheng-Bradley, Xiangqun; Sherry, Stephen T.; Khouri, Hoda M.; Paschall, Justin E.; Shumway, Martin F.; Xiao, Chunlin; McVean, Gil A.; Katzman, Sol J.; Abecasis, Gonçalo R.; Blackwell, Tom; Mardis, Elaine R.; Dooling, David; Fulton, Lucinda; Fulton, Robert; Koboldt, Daniel C.; Durbin, Richard M.; Balasubramaniam, Senduran; Coffey, Allison; Keane, Thomas M.; MacArthur, Daniel G.; Palotie, Aarno; Scott, Carol; Stalker, James; Tyler-Smith, Chris; Gerstein, Mark B.; Balasubramanian, Suganthi; Chakravarti, Aravinda; Knoppers, Bartha M.; Abecasis, Gonçalo R.; Bustamante, Carlos D.; Gharani, Neda; Gibbs, Richard A.; Jorde, Lynn; Kaye, Jane S.; Kent, Alastair; Li, Taosha; McGuire, Amy L.; McVean, Gil A.; Ossorio, Pilar N.; Rotimi, Charles N.; Su, Yeyang; Toji, Lorraine H.; TylerSmith, Chris; Brooks, Lisa D.; Felsenfeld, Adam L.; McEwen, Jean E.; Abdallah, Assya; Juenger, Christopher R.; Clemm, Nicholas C.; Collins, Francis S.; Duncanson, Audrey; Green, Eric D.; Guyer, Mark S.; Peterson, Jane L.; Schafer, Alan J.; Abecasis, Gonçalo R.; Altshuler, David L.; Auton, Adam; Brooks, Lisa D.; Durbin, Richard M.; Gibbs, Richard A.; Hurles, Matt E.; McVean, Gil A.

2011-01-01

High-throughput sequencing technology enables population-level surveys of human genomic variation. Here, we examine the joint allele frequency distributions across continental human populations and present an approach for combining complementary aspects of whole-genome, low-coverage data and targeted high-coverage data. We apply this approach to data generated by the pilot phase of the Thousand Genomes Project, including whole-genome 2–4× coverage data for 179 samples from HapMap European, Asian, and African panels as well as high-coverage target sequencing of the exons of 800 genes from 697 individuals in seven populations. We use the site frequency spectra obtained from these data to infer demographic parameters for an Out-of-Africa model for populations of African, European, and Asian descent and to predict, by a jackknife-based approach, the amount of genetic diversity that will be discovered as sample sizes are increased. We predict that the number of discovered nonsynonymous coding variants will reach 100,000 in each population after ∼1,000 sequenced chromosomes per population, whereas ∼2,500 chromosomes will be needed for the same number of synonymous variants. Beyond this point, the number of segregating sites in the European and Asian panel populations is expected to overcome that of the African panel because of faster recent population growth. Overall, we find that the majority of human genomic variable sites are rare and exhibit little sharing among diverged populations. Our results emphasize that replication of disease association for specific rare genetic variants across diverged populations must overcome both reduced statistical power because of rarity and higher population divergence. PMID:21730125

Coexisting oak species, including rear-edge populations, buffer climate stress through xylem adjustments.

PubMed

Granda, E; Alla, A Q; Laskurain, N A; Loidi, J; Sánchez-Lorenzo, A; Camarero, J J

2018-02-01

The ability of trees to cope with climate change is a pivotal feature of forest ecosystems, especially for rear-edge populations facing warm and dry conditions. To evaluate current and future forests threats, a multi-proxy focus on the growth, anatomical and physiological responses to climate change is needed. We examined the long-term xylem adjustments to climate variability of the temperate Quercus robur L. at its rear edge and the sub-Mediterranean Quercus pyrenaica Willd. Both species coexist at a mesic (ME, humid and warmer) and a xeric (XE, dry and cooler) site in northern Spain, the latter experiencing increasing temperatures in recent decades. We compared xylem traits at each site and assessed their trends, relationships and responses to climate (1960-2008). Traits included basal area increment, earlywood vessel hydraulic diameter, density and theoretical-specific hydraulic conductivity together with latewood oxygen (δ18O) stable isotopes and δ13C-derived water-use efficiency (iWUE). Quercus robur showed the highest growth at ME, likely through enhanced cambial activity. Quercus pyrenaica had higher iWUE at XE compared with ME, but limited plasticity of anatomical xylem traits was found for the two oak species. Similar physiological performance was found for both species. The iWUE augmented in recent years especially at XE, likely explained by stomatal closure given the increasing δ18O signal in response to drier and sunnier growing seasons. Overall, traits were more correlated at XE than at ME. The iWUE improvements were linked to higher growth up to a threshold (~85 μmol mol-1) after which reduced growth was found at XE. Our results are consistent with Q. pyrenaica and Q. robur coexisting at the central and dry edge of the climatic species distribution, respectively, showing similar responses to buffer warmer conditions. In fact, the observed adjustments found for Q. robur point towards growth stability of similar rear-edge oak populations under

Calculation of ground state rotational populations for kinetic gas homonuclear diatomic molecules including electron-impact excitation and wall collisions.

PubMed

Farley, David R

2010-09-07

A model has been developed to calculate the ground state rotational populations of homonuclear diatomic molecules in kinetic gases, including the effects of electron-impact excitation, wall collisions, and gas feed rate. The equations are exact within the accuracy of the cross sections used and of the assumed equilibrating effect of wall collisions. It is found that the inflow of feed gas and equilibrating wall collisions can significantly affect the rotational distribution in competition with nonequilibrating electron-impact effects. The resulting steady-state rotational distributions are generally Boltzmann for N≥3, with a rotational temperature between the wall and feed gas temperatures. The N=0,1,2 rotational level populations depend sensitively on the relative rates of electron-impact excitation versus wall collision and gas feed rates.

Effectiveness and cost-effectiveness of nationwide campaigns for awareness and case finding of hepatitis C targeted at people who inject drugs and the general population in the Netherlands.

PubMed

Helsper, Charles W; Janssen, Mart P; van Essen, Gerrit A; Croes, Esther A; van der Veen, Clary; de Wit, Ardine G; de Wit, Niek J

2017-09-01

Hepatitis C virus infection (HCV) is a serious, but underdiagnosed disease that can generally be treated successfully. Therefore, a nationwide HCV awareness campaign was implemented in the Netherlands targeting people who inject drugs (PWID) in addiction care ('PWID intervention') and high-risk groups in the general population ('public intervention'). The objective of this study is to assess the effectiveness and cost-effectiveness of the interventions used in this campaign. For the 'PWID' intervention, all addiction care centres in the Netherlands provided proactive individual HCV consultation and testing. The 'public intervention' consisted of health education through mass media and instruction of health care professionals. A Markov chain model was used to estimate incremental cost-effectiveness ratios (ICER, cost per QALY gained). We included a 'DAA treatment' scenario to estimate the effect of these treatment strategies on cost-effectiveness. The 'PWID intervention' identified 257 additional HCV-carriers. The ICER was €9056 (95% CI: €6043-€13,523) when compared to 'no intervention'. The 'public intervention' identified 38 additional HCV-carriers. The ICER was €18,421 (95% CI: €7376-€25,490,119) when compared to 'no intervention'. Probabilistic sensitivity analysis showed that the probability that the 'PWID intervention' was cost-effective was 100%. It also showed a probability of 34% that the 'public intervention' did not exceed the Dutch threshold for cost-effectiveness (€20,000). New treatment regimens are likely to improve cost-effectiveness of this strategy. In a nationwide HCV awareness and case finding campaign, the intervention targeting PWID was effective and cost-effective. An intervention targeting risk groups in the general population showed only a modest effect and is therefore less likely to be cost-effective. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Morphology of meteoroid and space debris craters on LDEF metal targets

NASA Technical Reports Server (NTRS)

Love, S. G.; Brownlee, D. E.; King, N. L.; Hoerz, F.

1994-01-01

We measured the depths, average diameters, and circularity indices of over 600 micrometeoroid and space debris craters on various metal surfaces exposed to space on the Long Duration Exposure Facility (LDEF) satellite, as a test of some of the formalisms used to convert the diameters of craters on space-exposed surfaces into penetration depths for the purpose of calculating impactor sizes or masses. The topics covered include the following: targe materials orientation; crater measurements and sample populations; effects of oblique impacts; effects of projectile velocity; effects of crater size; effects of target hardness; effects of target density; and effects of projectile properties.

Targeting Membrane-Bound Viral RNA Synthesis Reveals Potent Inhibition of Diverse Coronaviruses Including the Middle East Respiratory Syndrome Virus

PubMed Central

Bergström, Tomas; Kann, Nina; Adamiak, Beata; Hannoun, Charles; Kindler, Eveline; Jónsdóttir, Hulda R.; Muth, Doreen; Kint, Joeri; Forlenza, Maria; Müller, Marcel A.; Drosten, Christian; Thiel, Volker; Trybala, Edward

2014-01-01

Coronaviruses raise serious concerns as emerging zoonotic viruses without specific antiviral drugs available. Here we screened a collection of 16671 diverse compounds for anti-human coronavirus 229E activity and identified an inhibitor, designated K22, that specifically targets membrane-bound coronaviral RNA synthesis. K22 exerts most potent antiviral activity after virus entry during an early step of the viral life cycle. Specifically, the formation of double membrane vesicles (DMVs), a hallmark of coronavirus replication, was greatly impaired upon K22 treatment accompanied by near-complete inhibition of viral RNA synthesis. K22-resistant viruses contained substitutions in non-structural protein 6 (nsp6), a membrane-spanning integral component of the viral replication complex implicated in DMV formation, corroborating that K22 targets membrane bound viral RNA synthesis. Besides K22 resistance, the nsp6 mutants induced a reduced number of DMVs, displayed decreased specific infectivity, while RNA synthesis was not affected. Importantly, K22 inhibits a broad range of coronaviruses, including Middle East respiratory syndrome coronavirus (MERS–CoV), and efficient inhibition was achieved in primary human epithelia cultures representing the entry port of human coronavirus infection. Collectively, this study proposes an evolutionary conserved step in the life cycle of positive-stranded RNA viruses, the recruitment of cellular membranes for viral replication, as vulnerable and, most importantly, druggable target for antiviral intervention. We expect this mode of action to serve as a paradigm for the development of potent antiviral drugs to combat many animal and human virus infections. PMID:24874215

Estimating changes in urban land and urban population using refined areal interpolation techniques

NASA Astrophysics Data System (ADS)

Zoraghein, Hamidreza; Leyk, Stefan

2018-05-01

The analysis of changes in urban land and population is important because the majority of future population growth will take place in urban areas. U.S. Census historically classifies urban land using population density and various land-use criteria. This study analyzes the reliability of census-defined urban lands for delineating the spatial distribution of urban population and estimating its changes over time. To overcome the problem of incompatible enumeration units between censuses, regular areal interpolation methods including Areal Weighting (AW) and Target Density Weighting (TDW), with and without spatial refinement, are implemented. The goal in this study is to estimate urban population in Massachusetts in 1990 and 2000 (source zones), within tract boundaries of the 2010 census (target zones), respectively, to create a consistent time series of comparable urban population estimates from 1990 to 2010. Spatial refinement is done using ancillary variables such as census-defined urban areas, the National Land Cover Database (NLCD) and the Global Human Settlement Layer (GHSL) as well as different combinations of them. The study results suggest that census-defined urban areas alone are not necessarily the most meaningful delineation of urban land. Instead, it appears that alternative combinations of the above-mentioned ancillary variables can better depict the spatial distribution of urban land, and thus make it possible to reduce the estimation error in transferring the urban population from source zones to target zones when running spatially-refined temporal areal interpolation.

Assessing Coverage of Population-Based and Targeted Fortification Programs with the Use of the Fortification Assessment Coverage Toolkit (FACT): Background, Toolkit Development, and Supplement Overview.

PubMed

Friesen, Valerie M; Aaron, Grant J; Myatt, Mark; Neufeld, Lynnette M

2017-05-01

Food fortification is a widely used approach to increase micronutrient intake in the diet. High coverage is essential for achieving impact. Data on coverage is limited in many countries, and tools to assess coverage of fortification programs have not been standardized. In 2013, the Global Alliance for Improved Nutrition developed the Fortification Assessment Coverage Toolkit (FACT) to carry out coverage assessments in both population-based (i.e., staple foods and/or condiments) and targeted (e.g., infant and young child) fortification programs. The toolkit was designed to generate evidence on program coverage and the use of fortified foods to provide timely and programmatically relevant information for decision making. This supplement presents results from FACT surveys that assessed the coverage of population-based and targeted food fortification programs across 14 countries. It then discusses the policy and program implications of the findings for the potential for impact and program improvement.

Molecular characterization of oral squamous cell carcinoma using targeted next-generation sequencing.

PubMed

Er, Tze-Kiong; Wang, Yen-Yun; Chen, Chih-Chieh; Herreros-Villanueva, Marta; Liu, Ta-Chih; Yuan, Shyng-Shiou F

2015-10-01

Many genetic factors play an important role in the development of oral squamous cell carcinoma. The aim of this study was to assess the mutational profile in oral squamous cell carcinoma using formalin-fixed, paraffin-embedded tumors from a Taiwanese population by performing targeted sequencing of 26 cancer-associated genes that are frequently mutated in solid tumors. Next-generation sequencing was performed in 50 formalin-fixed, paraffin-embedded tumor specimens obtained from patients with oral squamous cell carcinoma. Genetic alterations in the 26 cancer-associated genes were detected using a deep sequencing (>1000X) approach. TP53, PIK3CA, MET, APC, CDH1, and FBXW7 were most frequently mutated genes. Most remarkably, TP53 mutations and PIK3CA mutations, which accounted for 68% and 18% of tumors, respectively, were more prevalent in a Taiwanese population. Other genes including MET (4%), APC (4%), CDH1 (2%), and FBXW7 (2%) were identified in our population. In summary, our study shows the feasibility of performing targeted sequencing using formalin-fixed, paraffin-embedded samples. Additionally, this study also reports the mutational landscape of oral squamous cell carcinoma in the Taiwanese population. We believe that this study will shed new light on fundamental aspects in understanding the molecular pathogenesis of oral squamous cell carcinoma and may aid in the development of new targeted therapies. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Highly targeted cholera vaccination campaigns in urban setting are feasible: The experience in Kalemie, Democratic Republic of Congo

PubMed Central

Massing, Louis Albert; Aboubakar, Soumah; Page, Anne-Laure; Cohuet, Sandra; Ngandwe, Adalbert; Mukomena Sompwe, Eric; Ramazani, Romain; Allheimen, Marcela; Levaillant, Philippe; Lechevalier, Pauline; Kashimi, Marie; de la Motte, Axelle; Calmejane, Arielle; Bouhenia, Malika; Dabire, Ernest; Bompangue, Didier; Kebela, Benoit; Porten, Klaudia

2018-01-01

Introduction Oral cholera vaccines are primarily recommended by the World Health Organization for cholera control in endemic countries. However, the number of cholera vaccines currently produced is very limited and examples of OCV use in endemic countries, and especially in urban settings, are scarce. A vaccination campaign was organized by Médecins Sans Frontières and the Ministry of Health in a highly endemic area in the Democratic Republic of Congo. This study aims to describe the vaccine coverage achieved with this highly targeted vaccination campaign and the acceptability among the vaccinated communities. Methods and findings We performed a cross-sectional survey using random spatial sampling. The study population included individuals one year old and above, eligible for vaccination, and residing in the areas targeted for vaccination in the city of Kalemie. Data sources were household interviews with verification by vaccination card. In total 2,488 people were included in the survey. Overall, 81.9% (95%CI: 77.9–85.3) of the target population received at least one dose of vaccine. The vaccine coverage with two doses was 67.2% (95%CI: 61.9–72.0) among the target population. The vaccine coverage was higher during the first round (74.0, 95%CI: 69.3–78.3) than during the second round of vaccination (69.1%, 95%CI: 63.9–74.0). Vaccination coverage was lower in male adults. The main reason for non-vaccination was to be absent during the campaign. No severe adverse events were notified during the interviews. Conclusions Cholera vaccination campaigns using highly targeted strategies are feasible in urban settings. High vaccination coverage can be obtained using door to door vaccination. However, alternative strategies should be considered to reach non-vaccinated populations like male adults and also in order to improve the efficiency of the interventions. PMID:29734337

Nuclear reactor target assemblies, nuclear reactor configurations, and methods for producing isotopes, modifying materials within target material, and/or characterizing material within a target material

DOE Office of Scientific and Technical Information (OSTI.GOV)

Toth, James J.; Wall, Donald; Wittman, Richard S.

Target assemblies are provided that can include a uranium-comprising annulus. The assemblies can include target material consisting essentially of non-uranium material within the volume of the annulus. Reactors are disclosed that can include one or more discrete zones configured to receive target material. At least one uranium-comprising annulus can be within one or more of the zones. Methods for producing isotopes within target material are also disclosed, with the methods including providing neutrons to target material within a uranium-comprising annulus. Methods for modifying materials within target material are disclosed as well as are methods for characterizing material within a targetmore » material.« less

Planar optical waveguide based sandwich assay sensors and processes for the detection of biological targets including early detection of cancers

DOEpatents

Martinez, Jennifer S [Santa Fe, NM; Swanson, Basil I [Los Alamos, NM; Shively, John E [Arcadia, CA; Li, Lin [Monrovia, CA

2009-06-02

An assay element is described including recognition ligands adapted for binding to carcinoembryonic antigen (CEA) bound to a film on a single mode planar optical waveguide, the film from the group of a membrane, a polymerized bilayer membrane, and a self-assembled monolayer containing polyethylene glycol or polypropylene glycol groups therein and an assay process for detecting the presence of CEA is described including injecting a possible CEA-containing sample into a sensor cell including the assay element, maintaining the sample within the sensor cell for time sufficient for binding to occur between CEA present within the sample and the recognition ligands, injecting a solution including a reporter ligand into the sensor cell; and, interrogating the sample within the sensor cell with excitation light from the waveguide, the excitation light provided by an evanescent field of the single mode penetrating into the biological target-containing sample to a distance of less than about 200 nanometers from the waveguide thereby exciting any bound reporter ligand within a distance of less than about 200 nanometers from the waveguide and resulting in a detectable signal.

Enhancing the population impact of collaborative care interventions: Mixed method development and implementation of stepped care targeting posttraumatic stress disorder and related comorbidities after acute trauma

PubMed Central

Zatzick, Douglas; Rivara, Frederick; Jurkovich, Gregory; Russo, Joan; Trusz, Sarah Geiss; Wang, Jin; Wagner, Amy; Stephens, Kari; Dunn, Chris; Uehara, Edwina; Petrie, Megan; Engel, Charles; Davydow, Dimitri; Katon, Wayne

2011-01-01

Objective To develop and implement a stepped collaborative care intervention targeting PTSD and related co-morbidities to enhance the population impact of early trauma-focused interventions. Method We describe the design and implementation of the Trauma Survivors Outcomes & Support Study (TSOS II). An interdisciplinary treatment development team was comprised of trauma surgical, clinical psychiatric and mental health services “change agents” who spanned the boundaries between front-line trauma center clinical care and acute care policy. Mixed method clinical epidemiologic and clinical ethnographic studies informed the development of PTSD screening and intervention procedures. Results Two-hundred and seven acutely injured trauma survivors with high early PTSD symptom levels were randomized into the study. The stepped collaborative care model integrated care management (i.e., posttraumatic concern elicitation and amelioration, motivational interviewing, and behavioral activation) with cognitive behavioral therapy and pharmacotherapy targeting PTSD. The model was feasibly implemented by front-line acute care MSW and ARNP providers. Conclusions Stepped care protocols targeting PTSD may enhance the population impact of early interventions developed for survivors of individual and mass trauma by extending the reach of collaborative care interventions to acute care medical settings and other non-specialty posttraumatic contexts. PMID:21596205

Use of an activated beta-catenin to identify Wnt pathway target genes in caenorhabditis elegans, including a subset of collagen genes expressed in late larval development.

PubMed

Jackson, Belinda M; Abete-Luzi, Patricia; Krause, Michael W; Eisenmann, David M

2014-04-16

The Wnt signaling pathway plays a fundamental role during metazoan development, where it regulates diverse processes, including cell fate specification, cell migration, and stem cell renewal. Activation of the beta-catenin-dependent/canonical Wnt pathway up-regulates expression of Wnt target genes to mediate a cellular response. In the nematode Caenorhabditis elegans, a canonical Wnt signaling pathway regulates several processes during larval development; however, few target genes of this pathway have been identified. To address this deficit, we used a novel approach of conditionally activated Wnt signaling during a defined stage of larval life by overexpressing an activated beta-catenin protein, then used microarray analysis to identify genes showing altered expression compared with control animals. We identified 166 differentially expressed genes, of which 104 were up-regulated. A subset of the up-regulated genes was shown to have altered expression in mutants with decreased or increased Wnt signaling; we consider these genes to be bona fide C. elegans Wnt pathway targets. Among these was a group of six genes, including the cuticular collagen genes, bli-1 col-38, col-49, and col-71. These genes show a peak of expression in the mid L4 stage during normal development, suggesting a role in adult cuticle formation. Consistent with this finding, reduction of function for several of the genes causes phenotypes suggestive of defects in cuticle function or integrity. Therefore, this work has identified a large number of putative Wnt pathway target genes during larval life, including a small subset of Wnt-regulated collagen genes that may function in synthesis of the adult cuticle.

Translational research: precision medicine, personalized medicine, targeted therapies: marketing or science?

PubMed

Marquet, Pierre; Longeray, Pierre-Henry; Barlesi, Fabrice; Ameye, Véronique; Augé, Pascale; Cazeneuve, Béatrice; Chatelut, Etienne; Diaz, Isabelle; Diviné, Marine; Froguel, Philippe; Goni, Sylvia; Gueyffier, François; Hoog-Labouret, Natalie; Mourah, Samia; Morin-Surroca, Michèle; Perche, Olivier; Perin-Dureau, Florent; Pigeon, Martine; Tisseau, Anne; Verstuyft, Céline

2015-01-01

Personalized medicine is based on: 1) improved clinical or non-clinical methods (including biomarkers) for a more discriminating and precise diagnosis of diseases; 2) targeted therapies of the choice or the best drug for each patient among those available; 3) dose adjustment methods to optimize the benefit-risk ratio of the drugs chosen; 4) biomarkers of efficacy, toxicity, treatment discontinuation, relapse, etc. Unfortunately, it is still too often a theoretical concept because of the lack of convenient diagnostic methods or treatments, particularly of drugs corresponding to each subtype of pathology, hence to each patient. Stratified medicine is a component of personalized medicine employing biomarkers and companion diagnostics to target the patients likely to present the best benefit-risk balance for a given active compound. The concept of targeted therapy, mostly used in cancer treatment, relies on the existence of a defined molecular target, involved or not in the pathological process, and/or on the existence of a biomarker able to identify the target population, which should logically be small as compared to the population presenting the disease considered. Targeted therapies and biomarkers represent important stakes for the pharmaceutical industry, in terms of market access, of return on investment and of image among the prescribers. At the same time, they probably represent only the first generation of products resulting from the combination of clinical, pathophysiological and molecular research, i.e. of translational research. © 2015 Société Française de Pharmacologie et de Thérapeutique.

Fillers in the skin of color population.

PubMed

Heath, Candrice R; Taylor, Susan C

2011-05-01

The skin of color population in the United States is rapidly growing and the cosmetic industry is responding to the demand for skin of color targeted treatments. The aging face in skin of color patients has a unique pattern that can be successfully augmented by dermal fillers. Though many subjects with skin of color were not included in the pre-market dermal filler clinical trials, some post-market studies have examined the safety and risks of adverse events in this population. The safety data from a selection of these studies was examined. Though pigmentary changes occurred, there have been no reports of keloid development. Developing a patient-specific care plan and instituting close follow up is emphasized.

Microsatellites as targets of natural selection.

PubMed

Haasl, Ryan J; Payseur, Bret A

2013-02-01

The ability to survey polymorphism on a genomic scale has enabled genome-wide scans for the targets of natural selection. Theory that connects patterns of genetic variation to evidence of natural selection most often assumes a diallelic locus and no recurrent mutation. Although these assumptions are suitable to selection that targets single nucleotide variants, fundamentally different types of mutation generate abundant polymorphism in genomes. Moreover, recent empirical results suggest that mutationally complex, multiallelic loci including microsatellites and copy number variants are sometimes targeted by natural selection. Given their abundance, the lack of inference methods tailored to the mutational peculiarities of these types of loci represents a notable gap in our ability to interrogate genomes for signatures of natural selection. Previous theoretical investigations of mutation-selection balance at multiallelic loci include assumptions that limit their application to inference from empirical data. Focusing on microsatellites, we assess the dynamics and population-level consequences of selection targeting mutationally complex variants. We develop general models of a multiallelic fitness surface, a realistic model of microsatellite mutation, and an efficient simulation algorithm. Using these tools, we explore mutation-selection-drift equilibrium at microsatellites and investigate the mutational history and selective regime of the microsatellite that causes Friedreich's ataxia. We characterize microsatellite selective events by their duration and cost, note similarities to sweeps from standing point variation, and conclude that it is premature to label microsatellites as ubiquitous agents of efficient adaptive change. Together, our models and simulation algorithm provide a powerful framework for statistical inference, which can be used to test the neutrality of microsatellites and other multiallelic variants.

Microsatellites as Targets of Natural Selection

PubMed Central

Haasl, Ryan J.; Payseur, Bret A.

2013-01-01

The ability to survey polymorphism on a genomic scale has enabled genome-wide scans for the targets of natural selection. Theory that connects patterns of genetic variation to evidence of natural selection most often assumes a diallelic locus and no recurrent mutation. Although these assumptions are suitable to selection that targets single nucleotide variants, fundamentally different types of mutation generate abundant polymorphism in genomes. Moreover, recent empirical results suggest that mutationally complex, multiallelic loci including microsatellites and copy number variants are sometimes targeted by natural selection. Given their abundance, the lack of inference methods tailored to the mutational peculiarities of these types of loci represents a notable gap in our ability to interrogate genomes for signatures of natural selection. Previous theoretical investigations of mutation-selection balance at multiallelic loci include assumptions that limit their application to inference from empirical data. Focusing on microsatellites, we assess the dynamics and population-level consequences of selection targeting mutationally complex variants. We develop general models of a multiallelic fitness surface, a realistic model of microsatellite mutation, and an efficient simulation algorithm. Using these tools, we explore mutation-selection-drift equilibrium at microsatellites and investigate the mutational history and selective regime of the microsatellite that causes Friedreich’s ataxia. We characterize microsatellite selective events by their duration and cost, note similarities to sweeps from standing point variation, and conclude that it is premature to label microsatellites as ubiquitous agents of efficient adaptive change. Together, our models and simulation algorithm provide a powerful framework for statistical inference, which can be used to test the neutrality of microsatellites and other multiallelic variants. PMID:23104080

A Systematic Review of Obesity Prevention Intervention Studies among Immigrant Populations in the US.

PubMed

Tovar, Alison; Renzaho, Andre M N; Guerrero, Alma D; Mena, Noereem; Ayala, Guadalupe X

2014-01-01

The aim of this review was to systematically assess the effectiveness of obesity prevention and control interventions in US immigrant populations across the life course, from preschool-age to adults. A systematic review of relevant studies was undertaken and eligible articles included. The initial search identified 684 potentially relevant articles, of which only 20 articles met the selection criteria, representing 20 unique studies. They were divided into interventions that targeted adults (n=7), interventions that targeted children (n=5) and pilot studies (n=8). The majority of interventions targeted Latinos, predominately Mexican-origin populations. Among the interventions targeting adults, five had an effect on obesity related outcomes. However, they tended to use less rigorous study designs. Among the interventions that targeted children, three had a positive effect on obesity-related outcomes. Three of the eight pilot studies had an effect on obesity-related outcomes. There is a paucity of data on effective interventions but a great need to address obesity prevention to help inform health policies and programs to reduce migration-related obesity inequalities.

Targeting Neurotrophins to Specific Populations of Neurons: NGF, BDNF, and NT-3 and Their Relevance for Treatment of Spinal Cord Injury.

PubMed

Keefe, Kathleen M; Sheikh, Imran S; Smith, George M

2017-03-03

Neurotrophins are a family of proteins that regulate neuronal survival, synaptic function, and neurotransmitter release, and elicit the plasticity and growth of axons within the adult central and peripheral nervous system. Since the 1950s, these factors have been extensively studied in traumatic injury models. Here we review several members of the classical family of neurotrophins, the receptors they bind to, and their contribution to axonal regeneration and sprouting of sensory and motor pathways after spinal cord injury (SCI). We focus on nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3), and their effects on populations of neurons within diverse spinal tracts. Understanding the cellular targets of neurotrophins and the responsiveness of specific neuronal populations will allow for the most efficient treatment strategies in the injured spinal cord.

Targeting Neurotrophins to Specific Populations of Neurons: NGF, BDNF, and NT-3 and Their Relevance for Treatment of Spinal Cord Injury

PubMed Central

Keefe, Kathleen M.; Sheikh, Imran S.; Smith, George M.

2017-01-01

Neurotrophins are a family of proteins that regulate neuronal survival, synaptic function, and neurotransmitter release, and elicit the plasticity and growth of axons within the adult central and peripheral nervous system. Since the 1950s, these factors have been extensively studied in traumatic injury models. Here we review several members of the classical family of neurotrophins, the receptors they bind to, and their contribution to axonal regeneration and sprouting of sensory and motor pathways after spinal cord injury (SCI). We focus on nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3), and their effects on populations of neurons within diverse spinal tracts. Understanding the cellular targets of neurotrophins and the responsiveness of specific neuronal populations will allow for the most efficient treatment strategies in the injured spinal cord. PMID:28273811

Culturally Targeted Strategies for Diabetes Prevention in Minority Populations: A Systematic Review and Framework

PubMed Central

Lagisetty, Pooja A.; Priyadarshini, Shubadra; Terrell, Stephanie; Hamati, Mary; Landgraf, Jessica; Chopra, Vineet; Heisler, Michele

2017-01-01

Purpose The purpose of this study is to (a) assess the effectiveness of culturally tailored diabetes prevention interventions in minority populations and (b) develop a novel framework to characterize four key domains of culturally tailored interventions. Prevention strategies specifically tailored to the culture of ethnic minority patients may help reduce the incidence of diabetes. Methods We searched PubMed, EMBASE, and CINAHL for English-language, randomized controlled trials (RCTs) or quasi-experimental (QE) trials testing culturally tailored interventions to prevent diabetes in minority populations. Two reviewers independently extracted data and assessed risk of bias. Inductive thematic analysis was used to develop a framework with four domains (FiLLM: Facilitating [i.e., delivering] Interventions through Language, Location and Message). The framework was used to assess the overall effectiveness of culturally tailored interventions. Results Thirty-four trials met eligibility criteria. Twelve studies were randomized controlled trials, and 22 were quasi-experimental trials. Twenty-five out of 34 studies (74%) that used cultural tailoring demonstrated significantly improved Hemoglobin A1C, fasting glucose, and/or weight loss. Of the 25 successful interventions, 21 (84%) incorporated at least three culturally targeted domains. Seven studies used all four domains and were all successful. The least utilized domain was delivery (4/34) of the intervention’s key educational message. Conclusions Culturally tailoring interventions across the four domains of facilitators, language, location, and messaging can be effective in improving risk factors for progression to diabetes among ethnic minority groups. Future studies should evaluate how specific tailoring approaches work compared to usual care as well as comparative effectiveness of each tailoring domain. Registration (PROSPERO registration: CRD42015016914) PMID:28118127

Strategies and Challenges in Clinical Trials Targeting Human Aging

PubMed Central

Newman, John C.; Milman, Sofiya; Hashmi, Shahrukh K.; Austad, Steve N.; Kirkland, James L.; Halter, Jeffrey B.

2016-01-01

Interventions that target fundamental aging processes have the potential to transform human health and health care. A variety of candidate drugs have emerged from basic and translational research that may target aging processes. Some of these drugs are already in clinical use for other purposes, such as metformin and rapamycin. However, designing clinical trials to test interventions that target the aging process poses a unique set of challenges. This paper summarizes the outcomes of an international meeting co-ordinated by the NIH-funded Geroscience Network to further the goal of developing a translational pipeline to move candidate compounds through clinical trials and ultimately into use. We review the evidence that some drugs already in clinical use may target fundamental aging processes. We discuss the design principles of clinical trials to test such interventions in humans, including study populations, interventions, and outcomes. As examples, we offer several scenarios for potential clinical trials centered on the concepts of health span (delayed multimorbidity and functional decline) and resilience (response to or recovery from an acute health stress). Finally, we describe how this discussion helped inform the design of the proposed Targeting Aging with Metformin study. PMID:27535968

The prediction of the cavitation phenomena including population balance modeling

NASA Astrophysics Data System (ADS)

Bannari, Rachid; Hliwa, Ghizlane Zineb; Bannari, Abdelfettah; Belghiti, Mly Taib

2017-07-01

Cavitation is the principal reason behind the behavior's modification of the hydraulic turbines. However, the experimental observations can not be appropriate to all cases due to the limitations in the measurement techniques. The mathematical models which have been implemented, use the mixture multiphase frame. As well as, most of the published work is limited by considering a constant bubble size distribution. However, this assumption is not realist. The aim of this article is the implementation and the use of a non-homogeneous multiphase model which solve two phases transport equation. The evolution of bubble size is considered by the population balance equation. This study is based on the eulerian-eulerian model, associated to the cavitation model. All the inter-phase forces such as drag, lift and virtual mass are used.

Identification of alkaptonuria in the general population: a United Kingdom experience describing the challenges, possible solutions and persistent barriers.

PubMed

Ranganath, L; Taylor, A M; Shenkin, A; Fraser, W D; Jarvis, J; Gallagher, J A; Sireau, N

2011-06-01

Progress in research into rare diseases is challenging. This paper discusses strategies to identify individuals with the rare genetic disease alkaptonuria (AKU) within the general population. Strategies used included a questionnaire survey of general practitioners, a dedicated website and patient network contact, targeted family screening and medical conference targeting. Primary care physicians of the UK were targeted by a postal survey that involved mailing 11,151 UK GPs; the response rate was 18.2%. We have identified 75 patients in the UK with AKU by the following means: postal survey (23), targeted family screening (11), patient networks and the website (41). Targeting medical conferences (AKU, rare diseases, rheumatology, clinical biochemistry, orthopaedics, general practitioners) did not lead to new identification in the UK but helped identify overseas cases. We are now aware of 626 patients worldwide including newly identified non-UK people with AKU in the following areas: Slovakia (208), the rest of Europe (including Turkey) (79), North America (including USA and Canada) (110), and the rest of the world (154). A mechanism for identifying individuals with AKU in the general population-not just in the UK but worldwide-has been established. Knowledge of patients with AKU, both in the UK and outside, is often confined to establishing their location in a particular GP practice or association with a particular medical professional. Mere identification, however, does not always lead to full engagement for epidemiological research purposes or targeting treatment since further barriers exist.

Improving food environments and tackling obesity: A realist systematic review of the policy success of regulatory interventions targeting population nutrition

PubMed Central

Sisnowski, Jana; Merlin, Tracy

2017-01-01

Background This systematic review (PROSPERO: CRD42015025276) employs a realist approach to investigate the effect of “real-world” policies targeting different aspects of the food environment that shape individual and collective nutrition. Objectives We were interested in assessing intermediate outcomes along the assumed causal pathway to “policy success”, in addition to the final outcome of changed consumption patterns. Data sources We performed a search of 16 databases through October 2015, with no initial restriction by language. Study eligibility criteria We included all publications that reported the effect of statutory provisions aimed at reducing the consumption of energy-dense foods and beverages in the general population. We allowed all methodological approaches that contained some measure of comparison, including studies of implementation progress. Study appraisal and synthesis methods We reviewed included studies using the appraisal tools for pre-post and observational studies developed by the National Heart, Lung, and Blood Institute. Given the considerable heterogeneity in interventions assessed, study designs employed, and outcome measures reported, we opted for a narrative synthesis of results. Results and implications Results drawn from 36 peer-reviewed articles and grey literature reports demonstrated that isolated regulatory interventions can improve intermediate outcomes, but fail to affect consumption at clinically significant levels. The included literature covered six different types of interventions, with 19 studies reporting on calorie posting on chain restaurant menus. The large majority of the identified interventions were conducted in the US. Early results from recent taxation measures were published after the review cut-off date but these suggested more favorable effects on consumption levels. Nevertheless, the evidence assessed in this review suggests that current policies are generally falling short of anticipated health impacts

Measurement of sedentary behaviour in population health surveys: a review and recommendations

PubMed Central

LeBlanc, Allana G.; Colley, Rachel C.; Saunders, Travis J.

2017-01-01

Background The purpose of this review was to determine the most valid and reliable questions for targeting key modes of sedentary behaviour (SB) in a broad range of national and international health surveillance surveys. This was done by reviewing the SB modules currently used in population health surveys, as well as examining SB questionnaires that have performed well in psychometric testing. Methods Health surveillance surveys were identified via scoping review and contact with experts in the field. Previous systematic reviews provided psychometric information on pediatric questionnaires. A comprehensive search of four bibliographic databases was used to identify studies reporting psychometric information for adult questionnaires. Only surveys/studies published/used in English or French were included. Results The review identified a total of 16 pediatric and 18 adult national/international surveys assessing SB, few of which have undergone psychometric testing. Fourteen pediatric and 35 adult questionnaires with psychometric information were included. While reliability was generally good to excellent for questions targeting key modes of SB, validity was poor to moderate, and reported much less frequently. The most valid and reliable questions targeting specific modes of SB were combined to create a single questionnaire targeting key modes of SB. Discussion Our results highlight the importance of including SB questions in survey modules that are adaptable, able to assess various modes of SB, and that exhibit adequate reliability and validity. Future research could investigate the psychometric properties of the module we have proposed in this paper, as well as other questionnaires currently used in national and international population health surveys. PMID:29250468

Measurement of sedentary behaviour in population health surveys: a review and recommendations.

PubMed

Prince, Stephanie A; LeBlanc, Allana G; Colley, Rachel C; Saunders, Travis J

2017-01-01

The purpose of this review was to determine the most valid and reliable questions for targeting key modes of sedentary behaviour (SB) in a broad range of national and international health surveillance surveys. This was done by reviewing the SB modules currently used in population health surveys, as well as examining SB questionnaires that have performed well in psychometric testing. Health surveillance surveys were identified via scoping review and contact with experts in the field. Previous systematic reviews provided psychometric information on pediatric questionnaires. A comprehensive search of four bibliographic databases was used to identify studies reporting psychometric information for adult questionnaires. Only surveys/studies published/used in English or French were included. The review identified a total of 16 pediatric and 18 adult national/international surveys assessing SB, few of which have undergone psychometric testing. Fourteen pediatric and 35 adult questionnaires with psychometric information were included. While reliability was generally good to excellent for questions targeting key modes of SB, validity was poor to moderate, and reported much less frequently. The most valid and reliable questions targeting specific modes of SB were combined to create a single questionnaire targeting key modes of SB. Our results highlight the importance of including SB questions in survey modules that are adaptable, able to assess various modes of SB, and that exhibit adequate reliability and validity. Future research could investigate the psychometric properties of the module we have proposed in this paper, as well as other questionnaires currently used in national and international population health surveys.

Population pharmacokinetics of rifampin in the treatment of Mycobacterium tuberculosis in Asian elephants.

PubMed

Egelund, E F; Isaza, R; Brock, A P; Alsultan, A; An, G; Peloquin, C A

2015-04-01

The objective of this study was to develop a population pharmacokinetic model for rifampin in elephants. Rifampin concentration data from three sources were pooled to provide a total of 233 oral concentrations from 37 Asian elephants. The population pharmacokinetic models were created using Monolix (version 4.2). Simulations were conducted using ModelRisk. We examined the influence of age, food, sex, and weight as model covariates. We further optimized the dosing of rifampin based upon simulations using the population pharmacokinetic model. Rifampin pharmacokinetics were best described by a one-compartment open model including first-order absorption with a lag time and first-order elimination. Body weight was a significant covariate for volume of distribution, and food intake was a significant covariate for lag time. The median Cmax of 6.07 μg/mL was below the target range of 8-24 μg/mL. Monte Carlo simulations predicted the highest treatable MIC of 0.25 μg/mL with the current initial dosing recommendation of 10 mg/kg, based upon a previously published target AUC0-24/MIC > 271 (fAUC > 41). Simulations from the population model indicate that the current dose of 10 mg/kg may be adequate for MICs up to 0.25 μg/mL. While the targeted AUC/MIC may be adequate for most MICs, the median Cmax for all elephants is below the human and elephant targeted ranges. © 2014 John Wiley & Sons Ltd.

The relationship between age of onset and risk factors including family history and life style in Korean population with type 2 diabetes mellitus.

PubMed

Noh, Jin-Won; Jung, Jin Hee; Park, Jeong Eun; Lee, Jung Hwa; Sim, Kang Hee; Park, Jumin; Kim, Min Hee; Yoo, Ki-Bong

2018-02-01

[Purpose] The purpose of the present study was to assess the relationship between age of onset and risk factors including family history and life style in Korean population with type 2 diabetes mellitus (T2D). [Subjects and Methods] Subjects with T2D patients who received outpatient care for blood sugar control were randomly sampled at 13 general hospitals and 969 subjects were included. Cox proportional hazard models were used to confirm associations between age of onset and risk factors including family history and life style in Korean population with T2D. [Results] Parent history of T2D was significantly associated with age of onset. Compared to none of family members with T2D, those whose both father and mother had a history showed the highest the risk of early-onset (HR=2.36; 95% CI=1.45-3.85). Mother and father's history of T2D (HR=1.73; 95% CI=1.46-2.05; HR=1.83; 95% CI=1.40-2.37) were associated with the risk of early-onset. Moreover, exercise (HR=1.23, CI=1.08-1.40) smoking status (HR=1.62, CI=1.32-1.99), and drinking (HR=1.32, CI=1.13-1.54) were associated with a higher risk for the early-onset. [Conclusion] Family history as well as life style including exercise, smoking, and drinking are the risk factors for early-onset factor in Korean population with T2D.

Haemophilus ducreyi Outer Membrane Determinants, Including DsrA, Define Two Clonal Populations

PubMed Central

White, Catherine Dinitra; Leduc, Isabelle; Olsen, Bonnie; Jeter, Chrystina; Harris, Chavala; Elkins, Christopher

2005-01-01

The Haemophilus ducreyi outer membrane component DsrA (for ducreyi serum resistance A) is necessary for complete resistance to normal human serum (NHS). When DsrA expression in 19 temporally and geographically diverse clinical isolates of H. ducreyi was examined by Western blotting, 5 of the strains expressed a different immunotype of the DsrA protein (DsrAII) than the well-characterized prototypical strain 35000HP (DsrAI). The predicted DsrA proteins expressed by the DsrAII strains were 100% identical to each other but only 48% identical to that of strain 35000HP. In addition to the DsrAII protein, class II strains also expressed variant forms of other outer membrane proteins (OMPs) including NcaA (necessary for collagen adhesion A), DltA (ducreyi lectin A), Hlp (H. ducreyi lipoprotein), major OMP, and/or OmpA2 (for OMP A2) and synthesized a distinct, faster-migrating lipooligosaccharide. Based on these data, strains expressing DsrAI were termed class I, and those expressing DsrAII were termed class II. Expression of dsrAII from strain CIP 542 ATCC in the class I dsrAI mutant FX517 (35000HP background), which does not express a DsrA protein, rendered this strain resistant to 50% NHS. This demonstrates that DsrAII protein is also critical to serum resistance. Taken together, these results indicate that there are two clonal populations of H. ducreyi. The implications of two classes of H. ducreyi strains differing in important antigenic outer membrane components are discussed. PMID:15784585

Targeting pre-exposure prophylaxis among men who have sex with men in the United States and Peru: partnership types, contact rates, and sexual role

PubMed Central

Carnegie, Nicole Bohme; Goodreau, Steven M.; Liu, Albert; Vittinghoff, Eric; Sanchez, Jorge; Lama, Javier R.; Buchbinder, Susan

2015-01-01

Background We aim to identify optimal strategies for deploying pre-exposure prophylaxis among men who have sex with men in the US and Peru to maximize population-level effectiveness in an efficient manner. We use epidemic models to simulate the impact of targeting strategies. Most studies have focused on targeting either the general population or high-risk MSM. Alternative strategies, including serodiscordant couples, may better balance effectiveness and efficiency. Methods We use dynamic, stochastic sexual network models based in exponential-family random graph modeling, parameterized from behavioral surveys of MSM in the US and Peru. These models represent main partnerships and casual contacts separately, permitting modeling of interventions targeting men whose risk derives from combinations of relational types. We also model varying rates of uptake and adherence to PrEP. We assess sensitivity of results to risk compensation via increases in condomless casual contacts and condomless sex in main partnerships. Results Targeting all men who are not exclusively insertive has the largest impact on HIV incidence, but targeting only those with high levels of casual activity yields comparable results using fewer person-years on PrEP. The effect is robust to risk compensation in the US, but less so in Peru. Targeting serodiscordant main partnerships does not significantly impact incidence, but requires fewer person-years on PrEP per infection averted than other strategies. Conclusions PrEP could be effective in reducing new infections at the population level in both settings. Serodiscordant partnerships are an attractive component of a targeting program, but targeting should include other high-risk men. PMID:25942463

Targeting pre-exposure prophylaxis among men who have sex with men in the United States and Peru: partnership types, contact rates, and sexual role.

PubMed

Carnegie, Nicole B; Goodreau, Steven M; Liu, Albert; Vittinghoff, Eric; Sanchez, Jorge; Lama, Javier R; Buchbinder, Susan

2015-05-01

We aim to identify optimal strategies for deploying pre-exposure prophylaxis among men who have sex with men (MSM) in the United States and Peru to maximize population-level effectiveness in an efficient manner. We use epidemic models to simulate the impact of targeting strategies. Most studies have focused on targeting either the general population or high-risk MSM. Alternative strategies, including serodiscordant couples, may better balance effectiveness and efficiency. We use dynamic stochastic sexual network models based on exponential-family random graph modeling, parameterized from behavioral surveys of MSM in the United States and Peru. These models represent main partnerships and casual contacts separately, permitting modeling of interventions targeting men whose risk derives from combinations of relational types. We also model varying rates of uptake and adherence to pre-exposure prophylaxis (PrEP). We assess sensitivity of results to risk compensation through increases in condomless casual contacts and condomless sex in main partnerships. Targeting all men who are not exclusively insertive has the largest impact on HIV incidence, but targeting only those with high levels of casual activity yields comparable results using fewer person-years on PrEP. The effect is robust to risk compensation in the United States, but less so in Peru. Targeting serodiscordant main partnerships does not significantly impact incidence, but requires fewer person-years on PrEP per infection averted than other strategies. PrEP could be effective in reducing new infections at the population level in both settings. Serodiscordant partnerships are an attractive component of a targeting program, but targeting should include other high-risk men.

Cytotoxic Tumor-Targeting Peptides From In Vivo Phage Display.

PubMed

Northup, Jessica R Newton; Deutscher, Susan L

2016-01-01

We previously utilized an in vivo peptide phage display selection technique, which included the use of detergent elution of phage from excised tumor, to obtain tumor-targeting phage with the ability to extravasate the vasculature and bind directly to prostate tumor tissue. It is hypothesized that this same in vivo phage selection technique can be used to functionally select for molecules that not only bind to cancer cells but also kill them. Here we analyzed two different in vivo phage display selected phage clones, G1 and H5, retrieved from PC-3 human prostate carcinoma xenografted tumors. First, cell de-attachment as an endpoint criterion for apoptosis and cell cycle was examined. After 2.5 hours incubation with G1 phage, PC-3 cell attachment was reduced by 23.8% and the percent of cell population in M phase reduced by 32.1%. In comparison, PC-3 cells incubated with H5 phage had a reduction of 25.0% cell attachment and 33.6% of cell population in M phase. These changes in combination with elevated caspase activation within cells in M phase, and no significant changes to G1/G0 or S phase cell populations suggest that the cytotoxic phages are targeting actively dividing PC-3 cells. Microscopic studies were also performed to further analyze the nature of cytotoxicity of these two phage clones. It was found that G1 phage induced and co- localized with tubulin based projections within apoptotic cells, while H5 phage did not. These phage may form the foundation for a new class of targeted prostate cancer therapeutic agents.

The Resolved Stellar Populations Early Release Science Program

NASA Astrophysics Data System (ADS)

Gilbert, Karoline; Weisz, Daniel; Resolved Stellar Populations ERS Program Team

2018-06-01

The Resolved Stellar Populations Early Release Science Program (PI D. Weisz) will observe Local Group targets covering a range of stellar density and star formation histories, including a globular cluster, and ultra-faint dwarf galaxy, and a star-forming dwarf galaxy. Using observations of these diverse targets we will explore a broad science program: we will measure star formation histories, the sub-solar stellar initial mass function, and proper motions, perform studies of evolved stars, and map extinction in the target fields. Our observations will be of high archival value for other science such as calibrating stellar evolution models, studying variable stars, and searching for metal-poor stars. We will determine optimal observational setups and develop data reduction techniques that will be common to JWST studies of resolved stellar populations. We will also design, test, and release point spread function (PSF) fitting software specific to NIRCam and NIRISS, required for the crowded stellar regime. Prior to the Cycle 2 Call for Proposals, we will release PSF fitting software, matched HST and JWST catalogs, and clear documentation and step-by-step tutorials (such as Jupyter notebooks) for reducing crowded stellar field data and producing resolved stellar photometry catalogs, as well as for specific resolved stellar photometry science applications.

Maldives. Package on population education for special interest groups developed.

PubMed

1995-01-01

The Population Education Program of the Non-Formal Education Center has developed a package of Population Education for Special Interest Groups comprising a learning package and fieldworker's guide. The learning package is especially developed for teaching population education for out-of-school populations. Special interest groups in Maldives include newly married couples, adolescents, and working youth. Produced under the guidance of UNESCO, Bangkok, the package contains 36 different materials such as posters, charts, leaflets, booklets, stories, and illustrated booklets which may be taught in 36 to 45 periods. The materials deal with eight themes, namely, family size and family welfare, population and resources, delayed marriage and parenthood, responsible parenthood, population-related values and beliefs, women in development, AIDS/STD, and respect for old people. Accompanying the learning package is the fieldworker's guide used to teach the package. It contains individual guides for each of the 36 learning materials. The guide gives the titles of the materials, format, objectives of the materials, messages, target groups, and an overview of the content of each learning materials. The methodologies used for teaching the learning materials include role playing, group discussion, questioning, brainstorming, survey, creative writing, problem-solving and evaluation. The package will be used by fieldworkers to conduct island-based population education courses. full text

[Patient first - The impact of characteristics of target populations on decisions about therapy effectiveness of complex interventions: Psychological variables to assess effectiveness in interdisciplinary multimodal pain therapy].

PubMed

Kaiser, Ulrike; Sabatowski, Rainer; Balck, Friedrich

2017-08-01

The assessment of treatment effectiveness in public health settings is ensured by indicators that reflect the changes caused by specific interventions. These indicators are also applied in benchmarking systems. The selection of constructs should be guided by their relevance for affected patients (patient reported outcomes). The interdisciplinary multimodal pain therapy (IMPT) is a complex intervention based on a biopsychosocial understanding of chronic pain. For quality assurance purposes, psychological parameters (depression, general anxiety, health-related quality of life) are included in standardized therapy assessment in pain medicine (KEDOQ), which can also be used for comparative analyses in a benchmarking system. The aim of the present study was to investigate the relevance of depressive symptoms, general anxiety and mental quality of life in patients undergoing IMPT under real life conditions. In this retrospective, one-armed and exploratory observational study we used secondary data of a routine documentation of IMST in routine care, applying several variables of the German Pain Questionnaire and the facility's comprehensive basic documentation. 352 participants with IMPT (from 2006 to 2010) were included, and the follow-up was performed over two years with six assessments. Because of statistically heterogeneous characteristics a complex analysis consisting of factor and cluster analyses was applied to build subgroups. These subgroups were explored to identify differences in depressive symptoms (HADS-D), general anxiety (HADS-A), and mental quality of life (SF 36 PSK) at the time of therapy admission and their development estimated by means of effect sizes. Analyses were performed using SPSS 21.0®. Six subgroups were derived and mainly proved to be clinically and psychologically normal, with the exception of one subgroup that consistently showed psychological impairment for all three parameters. The follow-up of the total study population revealed medium

Prescreening of microbial populations for the assessment of sequencing potential.

PubMed

Hanning, Irene B; Ricke, Steven C

2011-01-01

Next-generation sequencing (NGS) is a powerful tool that can be utilized to profile and compare microbial populations. By amplifying a target gene present in all bacteria and subsequently sequencing amplicons, the bacteria genera present in the populations can be identified and compared. In some scenarios, little to no difference may exist among microbial populations being compared in which case a prescreening method would be practical to determine which microbial populations would be suitable for further analysis by NGS. Denaturing density-gradient electrophoresis (DGGE) is relatively cheaper than NGS and the data comparing microbial populations are ready to be viewed immediately after electrophoresis. DGGE follows essentially the same initial methodology as NGS by targeting and amplifying the 16S rRNA gene. However, as opposed to sequencing amplicons, DGGE amplicons are analyzed by electrophoresis. By prescreening microbial populations with DGGE, more efficient use of NGS methods can be accomplished. In this chapter, we outline the protocol for DGGE targeting the same gene (16S rRNA) that would be targeted for NGS to compare and determine differences in microbial populations from a wide range of ecosystems.

Changing Urbania: Estimating Changes in Urban Land and Urban Population Using Refined Areal Interpolation Techniques

NASA Astrophysics Data System (ADS)

Zoraghein, H.; Leyk, S.; Balk, D.

2017-12-01

The analysis of changes in urban land and population is important because the majority of future population growth will take place in urban areas. The U.S. Census historically classifies urban land using population density and various land-use criteria. This study analyzes the reliability of census-defined urban lands for delineating the spatial distribution of urban population and estimating its changes over time. To overcome the problem of incompatible enumeration units between censuses, regular areal interpolation methods including Areal Weighting (AW) and Target Density Weighting (TDW), with and without spatial refinement, are implemented. The goal in this study is to estimate urban population in Massachusetts in 1990 and 2000 (source zones), within tract boundaries of the 2010 census (target zones), respectively, to create a consistent time series of comparable urban population estimates from 1990 to 2010. Spatial refinement is done using ancillary variables such as census-defined urban areas, the National Land Cover Database (NLCD) and the Global Human Settlement Layer (GHSL) as well as different combinations of them. The study results suggest that census-defined urban areas alone are not necessarily the most meaningful delineation of urban land. Instead it appears that alternative combinations of the above-mentioned ancillary variables can better depict the spatial distribution of urban land, and thus make it possible to reduce the estimation error in transferring the urban population from source zones to target zones when running spatially-refined temporal areal interpolation.

The evolution of antibiotic resistance in a structured host population.

PubMed

Blanquart, François; Lehtinen, Sonja; Lipsitch, Marc; Fraser, Christophe

2018-06-01

The evolution of antibiotic resistance in opportunistic pathogens such as Streptococcus pneumoniae , Escherichia coli or Staphylococcus aureus is a major public health problem, as infection with resistant strains leads to prolonged hospital stay and increased risk of death. Here, we develop a new model of the evolution of antibiotic resistance in a commensal bacterial population adapting to a heterogeneous host population composed of untreated and treated hosts, and structured in different host classes with different antibiotic use. Examples of host classes include age groups and geographic locations. Explicitly modelling the antibiotic treatment reveals that the emergence of a resistant strain is favoured by more frequent but shorter antibiotic courses, and by higher transmission rates. In addition, in a structured host population, localized transmission in host classes promotes both local adaptation of the bacterial population and the global maintenance of coexistence between sensitive and resistant strains. When transmission rates are heterogeneous across host classes, resistant strains evolve more readily in core groups of transmission. These findings have implications for the better management of antibiotic resistance: reducing the rate at which individuals receive antibiotics is more effective to reduce resistance than reducing the duration of treatment. Reducing the rate of treatment in a targeted class of the host population allows greater reduction in resistance, but determining which class to target is difficult in practice. © 2018 The Authors.

Population planning: a well co-ordinated approach required.

PubMed

1984-01-01

This discussion combines information obtained from 5 countries in the Economic and Social Commission for Asia and the Pacific (ESCAP) region on the role of population planning in the context of integrated policies and programs. The countries were asked what specific aspects of the present population policy and program would require concentrated inputs in order to achieve stated goals and targets. In Indonesia 2 program areas are identified for intensification: the organized transmigration scheme which aims at a balanced distribution of population and exploitation of potential resources throughout the country, including islands outside Java and Bali; and the national family planning program as a whole, in order to achieve the target of 60% prevalence rate of contraceptive use among eligible couples in 1990 and a decline of the crude birthrate from 33/1000 to 23/1000 by that date. Both programs are receiving high priority. Nepal policy and programs are aimed at achieving replacement level fertility by 2000. Steps that have been initiated in Bangladesh include intensive motivation activities with strong media inputs, the maintenance of a regular and adequate supply of contraceptives at the doorstep of clients, and strengthening the multisectoral program. The Philippines National Population Program advocates and promotes 4 norms in order to achieve a population growth rate of 2%, a prevalence rate of 54%, and contraceptive effectiveness of 80% by 1987: small family size; birth spacing; delayed marriages; and reduced incidence of teenage pregnancies. The goals envisaged for India are a reduction in the crude birthrate to not more than 21/1000, crude death rate of not more than 9/1000, and an infant mortality rate of less than 60/1000 live births by 2000. Concentrated efforts will be needed in the use of mass media and interpersonal communication strategies with services and supplies being provided as close to the doorstep of the acceptor as possible. In most countries

Pharmacogenomics of warfarin in populations of African descent

PubMed Central

Suarez-Kurtz, Guilherme; Botton, Mariana R

2013-01-01

Warfarin is the most commonly prescribed oral anticoagulant worldwide despite its narrow therapeutic index and the notorious inter- and intra-individual variability in dose required for the target clinical effect. Pharmacogenetic polymorphisms are major determinants of warfarin pharmacokinetic and dynamics and included in several warfarin dosing algorithms. This review focuses on warfarin pharmacogenomics in sub-Saharan peoples, African Americans and admixed Brazilians. These ‘Black’ populations differ in several aspects, notably their extent of recent admixture with Europeans, a factor which impacts on the frequency distribution of pharmacogenomic polymorphisms relevant to warfarin dose requirement for the target clinical effect. Whereas a small number of polymorphisms in VKORC1 (3673G > A, rs9923231), CYP2C9 (alleles *2 and *3, rs1799853 and rs1057910, respectively) and arguably CYP4F2 (rs2108622), may capture most of the pharmacogenomic influence on warfarin dose variance in White populations, additional polymorphisms in these, and in other, genes (e.g. CALU rs339097) increase the predictive power of pharmacogenetic warfarin dosing algorithms in the Black populations examined. A personalized strategy for initiation of warfarin therapy, allowing for improved safety and cost-effectiveness for populations of African descent must take into account their pharmacogenomic diversity, as well as socio-economical, cultural and medical factors. Accounting for this heterogeneity in algorithms that are ‘friendly’ enough to be adopted by warfarin prescribers worldwide requires gathering information from trials at different population levels, but demands also a critical appraisal of racial/ethnic labels that are commonly used in the clinical pharmacology literature but do not accurately reflect genetic ancestry and population diversity. PMID:22676711

Adapting an Evidence-Based Intervention Targeting HIV-Infected Prisoners in Malaysia

PubMed Central

Copenhaver, Michael M.; Tunku, Noor; Ezeabogu, Ifeoma; Potrepka, Jessica; Zahari, Muhammad Muhsin A.; Kamarulzaman, Adeeba; Altice, Frederick L.

2011-01-01

HIV-infected prisoners in Malaysia represent a critical target population for secondary HIV risk reduction interventions and care. We report on the process and outcome of our formative research aimed at systematically selecting and adapting an EBI designed to reduce secondary HIV risk and improve adherence to antiretroviral therapy among soon-to-be-released HIV-infected prisoners. Our formative work involved a critical examination of established EBIs and associated published reports complemented by data elicited through structured interviews and focus groups with key stakeholders, members of the target population, and their family members. Based on all information, we adapted the Holistic Health Recovery Program targeting people living with HIV (HHRP+), an EBI, to consist of eight 2-hour sessions that cover a range of specified topics so that participants may individually apply intervention content as needed to accommodate their particular substance abuse, HIV risk, and antiretroviral adherence issues. This study provides a complete example of the process of selecting and adapting an EBI—taking into account both empirical evidence and input from target organization stakeholders and target population members and their families—for use in real world prison settings where high-risk populations are concentrated. PMID:21860786

Targeted gene flow for conservation.

PubMed

Kelly, Ella; Phillips, Ben L

2016-04-01

Anthropogenic threats often impose strong selection on affected populations, causing rapid evolutionary responses. Unfortunately, these adaptive responses are rarely harnessed for conservation. We suggest that conservation managers pay close attention to adaptive processes and geographic variation, with an eye to using them for conservation goals. Translocating pre-adapted individuals into recipient populations is currently considered a potentially important management tool in the face of climate change. Targeted gene flow, which involves moving individuals with favorable traits to areas where these traits would have a conservation benefit, could have a much broader application in conservation. Across a species' range there may be long-standing geographic variation in traits or variation may have rapidly developed in response to a threatening process. Targeted gene flow could be used to promote natural resistance to threats to increase species resilience. We suggest that targeted gene flow is a currently underappreciated strategy in conservation that has applications ranging from the management of invasive species and their impacts to controlling the impact and virulence of pathogens. © 2015 Society for Conservation Biology.

Surveillance and response for high-risk populations: what can malaria elimination programmes learn from the experience of HIV?

PubMed

Jacobson, Jerry O; Cueto, Carmen; Smith, Jennifer L; Hwang, Jimee; Gosling, Roly; Bennett, Adam

2017-01-18

To eliminate malaria, malaria programmes need to develop new strategies for surveillance and response appropriate for the changing epidemiology that accompanies transmission decline, in which transmission is increasingly driven by population subgroups whose behaviours place them at increased exposure. Conventional tools of malaria surveillance and response are likely not sufficient in many elimination settings for accessing high-risk population subgroups, such as mobile and migrant populations (MMPs), given their greater likelihood of asymptomatic infections, illegal risk behaviours, limited access to public health facilities, and high mobility including extended periods travelling away from home. More adaptive, targeted strategies are needed to monitor transmission and intervention coverage effectively in these groups. Much can be learned from HIV programmes' experience with "second generation surveillance", including how to rapidly adapt surveillance and response strategies to changing transmission patterns, biological and behavioural surveys that utilize targeted sampling methods for specific behavioural subgroups, and methods for population size estimation. This paper reviews the strategies employed effectively for HIV programmes and offers considerations and recommendations for adapting them to the malaria elimination context.

Obesity and kidney disease: from population to basic science and the search for new therapeutic targets.

PubMed

Whaley-Connell, Adam; Sowers, James R

2017-08-01

The global burden of kidney disease is increasing strikingly in parallel with increases in obesity and diabetes. Indeed, chronic kidney disease (CKD) and end-stage renal disease (ESRD) coupled with comorbidities such as obesity, diabetes, and hypertension cost the health care system hundreds of billions of dollars in the US alone. The progression to ESRD in patients with obesity and diabetes continues despite widespread use of inhibitors of the renin-angiotensin-aldosterone system (RAAS) along with aggressive blood pressure and glycemic control in these high-risk populations. Thereby, it is increasingly important to better understand the underlying mechanisms involved in obesity-related CKD in order to develop new strategies that prevent or interrupt the progression of this costly disease. In this context, a key mechanism that drives development and progression of kidney disease in obesity is endothelial dysfunction and associated tubulointerstitial fibrosis. However, the precise interactive mechanisms in the development of aortic and kidney endothelial dysfunction and tubulointerstitial fibrosis remain unclear. Further, strategies specifically targeting kidney fibrosis have yielded inconclusive benefits in human studies. While clinical data support the benefits derived from inhibition of the RAAS, there is a tremendous amount of residual risk for the progression of kidney disease in individuals with obesity and diabetes. There is promising experimental data to suggest that exercise, targeting inflammation and oxidative stress, lowering uric acid, and targeting the mineralocorticoid receptor signaling and/or sodium channel inhibition could improve tubulointerstitial fibrosis and mitigate progression of kidney disease in persons with obesity and diabetes. Published by Elsevier Inc.

Effect of excess iodine intake on thyroid diseases in different populations: A systematic review and meta-analyses including observational studies

PubMed Central

Katagiri, Ryoko; Yuan, Xiaoyi; Kobayashi, Satomi; Sasaki, Satoshi

2017-01-01

Background Although several reports concerning the association of iodine excess and thyroid disease have appeared, no systematic review of the association between iodine excess intake and thyroid diseases, especially hyperthyroidism and hypothyroidism, has yet been reported. Method We conducted a systematic search of Ovid MEDLINE, PubMed, Cochrane Central Register of Controlled Trials databases, Ichushi-Web and CiNii database for intervention trials and observational studies. Search terms were constructed from related words for excess AND iodine intake or excretion AND thyroid hormones or diseases AND study designs. After considering the qualitative heterogeneity among studies, a meta-analysis was conducted and odds ratios and 95% confidence intervals (CI) were estimated in random-effects models. A protocol was registered with PROSPERO (No. CRD42015028081). Results 50 articles were included, including three intervention trials, six case-control studies, six follow-up studies and 35 cross-sectional studies. Three cross-sectional studies in adults included in meta-analysis. Odds ratio of overt and subclinical hypothyroidism between excess and adequate populations were 2.78 (CI:1.47 to 5.27) and 2.03 (CI:1.58 to 2.62) in adults, respectively. Source of excess iodine status was mainly iodized salt or water in included studies. Conclusion Although universal salt iodization has improved goiter rates, chronic exposure to excess iodine from water or poorly monitored salt are risk factors for hypothyroidism in free-living populations. Monitoring of both iodine concentration in salt as well as the iodine concentration in local drinking water are essential to preventing thyroid diseases. Hypothyroidism should be also carefully monitored in areas with excess iodine. Because of the low quality and limited number of included studies, further evidence and review are required. PMID:28282437

The relationship between age of onset and risk factors including family history and life style in Korean population with type 2 diabetes mellitus

PubMed Central

Noh, Jin-Won; Jung, Jin Hee; Park, Jeong Eun; Lee, Jung Hwa; Sim, Kang Hee; Park, Jumin; Kim, Min Hee; Yoo, Ki-Bong

2018-01-01

[Purpose] The purpose of the present study was to assess the relationship between age of onset and risk factors including family history and life style in Korean population with type 2 diabetes mellitus (T2D). [Subjects and Methods] Subjects with T2D patients who received outpatient care for blood sugar control were randomly sampled at 13 general hospitals and 969 subjects were included. Cox proportional hazard models were used to confirm associations between age of onset and risk factors including family history and life style in Korean population with T2D. [Results] Parent history of T2D was significantly associated with age of onset. Compared to none of family members with T2D, those whose both father and mother had a history showed the highest the risk of early-onset (HR=2.36; 95% CI=1.45–3.85). Mother and father’s history of T2D (HR=1.73; 95% CI=1.46–2.05; HR=1.83; 95% CI=1.40–2.37) were associated with the risk of early-onset. Moreover, exercise (HR=1.23, CI=1.08–1.40) smoking status (HR=1.62, CI=1.32–1.99), and drinking (HR=1.32, CI=1.13–1.54) were associated with a higher risk for the early-onset. [Conclusion] Family history as well as life style including exercise, smoking, and drinking are the risk factors for early-onset factor in Korean population with T2D. PMID:29545678

Targeting Neural Endophenotypes of Eating Disorders with Non-invasive Brain Stimulation

PubMed Central

Dunlop, Katharine A.; Woodside, Blake; Downar, Jonathan

2016-01-01

The term “eating disorders” (ED) encompasses a wide variety of disordered eating and compensatory behaviors, and so the term is associated with considerable clinical and phenotypic heterogeneity. This heterogeneity makes optimizing treatment techniques difficult. One class of treatments is non-invasive brain stimulation (NIBS). NIBS, including repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS), are accessible forms of neuromodulation that alter the cortical excitability of a target brain region. It is crucial for NIBS to be successful that the target is well selected for the patient population in question. Targets may best be selected by stepping back from conventional DSM-5 diagnostic criteria to identify neural substrates of more basic phenotypes, including behavior related to rewards and punishment, cognitive control, and social processes. These phenotypic dimensions have been recently laid out by the Research Domain Criteria (RDoC) initiative. Consequently, this review is intended to identify potential dimensions as outlined by the RDoC and the underlying behavioral and neurobiological targets associated with ED. This review will also identify candidate targets for NIBS based on these dimensions and review the available literature on rTMS and tDCS in ED. This review systematically reviews abnormal neural circuitry in ED within the RDoC framework, and also systematically reviews the available literature investigating NIBS as a treatment for ED. PMID:26909013

Off-target effects of sulforaphane include the derepression of long terminal repeats through histone acetylation events.

PubMed

Baier, Scott R; Zbasnik, Richard; Schlegel, Vicki; Zempleni, Janos

2014-06-01

Sulforaphane is a naturally occurring isothiocyanate in cruciferous vegetables. Sulforaphane inhibits histone deacetylases, leading to the transcriptional activation of genes including tumor suppressor genes. The compound has attracted considerable attention in the chemoprevention of prostate cancer. Here we tested the hypothesis that sulforaphane is not specific for tumor suppressor genes but also activates loci such as long terminal repeats (LTRs), which might impair genome stability. Studies were conducted using chemically pure sulforaphane in primary human IMR-90 fibroblasts and in broccoli sprout feeding studies in healthy adults. Sulforaphane (2.0 μM) caused an increase in LTR transcriptional activity in cultured cells. Consumption of broccoli sprouts (34, 68 or 102 g) by human volunteers caused a dose dependent elevation in LTR mRNA in circulating leukocytes, peaking at more than a 10-fold increase. This increase in transcript levels was associated with an increase in histone H3 K9 acetylation marks in LTR 15 in peripheral blood mononuclear cells from subjects consuming sprouts. Collectively, this study suggests that sulforaphane has off-target effects that warrant further investigation when recommending high levels of sulforaphane intake, despite its promising activities in chemoprevention. Copyright © 2014 Elsevier Inc. All rights reserved.

Audiovisual synchrony enhances BOLD responses in a brain network including multisensory STS while also enhancing target-detection performance for both modalities

PubMed Central

Marchant, Jennifer L; Ruff, Christian C; Driver, Jon

2012-01-01

The brain seeks to combine related inputs from different senses (e.g., hearing and vision), via multisensory integration. Temporal information can indicate whether stimuli in different senses are related or not. A recent human fMRI study (Noesselt et al. [2007]: J Neurosci 27:11431–11441) used auditory and visual trains of beeps and flashes with erratic timing, manipulating whether auditory and visual trains were synchronous or unrelated in temporal pattern. A region of superior temporal sulcus (STS) showed higher BOLD signal for the synchronous condition. But this could not be related to performance, and it remained unclear if the erratic, unpredictable nature of the stimulus trains was important. Here we compared synchronous audiovisual trains to asynchronous trains, while using a behavioral task requiring detection of higher-intensity target events in either modality. We further varied whether the stimulus trains had predictable temporal pattern or not. Synchrony (versus lag) between auditory and visual trains enhanced behavioral sensitivity (d') to intensity targets in either modality, regardless of predictable versus unpredictable patterning. The analogous contrast in fMRI revealed BOLD increases in several brain areas, including the left STS region reported by Noesselt et al. [2007: J Neurosci 27:11431–11441]. The synchrony effect on BOLD here correlated with the subject-by-subject impact on performance. Predictability of temporal pattern did not affect target detection performance or STS activity, but did lead to an interaction with audiovisual synchrony for BOLD in inferior parietal cortex. PMID:21953980

An Immunization Strategy for Hidden Populations.

PubMed

Chen, Saran; Lu, Xin

2017-06-12

Hidden populations, such as injecting drug users (IDUs), sex workers (SWs) and men who have sex with men (MSM), are considered at high risk of contracting and transmitting infectious diseases such as AIDS, gonorrhea, syphilis etc. However, public health interventions to such groups are prohibited due to strong privacy concerns and lack of global information, which is a necessity for traditional strategies such as targeted immunization and acquaintance immunization. In this study, we introduce an innovative intervention strategy to be used in combination with a sampling approach that is widely used for hidden populations, Respondent-driven Sampling (RDS). The RDS strategy is implemented in two steps: First, RDS is used to estimate the average degree (personal network size) and degree distribution of the target population with sample data. Second, a cut-off threshold is calculated and used to screen the respondents to be immunized. Simulations on model networks and real-world networks reveal that the efficiency of the RDS strategy is close to that of the targeted strategy. As the new strategy can be implemented with the RDS sampling process, it provides a cost-efficient and feasible approach for disease intervention and control for hidden populations.

Blood pressure targets for hypertension in older adults.

PubMed

Garrison, Scott R; Kolber, Michael R; Korownyk, Christina S; McCracken, Rita K; Heran, Balraj S; Allan, G Michael

2017-08-08

-cardiovascular mortality, unplanned hospitalisation, each component of cardiovascular serious adverse events separately (including cerebrovascular disease, cardiac disease, vascular disease, and renal failure), total serious adverse events, total minor adverse events, withdrawals due to adverse effects, systolic BP achieved, and diastolic BP achieved. We found and included three unblinded randomised trials in 8221 older adults (mean age 74.8 years), in which higher BP targets of less than 150/90 mmHg (two trials) and less than 160/90 mmHg (one trial) were compared to a lower target of less than 140/90 mmHg. Treatment to the two different BP targets over two to four years failed to produce a difference in any of our primary outcomes, including all-cause mortality (RR 1.24 95% CI 0.99 to 1.54), stroke (RR 1.25 95% CI 0.94 to 1.67) and total cardiovascular serious adverse events (RR 1.19 95% CI 0.98 to 1.45). However, the 95% confidence intervals of these outcomes suggest the lower BP target is probably not worse, and might offer a clinically important benefit. We judged all comparisons to be based on low-quality evidence. Data on adverse effects were not available from all trials and not different, including total serious adverse events, total minor adverse events, and withdrawals due to adverse effects. At the present time there is insufficient evidence to know whether a higher BP target (less than150 to 160/95 to 105 mmHg) or a lower BP target (less than 140/90 mmHg) is better for older adults with high BP. Additional good-quality trials assessing BP targets in this population are needed.

Using existing data to predict and quantify the risks of GM forage to a population of a non-target invertebrate species: a New Zealand case study.

PubMed

O'Callaghan, Maureen; Soboleva, Tanya K; Barratt, Barbara I P

2010-01-01

Determining the effects of genetically modified (GM) crops on non-target organisms is essential as many non-target species provide important ecological functions. However, it is simply not possible to collect field data on more than a few potential non-target species present in the receiving environment of a GM crop. While risk assessment must be rigorous, new approaches are necessary to improve the efficiency of the process. Utilisation of published information and existing data on the phenology and population dynamics of test species in the field can be combined with limited amounts of experimental biosafety data to predict possible outcomes on species persistence. This paper presents an example of an approach where data from laboratory experiments and field studies on phenology are combined using predictive modelling. Using the New Zealand native weevil species Nicaeana cervina as a case study, we could predict that oviposition rates of the weevil feeding on a GM ryegrass could be reduced by up to 30% without threat to populations of the weevil in pastoral ecosystems. In addition, an experimentally established correlation between feeding level and oviposition led to the prediction that a consistent reduction in feeding of 50% or higher indicated a significant risk to the species and could potentially lead to local extinctions. This approach to biosafety risk assessment, maximising the use of pre-existing field and laboratory data on non-target species, can make an important contribution to informed decision-making by regulatory authorities and developers of new technologies. © ISBR, EDP Sciences, 2011.

Targeting Interventions for Ethnic Minority and Low-Income Populations

ERIC Educational Resources Information Center

Kumanyika, Shiriki; Grier, Sonya

2006-01-01

Although rates of childhood obesity among the general population are alarmingly high, they are higher still in ethnic minority and low-income communities. The disparities pose a major challenge for policymakers and practitioners planning strategies for obesity prevention. In this article Shiriki Kumanyika and Sonya Grier summarize differences in…

Fetal Alcohol Spectrum Disorder (FASD) Associated Neural Defects: Complex Mechanisms and Potential Therapeutic Targets

PubMed Central

Muralidharan, Pooja; Sarmah, Swapnalee; Zhou, Feng C.; Marrs, James A.

2013-01-01

Fetal alcohol spectrum disorder (FASD), caused by prenatal alcohol exposure, can result in craniofacial dysmorphism, cognitive impairment, sensory and motor disabilities among other defects. FASD incidences are as high as 2% to 5 % children born in the US, and prevalence is higher in low socioeconomic populations. Despite various mechanisms being proposed to explain the etiology of FASD, the molecular targets of ethanol toxicity during development are unknown. Proposed mechanisms include cell death, cell signaling defects and gene expression changes. More recently, the involvement of several other molecular pathways was explored, including non-coding RNA, epigenetic changes and specific vitamin deficiencies. These various pathways may interact, producing a wide spectrum of consequences. Detailed understanding of these various pathways and their interactions will facilitate the therapeutic target identification, leading to new clinical intervention, which may reduce the incidence and severity of these highly prevalent preventable birth defects. This review discusses manifestations of alcohol exposure on the developing central nervous system, including the neural crest cells and sensory neural placodes, focusing on molecular neurodevelopmental pathways as possible therapeutic targets for prevention or protection. PMID:24961433

Fetal Alcohol Spectrum Disorder (FASD) Associated Neural Defects: Complex Mechanisms and Potential Therapeutic Targets.

PubMed

Muralidharan, Pooja; Sarmah, Swapnalee; Zhou, Feng C; Marrs, James A

2013-06-19

Fetal alcohol spectrum disorder (FASD), caused by prenatal alcohol exposure, can result in craniofacial dysmorphism, cognitive impairment, sensory and motor disabilities among other defects. FASD incidences are as high as 2% to 5 % children born in the US, and prevalence is higher in low socioeconomic populations. Despite various mechanisms being proposed to explain the etiology of FASD, the molecular targets of ethanol toxicity during development are unknown. Proposed mechanisms include cell death, cell signaling defects and gene expression changes. More recently, the involvement of several other molecular pathways was explored, including non-coding RNA, epigenetic changes and specific vitamin deficiencies. These various pathways may interact, producing a wide spectrum of consequences. Detailed understanding of these various pathways and their interactions will facilitate the therapeutic target identification, leading to new clinical intervention, which may reduce the incidence and severity of these highly prevalent preventable birth defects. This review discusses manifestations of alcohol exposure on the developing central nervous system, including the neural crest cells and sensory neural placodes, focusing on molecular neurodevelopmental pathways as possible therapeutic targets for prevention or protection.

Nuclease Target Site Selection for Maximizing On-target Activity and Minimizing Off-target Effects in Genome Editing

PubMed Central

Lee, Ciaran M; Cradick, Thomas J; Fine, Eli J; Bao, Gang

2016-01-01

The rapid advancement in targeted genome editing using engineered nucleases such as ZFNs, TALENs, and CRISPR/Cas9 systems has resulted in a suite of powerful methods that allows researchers to target any genomic locus of interest. A complementary set of design tools has been developed to aid researchers with nuclease design, target site selection, and experimental validation. Here, we review the various tools available for target selection in designing engineered nucleases, and for quantifying nuclease activity and specificity, including web-based search tools and experimental methods. We also elucidate challenges in target selection, especially in predicting off-target effects, and discuss future directions in precision genome editing and its applications. PMID:26750397

Using Population-Size Estimation and Cross-sectional Survey Methods to Evaluate HIV Service Coverage Among Key Populations in Burkina Faso and Togo.

PubMed

Holland, Claire E; Kouanda, Seni; Lougué, Marcel; Pitche, Vincent Palokinam; Schwartz, Sheree; Anato, Simplice; Ouedraogo, Henri Gautier; Tchalla, Jules; Yah, Clarence S; Kapesa, Laurent; Ketende, Sosthenes; Beyrer, Chris; Baral, Stefan

2016-11-01

The objective of our study was to measure progress toward the UNAIDS 90-90-90 HIV care targets among key populations in urban areas of 2 countries in West Africa: Burkina Faso and Togo. We recruited female sex workers (FSWs) and men who have sex with men (MSM) through respondent-driven sampling. From January to July 2013, 2738 participants were enrolled, tested for HIV, and completed interviewer-administered surveys. We used population-size estimation methods to calculate the number of people who were engaged in the HIV continuum of care. HIV prevalence ranged from 0.6% (2 of 329) of MSM in Kara, Togo, to 32.9% (115 of 350) of FSWs in Bobo Dioulasso, Burkina Faso. Of those confirmed to be HIV infected, a range of 0.0% (0 of 2) of MSM in Kara to 55.7% (64 of 115) of FSWs in Bobo Dioulasso were using ART. Based on population estimates, the percentage gap between HIV-infected people who should be using ART (per the 90-90-90 targets) and those who reported using ART ranged from 31.5% among FSWs in Bobo Dioulasso to 100.0% among MSM in Kara. HIV service coverage among MSM and FSWs in Burkina Faso and Togo was low in 2013. Interventions for improving engagement of these at-risk populations in the HIV continuum of care should include frequent, routine HIV testing and linkage to evidence-based HIV treatment services. Population-size estimates can be used to inform governments, policy makers, and funding agencies about where elements of HIV service coverage are most needed.

Guidelines for integrating population education into primary education and literacy programmes.

PubMed

1989-01-01

In recent seminars and workshops in the Asia and Pacific region the integration of population education into primary schools and literacy programs were the main topics. In most of the countries in this area separate courses in population education appear to be unfeasible for primary and secondary schools. In the nonformal area experience has indicated that population education acquires more meaning and relevance if it is integrated into an ongoing development program. The integration approach requires knowledge of the contents of the accommodating subjects or programs and knowledge of the contents of the accommodating subjects or programs and knowledge of the contents of population education. Guidelines suggested include the following steps in developing an integrated curriculum and instructional materials. First determine the needs, characteristics and other background information needed on the target group. Next prioritize the problems and needs of the target group, and formulate educational objectives from the identified needs and problems. Next determine and sequence the curriculum contents and then determine specific population education objectives and contents for integration, and what specific materials have to be developed. Then identify the specific type of format of materials to be developed, and write the first draft of the material. Also prepare illustrations and other art and graphic materials. Then the draft material should be reviewed and translated into the language of the target audience if needed. The materials should then be pretested, or field tested, using a sample of the intended users. To make sure the materials are reaching the target groups and being used effectively, a user's guide should be prepared and teachers and facilitators, as well as supervisors, should be prepared on the use of the material. In addition, a distribution and utilization plan should be prepared. Nonformal education materials can be distributed through libraries

A systematic review of suicide prevention interventions targeting indigenous peoples in Australia, United States, Canada and New Zealand

PubMed Central

2013-01-01

Background Indigenous peoples of Australia, Canada, United States and New Zealand experience disproportionately high rates of suicide. As such, the methodological quality of evaluations of suicide prevention interventions targeting these Indigenous populations should be rigorously examined, in order to determine the extent to which they are effective for reducing rates of Indigenous suicide and suicidal behaviours. This systematic review aims to: 1) identify published evaluations of suicide prevention interventions targeting Indigenous peoples in Australia, Canada, United States and New Zealand; 2) critique their methodological quality; and 3) describe their main characteristics. Methods A systematic search of 17 electronic databases and 13 websites for the period 1981–2012 (inclusive) was undertaken. The reference lists of reviews of suicide prevention interventions were hand-searched for additional relevant studies not identified by the electronic and web search. The methodological quality of evaluations of suicide prevention interventions was assessed using a standardised assessment tool. Results Nine evaluations of suicide prevention interventions were identified: five targeting Native Americans; three targeting Aboriginal Australians; and one First Nation Canadians. The main intervention strategies employed included: Community Prevention, Gatekeeper Training, and Education. Only three of the nine evaluations measured changes in rates of suicide or suicidal behaviour, all of which reported significant improvements. The methodological quality of evaluations was variable. Particular problems included weak study designs, reliance on self-report measures, highly variable consent and follow-up rates, and the absence of economic or cost analyses. Conclusions There is an urgent need for an increase in the number of evaluations of preventive interventions targeting reductions in Indigenous suicide using methodologically rigorous study designs across geographically

A systematic review of suicide prevention interventions targeting indigenous peoples in Australia, United States, Canada and New Zealand.

PubMed

Clifford, Anton C; Doran, Christopher M; Tsey, Komla

2013-05-13

Indigenous peoples of Australia, Canada, United States and New Zealand experience disproportionately high rates of suicide. As such, the methodological quality of evaluations of suicide prevention interventions targeting these Indigenous populations should be rigorously examined, in order to determine the extent to which they are effective for reducing rates of Indigenous suicide and suicidal behaviours. This systematic review aims to: 1) identify published evaluations of suicide prevention interventions targeting Indigenous peoples in Australia, Canada, United States and New Zealand; 2) critique their methodological quality; and 3) describe their main characteristics. A systematic search of 17 electronic databases and 13 websites for the period 1981-2012 (inclusive) was undertaken. The reference lists of reviews of suicide prevention interventions were hand-searched for additional relevant studies not identified by the electronic and web search. The methodological quality of evaluations of suicide prevention interventions was assessed using a standardised assessment tool. Nine evaluations of suicide prevention interventions were identified: five targeting Native Americans; three targeting Aboriginal Australians; and one First Nation Canadians. The main intervention strategies employed included: Community Prevention, Gatekeeper Training, and Education. Only three of the nine evaluations measured changes in rates of suicide or suicidal behaviour, all of which reported significant improvements. The methodological quality of evaluations was variable. Particular problems included weak study designs, reliance on self-report measures, highly variable consent and follow-up rates, and the absence of economic or cost analyses. There is an urgent need for an increase in the number of evaluations of preventive interventions targeting reductions in Indigenous suicide using methodologically rigorous study designs across geographically and culturally diverse Indigenous

Profiles of Brain Metastases: Prioritization of Therapeutic Targets.

PubMed

Ferguson, Sherise D; Zheng, Siyuan; Xiu, Joanne; Zhou, Shouhao; Khasraw, Mustafa; Brastianos, Priscilla K; Kesari, Santosh; Hu, Jethro; Rudnick, Jeremy; Salacz, Michael E; Piccioni, David; Huang, Suyun; Davies, Michael A; Glitza, Isabella C; Heymach, John V; Zhang, Jianjun; Ibrahim, Nuhad K; DeGroot, John F; McCarty, Joseph; O'Brien, Barbara J; Sawaya, Raymond; Verhaak, Roeland G W; Reddy, Sandeep K; Priebe, Waldemar; Gatalica, Zoran; Spetzler, David; Heimberger, Amy B

2018-06-19

We sought to compare the tumor profiles of brain metastases from common cancers with those of primary tumors and extracranial metastases in order to identify potential targets and prioritize rational treatment strategies. Tumor samples were collected from both the primary and metastatic sites of non-small cell lung cancer, breast cancer, and melanoma from patients in locations worldwide, and these were submitted to Caris Life Sciences for tumor multiplatform analysis, including gene sequencing (Sanger and next-generation sequencing with a targeted 47-gene panel), protein expression (assayed by immunohistochemistry), and gene amplification (assayed by in situ hybridization). The data analysis considered differential protein expression, gene amplification, and mutations among brain metastases, extracranial metastases, and primary tumors. The analyzed population included: 16,999 unmatched primary tumor and/or metastasis samples: 8178 non-small cell lung cancers (5098 primaries; 2787 systemic metastases; 293 brain metastases), 7064 breast cancers (3496 primaries; 3469 systemic metastases; 99 brain metastases), and 1757 melanomas (660 primaries; 996 systemic metastases; 101 brain metastases). TOP2A expression was increased in brain metastases from all 3 cancers, and brain metastases overexpressed multiple proteins clustering around functions critical to DNA synthesis and repair and implicated in chemotherapy resistance, including RRM1, TS, ERCC1, and TOPO1. cMET was overexpressed in melanoma brain metastases relative to primary skin specimens. Brain metastasis patients may particularly benefit from therapeutic targeting of enzymes associated with DNA synthesis, replication, and/or repair. This article is protected by copyright. All rights reserved. © 2018 UICC.

Pharmacogenomics of warfarin in populations of African descent.

PubMed

Suarez-Kurtz, Guilherme; Botton, Mariana R

2013-02-01

Warfarin is the most commonly prescribed oral anticoagulant worldwide despite its narrow therapeutic index and the notorious inter- and intra-individual variability in dose required for the target clinical effect. Pharmacogenetic polymorphisms are major determinants of warfarin pharmacokinetic and dynamics and included in several warfarin dosing algorithms. This review focuses on warfarin pharmacogenomics in sub-Saharan peoples, African Americans and admixed Brazilians. These 'Black' populations differ in several aspects, notably their extent of recent admixture with Europeans, a factor which impacts on the frequency distribution of pharmacogenomic polymorphisms relevant to warfarin dose requirement for the target clinical effect. Whereas a small number of polymorphisms in VKORC1 (3673G > A, rs9923231), CYP2C9 (alleles *2 and *3, rs1799853 and rs1057910, respectively) and arguably CYP4F2 (rs2108622), may capture most of the pharmacogenomic influence on warfarin dose variance in White populations, additional polymorphisms in these, and in other, genes (e.g. CALU rs339097) increase the predictive power of pharmacogenetic warfarin dosing algorithms in the Black populations examined. A personalized strategy for initiation of warfarin therapy, allowing for improved safety and cost-effectiveness for populations of African descent must take into account their pharmacogenomic diversity, as well as socio-economical, cultural and medical factors. Accounting for this heterogeneity in algorithms that are 'friendly' enough to be adopted by warfarin prescribers worldwide requires gathering information from trials at different population levels, but demands also a critical appraisal of racial/ethnic labels that are commonly used in the clinical pharmacology literature but do not accurately reflect genetic ancestry and population diversity. © 2012 The Authors. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.

TARGETING POLYMER THERAPEUTICS TO BONE

PubMed Central

Low, Stewart; Kopeček, Jindřich

2012-01-01

An aging population in the developing world has led to an increase in musculoskeletal diseases such as osteoporosis and bone metastases. Left untreated many bone diseases cause debilitating pain and in the case of cancer, death. Many potential drugs are effective in treating diseases but result in side effects preventing their efficacy in the clinic. Bone, however, provides an unique environment of inorganic solids, which can be exploited in order to effectively target drugs to diseased tissue. By integration of bone targeting moieties to drug-carrying water-soluble polymers, the payload to diseased area can be increased while side effects decreased. The realization of clinically relevant bone targeted polymer therapeutics depends on (1) understanding bone targeting moiety interactions, (2) development of controlled drug delivery systems, as well as (3) understanding drug interactions. The latter makes it possible to develop bone targeted synergistic drug delivery systems. PMID:22316530

Challenges of Sustaining the International Space Station through 2020 and Beyond: Including Epistemic Uncertainty in Reassessing Confidence Targets

NASA Technical Reports Server (NTRS)

Anderson, Leif; Carter-Journet, Katrina; Box, Neil; DiFilippo, Denise; Harrington, Sean; Jackson, David; Lutomski, Michael

2012-01-01

This paper introduces an analytical approach, Probability and Confidence Trade-space (PACT), which can be used to assess uncertainty in International Space Station (ISS) hardware sparing necessary to extend the life of the vehicle. There are several key areas under consideration in this research. We investigate what sparing confidence targets may be reasonable to ensure vehicle survivability and for completion of science on the ISS. The results of the analysis will provide a methodological basis for reassessing vehicle subsystem confidence targets. An ongoing annual analysis currently compares the probability of existing spares exceeding the total expected unit demand of the Orbital Replacement Unit (ORU) in functional hierarchies approximating the vehicle subsystems. In cases where the functional hierarchies availability does not meet subsystem confidence targets, the current sparing analysis further identifies which ORUs may require additional spares to extend the life of the ISS. The resulting probability is dependent upon hardware reliability estimates. However, the ISS hardware fleet carries considerable epistemic uncertainty (uncertainty in the knowledge of the true hardware failure rate), which does not currently factor into the annual sparing analysis. The existing confidence targets may be conservative. This paper will also discuss how confidence targets may be relaxed based on the inclusion of epistemic uncertainty for each ORU. The paper will conclude with strengths and limitations for implementing the analytical approach in sustaining the ISS through end of life, 2020 and beyond.

Cannabinoid Receptor 2 Signaling in Neurodegenerative Disorders: From Pathogenesis to a Promising Therapeutic Target

PubMed Central

Cassano, Tommaso; Calcagnini, Silvio; Pace, Lorenzo; De Marco, Federico; Romano, Adele; Gaetani, Silvana

2017-01-01

As a consequence of an increasingly aging population, the number of people affected by neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease and Huntington's disease, is rapidly increasing. Although the etiology of these diseases has not been completely defined, common molecular mechanisms including neuroinflammation, excitotoxicity and mitochondrial dysfunction have been confirmed and can be targeted therapeutically. Moreover, recent studies have shown that endogenous cannabinoid signaling plays a number of modulatory roles throughout the central nervous system (CNS), including the neuroinflammation and neurogenesis. In particular, the up-regulation of type-2 cannabinoid (CB2) receptors has been found in a number of neurodegenerative disorders. Thus, the modulation of CB2 receptor signaling may represent a promising therapeutic target with minimal psychotropic effects that can be used to modulate endocannabinoid-based therapeutic approaches and to reduce neuronal degeneration. For these reasons this review will focus on the CB2 receptor as a promising pharmacological target in a number of neurodegenerative diseases. PMID:28210207

A stereotaxic, population-averaged T1w ovine brain atlas including cerebral morphology and tissue volumes

PubMed Central

Nitzsche, Björn; Frey, Stephen; Collins, Louis D.; Seeger, Johannes; Lobsien, Donald; Dreyer, Antje; Kirsten, Holger; Stoffel, Michael H.; Fonov, Vladimir S.; Boltze, Johannes

2015-01-01

Standard stereotaxic reference systems play a key role in human brain studies. Stereotaxic coordinate systems have also been developed for experimental animals including non-human primates, dogs, and rodents. However, they are lacking for other species being relevant in experimental neuroscience including sheep. Here, we present a spatial, unbiased ovine brain template with tissue probability maps (TPM) that offer a detailed stereotaxic reference frame for anatomical features and localization of brain areas, thereby enabling inter-individual and cross-study comparability. Three-dimensional data sets from healthy adult Merino sheep (Ovis orientalis aries, 12 ewes and 26 neutered rams) were acquired on a 1.5 T Philips MRI using a T1w sequence. Data were averaged by linear and non-linear registration algorithms. Moreover, animals were subjected to detailed brain volume analysis including examinations with respect to body weight (BW), age, and sex. The created T1w brain template provides an appropriate population-averaged ovine brain anatomy in a spatial standard coordinate system. Additionally, TPM for gray (GM) and white (WM) matter as well as cerebrospinal fluid (CSF) classification enabled automatic prior-based tissue segmentation using statistical parametric mapping (SPM). Overall, a positive correlation of GM volume and BW explained about 15% of the variance of GM while a positive correlation between WM and age was found. Absolute tissue volume differences were not detected, indeed ewes showed significantly more GM per bodyweight as compared to neutered rams. The created framework including spatial brain template and TPM represent a useful tool for unbiased automatic image preprocessing and morphological characterization in sheep. Therefore, the reported results may serve as a starting point for further experimental and/or translational research aiming at in vivo analysis in this species. PMID:26089780

Metapopulation effective size and conservation genetic goals for the Fennoscandian wolf (Canis lupus) population

PubMed Central

Laikre, L; Olsson, F; Jansson, E; Hössjer, O; Ryman, N

2016-01-01

The Scandinavian wolf population descends from only five individuals, is isolated, highly inbred and exhibits inbreeding depression. To meet international conservation goals, suggestions include managing subdivided wolf populations over Fennoscandia as a metapopulation; a genetically effective population size of Ne⩾500, in line with the widely accepted long-term genetic viability target, might be attainable with gene flow among subpopulations of Scandinavia, Finland and Russian parts of Fennoscandia. Analytical means for modeling Ne of subdivided populations under such non-idealized situations have been missing, but we recently developed new mathematical methods for exploring inbreeding dynamics and effective population size of complex metapopulations. We apply this theory to the Fennoscandian wolves using empirical estimates of demographic parameters. We suggest that the long-term conservation genetic target for metapopulations should imply that inbreeding rates in the total system and in the separate subpopulations should not exceed Δf=0.001. This implies a meta-Ne of NeMeta⩾500 and a realized effective size of each subpopulation of NeRx⩾500. With current local effective population sizes and one migrant per generation, as recommended by management guidelines, the meta-Ne that can be reached is ~250. Unidirectional gene flow from Finland to Scandinavia reduces meta-Ne to ~130. Our results indicate that both local subpopulation effective sizes and migration among subpopulations must increase substantially from current levels to meet the conservation target. Alternatively, immigration from a large (Ne⩾500) population in northwestern Russia could support the Fennoscandian metapopulation, but immigration must be substantial (5–10 effective immigrants per generation) and migration among Fennoscandian subpopulations must nevertheless increase. PMID:27328654

Effects of seed mixture sowing with resistant and susceptible rice on population dynamics of target planthoppers and non-target stemborers and leaffolders.

PubMed

Li, Zhuo; Wan, Guijun; Wang, Long; Parajulee, Megha N; Zhao, Zihua; Chen, Fajun

2018-07-01

The widespread planting of insect-resistant crops has caused a dramatic shift in agricultural landscapes, thus raising concerns about the potential impact on both target and non-target pests worldwide. In this study, we examined the potential effects of six seed mixture ratios of insect-resistance dominance [100% (R100), 95% (S05R95), 90% (S10R90), 80% (S20R80), 60% (S40R60), and 0% (S100)] on target and non-target pests in a 2-year field trial in southern China. The occurrence of the target pests Nilaparvata lugens and Sogatella furcifera decreased with an increase in the ratio of resistant rice, and mixture ratios with ≥90% resistant rice significantly increased the pest suppression efficiency, with the lowest occurrences of the non-target pests Sesamia inferens, Chilo suppressalis and Cnaphalocrocis medinalis for S100 and S10R90 seed mixture ratios. Furthermore, there were no significant differences in the 1000-grain dry weight and grain yield between R100 and other treatments with ≥80% resistant seeds in the mixture (S20R80, S10R90 and S05R95). S10R90 produced a good yield and provided the most effective control of both target and non-target pests, with the potential to significantly reduce the application of chemical pesticides for integrated pest management in paddy fields. It is further presumed that the strategy of seed mixture with resistant and susceptible rice would be advantageous for rice yield stability. © 2018 Society of Chemical Industry. © 2018 Society of Chemical Industry.

In-depth resistome analysis by targeted metagenomics.

PubMed

Lanza, Val F; Baquero, Fernando; Martínez, José Luís; Ramos-Ruíz, Ricardo; González-Zorn, Bruno; Andremont, Antoine; Sánchez-Valenzuela, Antonio; Ehrlich, Stanislav Dusko; Kennedy, Sean; Ruppé, Etienne; van Schaik, Willem; Willems, Rob J; de la Cruz, Fernando; Coque, Teresa M

2018-01-15

Antimicrobial resistance is a major global health challenge. Metagenomics allows analyzing the presence and dynamics of "resistomes" (the ensemble of genes encoding antimicrobial resistance in a given microbiome) in disparate microbial ecosystems. However, the low sensitivity and specificity of available metagenomic methods preclude the detection of minority populations (often present below their detection threshold) and/or the identification of allelic variants that differ in the resulting phenotype. Here, we describe a novel strategy that combines targeted metagenomics using last generation in-solution capture platforms, with novel bioinformatics tools to establish a standardized framework that allows both quantitative and qualitative analyses of resistomes. We developed ResCap, a targeted sequence capture platform based on SeqCapEZ (NimbleGene) technology, which includes probes for 8667 canonical resistance genes (7963 antibiotic resistance genes and 704 genes conferring resistance to metals or biocides), and 2517 relaxase genes (plasmid markers) and 78,600 genes homologous to the previous identified targets (47,806 for antibiotics and 30,794 for biocides or metals). Its performance was compared with metagenomic shotgun sequencing (MSS) for 17 fecal samples (9 humans, 8 swine). ResCap significantly improves MSS to detect "gene abundance" (from 2.0 to 83.2%) and "gene diversity" (26 versus 14.9 genes unequivocally detected per sample per million of reads; the number of reads unequivocally mapped increasing up to 300-fold by using ResCap), which were calculated using novel bioinformatic tools. ResCap also facilitated the analysis of novel genes potentially involved in the resistance to antibiotics, metals, biocides, or any combination thereof. ResCap, the first targeted sequence capture, specifically developed to analyze resistomes, greatly enhances the sensitivity and specificity of available metagenomic methods and offers the possibility to analyze genes

A moving target--incorporating knowledge of the spatial ecology of fish into the assessment and management of freshwater fish populations.

PubMed

Cooke, Steven J; Martins, Eduardo G; Struthers, Daniel P; Gutowsky, Lee F G; Power, Michael; Doka, Susan E; Dettmers, John M; Crook, David A; Lucas, Martyn C; Holbrook, Christopher M; Krueger, Charles C

2016-04-01

Freshwater fish move vertically and horizontally through the aquatic landscape for a variety of reasons, such as to find and exploit patchy resources or to locate essential habitats (e.g., for spawning). Inherent challenges exist with the assessment of fish populations because they are moving targets. We submit that quantifying and describing the spatial ecology of fish and their habitat is an important component of freshwater fishery assessment and management. With a growing number of tools available for studying the spatial ecology of fishes (e.g., telemetry, population genetics, hydroacoustics, otolith microchemistry, stable isotope analysis), new knowledge can now be generated and incorporated into biological assessment and fishery management. For example, knowing when, where, and how to deploy assessment gears is essential to inform, refine, or calibrate assessment protocols. Such information is also useful for quantifying or avoiding bycatch of imperiled species. Knowledge of habitat connectivity and usage can identify critically important migration corridors and habitats and can be used to improve our understanding of variables that influence spatial structuring of fish populations. Similarly, demographic processes are partly driven by the behavior of fish and mediated by environmental drivers. Information on these processes is critical to the development and application of realistic population dynamics models. Collectively, biological assessment, when informed by knowledge of spatial ecology, can provide managers with the ability to understand how and when fish and their habitats may be exposed to different threats. Naturally, this knowledge helps to better evaluate or develop strategies to protect the long-term viability of fishery production. Failure to understand the spatial ecology of fishes and to incorporate spatiotemporal data can bias population assessments and forecasts and potentially lead to ineffective or counterproductive management actions.

Targeted Nanomaterials for Phototherapy

PubMed Central

Chitgupi, Upendra; Qin, Yiru; Lovell, Jonathan F.

2017-01-01

Phototherapies involve the irradiation of target tissues with light. To further enhance selectivity and potency, numerous molecularly targeted photosensitizers and photoactive nanoparticles have been developed. Active targeting typically involves harnessing the affinity between a ligand and a cell surface receptor for improved accumulation in the targeted tissue. Targeting ligands including peptides, proteins, aptamers and small molecules have been explored for phototherapy. In this review, recent examples of targeted nanomaterials used in phototherapy are summarized. PMID:29071178

Targeted mass media interventions promoting healthy behaviours to reduce risk of non-communicable diseases in adult, ethnic minorities.

PubMed

Mosdøl, Annhild; Lidal, Ingeborg B; Straumann, Gyri H; Vist, Gunn E

2017-02-17

Physical activity, a balanced diet, avoidance of tobacco exposure, and limited alcohol consumption may reduce morbidity and mortality from non-communicable diseases (NCDs). Mass media interventions are commonly used to encourage healthier behaviours in population groups. It is unclear whether targeted mass media interventions for ethnic minority groups are more or less effective in changing behaviours than those developed for the general population. To determine the effects of mass media interventions targeting adult ethnic minorities with messages about physical activity, dietary patterns, tobacco use or alcohol consumption to reduce the risk of NCDs. We searched CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, ERIC, SweMed+, and ISI Web of Science until August 2016. We also searched for grey literature in OpenGrey, Grey Literature Report, Eldis, and two relevant websites until October 2016. The searches were not restricted by language. We searched for individual and cluster-randomised controlled trials, controlled before-and-after studies (CBA) and interrupted time series studies (ITS). Relevant interventions promoted healthier behaviours related to physical activity, dietary patterns, tobacco use or alcohol consumption; were disseminated via mass media channels; and targeted ethnic minority groups. The population of interest comprised adults (≥ 18 years) from ethnic minority groups in the focal countries. Primary outcomes included indicators of behavioural change, self-reported behavioural change and knowledge and attitudes towards change. Secondary outcomes were the use of health promotion services and costs related to the project. Two authors independently reviewed the references to identify studies for inclusion. We extracted data and assessed the risk of bias in all included studies. We did not pool the results due to heterogeneity in comparisons made, outcomes, and study designs. We describe the results narratively and present them in 'Summary of findings

Effective treatment of glioblastoma requires crossing the blood–brain barrier and targeting tumors including cancer stem cells: The promise of nanomedicine

PubMed Central

Kim, Sang-Soo; Harford, Joe B.; Pirollo, Kathleen F.; Chang, Esther H.

2015-01-01

Glioblastoma multiforme (GBM) is the most aggressive and lethal type of brain tumor. Both therapeutic resistance and restricted permeation of drugs across the blood–brain barrier (BBB) play a major role in the poor prognosis of GBM patients. Accumulated evidence suggests that in many human cancers, including GBM, therapeutic resistance can be attributed to a small fraction of cancer cells known as cancer stem cells (CSCs). CSCs have been shown to have stem cell-like properties that enable them to evade traditional cytotoxic therapies, and so new CSC-directed anti-cancer therapies are needed. Nanoparticles have been designed to selectively deliver payloads to relevant target cells in the body, and there is considerable interest in the use of nanoparticles for CSC-directed anti-cancer therapies. Recent advances in the field of nanomedicine offer new possibilities for overcoming CSC-mediated therapeutic resistance and thus significantly improving management of GBM. In this review, we will examine the current nanomedicine approaches for targeting CSCs and their therapeutic implications. The inhibitory effect of various nanoparticle-based drug delivery system towards CSCs in GBM tumors is the primary focus of this review. PMID:26116770

A health promotion practicum targeting the college-age population.

PubMed

Diebold, C M; Chappell, H W; Robinson, M K

2000-01-01

Senior and sophomore baccalaureate nursing students at the University of Kentucky developed a health promotion exposition that targeted college students. This experience gave senior students the opportunity to practice leadership and management skills, such as planning, organizing, collaborating, delegating, evaluating, and time management and conflict resolution. Sophomore students developed teaching abilities, practiced assessment and communication techniques, and increased their knowledge of health-promoting behaviors. Both groups experienced team building and demonstrated accountability. Students reported a positive learning experience that met various course objectives in an innovative way.

Sharing reference data and including cows in the reference population improve genomic predictions in Danish Jersey

USDA-ARS?s Scientific Manuscript database

Small reference populations limit the accuracy of genomic prediction in numerically small breeds, such as the Danish Jersey. The objective of this study was to investigate two approaches to improve genomic prediction by increasing the size of the reference population for Danish Jerseys. The first ap...

Marketing and population problems.

PubMed

Farley, J U; Leavitt, H J

1971-07-01

There are many elements in population programs that are more familiar to marketing men than to some population experts. Advertising is essential to reach the target population, and advertising evaluation techniques (e.g., surrogate indexes or audience measures) might be useful for evaluating both population information activities and the import of the entire program. Fundamental research on basid demand for fertility control is needed and a marketer's experience with planning and evaluating test markets can be useful in assessing potential selling targets and evaluating alternative promotional and distributional strategies. Special family planning clinics have certain disadvantages: expensive and scarce personnel are needed; red tape may be present; the network is based on the assumption that the client is willing to travel relatively great distances repeatedly; and clinics lack anonymity which may scare potential acceptors away. Most developing cultures have an intensively functioning distribution structure which delivers basic commodities to the most remote areas, providing relatively anonymous outlets that are physically close to the customs. Materials requiring a prescription might be distributed in exchange for script issued at and ultimately redeemed by clinics, this requiring only an occasional visit to a clinic. Mail-order service can be used to supplement a clinic's distribution of some contraceptives. It should be remembered that population administrators often have an antipathetic view toward business and marketing and "suspect" the profit motive.

Feeling validated yet? A scoping review of the use of consumer-targeted wearable and mobile technology to measure and improve sleep.

PubMed

Baron, Kelly Glazer; Duffecy, Jennifer; Berendsen, Mark A; Cheung Mason, Ivy; Lattie, Emily G; Manalo, Natalie C

2017-12-20

The objectives of this review were to evaluate the use of consumer-targeted wearable and mobile sleep monitoring technology, identify gaps in the literature and determine the potential for use in behavioral interventions. We undertook a scoping review of studies conducted in adult populations using consumer-targeted wearable technology or mobile devices designed to measure and/or improve sleep. After screening for inclusion/exclusion criteria, data were extracted from the articles by two co-authors. Articles included in the search were using wearable or mobile technology to estimate or evaluate sleep, published in English and conducted in adult populations. Our search returned 3897 articles and 43 met our inclusion criteria. Results indicated that the majority of studies focused on validating technology to measure sleep (n = 23) or were observational studies (n = 10). Few studies were used to identify sleep disorders (n = 2), evaluate response to interventions (n = 3) or deliver interventions (n = 5). In conclusion, the use of consumer-targeted wearable and mobile sleep monitoring technology has largely focused on validation of devices and applications compared with polysomnography (PSG) but opportunities exist for observational research and for delivery of behavioral interventions. Multidisciplinary research is needed to determine the uses of these technologies in interventions as well as the use in more diverse populations including sleep disorders and other patient populations. Copyright © 2017 Elsevier Ltd. All rights reserved.

Development of a real-time PCR assay for monitoring anaerobic fungal and cellulolytic bacterial populations within the rumen.

PubMed

Denman, Stuart E; McSweeney, Christopher S

2006-12-01

Traditional methods for enumerating and identifying microbial populations within the rumen can be time consuming and cumbersome. Methods that involve culturing and microscopy can also be inconclusive, particularly when studying anaerobic rumen fungi. A real-time PCR SYBR Green assay, using PCR primers to target total rumen fungi and the cellulolytic bacteria Ruminococcus flavefaciens and Fibrobacter succinogenes, is described, including design and validation. The DNA and crude protein contents with respect to the fungal biomass of both polycentric and monocentric fungal isolates were investigated across the fungal growth stages to aid in standard curve generation. The primer sets used were found to be target specific with no detectable cross-reactivity. Subsequently, the real-time PCR assay was employed in a study to detect these populations within cattle rumen. The anaerobic fungal target was observed to increase 3.6-fold from 0 to 12 h after feeding. The results also indicated a 5.4-fold increase in F. succinogenes target between 0 and 12 h after feeding, whereas R. flavefaciens was observed to maintain more or less consistent levels. This is the first report of a real-time PCR assay to estimate the rumen anaerobic fungal population.

Pulsar population synthesis using palfa detections and pulsar search collaboratory discoveries including a wide DNS system and a nearby MSP

NASA Astrophysics Data System (ADS)

Swiggum, Joseph Karl

Using the ensemble of detections from pulsar surveys, we can learn about the sizes and characteristics of underlying populations. In this thesis, I analyze results from the Pulsar Arecibo L-band Feed Array (PALFA) precursor and Green Bank Telescope 350 MHz Drift Scan surveys; I examine survey sensitivity to see how detections can inform pulsar population models, I look at new ways of including young scientists -- high school students -- in the discovery process and I present timing solutions for students' discoveries (including a nearby millisecond pulsar and a pulsar in a wide-orbit double neutron star system). The PALFA survey is on-going and uses the ALFA 7-beam receiver at 1400 MHz to search both inner and outer Galactic sectors visible from Arecibo (32° ?£? 77° and 168° ?£? 214°) close to the Galactic plane (|b| ? 5°) for pulsars. The PALFA precursor survey observed a subset of this region, (|b| ? 1°) and detected 45 pulsars, including one known millisecond pulsar (MSP) and 11 previously unknown, long-period (normal) pulsars. I assess the sensitivity of the PALFA precursor survey and use the number of normal pulsar and MSP detections to infer the size of each underlying Galactic population. Based on 44 normal pulsar detections and one MSP, we constrain each population size to 107,000+36,000-25,000 and 15,000 +85,000-6,000 respectively with 95% confidence. Based on these constraints, we predict yields for the full PALFA survey and find a deficiency in normal pulsar detections, possibly due to radio frequency interference and/or scintillation, neither of which are currently accounted for in population simulations. The GBT 350 MHz Drift Scan survey collected data in the summer of 2007 while the GBT was stationary, undergoing track replacement. Results discussed here come from ~20% of the survey data, which were processed and donated to the Pulsar Search Collaboratory (PSC). The PSC is a joint outreach program between WVU and NRAO, involving high school

Communication Strategies Must Be Tailored to a Medication's Targeted Population: Lessons from the Case of BiDil.

PubMed

Hawkins-Taylor, Chamika; Carlson, Angeline M

2013-09-01

The American population's diversity continues to grow, and its racial and ethnic mixes are changing. The US healthcare system must confront this changing reality. The introduction of isosorbide dinitrate/hydralazine hydrochloride (BiDil) to the US marketplace was a move toward recognizing these changing consumer needs. BiDil was approved specifically as a secondary treatment for heart failure in African-American patients. It remains the first and only drug approved by the US Food and Drug Administration for a race-based indication. To ensure commercial success, a drug must be made "visible" to healthcare providers and to consumers. To describe and analyze the case of BiDil and its potential implications for drugs developed for targeted populations to help them avoid a similar fate of market withdrawal because of commercial considerations. This analysis is based on 12 comprehensive interviews with 5 clinical investigators, 1 minority healthcare provider, and 5 pharmaceutical representatives, as well as a review of the literature. Overall, 12 one-hour semistructured interviews were conducted. Of the 11 interviewees, 10 were interviewed once and 1 was interviewed once early in the process and then had a second interview by the end of the study. When the 12 scheduled interviews were completed, the recordings were transcribed and subjected to analysis through the use of a readily available computer software package, using concepts and themes collected from the literature and the interviewees' responses. The interviewees lacked consensus regarding the unique nature of BiDil. The clinical researchers considered it innovative in identifying that taking the 2 drugs together produced the greatest clinical effect in African-American patients with heart failure. For them, BiDil represented an innovation in the emerging field of personalized medicine. However, they were dismayed to see that these beliefs were challenged by the medical community and their physician colleagues

Stromal cells in breast cancer as a potential therapeutic target

PubMed Central

Dykes, Samantha S.; Hughes, Veronica S.; Wiggins, Jennifer M.; Fasanya, Henrietta O.; Tanaka, Mai; Siemann, Dietmar

2018-01-01

Breast cancer in the United States is the second most commonly diagnosed cancer in women. About 1 in 8 women will develop invasive breast cancer over the course of her lifetime and breast cancer remains the second leading cause of cancer-related death. In pursuit of novel therapeutic strategies, researchers have examined the tumor microenvironment as a potential anti-cancer target. In addition to neoplastic cells, the tumor microenvironment is composed of several critical normal cell types, including fibroblasts, vascular and lymph endothelial cells, osteoclasts, adipocytes, and immune cells. These cells have important roles in healthy tissue stasis, which frequently are altered in tumors. Indeed, tumor-associated stromal cells often contribute to tumorigenesis, tumor progression, and metastasis. Consequently, these host cells may serve as a possible target in anti-tumor and anti-metastatic therapeutic strategies. Targeting the tumor associated host cells offers the benefit that such cells do not mutate and develop resistance in response to treatment, a major cause of failure in cancer therapeutics targeting neoplastic cells. This review discusses the role of host cells in the tumor microenvironment during tumorigenesis, progression, and metastasis, and provides an overview of recent developments in targeting these cell populations to enhance cancer therapy efficacy.

A Primer on Population Health Management and Its Perioperative Application.

PubMed

Boudreaux, Arthur M; Vetter, Thomas R

2016-07-01

The movement toward value-based payment models, driven by governmental policies, federal statutes, and market forces, is propelling the importance of effectively managing the health of populations to the forefront in the United States and other developed countries. However, for many anesthesiologists, population health management is a new or even foreign concept. A primer on population health management and its potential perioperative application is thus presented here. Although it certainly continues to evolve, population health management can be broadly defined as the specific policies, programs, and interventions directed at optimizing population health. The Population Health Alliance has created a particularly cogent conceptual framework and interconnected and very useful population health process model, which together identify the key components of population health and its management. Population health management provides a useful rationale for patients, providers, payers, and policymakers to move collectively away from the traditional system of individual, siloed providers to a more integrated, coordinated, team-based approach, thus creating a holistic view of the patient population. The goal of population health management is to keep the targeted patient population as healthy as possible, thus minimizing the need for costly interventions such as emergency department visits, acute hospitalizations, laboratory testing and imaging, and diagnostic and therapeutic procedures. Population health management strategies are increasingly more important to leaders of health care systems as the health of populations for which they care, especially in a strong cost risk-sharing environment, must be optimized. Most population health management efforts rely on a patient-centric team approach, coordination of care, effective communication, robust outcomes data analysis, and continuous quality improvement. Anesthesiologists have an opportunity to help lead these efforts in

The representation of vulnerable populations in quality improvement studies.

PubMed

Rolnitsky, Asaph; Kirtsman, Maksim; Goldberg, Hanna R; Dunn, Michael; Bell, Chaim M

2018-05-01

A mapping review to quantify representation of vulnerable populations, who suffer from disparity and often inequitable healthcare, in quality improvement (QI) research. Studies published in 2004-2014 inclusive from Medline, Embase and Cochrane databases for English language research with the terms 'quality improvement' or 'quality control' or 'QI' and 'plan-do-study-act' or 'PDSA' in the years 2004-2014 inclusively. Published clinical research that was a QI-themed, as identified by its declared search terms, MESH terms, abstract or title. Three reviewers identified the eligible studies independently. Excluded were publications that were not trials, evaluations or analyses. Of 2039 results, 1660 were eligible for inclusion. There were 586 (33.5%) publications that targeted a specific vulnerable population: children (184, 10.54%), mental health patients (125, 7.16%), the elderly (100, 5.73%), women (57, 3.27%), the poor (30, 1.72%), rural residents (29, 1.66%), visible minorities (27, 1.55%), the terminally ill (17, 0.97%), adolescents (16, 0.92%) and prisoners (1 study). Seventy-four articles targeted two or more vulnerable populations, and 11 targeted three population categories. On average, there were 158 QI research studies published per year, increasing from 69 in 2004 to 396 in 2014 (R2 = 0.7, P < 0.001). The relative representation of vulnerable populations had a mean of 33.58% and was stable over the time period (standard deviation (SD) = 5.9%, R2 = 0.001). Seven countries contributed to over 85% of the publications targeting vulnerable populations, with the USA contributing 62% of the studies. Over 11 years, there has been a marked increase in QI publications. Roughly one-third of all published QI research is on vulnerable populations, a stable proportion over time. Nevertheless, some vulnerable populations are under-represented. Increased education, resources and attention are encouraged to improve the health of vulnerable populations through focused QI

Centredale Manor Superfund Site in Rhode Island included on EPA List of Targeted for Immediate Attention

EPA Pesticide Factsheets

Today, the U.S. Environmental Protection Agency released the list of Superfund sites that Administrator Pruitt has targeted for immediate and intense attention. The Centredale Manor Restoration Project superfund site is one of the 21 sites on the list.

Target-Pathogen: a structural bioinformatic approach to prioritize drug targets in pathogens.

PubMed

Sosa, Ezequiel J; Burguener, Germán; Lanzarotti, Esteban; Defelipe, Lucas; Radusky, Leandro; Pardo, Agustín M; Marti, Marcelo; Turjanski, Adrián G; Fernández Do Porto, Darío

2018-01-04

Available genomic data for pathogens has created new opportunities for drug discovery and development to fight them, including new resistant and multiresistant strains. In particular structural data must be integrated with both, gene information and experimental results. In this sense, there is a lack of an online resource that allows genome wide-based data consolidation from diverse sources together with thorough bioinformatic analysis that allows easy filtering and scoring for fast target selection for drug discovery. Here, we present Target-Pathogen database (http://target.sbg.qb.fcen.uba.ar/patho), designed and developed as an online resource that allows the integration and weighting of protein information such as: function, metabolic role, off-targeting, structural properties including druggability, essentiality and omic experiments, to facilitate the identification and prioritization of candidate drug targets in pathogens. We include in the database 10 genomes of some of the most relevant microorganisms for human health (Mycobacterium tuberculosis, Mycobacterium leprae, Klebsiella pneumoniae, Plasmodium vivax, Toxoplasma gondii, Leishmania major, Wolbachia bancrofti, Trypanosoma brucei, Shigella dysenteriae and Schistosoma Smanosoni) and show its applicability. New genomes can be uploaded upon request. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Target-Pathogen: a structural bioinformatic approach to prioritize drug targets in pathogens

PubMed Central

Sosa, Ezequiel J; Burguener, Germán; Lanzarotti, Esteban; Radusky, Leandro; Pardo, Agustín M; Marti, Marcelo

2018-01-01

Abstract Available genomic data for pathogens has created new opportunities for drug discovery and development to fight them, including new resistant and multiresistant strains. In particular structural data must be integrated with both, gene information and experimental results. In this sense, there is a lack of an online resource that allows genome wide-based data consolidation from diverse sources together with thorough bioinformatic analysis that allows easy filtering and scoring for fast target selection for drug discovery. Here, we present Target-Pathogen database (http://target.sbg.qb.fcen.uba.ar/patho), designed and developed as an online resource that allows the integration and weighting of protein information such as: function, metabolic role, off-targeting, structural properties including druggability, essentiality and omic experiments, to facilitate the identification and prioritization of candidate drug targets in pathogens. We include in the database 10 genomes of some of the most relevant microorganisms for human health (Mycobacterium tuberculosis, Mycobacterium leprae, Klebsiella pneumoniae, Plasmodium vivax, Toxoplasma gondii, Leishmania major, Wolbachia bancrofti, Trypanosoma brucei, Shigella dysenteriae and Schistosoma Smanosoni) and show its applicability. New genomes can be uploaded upon request. PMID:29106651

Enhanced Recovery After Surgery Program Implementation in 2 Surgical Populations in an Integrated Health Care Delivery System.

PubMed

Liu, Vincent X; Rosas, Efren; Hwang, Judith; Cain, Eric; Foss-Durant, Anne; Clopp, Molly; Huang, Mengfei; Lee, Derrick C; Mustille, Alex; Kipnis, Patricia; Parodi, Stephen

2017-07-19

Novel approaches to perioperative surgical care focus on optimizing nutrition, mobility, and pain management to minimize adverse events after surgical procedures. To evaluate the outcomes of an enhanced recovery after surgery (ERAS) program among 2 target populations: patients undergoing elective colorectal resection and patients undergoing emergency hip fracture repair. A pre-post difference-in-differences study before and after ERAS implementation in the target populations compared with contemporaneous surgical comparator groups (patients undergoing elective gastrointestinal surgery and emergency orthopedic surgery). Implementation began in February and March 2014 and concluded by the end of 2014 at 20 medical centers within the Kaiser Permanente Northern California integrated health care delivery system. A multifaceted ERAS program designed with a particular focus on perioperative pain management, mobility, nutrition, and patient engagement. The primary outcome was hospital length of stay. Secondary outcomes included hospital mortality, home discharge, 30-day readmission rates, and complication rates. The study included a total of 3768 patients undergoing elective colorectal resection (mean [SD] age, 62.7 [14.1] years; 1812 [48.1%] male) and 5002 patients undergoing emergency hip fracture repair (mean [SD] age, 79.5 [11.8] years; 1586 [31.7%] male). Comparator surgical patients included 5556 patients undergoing elective gastrointestinal surgery and 1523 patients undergoing emergency orthopedic surgery. Most process metrics had significantly greater changes in the ERAS target populations after implementation compared with comparator surgical populations, including those for ambulation, nutrition, and opioid use. Hospital length of stay and postoperative complication rates were also significantly lower among ERAS target populations after implementation. The rate ratios for postoperative complications were 0.68 (95% CI, 0.46-0.99; P = .04) for patients

Barriers and facilitators to intraorganizational collaboration in public health: Relational coordination across public health services targeting individuals and populations.

PubMed

McCullough, J Mac; Eisen-Cohen, Eileen; Lott, Breanne

2018-05-09

Modern public health emphasizes population-focused services, which may require collaborative work both across and within organizations. Studies have explored interorganizational collaborations, but there are little data regarding collaborations within public health organizations. We measured intraorganizational collaboration and identified barriers and facilitators to collaboration within a large public health department through a mixed-methods study. Our study occurred at the Maricopa County (Arizona) Department of Public Health, the third largest local public health jurisdiction in the United States. To measure collaboration, we surveyed staff using the relational coordination tool. To identify barriers and facilitators to collaboration, we performed key informant interviews with department personnel. Relational coordination scores varied according to the focus of the service; clinical services had significantly lower levels of relational coordination than population-focused services (p < .01). We found high levels of mutual respect and lower levels of shared knowledge across services. Facilitators to collaboration included purposive cross-program meetings around specific topics, the organization's structure and culture, and individuals' social identities. Barriers included raised expectations for collaboration, low slack resources, member's self-interest, and trust. The relational coordination of services varied significantly according to the focus of the service. Population-focused public health services had higher levels of relational coordination than individually focused services. Collaboration was facilitated and impeded by both well-known and potentially emergent factors, such as purposive cross-service meetings and organizational culture. Population-focused services possessed higher levels of collaboration than individually focused services. Intraorganizational collaboration for improved population health relies on deliberate support from senior

Building Better Planet Populations for EXOSIMS

NASA Astrophysics Data System (ADS)

Garrett, Daniel; Savransky, Dmitry

2018-01-01

The Exoplanet Open-Source Imaging Mission Simulator (EXOSIMS) software package simulates ensembles of space-based direct imaging surveys to provide a variety of science and engineering yield distributions for proposed mission designs. These mission simulations rely heavily on assumed distributions of planetary population parameters including semi-major axis, planetary radius, eccentricity, albedo, and orbital orientation to provide heuristics for target selection and to simulate planetary systems for detection and characterization. The distributions are encoded in PlanetPopulation modules within EXOSIMS which are selected by the user in the input JSON script when a simulation is run. The earliest written PlanetPopulation modules available in EXOSIMS are based on planet population models where the planetary parameters are considered to be independent from one another. While independent parameters allow for quick computation of heuristics and sampling for simulated planetary systems, results from planet-finding surveys have shown that many parameters (e.g., semi-major axis/orbital period and planetary radius) are not independent. We present new PlanetPopulation modules for EXOSIMS which are built on models based on planet-finding survey results where semi-major axis and planetary radius are not independent and provide methods for sampling their joint distribution. These new modules enhance the ability of EXOSIMS to simulate realistic planetary systems and give more realistic science yield distributions.

Profile: the Philippine Population Information Network.

PubMed

1991-06-01

The profile of Philippine Population Information Network (POPIN) is described in this article as having changed management structure from the Population Center Foundation to the Government's Population Commission, Information Management and Research Division (IMRD) in 1989. This restructuring resulted in the transfer in 1990 of the Department of Social Welfare and Development to the Office of the President. POPIN also serves Asia/Pacific POPIN. POPCOM makes policy and coordinates and monitors population activities. POPIN's goal is to improve the flow and utilization of population information nationwide. The National Population Library was moved in 1989 to the POPCOM Central Office Building and became the Philippine Information Center. The collection includes 6000 books, 400 research reports, and 4000 other documents (brochures, reprints, conference materials, and so on); 42 video tapes about the Philippine population program and a cassette player are available. In 1989, 14 regional centers were set up in POPCOM regional offices and designated Regional Population Information Centers. There are also school-based information centers operating as satellite information centers. The Regional and school-based centers serve the purpose of providing technical information through collection development, cataloguing, classification, storage and retrieval, and circulation. The target users are policy makers, government and private research agencies, researchers, and faculty and students. Publications developed and produced by the Center include the 3rd Supplement of the Union Catalogue of Population Literature, the 1987-88 Annotated Bibliography of Philippine Population Literature (PPL), the forthcoming 1989-90 edition of the Annotated Bibliography of PPL, and a biyearly newsletter, POPINEWS. Microcomputers have been acquired for the Regional Centers, with the idea of computerizing POPIN. Computer upgrading is also being done within the IMRD to provide POPLINE CD

Vaccine-preventable diseases in humanitarian emergencies among refugee and internally-displaced populations

PubMed Central

Lam, Eugene; McCarthy, Amanda; Brennan, Muireann

2015-01-01

Humanitarian emergencies may result in breakdown of regular health services including routine vaccination programs. Displaced populations including refugees and internally displaced persons are particularly susceptible to outbreaks of communicable diseases such as vaccine-preventable diseases (VPDs). Common VPDs encountered in humanitarian emergencies include measles, polio, and depending on geographical location, meningococcal meningitis, yellow fever, hepatitis A, and cholera. We conducted a review of 50 published articles from 2000 to 2015 concerning VPDs in humanitarian emergencies. This article provides an update on the available literature regarding vaccinations among this highly vulnerable population and describes the unique challenges of VPDs during humanitarian emergencies. Humanitarian emergencies place affected populations at risk for elevated morbidity and mortality from VPDs due to creation or exacerbation of factors associated with disease transmission such as mass population movements, overcrowding, malnutrition, and poor water and sanitation conditions. Vaccination is one of the most basic and critical health interventions for protecting vulnerable populations during emergencies. Growing insecurity, as seen in the increasing number of targeted attacks on health workers in recent years, as well as destruction of cold chain and infrastructure for transportation of supplies, are creating new challenges in provision of life saving vaccines in conflict settings. Population displacement can also threaten global VPD eradication and elimination efforts. While highly effective vaccines and guidelines to combat VPDs are available, the trend of increasing number of humanitarian emergencies globally poses new and emerging challenges in providing vaccination among displaced populations. PMID:26406333

Population pharmacokinetics of intravenous acyclovir in preterm and term infants.

PubMed

Sampson, Mario R; Bloom, Barry T; Lenfestey, Robert W; Harper, Barrie; Kashuba, Angela D; Anand, Ravinder; Benjamin, Daniel K; Capparelli, Edmund; Cohen-Wolkowiez, Michael; Smith, P Brian

2014-01-01

Acyclovir is used to treat herpes infections in preterm and term infants; however, the influence of maturation on drug disposition and dosing requirements is poorly characterized in this population. We administered intravenous acyclovir to preterm and term infants <31 days postnatal age and collected plasma samples. We performed a population pharmacokinetic analysis. The primary pharmacodynamic target was acyclovir concentration ≥3 mg/L for ≥50% of the dosing interval. The final model was simulated using infant data from a clinical database. The analysis included 28 infants (median 30 weeks gestation). Acyclovir pharmacokinetics was described by a 1-compartment model: clearance (L/h/kg) = 0.305 × [postmenstrual age (PMA)/31.3 weeks]. This equation predicts a 4.5-fold increase in clearance from 25 to 41 weeks PMA. With proposed dosing, the pharmacodynamic target was achieved in 91% of infants: 20 mg/kg every 12 hours in infants <30 weeks PMA; 20 mg/kg every 8 hours in infants 30 to <36 weeks PMA and 20 mg/kg every 6 hours in infants 36-41 weeks PMA. Acyclovir clearance increased with infant maturation. A dosing strategy based on PMA accounted for developmental changes in acyclovir disposition to achieve the surrogate pharmacodynamic target in many infants.

Including internal mammary lymph nodes in radiation therapy for synchronous bilateral breast cancer: an international survey of treatment technique and clinical priorities.

PubMed

Roumeliotis, M; Long, K; Phan, T; Graham, D; Quirk, S

2018-06-05

The aim of this study was to understand the international standard practice for radiation therapy treatment techniques and clinical priorities for institutions including the internal mammary lymph nodes (IMLNs) in the target volume for patients with synchronous bilateral breast cancer. An international survey was developed to include questions that would provide awareness of favored treatment techniques, treatment planning and delivery resource requirements, and the clinical priorities that may lead to the utilization of preferred treatment techniques. Of the 135 respondents, 82 indicated that IMLNs are regularly included in the target volume for radiation therapy (IMLN-inclusion) when the patient is otherwise generally indicated for regional nodal irradiation. Of the 82 respondents that regularly include IMLNs, five were removed as those respondents do not treat this population synchronously. Of the 77 respondents, institutional standard of care varied significantly, though VMAT (34%) and combined static photon and electron fields (21%) were the most commonly utilized techniques. Respondents did preferentially select target volume coverage (70%) as the most important clinical priority, followed by normal tissue sparing (25%). The results of the survey indicate that the IMLN-inclusion for radiation therapy has not yet been comprehensively adopted. As well, no consensus on best practice for radiation therapy treatment techniques has been reached.

Potential impact of spatially targeted adult tuberculosis vaccine in Gujarat, India

PubMed Central

Chatterjee, Susmita; Rao, Krishna D.; Dowdy, David W.

2016-01-01

Some of the most promising vaccines in the pipeline for tuberculosis (TB) target adolescents and adults. Unlike for childhood vaccines, high-coverage population-wide vaccination is significantly more challenging for adult vaccines. Here, we aimed to estimate the impact of vaccine delivery strategies that were targeted to high-incidence geographical ‘hotspots’ compared with randomly allocated vaccination. We developed a spatially explicit mathematical model of TB transmission that distinguished these hotspots from the general population. We evaluated the impact of targeted and untargeted vaccine delivery strategies in India—a country that bears more than 25% of global TB burden, and may be a potential early adopter of the vaccine. We collected TB notification data and conducted a demonstration study in the state of Gujarat to validate our estimates of heterogeneity in TB incidence. We then projected the impact of randomly vaccinating 8% of adults in a single mass campaign to a spatially targeted vaccination preferentially delivered to 80% of adults in the hotspots, with both strategies augmented by continuous adolescent vaccination. In consultation with vaccine developers, we considered a vaccine efficacy of 60%, and evaluated the population-level impact after 10 years of vaccination. Spatial heterogeneity in TB notification (per 100 000/year) was modest in Gujarat: 190 in the hotspots versus 125 in the remaining population. At this level of heterogeneity, the spatially targeted vaccination was projected to reduce TB incidence by 28% after 10 years, compared with a 24% reduction projected to achieve via untargeted vaccination—a 1.17-fold augmentation in the impact of vaccination by spatially targeting. The degree of the augmentation was robust to reasonable variation in natural history assumptions, but depended strongly on the extent of spatial heterogeneity and mixing between the hotspot and general population. Identifying high-incidence hotspots and

Emodin As an Effective Agent in Targeting Cancer Stem-Like Side Population Cells of Gallbladder Carcinoma

PubMed Central

Li, Xin-xing; Dong, Ying; Wang, Wei; Wang, Hao-lu; Chen, Yu-ying; Shi, Gui-ying; Yi, Jing

2013-01-01

Side population (SP) cells are previously identified from bone marrow based on their capacity to efflux of the fluorescent dye Hoechst 33342. Recent studies demonstrate that SP cells isolated from various cancer cell lines and primary tumors possess stem-cell-like properties. Thus, targeting tumor SP cells may provide new strategies for treatment in clinic. We previously showed that 1,3,8-trihydroxy-6-methylanthraquinone (emodin), a reactive oxygen species (ROS) generator, enhanced sensitivity of gallbladder cancer SGC-996 cells to cisplatin (CDDP) via generation of ROS and downregulation of multidrug-resistance-associated protein 1 (MRP1). To determine whether emodin also acts effectively on cancer stem cells of gallbladder carcinoma, we use SP cells as a model of cancer stem-cell-like cells. Here, we found that emodin, via ROS-related mechanism and suppressing the function of ATP-binding cassette super-family G member (ABCG2), which is known to be associated with Hoechst dye efflux activity of SP cells, not only reduced the ratio, inhibited clone formation, and eliminated sphere formation of SP cells effectively, but also promoted obviously the intracellular accumulation of doxorubicin, the main substrate of the efflux pump ABCG2. In addition, emodin could sensitize CDDP, via inhibition of expression of ABCG2, to overcome chemoresistance of SP cells. Importantly, similar to the experiment in vitro, emodin/CDDP co-treatment in vivo suppressed the tumor growth derived from SP cells through downregulating ABCG2 expression. Our results suggest that emodin is an effective agent targeting cancer stem-like SP cells of gallbladder carcinoma, either alone or acts as a chemotherapy enhancer. PMID:22974371

A systematic review of economic evaluations of population-based sodium reduction interventions.

PubMed

Hope, Silvia F; Webster, Jacqui; Trieu, Kathy; Pillay, Arti; Ieremia, Merina; Bell, Colin; Snowdon, Wendy; Neal, Bruce; Moodie, Marj

2017-01-01

To summarise evidence describing the cost-effectiveness of population-based interventions targeting sodium reduction. A systematic search of published and grey literature databases and websites was conducted using specified key words. Characteristics of identified economic evaluations were recorded, and included studies were appraised for reporting quality using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist. Twenty studies met the study inclusion criteria and received a full paper review. Fourteen studies were identified as full economic evaluations in that they included both costs and benefits associated with an intervention measured against a comparator. Most studies were modelling exercises based on scenarios for achieving salt reduction and assumed effects on health outcomes. All 14 studies concluded that their specified intervention(s) targeting reductions in population sodium consumption were cost-effective, and in the majority of cases, were cost saving. Just over half the studies (8/14) were assessed as being of 'excellent' reporting quality, five studies fell into the 'very good' quality category and one into the 'good' category. All of the identified evaluations were based on modelling, whereby inputs for all the key parameters including the effect size were either drawn from published datasets, existing literature or based on expert advice. Despite a clear increase in evaluations of salt reduction programs in recent years, this review identified relatively few economic evaluations of population salt reduction interventions. None of the studies were based on actual implementation of intervention(s) and the associated collection of new empirical data. The studies universally showed that population-based salt reduction strategies are likely to be cost effective or cost saving. However, given the reliance on modelling, there is a need for the effectiveness of new interventions to be evaluated in the field using strong

A systematic review of economic evaluations of population-based sodium reduction interventions

PubMed Central

Hope, Silvia F.; Webster, Jacqui; Trieu, Kathy; Pillay, Arti; Ieremia, Merina; Bell, Colin; Snowdon, Wendy; Neal, Bruce; Moodie, Marj

2017-01-01

Objective To summarise evidence describing the cost-effectiveness of population-based interventions targeting sodium reduction. Methods A systematic search of published and grey literature databases and websites was conducted using specified key words. Characteristics of identified economic evaluations were recorded, and included studies were appraised for reporting quality using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist. Results Twenty studies met the study inclusion criteria and received a full paper review. Fourteen studies were identified as full economic evaluations in that they included both costs and benefits associated with an intervention measured against a comparator. Most studies were modelling exercises based on scenarios for achieving salt reduction and assumed effects on health outcomes. All 14 studies concluded that their specified intervention(s) targeting reductions in population sodium consumption were cost-effective, and in the majority of cases, were cost saving. Just over half the studies (8/14) were assessed as being of ‘excellent’ reporting quality, five studies fell into the ‘very good’ quality category and one into the ‘good’ category. All of the identified evaluations were based on modelling, whereby inputs for all the key parameters including the effect size were either drawn from published datasets, existing literature or based on expert advice. Conclusion Despite a clear increase in evaluations of salt reduction programs in recent years, this review identified relatively few economic evaluations of population salt reduction interventions. None of the studies were based on actual implementation of intervention(s) and the associated collection of new empirical data. The studies universally showed that population-based salt reduction strategies are likely to be cost effective or cost saving. However, given the reliance on modelling, there is a need for the effectiveness of new

Magnetically attached sputter targets

DOEpatents

Makowiecki, Daniel M.; McKernan, Mark A.

1994-01-01

An improved method and assembly for attaching sputtering targets to cathode assemblies of sputtering systems which includes a magnetically permeable material. The magnetically permeable material is imbedded in a target base that is brazed, welded, or soldered to the sputter target, or is mechanically retained in the target material. Target attachment to the cathode is achieved by virtue of the permanent magnets and/or the pole pieces in the cathode assembly that create magnetic flux lines adjacent to the backing plate, which strongly attract the magnetically permeable material in the target assembly.

The greater snow goose Anser caerulescens atlanticus: Managing an overabundant population.

PubMed

Lefebvre, Josée; Gauthier, Gilles; Giroux, Jean-François; Reed, Austin; Reed, Eric T; Bélanger, Luc

2017-03-01

Between the early 1900s and the 1990s, the greater snow goose Anser caerulescens atlanticus population grew from 3000 individuals to more than 700 000. Because of concerns about Arctic degradation of natural habitats through overgrazing, a working group recommended the stabilization of the population. Declared overabundant in 1998, special management actions were then implemented in Canada and the United States. Meanwhile, a cost-benefit socioeconomic analysis was performed to set a target population size. Discussions aiming towards attaining a common vision were undertaken with stakeholders at multiple levels. The implemented measures have had varying success; but population size has been generally stable since 1999. To be effective and meet social acceptance, management actions must have a scientific basis, result from a consensus among stakeholders, and include an efficient monitoring programme. In this paper, historical changes in population size and management decisions along with past and current challenges encountered are discussed.

Temporal genetic stability of Stegomyia aegypti (= Aedes aegypti) populations.

PubMed

Gloria-Soria, A; Kellner, D A; Brown, J E; Gonzalez-Acosta, C; Kamgang, B; Lutwama, J; Powell, J R

2016-06-01

The mosquito Stegomyia aegypti (= Aedes aegypti) (Diptera: Culicidae) is the primary vector of viruses that cause yellow fever, dengue and Chikungunya fever. In the absence of effective vaccines, the reduction of these diseases relies on vector control strategies. The success of these strategies is tightly linked to the population dynamics of target populations. In the present study, 14 collections from St. aegypti populations separated by periods of 1-13 years were analysed to determine their temporal genetic stability. Although temporal structure is discernible in most populations, the degree of temporal differentiation is dependent on the population and does not obscure the geographic structure of the various populations. The results suggest that performing detailed studies in the years prior to and after population reduction- or modification-based control interventions at each target field site may be useful in assessing the probability of success. © 2016 The Royal Entomological Society.

Recruiting vulnerable populations into research: a systematic review of recruitment interventions.

PubMed

UyBico, Stacy J; Pavel, Shani; Gross, Cary P

2007-06-01

Members of vulnerable populations are underrepresented in research studies. To evaluate and synthesize the evidence regarding interventions to enhance enrollment of vulnerable populations into health research studies. Studies were identified by searching MEDLINE, the Web of Science database, personal sources, hand searching of related journals, and article references. Studies that contained data on recruitment interventions for vulnerable populations (minority, underserved, poor, rural, urban, or inner city) and for which the parent study (study for which recruitment was taking place) was an intervention study were included. A total of 2,648 study titles were screened and 48 articles met inclusion criteria, representing 56 parent studies. Two investigators extracted data from each study. African Americans were the most frequently targeted population (82% of the studies), while 46% targeted Hispanics/Latinos. Many studies assessed 2 or more interventions, including social marketing (82% of studies), community outreach (80%), health system recruitment (52%), and referrals (28%). The methodologic rigor varied substantially. Only 40 studies (71%) incorporated a control group and 21% used statistical analysis to compare interventions. Social marketing, health system, and referral recruitment were each found to be the most successful intervention about 35-45% of the studies in which they were attempted, while community outreach was the most successful intervention in only 2 of 16 studies (13%) in which it was employed. People contacted as a result of social marketing were no less likely to enroll than people contacted through other mechanisms. Further work with greater methodologic rigor is needed to identify evidence-based strategies for increasing minority enrollment in research studies; community outreach, as an isolated strategy, may be less successful than other strategies.

Development of Bone Targeting Drugs.

PubMed

Stapleton, Molly; Sawamoto, Kazuki; Alméciga-Díaz, Carlos J; Mackenzie, William G; Mason, Robert W; Orii, Tadao; Tomatsu, Shunji

2017-06-23

The skeletal system, comprising bones, ligaments, cartilage and their connective tissues, is critical for the structure and support of the body. Diseases that affect the skeletal system can be difficult to treat, mainly because of the avascular cartilage region. Targeting drugs to the site of action can not only increase efficacy but also reduce toxicity. Bone-targeting drugs are designed with either of two general targeting moieties, aimed at the entire skeletal system or a specific cell type. Most bone-targeting drugs utilize an affinity to hydroxyapatite, a major component of the bone matrix that includes a high concentration of positively-charged Ca 2+ . The strategies for designing such targeting moieties can involve synthetic and/or biological components including negatively-charged amino acid peptides or bisphosphonates. Efficient delivery of bone-specific drugs provides significant impact in the treatment of skeletal related disorders including infectious diseases (osteoarthritis, osteomyelitis, etc.), osteoporosis, and metabolic skeletal dysplasia. Despite recent advances, however, both delivering the drug to its target without losing activity and avoiding adverse local effects remain a challenge. In this review, we investigate the current development of bone-targeting moieties, their efficacy and limitations, and discuss future directions for the development of these specific targeted treatments.

Development of Bone Targeting Drugs

PubMed Central

Stapleton, Molly; Sawamoto, Kazuki; Alméciga-Díaz, Carlos J.; Mackenzie, William G.; Mason, Robert W.; Orii, Tadao; Tomatsu, Shunji

2017-01-01

The skeletal system, comprising bones, ligaments, cartilage and their connective tissues, is critical for the structure and support of the body. Diseases that affect the skeletal system can be difficult to treat, mainly because of the avascular cartilage region. Targeting drugs to the site of action can not only increase efficacy but also reduce toxicity. Bone-targeting drugs are designed with either of two general targeting moieties, aimed at the entire skeletal system or a specific cell type. Most bone-targeting drugs utilize an affinity to hydroxyapatite, a major component of the bone matrix that includes a high concentration of positively-charged Ca2+. The strategies for designing such targeting moieties can involve synthetic and/or biological components including negatively-charged amino acid peptides or bisphosphonates. Efficient delivery of bone-specific drugs provides significant impact in the treatment of skeletal related disorders including infectious diseases (osteoarthritis, osteomyelitis, etc.), osteoporosis, and metabolic skeletal dysplasia. Despite recent advances, however, both delivering the drug to its target without losing activity and avoiding adverse local effects remain a challenge. In this review, we investigate the current development of bone-targeting moieties, their efficacy and limitations, and discuss future directions for the development of these specific targeted treatments. PMID:28644392

Nuclear Security: Target Analysis-rev

DOE Office of Scientific and Technical Information (OSTI.GOV)

Singh, Surinder Paul; Gibbs, Philip W.; Bultz, Garl A.

2014-03-01

The objectives of this presentation are to understand target identification, including roll-up and protracted theft; evaluate target identification in the SNRI; recognize the target characteristics and consequence levels; and understand graded safeguards.

Patient safety is not enough: targeting quality improvements to optimize the health of the population.

PubMed

Woolf, Steven H

2004-01-06

Ensuring patient safety is essential for better health care, but preoccupation with niches of medicine, such as patient safety, can inadvertently compromise outcomes if it distracts from other problems that pose a greater threat to health. The greatest benefit for the population comes from a comprehensive view of population needs and making improvements in proportion with their potential effect on public health; anything less subjects an excess of people to morbidity and death. Patient safety, in context, is a subset of health problems affecting Americans. Safety is a subcategory of medical errors, which also includes mistakes in health promotion and chronic disease management that cost lives but do not affect "safety." These errors are a subset of lapses in quality, which result not only from errors but also from systemic problems, such as lack of access, inequity, and flawed system designs. Lapses in quality are a subset of deficient caring, which encompasses gaps in therapeutics, respect, and compassion that are undetected by normative quality indicators. These larger problems arguably cost hundreds of thousands more lives than do lapses in safety, and the system redesigns to correct them should receive proportionately greater emphasis. Ensuring such rational prioritization requires policy and medical leaders to eschew parochialism and take a global perspective in gauging health problems. The public's well-being requires policymakers to view the system as a whole and consider the potential effect on overall population health when prioritizing care improvements and system redesigns.

EGFR, HER2 and VEGF pathways: validated targets for cancer treatment.

PubMed

Press, Michael F; Lenz, Heinz-Josef

2007-01-01

Targeted therapies are rationally designed to interfere with specific molecular events that are important in tumour growth, progression or survival. Several targeted therapies with anti-tumour activity in human cancer cell lines and xenograft models have now been shown to produce objective responses, delay disease progression and, in some cases, improve survival of patients with advanced malignancies. These targeted therapies include cetuximab, an anti-epidermal growth factor receptor (EGFR) monoclonal antibody; gefitinib and erlotinib, EGFR-specific tyrosine kinase inhibitors; trastuzumab, an anti-human EGFR type 2 (HER2)-related monoclonal antibody; lapatinib, a dual inhibitor of both EGFR- and HER2-associated tyrosine kinases; and bevacizumab, an anti-vascular endothelial growth factor (VEGF) monoclonal antibody. On the basis of preclinical and clinical evidence, EGFR, HER2 and VEGF represent validated targets for cancer therapy and remain the subject of intensive investigation. Both EGFR and HER2 are targets found on cancer cells, whereas VEGF is a target that acts in the tumour microenvironment. Clinical studies are focusing on how to best incorporate targeted therapy into current treatment regimens and other studies are exploring whether different strategies for inhibiting these targets will offer greater benefit. It is clear that optimal use of targeted therapy will depend on understanding how these drugs work mechanistically, and recognising that their activities may differ across patient populations, tumour types and disease stages, as well as when and how they are used in cancer treatment. The results achieved with targeted therapies to date are promising, although they illustrate the need for additional preclinical and clinical study.

Cost estimation for the active debris removal of multiple priority targets

NASA Astrophysics Data System (ADS)

Braun, Vitali; Wiedemann, Carsten; Schulz, Eugen

The increasing number of space debris objects, especially in distinct low Earth orbit (LEO) altitudes between 600 and 1000 km, leads to an increase in the potential collision risk between the objects and threatens active satellites in that region. Several recent studies show that active debris removal (ADR) has to be performed in order to prevent a collisional cascading effect, also known as the Kessler syndrome. In order to stabilize the population growth in the critical LEO region, a removal of five prioritized objects per year has been recognized as a significant figure. Various proposals are addressing the technical issues for ADR missions, including the de-orbiting of objects by means of a service satellite using a chemical or an electric propulsion system. The servicer would rendezvous with a preselected target, perform a docking maneuver and then provide a de-orbit burn to transfer the target on a trajectory where it re-enters the Earth’s atmosphere within a given time frame. In this paper the technical aspects are complemented by a cost estimation model, focusing on multi target missions, which are based on a service satellite capable of de-orbiting more than one target within a single mission. The cost model for ADR includes initial development cost, production cost, launch cost and operation cost as well as the modelling of the propulsion system of the servicer. Therefore, different scenarios are defined for chemical and electric propulsion systems as applied to multi target missions, based on a literature review of concepts currently being under discussion. The costs of multi target missions are compared to a scenario where only one target is removed. Also, the results allow to determine an optimum number of objects to be removed per mission and provide numbers which can be used in future studies, e.g. those related to ADR cost and benefit analyses.

Genotype imputation in a tropical crossbred dairy cattle population.

PubMed

Oliveira Júnior, Gerson A; Chud, Tatiane C S; Ventura, Ricardo V; Garrick, Dorian J; Cole, John B; Munari, Danísio P; Ferraz, José B S; Mullart, Erik; DeNise, Sue; Smith, Shannon; da Silva, Marcos Vinícius G B

2017-12-01

The objective of this study was to investigate different strategies for genotype imputation in a population of crossbred Girolando (Gyr × Holstein) dairy cattle. The data set consisted of 478 Girolando, 583 Gyr, and 1,198 Holstein sires genotyped at high density with the Illumina BovineHD (Illumina, San Diego, CA) panel, which includes ∼777K markers. The accuracy of imputation from low (20K) and medium densities (50K and 70K) to the HD panel density and from low to 50K density were investigated. Seven scenarios using different reference populations (RPop) considering Girolando, Gyr, and Holstein breeds separately or combinations of animals of these breeds were tested for imputing genotypes of 166 randomly chosen Girolando animals. The population genotype imputation were performed using FImpute. Imputation accuracy was measured as the correlation between observed and imputed genotypes (CORR) and also as the proportion of genotypes that were imputed correctly (CR). This is the first paper on imputation accuracy in a Girolando population. The sample-specific imputation accuracies ranged from 0.38 to 0.97 (CORR) and from 0.49 to 0.96 (CR) imputing from low and medium densities to HD, and 0.41 to 0.95 (CORR) and from 0.50 to 0.94 (CR) for imputation from 20K to 50K. The CORR anim exceeded 0.96 (for 50K and 70K panels) when only Girolando animals were included in RPop (S1). We found smaller CORR anim when Gyr (S2) was used instead of Holstein (S3) as RPop. The same behavior was observed between S4 (Gyr + Girolando) and S5 (Holstein + Girolando) because the target animals were more related to the Holstein population than to the Gyr population. The highest imputation accuracies were observed for scenarios including Girolando animals in the reference population, whereas using only Gyr animals resulted in low imputation accuracies, suggesting that the haplotypes segregating in the Girolando population had a greater effect on accuracy than the purebred haplotypes. All

Mixture model normalization for non-targeted gas chromatography/mass spectrometry metabolomics data.

PubMed

Reisetter, Anna C; Muehlbauer, Michael J; Bain, James R; Nodzenski, Michael; Stevens, Robert D; Ilkayeva, Olga; Metzger, Boyd E; Newgard, Christopher B; Lowe, William L; Scholtens, Denise M

2017-02-02

Metabolomics offers a unique integrative perspective for health research, reflecting genetic and environmental contributions to disease-related phenotypes. Identifying robust associations in population-based or large-scale clinical studies demands large numbers of subjects and therefore sample batching for gas-chromatography/mass spectrometry (GC/MS) non-targeted assays. When run over weeks or months, technical noise due to batch and run-order threatens data interpretability. Application of existing normalization methods to metabolomics is challenged by unsatisfied modeling assumptions and, notably, failure to address batch-specific truncation of low abundance compounds. To curtail technical noise and make GC/MS metabolomics data amenable to analyses describing biologically relevant variability, we propose mixture model normalization (mixnorm) that accommodates truncated data and estimates per-metabolite batch and run-order effects using quality control samples. Mixnorm outperforms other approaches across many metrics, including improved correlation of non-targeted and targeted measurements and superior performance when metabolite detectability varies according to batch. For some metrics, particularly when truncation is less frequent for a metabolite, mean centering and median scaling demonstrate comparable performance to mixnorm. When quality control samples are systematically included in batches, mixnorm is uniquely suited to normalizing non-targeted GC/MS metabolomics data due to explicit accommodation of batch effects, run order and varying thresholds of detectability. Especially in large-scale studies, normalization is crucial for drawing accurate conclusions from non-targeted GC/MS metabolomics data.

Preliminary Genetic Analysis Supports Cave Populations as Targets for Conservation in the Endemic Endangered Puerto Rican Boa (Boidae: Epicrates inornatus)

PubMed Central

Revell, Liam J.

2013-01-01

The endemic Puerto Rican boa (Epicrates inornatus) has spent 42 years on the Endangered Species List with little evidence for recovery. One significant impediment to effective conservation planning has been a lack of knowledge of the distribution of genetic variability in the species. It has previously been suggested that boas might best be protected around caves that harbor large populations of bats. Prior study has found Puerto Rican boas at relatively high densities in and around bat caves, which they use both to feed and seek shelter. However, it is unknown whether these behaviorally distinctive populations represent a distinct evolutionary lineage, or (conversely) whether caves harbor representative genetic diversity for the species across the island. We provide the first genetic study of the Puerto Rican boa, and we examine and compare genetic diversity and divergence among two cave populations and two surface populations of boas. We find three haplogroups and an apparent lack of phylogeographic structure across the island. In addition, we find that the two cave populations appear no less diverse than the two surface populations, and harbor multiple mtDNA lineages. We discuss the conservation implications of these findings, including a call for the immediate protection of the remaining cave-associated populations of boas. PMID:23691110

Preliminary genetic analysis supports cave populations as targets for conservation in the endemic endangered Puerto Rican boa (Boidae: Epicrates inornatus).

PubMed

Puente-Rolón, Alberto R; Reynolds, R Graham; Revell, Liam J

2013-01-01

The endemic Puerto Rican boa (Epicrates inornatus) has spent 42 years on the Endangered Species List with little evidence for recovery. One significant impediment to effective conservation planning has been a lack of knowledge of the distribution of genetic variability in the species. It has previously been suggested that boas might best be protected around caves that harbor large populations of bats. Prior study has found Puerto Rican boas at relatively high densities in and around bat caves, which they use both to feed and seek shelter. However, it is unknown whether these behaviorally distinctive populations represent a distinct evolutionary lineage, or (conversely) whether caves harbor representative genetic diversity for the species across the island. We provide the first genetic study of the Puerto Rican boa, and we examine and compare genetic diversity and divergence among two cave populations and two surface populations of boas. We find three haplogroups and an apparent lack of phylogeographic structure across the island. In addition, we find that the two cave populations appear no less diverse than the two surface populations, and harbor multiple mtDNA lineages. We discuss the conservation implications of these findings, including a call for the immediate protection of the remaining cave-associated populations of boas.

Integrin Targeted MR Imaging

PubMed Central

Tan, Mingqian; Lu, Zheng-Rong

2011-01-01

Magnetic resonance imaging (MRI) is a powerful medical diagnostic imaging modality for integrin targeted imaging, which uses the magnetic resonance of tissue water protons to display tissue anatomic structures with high spatial resolution. Contrast agents are often used in MRI to highlight specific regions of the body and make them easier to visualize. There are four main classes of MRI contrast agents based on their different contrast mechanisms, including T1, T2, chemical exchange saturation transfer (CEST) agents, and heteronuclear contrast agents. Integrins are an important family of heterodimeric transmembrane glycoproteins that function as mediators of cell-cell and cell-extracellular matrix interactions. The overexpressed integrins can be used as the molecular targets for designing suitable integrin targeted contrast agents for MR molecular imaging. Integrin targeted contrast agent includes a targeting agent specific to a target integrin, a paramagnetic agent and a linker connecting the targeting agent with the paramagnetic agent. Proper selection of targeting agents is critical for targeted MRI contrast agents to effectively bind to integrins for in vivo imaging. An ideal integrin targeted MR contrast agent should be non-toxic, provide strong contrast enhancement at the target sites and can be completely excreted from the body after MR imaging. An overview of integrin targeted MR contrast agents based on small molecular and macromolecular Gd(III) complexes, lipid nanoparticles and superparamagnetic nanoparticles is provided for MR molecular imaging. By using proper delivery systems for loading sufficient Gd(III) chelates or superparamagnetic nanoparticles, effective molecular imaging of integrins with MRI has been demonstrated in animal models. PMID:21547154

Population Pharmacokinetics of Colistin Methanesulfonate in Rats: Achieving Sustained Lung Concentrations of Colistin for Targeting Respiratory Infections

PubMed Central

W. S. Yapa, Shalini; Li, Jian; Porter, Christopher J. H.; Nation, Roger L.

2013-01-01

Colistin methanesulfonate (CMS), the inactive prodrug of colistin, is administered by inhalation for the management of respiratory infections. However, limited pharmacokinetic data are available for CMS and colistin following pulmonary delivery. This study investigates the pharmacokinetics of CMS and colistin following intravenous (i.v.) and intratracheal (i.t.) administration in rats and determines the targeting advantage after direct delivery into the lungs. In addition to plasma, bronchoalveolar lavage (BAL) fluid was collected to quantify drug concentrations in lung epithelial lining fluid (ELF). The resulting data were analyzed using a population modeling approach in S-ADAPT. A three-compartment model described the disposition of both compounds in plasma following i.v. administration. The estimated mean clearance from the central compartment was 0.122 liters/h for CMS and 0.0657 liters/h for colistin. Conversion of CMS to colistin from all three compartments was required to fit the plasma data. The fraction of the i.v. dose converted to colistin in the systemic circulation was 0.0255. Two BAL fluid compartments were required to reflect drug kinetics in the ELF after i.t. dosing. A slow conversion of CMS (mean conversion time [MCTCMS] = 3.48 h) in the lungs contributed to high and sustained concentrations of colistin in ELF. The fraction of the CMS dose converted to colistin in ELF (fm,ELF = 0.226) was higher than the corresponding fractional conversion in plasma after i.v. administration. In conclusion, pulmonary administration of CMS achieves high and sustained exposures of colistin in lungs for targeting respiratory infections. PMID:23917323

Life histories predict genetic diversity and population structure within three species of octopus targeted by small-scale fisheries in Northwest Mexico

PubMed Central

Ceballos-Vázquez, Bertha P.; Arellano-Martínez, Marcial; García-Rodríguez, Francisco J.; Culver, Melanie; Reyes-Bonilla, Hector

2018-01-01

The fishery for octopus in Northwest Mexico has increased to over 2,000 tons annually, but to date the specific composition of the catch has been ignored. With at least three main species targeted by artisanal fisheries in the region with distinct life histories, the lack of basic biological information about the distribution, metapopulation size and structure of each species could impede effective fisheries management to avoid overexploitation. We tested if different life histories of three species of octopus could help predict observed patterns of genetic diversity, population dynamics, structure and connectivity and how this information could be relevant to the sustainable management of the fishery. We sequenced two mitochondrial genes and genotyped seven nuclear microsatellite loci to identify the distribution of each species in 20 locations from the Gulf of California and the west coast of the Baja California peninsula. We tested five hypotheses derived from population genetic theory based on differences in the fecundity and dispersal potential for each species. We discovered that Octopus bimaculoides with low fecundity and direct development (without a planktonic phase) had lower average effective population size and genetic diversity, but higher levels of kinship, population structure, and richness of private alleles, than the other two species. These features indicated limited dispersal and high local recruitment. In contrast, O. bimaculatus and O. hubbsorum with higher fecundity and planktonic phase as paralarvae had higher effective population size and genetic diversity, and overall lower kinship and population structure than O. bimaculoides. These observations supported higher levels of gene flow over a larger geographical scale. O. bimaculatus with the longest planktonic paralarval duration and therefore larger dispersal potential had differences in the calculated parameters possibly associated with increased connectivity. We propose O

Life histories predict genetic diversity and population structure within three species of octopus targeted by small-scale fisheries in Northwest Mexico.

PubMed

Domínguez-Contreras, José F; Munguia-Vega, Adrian; Ceballos-Vázquez, Bertha P; Arellano-Martínez, Marcial; García-Rodríguez, Francisco J; Culver, Melanie; Reyes-Bonilla, Hector

2018-01-01

The fishery for octopus in Northwest Mexico has increased to over 2,000 tons annually, but to date the specific composition of the catch has been ignored. With at least three main species targeted by artisanal fisheries in the region with distinct life histories, the lack of basic biological information about the distribution, metapopulation size and structure of each species could impede effective fisheries management to avoid overexploitation. We tested if different life histories of three species of octopus could help predict observed patterns of genetic diversity, population dynamics, structure and connectivity and how this information could be relevant to the sustainable management of the fishery. We sequenced two mitochondrial genes and genotyped seven nuclear microsatellite loci to identify the distribution of each species in 20 locations from the Gulf of California and the west coast of the Baja California peninsula. We tested five hypotheses derived from population genetic theory based on differences in the fecundity and dispersal potential for each species. We discovered that Octopus bimaculoides with low fecundity and direct development (without a planktonic phase) had lower average effective population size and genetic diversity, but higher levels of kinship, population structure, and richness of private alleles, than the other two species. These features indicated limited dispersal and high local recruitment. In contrast, O. bimaculatus and O. hubbsorum with higher fecundity and planktonic phase as paralarvae had higher effective population size and genetic diversity, and overall lower kinship and population structure than O. bimaculoides . These observations supported higher levels of gene flow over a larger geographical scale. O. bimaculatus with the longest planktonic paralarval duration and therefore larger dispersal potential had differences in the calculated parameters possibly associated with increased connectivity. We propose O

Microbial population index and community structure in saline-alkaline soil using gene targeted metagenomics.

PubMed

Keshri, Jitendra; Mishra, Avinash; Jha, Bhavanath

2013-03-30

Population indices of bacteria and archaea were investigated from saline-alkaline soil and a possible microbe-environment pattern was established using gene targeted metagenomics. Clone libraries were constructed using 16S rRNA and functional gene(s) involved in carbon fixation (cbbL), nitrogen fixation (nifH), ammonia oxidation (amoA) and sulfur metabolism (apsA). Molecular phylogeny revealed the dominance of Actinobacteria, Firmicutes and Proteobacteria along with archaeal members of Halobacteraceae. The library consisted of novel bacterial (20%) and archaeal (38%) genera showing ≤95% similarity to previously retrieved sequences. Phylogenetic analysis indicated ability of inhabitant to survive in stress condition. The 16S rRNA gene libraries contained novel gene sequences and were distantly homologous with cultured bacteria. Functional gene libraries were found unique and most of the clones were distantly related to Proteobacteria, while clones of nifH gene library also showed homology with Cyanobacteria and Firmicutes. Quantitative real-time PCR exhibited that bacterial abundance was two orders of magnitude higher than archaeal. The gene(s) quantification indicated the size of the functional guilds harboring relevant key genes. The study provides insights on microbial ecology and different metabolic interactions occurring in saline-alkaline soil, possessing phylogenetically diverse groups of bacteria and archaea, which may be explored further for gene cataloging and metabolic profiling. Copyright © 2012 Elsevier GmbH. All rights reserved.

Magnetically attached sputter targets

DOEpatents

Makowiecki, D.M.; McKernan, M.A.

1994-02-15

An improved method and assembly for attaching sputtering targets to cathode assemblies of sputtering systems which includes a magnetically permeable material is described. The magnetically permeable material is imbedded in a target base that is brazed, welded, or soldered to the sputter target, or is mechanically retained in the target material. Target attachment to the cathode is achieved by virtue of the permanent magnets and/or the pole pieces in the cathode assembly that create magnetic flux lines adjacent to the backing plate, which strongly attract the magnetically permeable material in the target assembly. 11 figures.

Evaluation of targeted exome sequencing for 28 protein-based blood group systems, including the homologous gene systems, for blood group genotyping.

PubMed

Schoeman, Elizna M; Lopez, Genghis H; McGowan, Eunike C; Millard, Glenda M; O'Brien, Helen; Roulis, Eileen V; Liew, Yew-Wah; Martin, Jacqueline R; McGrath, Kelli A; Powley, Tanya; Flower, Robert L; Hyland, Catherine A

2017-04-01

Blood group single nucleotide polymorphism genotyping probes for a limited range of polymorphisms. This study investigated whether massively parallel sequencing (also known as next-generation sequencing), with a targeted exome strategy, provides an extended blood group genotype and the extent to which massively parallel sequencing correctly genotypes in homologous gene systems, such as RH and MNS. Donor samples (n = 28) that were extensively phenotyped and genotyped using single nucleotide polymorphism typing, were analyzed using the TruSight One Sequencing Panel and MiSeq platform. Genes for 28 protein-based blood group systems, GATA1, and KLF1 were analyzed. Copy number variation analysis was used to characterize complex structural variants in the GYPC and RH systems. The average sequencing depth per target region was 66.2 ± 39.8. Each sample harbored on average 43 ± 9 variants, of which 10 ± 3 were used for genotyping. For the 28 samples, massively parallel sequencing variant sequences correctly matched expected sequences based on single nucleotide polymorphism genotyping data. Copy number variation analysis defined the Rh C/c alleles and complex RHD hybrids. Hybrid RHD*D-CE-D variants were correctly identified, but copy number variation analysis did not confidently distinguish between D and CE exon deletion versus rearrangement. The targeted exome sequencing strategy employed extended the range of blood group genotypes detected compared with single nucleotide polymorphism typing. This single-test format included detection of complex MNS hybrid cases and, with copy number variation analysis, defined RH hybrid genes along with the RHCE*C allele hitherto difficult to resolve by variant detection. The approach is economical compared with whole-genome sequencing and is suitable for a red blood cell reference laboratory setting. © 2017 AABB.

Population genetic characterization of Cyclospora cayetanensis from discrete geographical regions.

PubMed

Guo, Yaqiong; Li, Na; Ortega, Ynes R; Zhang, Longxian; Roellig, Dawn M; Feng, Yaoyu; Xiao, Lihua

2018-01-01

Cyclospora cayetanensis is an emerging pathogen that is endemic in developing countries and responsible for many large foodborne cyclosporiasis outbreaks in North America since 1990s. Because of the lack of typing targets, the genetic diversity and population genetics of C. cayetanensis have not been investigated. In this study, we undertook a population genetic analysis of multilocus sequence typing data we recently collected from 64 C. cayetanensis specimens. Despite the extensive genetic heterogeneity in the overall C. cayetanensis population, there were significant intra- and inter-genic linkage disequilibria (LD). A disappearance of LD was observed when only multilocus genotypes were included in the population genetic analysis, indicative of an epidemic nature of C. cayetanensis. Geographical segregation-associated sub-structuring was observed between specimens from China and those from Peru and the United States. The two subpopulations had reduced LD, indicating the likely occurrence of genetic exchange among isolates in endemic areas. Further analyses of specimens from other geographical regions are necessary to fully understand the population genetics of C. cayetanensis. Copyright © 2017 Elsevier Inc. All rights reserved.

[Population].

PubMed

1979-01-01

Data on the population of Venezuela between 1975 and 1977 are presented in descriptive tables and graphs. Information is included on the employed population according to category, sex, and type of economic activity, and by sex, age, and area on the employment rate and the total, the economically active, and the unemployed population.

A geodemographic analysis of the Denplan patient population in the North West Region.

PubMed

Tickle, M; Blinkhorn, A S; Brown, P J; Matthews, R

2000-11-11

To provide a preliminary descriptive investigation of Denplan patients in the North West Region, by plotting the age/gender and payment banding distribution, and to identify the area types where Denplan patients live and the areas in the North West Region where Denplan practices are most likely to thrive. North West Region of England The study included Denplan patients resident in the North West Region. Age/gender and payment banding frequency distributions were constructed. A market penetration ranking report using the Target Market level of the Super Profiles geodemographic classification was produced by a spreadsheet analysis in Microsoft Excel. A Lorenz curve was plotted to graphically represent the output of the market penetration analysis. Following the market penetration analysis the enumeration districts (EDs) of the six top ranked Target Markets in the North West Region were identified and mapped out across the Region. Finally, the number and percentage of EDs in the six top ranked Target Markets were identified for each health authority in the Region. 47,106 patients were registered with Denplan. In all but one 5-year age band (16-20-year-olds) female patients were in the majority. Patients were concentrated (40.5%) into the 40-55 age group. Nearly 50% (22,329) of patients were allocated to the second lowest payment banding. Under 0.5% of patients (N = 199) were categorised into the highest payment band. The Target Markets at the top of the penetration ranking were more affluent in nature, with a strong rural element and an older demographic profile as part of their descriptive titles. At the bottom of the ranking deprived area types with young demographic profiles predominated. About one half (49.9%) of Denplan patients were present in just over a quarter (25.7%) of the total population of the North West Region. The Lorenz curve demonstrated that Super Profiles at Target Market level had an effectiveness of 37.9% in segmenting the population of the North

[Population policies in Latin America: 10 years' experience].

PubMed

1983-12-01

The 1974 World Population Plan of Action (WPPA) recommended that the developing countries reduce their rate of population growth to 2.0% by 1985. The population of Latin America, which reached 357 million in 1980, grew at a rate of 2.41% in 1975-80; the rate for 1980-85 is estimated at 2.32%. Birth rates decreased in all countries; the overall rate is close to the WPPA target of 3%, although many countries exceed this rate. The fertility rate decreased in all countries except Argentina; the relative declines varied from 15% (Mexico) to less than 3% (Bolivia, Haiti). Global fertility rates ranged from 6 to less than 3 children. The WPPA goal of a life expectancy of 62 years in 1985 has been reached. Bolivia is the only country with an infant mortality exceeding the WPPA level of 120/1000 live births. Migration trends include a rise in urbanization (from 49.6% in 1960 to 63% in 1980), an increase (from 11 to 26) in the number of cities with more than 1 million inhabitants, and the movement of unskilled workers in search of jobs. Countries having explicit population policies comprise 2 groups: 1) those seeking to decrease their rate of population growth, and 2), those who want to increase their population. The former, which comprise 38% of the region's inhabitants, are trying to reduce fertility by promoting family planning through both public and private efforts. The 2nd group (Argentina, Bolivia, Chile), seek to increase fertility by hindering access to contraceptives and providing incentives for childbearing. Most Latin American countries, however, lack an explicit population policy; they provide family planning as part of their health services, but have not adopted specific demographic goals. Only a few countries are attempting to bring about a better distribution of their population. A review of the Latin American experience during the past decade leads to the following proposals: the integration of demographic policies within socioeconomic development plans, the

Churches as targets for cardiovascular disease prevention: comparison of genes, nutrition, exercise, wellness and spiritual growth (GoodNEWS) and Dallas County populations

PubMed Central

Powell-Wiley, Tiffany M.; Banks-Richard, Kamakki; Williams-King, Elicia; Tong, Liyue; Ayers, Colby R.; de Lemos, James A.; Gimpel, Nora; Lee, Jenny J.; DeHaven, Mark J.

2013-01-01

Background We compared cardiovascular (CV) risk factors (CVRFs) of community-based participatory research (CBPR) participants with the community population to better understand how CBPR participants relate to the population as a whole. Methods GoodNEWS participants in 20 African-American churches in Dallas, Texas were compared with age/sex-matched African-Americans in the Dallas Heart Study (DHS), a probability-based sample of Dallas County residents. DHS characteristics were sample-weight adjusted to represent the Dallas County population. Results Despite having more education (college education: 75 versus 51%, P< 0.0001), GoodNEWS participants were more obese (mean body mass index: 34 versus 31 kg/m2, P< 0.001) and had more diabetes (23 versus 12%, P< 0.001) and hyperlipidemia (53 versus 14%, P< 0.001) compared with African-Americans in Dallas County. GoodNEWS participants had higher rates of treatment and control of most CVRFs (treated hyperlipidemia: 95 versus 64%, P< 0.001; controlled diabetes: 95 versus 21%, P< 0.001; controlled hypertension: 70 versus 52%, P= 0.003), were more physically active (233 versus 177 metabolic equivalent units-min/week, P< 0.0001) and less likely to smoke (10 versus 30%, P< 0.001). Conclusions Compared with African-Americans in Dallas County, CBPR participants in church congregations were more educated, physically active and had more treatment and control of most CVRFs. Surprisingly, this motivated population had a greater obesity burden, identifying them as a prime target for CBPR-focused obesity treatment. PMID:22811446

Effective population size of korean populations.

PubMed

Park, Leeyoung

2014-12-01

Recently, new methods have been developed for estimating the current and recent changes in effective population sizes. Based on the methods, the effective population sizes of Korean populations were estimated using data from the Korean Association Resource (KARE) project. The overall changes in the population sizes of the total populations were similar to CHB (Han Chinese in Beijing, China) and JPT (Japanese in Tokyo, Japan) of the HapMap project. There were no differences in past changes in population sizes with a comparison between an urban area and a rural area. Age-dependent current and recent effective population sizes represent the modern history of Korean populations, including the effects of World War II, the Korean War, and urbanization. The oldest age group showed that the population growth of Koreans had already been substantial at least since the end of the 19th century.

Translational Approaches Targeting Reconsolidation

PubMed Central

Kroes, Marijn C.W.; LeDoux, Joseph E.; Phelps, Elizabeth A.

2017-01-01

Maladaptive learned responses and memories contribute to psychiatric disorders that constitute a significant socio-economic burden. Primary treatment methods teach patients to inhibit maladaptive responses, but do not get rid of the memory itself, which explains why many patients experience a return of symptoms even after initially successful treatment. This highlights the need to discover more persistent and robust techniques to diminish maladaptive learned behaviours. One potentially promising approach is to alter the original memory, as opposed to inhibiting it, by targeting memory reconsolidation. Recent research shows that reactivating an old memory results in a period of memory flexibility and requires restorage, or reconsolidation, for the memory to persist. This reconsolidation period allows a window for modification of a specific old memory. Renewal of memory flexibility following reactivation holds great clinical potential as it enables targeting reconsolidation and changing of specific learned responses and memories that contribute to maladaptive mental states and behaviours. Here, we will review translational research on non-human animals, healthy human subjects, and clinical populations aimed at altering memories by targeting reconsolidation using biological treatments (electrical stimulation, noradrenergic antagonists) or behavioural interference (reactivation–extinction paradigm). Both approaches have been used successfully to modify aversive and appetitive memories, yet effectiveness in treating clinical populations has been limited. We will discuss that memory flexibility depends on the type of memory tested and the brain regions that underlie specific types of memory. Further, when and how we can most effectively reactivate a memory and induce flexibility is largely unclear. Finally, the development of drugs that can target reconsolidation and are safe for use in humans would optimize cross-species translations. Increasing the understanding of

Generalized herd effects and vaccine evaluation: impact of live influenza vaccine on off-target bacterial colonisation.

PubMed

Mina, Michael J

2017-06-01

Interactions between pathogens and commensal microbes are major contributors to health and disease. Infectious diseases however are most often considered independent, viewed within a one-host one-pathogen paradigm and, by extension, the interventions used to treat and prevent them are measured and evaluated within this same paradigm. Vaccines, especially live vaccines, by stimulating immune responses or directly interacting with other microbes can alter the environment in which they act, with effects that span across pathogen species. Live attenuated infl uenza vaccines for example, while safe, increase upper respiratory tract bacterial carriage density of important human commensal pathogens like Streptococcus pneumoniae and Staphylococcus aureus. Further, by altering the ecological niche and dynamics of phylogenetically distinct microbes within the host, vaccines may unintentionally affect transmission of non-vaccine targeted pathogens. Thus, vaccine effects may span across species and across scales, from the individual to the population level. In keeping with traditional vaccine herd-effects that indirectly protect even unvaccinated individuals by reducing population prevalence of vaccine-targeted pathogens, we call these cross-species cross-scale effects "generalized herd-effects". As opposed to traditional herd-effects, "generalized" relaxes the assumption that the effect occurs at the level of the vaccine-target pathogen and "herd effect" implies, as usual, that the effects indirectly impact the population at large, including unvaccinated bystanders. Unlike traditional herd-effects that decrease population prevalence of the vaccine-target, generalized herd-effects may decrease or increase prevalence and disease by the off-target pathogen. LAIV, for example, by increasing pneumococcal density in the upper respiratory tract of vaccine recipients, especially children, may increase pneumococcal transmission and prevalence, leading to excess pneumococcal invasive

Examination of muscularity and body fat depictions in magazines that target heterosexual and gay men.

PubMed

Lanzieri, Nicholas; Cook, Brian J

2013-03-01

Previous content analyses of magazine images have typically examined within genres but failed to include comparisons between publications intended for various populations. The purpose of this study was to examine depictions of muscularity and thinness of male images in several widely distributed magazines that target male audiences from a variety of genres. Twenty-three magazine titles with the highest circulation rates that targeted heterosexual men, gay men, and general audiences were selected for image analyses. We found that magazines that target gay male audiences depicted images of men who were thinner in comparison to magazines targeting heterosexual men. Both gay and heterosexual magazines depicted male images with greater muscularity than magazines intended for general audiences. Differences in male image depictions in magazines may contribute to the promotion of an unattainable body ideal in some subgroups of gay culture. Copyright © 2012 Elsevier Ltd. All rights reserved.

Communication Strategies Must Be Tailored to a Medication's Targeted Population: Lessons from the Case of BiDil

PubMed Central

Hawkins-Taylor, Chamika; Carlson, Angeline M

2013-01-01

Background The American population's diversity continues to grow, and its racial and ethnic mixes are changing. The US healthcare system must confront this changing reality. The introduction of isosorbide dinitrate/hydralazine hydrochloride (BiDil) to the US marketplace was a move toward recognizing these changing consumer needs. BiDil was approved specifically as a secondary treatment for heart failure in African-American patients. It remains the first and only drug approved by the US Food and Drug Administration for a race-based indication. To ensure commercial success, a drug must be made “visible” to healthcare providers and to consumers. Objectives To describe and analyze the case of BiDil and its potential implications for drugs developed for targeted populations to help them avoid a similar fate of market withdrawal because of commercial considerations. Method This analysis is based on 12 comprehensive interviews with 5 clinical investigators, 1 minority healthcare provider, and 5 pharmaceutical representatives, as well as a review of the literature. Overall, 12 one-hour semistructured interviews were conducted. Of the 11 interviewees, 10 were interviewed once and 1 was interviewed once early in the process and then had a second interview by the end of the study. When the 12 scheduled interviews were completed, the recordings were transcribed and subjected to analysis through the use of a readily available computer software package, using concepts and themes collected from the literature and the interviewees' responses. Results The interviewees lacked consensus regarding the unique nature of BiDil. The clinical researchers considered it innovative in identifying that taking the 2 drugs together produced the greatest clinical effect in African-American patients with heart failure. For them, BiDil represented an innovation in the emerging field of personalized medicine. However, they were dismayed to see that these beliefs were challenged by the medical

Individualized population care: linking personal care to population care in general practice.

PubMed

Buetow, Stephen; Getz, Linn; Adams, Peter

2008-10-01

General practice is increasingly expected to deliver population care to individual patients. The feasibility and ethics of this policy shift have been challenged. Our aim is to suggest how to deliver population care while protecting personal care. We outline and discuss concepts of these types of care, their relation to the prevailing discourse regarding intervention benefits, and arguments for individualized population care. Individualized population care can enable general practice to meet the health targets of individual patients in the light of population-based goals. It unifies the concepts of personal care and whole population care. Personal care focuses on the individual good in particular consultations. Whole population care focuses on the overall health good of a population without reference to the individuality of each population member. These types of care constitute elements of a continuum that varies in purpose and objects of focus. The limitations of a crude dichotomy of personal care and population care are made explicit in a series of five arguments that lend support to the concept of individualized population care. We advocate a constructive but critical attitude towards the idea of population-based interventions in everyday general practice. Traditional personal care and whole population care can theoretically be integrated into individualized population care. However, this presupposes clinical-epidemiological expertise and moral awareness in practising clinicians.

Human target acquisition performance

NASA Astrophysics Data System (ADS)

Teaney, Brian P.; Du Bosq, Todd W.; Reynolds, Joseph P.; Thompson, Roger; Aghera, Sameer; Moyer, Steven K.; Flug, Eric; Espinola, Richard; Hixson, Jonathan

2012-06-01

The battlefield has shifted from armored vehicles to armed insurgents. Target acquisition (identification, recognition, and detection) range performance involving humans as targets is vital for modern warfare. The acquisition and neutralization of armed insurgents while at the same time minimizing fratricide and civilian casualties is a mounting concern. U.S. Army RDECOM CERDEC NVESD has conducted many experiments involving human targets for infrared and reflective band sensors. The target sets include human activities, hand-held objects, uniforms & armament, and other tactically relevant targets. This paper will define a set of standard task difficulty values for identification and recognition associated with human target acquisition performance.

Target population's requirements on a community-based intervention for stimulating physical activity in hard-to-reach physically disabled people: an interview study.

PubMed

Krops, Leonie A; Folkertsma, Nienke; Hols, Doortje H J; Geertzen, Jan H B; Dijkstra, Pieter U; Dekker, Rienk

2018-05-31

To explore ideas of the target population about a community-based intervention to stimulate physical activity in hard-to-reach physically disabled people. Semi-structured interviews were performed with 21 physically disabled people, and analyzed using thematic analyses. Findings were interpreted using the integrated Physical Activity for People with a Disability and Intervention Mapping model. The intervention should aim to stimulate intrinsic motivation and raise awareness for the health effects of physical activity. It should provide diverse activities, increase visibility of these activities, and improve image of physical activity for physically disabled people. Participants suggested to provide individual coaching sessions, increase marketing, present role models, and assign buddies. Potential users should be approached personally through intermediate organizations, or via social media and word of mouth promotion. Participants suggested that users, government, sponsors, and health insurers should finance the intervention. Self-responsibility for being physically active was strongly emphasized by participants. An intervention to stimulate physical activity in hard-to-reach physically disabled people should be individualized, include personal support, and should include marketing to improve image of physical activity of physically disabled people. The intervention that fulfills these requirements should be developed and tested for effects in future research. Implications for rehabilitation An intervention to stimulate physical activity in physically disabled people should aim to raise awareness for the health effects of physical activity, stimulate intrinsic motivation, offer diverse activities, increase the visibility of the possible activities, and improve the image of physical activity for physically disabled people. An intervention should include both individual- and environmental-level intervention methods. Physically disabled people most emphasized

Learning from experience: three community health population-based outreach projects for graduate and undergraduate students.

PubMed

D'Lugoff, Marion Isaacs; McCarter, Jeanne

2005-01-01

Three outreach activities by a school of nursing, in partnership with community agencies, provided learning experiences in primary and secondary preventive health care for graduate and undergraduate nursing students while addressing health needs in the community. The activities included administration of immunizations to a newly arrived Somali Bantu refugee population, targeted screening of an African-American population at risk for diabetic retinopathy, and general health screening for an underserved Hispanic immigrant population. These activities lend insight and depth to a community health curriculum by allowing students to provide needed services while engaging with culturally diverse clients of varying socioeconomic status. Learner objectives, resources, processes and outcomes are provided for each example.

A multiple-alignment based primer design algorithm for genetically highly variable DNA targets

PubMed Central

2013-01-01

Background Primer design for highly variable DNA sequences is difficult, and experimental success requires attention to many interacting constraints. The advent of next-generation sequencing methods allows the investigation of rare variants otherwise hidden deep in large populations, but requires attention to population diversity and primer localization in relatively conserved regions, in addition to recognized constraints typically considered in primer design. Results Design constraints include degenerate sites to maximize population coverage, matching of melting temperatures, optimizing de novo sequence length, finding optimal bio-barcodes to allow efficient downstream analyses, and minimizing risk of dimerization. To facilitate primer design addressing these and other constraints, we created a novel computer program (PrimerDesign) that automates this complex procedure. We show its powers and limitations and give examples of successful designs for the analysis of HIV-1 populations. Conclusions PrimerDesign is useful for researchers who want to design DNA primers and probes for analyzing highly variable DNA populations. It can be used to design primers for PCR, RT-PCR, Sanger sequencing, next-generation sequencing, and other experimental protocols targeting highly variable DNA samples. PMID:23965160

Policy options for alcohol price regulation: the importance of modelling population heterogeneity.

PubMed

Meier, Petra Sylvia; Purshouse, Robin; Brennan, Alan

2010-03-01

Context and aims Internationally, the repertoire of alcohol pricing policies has expanded to include targeted taxation, inflation-linked taxation, taxation based on alcohol-by-volume (ABV), minimum pricing policies (general or targeted), bans of below-cost selling and restricting price-based promotions. Policy makers clearly need to consider how options compare in reducing harms at the population level, but are also required to demonstrate proportionality of their actions, which necessitates a detailed understanding of policy effects on different population subgroups. This paper presents selected findings from a policy appraisal for the UK government and discusses the importance of accounting for population heterogeneity in such analyses. Method We have built a causal, deterministic, epidemiological model which takes account of differential preferences by population subgroups defined by age, gender and level of drinking (moderate, hazardous, harmful). We consider purchasing preferences in terms of the types and volumes of alcoholic beverages, prices paid and the balance between bars, clubs and restaurants as opposed to supermarkets and off-licenses. Results Age, sex and level of drinking fundamentally affect beverage preferences, drinking location, prices paid, price sensitivity and tendency to substitute for other beverage types. Pricing policies vary in their impact on different product types, price points and venues, thus having distinctly different effects on subgroups. Because population subgroups also have substantially different risk profiles for harms, policies are differentially effective in reducing health, crime, work-place absence and unemployment harms. Conclusion Policy appraisals must account for population heterogeneity and complexity if resulting interventions are to be well considered, proportionate, effective and cost-effective.

Why Targeted Therapies are Necessary for Systemic Lupus Erythematosus

PubMed Central

Durcan, Laura; Petri, Michelle

2016-01-01

Systemic lupus erythematosus (SLE) continues to have important morbidity and accelerated mortality despite therapeutic advances. Targeted therapies offer the possibility of improved efficacy with fewer side-effects. Current management strategies rely heavily on non-specific immunosuppressive agents. Prednisone, in particular, is responsible for a considerable burden of later organ damage. There are a multitude of diverse mechanisms of disease activity, immunogenic abnormalities and clinical manifestations to take into consideration in SLE. Many targeted agents with robust mechanistic pre-clinical data and promising early phase studies have ultimately been disappointing in phase III randomized controlled studies. Recent efforts have focused on B cell therapies, in particular given the success of belimumab in clinical trials, with limited success. We remain optimistic regarding other specific therapies being evaluated including interferon alpha blockade. It is likely that in SLE, given the heterogeneity of the population involved, precision medicine is needed, rather than expecting that any single biologic will be universally effective. PMID:27497251

Targets and processes for fabricating same

DOEpatents

Cowan, Thomas [Dresden, DE; Malekos, Steven [Reno, NV; Korgan, Grant [Reno, NV; Adams, Jesse [Reno, NV; Sentoku, Yasuhiko [Reno, NV; Le Galloudec, Nathalie [Reno, NV; Fuchs, Julien [Paris, FR

2012-07-24

In particular embodiments, the present disclosure provides targets including a metal layer and defining a hollow inner surface. The hollow inner surface has an internal apex. The distance between at least two opposing points of the internal apex is less than about 15 .mu.m. In particular examples, the distance is less than about 1 .mu.m. Particular implementations of the targets are free standing. The targets have a number of disclosed shaped, including cones, pyramids, hemispheres, and capped structures. The present disclosure also provides arrays of such targets. Also provided are methods of forming targets, such as the disclosed targets, using lithographic techniques, such as photolithographic techniques. In particular examples, a target mold is formed from a silicon wafer and then one or more sides of the mold are coated with a target material, such as one or more metals.

Targets and processes for fabricating same

DOEpatents

Adams, Jesse D; Malekos, Steven; Le Galloudec, Nathalie; Korgan, Grant; Cowan, Thomas; Sentoku, Yasuhiko

2016-05-17

In particular embodiments, the present disclosure provides targets including a metal layer and defining a hollow inner surface. The hollow inner surface has an internal apex. The distance between at least two opposing points of the internal apex is less than about 15 .mu.m. In particular examples, the distance is less than about 1 .mu.m. Particular implementations of the targets are free standing. The targets have a number of disclosed shaped, including cones, pyramids, hemispheres, and capped structures. The present disclosure also provides arrays of such targets. Also provided are methods of forming targets, such as the disclosed targets, using lithographic techniques, such as photolithographic techniques. In particular examples, a target mold is formed from a silicon wafer and then one or more sides of the mold are coated with a target material, such as one or more metals.

Targets and processes for fabricating same

DOEpatents

Cowna, Thomas; Malekos, Steven; Korgan, Grant; Adams, Jesse; Sentoku, Yasuhiko; LeGalloudec, Nathalie

2014-06-10

In particular embodiments, the present disclosure provides targets including a metal layer and defining a hollow inner surface. The hollow inner surface has an internal apex. The distance between at least two opposing points of the internal apex is less than about 15 .mu.m. In particular examples, the distance is less than about 1 .mu.m. Particular implementations of the targets are free standing. The targets have a number of disclosed shaped, including cones, pyramids, hemispheres, and capped structures. The present disclosure also provides arrays of such targets. Also provided are methods of forming targets, such as the disclosed targets, using lithographic techniques, such as photolithographic techniques. In particular examples, a target mold is formed from a silicon wafer and then one or more sides of the mold are coated with a target material, such as one or more metals.

Internal Targeting and External Control: Phototriggered Targeting in Nanomedicine.

PubMed

Arrue, Lily; Ratjen, Lars

2017-12-07

The photochemical control of structure and reactivity bears great potential for chemistry, biology, and life sciences. A key feature of photochemistry is the spatiotemporal control over secondary events. Well-established applications of photochemistry in medicine are photodynamic therapy (PDT) and photopharmacology (PP). However, although both are highly localizable through the application of light, they lack cell- and tissue-specificity. The combination of nanomaterial-based drug delivery and targeting has the potential to overcome limitations for many established therapy concepts. Even more privileged seems the merger of nanomedicine and cell-specific targeting (internal targeting) controlled by light (external control), as it can potentially be applied to many different areas of medicine and pharmaceutical research, including the aforementioned PDT and PP. In this review a survey of the interface of photochemistry, medicine and targeted drug delivery is given, especially focusing on phototriggered targeting in nanomedicine. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Target School Research Project: Change and Learning Community Development

ERIC Educational Resources Information Center

Simmerman, Herbert R., Jr.

2009-01-01

This study investigated the use of organizational learning community principles to effectively manage organizational change. Target is a pseudonym for a small public school in Southern New Jersey that has provided educational services to students with special needs since 1969. In 2004 Target began providing services to a new population of students…

HIV/AIDS National Strategic Plans of Sub-Saharan African countries: an analysis for gender equality and sex-disaggregated HIV targets.

PubMed

Sherwood, Jennifer; Sharp, Alana; Cooper, Bergen; Roose-Snyder, Beirne; Blumenthal, Susan

2017-12-01

National Strategic Plans (NSPs) for HIV/AIDS are country planning documents that set priorities for programmes and services, including a set of targets to quantify progress toward national and international goals. The inclusion of sex-disaggregated targets and targets to combat gender inequality is important given the high disease burden among young women and adolescent girls in Sub-Saharan Africa, yet no comprehensive gender-focused analysis of NSP targets has been performed. This analysis quantitatively evaluates national HIV targets, included in NSPs from eighteen Sub-Saharan African countries, for sex-disaggregation. Additionally, NSP targets aimed at reducing gender-based inequality in health outcomes are compiled and inductively coded to report common themes. On average, in the eighteen countries included in this analysis, 31% of NSP targets include sex-disaggregation (range 0-92%). Three countries disaggregated a majority (>50%) of their targets by sex. Sex-disaggregation in data reporting was more common for targets related to the early phases of the HIV care continuum: 83% of countries included any sex-disaggregated targets for HIV prevention, 56% for testing and linkage to care, 22% for improving antiretroviral treatment coverage, and 11% for retention in treatment. The most common target to reduce gender inequality was to prevent gender-based violence (present in 50% of countries). Other commonly incorporated target areas related to improving women's access to family planning, human and legal rights, and decision-making power. The inclusion of sex-disaggregated targets in national planning is vital to ensure that programmes make progress for all population groups. Improving the availability and quality of indicators to measure gender inequality, as well as evaluating programme outcomes by sex, is critical to tracking this progress. This analysis reveals an urgent need to set specific and separate targets for men and women in order to achieve an equitable

HIV/AIDS National Strategic Plans of Sub-Saharan African countries: an analysis for gender equality and sex-disaggregated HIV targets

PubMed Central

Sherwood, Jennifer; Sharp, Alana; Cooper, Bergen; Roose-Snyder, Beirne; Blumenthal, Susan

2017-01-01

Abstract National Strategic Plans (NSPs) for HIV/AIDS are country planning documents that set priorities for programmes and services, including a set of targets to quantify progress toward national and international goals. The inclusion of sex-disaggregated targets and targets to combat gender inequality is important given the high disease burden among young women and adolescent girls in Sub-Saharan Africa, yet no comprehensive gender-focused analysis of NSP targets has been performed. This analysis quantitatively evaluates national HIV targets, included in NSPs from eighteen Sub-Saharan African countries, for sex-disaggregation. Additionally, NSP targets aimed at reducing gender-based inequality in health outcomes are compiled and inductively coded to report common themes. On average, in the eighteen countries included in this analysis, 31% of NSP targets include sex-disaggregation (range 0–92%). Three countries disaggregated a majority (>50%) of their targets by sex. Sex-disaggregation in data reporting was more common for targets related to the early phases of the HIV care continuum: 83% of countries included any sex-disaggregated targets for HIV prevention, 56% for testing and linkage to care, 22% for improving antiretroviral treatment coverage, and 11% for retention in treatment. The most common target to reduce gender inequality was to prevent gender-based violence (present in 50% of countries). Other commonly incorporated target areas related to improving women’s access to family planning, human and legal rights, and decision-making power. The inclusion of sex-disaggregated targets in national planning is vital to ensure that programmes make progress for all population groups. Improving the availability and quality of indicators to measure gender inequality, as well as evaluating programme outcomes by sex, is critical to tracking this progress. This analysis reveals an urgent need to set specific and separate targets for men and women in order to achieve

Dementia Research: Populations, Progress, Problems, and Predictions.

PubMed

Hunter, Sally; Smailagic, Nadja; Brayne, Carol

2018-05-16

Alzheimer's disease (AD) is a clinicopathologically defined syndrome leading to cognitive impairment. Following the recent failures of amyloid-based randomized controlled trials to change the course of AD, there are growing calls for a re-evaluation of basic AD research. Epidemiology offers one approach to integrating the available evidence. Here we examine relationships between evidence from population-based, clinicopathological studies of brain aging and a range of hypotheses from all areas of AD research. We identify various problems, including a lack of systematic approach to measurement of clinical and neuropathological factors associated with dementia in experimental and clinical settings, poor understanding of the strengths and weaknesses of different observational and experimental designs, a lack of clarity in relation to disease definitions from the clinical, neuropathological, and molecular perspectives, inadequate characterization of brain aging in the human population, difficulties in translation between laboratory-based and population-based evidence bases, and a lack of communication between different sections of the dementia research community. Population studies highlight complexity and predict that therapeutic approaches based on single disease features will not be successful. Better characterization of brain aging in the human population is urgently required to select biomarkers and therapeutic targets that are meaningful to human disease. The generation of detailed and reliable evidence must be addressed before progress toward therapeutic interventions can be made.

Seedling root targets

Treesearch

Diane L. Haase

2011-01-01

Roots are critical to seedling performance after outplanting. Although root quality is not as quick and simple to measure as shoot quality, target root characteristics should be included in any seedling quality assessment program. This paper provides a brief review of root characteristics most commonly targeted for operational seedling production. These are: root mass...

Recruiting Vulnerable Populations into Research: A Systematic Review of Recruitment Interventions

PubMed Central

UyBico, Stacy J.; Pavel, Shani

2007-01-01

Background Members of vulnerable populations are underrepresented in research studies. Objective To evaluate and synthesize the evidence regarding interventions to enhance enrollment of vulnerable populations into health research studies. Data sources Studies were identified by searching MEDLINE, the Web of Science database, personal sources, hand searching of related journals, and article references. Studies that contained data on recruitment interventions for vulnerable populations (minority, underserved, poor, rural, urban, or inner city) and for which the parent study (study for which recruitment was taking place) was an intervention study were included. A total of 2,648 study titles were screened and 48 articles met inclusion criteria, representing 56 parent studies. Two investigators extracted data from each study. Results African Americans were the most frequently targeted population (82% of the studies), while 46% targeted Hispanics/Latinos. Many studies assessed 2 or more interventions, including social marketing (82% of studies), community outreach (80%), health system recruitment (52%), and referrals (28%). The methodologic rigor varied substantially. Only 40 studies (71%) incorporated a control group and 21% used statistical analysis to compare interventions. Social marketing, health system, and referral recruitment were each found to be the most successful intervention about 35–45% of the studies in which they were attempted, while community outreach was the most successful intervention in only 2 of 16 studies (13%) in which it was employed. People contacted as a result of social marketing were no less likely to enroll than people contacted through other mechanisms. Conclusions Further work with greater methodologic rigor is needed to identify evidence-based strategies for increasing minority enrollment in research studies; community outreach, as an isolated strategy, may be less successful than other strategies. PMID:17375358

Exploiting CRISPR-Cas to manipulate Enterococcus faecalis populations.

PubMed

Hullahalli, Karthik; Rodrigues, Marinelle; Palmer, Kelli L

2017-06-23

CRISPR-Cas provides a barrier to horizontal gene transfer in prokaryotes. It was previously observed that functional CRISPR-Cas systems are absent from multidrug-resistant (MDR) Enterococcus faecalis , which only possess an orphan CRISPR locus, termed CRISPR2, lacking cas genes. Here, we investigate how the interplay between CRISPR-Cas genome defense and antibiotic selection for mobile genetic elements shapes in vitro E. faecalis populations. We demonstrate that CRISPR2 can be reactivated for genome defense in MDR strains. Interestingly, we observe that E. faecalis transiently maintains CRISPR targets despite active CRISPR-Cas systems. Subsequently, if selection for the CRISPR target is present, toxic CRISPR spacers are lost over time, while in the absence of selection, CRISPR targets are lost over time. We find that forced maintenance of CRISPR targets induces a fitness cost that can be exploited to alter heterogeneous E. faecalis populations.

What magnitude are observed non-target impacts from weed biocontrol?

PubMed

Suckling, David Maxwell; Sforza, René François Henri

2014-01-01

A systematic review focused by plant on non-target impacts from agents deliberately introduced for the biological control of weeds found significant non-target impacts to be rare. The magnitude of direct impact of 43 biocontrol agents on 140 non-target plants was retrospectively categorized using a risk management framework for ecological impacts of invasive species (minimal, minor, moderate, major, massive). The vast majority of agents introduced for classical biological control of weeds (>99% of 512 agents released) have had no known significant adverse effects on non-target plants thus far; major effects suppressing non-target plant populations could be expected to be detectable. Most direct non-target impacts on plants (91.6%) were categorized as minimal or minor in magnitude with no known adverse long-term impact on non-target plant populations, but a few cacti and thistles are affected at moderate (n = 3), major (n = 7) to massive (n = 1) scale. The largest direct impacts are from two agents (Cactoblastis cactorum on native cacti and Rhinocyllus conicus on native thistles), but these introductions would not be permitted today as more balanced attitudes exist to plant biodiversity, driven by both society and the scientific community. Our analysis shows (as far as is known), weed biological control agents have a biosafety track record of >99% of cases avoiding significant non-target impacts on plant populations. Some impacts could have been overlooked, but this seems unlikely to change the basic distribution of very limited adverse effects. Fewer non-target impacts can be expected in future because of improved science and incorporation of wider values. Failure to use biological control represents a significant opportunity cost from the certainty of ongoing adverse impacts from invasive weeds. It is recommended that a simple five-step scale be used to better communicate the risk of consequences from both action (classical biological control) and no

What Magnitude Are Observed Non-Target Impacts from Weed Biocontrol?

PubMed Central

Suckling, David Maxwell; Sforza, René François Henri

2014-01-01

A systematic review focused by plant on non-target impacts from agents deliberately introduced for the biological control of weeds found significant non-target impacts to be rare. The magnitude of direct impact of 43 biocontrol agents on 140 non-target plants was retrospectively categorized using a risk management framework for ecological impacts of invasive species (minimal, minor, moderate, major, massive). The vast majority of agents introduced for classical biological control of weeds (>99% of 512 agents released) have had no known significant adverse effects on non-target plants thus far; major effects suppressing non-target plant populations could be expected to be detectable. Most direct non-target impacts on plants (91.6%) were categorized as minimal or minor in magnitude with no known adverse long-term impact on non-target plant populations, but a few cacti and thistles are affected at moderate (n = 3), major (n = 7) to massive (n = 1) scale. The largest direct impacts are from two agents (Cactoblastis cactorum on native cacti and Rhinocyllus conicus on native thistles), but these introductions would not be permitted today as more balanced attitudes exist to plant biodiversity, driven by both society and the scientific community. Our analysis shows (as far as is known), weed biological control agents have a biosafety track record of >99% of cases avoiding significant non-target impacts on plant populations. Some impacts could have been overlooked, but this seems unlikely to change the basic distribution of very limited adverse effects. Fewer non-target impacts can be expected in future because of improved science and incorporation of wider values. Failure to use biological control represents a significant opportunity cost from the certainty of ongoing adverse impacts from invasive weeds. It is recommended that a simple five-step scale be used to better communicate the risk of consequences from both action (classical biological control) and no

The relative importance of intrinsic and extrinsic drivers to population growth vary among local populations of Greater Sage-Grouse: An integrated population modeling approach

USGS Publications Warehouse

Coates, Peter S.; Prochazka, Brian G.; Ricca, Mark A.; Halstead, Brian J.; Casazza, Michael L.; Blomberg, Erik J.; Brussee, Brianne E.; Wiechman, Lief; Tebbenkamp, Joel; Gardner, Scott C.; Reese, Kerry P.

2018-01-01

Consideration of ecological scale is fundamental to understanding and managing avian population growth and decline. Empirically driven models for population dynamics and demographic processes across multiple spatial scales can be powerful tools to help guide conservation actions. Integrated population models (IPMs) provide a framework for better parameter estimation by unifying multiple sources of data (e.g., count and demographic data). Hierarchical structure within such models that include random effects allow for varying degrees of data sharing across different spatiotemporal scales. We developed an IPM to investigate Greater Sage-Grouse (Centrocercus urophasianus) on the border of California and Nevada, known as the Bi-State Distinct Population Segment. Our analysis integrated 13 years of lek count data (n > 2,000) and intensive telemetry (VHF and GPS; n > 350 individuals) data across 6 subpopulations. Specifically, we identified the most parsimonious models among varying random effects and density-dependent terms for each population vital rate (e.g., nest survival). Using a joint likelihood process, we integrated the lek count data with the demographic models to estimate apparent abundance and refine vital rate parameter estimates. To investigate effects of climatic conditions, we extended the model to fit a precipitation covariate for instantaneous rate of change (r). At a metapopulation extent (i.e. Bi-State), annual population rate of change λ (er) did not favor an overall increasing or decreasing trend through the time series. However, annual changes in λ were driven by changes in precipitation (one-year lag effect). At subpopulation extents, we identified substantial variation in λ and demographic rates. One subpopulation clearly decoupled from the trend at the metapopulation extent and exhibited relatively high risk of extinction as a result of low egg fertility. These findings can inform localized, targeted management actions for specific areas

Uncovering multiple pathways to substance use: a comparison of methods for identifying population subgroups.

PubMed

Dierker, Lisa; Rose, Jennifer; Tan, Xianming; Li, Runze

2010-12-01

This paper describes and compares a selection of available modeling techniques for identifying homogeneous population subgroups in the interest of informing targeted substance use intervention. We present a nontechnical review of the common and unique features of three methods: (a) trajectory analysis, (b) functional hierarchical linear modeling (FHLM), and (c) decision tree methods. Differences among the techniques are described, including required data features, strengths and limitations in terms of the flexibility with which outcomes and predictors can be modeled, and the potential of each technique for helping to inform the selection of targets and timing of substance intervention programs.

Anopheles darlingi polytene chromosomes: revised maps including newly described inversions and evidence for population structure in Manaus

PubMed Central

Cornel, Anthony J; Brisco, Katherine K; Tadei, Wanderli P; Secundino, Nágila FC; Rafael, Miriam S; Galardo, Allan KR; Medeiros, Jansen F; Pessoa, Felipe AC; Ríos-Velásquez, Claudia M; Lee, Yoosook; Pimenta, Paulo FP; Lanzaro, Gregory C

2016-01-01

Salivary gland polytene chromosomes of 4th instar Anopheles darlingi Root were examined from multiple locations in the Brazilian Amazon. Minor modifications were made to existing polytene photomaps. These included changes to the breakpoint positions of several previously described paracentric inversions and descriptions of four new paracentric inversions, two on the right arm of chromosome 3 and two on the left arm of chromosome 3 that were found in multiple locations. A total of 18 inversions on the X (n = 1) chromosome, chromosome 2 (n = 7) and 3 (n = 11) were scored for 83 individuals from Manaus, Macapá and Porto Velho municipalities. The frequency of 2Ra inversion karyotypes in Manaus shows significant deficiency of heterozygotes (p < 0.0009). No significant linkage disequilibrium was found between inversions on chromosome 2 and 3. We hypothesize that at least two sympatric subpopulations exist within the An. darlingi population at Manaus based on inversion frequencies. PMID:27223867

Population pharmacokinetic characterization of BAY 81-8973, a full-length recombinant factor VIII: lessons learned - importance of including samples with factor VIII levels below the quantitation limit.

PubMed

Garmann, D; McLeay, S; Shah, A; Vis, P; Maas Enriquez, M; Ploeger, B A

2017-07-01

The pharmacokinetics (PK), safety and efficacy of BAY 81-8973, a full-length, unmodified, recombinant human factor VIII (FVIII), were evaluated in the LEOPOLD trials. The aim of this study was to develop a population PK model based on pooled data from the LEOPOLD trials and to investigate the importance of including samples with FVIII levels below the limit of quantitation (BLQ) to estimate half-life. The analysis included 1535 PK observations (measured by the chromogenic assay) from 183 male patients with haemophilia A aged 1-61 years from the 3 LEOPOLD trials. The limit of quantitation was 1.5 IU dL -1 for the majority of samples. Population PK models that included or excluded BLQ samples were used for FVIII half-life estimations, and simulations were performed using both estimates to explore the influence on the time below a determined FVIII threshold. In the data set used, approximately 16.5% of samples were BLQ, which is not uncommon for FVIII PK data sets. The structural model to describe the PK of BAY 81-8973 was a two-compartment model similar to that seen for other FVIII products. If BLQ samples were excluded from the model, FVIII half-life estimations were longer compared with a model that included BLQ samples. It is essential to assess the importance of BLQ samples when performing population PK estimates of half-life for any FVIII product. Exclusion of BLQ data from half-life estimations based on population PK models may result in an overestimation of half-life and underestimation of time under a predetermined FVIII threshold, resulting in potential underdosing of patients. © 2017 Bayer AG. Haemophilia Published by John Wiley & Sons Ltd.

Impact of Hospital Population Case-Mix, Including Poverty, on Hospital All-Cause and Infection-Related 30-Day Readmission Rates.

PubMed

Gohil, Shruti K; Datta, Rupak; Cao, Chenghua; Phelan, Michael J; Nguyen, Vinh; Rowther, Armaan A; Huang, Susan S

2015-10-15

Reducing hospital readmissions, including preventable healthcare-associated infections, is a national priority. The proportion of readmissions due to infections is not well-understood. Better understanding of hospital risk factors for readmissions and infection-related readmissions may help optimize interventions to prevent readmissions. Retrospective cohort study of California acute care hospitals and their patient populations discharged between 2009 and 2011. Demographics, comorbidities, and socioeconomic status were entered into a hierarchical generalized linear mixed model predicting all-cause and infection-related readmissions. Crude verses adjusted hospital rankings were compared using Cohen's kappa. We assessed 30-day readmission rates from 323 hospitals, accounting for 213 879 194 post-discharge person-days of follow-up. Infection-related readmissions represented 28% of all readmissions and were associated with discharging a high proportion of patients to skilled nursing facilities. Hospitals serving populations with high proportions of males, comorbidities, prolonged length of stay, and populations living in a federal poverty area, had higher all-cause and infection-related readmission rates. Academic hospitals had higher all-cause and infection-related readmission rates (odds ratio 1.24 and 1.15, respectively). When comparing adjusted vs crude hospital rankings for infection-related readmission rates, adjustment revealed 31% of hospitals changed performance category for infection-related readmissions. Infection-related readmissions accounted for nearly 30% of all-cause readmissions. High hospital infection-related readmissions were associated with serving a high proportion of patients with comorbidities, long lengths of stay, discharge to skilled nursing facility, and those living in federal poverty areas. Preventability of these infections needs to be assessed. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases

The Population Care Coordination Process.

PubMed

Rushton, Sharron

2015-01-01

The purpose of the article was to outline a population-based approach to providing care coordination. The Population Care Coordination Process provides a framework for each provider and/or organization to provide multilevel care based on population- and patient-centered principles. The Population Care Coordination Process is scalable. It can be utilized in a smaller scale such as single provider office or in a larger scale such as an accountable care organization. There are many issues within our current health care structure that must be addressed. Care coordination has been identified as a potential solution to address the needs of complex patients within the system. The expansion to consider populations allows for a more targeted and efficient approach. The population care process entails a data-driven approach to care coordination. The inclusion of populations in the care coordination process provides an opportunity to maximize efforts and improve outcomes.

Population

EPA Science Inventory

Population growth influences many stressors on Narragansett Bay and its Watershed, including all landscape and chemical stressors discussed in other chapters of this report. In numerous ways, population growth affects the condition of the Bay ecosystem, Watershed ecosystem, and h...

Selective whole genome amplification for resequencing target microbial species from complex natural samples.

PubMed

Leichty, Aaron R; Brisson, Dustin

2014-10-01

Population genomic analyses have demonstrated power to address major questions in evolutionary and molecular microbiology. Collecting populations of genomes is hindered in many microbial species by the absence of a cost effective and practical method to collect ample quantities of sufficiently pure genomic DNA for next-generation sequencing. Here we present a simple method to amplify genomes of a target microbial species present in a complex, natural sample. The selective whole genome amplification (SWGA) technique amplifies target genomes using nucleotide sequence motifs that are common in the target microbe genome, but rare in the background genomes, to prime the highly processive phi29 polymerase. SWGA thus selectively amplifies the target genome from samples in which it originally represented a minor fraction of the total DNA. The post-SWGA samples are enriched in target genomic DNA, which are ideal for population resequencing. We demonstrate the efficacy of SWGA using both laboratory-prepared mixtures of cultured microbes as well as a natural host-microbe association. Targeted amplification of Borrelia burgdorferi mixed with Escherichia coli at genome ratios of 1:2000 resulted in >10(5)-fold amplification of the target genomes with <6.7-fold amplification of the background. SWGA-treated genomic extracts from Wolbachia pipientis-infected Drosophila melanogaster resulted in up to 70% of high-throughput resequencing reads mapping to the W. pipientis genome. By contrast, 2-9% of sequencing reads were derived from W. pipientis without prior amplification. The SWGA technique results in high sequencing coverage at a fraction of the sequencing effort, thus allowing population genomic studies at affordable costs. Copyright © 2014 by the Genetics Society of America.

Targeting HIV services to male migrant workers in southern Africa would not reverse generalized HIV epidemics in their home communities: a mathematical modeling analysis

PubMed Central

Klein, Daniel J.; Eckhoff, Philip A.; Bershteyn, Anna

2015-01-01

Background Migrant populations such as mine workers contributed to the spread of HIV in sub-Saharan Africa. We used a mathematical model to estimate the community-wide impact of targeting treatment and prevention to male migrants. Methods We augmented an individual-based network model, EMOD-HIV v0.8, to include an age-dependent propensity for males to migrate. Migrants were exposed to HIV outside their home community, but continued to participate in HIV transmission in the community during periodic visits. Results Migrant-targeted interventions would have been transformative in the 1980s to 1990s, but post-2015 impacts were more modest. When targetable migrants comprised 2% of adult males, workplace HIV prevention averted 3.5% of community-wide infections over 20 years. Targeted treatment averted 8.5% of all-cause deaths among migrants. When migrants comprised 10% of males, workplace prevention averted 16.2% of infections in the community, one-quarter of which were among migrants. Workplace prevention and treatment acted synergistically, averting 17.1% of community infections and 11.6% of deaths among migrants. These estimates do not include prevention of secondary spread of HIV or tuberculosis at the workplace. Conclusions Though cost-effective, targeting migrants cannot collapse generalized epidemics in their home communities. Such a strategy would only have been possible prior to the early 1990s. However, migrant-targeted interventions synergize with general-population expansion of HIV services. PMID:25733560

Fitts’ Law in the Control of Isometric Grip Force With Naturalistic Targets

PubMed Central

Thumser, Zachary C.; Slifkin, Andrew B.; Beckler, Dylan T.; Marasco, Paul D.

2018-01-01

Fitts’ law models the relationship between amplitude, precision, and speed of rapid movements. It is widely used to quantify performance in pointing tasks, study human-computer interaction, and generally to understand perceptual-motor information processes, including research to model performance in isometric force production tasks. Applying Fitts’ law to an isometric grip force task would allow for quantifying grasp performance in rehabilitative medicine and may aid research on prosthetic control and design. We examined whether Fitts’ law would hold when participants attempted to accurately produce their intended force output while grasping a manipulandum when presented with images of various everyday objects (we termed this the implicit task). Although our main interest was the implicit task, to benchmark it and establish validity, we examined performance against a more standard visual feedback condition via a digital force-feedback meter on a video monitor (explicit task). Next, we progressed from visual force feedback with force meter targets to the same targets without visual force feedback (operating largely on feedforward control with tactile feedback). This provided an opportunity to see if Fitts’ law would hold without vision, and allowed us to progress toward the more naturalistic implicit task (which does not include visual feedback). Finally, we changed the nature of the targets from requiring explicit force values presented as arrows on a force-feedback meter (explicit targets) to the more naturalistic and intuitive target forces implied by images of objects (implicit targets). With visual force feedback the relation between task difficulty and the time to produce the target grip force was predicted by Fitts’ law (average r2 = 0.82). Without vision, average grip force scaled accurately although force variability was insensitive to the target presented. In contrast, images of everyday objects generated more reliable grip forces without the

Fitts' Law in the Control of Isometric Grip Force With Naturalistic Targets.

PubMed

Thumser, Zachary C; Slifkin, Andrew B; Beckler, Dylan T; Marasco, Paul D

2018-01-01

Fitts' law models the relationship between amplitude, precision, and speed of rapid movements. It is widely used to quantify performance in pointing tasks, study human-computer interaction, and generally to understand perceptual-motor information processes, including research to model performance in isometric force production tasks. Applying Fitts' law to an isometric grip force task would allow for quantifying grasp performance in rehabilitative medicine and may aid research on prosthetic control and design. We examined whether Fitts' law would hold when participants attempted to accurately produce their intended force output while grasping a manipulandum when presented with images of various everyday objects (we termed this the implicit task). Although our main interest was the implicit task, to benchmark it and establish validity, we examined performance against a more standard visual feedback condition via a digital force-feedback meter on a video monitor (explicit task). Next, we progressed from visual force feedback with force meter targets to the same targets without visual force feedback (operating largely on feedforward control with tactile feedback). This provided an opportunity to see if Fitts' law would hold without vision, and allowed us to progress toward the more naturalistic implicit task (which does not include visual feedback). Finally, we changed the nature of the targets from requiring explicit force values presented as arrows on a force-feedback meter (explicit targets) to the more naturalistic and intuitive target forces implied by images of objects (implicit targets). With visual force feedback the relation between task difficulty and the time to produce the target grip force was predicted by Fitts' law (average r 2 = 0.82). Without vision, average grip force scaled accurately although force variability was insensitive to the target presented. In contrast, images of everyday objects generated more reliable grip forces without the visualized

Mohawk Tannery Hazardous Waste Site in New Hampshire included on EPA List of Targeted for Immediate Attention

EPA Pesticide Factsheets

Today, the U.S. Environmental Protection Agency released the list of Superfund sites that Administrator Pruitt has targeted for immediate and intense attention. The former Mohawk Tannery facility (a.k.a. Granite State Leathers) is one of the 21 sites on th

Food and Drug Administration Perspective on Negative Symptoms in Schizophrenia as a Target for a Drug Treatment Claim

PubMed Central

Laughren, Thomas; Levin, Robert

2006-01-01

Negative symptoms of schizophrenia are not adequately addressed by available treatments for schizophrenia. Thus, it is reasonable to consider them as a target for a drug claim. This article describes the thought process that the Food and Drug Administration (FDA) will undertake in considering negative symptoms of schizophrenia as a novel and distinct drug target. Beyond this basic question, this article identifies a number of design issues that the FDA needs to consider regarding how best to conduct studies to support claims for this target. These design issues include (1) what population to study, (2) what phase of illness to target, (3) whether to focus on the negative symptom domain overall or on some specific aspect of negative symptoms, (4) the role of functional measures in negative symptom trials, and (5) optimal designs for targeting drugs for add-on therapy or broad-spectrum agents. PMID:16079389

Addressing population health and health inequalities: the role of fundamental causes.

PubMed

Cerdá, Magdalena; Tracy, Melissa; Ahern, Jennifer; Galea, Sandro

2014-09-01

As a case study of the impact of universal versus targeted interventions on population health and health inequalities, we used simulations to examine (1) whether universal or targeted manipulations of collective efficacy better reduced population-level rates and racial/ethnic inequalities in violent victimization; and (2) whether experiments reduced disparities without addressing fundamental causes. We applied agent-based simulation techniques to the specific example of an intervention on neighborhood collective efficacy to reduce population-level rates and racial/ethnic inequalities in violent victimization. The agent population consisted of 4000 individuals aged 18 years and older with sociodemographic characteristics assigned to match distributions of the adult population in New York City according to the 2000 U.S. Census. Universal experiments reduced rates of victimization more than targeted experiments. However, neither experiment reduced inequalities. To reduce inequalities, it was necessary to eliminate racial/ethnic residential segregation. These simulations support the use of universal intervention but suggest that it is not possible to address inequalities in health without first addressing fundamental causes.

Age-standardisation when target setting and auditing performance of Down syndrome screening programmes.

PubMed

Cuckle, Howard; Aitken, David; Goodburn, Sandra; Senior, Brian; Spencer, Kevin; Standing, Sue

2004-11-01

To describe and illustrate a method of setting Down syndrome screening targets and auditing performance that allows for differences in the maternal age distribution. A reference population was determined from a Gaussian model of maternal age. Target detection and false-positive rates were determined by standard statistical modelling techniques, except that the reference population rather than an observed population was used. Second-trimester marker parameters were obtained for Down syndrome from a large meta-analysis, and for unaffected pregnancies from the combined results of more than 600,000 screens in five centres. Audited detection and false-positive rates were the weighted average of the rates in five broad age groups corrected for viability bias. Weights were based on the age distributions in the reference population. Maternal age was found to approximate reasonably well to a Gaussian distribution with mean 27 years and standard deviation 5.5 years. Depending on marker combination, the target detection rates were 59 to 64% and false-positive rate 4.2 to 5.4% for a 1 in 250 term cut-off; 65 to 68% and 6.1 to 7.3% for 1 in 270 at mid-trimester. Among the five centres, the audited detection rate ranged from 7% below target to 10% above target, with audited false-positive rates better than the target by 0.3 to 1.5%. Age-standardisation should help to improve screening quality by allowing for intrinsic differences between programmes, so that valid comparisons can be made. Copyright 2004 John Wiley & Sons, Ltd.

Estimation of genomic prediction accuracy from reference populations with varying degrees of relationship.

PubMed

Lee, S Hong; Clark, Sam; van der Werf, Julius H J

2017-01-01

Genomic prediction is emerging in a wide range of fields including animal and plant breeding, risk prediction in human precision medicine and forensic. It is desirable to establish a theoretical framework for genomic prediction accuracy when the reference data consists of information sources with varying degrees of relationship to the target individuals. A reference set can contain both close and distant relatives as well as 'unrelated' individuals from the wider population in the genomic prediction. The various sources of information were modeled as different populations with different effective population sizes (Ne). Both the effective number of chromosome segments (Me) and Ne are considered to be a function of the data used for prediction. We validate our theory with analyses of simulated as well as real data, and illustrate that the variation in genomic relationships with the target is a predictor of the information content of the reference set. With a similar amount of data available for each source, we show that close relatives can have a substantially larger effect on genomic prediction accuracy than lesser related individuals. We also illustrate that when prediction relies on closer relatives, there is less improvement in prediction accuracy with an increase in training data or marker panel density. We release software that can estimate the expected prediction accuracy and power when combining different reference sources with various degrees of relationship to the target, which is useful when planning genomic prediction (before or after collecting data) in animal, plant and human genetics.

Cancer in the Minnesota Hmong population.

PubMed

Ross, Julie A; Xie, Yang; Kiffmeyer, William R; Bushhouse, Sally; Robison, Leslie L

2003-06-15

The Hmong are an isolated, agrarian people who settled in the mountainous regions of what today are Vietnam, Cambodia, and Laos. After the Vietnam War, many Hmong were relocated to the U.S. Minnesota has the second largest population (after California) of Hmong individuals. The objective of this study was to examine cancer incidence in this population, because it may indicate areas for targeted surveillance and intervention. The Minnesota Cancer Surveillance System database was screened for Hmong surnames, and proportional incidence ratios (PIRs) were calculated for the period 1988-1999. Compared with all Minnesotans, the Hmong population had increased PIRs for nasopharyngeal cancer (PIR, 39.39; 95% confidence interval [95% CI], 21.01-66.86), gastric cancer (PIR, 8.70; 95% CI, 5.39-13.25), hepatic cancer (PIR, 8.08; 95% CI, 3.88-14.71), and cervical cancer (PIR, 3.72; 95% CI, 2.04-6.20) and had decreased PIRs for prostate cancer, breast cancer, Hodgkin disease, and melanoma. The current observations have implications for cancer control interventions. In particular, an increased incidence of cervical cancer might be addressed in part by targeting culturally sensitive screening programs in the Hmong population. Copyright 2003 American Cancer Society.

Role of Non-Myocyte Gap Junctions and Connexin Hemichannels in Cardiovascular Health and Disease: Novel Therapeutic Targets?

PubMed

Johnson, Robert D; Camelliti, Patrizia

2018-03-15

The heart is a complex organ composed of multiple cell types, including cardiomyocytes and different non-myocyte populations, all working closely together to determine the hearts properties and maintain normal cardiac function. Connexins are abundantly expressed proteins that form plasma membrane hemichannels and gap junctions between cells. Gap junctions are intracellular channels that allow for communication between cells, and in the heart they play a crucial role in cardiac conduction by coupling adjacent cardiomyocytes. Connexins are expressed in both cardiomyocytes and non-myocytes, including cardiac fibroblasts, endothelial cells, and macrophages. Non-myocytes are the largest population of cells in the heart, and therefore it is important to consider what roles connexins, hemichannels, and gap junctions play in these cell types. The aim of this review is to provide insight into connexin-based signalling in non-myocytes during health and disease, and highlight how targeting these proteins could lead to the development of novel therapies. We conclude that connexins in non-myocytes contribute to arrhythmias and adverse ventricular remodelling following myocardial infarction, and are associated with the initiation and development of atherosclerosis. Therefore, therapeutic interventions targeting these connexins represent an exciting new research avenue with great potential.

Coral reef fish populations can persist without immigration

PubMed Central

Salles, Océane C.; Maynard, Jeffrey A.; Joannides, Marc; Barbu, Corentin M.; Saenz-Agudelo, Pablo; Almany, Glenn R.; Berumen, Michael L.; Thorrold, Simon R.; Jones, Geoffrey P.; Planes, Serge

2015-01-01

Determining the conditions under which populations may persist requires accurate estimates of demographic parameters, including immigration, local reproductive success, and mortality rates. In marine populations, empirical estimates of these parameters are rare, due at least in part to the pelagic dispersal stage common to most marine organisms. Here, we evaluate population persistence and turnover for a population of orange clownfish, Amphiprion percula, at Kimbe Island in Papua New Guinea. All fish in the population were sampled and genotyped on five occasions at 2-year intervals spanning eight years. The genetic data enabled estimates of reproductive success retained in the same population (reproductive success to self-recruitment), reproductive success exported to other subpopulations (reproductive success to local connectivity), and immigration and mortality rates of sub-adults and adults. Approximately 50% of the recruits were assigned to parents from the Kimbe Island population and this was stable through the sampling period. Stability in the proportion of local and immigrant settlers is likely due to: low annual mortality rates and stable egg production rates, and the short larval stages and sensory capacities of reef fish larvae. Biannual mortality rates ranged from 0.09 to 0.55 and varied significantly spatially. We used these data to parametrize a model that estimated the probability of the Kimbe Island population persisting in the absence of immigration. The Kimbe Island population was found to persist without significant immigration. Model results suggest the island population persists because the largest of the subpopulations are maintained due to having low mortality and high self-recruitment rates. Our results enable managers to appropriately target and scale actions to maximize persistence likelihood as disturbance frequencies increase. PMID:26582017

Coral reef fish populations can persist without immigration.

PubMed

Salles, Océane C; Maynard, Jeffrey A; Joannides, Marc; Barbu, Corentin M; Saenz-Agudelo, Pablo; Almany, Glenn R; Berumen, Michael L; Thorrold, Simon R; Jones, Geoffrey P; Planes, Serge

2015-11-22

Determining the conditions under which populations may persist requires accurate estimates of demographic parameters, including immigration, local reproductive success, and mortality rates. In marine populations, empirical estimates of these parameters are rare, due at least in part to the pelagic dispersal stage common to most marine organisms. Here, we evaluate population persistence and turnover for a population of orange clownfish, Amphiprion percula, at Kimbe Island in Papua New Guinea. All fish in the population were sampled and genotyped on five occasions at 2-year intervals spanning eight years. The genetic data enabled estimates of reproductive success retained in the same population (reproductive success to self-recruitment), reproductive success exported to other subpopulations (reproductive success to local connectivity), and immigration and mortality rates of sub-adults and adults. Approximately 50% of the recruits were assigned to parents from the Kimbe Island population and this was stable through the sampling period. Stability in the proportion of local and immigrant settlers is likely due to: low annual mortality rates and stable egg production rates, and the short larval stages and sensory capacities of reef fish larvae. Biannual mortality rates ranged from 0.09 to 0.55 and varied significantly spatially. We used these data to parametrize a model that estimated the probability of the Kimbe Island population persisting in the absence of immigration. The Kimbe Island population was found to persist without significant immigration. Model results suggest the island population persists because the largest of the subpopulations are maintained due to having low mortality and high self-recruitment rates. Our results enable managers to appropriately target and scale actions to maximize persistence likelihood as disturbance frequencies increase. © 2015 The Author(s).

Role of women in population.

PubMed

Srivasdava, T N

Population control through voluntary adoption of family planning is emphasized in India's family planning policy. The 1981 census figures have not shown an arresting rate of population growth. The social and attitudinal barriers to promoting the concept of the small family are great where men and women are not exposed to new ideas. The target groups for family planning include the 75% of the population residing in rural areas. The literacy rate for women in rural areas in 1971 was 18.69. Motivation is difficult unless supported by systematic education. Women play an important role in the determination of family size. Participation in social and economic activities may help to promote small family size by meeting the necessary conditions of emotional and social fulfillment of women outside the family context. Adquate education for women in rural as well as urban areas can elucidate alternatives to childbearing and enable women to appreciate the need for and use of contraception. Employment opportunities enhance women's familial decision making power through the acquisition of an alternative social and economic role, which may help them to adopt birth control practices, space their children, and limit family size. Motivational schemes may change the attitudes of a small number of families, however, greater gains could be achieved through an investment in women's education and employment.

Identification of a target population for immunisation against East Coast fever in coastal Kenya.

PubMed

Maloo, S H; Ngumi, P; Mbogo, S; Williamson, S; Thorpe, W; Rowlands, G J; Perry, B D

2001-11-02

Two experiments were carried out to identify the target population of cattle for immunisation against East Coast fever (ECF) using the infection-and-treatment method. Firstly, a sentinel-calf study was used to determine the age window for ECF immunisation by determining ages at clinical detection of infection with Theileria parva. Six groups of five naive cross-bred (Bos taurus/Bos indicus) male calves, introduced at intervals of 2 months at a mean age of 26 days, were exposed to natural tick challenge on a high ECF-risk, small-holder farm in the coastal lowland, coconut-cassava agro-ecological zone of coastal Kenya. Secondly, a challenge study evaluated the relationship between the presence of T. parva antibodies and immunity. Ten indigenous adult Zebu cattle and nine Zebu young stock purchased from farmers in the same zone, and eight cross-bred calves (survivors of the sentinel-calf study) were challenged with 10 times the immunising dose of T. parva Marikebuni stock. Twenty-four of these 27 cattle had high antibody titres before challenge. Two cross-bred calves, obtained from an ECF-free area and seronegative to T. parva schizont antigen, also were challenged and used as susceptible controls. Twenty-five (83%) of the 30 sentinel calves contracted ECF over an age range of 36-116 days (mean 72 days). The remaining five calves died of other causes within 2 months of arrival on the farm. Fourteen of the 25 calves survived the infection and developed antibodies to T. parva. Despite tick control, seven of these 14 calves had a second episode of ECF and two died. In total, 13 of the 25 calves that contracted ECF died. Only one of 19 indigenous Zebu animals developed clinical ECF when challenged with T. parva Marikebuni (mild clinical signs with spontaneous recovery). Of the eight cross-bred survivors from the first experiment, only one succumbed to ECF when challenged and it died. Both susceptible cross-bred calves developed severe clinical signs of ECF and one died

Cost-effectiveness of first trimester non-invasive fetal RHD screening for targeted antenatal anti-D prophylaxis in RhD-negative pregnant women: a model-based analysis.

PubMed

Neovius, M; Tiblad, E; Westgren, M; Kublickas, M; Neovius, K; Wikman, A

2016-07-01

To estimate the cost-effectiveness of first trimester non-invasive fetal RHD screening for targeted antenatal versus no routine antenatal anti-D prophylaxis (RAADP) or versus non-targeted RAADP. Model based on a population-based cohort study. The Swedish health service. Intervention subjects in the underlying cohort study were RhD-negative pregnant women receiving first trimester fetal RHD screening followed by targeted anti-D in 2010-2011 (n = 6723). Historical comparators were RhD-negative women who delivered in 2008-2009 when standard care did not include RAADP (n = 7099). Healthcare costs for the three strategies were included for the first and subsequent pregnancies. For the comparison with non-targeted RAADP, the immunisation rate was based on the observed rate for targeted therapy and adjusted downwards by removing the influence of false negatives. Additional cost per RhD immunisation averted. Compared with RAADP, targeted prophylaxis was associated with fewer immunisations (0.19 versus 0.46% per pregnancy) and lower costs (cost-savings of €32 per RhD-negative woman). The savings were from lower costs during pregnancy and delivery, and lower costs of future pregnancies through fewer immunisations. Non-targeted anti-D was estimated to result in 0.06% fewer immunisations and an additional €16 in cost-savings per mother, compared with targeted anti-D. Based on effect data from a population-based cohort study, targeted prophylaxis was associated with lower immunisation risk and costs versus no RAADP. Based on effect data from theoretical calculations, non-targeted RAADP was predicted to result in lower costs and immunisation risk compared with targeted prophylaxis. Fetal RHD screening and targeted prophylaxis resulted in lower immunisation risk and costs compared with no RAADP. © 2015 Royal College of Obstetricians and Gynaecologists.

Tritium target manufacturing for use in accelerators

NASA Astrophysics Data System (ADS)

Bach, P.; Monnin, C.; Van Rompay, M.; Ballanger, A.

2001-07-01

As a neutron tube manufacturer, SODERN is now in charge of manufacturing tritium targets for accelerators, in cooperation with CEA/DAM/DTMN in Valduc. Specific deuterium and tritium targets are manufactured on request, according to the requirements of the users, starting from titanium target on copper substrate, and going to more sophisticated devices. A wide range of possible uses is covered, including thin targets for neutron calibration, thick targets with controlled loading of deuterium and tritium, rotating targets for higher lifetimes, or large size rotating targets for accelerators used in boron neutron therapy. Activity of targets lies in the 1 to 1000 Curie, diameter of targets being up to 30 cm. Special targets are also considered, including surface layer targets for lowering tritium desorption under irradiation, or those made from different kinds of occluders such as titanium, zirconium, erbium, scandium, with different substrates. It is then possible to optimize either neutron output, or lifetime and stability, or thermal behavior.

Comorbid subjective health complaints in patients with sciatica: a prospective study including comparison with the general population.

PubMed

Grøvle, Lars; Haugen, Anne J; Ihlebaek, Camilla M; Keller, Anne; Natvig, Bård; Brox, Jens I; Grotle, Margreth

2011-06-01

Chronic nonspecific low back pain is accompanied by high rates of comorbid mental and physical conditions. The aims of this study were to investigate if patients with specific back pain, that is, sciatica caused by lumbar herniation, report higher rates of subjective health complaints (SHCs) than the general population and if there is an association between change in sciatica symptoms and change in SHCs over a 12-month period. A multicenter cohort study of 466 sciatica patients was conducted with follow-up at 3 months and 1 year. Comorbid SHCs were measured by 27 items of the SHC inventory. Odds ratios (ORs) for each SHC were calculated with comparison to a general population sample (n=928) by logistic regression. The SHC number was calculated by summing all complaints present. At baseline, the ORs for reporting SHCs for the sciatica patients were significantly elevated in 15 of the 27 items with a mean (S.D.) SHC number of 7.5 (4.4), compared to 5.2 (4.4) in the general population (P<.01). Among those who during the 1-year follow-up period fully recovered from their sciatica, the SHC number was reduced to normal levels. Among those with persisting or worsening sciatica, the number increased to a level almost double that of the general population. Compared to the general population, the prevalence of subjective health complaints in sciatica is increased. During follow-up, the number of health complaints increased in patients with persisting or worsening sciatica. Copyright © 2010 Elsevier Inc. All rights reserved.

A review of programs that targeted environmental determinants of Aboriginal and Torres Strait Islander health.

PubMed

Johnston, Leah; Doyle, Joyce; Morgan, Bec; Atkinson-Briggs, Sharon; Firebrace, Bradley; Marika, Mayatili; Reilly, Rachel; Cargo, Margaret; Riley, Therese; Rowley, Kevin

2013-08-09

Effective interventions to improve population and individual health require environmental change as well as strategies that target individual behaviours and clinical factors. This is the basis of implementing an ecological approach to health programs and health promotion. For Aboriginal People and Torres Strait Islanders, colonisation has made the physical and social environment particularly detrimental for health. We conducted a literature review to identify Aboriginal health interventions that targeted environmental determinants of health, identifying 21 different health programs. Program activities that targeted environmental determinants of health included: Caring for Country; changes to food supply and/or policy; infrastructure for physical activity; housing construction and maintenance; anti-smoking policies; increased workforce capacity; continuous quality improvement of clinical systems; petrol substitution; and income management. Targets were categorised according to Miller's Living Systems Theory. Researchers using an Indigenous community based perspective more often identified interpersonal and community-level targets than were identified using a Western academic perspective. Although there are relatively few papers describing interventions that target environmental determinants of health, many of these addressed such determinants at multiple levels, consistent to some degree with an ecological approach. Interpretation of program targets sometimes differed between academic and community-based perspectives, and was limited by the type of data reported in the journal articles, highlighting the need for local Indigenous knowledge for accurate program evaluation. While an ecological approach to Indigenous health is increasingly evident in the health research literature, the design and evaluation of such programs requires a wide breadth of expertise, including local Indigenous knowledge.

A Review of Programs That Targeted Environmental Determinants of Aboriginal and Torres Strait Islander Health

PubMed Central

Johnston, Leah; Doyle, Joyce; Morgan, Bec; Atkinson-Briggs, Sharon; Firebrace, Bradley; Marika, Mayatili; Reilly, Rachel; Cargo, Margaret; Riley, Therese; Rowley, Kevin

2013-01-01

Objective: Effective interventions to improve population and individual health require environmental change as well as strategies that target individual behaviours and clinical factors. This is the basis of implementing an ecological approach to health programs and health promotion. For Aboriginal People and Torres Strait Islanders, colonisation has made the physical and social environment particularly detrimental for health. Methods and Results: We conducted a literature review to identify Aboriginal health interventions that targeted environmental determinants of health, identifying 21 different health programs. Program activities that targeted environmental determinants of health included: Caring for Country; changes to food supply and/or policy; infrastructure for physical activity; housing construction and maintenance; anti-smoking policies; increased workforce capacity; continuous quality improvement of clinical systems; petrol substitution; and income management. Targets were categorised according to Miller’s Living Systems Theory. Researchers using an Indigenous community based perspective more often identified interpersonal and community-level targets than were identified using a Western academic perspective. Conclusions: Although there are relatively few papers describing interventions that target environmental determinants of health, many of these addressed such determinants at multiple levels, consistent to some degree with an ecological approach. Interpretation of program targets sometimes differed between academic and community-based perspectives, and was limited by the type of data reported in the journal articles, highlighting the need for local Indigenous knowledge for accurate program evaluation. Implications: While an ecological approach to Indigenous health is increasingly evident in the health research literature, the design and evaluation of such programs requires a wide breadth of expertise, including local Indigenous knowledge. PMID

Targeting solid tumors with non-pathogenic obligate anaerobic bacteria.

PubMed

Taniguchi, Shun'ichiro; Fujimori, Minoru; Sasaki, Takayuki; Tsutsui, Hiroko; Shimatani, Yuko; Seki, Keiichi; Amano, Jun

2010-09-01

Molecular-targeting drugs with fewer severe adverse effects are attracting great attention as the next wave of cancer treatment. There exist, however, populations of cancer cells resistant to these drugs that stem from the instability of tumor cells and/or the existence of cancer stem cells, and thus specific toxicity is required to destroy them. If such selectivity is not available, these targets may be sought out not by the cancer cell types themselves, but rather in their adjacent cancer microenvironments by means of hypoxia, low pH, and so on. The anaerobic conditions present in malignant tumor tissues have previously been regarded as a source of resistance in cancer cells against conventional therapy. However, there now appears to be a way to make use of these limiting factors as a selective target. In this review, we will refer to several trials, including our own, to direct attention to the utilizable anaerobic conditions present in malignant tumor tissues and the use of bacteria as carriers to target them. Specifically, we have been developing a method to attack solid cancers using the non-pathogenic obligate anaerobic bacterium Bifidobacterium longum as a vehicle to selectively recognize and target the anaerobic conditions in solid cancer tissues. We will also discuss the existence of low oxygen pressure in tumor masses in spite of generally enhanced angiogenesis, overview current cancer therapies, especially the history and present situation of bacterial utility to treat solid tumors, and discuss the rationality and future possibilities of this novel mode of cancer treatment. © 2010 Japanese Cancer Association.

Effectiveness of influenza vaccine against laboratory-confirmed influenza, in the late 2011–2012 season in Spain, among population targeted for vaccination

PubMed Central

2013-01-01

Background In Spain, the influenza vaccine effectiveness (VE) was estimated in the last three seasons using the observational study cycEVA conducted in the frame of the existing Spanish Influenza Sentinel Surveillance System. The objective of the study was to estimate influenza vaccine effectiveness (VE) against medically attended, laboratory-confirmed influenza-like illness (ILI) among the target groups for vaccination in Spain in the 2011–2012 season. We also studied influenza VE in the early (weeks 52/2011-7/2012) and late (weeks 8-14/2012) phases of the epidemic and according to time since vaccination. Methods Medically attended patients with ILI were systematically swabbed to collect information on exposure, laboratory outcome and confounding factors. Patients belonging to target groups for vaccination and who were swabbed <8 days after symptom onset were included. Cases tested positive for influenza and controls tested negative for any influenza virus. To examine the effect of a late season, analyses were performed according to the phase of the season and according to the time between vaccination and symptoms onset. Results The overall adjusted influenza VE against A(H3N2) was 45% (95% CI, 0–69). The estimated influenza VE was 52% (95% CI, -3 to 78), 40% (95% CI, -40 to 74) and 22% (95% CI, -135 to 74) at 3.5 months, 3.5-4 months, and >4 months, respectively, since vaccination. A decrease in VE with time since vaccination was only observed in individuals aged ≥ 65 years. Regarding the phase of the season, decreasing point estimates were only observed in the early phase, whereas very low or null estimates were obtained in the late phase for the shortest time interval. Conclusions The 2011–2012 influenza vaccine showed a low-to-moderate protective effect against medically attended, laboratory-confirmed influenza in the target groups for vaccination, in a late season and with a limited match between the vaccine and circulating strains. The

Human immune cell targeting of protein nanoparticles - caveospheres

NASA Astrophysics Data System (ADS)

Glass, Joshua J.; Yuen, Daniel; Rae, James; Johnston, Angus P. R.; Parton, Robert G.; Kent, Stephen J.; de Rose, Robert

2016-04-01

Nanotechnology has the power to transform vaccine and drug delivery through protection of payloads from both metabolism and off-target effects, while facilitating specific delivery of cargo to immune cells. However, evaluation of immune cell nanoparticle targeting is conventionally restricted to monocultured cell line models. We generated human caveolin-1 nanoparticles, termed caveospheres, which were efficiently functionalized with monoclonal antibodies. Using this platform, we investigated CD4+ T cell and CD20+ B cell targeting within physiological mixtures of primary human blood immune cells using flow cytometry, imaging flow cytometry and confocal microscopy. Antibody-functionalization enhanced caveosphere binding to targeted immune cells (6.6 to 43.9-fold) within mixed populations and in the presence of protein-containing fluids. Moreover, targeting caveospheres to CCR5 enabled caveosphere internalization by non-phagocytic CD4+ T cells--an important therapeutic target for HIV treatment. This efficient and flexible system of immune cell-targeted caveosphere nanoparticles holds promise for the development of advanced immunotherapeutics and vaccines.

A common agenda of global challenges. Japan and U.S. pool resources to tackle global issues including population and HIV / AIDS.

PubMed

1998-05-01

The Common Agenda for Cooperation in Global Perspective is a bilateral partnership established in 1993 between the US and Japan to address important global challenges of the 21st century such as global health and human development, including population and HIV/AIDS, global stability, protection of the global environment, and the advancement of science and technology. On the fifth anniversary of the agenda, representatives of the Japan and the US governments, international organizations, and private sectors discussed ways to further promote US-Japan cooperation under the agenda at a meeting held in Tokyo during March 12-13. Participants of the Common Agenda Open Forum also reviewed efforts made by Japan and the US under the agenda to address population and the environment. Forum participants focused upon developing new ideas for future cooperation between the governments, the private sector, and other nations, especially in the areas of health and the environment. The meeting was jointly organized by Japan's Ministry of Foreign Affairs and the US Department of State. Attention was also given during talks to diminishing international assistance budgets worldwide.

Targeted cardiopulmonary resuscitation training focused on the family members of high-risk patients at a regional medical center: A comparison between family members of high-risk and no-risk patients.

PubMed

Han, Kap Su; Lee, Ji Sung; Kim, Su Jin; Lee, Sung Woo

2018-05-01

We developed a hospital-based cardiopulmonary resuscitation (CPR) training model focused on the target population (family members of patients with potential risks for cardiac arrest) and compared the outcome of CPR training between target and non-target populations for validity. Family members of patients in training were divided into three groups on the basis of patients' diseases, as follows: 1) the cardio-specific (CS) risk group, including family members of patients with cardiac disease at risk of cardiac arrest; 2) the cardiovascular (CV) risk group, including family members of patients with risk factors for cardiovascular disease; and 3) the no-risk group. Pre- and posttraining surveys and skill tests as well as a post-training 3-month telephone survey were conducted. Educational outcomes were analyzed. A total of 203 family members were enrolled into 21 CPR training classes. The CS group (n=88) included elderly persons and housewives with a lower level of education compared with the CV (n=79) and no-risk groups (n=36). The CS group was motivated by healthcare professionals and participated in the training course. The CS, CV, and no-risk groups showed improvements in knowledge, willingness to perform CPR, and skills. Despite the older age and lower level of education in the CS group, the effects of education were similar to those in the other groups. A high rate of response and secondary propagation of CPR training were observed in the CS group. Family members of patients with heart disease could be an appropriate target population for CPR training, particularly in terms of recruitment and secondary propagation. Targeted intervention may be an effective training strategy to improve bystander CPR rates.

[Experience of knowledge translation in the ITSAL (immigration, work and health) research project with representatives of the target population].

PubMed

Ronda, Elena; López-Jacob, M José; Paredes-Carbonell, Joan J; López, Pilar; Boix, Pere; García, Ana M

2014-01-01

This article describes the experience of knowledge translation between researchers of the ITSAL (immigration, work and health) project and representatives of organizations working with immigrants to discuss the results obtained in the project and future research lines. A meeting was held, attended by three researchers and 18 representatives from 11 institutions. Following a presentation of the methodology and results of the project, the participants discussed the results presented and research areas of interest, thus confirming matches between the two sides and obtaining proposals of interest for the ITSAL project. We understand the process described as an approach to social validation of some of the main results of this project. This experience has allowed us to open a channel of communication with the target population of the study, in line with the necessary two-way interaction between researchers and users. Copyright © 2013 SESPAS. Published by Elsevier Espana. All rights reserved.

Targeting male mosquito swarms to control malaria vector density

PubMed Central

Sawadogo, Simon Peguedwinde; Niang, Abdoulaye; Bilgo, Etienne; Millogo, Azize; Maïga, Hamidou; Dabire, Roch K.; Tripet, Frederic; Diabaté, Abdoulaye

2017-01-01

Malaria control programs are being jeopardized by the spread of insecticide resistance in mosquito vector populations. It has been estimated that the spread of resistance could lead to an additional 120000 deaths per year, and interfere with the prospects for sustained control or the feasibility of achieving malaria elimination. Another complication for the development of resistance management strategies is that, in addition to insecticide resistance, mosquito behavior evolves in a manner that diminishes the impact of LLINs and IRS. Mosquitoes may circumvent LLIN and IRS control through preferential feeding and resting outside human houses and/or being active earlier in the evening before people go to sleep. Recent developments in our understanding of mosquito swarming suggest that new tools targeting mosquito swarms can be designed to cut down the high reproductive rate of malaria vectors. Targeting swarms of major malaria vectors may provide an effective control method to counteract behavioral resistance developed by mosquitoes. Here, we evaluated the impact of systematic spraying of swarms of Anopheles gambiae s.l. using a mixed carbamate and pyrethroid aerosol. The impact of this intervention on vector density, female insemination rates and the age structure of males was measured. We showed that the resulting mass killing of swarming males and some mate-seeking females resulted in a dramatic 80% decrease in population size compared to a control population. A significant decrease in female insemination rate and a significant shift in the age structure of the male population towards younger males incapable of mating were observed. This paradigm-shift study therefore demonstrates that targeting primarily males rather than females, can have a drastic impact on mosquito population. PMID:28278212

Fertility preferences among Malaysian women: an analysis of responses to the new population policy.

PubMed

Khor, G L

1990-10-01

About 10% of 3887 ever-married women included in the 1984-85 Malaysian Population and Family Survey revealed that they were influenced by the new population policy to desire more children than they had originally wanted. These women were more likely to be rural Malays from the lower socioeconomic class. Ideal family size was more than four children. Children are desired for economic benefits and emotional support. The natality of the Malays has risen since 1980: their total fertility rate has increased while their contraceptive prevalence rate has dropped sharply. Coupled with a decline in the crude death rate, the present fertility preferences and behaviour of the Malays will render the target of the population policy more attainable than is reflected by the survey data.

Communicating effectively with vulnerable populations during water contamination events.

PubMed

Nsiah-Kumi, Phyllis A

2008-01-01

Water contamination events are a public health concern worldwide with significant potential to impact the global community. When communicating with the public during these crisis situations, it is vital to consider the multiple audiences who receive the messages. Before developing or delivering messages to a particular community, it is essential to be familiar with the community's characteristics, needs, concerns, and who is considered credible to that community. Vulnerable populations are those with difficulties in comprehension or accessibility that may limit their full understanding of risks and may mitigate the effectiveness of public health strategies. Vulnerable populations include, but are not limited to, the urban/rural poor, those who are mentally ill, intellectually disabled, medically vulnerable, at the extremes of age (children and the elderly), racial/ethnic minorities, and those with low literacy or limited English proficiency.A water contamination event poses a unique opportunity to work with diverse populations to effectively convey important health messages. Each population needs to receive appropriate public health messages. Becoming familiar with vulnerable populations and their needs prior to a water contamination event will help in identifying barriers and developing and refining effective messages in such a crisis. In water contamination crises, our publics' health depends on effective, targeted crisis communication.

Targets and methods for target preparation for radionuclide production

DOEpatents

Zhuikov, Boris L; Konyakhin, Nicolai A; Kokhanyuk, Vladimir M; Srivastava, Suresh C

2012-10-16

The invention relates to nuclear technology, and to irradiation targets and their preparation. One embodiment of the present invention includes a method for preparation of a target containing intermetallic composition of antimony Ti--Sb, Al--Sb, Cu--Sb, or Ni--Sb in order to produce radionuclides (e.g., tin-117 m) with a beam of accelerated particles. The intermetallic compounds of antimony can be welded by means of diffusion welding to a copper backing cooled during irradiation on the beam of accelerated particles. Another target can be encapsulated into a shell made of metallic niobium, stainless steel, nickel or titanium cooled outside by water during irradiation. Titanium shell can be plated outside by nickel to avoid interaction with the cooling water.

Concordance with dietary and lifestyle population goals for cancer prevention in Dutch, Scottish, Mexican, and Guatemalan population samples.

PubMed

Vossenaar, Marieke; Solomons, Noel W; Valdés-Ramos, Roxana; Anderson, Annie S

2010-01-01

We assessed concordance with selected population goal components of the 1997 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) diet and lifestyle recommendations to decrease cancer risk across four population samples. This was a prospectively designed survey examining concordance with the population goals of the WCRF/AICR recommendations using target criteria across sites. Population samples were from the Netherlands, Scotland, Mexico, and Guatemala. A total of 3564 men and women aged 18 to 70 y were recruited in equal proportions by site and gender. None of the four pooled samples met the target population average criteria for body mass index or refined sugar intake. The Guatemalan sample had concordance with the largest number of recommended cancer-prevention goals (10 of 12 selected WCRF/AICR components). Successively, Mexican, Scottish, and Dutch samples were concordant with seven, four, and three selected components, respectively. A prospectively designed research instrument and exhaustive prior examination of operative criteria allow for the assessment of group-level concordance with cancer-prevention goals. To the extent that the study samples reflect the respective national situations, geographic variance in concordance exists, with conditions and behaviors in Guatemala bringing that nation into more general compliance with the 1997 WCRF/AICR goals.

Best Fitting Prediction Equations for Basal Metabolic Rate: Informing Obesity Interventions in Diverse Populations

PubMed Central

Sabounchi, Nasim S.; Rahmandad, Hazhir; Ammerman, Alice

2014-01-01

Basal Metabolic Rate (BMR) represents the largest component of total energy expenditure and is a major contributor to energy balance. Therefore, accurately estimating BMR is critical for developing rigorous obesity prevention and control strategies. Over the past several decades, numerous BMR formulas have been developed targeted to different population groups. A comprehensive literature search revealed 248 BMR estimation equations developed using diverse ranges of age, gender, race, fat free mass, fat mass, height, waist-to-hip ratio, body mass index, and weight. A subset of 47 studies included enough detail to allow for development of meta-regression equations. Utilizing these studies, meta-equations were developed targeted to twenty specific population groups. This review provides a comprehensive summary of available BMR equations and an estimate of their accuracy. An accompanying online BMR prediction tool (available at http://www.sdl.ise.vt.edu/tutorials.html) was developed to automatically estimate BMR based on the most appropriate equation after user-entry of individual age, race, gender, and weight. PMID:23318720

Epidemiology Characteristics of Constipation for General Population, Pediatric Population, and Elderly Population in China

PubMed Central

Chu, Huikuan; Zhong, Likun; Li, Hai; Zhang, Xiujing; Zhang, Jingzhi; Hou, Xiaohua

2014-01-01

Objective. To acquire more data about the epidemiologic characteristics of constipation in different kinds of populations in China. Methods. Using “constipation” and “China” as search terms; relevant papers were searched from January 1995 to April 2014. Data on prevalence, gender, diagnostic criteria, geographical area, educational class, age, race, and physician visit results were extracted and analyzed. Results. 36 trials were included. Prevalence rates of constipation in elderly population (18.1%) and pediatric population (18.8%) were significantly higher than that in general population (8.2%). Prevalence of constipation defined by non-Rome criteria was higher than that by Rome criteria in general population. Prevalence rates of constipation were different for different geographical area. People with less education were predisposed to constipation. In pediatric population, prevalence of constipation was the lowest in children aged 2–6 years. Prevalence of constipation in ethnic minorities was higher than that in Han people. People with constipation were predisposed to FD, haemorrhoid, and GERD. Only 22.2% patients seek medical advice in general population. Conclusions. In China, prevalence of constipation was lower compared with most of other countries. The factors including female gender, diagnostic criteria, geographical area, age, educational class, and race seemed to have major effects on prevalence of constipation. PMID:25386187

How dietary intake methodology is adapted for use in European immigrant population groups - a review.

PubMed

Ngo, Joy; Gurinovic, Mirjana; Frost-Andersen, Lene; Serra-Majem, Lluís

2009-07-01

Immigrants comprise a noteworthy segment of the European population whose numbers are increasing. Research on the dietary habits of immigrants is critical for correctly providing diet counselling and implementing effective interventions. The aim of the present study was to identify the presently used methods and adaptations required for measuring dietary intake in European immigrant groups. A comprehensive review strategy included a structured MEDLINE search, related references and key expert consultations. The review targeted adults from non-European union (European union-15 countries) ethnic groups having the largest populations in Europe. As studies evaluating nutrient intake were scarce, papers evaluating intake at the level of foods were included. Forty-six papers were selected. Although Eastern Europe, Turkey, Africa (North, Sub-Saharan and Afro-Caribbean), Asia and Latin America represented the most numerous immigrant groups, papers on dietary intake were not available for all populations. Interview-administered FFQ and repeated 24 hour recalls were the most frequently applied instruments. Inclusion of ethnic foods and quantification of specific portion sizes of traditional foods and dishes in assessment tools as well as food composition databases were commonly identified problems. For FFQ, food list elaboration required particular consideration to reflect key ethnic foods and relative contribution to nutrient intake. Extra efforts were observed to overcome cultural barriers to study participation. Evaluating dietary intake of immigrant populations requires special attention to various methodological aspects (sampling, recruiting, instruments used, method of administration, food composition database, acculturation, etc.) so as to adequately address the range of socio-cultural factors inherent in these nutritionally at risk target groups.

Dual-targeting siRNAs

PubMed Central

Tiemann, Katrin; Höhn, Britta; Ehsani, Ali; Forman, Stephen J.; Rossi, John J.; Sætrom, Pål

2010-01-01

We have developed an algorithm for the prediction of dual-targeting short interfering RNAs (siRNAs) in which both strands are deliberately designed to separately target different mRNA transcripts with complete complementarity. An advantage of this approach versus the use of two separate duplexes is that only two strands, as opposed to four, are competing for entry into the RNA-induced silencing complex. We chose to design our dual-targeting siRNAs as Dicer substrate 25/27mer siRNAs, since design features resembling pre-microRNAs (miRNAs) can be introduced for Dicer processing. Seven different dual-targeting siRNAs targeting genes that are potential targets in cancer therapy have been developed including Bcl2, Stat3, CCND1, BIRC5, and MYC. The dual-targeting siRNAs have been characterized for dual target knockdown in three different cell lines (HEK293, HCT116, and PC3), where they were as effective as their corresponding single-targeting siRNAs in target knockdown. The algorithm developed in this study should prove to be useful for predicting dual-targeting siRNAs in a variety of different targets and is available from http://demo1.interagon.com/DualTargeting/. PMID:20410240

Including pork in the Mediterranean diet for an Australian population: Protocol for a randomised controlled trial assessing cardiovascular risk and cognitive function.

PubMed

Wade, Alexandra T; Davis, Courtney R; Dyer, Kathryn A; Hodgson, Jonathan M; Woodman, Richard J; Keage, Hannah A D; Murphy, Karen J

2017-12-22

The Mediterranean diet is characterised by the high consumption of extra virgin olive oil, fruits, vegetables, grains, legumes and nuts; moderate consumption of fish, poultry, eggs and dairy; and low consumption of red meat and sweets. Cross sectional, longitudinal and intervention studies indicate that a Mediterranean diet may be effective for the prevention of cardiovascular disease and dementia. However, previous research suggests that an Australian population may find red meat restrictions difficult, which could affect long term sustainability of the diet. This paper outlines the protocol for a randomised controlled trial that will assess the cardiovascular and cognitive benefits of a Mediterranean diet modified to include 2-3 weekly serves of fresh, lean pork. A 24-week cross-over design trial will compare a modified Mediterranean diet with a low-fat control diet in at-risk men and women. Participants will follow each of the two diets for 8 weeks, with an 8-week washout period separating interventions. Home measured systolic blood pressure will be the primary outcome measure. Secondary outcomes will include body mass index, body composition, fasting blood lipids, C-reactive protein, fasting plasma glucose, fasting serum insulin, erythrocyte fatty acids, cognitive function, psychological health and well-being, and dementia risk. To our knowledge this research is the first to investigate whether an alternate source of protein can be included in the Mediterranean diet to increase sustainability and feasibility for a non-Mediterranean population. Findings will be significant for the prevention of cardiovascular disease and age-related decline, and may inform individuals, clinicians and public health policy. ACTRN12616001046493 . Registered 5 August 2016.

Health services utilization for people with HIV infection: comparison of a population targeted for outreach with the U.S. population in care.

PubMed

Cunningham, William E; Sohler, Nancy L; Tobias, Carol; Drainoni, Mari-lynn; Bradford, Judith; Davis, Cynthia; Cabral, Howard J; Cunningham, Chinazo O; Eldred, Lois; Wong, Mitchell D

2006-11-01

Many persons with HIV infection do not receive consistent ambulatory medical care and are excluded from studies of patients in medical care. However, these hard-to-reach groups are important to study because they may be in greatest need of services. This study compared the sociodemographic, clinical, and health care utilization characteristics of a multisite sample of HIV-positive persons who were hard to reach with a nationally representative cohort of persons with HIV infection who were receiving care from known HIV providers in the United States and examined whether the independent correlates of low ambulatory utilization differed between the 2 samples. We compared sociodemographic, clinical, and health care utilization characteristics in 2 samples of adults with HIV infection: 1286 persons from 16 sites across the United States interviewed in 2001-2002 for the Targeted HIV Outreach and Intervention Initiative (Outreach), a study of underserved persons targeted for supportive outreach services; and 2267 persons from the HIV Costs and Services Utilization Study (HCSUS), a probability sample of persons receiving care who were interviewed in 1998. We conducted logistic regression analyses to identify differences between the 2 samples in sociodemographic and clinical associations with ambulatory medical visits. Compared with the HCSUS sample, the Outreach sample had notably greater proportions of black respondents (59% vs. 32%, P = 0.0001), Hispanics (20% vs. 16%), Spanish-speakers (9% vs. 2%, P = 0.02), those with low socioeconomic status (annual income < Dollars 10,000 75% vs. 45%, P = 0.0001), the unemployed, and persons with homelessness, no insurance, and heroin or cocaine use (58% vs. 47%, P = 0.05). They also were more likely to have fewer than 2 ambulatory visits (26% vs. 16%, P = 0.0001), more likely to have emergency room visits or hospitalizations in the prior 6 months, and less likely to be on antiretroviral treatment (82% vs. 58%, P = 0.0001). Nearly

Population patch clamp electrophysiology: a breakthrough technology for ion channel screening.

PubMed

Dale, Tim J; Townsend, Claire; Hollands, Emma C; Trezise, Derek J

2007-10-01

Population patch clamp (PPC) is a novel high throughput planar array electrophysiology technique that allows ionic currents to be recorded from populations of cells under voltage clamp. For the drug discovery pharmacologist, PPC promises greater speed and precision than existing methods for screening compounds at voltage-gated ion channel targets. Moreover, certain constitutively active or slow-ligand gated channels that have hitherto proved challenging to screen with planar array electrophysiology (e.g. SK/IK channels) are now more accessible. In this article we review early findings using PPC and provide a perspective on its likely impact on ion channel drug discovery. To support this, we include some new data on ion channel assay duplexing and on modulator assays, approaches that have thus far not been described.

Farm Population of the United States: 1975. Current Population Reports: Farm Population.

ERIC Educational Resources Information Center

Banks, Vera J.; And Others

Presented via narrative and tabular data, this report includes: Population of the U.S., Total and Farm: 1960-1975; Metropolitan-Nonmetropolitan Residence of the Farm and Nonfarm Population, by Race: 1975; Fertility Characteristics of Farm and Nonfarm Women, by Race: 1975; Persons 14 Years Old and Over Employed in Agriculture, by Farm-Nonfarm…

Meeting the Sustainable Development Goals leads to lower world population growth.

PubMed

Abel, Guy J; Barakat, Bilal; Kc, Samir; Lutz, Wolfgang

2016-12-13

Here we show the extent to which the expected world population growth could be lowered by successfully implementing the recently agreed-upon Sustainable Development Goals (SDGs). The SDGs include specific quantitative targets on mortality, reproductive health, and education for all girls by 2030, measures that will directly and indirectly affect future demographic trends. Based on a multidimensional model of population dynamics that stratifies national populations by age, sex, and level of education with educational fertility and mortality differentials, we translate these goals into SDG population scenarios, resulting in population sizes between 8.2 and 8.7 billion in 2100. Because these results lie outside the 95% prediction range given by the 2015 United Nations probabilistic population projections, we complement the study with sensitivity analyses of these projections that suggest that those prediction intervals are too narrow because of uncertainty in baseline data, conservative assumptions on correlations, and the possibility of new policies influencing these trends. Although the analysis presented here rests on several assumptions about the implementation of the SDGs and the persistence of educational, fertility, and mortality differentials, it quantitatively illustrates the view that demography is not destiny and that policies can make a decisive difference. In particular, advances in female education and reproductive health can contribute greatly to reducing world population growth.

A compound chimeric antigen receptor strategy for targeting multiple myeloma.

PubMed

Chen, K H; Wada, M; Pinz, K G; Liu, H; Shuai, X; Chen, X; Yan, L E; Petrov, J C; Salman, H; Senzel, L; Leung, E L H; Jiang, X; Ma, Y

2018-02-01

Current clinical outcomes using chimeric-antigen receptors (CARs) against multiple myeloma show promise in the eradication of bulk disease. However, these anti-BCMA (CD269) CARs observe relapse as a common phenomenon after treatment due to the reemergence of either antigen-positive or -negative cells. Hence, the development of improvements in CAR design to target antigen loss and increase effector cell persistency represents a critical need. Here, we report on the anti-tumor activity of a CAR T-cell possessing two complete and independent CAR receptors against the multiple myeloma antigens BCMA and CS1. We determined that the resulting compound CAR (cCAR) T-cell possesses consistent, potent and directed cytotoxicity against each target antigen population. Using multiple mouse models of myeloma and mixed cell populations, we are further able to show superior in vivo survival by directed cytotoxicity against multiple populations compared to a single-expressing CAR T-cell. These findings indicate that compound targeting of BCMA and CS1 on myeloma cells can potentially be an effective strategy for augmenting the response against myeloma bulk disease and for initiation of broader coverage CAR therapy.

Deep Search for Satellites Around the Lucy Mission Targets

NASA Astrophysics Data System (ADS)

Noll, Keith

2017-08-01

By performing the first deep search for Trojan satellites with HST we will obtain unique constraints on satellite-forming processes in this population. We have selected the targets from NASA's Lucy mission because they represent a taxonomically and physically diverse set of targets that allow intercomparisons from a small survey. Also, by searching now to identify any orbiting material around the Lucy targets, it will be possible impact hardware decisions and plan for maximum scientific return from the mission. This search also is a necessary step to assure mission safety as the Lucy spacecraft will fly within 1000 km of the targets, well within the region where stable orbits can exist.

A novel W1999S mutation and non-target site resistance impact on acetyl-CoA carboxylase inhibiting herbicides to varying degrees in a UK Lolium multiflorum population.

PubMed

Kaundun, Shiv Shankhar; Bailly, Geraldine C; Dale, Richard P; Hutchings, Sarah-Jane; McIndoe, Eddie

2013-01-01

Acetyl-CoA carboxylase (ACCase) inhibiting herbicides are important products for the post-emergence control of grass weed species in small grain cereal crops. However, the appearance of resistance to ACCase herbicides over time has resulted in limited options for effective weed control of key species such as Lolium spp. In this study, we have used an integrated biological and molecular biology approach to investigate the mechanism of resistance to ACCase herbicides in a Lolium multiflorum Lam. from the UK (UK21). The study revealed a novel tryptophan to serine mutation at ACCase codon position 1999 impacting on ACCase inhibiting herbicides to varying degrees. The W1999S mutation confers dominant resistance to pinoxaden and partially recessive resistance to cycloxydim and sethoxydim. On the other hand, plants containing the W1999S mutation were sensitive to clethodim and tepraloxydim. Additionally population UK21 is characterised by other resistance mechanisms, very likely non non-target site based, affecting several aryloxyphenoxyproprionate (FOP) herbicides but not the practical field rate of pinoxaden. The positive identification of wild type tryptophan and mutant serine alleles at ACCase position 1999 could be readily achieved with an original DNA based derived cleaved amplified polymorphic sequence (dCAPS) assay that uses the same PCR product but two different enzymes for positively identifying the wild type tryptophan and mutant serine alleles identified here. This paper highlights intrinsic differences between ACCase inhibiting herbicides that could be exploited for controlling ryegrass populations such as UK21 characterised by compound-specific target site and non-target site resistance.

Human Population Problems

ERIC Educational Resources Information Center

Emmel, Thomas C.; Sligh, Michael M.

1970-01-01

Asserts that overpopulation is the most pressing world problem. Topics discussed include population control in primitive societies, population growth and control in modern societies, methods of motivational population control, consequences of no population control, and mass famines during the 1970's in underdeveloped countries. Cities 33…

Sustainability in single-species population models.

PubMed

Quinn, Terrance J; Collie, Jeremy S

2005-01-29

In this paper, we review the concept of sustainability with regard to a single-species, age-structured fish population with density dependence at some stage of its life history. We trace the development of the view of sustainability through four periods. The classical view of sustainability, prevalent in the 1970s and earlier, developed from deterministic production models, in which equilibrium abundance or biomass is derived as a function of fishing mortality. When there is no fishing mortality, the population equilibrates about its carrying capacity. We show that carrying capacity is the result of reproductive and mortality processes and is not a fixed constant unless these processes are constant. There is usually a fishing mortality, F(MSY), which results in MSY, and a higher value, F(ext), for which the population is eventually driven to extinction. For each F between 0 and F(ext), there is a corresponding sustainable population. From this viewpoint, the primary tool for achieving sustainability is the control of fishing mortality. The neoclassical view of sustainability, developed in the 1980s, involved population models with depensation and stochasticity. This view point is in accord with the perception that a population at a low level is susceptible to collapse or to a lack of rebuilding regardless of fishing. Sustainability occurs in a more restricted range from that in the classical view and includes an abundance threshold. A variety of studies has suggested that fishing mortality should not let a population drop below a threshold at 10-20% of carrying capacity. The modern view of sustainability in the 1990s moves further in the direction of precaution. The fishing mortality limit is the former target of F(MSY) (or some proxy), and the target fishing mortality is set lower. This viewpoint further reduces the range of permissible fishing mortalities and resultant desired population sizes. The objective has shifted from optimizing long-term catch to

Sustainability in single-species population models

PubMed Central

Quinn, Terrance J.; Collie, Jeremy S.

2005-01-01

In this paper, we review the concept of sustainability with regard to a single-species, age-structured fish population with density dependence at some stage of its life history. We trace the development of the view of sustainability through four periods. The classical view of sustainability, prevalent in the 1970s and earlier, developed from deterministic production models, in which equilibrium abundance or biomass is derived as a function of fishing mortality. When there is no fishing mortality, the population equilibrates about its carrying capacity. We show that carrying capacity is the result of reproductive and mortality processes and is not a fixed constant unless these processes are constant. There is usually a fishing mortality, FMSY, which results in MSY, and a higher value, Fext, for which the population is eventually driven to extinction. For each F between 0 and Fext, there is a corresponding sustainable population. From this viewpoint, the primary tool for achieving sustainability is the control of fishing mortality. The neoclassical view of sustainability, developed in the 1980s, involved population models with depensation and stochasticity. This viewpoint is in accord with the perception that a population at a low level is susceptible to collapse or to a lack of rebuilding regardless of fishing. Sustainability occurs in a more restricted range from that in the classical view and includes an abundance threshold. A variety of studies has suggested that fishing mortality should not let a population drop below a threshold at 10–20% of carrying capacity. The modern view of sustainability in the 1990s moves further in the direction of precaution. The fishing mortality limit is the former target of FMSY (or some proxy), and the target fishing mortality is set lower. This viewpoint further reduces the range of permissible fishing mortalities and resultant desired population sizes. The objective has shifted from optimizing long-term catch to preserving

Targeted interventions for improved equity in maternal and child health in low- and middle-income settings: a systematic review and meta-analysis.

PubMed

Målqvist, Mats; Yuan, Beibei; Trygg, Nadja; Selling, Katarina; Thomsen, Sarah

2013-01-01

Targeted interventions to improve maternal and child health is suggested as a feasible and sometimes even necessary strategy to reduce inequity. The objective of this systematic review was to gather the evidence of the effectiveness of targeted interventions to improve equity in MDG 4 and 5 outcomes. We identified primary studies in all languages by searching nine health and social databases, including grey literature and dissertations. Studies evaluating the effect of an intervention tailored to address a structural determinant of inequity in maternal and child health were included. Thus general interventions targeting disadvantaged populations were excluded. Outcome measures were limited to indicators proposed for Millennium Development Goals 4 and 5. We identified 18 articles, whereof 15 evaluated various incentive programs, two evaluated a targeted policy intervention, and only one study evaluated an intervention addressing a cultural custom. Meta-analyses of the effectiveness of incentives programs showed a pooled effect size of RR 1.66 (95% CI 1.43-1.93) for antenatal care attendance (four studies with 2,476 participants) and RR 2.37 (95% CI 1.38-4.07) for health facility delivery (five studies with 25,625 participants). Meta-analyses were not performed for any of the other outcomes due to scarcity of studies. The targeted interventions aiming to improve maternal and child health are mainly limited to addressing economic disparities through various incentive schemes like conditional cash transfers and voucher schemes. This is a feasible strategy to reduce inequity based on income. More innovative action-oriented research is needed to speed up progress in maternal and child survival among the most disadvantaged populations through interventions targeting the underlying structural determinants of inequity.

Enantioselective Effects of Chiral Pesticides on their Primary Targets and Secondary Targets.

PubMed

Yang, Ye; Zhang, Jianyun; Yao, Yijun

2017-01-01

Enantioselectivity has been well recognized in the environmental fate and effects of chiral pesticides. Enantiospecific action of the optical enantiomers on the biological molecules establishes the mechanistic basis for the enantioselective toxicity of chiral pesticides to both target and non-target organisms. We undertook a structured search of bibliographic databases for research literature concerning the enantioselective effects of chiral pesticides, including insecticides, herbicides and fungicides, on biomolecules in various species by using some key words. The results of the relevant literatures were reviewed in the text and summarized in tables. Pesticides generally exert their activity on the target organisms via disrupting the primary target biomolecules. In non-target species, effects of pesticides on the secondary targets distinguished from the primary ones make great contribution to their toxicity. Recent investigations have provided convincing evidence of enantioselective toxicity of chiral pesticides to both target and non-target species which is recognized to result from their enantiospecific action on the primary or secondary targets in organisms. This review confirms that chiral pesticides have enantiospecific effects on both primary and secondary target biomolecules in organisms. Future studies regarding toxicological effects of chiral pesticides should focus on the relationship between the enantiomeric difference in the compound-biomolecules interaction and the enantioselectivity in their toxicity.

Use of principal component analysis in the evaluation of adherence to statin treatment: a method to determine a potential target population for public health intervention.

PubMed

Latry, Philippe; Martin-Latry, Karin; Labat, Anne; Molimard, Mathieu; Peter, Claude

2011-08-01

The prevalence of statin use is high but adherence low. For public health intervention to be rational, subpopulations of nonadherent subjects must be defined. To categorise statin users with respect to patterns of reimbursement, this study was performed using the main French health reimbursement database for the Aquitaine region of south-western France. The cohort included subjects who submitted a reimbursement for at least one delivery of a statin (index) during the inclusion period (1st of September 2004-31st of December 2004). Indicators of adherence from reimbursement data were considered for principal component analysis. The 119,570 subjects included and analysed had a sex ratio of 1.1, mean (SD) age of 65.9 (11.9), and 13% were considered incident statin users. Principal component analysis found three dimensions that explained 67% of the variance. Using a K-means classification combined with a hierarchical ascendant classification, six groups were characterised. One group was considered nonadherent (10% of study population) and one group least adherent (1%). This novel application of principal component analysis identified groups that may be potential targets for intervention. The least adherent group appears to be one of the most appropriate because of both its relatively small size for case review with prescribing physicians and its very poor adherence. © 2010 The Authors Fundamental and Clinical Pharmacology © 2010 Société Française de Pharmacologie et de Thérapeutique.

Discovery of rare mutations in populations: TILLING by sequencing

USDA-ARS?s Scientific Manuscript database

Discovery of rare mutations in populations requires methods for processing and analyzing in parallel many individuals. Previous TILLING methods employed enzymatic or physical discrimination of heteroduplexed from homoduplexed target DNA. We used mutant populations of rice and wheat to develop a meth...

Population Connectivity Measures of Fishery-Targeted Coral Reef Species to Inform Marine Reserve Network Design in Fiji.

PubMed

Eastwood, Erin K; López, Elora H; Drew, Joshua A

2016-01-25

Coral reef fish serve as food sources to coastal communities worldwide, yet are vulnerable to mounting anthropogenic pressures like overfishing and climate change. Marine reserve networks have become important tools for mitigating these pressures, and one of the most critical factors in determining their spatial design is the degree of connectivity among different populations of species prioritized for protection. To help inform the spatial design of an expanded reserve network in Fiji, we used rapidly evolving mitochondrial genes to investigate connectivity patterns of three coral reef species targeted by fisheries in Fiji: Epinephelus merra (Serranidae), Halichoeres trimaculatus (Labridae), and Holothuria atra (Holothuriidae). The two fish species, E. merra and Ha. trimaculatus, exhibited low genetic structuring and high amounts of gene flow, whereas the sea cucumber Ho. atra displayed high genetic partitioning and predominantly westward gene flow. The idiosyncratic patterns observed among these species indicate that patterns of connectivity in Fiji are likely determined by a combination of oceanographic and ecological characteristics. Our data indicate that in the cases of species with high connectivity, other factors such as representation or political availability may dictate where reserves are placed. In low connectivity species, ensuring upstream and downstream connections is critical.

Serving Special Needs Populations in Postsecondary Occupational Education: A Synthesis of Program Approaches.

ERIC Educational Resources Information Center

Fadale, LaVerna M.; Winter, Gene M.

The Two-Year College Development Center undertook a project to identify two-year college programs in New York State that successfully serve one or more of the special needs populations targeted by the Carl D. Perkins Act. Four special needs populations were targeted for in-depth study: single parents/homemakers, learning disabled, limited English…

DSL prescriptive targets for bone conduction devices: adaptation and comparison to clinical fittings.

PubMed

Hodgetts, William E; Scollie, Susan D

2017-07-01

To develop an algorithm that prescribes targets for bone conduction frequency response shape, compression, and output limiting, along with a clinical method that ensures accurate transforms between assessment and verification stages of the clinical workflow. Technical report of target generation and validation. We recruited 39 adult users of unilateral percutaneous bone conduction hearing aids with a range of unilateral, bilateral, mixed and conductive hearing losses across the sample. The initial algorithm over-prescribed output compared to the user's own settings in the low frequencies, but provided a good match to user settings in the high frequencies. Corrections to the targets were derived and implemented as a low-frequency cut aimed at improving acceptance of the wearer's own voice during device use. The DSL-BCD prescriptive algorithm is compatible with verification of devices and fine-tuning to target for percutaneous bone conduction hearing devices that can be coupled to a skull simulator. Further study is needed to investigate the appropriateness of this prescriptive algorithm for other input levels, and for other clinical populations including those with single-sided deafness, bilateral devices, children and users of transcutaneous bone conduction hearing aids.

Targeted therapies: a nursing perspective.

PubMed

Kay, Polly

2006-02-01

To review the development of targeted therapies and the biology of relevant therapeutic targets. To analyze the relevance of targeted agents as part of current clinical practice. Research articles. Several targeted agents are now available for clinical use. Their mechanisms of action are more specific against tumor cells than traditional cytotoxics. Monotherapy regimens based on targeted agents tend to be better tolerated than chemotherapy, and most combination regimens with targeted agents have proven feasible. Their availability has greatly expanded cancer treatment options, especially for chemorefractory patients. Nurses involved in the care of patients with cancer can benefit from an increased understanding of targeted therapies, including their mechanisms of action, their efficacy profile, as well as prophylaxis and management of adverse events and administration procedures.

The Poughkeepsie Survey. A Report on Employment and Unemployment in a "Target Area" under the Model Cities Program.

ERIC Educational Resources Information Center

Kuper, Irvin, Ed.

Located in the heart of the Mid-Hudson area, Poughkeepsie is in one of the fastest growing regions of New York State, but the city itself has grown very little in the last five decades. The local Model Cities agency has created a target area which includes most of the older part of the city. In July 1967, the population was 35,970. A total of…

Population-level interventions to reduce alcohol-related harm: an overview of systematic reviews.

PubMed

Martineau, Fred; Tyner, Elizabeth; Lorenc, Theo; Petticrew, Mark; Lock, Karen

2013-10-01

To analyse available review-level evidence on the effectiveness of population-level interventions in non-clinical settings to reduce alcohol consumption or related health or social harm. Health, social policy and specialist review databases between 2002 and 2012 were searched for systematic reviews of the effectiveness of population-level alcohol interventions on consumption or alcohol-related health or social outcomes. Data were extracted on review research aim, inclusion criteria, outcome indicators, results, conclusions and limitations. Reviews were quality-assessed using AMSTAR criteria. A narrative synthesis was conducted overall and by policy area. Fifty-two reviews were included from ten policy areas. There is good evidence for policies and interventions to limit alcohol sale availability, to reduce drink-driving, to increase alcohol price or taxation. There is mixed evidence for family- and community-level interventions, school-based interventions, and interventions in the alcohol server setting and the mass media. There is weak evidence for workplace interventions and for interventions targeting illicit alcohol sales. There is evidence of the ineffectiveness of interventions in higher education settings. There is a pattern of support from the evidence base for regulatory or statutory enforcement interventions over local non-regulatory approaches targeting specific population groups. © 2013.

Population Health Management for Older Adults

PubMed Central

Tkatch, Rifky; Musich, Shirley; MacLeod, Stephanie; Alsgaard, Kathleen; Hawkins, Kevin; Yeh, Charlotte S.

2016-01-01

Background: The older adult population is expanding, living longer, with multiple chronic conditions. Understanding and managing their needs over time is an integral part of defining successful aging. Population health is used to describe the measurement and health outcomes of a population. Objectives: To define population health as applied to older adults, summarize lessons learned from current research, and identify potential interventions designed to promote successful aging and improved health for this population. Method: Online search engines were utilized to identify research on population health and health interventions for older adults. Results: Population health management (PHM) is one strategy to promote the health and well-being of target populations. Interventions promoting health across a continuum tend to be disease, risk, or health behavior specific rather than encompassing a global concept of health. Conclusion: Many existing interventions for older adults are simply research based with limited generalizability; as such, further work in this area is warranted. PMID:28680938

An experimental test of alternative population augmentation scenarios.

PubMed

Kronenberger, John A; Gerberich, Jill C; Fitzpatrick, Sarah W; Broder, E Dale; Angeloni, Lisa M; Funk, W Chris

2018-01-19

Human land use is fragmenting habitats worldwide and inhibiting dispersal among previously connected populations of organisms, often leading to inbreeding depression and reduced evolutionary potential in the face of rapid environmental change. To combat this augmentation of isolated populations with immigrants is sometimes used to facilitate demographic and genetic rescue. Augmentation with immigrants that are genetically and adaptively similar to the target population effectively increases population fitness, but if immigrants are very genetically or adaptively divergent, augmentation can lead to outbreeding depression. Despite well-cited guidelines for the best practice selection of immigrant sources, often only highly divergent populations remain, and experimental tests of these riskier augmentation scenarios are essentially nonexistent. We conducted a mesocosm experiment with Trinidadian guppies (Poecilia reticulata) to test the multigenerational demographic and genetic effects of augmenting 2 target populations with 3 types of divergent immigrants. We found no evidence of demographic rescue, but we did observe genetic rescue in one population. Divergent immigrant treatments tended to maintain greater genetic diversity, abundance, and hybrid fitness than controls that received immigrants from the source used to seed the mesocosms. In the second population, divergent immigrants had a slightly negative effect in one treatment, and the benefits of augmentation were less apparent overall, likely because this population started with higher genetic diversity and a lower reproductive rate that limited genetic admixture. Our results add to a growing consensus that gene flow can increase population fitness even when immigrants are more highly divergent and may help reduce uncertainty about the use of augmentation in conservation. © 2018 Society for Conservation Biology.

Geographic Clusters of Basal Cell Carcinoma in a Northern California Health Plan Population.

PubMed

Ray, G Thomas; Kulldorff, Martin; Asgari, Maryam M

2016-11-01

Rates of skin cancer, including basal cell carcinoma (BCC), the most common cancer, have been increasing over the past 3 decades. A better understanding of geographic clustering of BCCs can help target screening and prevention efforts. Present a methodology to identify spatial clusters of BCC and identify such clusters in a northern California population. This retrospective study used a BCC registry to determine rates of BCC by census block group, and used spatial scan statistics to identify statistically significant geographic clusters of BCCs, adjusting for age, sex, and socioeconomic status. The study population consisted of white, non-Hispanic members of Kaiser Permanente Northern California during years 2011 and 2012. Statistically significant geographic clusters of BCC as determined by spatial scan statistics. Spatial analysis of 28 408 individuals who received a diagnosis of at least 1 BCC in 2011 or 2012 revealed distinct geographic areas with elevated BCC rates. Among the 14 counties studied, BCC incidence ranged from 661 to 1598 per 100 000 person-years. After adjustment for age, sex, and neighborhood socioeconomic status, a pattern of 5 discrete geographic clusters emerged, with a relative risk ranging from 1.12 (95% CI, 1.03-1.21; P = .006) for a cluster in eastern Sonoma and northern Napa Counties to 1.40 (95% CI, 1.15-1.71; P < .001) for a cluster in east Contra Costa and west San Joaquin Counties, compared with persons residing outside that cluster. In this study of a northern California population, we identified several geographic clusters with modestly elevated incidence of BCC. Knowledge of geographic clusters can help inform future research on the underlying etiology of the clustering including factors related to the environment, health care access, or other characteristics of the resident population, and can help target screening efforts to areas of highest yield.

[Therapeutic strategies targeting brain tumor stem cells].

PubMed

Toda, Masahiro

2009-07-01

Progress in stem cell research reveals cancer stem cells to be present in a variety of malignant tumors. Since they exhibit resistance to anticancer drugs and radiotherapy, analysis of their properties has been rapidly carried forward as an important target for the treatment of intractable malignancies, including brain tumors. In fact, brain cancer stem cells (BCSCs) have been isolated from brain tumor tissue and brain tumor cell lines by using neural stem cell culture methods and isolation methods for side population (SP) cells, which have high drug-efflux capacity. Although the analysis of the properties of BCSCs is the most important to developing methods in treating BCSCs, the absence of BCSC purification methods should be remedied by taking it up as an important research task in the immediate future. Thus far, there are no effective treatment methods for BCSCs, and several treatment methods have been proposed based on the cell biology characteristics of BCSCs. In this article, I outline potential treatment methods damaging treatment-resistant BCSCs, including immunotherapy which is currently a topic of our research.

Large Eddy Simulation including population dynamics model for polydisperse droplet evolution

NASA Astrophysics Data System (ADS)

Aiyer, Aditya; Yang, Di; Chamecki, Marcelo; Meneveau, Charles

2017-11-01

Previous studies have shown that dispersion patterns of oil droplets in the ocean following a deep sea oil spill depend critically on droplet diameter. Hence predicting the evolution of the droplet size distribution is of critical importance for predicting macroscopic features of dispersion in the ocean. We adopt a population dynamics model of polydisperse droplet distributions for use in LES. We generalize a breakup model from Reynolds averaging approaches to LES in which the breakup is modeled as due to bombardment of droplets by turbulent eddies of various sizes. The breakage rate is expressed as an integral of a collision frequency times a breakage efficiency over all eddy sizes. An empirical fit to the integral is proposed in order to avoid having to recalculate the integral at every LES grid point and time step. The fit is tested by comparison with various stirred tank experiments. As a flow application for LES we consider a jet of bubbles and large droplets injected at the bottom of the tank. The advected velocity and concentration fields of the drops are described using an Eulerian approach. We study the change of the oil droplet distribution due to breakup caused by interaction of turbulence with the oil droplets. This research was made possible by a Grant from the Gulf of Mexico Research Initiative.

Mechanism of resistance to mesotrione in an Amaranthus tuberculatus population from Nebraska, USA

PubMed Central

Hutchings, Sarah-Jane; Dale, Richard P.; Howell, Anushka; Morris, James A.; Kramer, Vance C.; Shivrain, Vinod K.; Mcindoe, Eddie

2017-01-01

Amaranthus tuberculatus is a troublesome weed in corn and soybean production systems in Midwestern USA, due in part to its ability to evolve multiple resistance to key herbicides including 4-hydroxyphenylpyruvate dioxygenase (HPPD). Here we have investigated the mechanism of resistance to mesotrione, an important chemical for managing broadleaf weeds in corn, in a multiple herbicide resistant population (NEB) from Nebraska. NEB showed a 2.4-fold and 45-fold resistance increase to mesotrione compared to a standard sensitive population (SEN) in pre-emergence and post-emergence dose-response pot tests, respectively. Sequencing of the whole HPPD gene from 12 each of sensitive and resistant plants did not detect any target-site mutations that could be associated with post-emergence resistance to mesotrione in NEB. Resistance was not due to HPPD gene duplication or over-expression before or after herbicide treatment, as revealed by qPCR. Additionally, no difference in mesotrione uptake was detected between NEB and SEN. In contrast, higher levels of mesotrione metabolism via 4-hydroxylation of the dione ring were observed in NEB compared to the sensitive population. Overall, the NEB population was characterised by lower levels of parent mesotrione exported to other parts of the plant, either as a consequence of metabolism in the treated leaves and/or impaired translocation of the herbicide. This study demonstrates another case of non-target-site based resistance to an important class of herbicides in an A. tuberculatus population. The knowledge generated here will help design strategies for managing multiple herbicide resistance in this problematic weed species. PMID:28662111

Neurochemical differences between target-specific populations of rat dorsal raphe projection neurons.

PubMed

Prouty, Eric W; Chandler, Daniel J; Waterhouse, Barry D

2017-11-15

Serotonin (5-HT)-containing neurons in the dorsal raphe (DR) nucleus project throughout the forebrain and are implicated in many physiological processes and neuropsychiatric disorders. Diversity among these neurons has been characterized in terms of their neurochemistry and anatomical organization, but a clear sense of whether these attributes align with specific brain functions or terminal fields is lacking. DR 5-HT neurons can co-express additional neuroactive substances, increasing the potential for individualized regulation of target circuits. The goal of this study was to link DR neurons to a specific functional role by characterizing cells according to both their neurotransmitter expression and efferent connectivity; specifically, cells projecting to the medial prefrontal cortex (mPFC), a region implicated in cognition, emotion, and responses to stress. Following retrograde tracer injection, brainstem sections from Sprague-Dawley rats were immunohistochemically stained for markers of serotonin, glutamate, GABA, and nitric oxide (NO). 98% of the mPFC-projecting serotonergic neurons co-expressed the marker for glutamate, while the markers for NO and GABA were observed in 60% and less than 1% of those neurons, respectively. To identify potential target-specific differences in co-transmitter expression, we also characterized DR neurons projecting to a visual sensory structure, the lateral geniculate nucleus (LGN). The proportion of serotonergic neurons co-expressing NO was greater amongst cells targeting the mPFC vs LGN (60% vs 22%). The established role of 5-HT in affective disorders and the emerging role of NO in stress signaling suggest that the impact of 5-HT/NO co-localization in DR neurons that regulate mPFC circuit function may be clinically relevant. Copyright © 2017 Elsevier B.V. All rights reserved.

Setting numerical population objectives for priority landbird species

Treesearch

Kenneth V. Rosenberg; Peter J. Blancher

2005-01-01

Following the example of the North American Waterfowl Management Plan, deriving numerical population estimates and conservation targets for priority landbird species is considered a desirable, if not necessary, element of the Partners in Flight planning process. Methodology for deriving such estimates remains in its infancy, however, and the use of numerical population...

Machine Learning Based Classification of Microsatellite Variation: An Effective Approach for Phylogeographic Characterization of Olive Populations.

PubMed

Torkzaban, Bahareh; Kayvanjoo, Amir Hossein; Ardalan, Arman; Mousavi, Soraya; Mariotti, Roberto; Baldoni, Luciana; Ebrahimie, Esmaeil; Ebrahimi, Mansour; Hosseini-Mazinani, Mehdi

2015-01-01

Finding efficient analytical techniques is overwhelmingly turning into a bottleneck for the effectiveness of large biological data. Machine learning offers a novel and powerful tool to advance classification and modeling solutions in molecular biology. However, these methods have been less frequently used with empirical population genetics data. In this study, we developed a new combined approach of data analysis using microsatellite marker data from our previous studies of olive populations using machine learning algorithms. Herein, 267 olive accessions of various origins including 21 reference cultivars, 132 local ecotypes, and 37 wild olive specimens from the Iranian plateau, together with 77 of the most represented Mediterranean varieties were investigated using a finely selected panel of 11 microsatellite markers. We organized data in two '4-targeted' and '16-targeted' experiments. A strategy of assaying different machine based analyses (i.e. data cleaning, feature selection, and machine learning classification) was devised to identify the most informative loci and the most diagnostic alleles to represent the population and the geography of each olive accession. These analyses revealed microsatellite markers with the highest differentiating capacity and proved efficiency for our method of clustering olive accessions to reflect upon their regions of origin. A distinguished highlight of this study was the discovery of the best combination of markers for better differentiating of populations via machine learning models, which can be exploited to distinguish among other biological populations.

Beyond Monoamines-Novel Targets for Treatment-Resistant Depression: A Comprehensive Review

PubMed Central

Rosenblat, Christian; McIntyre, Roger S.; Alves, Gilberto S.; Fountoulakis, Konstantinos N.; Carvalho, André F.

2015-01-01

Major depressive disorder (MDD) is a leading cause of disability worldwide. Current first line therapies target modulation of the monoamine system. A large variety of agents are currently available that effectively alter monoamine levels; however, approximately one third of MDD patients remain treatment refractory after adequate trials of multiple monoamine based therapies. Therefore, patients with treatment-resistant depression (TRD) may require modulation of pathways outside of the classic monoamine system. The purpose of this review was thus to discuss novel targets for TRD, to describe their potential mechanisms of action, the available clinical evidence for these targets, the limitations of available evidence as well as future research directions. Several alternate pathways involved in the patho-etiology of TRD have been uncovered including the following: inflammatory pathways, the oxidative stress pathway, the hypothalamic-pituitary-adrenal (HPA) axis, the metabolic and bioenergetics system, neurotrophic pathways, the glutamate system, the opioid system and the cholinergic system. For each of these systems, several targets have been assessed in preclinical and clinical models. Preclinical models strongly implicate these pathways in the patho-etiology of MDD. Clinical trials for TRD have been conducted for several novel targets; however, most of the trials discussed are small and several are uncontrolled. Therefore, further clinical trials are required to assess the true efficacy of these targets for TRD. As well, several promising novel agents have been clinically tested in MDD populations, but have yet to be assessed specifically for TRD. Thus, their applicability to TRD remains unknown. PMID:26467412

[Blood pressure targets : The lower the better does not suit all].

PubMed

Hoffmann, U

2018-04-01

The systolic blood pressure intervention trial (SPRINT) published in 2015 has opened up new discussions on whether a lower blood pressure target as recommended by the current guidelines would be better for some patient groups. To review patient groups in which lower blood pressure targets would not be better. The results of SPRINT, its post-hoc and subgroup analyses, other studies and newer studies, as well as metaanalyses on the topic of blood pressure targets are reviewed and discussed. Studies with patients excluded from the SPRINT study were also analysed. The current international guidelines and recommendations of the Deutsche Hochdruckliga e. V. DHL® are included. Blood pressure monitoring methods differed considerably in the previously published studies. The low blood pressure value in SPRINT was mainly achieved due to the unusual method of blood pressure monitoring used and, as such, cannot be compared with blood pressure values in other studies. Based on current evidence, "the lower the better" should not be recommended in the following patient groups: older patients, in particular infirm older patients, patients with diabetes, patients without coronary heart disease or with low cardiovascular risk. When determining a blood pressure target, the method of blood pressure monitoring should be defined. A lower blood pressure target has been shown to be better in some well defined patient groups. However, adverse events due to antihypertensive medications should always be taken into account. Given the multiple exclusion criteria in trials and the results of many studies, "new" lower blood pressure targets could not be recommended in a large population of patients.

Processing negative valence of word pairs that include a positive word.

PubMed