Schuster, Stephen J.; Neelapu, Sattva S.; Gause, Barry L.; Janik, John E.; Muggia, Franco M.; Gockerman, Jon P.; Winter, Jane N.; Flowers, Christopher R.; Nikcevich, Daniel A.; Sotomayor, Eduardo M.; McGaughey, Dean S.; Jaffe, Elaine S.; Chong, Elise A.; Reynolds, Craig W.; Berry, Donald A.; Santos, Carlos F.; Popa, Mihaela A.; McCord, Amy M.; Kwak, Larry W.
2011-01-01
Purpose Vaccination with hybridoma-derived autologous tumor immunoglobulin (Ig) idiotype (Id) conjugated to keyhole limpet hemocyanin (KLH) and administered with granulocyte-monocyte colony-stimulating factor (GM-CSF) induces follicular lymphoma (FL) –specific immune responses. To determine the clinical benefit of this vaccine, we conducted a double-blind multicenter controlled phase III trial. Patients and Methods Treatment-naive patients with advanced stage FL achieving complete response (CR) or CR unconfirmed (CRu) after chemotherapy were randomly assigned two to one to receive either Id vaccine (Id-KLH + GM-CSF) or control (KLH + GM-CSF). Primary efficacy end points were disease-free survival (DFS) for all randomly assigned patients and DFS for randomly assigned patients receiving at least one dose of Id vaccine or control. Results Of 234 patients enrolled, 177 (81%) achieved CR/CRu after chemotherapy and were randomly assigned. For 177 randomly assigned patients, including 60 patients not vaccinated because of relapse (n = 55) or other reasons (n = 5), median DFS between Id-vaccine and control arms was 23.0 versus 20.6 months, respectively (hazard ratio [HR], 0.81; 95% CI, 0.56 to 1.16; P = .256). For 117 patients who received Id vaccine (n = 76) or control (n = 41), median DFS after randomization was 44.2 months for Id-vaccine arm versus 30.6 months for control arm (HR, 0.62; 95% CI, 0.39 to 0.99; P = .047) at median follow-up of 56.6 months (range, 12.6 to 89.3 months). In an unplanned subgroup analysis, median DFS was significantly prolonged for patients receiving IgM-Id (52.9 v 28.7 months; P = .001) but not IgG-Id vaccine (35.1 v 32.4 months; P = .807) compared with isotype-matched control-treated patients. Conclusion Vaccination with patient-specific hybridoma-derived Id vaccine after chemotherapy-induced CR/CRu may prolong DFS in patients with FL. Vaccine isotype may affect clinical outcome and explain differing results between this and other controlled Id-vaccine trials. PMID:21632504
Gorse, Geoffrey J; Falsey, Ann R; Johnson, Carol M; Morrison, Dennis; Fried, David L; Ervin, John E; Greenberg, David P; Ozol-Godfrey, Ayca; Landolfi, Victoria; Tsang, Peter H
Vélez, I D; del Pilar Agudelo, S; Arbelaez, M P; Gilchrist, K; Robledo, S M; Puerta, J A; Zicker, F; Berman, J; Modabber, F
2000-01-01
The safety and immunogenicity of an intramuscular (i.m.) and intradermal (ID) formulation of autoclaved Leishmania (Leishmania) amazonensis vaccine was evaluated in 296 volunteers in a randomized, placebo-controlled, double-blind trial in Colombia. There were 4 vaccination groups: i.m. vaccine, i.m. placebo, ID vaccine, and ID placebo. The ID formulations were mixed with BCG as adjuvant at the time of injection. For each group, 3 vaccinations were given with a 20-day interval between injections, and adverse events were monitored at 20 min, and at 2, 7 and 21 days after each injection. BCG-induced adverse reactions resulted in cancellation of the third vaccine administration in the ID groups. Antibody titres did not differ significantly between the groups. Montenegro skin-test conversion was achieved by 86.4% and 90% of the i.m. vaccine group and by 25% and 5% of the i.m. placebo group 80 days and 1 year after vaccination, respectively. A significant increase in mean Leishmania-antigen lymphocyte proliferation indexes was observed after i.m. vaccine immunization, but not after i.m. placebo immunization, 80 days and 1 year after vaccination. Significant levels of IFN gamma but not IL-10 were observed 1 year after vaccination in the i.m. vaccine group compared to the i.m. placebo group. The good safety profile and evidence of Th1 immune reactions due to i.m. vaccination in this phase-I/II study suggest that a population-based phase-III efficacy trial of the i.m. vaccine should be initiated.
Coudeville, Laurent; Andre, Philippe; Bailleux, Fabrice; Weber, Françoise; Plotkin, Stanley
2010-10-01
Despite their pivotal role in the assessment of influenza vaccines, limited attempts have been made to use haemagglutination inhibition (HI) titers for predicting vaccine efficacy against laboratory-confirmed influenza. We present here the second step of a two-step approach allowing performing such predictions and use it to compare a new trivalent inactivated influenza vaccine administered by the intradermal (ID) route (INTANZA® /IDFlu®) with the vaccine administered by the classical intramuscular (IM) route. The first step corresponding to the estimation of the level of protection against laboratory-confirmed influenza that can be linked to each HI titer, referred to as the HI protection curve, was achieved by using a meta-analytical approach based on published information. Vaccine efficacy and differences in vaccine efficacy are predicted in a second step using this HI protection curve alongside the results of two randomized clinical trials providing comparative information on the immunogenicity of trivalent inactivated influenza vaccines administered ID or IM in 3503 & 1645 elderly participants, respectively. Pooling all available immunogenicity data, the predicted vaccine efficacy was 63.3% [CI: 58.1; 68.7] for ID route and 54.4% [CI: 49.4; 59.2] for IM route. The corresponding relative increase in efficacy that is of 16.5% [CI: 12.7; 20.1]. Predicted vaccine efficacies decreased with age for both vaccines, but the decrease was less marked by ID route: the relative increase in efficacy for subjects aged 70 years and above is of 18.0% [CI:12;24]. The analysis performed confirmed that the superior immune response provided by the vaccine using the ID route should translate into a higher vaccine efficacy against laboratory-confirmed influenza.
Intanza® 9 μg (Sanofi Pasteur), a trivalent split-virion vaccine administered by intradermal (ID) injection, was approved in Europe in 2009 for the prevention of seasonal influenza in adults 18 to 59 years. Here, we examined the immune responses induced in adults by the ID 9 μg vaccine and the standard trivalent intramuscular (IM) vaccine (Vaxigrip® 15 μg, Sanofi Pasteur). This trial was a randomized, controlled, single-center, open-label study in healthy adults 18 to 40 years of age during the 2007/8 influenza season. Subjects received a single vaccination with the ID 9 μg (n = 38) or IM 15 μg (n = 42) vaccine. Serum, saliva, and peripheral blood mononuclear cells were collected up to 180 days post-vaccination. Geometric mean hemagglutination inhibition titers, seroprotection rates, seroconversion rates, and pre-vaccination-to-post-vaccination ratios of geometric mean hemagglutination inhibition titers did not differ between the two vaccines. Compared with pre-vaccination, the vaccines induced similar increases in vaccine-specific circulating B cells at day 7 but did not induce significant increases in vaccine-specific memory B cells at day 180. Cell-mediated immunity to all three vaccine strains, measured in peripheral blood mononuclear cells, was high at baseline and not increased by either vaccine. Neither vaccine induced a mucosal immune response. These results show that the humoral and cellular immune responses to the ID 9 μg vaccine are similar to those to the standard IM 15 μg vaccine. PMID:25483667
Intanza® 9 μg (Sanofi Pasteur), a trivalent split-virion vaccine administered by intradermal (ID) injection, was approved in Europe in 2009 for the prevention of seasonal influenza in adults 18 to 59 years. Here, we examined the immune responses induced in adults by the ID 9 μg vaccine and the standard trivalent intramuscular (IM) vaccine (Vaxigrip® 15 μg, Sanofi Pasteur). This trial was a randomized, controlled, single-center, open-label study in healthy adults 18 to 40 years of age during the 2007/8 influenza season. Subjects received a single vaccination with the ID 9 μg (n=38) or IM 15 μg (n=42) vaccine. Serum, saliva, and peripheral blood mononuclear cells were collected up to 180 days post-vaccination. Geometric mean hemagglutination inhibition titers, seroprotection rates, seroconversion rates, and pre-vaccination-to-post-vaccination ratios of geometric mean hemagglutination inhibition titers did not differ between the two vaccines. Compared with pre-vaccination, the vaccines induced similar increases in vaccine-specific circulating B cells at day 7 but did not induce significant increases in vaccine-specific memory B cells at day 180. Cell-mediated immunity to all three vaccine strains, measured in peripheral blood mononuclear cells, was high at baseline and not increased by either vaccine. Neither vaccine induced a mucosal immune response. These results show that the humoral and cellular immune responses to the ID 9 μg vaccine are similar to those to the standard IM 15 μg vaccine.
Warrell, Mary J; Riddell, Anna; Yu, Ly-Mee; Phipps, Judith; Diggle, Linda; Bourhy, Hervé; Deeks, Jonathan J; Fooks, Anthony R; Audry, Laurent; Brookes, Sharon M; Meslin, François-Xavier; Moxon, Richard; Pollard, Andrew J; Warrell, David A
2008-04-23
The need for economical rabies post-exposure prophylaxis (PEP) is increasing in developing countries. Implementation of the two currently approved economical intradermal (ID) vaccine regimens is restricted due to confusion over different vaccines, regimens and dosages, lack of confidence in intradermal technique, and pharmaceutical regulations. We therefore compared a simplified 4-site economical PEP regimen with standard methods. Two hundred and fifty-four volunteers were randomly allocated to a single blind controlled trial. Each received purified vero cell rabies vaccine by one of four PEP regimens: the currently accepted 2-site ID; the 8-site regimen using 0.05 ml per ID site; a new 4-site ID regimen (on day 0, approximately 0.1 ml at 4 ID sites, using the whole 0.5 ml ampoule of vaccine; on day 7, 0.1 ml ID at 2 sites and at one site on days 28 and 90); or the standard 5-dose intramuscular regimen. All ID regimens required the same total amount of vaccine, 60% less than the intramuscular method. Neutralising antibody responses were measured five times over a year in 229 people, for whom complete data were available. All ID regimens showed similar immunogenicity. The intramuscular regimen gave the lowest geometric mean antibody titres. Using the rapid fluorescent focus inhibition test, some sera had unexpectedly high antibody levels that were not attributable to previous vaccination. The results were confirmed using the fluorescent antibody virus neutralisation method. This 4-site PEP regimen proved as immunogenic as current regimens, and has the advantages of requiring fewer clinic visits, being more practicable, and having a wider margin of safety, especially in inexperienced hands, than the 2-site regimen. It is more convenient than the 8-site method, and can be used economically with vaccines formulated in 1.0 or 0.5 ml ampoules. The 4-site regimen now meets all requirements of immunogenicity for PEP and can be introduced without further studies. Controlled-Trials.com ISRCTN 30087513.
Frenck, Robert W.; Belshe, Robert; Brady, Rebecca C; Winokur, Patricia L.; Campbell, James D.; Treanor, John; Hay, Christine M.; Dekker, Cornelia L.; Walter, Emmanuel B.; Cate, Thomas R.; Edwards, Kathryn M.; Hill, Heather; Wolff, Mark; LeDuc, Tom; Tornieporth, Nadia
2011-01-01
The aim of the study was to determine whether reduced doses of trivalent inactivated influenza vaccine (TIV) administered by the intradermal (ID) route generated similar immune responses to standard TIV given intramuscularly (IM) with comparable safety profiles. Recent changes in immunization recommendations have increased the number of people for whom influenza vaccination is recommended. Thus, given this increased need and intermittent vaccine shortages, means to rapidly expand the vaccine supply are needed. Previously healthy subjects 18-64 years of age were randomly assigned to one of four TIV vaccine groups: standard 15 μg HA/strain TIV IM, either 9 μg or 6 μg HA/strain of TIV ID given using a new microinjection system, (BD Soluvia™ Microinjection Systema), or 3 μg HA/strain of TIV ID given by Mantoux technique. All vaccines contained A/New Caledonia (H1N1), A/Wyoming (H3N2) and B/Jiangsu strains of influenza. Sera were obtained 21 days after vaccination and hemagglutination inhibition (HAI) assays were performed and geometric mean titers (GMT) were compared among the groups. Participants were queried immediately following vaccination regarding injection pain and quality of the experience. Local and systemic reactions were collected for 7 days following vaccination and compared. Ten study sites enrolled 1592 subjects stratified by age; 18-49 years, [N=814] and 50-64 years, [N=778]. Among all subjects, for each of the three vaccine strains, the GMTs at 21 days post-vaccination for both the 9 μg and the 6 μg doses of each strain given ID were non inferior to GMTs generated after standard 15 μg doses/strain IM. However, for the 3 μg ID dose, only the A/Wyoming antigen produced a GMT that was non-inferior to the standard IM dose. Additionally, in the subgroup of subjects 50-64 years of age, the 6 μg dose given ID induced GMTs that were inferior to the standard IM TIV for the A/H1N1 and B strains. No ID dose produced a GMT superior to that seen after standard IM TIV. Local erythema and swelling were significantly more common in the ID groups but the reactions were mild to moderate and short-lived. No significant safety issues related to intradermal administration were identified. Participants given TIV ID provided favorable responses to questions about their experiences with ID administration. In conclusion, for the aggregated cohorts of adults 18 to 64 years of age, reduced doses (6 μg and 9 μg) of TIV delivered ID using a novel microinjection system stimulated comparable HAI antibody responses to standard TIV given IM. The reduced 3 μg dose administered ID by needle and syringe, as well as the 6 μg ID for subjects aged 50-64 years of age generated poorer immune responses as compared to the 15 μg IM dose. PMID:21699951
Warrell, Mary J.; Riddell, Anna; Yu, Ly-Mee; Phipps, Judith; Diggle, Linda; Bourhy, Hervé; Deeks, Jonathan J.; Fooks, Anthony R.; Audry, Laurent; Brookes, Sharon M.; Meslin, François-Xavier; Moxon, Richard; Pollard, Andrew J.; Warrell, David A.
2008-01-01
Background The need for economical rabies post-exposure prophylaxis (PEP) is increasing in developing countries. Implementation of the two currently approved economical intradermal (ID) vaccine regimens is restricted due to confusion over different vaccines, regimens and dosages, lack of confidence in intradermal technique, and pharmaceutical regulations. We therefore compared a simplified 4-site economical PEP regimen with standard methods. Methods Two hundred and fifty-four volunteers were randomly allocated to a single blind controlled trial. Each received purified vero cell rabies vaccine by one of four PEP regimens: the currently accepted 2-site ID; the 8-site regimen using 0.05 ml per ID site; a new 4-site ID regimen (on day 0, approximately 0.1 ml at 4 ID sites, using the whole 0.5 ml ampoule of vaccine; on day 7, 0.1 ml ID at 2 sites and at one site on days 28 and 90); or the standard 5-dose intramuscular regimen. All ID regimens required the same total amount of vaccine, 60% less than the intramuscular method. Neutralising antibody responses were measured five times over a year in 229 people, for whom complete data were available. Findings All ID regimens showed similar immunogenicity. The intramuscular regimen gave the lowest geometric mean antibody titres. Using the rapid fluorescent focus inhibition test, some sera had unexpectedly high antibody levels that were not attributable to previous vaccination. The results were confirmed using the fluorescent antibody virus neutralisation method. Conclusions This 4-site PEP regimen proved as immunogenic as current regimens, and has the advantages of requiring fewer clinic visits, being more practicable, and having a wider margin of safety, especially in inexperienced hands, than the 2-site regimen. It is more convenient than the 8-site method, and can be used economically with vaccines formulated in 1.0 or 0.5 ml ampoules. The 4-site regimen now meets all requirements of immunogenicity for PEP and can be introduced without further studies. Trial Registration Controlled-Trials.com ISRCTN 30087513 PMID:18431444
Carey, John B.; Vrdoljak, Anto; O'Mahony, Conor; Hill, Adrian V. S.; Draper, Simon J.; Moore, Anne C.
2014-01-01
Substantial effort has been placed in developing efficacious recombinant attenuated adenovirus-based vaccines. However induction of immunity to the vector is a significant obstacle to its repeated use. Here we demonstrate that skin-based delivery of an adenovirus-based malaria vaccine, HAdV5-PyMSP142, to mice using silicon microneedles induces equivalent or enhanced antibody responses to the encoded antigen, however it results in decreased anti-vector responses, compared to intradermal delivery. Microneedle-mediated vaccine priming and resultant induction of low anti-vector antibody titres permitted repeated use of the same adenovirus vaccine vector. This resulted in significantly increased antigen-specific antibody responses in these mice compared to ID-treated mice. Boosting with a heterologous vaccine; MVA-PyMSP142 also resulted in significantly greater antibody responses in mice primed with HAdV5-PyMSP142 using MN compared to the ID route. The highest protection against blood-stage malaria challenge was observed when a heterologous route of immunization (MN/ID) was used. Therefore, microneedle-mediated immunization has potential to both overcome some of the logistic obstacles surrounding needle-and-syringe-based immunization as well as to facilitate the repeated use of the same adenovirus vaccine thereby potentially reducing manufacturing costs of multiple vaccines. This could have important benefits in the clinical ease of use of adenovirus-based immunization strategies. PMID:25142082
Carey, John B; Vrdoljak, Anto; O'Mahony, Conor; Hill, Adrian V S; Draper, Simon J; Moore, Anne C
2014-08-21
Substantial effort has been placed in developing efficacious recombinant attenuated adenovirus-based vaccines. However induction of immunity to the vector is a significant obstacle to its repeated use. Here we demonstrate that skin-based delivery of an adenovirus-based malaria vaccine, HAdV5-PyMSP1₄₂, to mice using silicon microneedles induces equivalent or enhanced antibody responses to the encoded antigen, however it results in decreased anti-vector responses, compared to intradermal delivery. Microneedle-mediated vaccine priming and resultant induction of low anti-vector antibody titres permitted repeated use of the same adenovirus vaccine vector. This resulted in significantly increased antigen-specific antibody responses in these mice compared to ID-treated mice. Boosting with a heterologous vaccine; MVA-PyMSP1₄₂ also resulted in significantly greater antibody responses in mice primed with HAdV5-PyMSP1₄₂ using MN compared to the ID route. The highest protection against blood-stage malaria challenge was observed when a heterologous route of immunization (MN/ID) was used. Therefore, microneedle-mediated immunization has potential to both overcome some of the logistic obstacles surrounding needle-and-syringe-based immunization as well as to facilitate the repeated use of the same adenovirus vaccine thereby potentially reducing manufacturing costs of multiple vaccines. This could have important benefits in the clinical ease of use of adenovirus-based immunization strategies.
Johnston, Jessica A; Tincher, Lindsey B; Lowe, Denise K
2013-12-01
To review the literature regarding booster or higher doses of influenza antigen for increasing immunogenicity of inactivated influenza vaccine (IIV) in HIV-infected patients. MEDLINE (1966 to September 2013) was searched using the terms immunize, influenza, vaccine, and HIV or AIDS in combination with two-dose, booster-dose, increased antigen, or high-dose. One trial of booster dosing with standard doses (SDs) of IIV, trivalent (IIV3); 2 trials of booster dosing with intermediate doses (ID) of H1N1 IIV or IIV3; and 1 trial of high-dose (HD) IIV3 were identified. Trials administering 2-dose, booster-dose, or increased antigen of influenza vaccine to patients with HIV were reviewed. Because adjuvanted IIV is not available and IIV, quadrivalent was recently approved in the United States, studies evaluating these vaccines were excluded. HIV-infected individuals are at high risk for influenza-related complications; however, vaccination with SD IIV may not confer optimal protection. It has been postulated that booster or higher doses of influenza antigen may lead to increased immunogenicity. When ID and SD or ID with boosters were evaluated in HIV-infected patients, significant increases in surrogate markers for influenza protection were not achieved. However, HD IIV3 did result in significant increases in seroprotective antibody levels, though 'clinical' influenza was not evaluated. Currently, evidence is insufficient to reach conclusions about the efficacy of booster dosing, ID, or HD influenza vaccine in HIV-infected patients. Trials evaluating booster or higher-antigen doses of IIV for 'clinical' influenza are necessary before routinely recommending for HIV-infected patients.
Racial/ethnic minorities are underrepresented in actual HIV vaccine trials in North America, and willingness to participate (WTP) and retention in an HIV vaccine trial may differ from that in Whites. In this review, the authors identified HIV vaccine preparedness studies (VPS) in North America in high-risk populations that examined the relationship between race/ethnicity and WTP in a preventive phase 3 HIV vaccine trial, and the relationship to retention. Studies were categorized by risk group, and comparison group (Whites vs. non-Whites). Other types of trials of biomedical prevention were also identified, and WTP and retention rates were compared and contrasted to actual HIV vaccine trials. In the studies identified, WTP in a hypothetical trial HIV vaccine trial did not differ by race/ethnicity. In contrast, actual HIV vaccine trials, an HIV acquisition trial, and a phase 2B preexposure prophylaxis (PrEP) trial have enrolled a large percentage of White men. Human papilloma virus (HPV) privately-funded trials have also enrolled a large number of Whites, due to convenience sampling. Retention in the HIV acquisition trial was lower in African-Americans compared with Whites. Strategies to increase WTP and enhanced retention (ER) strategies may help in recruiting and retaining minority participants in actual HIV vaccine trials and other trials of biomedical prevention.
Abdalla, A O; Kokhaei, P; Hansson, L; Mellstedt, H; Osterborg, A
2008-06-01
Circulating myeloma cells (CMC), exhibiting the same immunoglobulin heavy-chain gene rearrangements as the plasma cells, are part of the myeloma clone. In this study, we evaluated the effect of idiotype (Id) vaccination on CMC. Eleven patients were immunized with the autologous Id in combinations with granulocyte-macrophage colony-stimulating factor and interleukin 12, and followed for CMC by quantitative real-time allele-specific PCR. Id-specific T cells were monitored by proliferation assay, enzyme-linked immunospot (interferon-gamma) assay, and quantitative real-time PCR for cytokines. Regulatory T (T(reg)) cells were analyzed by flow cytometry. CMC were detected in 9 of 11 patients at start of vaccination. In four patients, CMC declined and two had a complete molecular remission. Further two patients had stable levels of CMC during follow-up, while in three patients CMC progressively increased. Six patients had a vaccine-induced Id-specific T-cell response. A significant correlation was observed between reduced/stable levels of CMC and the Id-specific T cells (P < 0.02). The frequency of T(reg) cells was decreased in immune responders, but increased in immune nonresponders (P < 0.05). No significant change in the serum M-protein concentration was, however, observed in any patient. Id vaccination reduced CMC, which correlated with vaccine-induced Id-specific T cells. Further studies are warranted to analyze the clinical significance of CMC and clinical effects of Id vaccination.
The potential of DNA vaccines has not been realised due to suboptimal delivery, poor antigen expression and the lack of localised inflammation, essential for antigen presentation and an effective immune response to the immunogen. Initially, we examined the delivery of a DNA vaccine encoding a model antigen, luciferase (LUC), to the respiratory tract of mice by encapsulation in a virosome. Virosomes that incorporated influenza virus haemagglutinin effectively delivered DNA to cells in the mouse respiratory tract and resulted in antigen expression and systemic and mucosal immune responses to the immunogen after an intranasal (IN) prime/intradermal (ID) boost regimen, whereas a multidose ID regimen only generated systemic immunity. We also examined systemic immune responses to LUC after ID vaccination with a DNA vaccine, which also encoded one of the several cytolytic or toxic proteins. Although the herpes simplex virus thymidine kinase, in the presence of the prodrug, ganciclovir, resulted in cell death, this failed to increase the humoral or cell-mediated immune responses. In contrast, the co-expression of LUC with the rotavirus non-structural protein 4 (NSP4) protein or a mutant form of mouse perforin, proteins which are directly cytolytic, resulted in increased LUC-specific humoral and cell-mediated immunity. On the other hand, co-expression of LUC with diphtheria toxin subunit A or overexpression of perforin or NSP4 resulted in a lower level of immunity. In summary, the efficacy of DNA vaccines can be improved by targeted IN delivery of DNA or by the induction of cell death in vaccine-targeted cells after ID delivery.
Carey, John B.; Pearson, Frances E.; Vrdoljak, Anto; McGrath, Marie G.; Crean, Abina M.; Walsh, Patrick T.; Doody, Timothy; O'Mahony, Conor; Hill, Adrian V. S.; Moore, Anne C.
2011-01-01
Background Vaccine delivery into the skin has received renewed interest due to ease of access to the immune system and microvasculature, however the stratum corneum (SC), must be breached for successful vaccination. This has been achieved by removing the SC by abrasion or scarification or by delivering the vaccine intradermally (ID) with traditional needle-and-syringes or with long microneedle devices. Microneedle patch-based transdermal vaccine studies have predominantly focused on antibody induction by inactivated or subunit vaccines. Here, our principal aim is to determine if the design of a microneedle patch affects the CD8+ T cell responses to a malaria antigen induced by a live vaccine. Methodology and Findings Recombinant modified vaccinia virus Ankara (MVA) expressing a malaria antigen was percutaneously administered to mice using a range of silicon microneedle patches, termed ImmuPatch, that differed in microneedle height, density, patch area and total pore volume. We demonstrate that microneedle arrays that have small total pore volumes induce a significantly greater proportion of central memory T cells that vigorously expand to secondary immunization. Microneedle-mediated vaccine priming induced significantly greater T cell immunity post-boost and equivalent protection against malaria challenge compared to ID vaccination. Notably, unlike ID administration, ImmuPatch-mediated vaccination did not induce inflammatory responses at the site of immunization or in draining lymph nodes. Conclusions/Significance This study demonstrates that the design of microneedle patches significantly influences the magnitude and memory of vaccine-induced CD8+ T cell responses and can be optimised for the induction of desired immune responses. Furthermore, ImmuPatch-mediated delivery may be of benefit to reducing unwanted vaccine reactogenicity. In addition to the advantages of low cost and lack of pain, the development of optimised microneedle array designs for the induction of T cell responses by live vaccines aids the development of solutions to current obstacles of immunization programmes. PMID:21799855
Kwilas, Steve; Kishimori, Jennifer M; Josleyn, Matthew; Jerke, Kurt; Ballantyne, John; Royals, Michael; Hooper, Jay W
2014-01-01
Sin Nombre virus (SNV) and Andes virus (ANDV) cause most of the hantavirus pulmonary syndrome (HPS) cases in North and South America, respectively. The chances of a patient surviving HPS are only two in three. Previously, we demonstrated that SNV and ANDV DNA vaccines encoding the virus envelope glycoproteins elicit high-titer neutralizing antibodies in laboratory animals, and (for ANDV) in nonhuman primates (NHPs). In those studies, the vaccines were delivered by gene gun or muscle electroporation. Here, we tested whether a combined SNV/ANDV DNA vaccine (HPS DNA vaccine) could be delivered effectively using a disposable syringe jet injection (DSJI) system (PharmaJet, Inc). PharmaJet intramuscular (IM) and intradermal (ID) needle-free devices are FDA 510(k)-cleared, simple to use, and do not require electricity or pressurized gas. First, we tested the SNV DNA vaccine delivered by PharmaJet IM or ID devices in rabbits and NHPs. Both IM and ID devices produced high-titer anti-SNV neutralizing antibody responses in rabbits and NHPs. However, the ID device required at least two vaccinations in NHP to detect neutralizing antibodies in most animals, whereas all animals vaccinated once with the IM device seroconverted. Because the IM device was more effective in NHP, the Stratis(®) (PharmaJet IM device) was selected for follow-up studies. We evaluated the HPS DNA vaccine delivered using Stratis(®) and found that it produced high-titer anti-SNV and anti-ANDV neutralizing antibodies in rabbits (n=8/group) as measured by a classic plaque reduction neutralization test and a new pseudovirion neutralization assay. We were interested in determining if the differences between DSJI delivery (e.g., high-velocity liquid penetration through tissue) and other methods of vaccine injection, such as needle/syringe, might result in a more immunogenic DNA vaccine. To accomplish this, we compared the HPS DNA vaccine delivered by DSJI versus needle/syringe in NHPs (n=8/group). We found that both the anti-SNV and anti-ANDV neutralizing antibody titers were significantly higher (p-value 0.0115) in the DSJI-vaccinated groups than the needle/syringe group. For example, the anti-SNV and anti-ANDV PRNT50 geometric mean titers (GMTs) were 1,974 and 349 in the DSJI-vaccinated group versus 87 and 42 in the needle/syringe group. These data demonstrate, for the first time, that a spring-powered DSJI device is capable of effectively delivering a DNA vaccine to NHPs. Whether this HPS DNA vaccine, or any DNA vaccine, delivered by spring-powered DSJI will elicit a strong immune response in humans, requires clinical trials.
ABSTRACT Intradermal (ID) vaccination induces a more potent immune response and requires lower vaccine doses as compared with standard vaccination routes. To deliver ID vaccines effectively and consistently, an ID delivery device has been developed and is commercially available for adults. The clinical application of ID vaccines for infants and children is much anticipated because children receive several vaccines, on multiple occasions, during infancy and childhood. However, experience with ID vaccines is limited and present evidence is sparse and inconsistent. ID delivery devices are not currently available for infants and children, but recent studies have examined skin thickness in this population and reported that it did not differ in proportion to body size in infants, children, and adults. These results are helpful in developing new ID devices and for preparing new vaccines in infants and children. PMID:27135736
The aim of the present study was to describe the seasonal influenza vaccination rate and to examine its determinants for children and adolescents with intellectual disabilities (ID) living in the community. A cross-sectional survey was conducted to analyze the data on seasonal influenza vaccination rate among 1055 ID individuals between the ages…
Background Vaccine literature indexing is poorly performed in PubMed due to limited hierarchy of Medical Subject Headings (MeSH) annotation in the vaccine field. Vaccine Ontology (VO) is a community-based biomedical ontology that represents various vaccines and their relations. SciMiner is an in-house literature mining system that supports literature indexing and gene name tagging. We hypothesize that application of VO in SciMiner will aid vaccine literature indexing and mining of vaccine-gene interaction networks. As a test case, we have examined vaccines for Brucella, the causative agent of brucellosis in humans and animals. Results The VO-based SciMiner (VO-SciMiner) was developed to incorporate a total of 67 Brucella vaccine terms. A set of rules for term expansion of VO terms were learned from training data, consisting of 90 biomedical articles related to Brucella vaccine terms. VO-SciMiner demonstrated high recall (91%) and precision (99%) from testing a separate set of 100 manually selected biomedical articles. VO-SciMiner indexing exhibited superior performance in retrieving Brucella vaccine-related papers over that obtained with MeSH-based PubMed literature search. For example, a VO-SciMiner search of "live attenuated Brucella vaccine" returned 922 hits as of April 20, 2011, while a PubMed search of the same query resulted in only 74 hits. Using the abstracts of 14,947 Brucella-related papers, VO-SciMiner identified 140 Brucella genes associated with Brucella vaccines. These genes included known protective antigens, virulence factors, and genes closely related to Brucella vaccines. These VO-interacting Brucella genes were significantly over-represented in biological functional categories, including metabolite transport and metabolism, replication and repair, cell wall biogenesis, intracellular trafficking and secretion, posttranslational modification, and chaperones. Furthermore, a comprehensive interaction network of Brucella vaccines and genes were identified. The asserted and inferred VO hierarchies provide semantic support for inferring novel knowledge of association of vaccines and genes from the retrieved data. New hypotheses were generated based on this analysis approach. Conclusion VO-SciMiner can be used to improve the efficiency for PubMed searching in the vaccine domain. PMID:21871085
A Phase 1 clinical trial of a DNA vaccine for Venezuelan equine encephalitis delivered by intramuscular or intradermal electroporation Drew... vaccines against VEEV available in the United States. We developed a candidate DNA vaccine expressing the E3-E2-6K-E1 genes of VEEV (pWRG/VEEV) and...groups and were vaccinated with high and low doses of pWRG/VEE or a saline placebo by intramuscular (IM) or intradermal (ID) electroporation (EP
Hur, Junguk; Xiang, Zuoshuang; Feldman, Eva L; He, Yongqun
2011-08-26
Vaccine literature indexing is poorly performed in PubMed due to limited hierarchy of Medical Subject Headings (MeSH) annotation in the vaccine field. Vaccine Ontology (VO) is a community-based biomedical ontology that represents various vaccines and their relations. SciMiner is an in-house literature mining system that supports literature indexing and gene name tagging. We hypothesize that application of VO in SciMiner will aid vaccine literature indexing and mining of vaccine-gene interaction networks. As a test case, we have examined vaccines for Brucella, the causative agent of brucellosis in humans and animals. The VO-based SciMiner (VO-SciMiner) was developed to incorporate a total of 67 Brucella vaccine terms. A set of rules for term expansion of VO terms were learned from training data, consisting of 90 biomedical articles related to Brucella vaccine terms. VO-SciMiner demonstrated high recall (91%) and precision (99%) from testing a separate set of 100 manually selected biomedical articles. VO-SciMiner indexing exhibited superior performance in retrieving Brucella vaccine-related papers over that obtained with MeSH-based PubMed literature search. For example, a VO-SciMiner search of "live attenuated Brucella vaccine" returned 922 hits as of April 20, 2011, while a PubMed search of the same query resulted in only 74 hits. Using the abstracts of 14,947 Brucella-related papers, VO-SciMiner identified 140 Brucella genes associated with Brucella vaccines. These genes included known protective antigens, virulence factors, and genes closely related to Brucella vaccines. These VO-interacting Brucella genes were significantly over-represented in biological functional categories, including metabolite transport and metabolism, replication and repair, cell wall biogenesis, intracellular trafficking and secretion, posttranslational modification, and chaperones. Furthermore, a comprehensive interaction network of Brucella vaccines and genes were identified. The asserted and inferred VO hierarchies provide semantic support for inferring novel knowledge of association of vaccines and genes from the retrieved data. New hypotheses were generated based on this analysis approach. VO-SciMiner can be used to improve the efficiency for PubMed searching in the vaccine domain.
hepatitis (A, B and non-A non-B), infectious mononucleosis and cytomegalovirus infection. IMMUNOGENICITY STUDIES A randomized, partly blinded...Klebsiella, Pseudomonas). Enterics, Foreign, Hepatitis A, Hepatitis B, Infectious Diseases, Vaccines, Biotechnology, ID, RA I Unclassified Unclassified...INTRODUCTION MILITARY IMPORTANCE OF THE STUDY AND MEDICAL APPLICATIONS A number of infectious diseases are of particular importance in military
We compared safety and immunogenicity of intradermal (ID) vaccination with and without electroporation (EP) in a phase I randomized placebo-controlled trial of an HIV-DNA prime HIV-MVA boost vaccine in healthy Swedish volunteers. HIV-DNA plasmids encoding HIV-1 genes gp160 subtypes A, B and C; Rev B; Gag A and B and RTmut B were given ID at weeks 0, 6 and 12 in a dose of 0.6 mg. Twenty-five volunteers received vaccine using a needle-free device (ZetaJet) with (n=16) or without (n=9) ID EP (Dermavax). Five volunteers were placebo recipients. Boosting with recombinant MVA-CMDR expressing HIV-1 Env, Gag, Pol of CRF01_AE (HIV-MVA) or placebo was performed at weeks 24 and 40. Nine of the vaccinees received a subtype C CN54 gp140 protein boost together with HIV-MVA. The ID/EP delivery was very well tolerated. After three HIV-DNA immunizations, no statistically significant difference was seen in the IFN-γ ELISpot response rate to Gag between HIV-DNA ID/EP recipients (5/15, 33%) and HIV-DNA ID recipients (1/7, 14%, p=0.6158). The first HIV-MVA or HIV-MVA+gp140 vaccination increased the IFN-γ ELISpot response rate to 18/19 (95%). CD4+ and/or CD8+ T cell responses to Gag or Env were demonstrable in 94% of vaccinees. A balanced CD4+ and CD8+ T cell response was noted, with 78% and 71% responders, respectively. IFN-γ and IL-2 dominated the CD4+ T cell response to Gag and Env. The CD8+ response to Gag was broader with expression of IFN-γ, IL-2, MIP-1β and/or CD107. No differences were seen between DNA vaccine groups. Binding antibodies were induced after the second HIV-MVA+/-gp140 in 93% of vaccinees to subtype C Env, with the highest titers among EP/gp140 recipients. Intradermal electroporation of HIV-DNA was well tolerated. Strong cell- and antibody-mediated immune responses were elicited by the HIV-DNA prime and HIV-MVA boosting regimen, with or without intradermal electroporation use. International Standard Randomised Controlled Trial Number (ISRCTN) 60284968.
Our goal is to apply an anti-idiotype (Id) antibody based vaccine approach for the treatment of Her-2/neu-positive human cancer. Amplification and/or over-expression of Her-2/neu occur in multiple human malignancies and are associated with poor prognosis. Her-2/neu proto-oncogene is a suitable target for cancer immunotherapy. We have developed and characterized a murine monoclonal anti-Id antibody, 6D12 that mimics a specific epitope of Her-2/neu and can be used as a surrogate antigen for Her-2/neu. In this study, the efficacy of 6D12 as a tumor vaccine was evaluated in a murine tumor model. Immunization of immunocompetent C57BL/6 mice with 6D12 conjugated to keyhole limpet hemocyanin and mixed with Freund's adjuvant or 6D12 combined with the adjuvant QS21 induced anti-6D12 as well as anti-Her-2/neu immunity. Her-2/neu-positive human breast carcinoma cells, SK-BR-3 reacted with immunized mice sera as determined by ELISA and flow cytometry. Flow cytometry analysis also demonstrated strong reactivity of immunized mice sera with human Her-2/neu transfected EL4 cells (EL4-Her-2), but no reactivity with nontransfected parental EL4 cells. Antibody dependent cellular cytotoxicity against EL4-Her-2 cells was also observed in presence of immune sera. Mice immunized with 6D12 were protected against a challenge with lethal doses of EL4-Her-2 cells, whereas no protection was observed against parental EL4 cells or when mice were immunized with an unrelated anti-Id antibody and challenged with EL4-Her-2 cells. These data suggest that anti-Id 6D12 vaccine can induce protective Her-2/neu specific antitumor immunity and may serve as a potential network antigen for the treatment of patients with Her-2/neu-positive tumors.
Bardel, Emilie; Doucet-Ladeveze, Remi; Mathieu, Cyrille; Harandi, Ali M; Dubois, Bertrand; Kaiserlian, Dominique
2016-01-01
Development of vaccines able to induce mucosal immunity in the genital and gastrointestinal tracts is a major challenge to counter sexually transmitted pathogens such as HIV-1 and HSV-2. Herein, we showed that intradermal (ID) immunisation with sub-unit vaccine antigens (i.e., HIV-1 gp140 and HSV-2 gD) delivered with Poly(I:C) or CpG1668 as adjuvant induces long-lasting virus-specific immunoglobulin (Ig)-G and IgA antibodies in the vagina and feces. Poly(I:C)-supplemented sub-unit viral vaccines caused minimal skin reactogenicity at variance to those containing CpG1668, promoted a delayed-type hypersensitivity (DTH) to the vaccine and protected mice from genital and neurological symptoms after a lethal vaginal HSV-2 challenge. Interestingly, Poly(I:C12U) (Ampligen), a Poly(I:C) structural analogue that binds to TLR3 but not MDA-5, promoted robust mucosal and systemic IgG antibodies, a weak skin DTH to the vaccine but not IgA responses and failed to confer protection against HSV-2 infection. Moreover, Poly(I:C) was far superior to Poly(I:C12U) at inducing prompt and robust upregulation of IFNß transcripts in lymph nodes draining the injection site. These data illustrate that ID vaccination with glycoproteins and Poly(I:C) as adjuvant promotes long-lasting mucosal immunity and protection from genital HSV-2 infection, with an acceptable skin reactogenicity profile. The ID route thus appears to be an unexpected inductive site for mucosal immunity and anti-viral protection suitable for sub-unit vaccines. This works further highlights that TLR3/MDA5 agonists such as Poly(I:C) may be valuable adjuvants for ID vaccination against sexually transmitted diseases. PMID:29263853
Goswami, Neela D; Pfeiffer, Christopher D; Horton, John R; Chiswell, Karen; Tasneem, Asba; Tsalik, Ephraim L
2013-01-01
There is a paucity of clinical trials informing specific questions faced by infectious diseases (ID) specialists. The ClinicalTrials.gov registry offers an opportunity to evaluate the ID clinical trials portfolio. We examined 40,970 interventional trials registered with ClinicalTrials.gov from 2007-2010, focusing on study conditions and interventions to identify ID-related trials. Relevance to ID was manually confirmed for each programmatically identified trial, yielding 3570 ID trials and 37,400 non-ID trials for analysis. The number of ID trials was similar to the number of trials identified as belonging to cardiovascular medicine (n = 3437) or mental health (n = 3695) specialties. Slightly over half of ID trials were treatment-oriented trials (53%, vs. 77% for non-ID trials) followed by prevention (38%, vs. 8% in non-ID trials). ID trials tended to be larger than those of other specialties, with a median enrollment of 125 subjects (interquartile range [IQR], 45-400) vs. 60 (IQR, 30-160) for non-ID trials. Most ID studies are randomized (73%) but nonblinded (56%). Industry was the funding source in 51% of ID trials vs. 10% that were primarily NIH-funded. HIV-AIDS trials constitute the largest subset of ID trials (n = 815 [23%]), followed by influenza vaccine (n = 375 [11%]), and hepatitis C (n = 339 [9%]) trials. Relative to U.S. and global mortality rates, HIV-AIDS and hepatitis C virus trials are over-represented, whereas lower respiratory tract infection trials are under-represented in this large sample of ID clinical trials. This work is the first to characterize ID clinical trials registered in ClinicalTrials.gov, providing a framework to discuss prioritization, methodology, and policy.
Newman, Peter A; Logie, Carmen; James, Llana; Charles, Tamicka; Maxwell, John; Salam, Khaled; Woodford, Michael
2011-09-01
We investigated how persons from key populations at higher risk of HIV exposure interpreted the process and outcomes of the Step Study HIV-1 vaccine trial, which was terminated early, and implications for willingness to participate in and community support for HIV vaccine research. We used qualitative methods and a community-based approach in 9 focus groups (n = 72) among ethnically and sexually diverse populations and 6 semistructured key informant interviews in Ontario, Canada, in 2007 to 2008. Participants construed social meaning from complex clinical and biomedical phenomena. Social representations and mental models emerged in fears of vaccine-induced infection, conceptualizations of unfair recruitment practices and increased risk behaviors among trial participants, and questioning of informed consent. Narratives of altruism and the common good demonstrated support for future trials. Public discourse on HIV vaccine trials is a productive means of interpreting complex clinical trial processes and outcomes in the context of existing beliefs and experiences regarding HIV vaccines, medical research, and historical disenfranchisement. Strategic engagement with social representations and mental models may promote meaningful community involvement in biomedical HIV prevention research.
Background We compared safety and immunogenicity of intradermal (ID) vaccination with and without electroporation (EP) in a phase I randomized placebo-controlled trial of an HIV-DNA prime HIV-MVA boost vaccine in healthy Swedish volunteers. Methods HIV-DNA plasmids encoding HIV-1 genes gp160 subtypes A, B and C; Rev B; Gag A and B and RTmut B were given ID at weeks 0, 6 and 12 in a dose of 0.6 mg. Twenty-five volunteers received vaccine using a needle-free device (ZetaJet) with (n=16) or without (n=9) ID EP (Dermavax). Five volunteers were placebo recipients. Boosting with recombinant MVA-CMDR expressing HIV-1 Env, Gag, Pol of CRF01_AE (HIV-MVA) or placebo was performed at weeks 24 and 40. Nine of the vaccinees received a subtype C CN54 gp140 protein boost together with HIV-MVA. Results The ID/EP delivery was very well tolerated. After three HIV-DNA immunizations, no statistically significant difference was seen in the IFN-γ ELISpot response rate to Gag between HIV-DNA ID/EP recipients (5/15, 33%) and HIV-DNA ID recipients (1/7, 14%, p=0.6158). The first HIV-MVA or HIV-MVA+gp140 vaccination increased the IFN-γ ELISpot response rate to 18/19 (95%). CD4+ and/or CD8+ T cell responses to Gag or Env were demonstrable in 94% of vaccinees. A balanced CD4+ and CD8+ T cell response was noted, with 78% and 71% responders, respectively. IFN-γ and IL-2 dominated the CD4+ T cell response to Gag and Env. The CD8+ response to Gag was broader with expression of IFN-γ, IL-2, MIP-1β and/or CD107. No differences were seen between DNA vaccine groups. Binding antibodies were induced after the second HIV-MVA+/-gp140 in 93% of vaccinees to subtype C Env, with the highest titers among EP/gp140 recipients. Conclusion Intradermal electroporation of HIV-DNA was well tolerated. Strong cell- and antibody-mediated immune responses were elicited by the HIV-DNA prime and HIV-MVA boosting regimen, with or without intradermal electroporation use. Trial Registration International Standard Randomised Controlled Trial Number (ISRCTN) 60284968 PMID:26121679
Objectives. We investigated how persons from key populations at higher risk of HIV exposure interpreted the process and outcomes of the Step Study HIV-1 vaccine trial, which was terminated early, and implications for willingness to participate in and community support for HIV vaccine research. Methods. We used qualitative methods and a community-based approach in 9 focus groups (n = 72) among ethnically and sexually diverse populations and 6 semistructured key informant interviews in Ontario, Canada, in 2007 to 2008. Results. Participants construed social meaning from complex clinical and biomedical phenomena. Social representations and mental models emerged in fears of vaccine-induced infection, conceptualizations of unfair recruitment practices and increased risk behaviors among trial participants, and questioning of informed consent. Narratives of altruism and the common good demonstrated support for future trials. Conclusions. Public discourse on HIV vaccine trials is a productive means of interpreting complex clinical trial processes and outcomes in the context of existing beliefs and experiences regarding HIV vaccines, medical research, and historical disenfranchisement. Strategic engagement with social representations and mental models may promote meaningful community involvement in biomedical HIV prevention research. PMID:21778490
ABSTRACT Although vaccines and antiretroviral (ARV) prevention have demonstrated partial success against human immunodeficiency virus (HIV) infection in clinical trials, their combined introduction could provide more potent protection. Furthermore, combination approaches could ameliorate the potential increased risk of infection following vaccination in the absence of protective immunity. We used a nonhuman primate model to determine potential interactions of combining a partially effective ARV microbicide with an envelope-based vaccine. The vaccine alone provided no protection from infection following 12 consecutive low-dose intravaginal challenges with simian-HIV strain SF162P3, with more animals infected compared to naive controls. The microbicide alone provided a 68% reduction in the risk of infection relative to that of the vaccine group and a 45% reduction relative to that of naive controls. The vaccine-microbicide combination provided an 88% reduction in the per-exposure risk of infection relative to the vaccine alone and a 79% reduction relative to that of the controls. Protected animals in the vaccine-microbicide group were challenged a further 12 times in the absence of microbicide and demonstrated a 98% reduction in the risk of infection. A total risk reduction of 91% was observed in this group over 24 exposures (P = 0.004). These important findings suggest that combined implementation of new biomedical prevention strategies may provide significant gains in HIV prevention. IMPORTANCE There is a pressing need to maximize the impact of new biomedical prevention tools in the face of the 2 million HIV infections that occur each year. Combined implementation of complementary biomedical approaches could create additive or synergistic effects that drive improved reduction of HIV incidence. Therefore, we assessed a combination of an untested vaccine with an ARV-based microbicide in a nonhuman primate vaginal challenge model. The vaccine alone provided no protection (and may have increased susceptibility to a simian-HIV vaginal challenge), while the microbicide reduced the infection risk compared to that of vaccinated and naive animals. Importantly, the combined interventions provided the greatest level of protection, which was sustained following withdrawal of the microbicide. The data suggest that provision of ARV prophylaxis during vaccination reduces the potential for unexpected increased risks of infection following immunization and augments vaccine efficacy. These findings are important for the potential adoption of ARV prophylaxis as the baseline intervention for future HIV/AIDS vaccines. PMID:27009957
Kafi, Kamran; Betting, David J.; Yamada, Reiko E.; Bacica, Michael; Steward, Kristopher K.; Timmerman, John M.
2009-01-01
The collection of epitopes present within the variable regions of the tumor-specific clonal immunoglobulin expressed by B cell lymphomas (idiotype, Id) can serve as a target for active immunotherapy. Traditionally, tumor-derived Id protein is chemically-conjugated to the immunogenic foreign carrier protein keyhole limpet hemocyanin (KLH) using glutaraldehyde to serve as a therapeutic vaccine. While this approach offered promising results for some patients treated in early clinical trials, glutaraldehyde Id-KLH vaccines have failed to induce immune and clinical responses in many vaccinated subjects. We recently described an alternative conjugation method employing maleimide-sulfhydryl chemistry that significantly increased the therapeutic efficacy of Id-KLH vaccines in three different murine B cell lymphoma models, with protection mediated by either CD8+ T cells or antibodies. We now define in detail the methods and parameters critical for enhancing the in vivo immunogenicity of human as well as murine Id-KLH conjugate vaccines. Optimal conditions for Id sulfhydryl pre-reduction were determined, and maleimide Id-KLH conjugates maintained stability and potency even after prolonged storage. Field flow fractionation analysis of Id-KLH particle size revealed that maleimide conjugates were far more uniform in size than glutaraldehyde conjugates. Under increasingly stringent conditions, maleimide Id-KLH vaccines maintained superior efficacy over glutaraldehyde Id-KLH in treating established, disseminated murine lymphoma. More importantly, human maleimide Id-KLH conjugates were consistently superior to glutaraldehyde Id-KLH conjugates in inducing Id-specific antibody and T cell responses. The described methods should be easily adaptable to the production of clinical grade vaccines for human trials in B cell malignancies. PMID:19046770
BACKGROUND: The PubMed database contains nearly 15 million references from more than 4,800 biomedical journals. In general, authors of scientific articles are addressed by their last name and forename initial. DISCUSSION: In general, names can be too common and not unique enough to be search criteria. Today, Ph.D. students, other researchers and women publish scientific work. A person may not only have one name but several names and publish under each name. A Unique Scientist ID could help to address people in peer-to-peer (P2P) networks. As a starting point, perhaps PubMed could generate and manage such a scientist ID. SUMMARY: A Unique Scientist ID would improve knowledge management in science. Unfortunately in some of the publications, and then within the online databases, only one letter abbreviates the author's forename. A common name with only one initial could retrieve pertinent citations, but include many false drops (retrieval matching searched criteria but indisputably irrelevant).
The "Vaccine and Drug Ontology Studies" (VDOS) international workshop series focuses on vaccine- and drug-related ontology modeling and applications. Drugs and vaccines have been critical to prevent and treat human and animal diseases. Work in both (drugs and vaccines) areas is closely related - from preclinical research and development to manufacturing, clinical trials, government approval and regulation, and post-licensure usage surveillance and monitoring. Over the last decade, tremendous efforts have been made in the biomedical ontology community to ontologically represent various areas associated with vaccines and drugs - extending existing clinical terminology systems such as SNOMED, RxNorm, NDF-RT, and MedDRA, developing new models such as the Vaccine Ontology (VO) and Ontology of Adverse Events (OAE), vernacular medical terminologies such as the Consumer Health Vocabulary (CHV). The VDOS workshop series provides a platform for discussing innovative solutions as well as the challenges in the development and applications of biomedical ontologies for representing and analyzing drugs and vaccines, their administration, host immune responses, adverse events, and other related topics. The five full-length papers included in this 2014 thematic issue focus on two main themes: (i) General vaccine/drug-related ontology development and exploration, and (ii) Interaction and network-related ontology studies.
The live-attenuated oral polio vaccine (OPV) will be no longer used when wild poliovirus (WPV) eliminating in worldwide, according to GPEI (the Global Polio Eradication Initiative) Reports. It is planning to replace OPV by Sabin-based inactivated poliovirus vaccine (sIPV) in developing countries, with purpose of reducing of the economic burden and maintaining of the appropriate antibody levels in population. It studied serial fractional doses immunized by intradermal injection (ID) in rats, to reduce consume of antigen and financial burden, maintaining sufficient immunogenicity; Methods: Study groups were divided in 4 groups of dose gradient, which were one-tenth (1/10), one-fifth (1/5), one-third (1/3) and one-full dose (1/1), according to the volume of distribution taken from the same batch of vaccine (sIPV). Wistar rats were injected intradermally with the needle and syringe sing the mantoux technique taken once month for 3 times. It was used as positive control that intramuscular inoculation (IM) was injected with one-full dose (1/1) with same batch of sIPV. PBS was used as negative control. Blood samples were collected via tail vein. After 30 d with 3 round of immunization, it analyzed the changes of neutralization antibody titers in the each group by each immunization program end; Results: The results of seroconversion had positive correlation with different doses in ID groups. The higher concentration of D-antigen (D-Ag) could conduct higher seroconversion. Furthermore, different types of viruses had different seroconversion trend. It showed that the geometric mean titers (GMTs) of each fractional-dose ID groups increased by higher concentration of D-Ag, and it got significant lower than the full-dose IM group. At 90 th days of immunization, the GMTs for each poliovirus subtypes of fractional doses were almost higher than 1:8, implied that it could be meaning positive seroprotection titer for polio vaccine types, according to WHO suggestion; Conclusions: The fractional dose with one-fifth (1/5) could be used by intradermal injection to prevent poliovirus infection, if there were more human clinical detail research consistent with this findings in rats.
Biomedical preventions for HIV, such as vaccines, microbicides or pre-exposure prophylaxis (PrEP) with antiretroviral drugs, can each only partially prevent HIV-1 infection in most human trials. Oral PrEP is now FDA approved for HIV-prevention in high risk groups, but partial adherence reduces efficacy. If combined as biomedical preventions (CBP) an HIV vaccine could provide protection when PrEP adherence is low and PrEP could prevent vaccine breakthroughs. Other types of PrEP or microbicides may also be partially protective. When licensed, first generation HIV vaccines are likely to be partially effective. Individuals at risk for HIV may receive an HIV vaccine combined with other biomedical preventions, in series or in parallel, in clinical trials or as part of standard of care, with the goal of maximally increasing HIV prevention. In human studies, it is challenging to determine which preventions are best combined, how they interact and how effective they are. Animal models can determine CBP efficacy, whether additive or synergistic, the efficacy of different products and combinations, dose, timing and mechanisms. CBP studies in macaques have shown that partially or minimally effective candidate HIV vaccines combined with partially effective oral PrEP, vaginal PrEP or microbicide generally provided greater protection than either prevention alone against SIV or SHIV challenges. Since human CBP trials will be complex, animal models can guide their design, sample size, endpoints, correlates and surrogates of protection. This review focuses on animal studies and human models of CBP and discusses implications for HIV prevention.
Ruiz, Jennifer; Gilleskie, Gary L.; Brown, Patty; Burnett, Bruce; Carbonell, Ruben G.
2014-01-01
The critical need for enhancing influenza pandemic preparedness in many developing nations has led the World Health Organization (WHO) and the Biomedical Advanced Research and Development Authority (BARDA), part of the U.S. Department of Health and Human Services (HHS), to develop an international influenza vaccine capacity-building program. Among…
Influenza Antivirals" PI: Patrick Iversen, AVI BioPharma DTRA-TMTI (Subcontract) "Rapid Development of Dengue Antivirals" PI: Patrick Iversen, AVI... BioPharma (PI) Lisa Morici, PhD: Defense Threat Reduction Agency HDTRA 1-13-C-0002 "Outer membrane vesicle vaccine-mediated protection against
Bourke, Jenny; de Klerk, Nick; Smith, Timothy; Leonard, Helen
2016-01-01
Abstract To investigate the prevalence of intellectual disability (ID) and/or autism spectrum disorders (ASDs) in Western Australia (WA). A cohort of children born from 1983 to 2010 in WA with an ID and/or ASD were identified using the population-based IDEA (Intellectual Disability Exploring Answers) database, which ascertains cases through the Disability Services Commission (DSC) as well as education sources. Information on race, gender, mother's residence at birth and deaths was obtained through linkage to the Midwives Notification System and the Mortality Register. Diagnostic information on the cause of ID was obtained through review of medical records where available and children were classified as biomedical cause, ASD, or unknown cause. An overall prevalence of ID of 17.0/1000 livebirths (95% CI: 16.7, 17.4) showed an increase from the 10-year previous prevalence of 14.3/1000. The prevalence for mild or moderate ID was 15.0 (95% CI: 14.6, 15.3), severe ID was 1.2 (95% CI: 1.1, 1.3), and unknown level of ID was 0.9 (95% CI: 0.8, 1.0)/1000 livebirths. The prevalence for Aboriginal children was 39.0/1000 compared with 15.7/1000 for non-Aboriginal children, giving a prevalence ratio of 2.5 (95% CI: 2.4, 2.6). Prevalence of all ASD was 5.1/1000 of which 3.8/1000 had ASD and ID. The prevalence of ID has risen in WA over the last 10 years with most of this increase due to mild or moderate ID. Whilst the prevalence of ASD has also increased over this time this does not fully explain the observed increase. Aboriginal children are at a 2.5-fold risk of ID but are less likely to be accessing disability services. PMID:27227936
Background Over the last few decades, biomedical HIV prevention research had engaged multiple African stakeholders. There have however been few platforms to enable regional stakeholders to engage with one another. In partnership with the World AIDS Campaign International, the Institute of Public Health of Obafemi Awolowo University, and the National Agency for the Control of AIDS in Nigeria, the New HIV Vaccine and Microbicide Advocacy Society hosted a forum on biomedical HIV prevention research in Africa. Stakeholders’ present explored evidences related to biomedical HIV prevention research and development in Africa, and made recommendations to inform policy, guidelines and future research agenda. Discussion The BHPF hosted 342 participants. Topics discussed included the use of antiretrovirals for HIV prevention, considerations for biomedical HIV prevention among key populations; HIV vaccine development; HIV cure; community and civil society engagement; and ethical considerations in implementation of biomedical HIV prevention research. Participants identified challenges for implementation of proven efficacious interventions and discovery of other new prevention options for Africa. Concerns raised included limited funding by African governments, lack of cohesive advocacy and policy agenda for biomedical HIV prevention research and development by Africa, varied ethical practices, and limited support to communities’ capacity to actively engaged with clinical trial conducts. Participants recommended that the African Government implement the Abuja +12 declaration; the civil society build stronger partnerships with diverse stakeholders, and develop a coherent advocacy agenda that also enhances community research literacy; and researchers and sponsors of trials on the African continent establish a process for determining appropriate standards for trial conduct on the continent. Conclusion By highlighting key considerations for biomedical HIV prevention research and development in Africa, the forum has helped identify key advocacy issues that Civil Society can expend efforts on so as to strengthen support for future biomedical HIV prevention research on the continent. PMID:26636825
ABSTRACT Biomedical preventions for HIV, such as vaccines, microbicides or pre-exposure prophylaxis (PrEP) with antiretroviral drugs, can each only partially prevent HIV-1 infection in most human trials. Oral PrEP is now FDA approved for HIV-prevention in high risk groups, but partial adherence reduces efficacy. If combined as biomedical preventions (CBP) an HIV vaccine could provide protection when PrEP adherence is low and PrEP could prevent vaccine breakthroughs. Other types of PrEP or microbicides may also be partially protective. When licensed, first generation HIV vaccines are likely to be partially effective. Individuals at risk for HIV may receive an HIV vaccine combined with other biomedical preventions, in series or in parallel, in clinical trials or as part of standard of care, with the goal of maximally increasing HIV prevention. In human studies, it is challenging to determine which preventions are best combined, how they interact and how effective they are. Animal models can determine CBP efficacy, whether additive or synergistic, the efficacy of different products and combinations, dose, timing and mechanisms. CBP studies in macaques have shown that partially or minimally effective candidate HIV vaccines combined with partially effective oral PrEP, vaginal PrEP or microbicide generally provided greater protection than either prevention alone against SIV or SHIV challenges. Since human CBP trials will be complex, animal models can guide their design, sample size, endpoints, correlates and surrogates of protection. This review focuses on animal studies and human models of CBP and discusses implications for HIV prevention. PMID:27679928
Over the last few decades, biomedical HIV prevention research had engaged multiple African stakeholders. There have however been few platforms to enable regional stakeholders to engage with one another. In partnership with the World AIDS Campaign International, the Institute of Public Health of Obafemi Awolowo University, and the National Agency for the Control of AIDS in Nigeria, the New HIV Vaccine and Microbicide Advocacy Society hosted a forum on biomedical HIV prevention research in Africa. Stakeholders' present explored evidences related to biomedical HIV prevention research and development in Africa, and made recommendations to inform policy, guidelines and future research agenda. The BHPF hosted 342 participants. Topics discussed included the use of antiretrovirals for HIV prevention, considerations for biomedical HIV prevention among key populations; HIV vaccine development; HIV cure; community and civil society engagement; and ethical considerations in implementation of biomedical HIV prevention research. Participants identified challenges for implementation of proven efficacious interventions and discovery of other new prevention options for Africa. Concerns raised included limited funding by African governments, lack of cohesive advocacy and policy agenda for biomedical HIV prevention research and development by Africa, varied ethical practices, and limited support to communities' capacity to actively engaged with clinical trial conducts. Participants recommended that the African Government implement the Abuja +12 declaration; the civil society build stronger partnerships with diverse stakeholders, and develop a coherent advocacy agenda that also enhances community research literacy; and researchers and sponsors of trials on the African continent establish a process for determining appropriate standards for trial conduct on the continent. By highlighting key considerations for biomedical HIV prevention research and development in Africa, the forum has helped identify key advocacy issues that Civil Society can expend efforts on so as to strengthen support for future biomedical HIV prevention research on the continent.
This Memorandum discusses the coordination and standardization of malaria vaccine research in non-human primates to encourage optimum use of the available animals in experiments that are fully justified both scientifically and ethically. The requirements for experimentation in non-human primates, the availability of suitable animals for malaria vaccine studies, and the criteria for testing candidate vaccines are considered. The policy and legislation relevant to the use of non-human primates in biomedical research are also briefly discussed. The Memorandum concludes with eight recommendations. PMID:3266112
Bourke, Jenny; de Klerk, Nick; Smith, Timothy; Leonard, Helen
2016-05-01
To investigate the prevalence of intellectual disability (ID) and/or autism spectrum disorders (ASDs) in Western Australia (WA).A cohort of children born from 1983 to 2010 in WA with an ID and/or ASD were identified using the population-based IDEA (Intellectual Disability Exploring Answers) database, which ascertains cases through the Disability Services Commission (DSC) as well as education sources. Information on race, gender, mother's residence at birth and deaths was obtained through linkage to the Midwives Notification System and the Mortality Register. Diagnostic information on the cause of ID was obtained through review of medical records where available and children were classified as biomedical cause, ASD, or unknown cause.An overall prevalence of ID of 17.0/1000 livebirths (95% CI: 16.7, 17.4) showed an increase from the 10-year previous prevalence of 14.3/1000. The prevalence for mild or moderate ID was 15.0 (95% CI: 14.6, 15.3), severe ID was 1.2 (95% CI: 1.1, 1.3), and unknown level of ID was 0.9 (95% CI: 0.8, 1.0)/1000 livebirths. The prevalence for Aboriginal children was 39.0/1000 compared with 15.7/1000 for non-Aboriginal children, giving a prevalence ratio of 2.5 (95% CI: 2.4, 2.6). Prevalence of all ASD was 5.1/1000 of which 3.8/1000 had ASD and ID.The prevalence of ID has risen in WA over the last 10 years with most of this increase due to mild or moderate ID. Whilst the prevalence of ASD has also increased over this time this does not fully explain the observed increase. Aboriginal children are at a 2.5-fold risk of ID but are less likely to be accessing disability services.
... set forth in sections 552b(c)(4) and 552b(c)(6), Title 5 U.S.C., as amended. The grant applications... will be asked to show one form of identification (for example, a government-issued photo ID, driver's... Domestic Assistance Program Nos. 93.375, Minority Biomedical Research Support; 93.821, Cell Biology and...
... set forth in sections 552b(c)(4) and 552b(c)(6), Title 5 U.S.C., as amended. The grant applications... be asked to show one form of identification (for example, a government-issued photo ID, driver's... Domestic Assistance Program Nos. 93.375, Minority Biomedical Research Support; 93.821, Cell Biology and...
The metadata of 10 published studies and 3 vaccine trial reports comprising of 19 vaccine cohorts from four countries conducted over a period of 23 years (1986–2009) was used for metaanalysis. The vaccines studied were purified chick embryo cell vaccine (Rabipur, India and Germany), purified vero cell rabies vaccine (Verorab, France; Indirab, India) and human diploid cell vaccine (MIRV, France). The potency of these vaccines varied from 0.55 IU to 2.32 IU per intradermal dose of 0.1 ml per site. The vaccines were administered to 1,011 subjects comprising of 19 cohorts and using five different ID regimens. The immunogenicity was measured by assays of rabies virus neutralizing antibody (RVNA) titres using rapid fluorescent focus inhibition test (RFFIT) [15 cohorts] and mouse neutralization test (MNT) [4 cohorts]. The statistical analysis of the data was done by Karl Pearson's correlation coefficient to measure the relationship between antigenicity and immunogenicity. It was revealed that, there was no significant linear relationship between antigenicity and immunogenicity of rabies vaccines when administered by intradermal route (p > 0.230 and p > 0.568). PMID:20523131
Background Rabies is the most severe and neglected public health problem in India. Management of animal bite with post exposure prophylaxis is the only existent strategy to prevent rabies related deaths. Cost-effective and sustainable programme for provision of post exposure prophylaxis (PEP) is needed in India. Methods In this study, we have documented the experience of implementation of intra-dermal anti rabies vaccination in Animal Bite Management (ABM) clinic at Primary Health Centre (PHC). This study facility belonged to Comprehensive Rural Health Services Project, Ballabgarh in Faridabad district of Haryana. Hospital service record of ABM clinic was analyzed and various feasibility issues such as costing of services, vaccine wastage and other operational issues in providing PEP services at PHC level were documented. Results A total of 619 patients were treated in the ABM clinic. Service utilization of ABM clinic was increased by 38% in the second year of implementation. Mean age of the patients was 23.9 years (SD: 18.8) and majority (70.4%) were males. Majority (86%) of the patients received the first dose of anti-rabies vaccine within the recommended 48 hours. A total 446 vaccine vials (1 ml) were consumed of which 20.8% was contributed in vaccine wastage. User-fee (350 Indian Rupees) collected from the patients. User-fee was re-used to purchase vaccines, intradermal (ID) syringes and other consumables required to ensure regular availability of ARV services at the PHC. Conclusions This study demonstrated the cost-effective and sustainable model of provision of PEP against rabies at primary care level. ID PEP provision at primary care level not only address the unmet need of animal bite management in the community also reduces the out of pocket expenditure of the patients. PMID:24965875
Skin is protected by a tough but flexible multilayered barrier and is a front line for immune responses against invading particles. For many years now, skin has been a tissue where certain vaccines are injected for the prevention of infectious disease, however, the detailed mechanisms of the skin immune response are not yet well understood. Using thin and small injection needles, we carefully injected OVA into a restricted region of mouse skin, i.e., intradermal (ID), and examined the antibody response in comparison with subcutaneous (SC) injection or epicutaneous patch administration of OVA. Epicutaneous patches induced a high IgE response against OVA, but IgG production was low. High IgG production was induced by both ID and SC injection, moreover, ID injection induced higher IgG production without any adjutants. Furthermore, OVA-specific IgE production was diminished by ID injection. We found that ID injection could efficiently stimulate skin resident DCs, drive Th1-biased conditions and diminish IgE production. The ID injection response was regulated by Langerin+ dermal DCs, because OVA was taken up mainly by these cells and, after transiently deleting them, the IgE response was no longer diminished and IgG1 production was enhanced. We also tested whether ID injection might be an effective allergy treatment by attempting to inhibit ongoing IgE production in mice with experimentally induced high serum IgE levels. Multiple ID injections of OVA were shown to prevent elevation of serum OVA-specific IgE after repeated allergen challenge. In contrast, SC OVA injection could only transiently inhibit the OVA-specific IgE production. These findings indicated that ID injection results in higher induction of antigen-specific IgG, and thus may be useful for vaccine delivery with little or no adjuvant components. Moreover, the observed diminishment of IgE and induction of Th1-biased immune responses suggest that ID may be a useful injection route for allergy immunotherapy. PMID:27973543
New vaccine pricing is a complicated process that could have substantial long-standing scientific, medical and public health ramifications. Pricing can have a considerable impact on new vaccine adoption and, thereby, either culminate or thwart years of research and development and public health efforts. Typically, pricing strategy consists of the following eleven components: (1) Conduct a target population analysis; (2) Map potential competitors and alternatives; (3) Construct a vaccine target product profile (TPP) and compare it to projected or actual TPPs of competing vaccines; (4) Quantify the incremental value of the new vaccine's characteristics; (5) Determine vaccine positioning in the marketplace; (6) Estimate the vaccine price-demand curve; (7) Calculate vaccine costs (including those of manufacturing, distribution, and research and development); (8) Account for various legal, regulatory, third party payer and competitor factors; (9) Consider the overall product portfolio; (10) Set pricing objectives; (11) Select pricing and pricing structure. While the biomedical literature contains some studies that have addressed these components, there is still considerable room for more extensive evaluation of this important area. PMID:20861678
09-C-0119 BAA09-31 & BAA-10-55 Final Report Date of Proposal: Prepared by Sanofi Pasteur VaxDesign Campus...Sciences, seasonal influenza trivalent intramuscular (TIV-IM) or intradermal (TIV-ID) vaccines, and a quadrivalent influenza vaccine (QIV) from Sanofi . We
After the end of the Second World War, cancer virus research experienced a remarkable revival, culminating in the creation in 1964 of the United States National Cancer Institute's Special Virus Leukemia Program (SVLP), an ambitious program of directed biomedical research to accelerate the development of a leukemia vaccine. Studies of cancer viruses soon became the second most highly funded area of research at the Institute, and by far the most generously funded area of biological research. Remarkably, this vast infrastructure for cancer vaccine production came into being before a human leukemia virus was shown to exist. The origins of the SVLP were rooted in as much as shifts in American society as laboratory science. The revival of cancer virus studies was a function of the success advocates and administrators achieved in associating cancer viruses with campaigns against childhood diseases such as polio and leukemia. To address the urgency borne of this new association, the SVLP's architects sought to lessen the power of peer review in favor of centralized Cold War management methods, fashioning viruses as "administrative objects" in order to accelerate the tempo of biomedical research and discovery.
New vaccine pricing is a complicated process that could have substantial long-standing scientific, medical, and public health ramifications. Pricing can have a considerable impact on new vaccine adoption and, thereby, either culminate or thwart years of research and development and public health efforts. Typically, pricing strategy consists of the following ten components: 1. Conduct a target population analysis; 2. Map potential competitors and alternatives; 3. Construct a vaccine target product profile (TPP) and compare it to projected or actual TPPs of competing vaccines; 4. Quantify the incremental value of the new vaccine's characteristics; 5. Determine vaccine positioning in the marketplace; 6. Estimate the vaccine price-demand curve; 7. Calculate vaccine costs (including those of manufacturing, distribution, and research and development); 8. Account for various legal, regulatory, third party payer, and competitor factors; 9. Consider the overall product portfolio; 10. Set pricing objectives; 11. Select pricing and pricing structure. While the biomedical literature contains some studies that have addressed these components, there is still considerable room for more extensive evaluation of this important area.
The three antiviral vaccines discovered in the 18th century (smallpox), 19th century (rabies), and 20th century (polio) share a common feature: none would ever be licensed today for human vaccination. Yet Jenner's smallpox vaccine led to the eradication of smallpox, Pasteur's rabies vaccine represented the first successful post-exposure treatment of people bitten by rabid animals, and polio vaccine administered since its discovery in 1950 is leading to the eradication of polio (in the years 2004-2005) from the earth. However, in the case of rabies, efforts at complete eradication are unrealistic, despite the availability of a very effective vaccine, since rabies, unlike smallpox and polio, is not limited to humans and can infect all domestic and wild mammalian species. Rabies is probably the oldest known infectious disease, yet knowledge of the virus and the disease is far from complete. For instance, the appearance of 24 cases of "cryptic" rabies in the USA, i.e. cases not associated with any bite or scratch, with an incubation period in humans extending 6-8 years, is a puzzling phenomenon that cannot be readily explained. On the other hand, rabies is one of the few strictly neuronal infections and, as such, is an excellent model for the study of neurotropic virus distribution in the brain. Apoptosis induced by a rabies strain expressing high levels of glycoprotein spreads much more slowly through brain tissue than that induced by strains producing lower glycoprotein levels. Attenuated rabies virus constructed to express twice the normal glycoprotein levels is also an excellent antigen for induction of immune responses in the host. Foreign antigens using this vector may also produce highly immunogenic vaccines. Global approach to immunization. Those monitoring the spread of AIDS in many parts of the world know that cost of treatment is one of the major problems in combating the disease. Vaccines against HIV face the same problem. In general, the price of vaccines and sera is exorbitant for the afflicted population in developing countries. In addition, the dearth of syringes, the unavailability of nurses and doctors to administer multiple vaccine injections, and other factors in these countries require a drastic change in current vaccine production approaches. About 12 years ago, plants became vehicles to produce biomedical reagents. Plants can be exposed directly to a construct containing a foreign gene and Agrobacterium to create a transgenic plant that, over several generations, produces the desired product. Alternatively, plants infected with a plant virus (e.g. alfalfa mosaic virus) fused with a foreign gene can propagate the foreign antigen as the virus multiplies. Extraction of the plant virus followed by purification provides the desired biomedical product. Our use of either of these systems has led to the creation of plants producing vaccines, sera, hormones, and other biological reagents. In two clinical trials at the Institute of Bioorganic Chemistry of the Polish Academy of Sciences in Poznań (Poland), volunteers who ingested lettuce expressing hepatitis B vaccine showed hepatitis B antibodies in their sera. In another trial carried out at the Biotechnology Foundation Laboratories in Philadelphia (USA), volunteers ingesting a spinach-rabies vaccine showed an immunological priming effect, since only one injection of commercially available rabies vaccine significantly raised the level of rabies-specific antibodies. Vaccines against HIV gp120 and Tat have been produced in spinach, and a construct of gp120 with the CD4 receptor is now being adapted to this plant. Two types of antibodies against rabies and against colorectal cancer are being produced in tobacco and in lettuce. The suboptimal quality of the currently available anthrax vaccine prompted our efforts to produce the anthrax protective antigen (PA) in tobacco and lettuce. Quite clearly, plants will play a prominent role in producing a variety of biomedical reagents in the future.
Sokolow, Leslie Z.; Broder, Karen R.; Walter, Emmanuel B.; Bresee, Joseph S.; Fry, Alicia M.; Jernigan, Daniel B.
2017-01-01
Summary This report updates the 2016–17 recommendations of the Advisory Committee on Immunization Practices (ACIP) regarding the use of seasonal influenza vaccines (MMWR Recomm Rep 2016;65[No. RR-5]). Routine annual influenza vaccination is recommended for all persons aged ≥6 months who do not have contraindications. A licensed, recommended, and age-appropriate vaccine should be used. For the 2017–18 season, quadrivalent and trivalent influenza vaccines will be available. Inactivated influenza vaccines (IIVs) will be available in trivalent (IIV3) and quadrivalent (IIV4) formulations. Recombinant influenza vaccine (RIV) will be available in trivalent (RIV3) and quadrivalent (RIV4) formulations. Live attenuated influenza vaccine (LAIV4) is not recommended for use during the 2017–18 season due to concerns about its effectiveness against (H1N1)pdm09 viruses during the 2013–14 and 2015–16 seasons. Recommendations for different vaccine types and specific populations are discussed. No preferential recommendation is made for one influenza vaccine product over another for persons for whom more than one licensed, recommended product is available. Updates to the recommendations described in this report reflect discussions during public meetings of ACIP held on October 20, 2016; February 22, 2017; and June 21, 2017. New and updated information in this report includes the following: •Vaccine viruses included in the 2017–18 U.S. trivalent influenza vaccines will be an A/Michigan/45/2015 (H1N1)pdm09–like virus, an A/Hong Kong/4801/2014 (H3N2)-like virus, and a B/Brisbane/60/2008–like virus (Victoria lineage). Quadrivalent influenza vaccines will contain these three viruses and an additional influenza B vaccine virus, a B/Phuket/3073/2013–like virus (Yamagata lineage). • Information on recent licensures and labelling changes is discussed, including licensure of Afluria Quadrivalent (IIV4; Seqirus, Parkville, Victoria, Australia); Flublok Quadrivalent (RIV4; Protein Sciences, Meriden, Connecticut); and expansion of the age indication for FluLaval Quadrivalent (IIV4; ID Biomedical Corporation of Quebec, Quebec City, Quebec, Canada), previously licensed for ≥3 years, to ≥6 months. • Pregnant women may receive any licensed, recommended, age-appropriate influenza vaccine. • Afluria (IIV3; Seqirus, Parkville, Victoria, Australia) may be used for persons aged ≥5 years, consistent with Food and Drug Administration–approved labeling. • FluMist Quadrivalent (LAIV4; MedImmune, Gaithersburg, Maryland) should not be used during the 2017–18 season due to concerns about its effectiveness against influenza A(H1N1)pdm09 viruses in the United States during the 2013–14 and 2015–16 influenza seasons. This report focuses on the recommendations for use of vaccines for the prevention and control of influenza during the 2017–18 season in the United States. A Background Document containing further information and a summary of these recommendations are available at https://www.cdc.gov/vaccines/hcp/acip-recs/vacc-specific/flu.html. These recommendations apply to licensed influenza vaccines used within Food and Drug Administration–licensed indications, including those licensed after the publication date of this report. Updates and other information are available at CDC’s influenza website (https://www.cdc.gov/flu). Vaccination and health care providers should check CDC’s influenza website periodically for additional information. PMID:28841201
Shin, Soo-Yong; Lyu, Yongman; Shin, Yongdon; Choi, Hyo Joung; Park, Jihyun; Kim, Woo-Sung
2013-01-01
Objectives The Korean government has enacted two laws, namely, the Personal Information Protection Act and the Bioethics and Safety Act to prevent the unauthorized use of medical information. To protect patients' privacy by complying with governmental regulations and improve the convenience of research, Asan Medical Center has been developing a de-identification system for biomedical research. Methods We reviewed Korean regulations to define the scope of the de-identification methods and well-known previous biomedical research platforms to extract the functionalities of the systems. Based on these review results, we implemented necessary programs based on the Asan Medical Center Information System framework which was built using the Microsoft. NET Framework and C#. Results The developed de-identification system comprises three main components: a de-identification tool, a search tool, and a chart review tool. The de-identification tool can substitute a randomly assigned research ID for a hospital patient ID, remove the identifiers in the structured format, and mask them in the unstructured format, i.e., texts. This tool achieved 98.14% precision and 97.39% recall for 6,520 clinical notes. The search tool can find the number of patients which satisfies given search criteria. The chart review tool can provide de-identified patient's clinical data for review purposes. Conclusions We found that a clinical data warehouse was essential for successful implementation of the de-identification system, and this system should be tightly linked to an electronic Institutional Review Board system for easy operation of honest brokers. Additionally, we found that a secure cloud environment could be adopted to protect patients' privacy more thoroughly. PMID:23882415
Sudarshan, M K; Madhusudana, S N; Mahendra, B J; Ashwath Narayana, D H; Ananda Giri, M S; Popova, O; Vakil, H B
2005-07-01
Human rabies is an ongoing significant public health problem inmany developing countries, with India reporting the highest incidence of rabies-related deaths (∼20,000 per year). Many people living in India cannot afford the standard IM postexposure prophylaxis (PEP) with cell-culture vaccines, which are administered using a 5-dose regimen developed in Essen, Germany. A potentially less expensive intradermal (ID) regimen, based on the Essen regimen, has been developed at the Kempegowda Institute of Medical Sciences (KIMS), Bangalore, India. The objective of this study was to compare the immunogenicity and local and systemic tolerability of the KIMS-1D regimen with those of the standard Essen IM regimen in healthy adult volunteers in India. This randomized, open-label, active-controlled trial was conductedat the Antirabies Clinic, Medical College, KIMS. Healthy adult volunteers were randomly assigned to receive purified chick embryo cell vaccine (PCECV) using the KIMS-1D regimen (0.1 mL injected ID at 2 body sites on days 0, 3, 7, 14, and 28 ["2-2-2-2-2"]) or the Essen IM regimen (1 mL injected IM at 1 body site on the same days Subjects were followed up for 365 days by the treating physician and encouraged to voluntarily report any adverse events (AEs). Serum rabies virus-neutralizing antibody (RVNA) concentrations were measured before the first injection on day 0 (baseline) and on days 14, 28, 90, 180, and 365, using the rapid fluorescent focus inhibition test. Ninety-one subjects were enrolled and included in the tolerabilityand immunogenicity analyses. The ID group comprised 45 subjects (26 men, 19 women; mean [SD] age, 20.84 [1.48] years); the IM group, 46 subjects (28 men, 18 women; mean [SD] age, 21.02 [1.16] years). The most common local AEs were pain at the injection site (2/225 [0.9%] in the ID group and 10/230 [4.3%] in the IM group; P < 0.006) and itching at the injection site (5/225 [2.2%] in the ID group and none in the IM group; P = 0.026). All of the AEs were transient and resolved without the need for medication. All subjects had serum RVNA concentrations ≥0.5 IU/mL-considered protective by the World Health Organization-at all follow-up visits. However, the mean RVNA concentrations in the IM group were significantly higher compared with those in the ID group from days 14 to 365 (all, P < 0.001). In this study in healthy volunteers, PEP with PCECV administered using the KIMS-ID regimen was well tolerated and immunologically efficacious for 365 days. Adequate RVNA levels were maintained with the KIMS-ID regimen from days 14 to 365, although these levels were significantly lower than those achieved in the group receiving the Essen IM regimen (all, P < 0.001).
Background: Human rabies is an ongoing significant public health problem inmany developing countries, with India reporting the highest incidence of rabies-related deaths (∼20,000 per year). Many people living in India cannot afford the standard IM postexposure prophylaxis (PEP) with cell-culture vaccines, which are administered using a 5-dose regimen developed in Essen, Germany. A potentially less expensive intradermal (ID) regimen, based on the Essen regimen, has been developed at the Kempegowda Institute of Medical Sciences (KIMS), Bangalore, India. Objective: The objective of this study was to compare the immunogenicity and local and systemic tolerability of the KIMS-1D regimen with those of the standard Essen IM regimen in healthy adult volunteers in India. Methods: This randomized, open-label, active-controlled trial was conductedat the Antirabies Clinic, Medical College, KIMS. Healthy adult volunteers were randomly assigned to receive purified chick embryo cell vaccine (PCECV) using the KIMS-1D regimen (0.1 mL injected ID at 2 body sites on days 0, 3, 7, 14, and 28 [“2-2-2-2-2”]) or the Essen IM regimen (1 mL injected IM at 1 body site on the same days Subjects were followed up for 365 days by the treating physician and encouraged to voluntarily report any adverse events (AEs). Serum rabies virus-neutralizing antibody (RVNA) concentrations were measured before the first injection on day 0 (baseline) and on days 14, 28, 90, 180, and 365, using the rapid fluorescent focus inhibition test. Results: Ninety-one subjects were enrolled and included in the tolerabilityand immunogenicity analyses. The ID group comprised 45 subjects (26 men, 19 women; mean [SD] age, 20.84 [1.48] years); the IM group, 46 subjects (28 men, 18 women; mean [SD] age, 21.02 [1.16] years). The most common local AEs were pain at the injection site (2/225 [0.9%] in the ID group and 10/230 [4.3%] in the IM group; P < 0.006) and itching at the injection site (5/225 [2.2%] in the ID group and none in the IM group; P = 0.026). All of the AEs were transient and resolved without the need for medication. All subjects had serum RVNA concentrations ≥0.5 IU/mL—considered protective by the World Health Organization—at all follow-up visits. However, the mean RVNA concentrations in the IM group were significantly higher compared with those in the ID group from days 14 to 365 (all, P < 0.001). Conclusion: In this study in healthy volunteers, PEP with PCECV administered using the KIMS-ID regimen was well tolerated and immunologically efficacious for 365 days. Adequate RVNA levels were maintained with the KIMS-ID regimen from days 14 to 365, although these levels were significantly lower than those achieved in the group receiving the Essen IM regimen (all, P < 0.001). PMID:24672132
Shin, Soo-Yong; Lyu, Yongman; Shin, Yongdon; Choi, Hyo Joung; Park, Jihyun; Kim, Woo-Sung; Lee, Jae Ho
2013-06-01
The Korean government has enacted two laws, namely, the Personal Information Protection Act and the Bioethics and Safety Act to prevent the unauthorized use of medical information. To protect patients' privacy by complying with governmental regulations and improve the convenience of research, Asan Medical Center has been developing a de-identification system for biomedical research. We reviewed Korean regulations to define the scope of the de-identification methods and well-known previous biomedical research platforms to extract the functionalities of the systems. Based on these review results, we implemented necessary programs based on the Asan Medical Center Information System framework which was built using the Microsoft. NET Framework and C#. The developed de-identification system comprises three main components: a de-identification tool, a search tool, and a chart review tool. The de-identification tool can substitute a randomly assigned research ID for a hospital patient ID, remove the identifiers in the structured format, and mask them in the unstructured format, i.e., texts. This tool achieved 98.14% precision and 97.39% recall for 6,520 clinical notes. The search tool can find the number of patients which satisfies given search criteria. The chart review tool can provide de-identified patient's clinical data for review purposes. We found that a clinical data warehouse was essential for successful implementation of the de-identification system, and this system should be tightly linked to an electronic Institutional Review Board system for easy operation of honest brokers. Additionally, we found that a secure cloud environment could be adopted to protect patients' privacy more thoroughly.
Wysokinski, T. W.; Chapman, D.; Adams, G.; Renier, M.; Suortti, P.; Thomlinson, W.
2013-03-01
The BioMedical Imaging and Therapy (BMIT) facility provides a world class facility with unique synchrotron-specific imaging and therapy capabilities. This paper describes Insertion Device (ID) beamline 05ID-2 with the beam terminated in the first experimental hutch: POE-2. The experimental methods available in POE-2 include: Microbeam Radiation Therapy (MRT), Synchrotron Stereotactic Radiation Therapy (SSRT) and absorption imaging (projection and Computed Tomography (CT)). The source for the ID beamline is a multi-pole superconductive 4.3 T wiggler, which can generate ~30 kW of radiative power and deliver dose as high as 3000 Gy/s required for MRT program. The optics in POE-1 hutch prepares either monochromatic or filtered white beam that is used in POE-2. The Double Crystal (DC), bent Laue monochromator will prepare a beam over 10 cm wide at sample point, while spanning an energy range appropriate for imaging studies of animals (20-100+ keV). The experimental hutch will have a flexible positioning system that can handle subjects up to 120 kg. Several different cameras will be available with resolutions ranging from 4 μm to 150 μm. The latest update on the status of 05B1-1 bending magnet (BM) beamline, described in Part 1 [1], is also included.
Grohskopf, Lisa A; Sokolow, Leslie Z; Broder, Karen R; Walter, Emmanuel B; Bresee, Joseph S; Fry, Alicia M; Jernigan, Daniel B
2017-08-25
This report updates the 2016-17 recommendations of the Advisory Committee on Immunization Practices (ACIP) regarding the use of seasonal influenza vaccines (MMWR Recomm Rep 2016;65[No. RR-5]). Routine annual influenza vaccination is recommended for all persons aged ≥6 months who do not have contraindications. A licensed, recommended, and age-appropriate vaccine should be used.For the 2017-18 season, quadrivalent and trivalent influenza vaccines will be available. Inactivated influenza vaccines (IIVs) will be available in trivalent (IIV3) and quadrivalent (IIV4) formulations. Recombinant influenza vaccine (RIV) will be available in trivalent (RIV3) and quadrivalent (RIV4) formulations. Live attenuated influenza vaccine (LAIV4) is not recommended for use during the 2017-18 season due to concerns about its effectiveness against (H1N1)pdm09 viruses during the 2013-14 and 2015-16 seasons. Recommendations for different vaccine types and specific populations are discussed. No preferential recommendation is made for one influenza vaccine product over another for persons for whom more than one licensed, recommended product is available.Updates to the recommendations described in this report reflect discussions during public meetings of ACIP held on October 20, 2016; February 22, 2017; and June 21, 2017. New and updated information in this report includes the following:•Vaccine viruses included in the 2017-18 U.S. trivalent influenza vaccines will be an A/Michigan/45/2015 (H1N1)pdm09-like virus, an A/Hong Kong/4801/2014 (H3N2)-like virus, and a B/Brisbane/60/2008-like virus (Victoria lineage). Quadrivalent influenza vaccines will contain these three viruses and an additional influenza B vaccine virus, a B/Phuket/3073/2013-like virus (Yamagata lineage).• Information on recent licensures and labelling changes is discussed, including licensure of Afluria Quadrivalent (IIV4; Seqirus, Parkville, Victoria, Australia); Flublok Quadrivalent (RIV4; Protein Sciences, Meriden, Connecticut); and expansion of the age indication for FluLaval Quadrivalent (IIV4; ID Biomedical Corporation of Quebec, Quebec City, Quebec, Canada), previously licensed for ≥3 years, to ≥6 months.• Pregnant women may receive any licensed, recommended, age-appropriate influenza vaccine.• Afluria (IIV3; Seqirus, Parkville, Victoria, Australia) may be used for persons aged ≥5 years, consistent with Food and Drug Administration-approved labeling.• FluMist Quadrivalent (LAIV4; MedImmune, Gaithersburg, Maryland) should not be used during the 2017-18 season due to concerns about its effectiveness against influenza A(H1N1)pdm09 viruses in the United States during the 2013-14 and 2015-16 influenza seasons.This report focuses on the recommendations for use of vaccines for the prevention and control of influenza during the 2017-18 season in the United States. A Background Document containing further information and a summary of these recommendations are available at https://www.cdc.gov/vaccines/hcp/acip-recs/vacc-specific/flu.html. These recommendations apply to licensed influenza vaccines used within Food and Drug Administration-licensed indications, including those licensed after the publication date of this report. Updates and other information are available at CDC's influenza website (https://www.cdc.gov/flu). Vaccination and health care providers should check CDC's influenza website periodically for additional information.
Background We conducted a phase I/II randomized placebo-controlled trial with the aim of exploring whether priming with a low intradermal dose of a multiclade, multigene HIV-1 DNA vaccine could improve the immunogenicity of the same vaccine given intramuscularly prior to boosting with a heterologous HIV-1 MVA among healthy adults in Dar es Salaam, Tanzania. Methods Sixty HIV-uninfected volunteers were randomized to receive DNA plasmid vaccine 1 mg intradermally (id), n = 20, or 3.8 mg intramuscularly (im), n = 20, or placebo, n = 20, using a needle-free injection device. DNA plasmids encoding HIV-1 genes gp160 subtype A, B, C; rev B; p17/p24 gag A, B and Rtmut B were given at weeks 0, 4 and 12. Recombinant MVA (108 pfu) expressing HIV-1 Env, Gag, Pol of CRF01_AE or placebo was administered im at month 9 and 21. Results The vaccines were well tolerated. Two weeks after the third HIV-DNA injection, 22/38 (58%) vaccinees had IFN-γ ELISpot responses to Gag. Two weeks after the first HIV-MVA boost all 35 (100%) vaccinees responded to Gag and 31 (89%) to Env. Two to four weeks after the second HIV-MVA boost, 28/29 (97%) vaccinees had IFN-γ ELISpot responses, 27 (93%) to Gag and 23 (79%) to Env. The id-primed recipients had significantly higher responses to Env than im recipients. Intracellular cytokine staining for Gag-specific IFN-γ/IL-2 production showed both CD8+ and CD4+ T cell responses. All vaccinees had HIV-specific lymphoproliferative responses. All vaccinees reacted in diagnostic HIV serological tests and 26/29 (90%) had antibodies against gp160 after the second HIV-MVA boost. Furthermore, while all of 29 vaccinee sera were negative for neutralizing antibodies against clade B, C and CRF01 AE pseudoviruses in the TZM-bl neutralization assay, in a PBMC assay, the response rate ranged from 31% to 83% positives, depending upon the clade B or CRF01_AE virus tested. This vaccine approach is safe and highly immunogenic. Low dose, id HIV-DNA priming elicited higher and broader cell-mediated immune responses to Env after HIV-MVA boost compared to a higher HIV-DNA priming dose given im. Three HIV-DNA priming immunizations followed by two HIV-MVA boosts efficiently induced Env-antibody responses. PMID:21864626
Jacobson, Sheldon H; Sewell, Edward C; Allwine, Daniel A; Medina, Enrique A; Weniger, Bruce G
2003-02-01
The National Immunization Program, housed within the Centers for Disease Control and Prevention in the USA, has identified several challenges that must be faced in childhood immunization programs to deliver and procure vaccines that immunize children from the plethora of childhood diseases. The biomedical issues cited include how drug manufacturers can combine and formulate vaccines, how such vaccines are scheduled and administered and how economically sound vaccine procurement can be achieved. This review discusses how operations research models can be used to address the economics of pediatric vaccine formulary design and pricing, as well as how such models can be used to address a new set of pediatric formulary problems that will surface with the introduction of pediatric combination vaccines into the US pediatric immunization market.
pre-fusion 119 EBOV GP1,2 ΔTM structure ( PDB ID: 3CSY) that lacks the MLD was performed as previously 120 described (22, 23). Briefly, the published... structure lacks four NGS in GP1 due to disordered 121 regions missing from the structure (N204 and N296) or mutations that promoted crystallization...122 (N40 and N228) (20, 21). The EBOV GP sequence was submitted to the PHYRE2 protein fold 123 recognition server (16), which provided a structure
An HIV vaccine trial scheduled for 1997 involves 2000 male and female members of the Uganda People's Defence Force. The volunteers are 18-40 years old and have been evaluated for 18 months. The trial of Alvac-HIV vaccine developed by Pasteur Manieux Connaught will be conducted by the Joint Clinical Research Council, a joint venture of Makerere University and the Ministries of Health and Defence, in collaboration with the Johns Hopkins University. The vaccine has already been tested on 300 volunteers in France and the US. The initial stage of testing will involve a randomized, placebo-controlled, double-blind trial comparing the safety and immunogenicity of four successive injections in 20 HIV-negative and 20 HIV-positive volunteers. Follow-up will continue for a year. While volunteers will get free medical attention if they develop a severe reaction to the vaccine and will receive a full explanation about the experimental nature of the vaccine, it has not been determined how volunteers will be compensated if something unforeseen goes wrong. Additional concerns revolve around Uganda's readiness to institute proper legal controls and ethical standards in cases of biomedical research.
Lau, Chuen-Yen; Swann, Edith M; Singh, Sagri; Kafaar, Zuhayr; Meissner, Helen I; Stansbury, James P
2011-10-13
HIV vaccine clinical research occurs within a context where biomedical science and social issues are interlinked. Previous HIV vaccine research has considered behavioral and social issues, but often treated them as independent of clinical research processes. Systematic attention to the intersection of behavioral and social issues within a defined clinical research framework is needed to address gaps, such as those related to participation in trials, completion of trials, and the overall research experience. Rigorous attention to these issues at project inception can inform trial design and conduct by matching research approaches to the context in which trials are to be conducted. Conducting behavioral and social sciences research concurrent with vaccine clinical research is important because it can help identify potential barriers to trial implementation, as well as ultimate acceptance and dissemination of trial results. We therefore propose a conceptual framework for behavioral and social science in HIV vaccine clinical research and use examples from the behavioral and social science literature to demonstrate how the model can facilitate identification of significant areas meriting additional exploration. Standardized use of the conceptual framework could improve HIV vaccine clinical research efficiency and relevance. Published by Elsevier Ltd.
Vaccine is the one of the greatest inventions of modern medicine that has contributed most to the relief of human misery and the exciting increase in life expectancy. In 1796, an English country physician, Edward Jenner, discovered that inoculating mankind with cowpox can protect them from smallpox (Riedel S, Edward Jenner and the history of smallpox and vaccination. Proceedings (Baylor University. Medical Center) 18(1):21, 2005). Based on the vaccination worldwide, we finally succeeded in the eradication of smallpox in 1977 (Henderson, Vaccine 29:D7-D9, 2011). Other disabling and lethal diseases, like poliomyelitis and measles, are targeted for eradication (Bonanni, Vaccine 17:S120-S125, 1999).Although vaccine development and administration are tremendously successful and cost-effective practices to human health, no vaccine is 100% safe for everyone because each person reacts to vaccinations differently given different genetic background and health conditions. Although all licensed vaccines are generally safe for the majority of people, vaccinees may still suffer adverse events (AEs) in reaction to various vaccines, some of which can be serious or even fatal (Haber et al., Drug Saf 32(4):309-323, 2009). Hence, the double-edged sword of vaccination remains a concern.To support integrative AE data collection and analysis, it is critical to adopt an AE normalization strategy. In the past decades, different controlled terminologies, including the Medical Dictionary for Regulatory Activities (MedDRA) (Brown EG, Wood L, Wood S, et al., Drug Saf 20(2):109-117, 1999), the Common Terminology Criteria for Adverse Events (CTCAE) (NCI, The Common Terminology Criteria for Adverse Events (CTCAE). Available from: http://evs.nci.nih.gov/ftp1/CTCAE/About.html . Access on 7 Oct 2015), and the World Health Organization (WHO) Adverse Reactions Terminology (WHO-ART) (WHO, The WHO Adverse Reaction Terminology - WHO-ART. Available from: https://www.umc-products.com/graphics/28010.pdf ), have been developed with a specific aim to standardize AE categorization. However, these controlled terminologies have many drawbacks, such as lack of textual definitions, poorly defined hierarchies, and lack of semantic axioms that provide logical relations among terms. A biomedical ontology is a set of consensus-based and computer and human interpretable terms and relations that represent entities in a specific biomedical domain and how they relate each other. To represent and analyze vaccine adverse events (VAEs), our research group has initiated and led the development of a community-based ontology: the Ontology of Adverse Events (OAE) (He et al., J Biomed Semant 5:29, 2014). The OAE has been found to have advantages to overcome the drawbacks of those controlled terminologies (He et al., Curr Pharmacol Rep :1-16. doi:10.1007/s40495-016-0055-0, 2014). By expanding the OAE and the community-based Vaccine Ontology (VO) (He et al., VO: vaccine ontology. In The 1st International Conference on Biomedical Ontology (ICBO-2009). Nature Precedings, Buffalo. http://precedings.nature.com/documents/3552/version/1 ; J Biomed Semant 2(Suppl 2):S8; J Biomed Semant 3(1):17, 2009; Ozgur et al., J Biomed Semant 2(2):S8, 2011; Lin Y, He Y, J Biomed Semant 3(1):17, 2012), we have also developed the Ontology of Vaccine Adverse Events (OVAE) to represent known VAEs associated with licensed vaccines (Marcos E, Zhao B, He Y, J Biomed Semant 4:40, 2013).In this book chapter, we will first introduce the basic information of VAEs, VAE safety surveillance systems, and how to specifically query and analyze VAEs using the US VAE database VAERS (Chen et al., Vaccine 12(10):960-960, 1994). In the second half of the chapter, we will introduce the development and applications of the OAE and OVAE. Throughout this chapter, we will use the influenza vaccine Flublok as the vaccine example to launch the corresponding elaboration (Huber VC, McCullers JA, Curr Opin Mol Ther 10(1):75-85, 2008). Flublok is a recombinant hemagglutinin influenza vaccine indicated for active immunization against disease caused by influenza virus subtypes A and type B. On January 16, 2013, Flublok was approved by the FDA for the prevention of seasonal influenza in people 18 years and older in the USA. Now, more than 3 years later, an exploration of the reported AEs associated with this vaccine is urgently needed.
Lau, Chuen-Yen; Swann, Edith M.; Singh, Sagri; Kafaar, Zuhayr; Meissner, Helen I.; Stansbury, James P.
2011-01-01
HIV vaccine clinical research occurs within a context where biomedical science and social issues are interlinked. Previous HIV vaccine research has considered behavioral and social issues, but often treated them as independent of clinical research processes. Systematic attention to the intersection of behavioral and social issues within a defined clinical research framework is needed to address gaps, such as those related to participation in trials, completion of trials, and the overall research experience. Rigorous attention to these issues at project inception can inform trial design and conduct by matching research approaches to the context in which trials are to be conducted. Conducting behavioral and social sciences research concurrent with vaccine clinical research is important because it can help identify potential barriers to trial implementation, as well as ultimate acceptance and dissemination of trial results. We therefore propose a conceptual framework for behavioral and social science in HIV vaccine clinical research and use examples from the behavioral and social science literature to demonstrate how the model can facilitate identification of significant areas meriting additional exploration. Standardized use of the conceptual framework could improve HIV vaccine clinical research efficiency and relevance. PMID:21821083
Levy, Ronald; Ganjoo, Kristen N.; Leonard, John P.; Vose, Julie M.; Flinn, Ian W.; Ambinder, Richard F.; Connors, Joseph M.; Berinstein, Neil L.; Belch, Andrew R.; Bartlett, Nancy L.; Nichols, Craig; Emmanouilides, Christos E.; Timmerman, John M.; Gregory, Stephanie A.; Link, Brian K.; Inwards, David J.; Freedman, Arnold S.; Matous, Jeffrey V.; Robertson, Michael J.; Kunkel, Lori A.; Ingolia, Diane E.; Gentles, Andrew J.; Liu, Chih Long; Tibshirani, Robert; Alizadeh, Ash A.; Denney, Dan W.
2014-01-01
Purpose Idiotypes (Ids), the unique portions of tumor immunoglobulins, can serve as targets for passive and active immunotherapies for lymphoma. We performed a multicenter, randomized trial comparing a specific vaccine (MyVax), comprising Id chemically coupled to keyhole limpet hemocyanin (KLH) plus granulocyte macrophage colony-stimulating factor (GM-CSF) to a control immunotherapy with KLH plus GM-CSF. Patients and Methods Patients with previously untreated advanced-stage follicular lymphoma (FL) received eight cycles of chemotherapy with cyclophosphamide, vincristine, and prednisone. Those achieving sustained partial or complete remission (n = 287 [44%]) were randomly assigned at a ratio of 2:1 to receive one injection per month for 7 months of MyVax or control immunotherapy. Anti-Id antibody responses (humoral immune responses [IRs]) were measured before each immunization. The primary end point was progression-free survival (PFS). Secondary end points included IR and time to subsequent antilymphoma therapy. Results At a median follow-up of 58 months, no significant difference was observed in either PFS or time to next therapy between the two arms. In the MyVax group (n = 195), anti-Id IRs were observed in 41% of patients, with a median PFS of 40 months, significantly exceeding the median PFS observed in patients without such Id-induced IRs and in those receiving control immunotherapy. Conclusion This trial failed to demonstrate clinical benefit of specific immunotherapy. The subset of vaccinated patients mounting specific anti-Id responses had superior outcomes. Whether this reflects a therapeutic benefit or is a marker for more favorable underlying prognosis requires further study. PMID:24799467
Wang, Yuhuan; Vlasova, Anastasia; Velasquez, Daniel E.; Saif, Linda J.; Kandasamy, Sukumar; Kochba, Efrat; Levin, Yotam; Jiang, Baoming
2016-01-01
Live-attenuated oral rotavirus (RV) vaccines have lower efficacy in low income countries, and additionally are associated with a rare but severe adverse event, intussusception. We have been pursuing the development of an inactivated rotavirus vaccine (IRV) using the human rotavirus strain CDC-9 (G1P[8]) through parenteral immunization and previously demonstrated dose sparing and enhanced immunogenicity of intradermal (ID) unadjuvanted IRV using a coated microneedle patch in comparison with intramuscular (IM) administration in mice. The aim of this study was to evaluate the immune response and protection against RV infection and diarrhea conferred by the administration of the ID unadjuvanted IRV using the microneedle device MicronJet600® in neonatal gnotobiotic (Gn) piglets challenged with virulent Wa G1P[8] human RV. Three doses of 5 μg IRV when administered intradermally and 5 μg IRV formulated with aluminum hydroxide [Al(OH)3] when administered intramuscularly induced comparable rotavirus-specific antibody titers of IgA, IgG, IgG avidity index and neutralizing activity in sera of neonatal piglets. Both IRV vaccination regimens protected against RV antigen shedding in stools, and reduced the cumulative diarrhea scores in the piglets. This study demonstrated that the ID and IM administrations of IRV are immunogenic and protective against RV-induced diarrhea in neonatal piglets. Our findings highlight the potential value of an adjuvant sparing effect of the IRV ID delivery route. PMID:27824918
Le, Quoc Minh; Huong Tran, Thu; Huong Nguyen, Thanh; Khuyen Hoang, Thi; Binh Nguyen, Thanh; Do, Khanh Tung; Tran, Kim Anh; Hien Nguyen, Dang; Luan Le, Thi; Quy Nguyen, Thi; Dung Dang, Mai; Thu Nguyen, Nu Anh; Nguyen, Van Man
2012-09-01
We report for the first time the preparation of luminescent lanthanide nanomaterial (LLN) linked bioconjugates and their application as a label tool for recognizing virus in the processing line of vaccine industrial fabrication. Several LLNs with the nanostructure forms of particles or rods/wires with europium (III) and terbium (III) ions in lattices of vanadate, phosphate and metal organic complex were prepared to develop novel fluorescent conjugates able to be applied as labels in fluorescence immunoassay analysis of virus/vaccine. With regard to the LLNs, we have successfully synthesized nanoparticles around 10 nm of YVO4:Eu(III), with high emission in the red spectral region, nanorod and nanowire of TbPO4·H2O and Eu1-xTbxPO4·H2O, width 5-7 nm and length 300 nm, showing very bright luminescence in green, and core/shell nanosized Eu(III) and Tb(III)/Eu(III) complexes with naphthoyl trifluoroacetone and tri-n-octylphosphineoxide (Eu.NTA.TOPO@PVP, EuXTb1-X.NTA.TOPO). The appropriated core/shell structures can play a double role, one for enhancing luminescence efficiency and another for providing nanophosphors with better stability in water media for facilitating the penetration of nanophosphor core into a biomedical environment. The organic functionalizations of the obtained LLNs were done through their surface encapsulation with a functional polysiloxane including active groups such as amine (NH2), thiocyanate (SCN) or mecarpto (SH). The properties of functional sol-gel matrix have great influence on the luminescence properties, especially luminescence intensity of YVO4:Eu(III), Eu.NTA.TOPO@PVP, TbPO4·H2O and EuxTb1-xPO4·H2O. Bioconjugation processes of the functionalized LLNs have been studied with some bioactive molecules such as biotin, protein immunoglobulin G (IgG) or bovine serum albumin (BSA). The results of LLN-bioconjugate linking with IgG for recognizing virus (vaccine) will be presented in brief. It is consistent to state that the LLN bioconjugates prepared from YVO4:Eu(III)-nanoparticles, TbPO4·H2O nanorod or wire and EuNTA.TOPO@PVP nanosized core/shell complex could be used as labels for recognizing virus in diagnosis or in vaccine production by use of the fluorescence immunoassay (FIA) method. The fluorescence images of the incubated specimens consisting of LLN bioconjugate and vaccine fabricate could be obtained well in terms of sharpness, reproductivity and stability. However, much work still needs to be done to develop an ordinary LLN-conjugate using the FIA method for analysis of virus and, moreover, to extend the study of biomedical cell processes at nano/microscale in practical application.
Protsenko Project Role: Research Assistant Researcher Identifier (ORCID ID): N /A Nearest Person Month Worked: 2 Contribution to Project: Recruited and...586-592 (2015). 8. Zurcher, N . R. et al. NeuroImage Clin 7, 409-414 (2015). 9. Albrecht, D. S. et al. ACS Chem Neurosci 7(4), 470-83. 10. Lyoo, H. L...Edwards4, Ciprian Catana1, Oluwaseun Akeju4, George Cohen5, J. M. Hooker1, Vitaly Napadow1, M. L. Loggia1 1A. A. Martinos Center for Biomedical
Wang, Yuhuan; Vlasova, Anastasia; Velasquez, Daniel E; Saif, Linda J; Kandasamy, Sukumar; Kochba, Efrat; Levin, Yotam; Jiang, Baoming
2016-01-01
Live-attenuated oral rotavirus (RV) vaccines have lower efficacy in low income countries, and additionally are associated with a rare but severe adverse event, intussusception. We have been pursuing the development of an inactivated rotavirus vaccine (IRV) using the human rotavirus strain CDC-9 (G1P[8]) through parenteral immunization and previously demonstrated dose sparing and enhanced immunogenicity of intradermal (ID) unadjuvanted IRV using a coated microneedle patch in comparison with intramuscular (IM) administration in mice. The aim of this study was to evaluate the immune response and protection against RV infection and diarrhea conferred by the administration of the ID unadjuvanted IRV using the microneedle device MicronJet600® in neonatal gnotobiotic (Gn) piglets challenged with virulent Wa G1P[8] human RV. Three doses of 5 μg IRV when administered intradermally and 5 μg IRV formulated with aluminum hydroxide [Al(OH)3] when administered intramuscularly induced comparable rotavirus-specific antibody titers of IgA, IgG, IgG avidity index and neutralizing activity in sera of neonatal piglets. Both IRV vaccination regimens protected against RV antigen shedding in stools, and reduced the cumulative diarrhea scores in the piglets. This study demonstrated that the ID and IM administrations of IRV are immunogenic and protective against RV-induced diarrhea in neonatal piglets. Our findings highlight the potential value of an adjuvant sparing effect of the IRV ID delivery route.
personnel, collected data Funding Support: Name: Courtney Bergan Project Role: Research Assistant Researcher Identifier (ORCID ID): N /A Nearest...2015). 6. Owen, D. R. et al. Clin and Transl Imaging, 1-6 (2015). 7. Turkheimer, et al., Biochem Soc Trans 43(4), 586-592 (2015). 8. Zurcher, N . R. et...Oluwaseun Akeju4, George Cohen5, J. M. Hooker1, Vitaly Napadow1, M. L. Loggia1 1A. A. Martinos Center for Biomedical Imaging, Department of Radiology
In this work, we present a novel CMOS-based optical energy harvesting technology for implantable and Internet of Things (IoT) devices. In the proposed system, a CMOS energy-harvesting circuit accumulates a small amount of photoelectrically converted energy in an external capacitor, and intermittently supplies this power to a target device. Two optical energy-harvesting circuit types were implemented and evaluated. Furthermore, we developed a photoelectrically powered optical identification (ID) circuit that is suitable for IoT technology applications.
Vaccines represent one of the most compelling examples of how biomedical research has improved society by saving lives and dramatically reducing the burden of infectious disease. Despite the importance of vaccinology, we are still in the early stages of understanding how the best vaccines work and how we can achieve better protective efficacy through improved vaccine design. Most successful vaccines have been developed empirically, but recent advances in immunology are beginning to shed new light on the mechanisms of vaccine-mediated protection and development of long-term immunity. Although natural infection will often elicit lifelong immunity, almost all current vaccines require booster vaccination in order to achieve durable protective humoral immune responses, regardless of whether the vaccine is based on infection with replicating live-attenuated vaccine strains of the specific pathogen or whether they are derived from immunization with inactivated, non-replicating vaccines or subunit vaccines. The form of the vaccine antigen (e.g., soluble or particulate/aggregate) appears to play an important role in determining immunogenicity and the interactions between dendritic cells, B cells and T cells in the germinal center are likely to dictate the magnitude and duration of protective immunity. By learning how to optimize these interactions, we may be able to elicit more effective and long-lived immunity with fewer vaccinations. PMID:24709587
Albert B. Sabin, MD, developer of the oral polio vaccine, was also a major proponent of its use in annual vaccination campaigns aimed at the elimination of polio. Sabin argued that administering his vaccine simultaneously to every child in a country would break polio's chains of transmission. Although he was already promoting mass vaccination by the 1960s, Sabin's efforts expanded considerably when he became an adviser to groups fighting polio in the Americas in the 1980s. Sabin's experiences provide a window into both the formation of the coalition that eliminated poliomyelitis from the Western Hemisphere and what can happen when biomedical researchers become public health policy advisers. Although the polio elimination coalition succeeded in part because member groups often accommodated each other's priorities, Sabin was often limited by his indifference to the interests of those he was advising and to the shortcomings of his vaccine.
Albert B. Sabin, MD, developer of the oral polio vaccine, was also a major proponent of its use in annual vaccination campaigns aimed at the elimination of polio. Sabin argued that administering his vaccine simultaneously to every child in a country would break polio's chains of transmission. Although he was already promoting mass vaccination by the 1960s, Sabin's efforts expanded considerably when he became an adviser to groups fighting polio in the Americas in the 1980s. Sabin's experiences provide a window into both the formation of the coalition that eliminated poliomyelitis from the Western Hemisphere and what can happen when biomedical researchers become public health policy advisers. Although the polio elimination coalition succeeded in part because member groups often accommodated each other's priorities, Sabin was often limited by his indifference to the interests of those he was advising and to the shortcomings of his vaccine. PMID:19008524
Background Cervical cancer is the leading cause of female cancer-related deaths in Tanzania. Vaccination against human papillomavirus (HPV) offers a new opportunity to control this disease. This study aimed to estimate the costs of a school-based HPV vaccination project in three districts in Mwanza Region (NCT ID: NCT01173900), Tanzania and to model incremental scaled-up costs of a regional vaccination program. Methods We first conducted a top-down cost analysis of the vaccination project, comparing observed costs of age-based (girls born in 1998) and class-based (class 6) vaccine delivery in a total of 134 primary schools. Based on the observed project costs, we then modeled incremental costs of a scaled-up vaccination program for Mwanza Region from the perspective of the Tanzanian government, assuming that HPV vaccines would be delivered through the Expanded Programme on Immunization (EPI). Results Total economic project costs for delivering 3 doses of HPV vaccine to 4,211 girls were estimated at about US$349,400 (including a vaccine price of US$5 per dose). Costs per fully-immunized girl were lower for class-based delivery than for age-based delivery. Incremental economic scaled-up costs for class-based vaccination of 50,290 girls in Mwanza Region were estimated at US$1.3 million. Economic scaled-up costs per fully-immunized girl were US$26.41, including HPV vaccine at US$5 per dose. Excluding vaccine costs, vaccine could be delivered at an incremental economic cost of US$3.09 per dose and US$9.76 per fully-immunized girl. Financial scaled-up costs, excluding costs of the vaccine and salaries of existing staff were estimated at US$1.73 per dose. Conclusions Project costs of class-based vaccination were found to be below those of age-based vaccination because of more eligible girls being identified and higher vaccine uptake. We estimate that vaccine can be delivered at costs that would make HPV vaccination a very cost-effective intervention. Potentially, integrating HPV vaccine delivery with cost-effective school-based health interventions and a reduction of vaccine price below US$5 per dose would further reduce the costs per fully HPV-immunized girl. PMID:23148516
DNA immunization was discovered in early 1990s and its use has been expanded from vaccine studies to a broader range of biomedical research, such as the generation of high quality polyclonal and monoclonal antibodies as research reagents. In this unit, three common DNA immunization methods are described: needle injection, electroporation and gene gun. In addition, several common considerations related to DNA immunization are discussed. PMID:24510291
Cervical cancer is the leading cause of female cancer-related deaths in Tanzania. Vaccination against human papillomavirus (HPV) offers a new opportunity to control this disease. This study aimed to estimate the costs of a school-based HPV vaccination project in three districts in Mwanza Region (NCT ID: NCT01173900), Tanzania and to model incremental scaled-up costs of a regional vaccination program. We first conducted a top-down cost analysis of the vaccination project, comparing observed costs of age-based (girls born in 1998) and class-based (class 6) vaccine delivery in a total of 134 primary schools. Based on the observed project costs, we then modeled incremental costs of a scaled-up vaccination program for Mwanza Region from the perspective of the Tanzanian government, assuming that HPV vaccines would be delivered through the Expanded Programme on Immunization (EPI). Total economic project costs for delivering 3 doses of HPV vaccine to 4,211 girls were estimated at about US$349,400 (including a vaccine price of US$5 per dose). Costs per fully-immunized girl were lower for class-based delivery than for age-based delivery. Incremental economic scaled-up costs for class-based vaccination of 50,290 girls in Mwanza Region were estimated at US$1.3 million. Economic scaled-up costs per fully-immunized girl were US$26.41, including HPV vaccine at US$5 per dose. Excluding vaccine costs, vaccine could be delivered at an incremental economic cost of US$3.09 per dose and US$9.76 per fully-immunized girl. Financial scaled-up costs, excluding costs of the vaccine and salaries of existing staff were estimated at US$1.73 per dose. Project costs of class-based vaccination were found to be below those of age-based vaccination because of more eligible girls being identified and higher vaccine uptake. We estimate that vaccine can be delivered at costs that would make HPV vaccination a very cost-effective intervention. Potentially, integrating HPV vaccine delivery with cost-effective school-based health interventions and a reduction of vaccine price below US$5 per dose would further reduce the costs per fully HPV-immunized girl.
Botsis, Taxiarchis; Foster, Matthew; Kreimeyer, Kory; Pandey, Abhishek; Forshee, Richard
2017-01-01
Literature review is critical but time-consuming in the post-market surveillance of medical products. We focused on the safety signal of intussusception after the vaccination of infants with the Rotashield Vaccine in 1999 and retrieved all PubMed abstracts for rotavirus vaccines published after January 1, 1998. We used the Event-based Text-mining of Health Electronic Records system, the MetaMap tool, and the National Center for Biomedical Ontologies Annotator to process the abstracts and generate coded terms stamped with the date of publication. Data were analyzed in the Pattern-based and Advanced Network Analyzer for Clinical Evaluation and Assessment to evaluate the intussusception-related findings before and after the release of the new rotavirus vaccines in 2006. The tight connection of intussusception with the historical signal in the first period and the absence of any safety concern for the new vaccines in the second period were verified. We demonstrated the feasibility for semi-automated solutions that may assist medical reviewers in monitoring biomedical literature.
ZHURNAL MIKROBIOLOGII, EPIDEMIOLOGII I IMMUNOBIOLOGII, No 11, 1983) 135 Dehydrogenase Activity of Plague Vaccine Strains as Indirect Indicator of...Arabia 2. Israel 10. Syria 3. Indonesia 11. Thailand 4. Jordan 12. Turkey 5. Iraq 13. Philippines 6. Iran 14. Sri Lanka 7. Kuwait 15. Japan 8...established that the majority of bacterial toxins have a protein nature and have receptor and activator functions. The part of the toxin molecule that
DNA hairpin plays a critical role in the regulation of gene expression and DNA recombination. We studied the conformation of the DNA hairpin, d(ATCCAT-GTTA-TAGGAT) (PDB id:1AC7), employing molecular dynamics (MD) simulation. Despite the non-canonical Watson-Crick base pair (G:A) in the tetraloop (GTTA), MD simulation reveals that the conformation of the DNA hairpin is remarkably stable. In this study, we discuss about the physical/chemical origin of the stability of the DNA hairpin. Department of Biomedical Engineering, Korea University, Seoul 136-703, Korea.
Hoon Han, Sang; Hee Woo, Jun; Weber, Francoise; Joo Kim, Woo; Ran Peck, Kyong; Il Kim, Sang; Hwa Choi, Young; Myung Kim, June
2013-09-01
Intanza(®)/IDflu(®) (Sanofi Pasteur, Lyon, France) is an intradermal inactivated trivalent influenza vaccine developed as an alternative to intramuscular influenza vaccine. The objective of this study was to confirm the immunogenicity and safety of Intanza/IDflu in South Korean adults. In a phase IV multicenter trial, South Korean adults 18-59 y old (n = 120) and ≥ 60 y old (n = 120) were randomized 1:1 to receive a single dose of Intanza/IDflu (9 µg for 18-59 y, 15 µg for ≥ 60 y) or trivalent intramuscular vaccine (Vaxigrip(®) 15 µg, Sanofi Pasteur, Lyon, France). Blood was collected on pre-vaccination (day 0) and on day 21. Hemagglutination inhibition titers, seroprotection rates and seroconversion rates were determined on day 21. Geometric mean titers, seroprotection and seroconversion rates were similar between the intradermal and intramuscular vaccines in both age groups for all three vaccine strains (A/H1N1, A/H3N2 and B). Both vaccines met Committee for Medicinal Products for Human Use criteria for all three strains. Solicited systemic reactions of the intradermal groups were generally mild, transient, and similar to those of the intramuscular groups. Solicited injection site reactions were more frequent in the intradermal groups but were mostly mild, transient, and consisted mainly of pain, erythema, and pruritus. No treatment-related serious adverse events or other safety concerns were reported. These results confirm that Intanza/IDflu is an effective and well-tolerated alternative to IM influenza vaccination. (Clinicaltrials.gov NCT ID: NCT01215669).
Chitosan, a natural biodegradable polymer, is of great interest in biomedical research due to its excellent properties including bioavailability, nontoxicity, high charge density, and mucoadhesivity, which creates immense potential for various pharmaceutical applications. It has gelling properties when it interacts with counterions such as sulfates or polyphosphates and when it crosslinks with glutaraldehyde. This characteristic facilitates its usefulness in the coating or entrapment of biochemicals, drugs, antigenic molecules as a vaccine candidate, and microorganisms. Therefore, chitosan together with the advance of nanotechnology can be effectively applied as a carrier system for vaccine delivery. In fact, chitosan microspheres have been studied as a promising carrier system for mucosal vaccination, especially via the oral and nasal route to induce enhanced immune responses. Moreover, the thiolated form of chitosan is of considerable interest due to its improved mucoadhesivity, permeability, stability, and controlled/extended release profile. This review describes the various methods used to design and synthesize chitosan microspheres and recent updates on their potential applications for oral and nasal delivery of vaccines. The potential use of thiolated chitosan microspheres as next-generation mucosal vaccine carriers is also discussed. PMID:23271909
Disaster-affected populations are highly vulnerable to outbreaks of measles. Therefore, a mass vaccination against measles was conducted in Aila cyclone-affected blocks of West Bengal, India in July 2009. The objectives of the present report were to conduct an in depth analysis of the campaign, and to discuss the major challenges. A block level micro-plan, which included mapping of the villages, health facilities, temporary settlements of disaster-affected population, communications available, formation of vaccination team, information education communication, vaccine storage, waste disposal, surveillance for adverse events following immunization, supervision and monitoring was developed. The rate of six months to five years old children, who were vaccinated by measles vaccine, was 70.7% and that of those who received one dose of vitamin A was 71.3%. Wastage factor for vaccine doses and auto-disable syringes were 1.09 and 1.07, respectively. Only 13 cases of adverse events following immunization were reported. An average of 0.91 puncture-proof containers per vaccination session was used. Despite the major challenges faced due to difficult to reach areas, inadequate infrastructure, manpower and communication, problems of vaccine storage and transport, the campaign achieved a remarkable success regarding measles vaccine coverage, improvements of cold chain infrastructure, formulating an efficient surveillance and reporting system for adverse events following immunization, building self-confidence of the stakeholders, and developing a biomedical waste disposal system. PMID:23115416
A system of ambulatory, halter, electrocardiography (ECG) monitoring system has already been commercially available for recording and transmitting heartbeats data by the Internet. However, it enjoys the confidence with a reservation and thus a limited market penetration, our system was targeting at aging global villagers having an increasingly biomedical wellness (BMW) homecare needs, not hospital related BMI (biomedical illness). It was designed within SWaP-C (Size, Weight, and Power, Cost) using 3 innovative modules: (i) Smart Electrode (lowpower mixed signal embedded with modern compressive sensing and nanotechnology to improve the electrodes' contact impedance); (ii) Learnable Database (in terms of adaptive wavelets transform QRST feature extraction, Sequential Query Relational database allowing home care monitoring retrievable Aided Target Recognition); (iii) Smartphone (touch screen interface, powerful computation capability, caretaker reporting with GPI, ID, and patient panic button for programmable emergence procedure). It can provide a supplementary home screening system for the post or the pre-diagnosis care at home with a build-in database searchable with the time, the place, and the degree of urgency happened, using in-situ screening.
Disaster-affected populations are highly vulnerable to outbreaks of measles. Therefore, a mass vaccination against measles was conducted in Aila cyclone-affected blocks of West Bengal, India in July 2009. The objectives of the present report were to conduct an in depth analysis of the campaign, and to discuss the major challenges. A block level micro-plan, which included mapping of the villages, health facilities, temporary settlements of disaster-affected population, communications available, formation of vaccination team, information education communication, vaccine storage, waste disposal, surveillance for adverse events following immunization, supervision and monitoring was developed. The rate of six months to five years old children, who were vaccinated by measles vaccine, was 70.7% and that of those who received one dose of vitamin A was 71.3%. Wastage factor for vaccine doses and auto-disable syringes were 1.09 and 1.07, respectively. Only 13 cases of adverse events following immunization were reported. An average of 0.91 puncture-proof containers per vaccination session was used. Despite the major challenges faced due to difficult to reach areas, inadequate infrastructure, manpower and communication, problems of vaccine storage and transport, the campaign achieved a remarkable success regarding measles vaccine coverage, improvements of cold chain infrastructure, formulating an efficient surveillance and reporting system for adverse events following immunization, building self-confidence of the stakeholders, and developing a biomedical waste disposal system.
Martzoukos, Yannis; Papavlasopoulos, Sozon; Poulos, Marios; Syrrou, Maria
2017-01-01
In recent years there has been an increasingly amount of data stored in biomedical Databases due to the breakthroughs in biology and bioinformatics, biomedical information is growing exponentially making efficient information retrieval from scientist more and more challenging. New Scientific fields as Bioinformatics seem to be the tool needed to extract scientifically important data based on experimental results and information provided by papers and journals. In this paper we are going to implement a custom made IT system in order to find connections between genes in the breast cancer pathways such the BRCA1 with the electrical energy in the human brain with UGDH gene via the TP53 tumor gene. The proposed system will be able to identify the appearance of each gene ID and compare the coexistence of two genes in PubMed articles/papers. The final system could become a useful tool against the struggle of scientists and medical professionals in the near future.
Although vaccination has prevented millions of deaths, the development of highly immunogenic subunit vaccines is still required. Since the number of adjuvants approved for human use is limited, the new paths for the development of delivery vehicles offered by nanotechnology are of key relevance. Areas covered: Herein, the potential of silica nanoparticles (SP) as both adjuvants and vaccine delivery vehicles is discussed based on the analysis of the current biomedical literature. Expert commentary: SP are reported not only as biodegradable and biocompatible material but also as easy to modify and with a low production cost. Additionally, several reports suggest that SP enhance the immune response. Therefore, SP are a promising delivery vehicle and/or adjuvant in vaccines. However, knowledge on the industrial production and specific aspects of immunity are still required.
In order to ensure the quality of biomedical products, an experimental test for every single manufactured batch is required for many products. Especially in vaccine testing, animal experiments are traditionally used for this purpose. For example, efficacy is often determined via challenge experiments in laboratory animals. Safety tests of vaccine batches are also mostly performed using laboratory animals. However, many animal experiments have clear inherent disadvantages (low accuracy, questionable transferability to humans, unclear significance). Furthermore, for ethical reasons and animal welfare aspects animal experiments are also seen very critical by the public. Therefore, there is a strong trend towards replacing animal experiments with methods in which no animals are used ("replacement"). If a replacement is not possible, the required animal experiments should be improved in order to minimize the number of animals necessary ("reduction") and to reduce pain and suffering caused by the experiment to a minimum ("refinement"). This "3R concept" is meanwhile firmly established in legislature. In recent years many mandatory animal experiments have been replaced by alternative in vitro methods or improved according to the 3R principles; numerous alternative methods are currently under development. Nevertheless, the process from the development of a new method to its legal implementation takes a long time. Therefore, supplementary regulatory measures to facilitate validation and acceptance of new alternative methods could contribute to a faster and more consequent implementation of the 3R concept in the testing of biomedical products.
To examine perceptions of phase-I human immunodeficiency virus (HIV) vaccine trial participation among African-Americans and Hispanics in San Francisco, California. Qualitative, semistructured interviews. San Francisco Department of Health. Thirty-six African-American and Hispanic men and women, 18 to 50 years of age, residing in the San Francisco Bay Area. Purposive sampling using advertisements, community-based organization rosters, and snowball referrals. Thematic analysis of transcripts identified salient themes and patterns. Participants viewed participation in HIV research as important; however, they held that HIV was not a health priority given limited awareness about HIV research or beliefs that only infected or high-risk persons were eligible for participation. Altruism and personal gain, trustworthy trial staff, convenient schedules and facilities, and involvement of trusted community groups in recruitment were perceived to motivate participants. Concerns about the social consequences of participating in HIV research and product-related side effects were seen as discouraging participation. Limitations include the possibility that participants in interview research have more favorable views of biomedical research than those who refuse to participate. Historically, African-Americans and Hispanics in the United States have had limited participation in HIV trials. Understanding their perceptions of HIV biomedical research, identifying facilitators and barriers to participation, addressing misinformation about HIV, distorted risk perceptions, HIV stigma, and providing accessible opportunities to participate are imperative to ensure health equity and generalizability of findings.
Synthetic biology is a relatively new field with the key aim of designing and constructing biological systems with novel functionalities. Today, synthetic biology devices are making their first steps in contributing new solutions to a number of biomedical challenges, such as emerging bacterial antibiotic resistance and cancer therapy. This review discusses some synthetic biology approaches and applications that were recently used in disease mechanism investigation and disease modeling, drug discovery and production, as well as vaccine development and treatment of infectious diseases, cancer, and metabolic disorders.
Synthetic biology is a relatively new field with the key aim of designing and constructing biological systems with novel functionalities. Today, synthetic biology devices are making their first steps in contributing new solutions to a number of biomedical challenges, such as emerging bacterial antibiotic resistance and cancer therapy. This review discusses some synthetic biology approaches and applications that were recently used in disease mechanism investigation and disease modeling, drug discovery and production, as well as vaccine development and treatment of infectious diseases, cancer, and metabolic disorders.
Synthetic biology is a relatively new field with the key aim of designing and constructing biological systems with novel functionalities. Today, synthetic biology devices are making their first steps in contributing new solutions to a number of biomedical challenges, such as emerging bacterial antibiotic resistance and cancer therapy. This review discusses some synthetic biology approaches and applications that were recently used in disease mechanism investigation and disease modeling, drug discovery and production, as well as vaccine development and treatment of infectious diseases, cancer, and metabolic disorders. PMID:25098838
Ross, Ted M; Pereira, Lara E; Luckay, Amara; McNicholl, Janet M; García-Lerma, J Gerardo; Heneine, Walid; Eugene, Hermancia S; Pierce-Paul, Brooke R; Zhang, Jining; Hendry, R Michael; Smith, James M
2014-11-01
Vaccination and preexposure prophylaxis (PrEP) with antiretrovirals have shown only partial protection from HIV-1 infection in human trials. Oral Truvada (emtricitabine/tenofovir disoproxil fumarate) is FDA approved as PrEP but partial adherence reduces efficacy. If combined as biomedical preventions (CBP), an HIV vaccine could protect when PrEP adherence is low and PrEP could prevent vaccine breakthroughs. The efficacy of combining oral PrEP with an HIV vaccine has not been evaluated in humans. We determined the efficacy of combining a DNA/virus-like particle (VLP) vaccine with partially effective intermittent PrEP in Indian rhesus macaques (RM). Eight RM received intramuscular inoculations of five DNA plasmids encoding four HIV-1 Clade B primary isolate Envs and SIVmac239 Gag (at weeks 0 and 4), followed by intramuscular and intranasal inoculations of homologous Gag VLPs and four Env VLPs (at weeks 12, 16, and 53). At week 61, we initiated weekly rectal exposures with heterologous SHIV162p3 (10 TCID50) along with oral Truvada (TDF, 22 mg/kg; FTC 20 mg/kg) dosing 2 h before and 22 h after each exposure. This PrEP regimen previously demonstrated 50% efficacy. Five controls (no vaccine, no PrEP) received weekly SHIV162p3. All controls were infected after a median of four exposures; the mean peak plasma viral load (VL) was 3.9×10(7) vRNA copies/ml. CBP protected seven of eight (87.5%) RM. The one infected CBP RM had a reduced peak VL of 8.8×10(5) copies/ml. SHIV exposures during PrEP amplified Gag and Env antibody titers in protected RM. These results suggest that combining oral PrEP with HIV vaccines could enhance protection against HIV-1 infection.
In March 1930, reports of the discovery of an organism causative of multiple sclerosis circulated in the British press. At the same time, news of a therapeutically efficacious vaccine also reached the ears of neurologists and patients afflicted with the debilitating degenerative disease. It was soon shown that no organism had been discovered. The events leading up to this ultimately painful episode reveal many of the central problems created when social conventions and a sense of decorum scripted received understanding of good scientific practice rather than actual regulatory frameworks. In the absence of such frameworks, few means were present to censor inappropriate scientific conduct. This story thus provides a window into an emergent world of state-sponsored biomedical research; a world where recrimination, gossip, misogyny, uncertainty, exaggeration, and dreams and delusions of scientific and therapeutic progress were collapsed together. PMID:20478897
Cardenas, L.; MacLeod, J.; Lipton-Duffin, J.; Seifu, D. G.; Popescu, F.; Siaj, M.; Mantovani, D.; Rosei, F.
2014-07-01
We report a new method for the growth of reduced graphene oxide (rGO) on the 316L alloy of stainless steel (SS) and its relevance for biomedical applications. We demonstrate that electrochemical etching increases the concentration of metallic species on the surface and enables the growth of rGO. This result is supported through a combination of Raman spectroscopy, X-ray photoelectron spectroscopy (XPS), atomic force microscopy (AFM), scanning electron microscopy (SEM), density functional theory (DFT) calculations and static water contact angle measurements. Raman spectroscopy identifies the G and D bands for oxidized species of graphene at 1595 cm-1 and 1350 cm-1, respectively, and gives an ID/IG ratio of 1.2, indicating a moderate degree of oxidation. XPS shows -OH and -COOH groups in the rGO stoichiometry and static contact angle measurements confirm the wettability of rGO. SEM and AFM measurements were performed on different substrates before and after coronene treatment to confirm rGO growth. Cell viability studies reveal that these rGO coatings do not have toxic effects on mammalian cells, making this material suitable for biomedical and biotechnological applications.
Reconstructing some of the experiences of people living with tuberculosis in Argentina in the first half of the twentieth century, as reflected not only in written and oral accounts but also in individual and collective actions, this article explores the ways in which patients came to grips with medical expertise in times of biomedical uncertainty. These negotiations, which inevitably included adaptations as well as confrontations, highlight a much less passive and submissive patient-physician relationship than is often assumed. Though patients were certainly subordinate to medical doctors' knowledge and practices, that subordination, far from absolute, was limited and often overthrown. The article focuses on patients' demands to gain access to a vaccine not approved by the medical establishment. By engaging with media organizations, the sick invoked their "right to health" in order to obtain access to experimental treatments when biomedicine was unable to deliver efficient therapies.
Juárez-Montiel, Margarita; Romero-Maldonado, Andrea; Monreal-Escalante, Elizabeth; Becerra-Flora, Alicia; Korban, Schuyler S; Rosales-Mendoza, Sergio; Jiménez-Bremont, Juan Francisco
2015-01-01
The development of new alternative platforms for subunit vaccine production is a priority in the biomedical field. In this study, Ustilago maydis, the causal agent of common corn smut or 'huitlacoche'has been genetically engineered to assess expression and immunogenicity of the B subunit of the cholera toxin (CTB), a relevant immunomodulatory agent in vaccinology. An oligomeric CTB recombinant protein was expressed in corn smut galls at levels of up to 1.3 mg g-1 dry weight (0.8% of the total soluble protein). Mice orally immunized with 'huitlacoche'-derived CTB showed significant humoral responses that were well-correlated with protection against challenge with the cholera toxin (CT). These findings demonstrate the feasibility of using edible corn smut as a safe, effective, and low-cost platform for production and delivery of a subunit oral vaccine. The implications of this platform in the area of molecular pharming are discussed.
Juárez-Montiel, Margarita; Romero-Maldonado, Andrea; Monreal-Escalante, Elizabeth; Becerra-Flora, Alicia; Korban, Schuyler S.; Rosales-Mendoza, Sergio; Jiménez-Bremont, Juan Francisco
2015-01-01
The development of new alternative platforms for subunit vaccine production is a priority in the biomedical field. In this study, Ustilago maydis, the causal agent of common corn smut or ‘huitlacoche’has been genetically engineered to assess expression and immunogenicity of the B subunit of the cholera toxin (CTB), a relevant immunomodulatory agent in vaccinology. An oligomeric CTB recombinant protein was expressed in corn smut galls at levels of up to 1.3 mg g-1 dry weight (0.8% of the total soluble protein). Mice orally immunized with ‘huitlacoche’-derived CTB showed significant humoral responses that were well-correlated with protection against challenge with the cholera toxin (CT). These findings demonstrate the feasibility of using edible corn smut as a safe, effective, and low-cost platform for production and delivery of a subunit oral vaccine. The implications of this platform in the area of molecular pharming are discussed. PMID:26207365
Abdur-Rashid, Khalil; Furber, Steven Woodward; Abdul-Basser, Taha
2013-04-01
We survey the meta-ethical tools and institutional processes that traditional Islamic ethicists apply when deliberating on bioethical issues. We present a typology of these methodological elements, giving particular attention to the meta-ethical techniques and devices that traditional Islamic ethicists employ in the absence of decisive or univocal authoritative texts or in the absence of established transmitted cases. In describing how traditional Islamic ethicists work, we demonstrate that these experts possess a variety of discursive tools. We find that the ethical responsa-i.e., the products of the application of the tools that we describe-are generally characterized by internal consistency. We also conclude that Islamic ethical reasoning on bioethical issues, while clearly scripture-based, is also characterized by strong consequentialist elements and possesses clear principles-based characteristics. The paper contributes to the study of bioethics by familiarizing non-specialists in Islamic ethics with the role, scope, and applicability of key Islamic ethical concepts, such as "aims" (maqāṣid), "universals" (kulliyyāt), "interest" (maṣlaḥa), "maxims" (qawā`id), "controls" (ḍawābit), "differentiators" (furūq), "preponderization" (tarjīḥ), and "extension" (tafrī`).
The sciences of vaccinology and of immunology were created just two centuries ago by Jenner's scientific studies of prevention of smallpox through inoculation with cowpox virus. This rudimentary beginning was expanded greatly by the giants of late 19th and early twentieth centuries biomedical sciences. The period from 1930 to 1950 was a transitional era with the introduction of chick embryos and minced tissues for propagating viruses and Rickettsiae in vitro for vaccines. Modern era vaccinology began about 1950 as a continuum following notable advances made during the 1940s and World War II. Its pursuit has been based largely on breakthroughs in cell culture, bacterial polysaccharide chemistry, molecular biology and immunology, which have yielded many live and killed viral and bacterial vaccines plus the recombinant-expressed hepatitis B vaccine. The present paper was presented as a lecture given(1) on August 30, 1999 and recounts, by invitation, more than five-and-half decades of vaccine research from the venue of personal experience and attainment by the author. The paper is intentionally brief and truncated with focus only on highlights and limited referencing. Detailed recounting and referencing are given elsewhere in text references [Hilleman MR. Six decades of vaccine development - a personal history. Nat. Med. 1998;4 (Vaccine Suppl.): 507-14] and [Hilleman MR. Personal historical chronicle of six decades of basic and applied research in virology, immunology and vaccinology. Immunol. Rev. (in press)]. This narration will have achieved its purpose if it provides a background of understanding and guidelines that will assist others who seek to engage in creation of new vaccines.
New biomedical prevention technologies (NPTs) may contribute to substantially reducing incident HIV infections globally. We explored acceptability and preferences for NPTs among key and other vulnerable populations in two South African townships. We conducted six focus groups and 12 in-depth interviews with adolescents, and adult heterosexual men, women, and men who have sex with men (MSM) (n = 48), and eight in-depth interviews with key informant healthcare workers. The interview guide described pre-exposure prophylaxis (PrEP), vaginal rings, rectal microbicides and HIV vaccines, and explored acceptability and product preferences. Focus groups and in-depth interviews (45-80 minutes) were conducted in Xhosa, audiotaped, and transcribed and translated into English. Data were coded and reviewed using framework analysis with NVivo software. Overall, initial enthusiasm and willingness to use NPTs evolved into concerns about how particular NPTs might affect or require alterations in one's everyday lifestyle and practices. Different product preferences and motivations emerged by population based on similarity to existing practices and contexts of vulnerability. Adult women and female adolescents preferred a vaginal ring and HIV vaccine, motivated by longer duration of protection to mitigate feared repercussions from male partners, including threats to their marriage and safety, and a context of ubiquitous rape. Male adolescents preferred an HIV vaccine, seen as protection in serodiscordant relationships and convenient in obviating the HIV stigma and cost involved in buying condoms. Adult men preferred PrEP, given familiarity with oral medications and mistrust of injections, seen as enabling serodiscordant couples to have a child. MSM preferred a rectal microbicide given familiarity with gel-based lubricants, with concerns about duration of protection in the context of unplanned consensual sex and rape. Biomedical interventions to prevent HIV transmission, rather than obviating social-structural factors that produce vulnerability, may be limited by these same factors. Implementation of NPTs should engage local communities to understand real-world constraints and strategise to deliver effective, multi-level combination prevention.
Natural pharmaceutical excipients have been applied extensively in the past decades owing to their safety and biocompatibility. Zein, a natural protein of plant origin offers great benefit over other synthetic polymers used in controlled drug and biomedical delivery systems. It was used in a variety of medical fields including pharmaceutical and biomedical drug targeting, vaccine, tissue engineering, and gene delivery. Being biodegradable and biocompatible, the current review focuses on the history and the medical application of zein as an attractive still promising biopolymer. Areas covered: The current review gives a broadscope on zein as a still promising protein excipient in different fields. Zein- based drug and biomedical delivery systems are discussed with special focus on current and potential application in controlled drug delivery systems, and tissue engineering. Expert opinion: Zein as a protein of natural origin can still be considered a promising polymer in the field of drug delivery systems as well as in tissue engineering. Although different researchers spotted light on zein application in different industrial fields extensively, the feasibility of its use in the field of drug delivery replenished by investigators in recent years has not yet been fully approached.
Frise, Matthew C.; Cheng, Hung-Yuan; Nickol, Annabel H.; Curtis, M. Kate; Pollard, Karen A.; Roberts, David J.; Ratcliffe, Peter J.; Dorrington, Keith L.; Robbins, Peter A.
2016-01-01
BACKGROUND. Iron bioavailability has been identified as a factor that influences cellular hypoxia sensing, putatively via an action on the hypoxia-inducible factor (HIF) pathway. We therefore hypothesized that clinical iron deficiency would disturb integrated human responses to hypoxia. METHODS. We performed a prospective, controlled, observational study of the effects of iron status on hypoxic pulmonary hypertension. Individuals with absolute iron deficiency (ID) and an iron-replete (IR) control group were exposed to two 6-hour periods of isocapnic hypoxia. The second hypoxic exposure was preceded by i.v. infusion of iron. Pulmonary artery systolic pressure (PASP) was serially assessed with Doppler echocardiography. RESULTS. Thirteen ID individuals completed the study and were age- and sex-matched with controls. PASP did not differ by group or study day before each hypoxic exposure. During the first 6-hour hypoxic exposure, the rise in PASP was 6.2 mmHg greater in the ID group (absolute rises 16.1 and 10.7 mmHg, respectively; 95% CI for difference, 2.7–9.7 mmHg, P = 0.001). Intravenous iron attenuated the PASP rise in both groups; however, the effect was greater in ID participants than in controls (absolute reductions 11.1 and 6.8 mmHg, respectively; 95% CI for difference in change, –8.3 to –0.3 mmHg, P = 0.035). Serum erythropoietin responses to hypoxia also differed between groups. CONCLUSION. Clinical iron deficiency disturbs normal responses to hypoxia, as evidenced by exaggerated hypoxic pulmonary hypertension that is reversed by subsequent iron administration. Disturbed hypoxia sensing and signaling provides a mechanism through which iron deficiency may be detrimental to human health. TRIAL REGISTRATION. ClinicalTrials.gov (NCT01847352). FUNDING. M.C. Frise is the recipient of a British Heart Foundation Clinical Research Training Fellowship (FS/14/48/30828). K.L. Dorrington is supported by the Dunhill Medical Trust (R178/1110). D.J. Roberts was supported by R&D funding from National Health Service (NHS) Blood and Transplant and a National Institute for Health Research (NIHR) Programme grant (RP-PG-0310-1004). This research was funded by the NIHR Oxford Biomedical Research Centre Programme. PMID:27140401
Cervical cancer is the fourth most common neoplasm in women worldwide and its incidence is associated with profound social inequities. In Chile, it is the second cause of death in women of reproductive age. The Chilean clinical guideline identifies the vaccine against Human Papillomavirus (HPV) as the main preventive measure. Since 2014, the Ministry of Health has implemented free immunization against HPV for girls and female adolescents. This article critically analyzes this public policy from the viewpoint of health equity, using as framework the Social Determinants of Health Model. Specifically, we address the structural determinants of income and gender, which act as material and social barriers for achieving immunization, affecting protection against cervical cancer. These barriers correspond to the high cost of the vaccine, and social attitudes/cultural beliefs towards sexual behavior in Latin America and Chile that affect the acceptability of vaccination. The Social Determinants of Health Model constitutes a useful tool for identifying health inequities and understanding public policy from an equity viewpoint that complements the biomedical and epidemiological understanding of disease. In this topic, the initiative aims to strengthen the idea of health as a human right and health promotion as an essential function of public health policy.
Bellino, S; Francavilla, V; Longo, O; Tripiciano, A; Paniccia, G; Arancio, A; Fiorelli, V; Scoglio, A; Collacchi, B; Campagna, M; Lazzarin, A; Tambussi, G; Din, C Tassan; Visintini, R; Narciso, P; Antinori, A; D'Offizi, G; Giulianelli, M; Carta, M; Di Carlo, A; Palamara, G; Giuliani, M; Laguardia, M E; Monini, P; Magnani, M; Ensoli, F; Ensoli, B
2009-09-01
The native HIV-1 Tat protein was chosen as vaccine candidate for phase I clinical trials in both uninfected (ClinicalTrials.gov identifier: NCT00529698) and infected volunteers (ClinicalTrials.gov identifier: NCT00505401). The rationale was based on the role of Tat in the natural infection and AIDS pathogenesis, on the association of Tat-specific immune responses with the asymptomatic stage and slow-progression rate as well as on its sequence conservation among HIV clades (http://www.hiv1tat-vaccines.info/). The parallel conduction in the same clinical centers of randomized, double blind, placebo-controlled phase I studies both in healthy, immunologically competent adults and in HIV-infected, clinically asymptomatic, individuals represents a unique occasion to compare the vaccine-induced immune response in both the preventive and therapeutic setting. In both studies, the same lot of the native Tat protein was administered 5 times, every four weeks, subcute (SC) with alum adjuvant or intradermic (ID), in the absence of adjuvant, at 7.5 microg, 15 microg or 30 microg doses, respectively. The primary and secondary endpoints of these studies were the safety and immunogenicity of the vaccine candidate, respectively. The study lasted 52 weeks and monitoring was conducted for on additional 3 years. The results of both studies indicated that the Tat vaccine is safe and well tolerated both locally and systemically and it is highly immunogenic at all the dosages and by both routes of administration. Vaccination with Tat induced a balanced immune response in uninfected and infected individuals. In particular, therapeutic immunization induced functional antibodies and partially reverted the marked Th1 polarization of anti-Tat immunity seen in natural infection, and elicited a more balanced Th1/Th2 immune response. Further, the number of CD4 T cells correlated positively with anti-Tat antibody titers. Based on these results, a phase II study is ongoing in infected drug-treated individuals (http://www.hiv1tat-vaccines.info/).
Pearson, Frances E; McNeilly, Celia L; Crichton, Michael L; Primiero, Clare A; Yukiko, Sally R; Fernando, Germain J P; Chen, Xianfeng; Gilbert, Sarah C; Hill, Adrian V S; Kendall, Mark A F
2013-01-01
The disadvantages of needle-based immunisation motivate the development of simple, low cost, needle-free alternatives. Vaccine delivery to cutaneous environments rich in specialised antigen-presenting cells using microprojection patches has practical and immunological advantages over conventional needle delivery. Additionally, stable coating of vaccine onto microprojections removes logistical obstacles presented by the strict requirement for cold-chain storage and distribution of liquid vaccine, or lyophilised vaccine plus diluent. These attributes make these technologies particularly suitable for delivery of vaccines against diseases such as malaria, which exerts its worst effects in countries with poorly-resourced healthcare systems. Live viral vectors including adenoviruses and poxviruses encoding exogenous antigens have shown significant clinical promise as vaccines, due to their ability to generate high numbers of antigen-specific T cells. Here, the simian adenovirus serotype 63 and the poxvirus modified vaccinia Ankara--two vectors under evaluation for the delivery of malaria antigens to humans--were formulated for coating onto Nanopatch microprojections and applied to murine skin. Co-formulation with the stabilising disaccharides trehalose and sucrose protected virions during the dry-coating process. Transgene-specific CD8(+) T cell responses following Nanopatch delivery of both vectors were similar to intradermal injection controls after a single immunisation (despite a much lower delivered dose), though MVA boosting of pre-primed responses with Nanopatch was found to be less effective than the ID route. Importantly, disaccharide-stabilised ChAd63 could be stored for 10 weeks at 37°C with less than 1 log10 loss of viability, and retained single-dose immunogenicity after storage. These data support the further development of microprojection patches for the deployment of live vaccines in hot climates.
Pearson, Frances E.; McNeilly, Celia L.; Crichton, Michael L.; Primiero, Clare A.; Yukiko, Sally R.; Fernando, Germain J. P.; Chen, Xianfeng; Gilbert, Sarah C.; Hill, Adrian V. S.; Kendall, Mark A. F.
2013-01-01
The disadvantages of needle-based immunisation motivate the development of simple, low cost, needle-free alternatives. Vaccine delivery to cutaneous environments rich in specialised antigen-presenting cells using microprojection patches has practical and immunological advantages over conventional needle delivery. Additionally, stable coating of vaccine onto microprojections removes logistical obstacles presented by the strict requirement for cold-chain storage and distribution of liquid vaccine, or lyophilised vaccine plus diluent. These attributes make these technologies particularly suitable for delivery of vaccines against diseases such as malaria, which exerts its worst effects in countries with poorly-resourced healthcare systems. Live viral vectors including adenoviruses and poxviruses encoding exogenous antigens have shown significant clinical promise as vaccines, due to their ability to generate high numbers of antigen-specific T cells. Here, the simian adenovirus serotype 63 and the poxvirus modified vaccinia Ankara – two vectors under evaluation for the delivery of malaria antigens to humans – were formulated for coating onto Nanopatch microprojections and applied to murine skin. Co-formulation with the stabilising disaccharides trehalose and sucrose protected virions during the dry-coating process. Transgene-specific CD8+ T cell responses following Nanopatch delivery of both vectors were similar to intradermal injection controls after a single immunisation (despite a much lower delivered dose), though MVA boosting of pre-primed responses with Nanopatch was found to be less effective than the ID route. Importantly, disaccharide-stabilised ChAd63 could be stored for 10 weeks at 37°C with less than 1 log10 loss of viability, and retained single-dose immunogenicity after storage. These data support the further development of microprojection patches for the deployment of live vaccines in hot climates. PMID:23874462
Reducing the incidence of HIV infection continues to be a crucial public health priority in the United States, especially among populations at elevated risk such as men who have sex with men, transgender women, people who inject drugs, and racial and ethnic minority communities. Although most HIV prevention efforts to date have focused on changing risky behaviors, the past decade has yielded efficacious new biomedical technologies designed to prevent infection, such as the prophylactic use of antiretroviral drugs and the first indications of an efficacious vaccine. Access to prevention technologies will be a significant part of the next decade’s response to HIV, and advocates are mobilizing to achieve more widespread use of these interventions. These breakthroughs, however, arrive at a time of escalating healthcare costs; health insurance coverage therefore raises pressing new questions about priority-setting and the allocation of responsibility for public health. The goals of this Article are to identify legal challenges and potential solutions for expanding access to biomedical HIV prevention through health insurance coverage. This Article discusses the public policy implications of HIV prevention coverage decisions, assesses possible legal grounds on which insurers may initially deny coverage for these technologies, and evaluates the extent to which these denials may survive external and judicial review. Because several of these legal grounds may be persuasive, particularly denials on the basis of medical necessity, this Article also explores alternative strategies for financing biomedical HIV prevention efforts. PMID:23356098
Frew, Paula M; Archibald, Matthew; Diallo, Dazon Dixon; Hou, Su-I; Horton, Takeia; Chan, Kayshin; Mulligan, Mark J; del Rio, Carlos
2010-06-01
In the United States, the number and proportion of HIV/AIDS cases among black/African Americans continue to highlight the need for new biomedical prevention interventions, including an HIV vaccine, microbicide, or new antiretroviral (ARV) prevention strategies such as pre-exposure prophylaxis (PrEP) to complement existing condom usage, harm reduction methods, and behavioral change strategies to stem the HIV epidemic. Although black/African Americans are disproportionately impacted by HIV/AIDS, their participation in HIV clinical research continues to have unique challenges. We theorize that interaction among multilevel factors creates ideal alignment for minority participation in HIV clinical studies. Thus, we initially set out to test an extended model of reasoned action with 362 participants to understand the interplay of sociopsychological and network-level considerations influencing minority participation in HIV prevention research efforts. In this study, we linked the intrapersonal dimensions of attitudes, beliefs, and normative concerns to community-level components, appraisal of involvement with the clinical research organization, an entity which operates within a networked structure of community partner agencies, and identification with coalition advocacy aims. Various participatory outcomes were explored including involvement in future HIV vaccine community functions, participation in community promotion of HIV vaccine research, and community mobilization. Three-stage least squares estimates indicated similar findings across three models. Significant effects demonstrate the importance of positive attitudes toward HIV vaccine research, favorable health research beliefs, perceived social support for participation, HIV/AIDS issue engagement, and perceived relevance of the clinical research site's mission and values. Identification of these nuanced pathway effects provides implications for tailored community program development.
Frew, Paula M.; Archibald, Matthew; Diallo, Dazon Dixon; Hou, Su-I; Horton, Takeia; Chan, Kayshin; Mulligan, Mark J.; del Rio, Carlos
2010-01-01
In the United States, the number and proportion of HIV/AIDS cases among black/African Americans continue to highlight the need for new biomedical prevention interventions, including an HIV vaccine, microbicide, or new antiretroviral (ARV) prevention strategies such as pre-exposure prophylaxis (PrEP) to complement existing condom usage, harm reduction methods, and behavioral change strategies to stem the HIV epidemic. Although black/African Americans are disproportionately impacted by HIV/AIDS, their participation in HIV clinical research continues to have unique challenges. We theorize that interaction among multilevel factors creates ideal alignment for minority participation in HIV clinical studies. Thus, we initially set out to test an extended model of reasoned action with 362 participants to understand the interplay of sociopsychological and network-level considerations influencing minority participation in HIV prevention research efforts. In this study, we linked the intrapersonal dimensions of attitudes, beliefs, and normative concerns to community-level components, appraisal of involvement with the clinical research organization, an entity which operates within a networked structure of community partner agencies, and identification with coalition advocacy aims. Various participatory outcomes were explored including involvement in future HIV vaccine community functions, participation in community promotion of HIV vaccine research, and community mobilization. Three-stage least squares estimates indicated similar findings across three models. Significant effects demonstrate the importance of positive attitudes toward HIV vaccine research, favorable health research beliefs, perceived social support for participation, HIV/AIDS issue engagement, and perceived relevance of the clinical research site’s mission and values. Identification of these nuanced pathway effects provides implications for tailored community program development. PMID:20012200
Teloni, R; von Hunolstein, C; Mariotti, S; Donati, S; Orefici, G; Nisini, R
2004-05-01
Type-specific antibodies against M protein are critical for human protection as they enhance phagocytosis and are protective. An ideal vaccine for the protection against Streptococcus pyogenes would warrant mucosal immunity, but mucosally administered M-protein has been shown to be poorly immunogenic in animals. We used a recombinant M type 6 protein to immunize mice in the presence of synthetic oligodeoxynucleotides containing CpG motifs (immunostimulatory sequences: ISS) or cholera toxin (CT) to explore its possible usage in a mucosal vaccine. Mice were immunized by intranasal (in) or intradermal (id) administration with four doses at weekly intervals of M6-protein (10 microg/mouse) with or without adjuvant (ISS, 10 microg/mouse or CT, 0,5 microg/mouse). M6 specific antibodies were measured by enzyme linked immunosorbent assay using class and subclass specific monoclonal antibodies. The use of ISS induced an impressive anti M-protein serum IgG response but when id administered was not detectable in the absence of adjuvant. When used in, M-protein in the presence of both ISS and CT induced anti M-protein IgA in the bronchoalveolar lavage, as well as specific IgG in the serum. IgG were able to react with serotype M6 strains of S. pyogenes. The level of antibodies obtained by immunizing mice in with M-protein and CT was higher in comparison to M-protein and ISS. The analysis of anti-M protein specific IgG subclasses showed high levels of IgG1, IgG2a and IgG2b, and low levels of IgG3 when ISS were used as adjuvant. Thus, in the presence of ISS, the ratio IgG2a/IgG1 and (IgG2a+IgG3)/IgG1 >1 indicated a type 1-like response obtained both in mucosally or systemically vaccinated mice. Our study offers a reproducible model of anti-M protein vaccination that could be applied to test new antigenic formulations to induce an anti-group A Streptococcus (GAS) vaccination suitable for protection against the different diseases caused by this bacterium.
Rejinold, N Sanoj; Shin, Ju-Hyung; Seok, Hae Yong; Kim, Yeu-Chun
2016-01-01
The skin, as the largest organ, is a better option for drug delivery in many diseases. However, most transdermal delivery is difficult due to the low permeability of therapeutics across the various skin layers. There have been many innovations in transdermal drug delivery to enhance the therapeutic efficacy of the drugs administered. Microneedles (MN), micron sized needles, are of great interest to scientists as a new therapeutic vehicle through transdermal routes, especially for vaccines, drugs, small molecules, etc. This review covers new insights into different types of MNs such as solid, hollow, coated and dissolving MNs (SMNs, HMNs, CMNs, and DMNs) for selected biomedical applications in detail. Specific focus has been given to CMNs and DMNs for vaccine and drug delivery applications with recent developments in new MNs covered. This review explores the feasibility of innovative MNs used as a drug delivery carrier. Because most of the SMNs and HMNs have many limitations, it is difficult to achieve therapeutic efficacy. Therefore, many scientists are investigating functional modifications of MNs through covalent and non-covalent methods, especially for CMNs and DMNs. The biomedical applications of MNs are growing and new exciting improvements could be achieved, thus resulting in better micro/nano technologies in the near future.
Topuzogullari, Murat; Cakir Koc, Rabia; Dincer Isoglu, Sevil; Bagirova, Melahat; Akdeste, Zeynep; Elcicek, Serhat; Oztel, Olga N; Yesilkir Baydar, Serap; Canim Ates, Sezen; Allahverdiyev, Adil M
2013-06-03
Research on the conjugates of synthetic polyelectrolytes with antigenic molecules, such as proteins, peptides, or carbohydrates, is an attractive area due to their highly immunogenic character in comparison to classical adjuvants. For example, polyacrylic acid (PAA) is a weak polyelectrolyte and has been used in several biomedical applications such as immunological studies, drug delivery, and enzyme immobilization. However, to our knowledge, there are no studies that document immune-stimulant properties of PAA in Leishmania infection. Therefore, we aimed to develop a potential vaccine candidate against leishmaniasis by covalently conjugating PAA with an immunologically vital molecule of lipophosphoglycan (LPG) found in Leishmania parasites. In the study, LPG and PAA were conjugated by a multi-step procedure, and final products were analyzed with GPC and MALDI-TOF MS techniques. In cytotoxicity experiments, LPG-PAA conjugates did not indicate toxic effects on L929 and J774 murine macrophage cells. We assume that LPG-PAA conjugate can be a potential vaccine candidate, and will be immunologically characterized in further studies to prove its potential.
The Internet plays a large role in disseminating anti-vaccination information. This paper builds upon previous research by analyzing the arguments proffered on anti-vaccination websites, determining the extent of misinformation present, and examining discourses used to support vaccine objections. Arguments around the themes of safety and effectiveness, alternative medicine, civil liberties, conspiracy theories, and morality were found on the majority of websites analyzed; misinformation was also prevalent. The most commonly proposed method of combating this misinformation is through better education, although this has proven ineffective. Education does not consider the discourses supporting vaccine rejection, such as those involving alternative explanatory models of health, interpretations of parental responsibility, and distrust of expertise. Anti-vaccination protestors make postmodern arguments that reject biomedical and scientific "facts" in favour of their own interpretations. Pro-vaccination advocates who focus on correcting misinformation reduce the controversy to merely an "educational" problem; rather, these postmodern discourses must be acknowledged in order to begin a dialogue. Copyright (c) 2009 Elsevier Ltd. All rights reserved.
It is time-consuming to build an ontology with many terms and axioms. Thus it is desired to automate the process of ontology development. Ontology Design Patterns (ODPs) provide a reusable solution to solve a recurrent modeling problem in the context of ontology engineering. Because ontology terms often follow specific ODPs, the Ontology for Biomedical Investigations (OBI) developers proposed a Quick Term Templates (QTTs) process targeted at generating new ontology classes following the same pattern, using term templates in a spreadsheet format. Inspired by the ODPs and QTTs, the Ontorat web application is developed to automatically generate new ontology terms, annotations of terms, and logical axioms based on a specific ODP(s). The inputs of an Ontorat execution include axiom expression settings, an input data file, ID generation settings, and a target ontology (optional). The axiom expression settings can be saved as a predesigned Ontorat setting format text file for reuse. The input data file is generated based on a template file created by a specific ODP (text or Excel format). Ontorat is an efficient tool for ontology expansion. Different use cases are described. For example, Ontorat was applied to automatically generate over 1,000 Japan RIKEN cell line cell terms with both logical axioms and rich annotation axioms in the Cell Line Ontology (CLO). Approximately 800 licensed animal vaccines were represented and annotated in the Vaccine Ontology (VO) by Ontorat. The OBI team used Ontorat to add assay and device terms required by ENCODE project. Ontorat was also used to add missing annotations to all existing Biobank specific terms in the Biobank Ontology. A collection of ODPs and templates with examples are provided on the Ontorat website and can be reused to facilitate ontology development. With ever increasing ontology development and applications, Ontorat provides a timely platform for generating and annotating a large number of ontology terms by following design patterns. http://ontorat.hegroup.org/.
The expression vector of SmIg scFv fragment was constructed in patient with B cell chronic lymphocyte leukemia (B-CLL) and expressed in E. coli to obtain scFv fragment, and the effect of the protein on the proliferation of stimulated peripheral blood mononuclear cells (PBMC) was investigated in vitro. Two pairs of primers were designed, and variable region genes of light chain and heavy chain were amplified by PCR respectively from the pGEM-T vectors previously constructed in our laboratory which containing light chain gene or Fd fragment of heavy chain gene. The PCR product was digested, purified and inserted into pHEN2 vector to construct the soluble expression vector pHEN2-scFv. After the induction by IPTG, the scFv protein was identified by SDS-PAGE electrophoresis and purified by Ni-NTA-Chromatography. MTT was used to determine the effect of purified protein on the proliferation of stimulated PBMC in vitro. Plasmid PCR and restriction enzyme digestion of pHEN2-scFv revealed the pHEN2-scFv vector was constructed successfully. Id-scFv protein was expressed in positive clone after induced by IPTG. SDS-PAGE analysis showed that the relative molecular weight of fusion protein was about 30 kD (1 kD= 0.9921 ku), which was consistent with the theoretically predicted value. Proliferation of PBMC could be induced by purified Id-scFv. It was suggested that the expression vector of SmIg scFv fragment was constructed successfully, and scFv protein was expressed and secreted from E. coli, which could induce proliferation of PBMC. This may lay an experimental foundation for further research of Id-HSP complex vaccine for B-CLL.
Savage, D; Liu, X; Curley, S; Ferrari, M; Serda, RE
2013-01-01
Biomedical applications of porous silicon include drug delivery, imaging, diagnostics and immunotherapy. This review summarizes new silicon particle fabrication techniques, dynamics of cellular transport, advances in the multistage vector approach to drug delivery, and the use of porous silicon as immune adjuvants. Recent findings support superior therapeutic efficacy of the multistage vector approach over single particle drug delivery systems in mouse models of ovarian and breast cancer. With respect to vaccine development, multivalent presentation of pathogen-associated molecular patterns on the particle surface creates powerful platforms for immunotherapy, with the porous matrix able to carry both antigens and immune modulators. PMID:23845260
Even students who reject evolution are often willing to consider cases in which evolutionary biology contributes to, or undermines, biomedical interventions. Moreover the intersection of evolutionary biology and biomedicine is fascinating in its own right. This review offers an overview of the ways in which evolution has impacted the design and deployment of live-attenuated virus vaccines, with subsections that may be useful as lecture material or as the basis for case studies in classes at a variety of levels. Live- attenuated virus vaccines have been modified in ways that restrain their replication in a host, so that infection (vaccination) produces immunity but not disease. Applied evolution, in the form of serial passage in novel host cells, is a “classical” method to generate live-attenuated viruses. However many live-attenuated vaccines exhibit reversion to virulence through back-mutation of attenuating mutations, compensatory mutations elsewhere in the genome, recombination or reassortment, or changes in quasispecies diversity. Additionally the combination of multiple live-attenuated strains may result in competition or facilitation between individual vaccine viruses, resulting in undesirable increases in virulence or decreases in immunogenicity. Genetic engineering informed by evolutionary thinking has led to a number of novel approaches to generate live-attenuated virus vaccines that contain substantial safeguards against reversion to virulence and that ameliorate interference among multiple vaccine strains. Finally, vaccines have the potential to shape the evolution of their wild type counterparts in counter-productive ways; at the extreme vaccine-driven eradication of a virus may create an empty niche that promotes the emergence of new viral pathogens. PMID:22468165
Background The European (EU) genotype of porcine reproductive and respiratory syndrome virus (Genotype-I PRRSV) has recently emerged in China. The coexistence of Genotype-I and -II PRRSV strains could cause seriously affect PRRSV diagnosis and management. Current vaccines are not able to protect against PRRSV infection completely and have inherent drawbacks. Thus, genetically engineered vaccines, including DNA vaccine and live vector engineered vaccines, have been developed. This study aimed to determine the enhanced immune responses of mice inoculated with a DNA vaccine coexpressing GP3 and GP5 of a Genotype-I PRRSV. Results To evaluate the immunogenicity of GP3 and GP5 proteins from European-type PRRSV, three DNA vaccines, pVAX1-EU-ORF3-ORF5, pVAX1-EU-ORF3 and pVAX1-EU-ORF5, were constructed, which were based on a Genotype-I LV strain (GenBank ID: M96262). BALB/c mice were immunized with the DNA vaccines; delivered in the form of chitosan-DNA nanoparticles. To increase the efficiency of the vaccine, Quil A (Quillaja) was used as an adjuvant. GP3 and GP5-specific antibodies, neutralizing antibodies and cytokines (IL-2, IL-4, IL-10 and IFN gamma) from the immunized mice sera, and other immune parameters, were examined, including T-cell proliferation responses and subgroups of spleen T-lymphocytes. The results showed that ORF3 and ORF5 proteins of Genotype-I PRRSV induced GP3 and GP5-specific antibodies that could neutralize the virus. The levels of Cytokines IL-2, IL-4, IL-10, and IFN–γ of the experimental groups were significantly higher than those of control groups after booster vaccination (P < 0.05). The production of CD3+CD4+ and CD3+CD8+ T lymphocyte was also induced. T lymphocyte proliferation assays showed that the PRRSV LV strain virus could stimulate the proliferation of T lymphocytes in mice in the experimental group. Conclusions Using Quil A as adjuvant, Genotype-I PRRSV GP3 and GP5 proteins produced good immunogenicity and reactivity. More importantly, better PRRSV-specific neutralizing antibody titers and cell-mediated immune responses were observed in mice immunized with the DNA vaccine co-expressing GP3 and GP5 proteins than in mice immunized with a DNA vaccine expressing either protein singly. The results of this study demonstrated that co-immunization with GP3 and GP5 produced a better immune response in mice. PMID:24916952
McCluskie, M. J.; Brazolot Millan, C. L.; Gramzinski, R. A.; Robinson, H. L.; Santoro, J. C.; Fuller, J. T.; Widera, G.; Haynes, J. R.; Purcell, R. H.; Davis, H. L.
1999-01-01
BACKGROUND: In spite of the large number of studies that have evaluated DNA-based immunization, few have directly compared the immune responses generated by different routes of immunization, particularly in non-human primates. Here we examine the ability of a hepatitis B surface antigen (HBsAg)-encoding plasmid to induce immune responses in mice and non-human primates (rhesus monkeys: Macaca mulatta) after delivery by a number of routes. MATERIALS AND METHODS: Eight different injected [intraperitoneal (IP), intradermal (ID), intravenous (IV), intramuscular (IM), intraperineal (IPER), subcutaneous (SC), sublingual (SL), vaginal wall (VW)] and six noninjected [intranasal inhalation (INH), intranasal instillation (INS), intrarectal (IR), intravaginal (IVAG), ocular (Oc), oral feeding (oral)] routes and the gene gun (GG) were used to deliver HBsAg-expressing plasmid DNA to BALB/c mice. Sera were assessed for HBsAg-specific antibodies (anti-HBs, IgG, IgG1, IgG2a) and cytotoxic T lymphocyte (CTL) activity measured. Three of the most commonly used routes (IM, ID, GG) were compared in rhesus monkeys, also using HBsAg-expressing vectors. Monkeys were immunized with short (0-, 4- and 8-week) or long (0-, 12- and 24-week) intervals between boosts, and in the case of GG, also with different doses, and their sera were assessed for anti-HBs. RESULTS: In one study, anti-HBs were detected in plasma of mice treated by five of eight of the injected and none of the six noninjected routes. The highest levels of anti-HBs were induced by IM and IV injections, although significant titers were also obtained with SL and ID. Each of these routes also induced CTL, as did IPER and VW and one noninjected route (INH) that failed to induce antibodies. In a second study, GG (1.6 microg) was compared to ID and IM (100 microg) delivery. Significant titers were obtained by all routes after only one boost, with the highest levels detected by IM. Delivery to the skin by GG induced exclusively IgG1 antibodies (Th2-like) at 4 weeks and only very low IgG2a levels at later times; ID-immunized mice had predominantly IgG1 at 4 weeks and this changed to mixed IgG1/IgG2a over time. Responses with IM injection (in the leg or tongue) were predominantly IgG2a (Th1-like) at all times. IV injection gave mixed IgG1/IgG2a responses. In monkeys, in the first experiment, 1 mg DNA IM or ID at 0, 4, and 8 weeks gave equivalent anti-HB titers and 0.4 microg at the same times by GG induced lower titers. In the second experiment, 1 mg DNA IM or ID, or 3.2 microg by GG, at 0, 12, and 24 weeks, gave anti-HB values in the hierarchy of GG > IM > ID. Furthermore, high titers were retained after a single immunization in mice but fell off over time in the monkeys, even after boost. CONCLUSIONS: Route of administration of plasmid DNA vaccines influences the strength and nature of immune responses in mice and non-human primates. However, the results in mice were not always predictive of those in monkeys and this is likely true for humans as well. Optimal dose and immunization schedule will most likely vary between species. It is not clear whether results in non-human primates will be predictive of results in humans, thus additional studies are required. http://link.springer-ny.com/link/service/journals/00020/bibs /5n5p287. html Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:10390545
Lowe, Daniel M.; O’Boyle, Noel M.; Sayle, Roger A.
2016-01-01
Awareness of the adverse effects of chemicals is important in biomedical research and healthcare. Text mining can allow timely and low-cost extraction of this knowledge from the biomedical literature. We extended our text mining solution, LeadMine, to identify diseases and chemical-induced disease relationships (CIDs). LeadMine is a dictionary/grammar-based entity recognizer and was used to recognize and normalize both chemicals and diseases to Medical Subject Headings (MeSH) IDs. The disease lexicon was obtained from three sources: MeSH, the Disease Ontology and Wikipedia. The Wikipedia dictionary was derived from pages with a disease/symptom box, or those where the page title appeared in the lexicon. Composite entities (e.g. heart and lung disease) were detected and mapped to their composite MeSH IDs. For CIDs, we developed a simple pattern-based system to find relationships within the same sentence. Our system was evaluated in the BioCreative V Chemical–Disease Relation task and achieved very good results for both disease concept ID recognition (F1-score: 86.12%) and CIDs (F1-score: 52.20%) on the test set. As our system was over an order of magnitude faster than other solutions evaluated on the task, we were able to apply the same system to the entirety of MEDLINE allowing us to extract a collection of over 250 000 distinct CIDs. PMID:27060160
In the post-genomic era, the development of high-throughput gene expression detection technology provides huge amounts of experimental data, which challenges the traditional pipelines for data processing and analyzing in scientific researches. In our work, we integrated gene expression information from Gene Expression Omnibus (GEO), biomedical ontology from Medical Subject Headings (MeSH) and signaling pathway knowledge from sigPathway entries to develop a context mining tool for gene expression analysis - GEOGLE. GEOGLE offers a rapid and convenient way for searching relevant experimental datasets, pathways and biological terms according to multiple types of queries: including biomedical vocabularies, GDS IDs, gene IDs, pathway names and signature list. Moreover, GEOGLE summarizes the signature genes from a subset of GDSes and estimates the correlation between gene expression and the phenotypic distinction with an integrated p value. This approach performing global searching of expression data may expand the traditional way of collecting heterogeneous gene expression experiment data. GEOGLE is a novel tool that provides researchers a quantitative way to understand the correlation between gene expression and phenotypic distinction through meta-analysis of gene expression datasets from different experiments, as well as the biological meaning behind. The web site and user guide of GEOGLE are available at: http://omics.biosino.org:14000/kweb/workflow.jsp?id=00020.
The term 'social vaccine' is designed to encourage the biomedically orientated health sector to recognize the legitimacy of action on the distal social and economic determinants of health. It is proposed as a term to assist the health promotion movement in arguing for a social view of health which is so often counter to medical and popular conceptions of health. The idea of a social vaccine builds on a long tradition in social medicine as well as on a biomedical tradition of preventing illness through vaccines that protect against disease. Social vaccines would be promoted as a means to encourage popular mobilization and advocacy to change the social and economic structural conditions that render people and communities vulnerable to disease. They would facilitate social and political processes that develop popular and political will to protect and promote health through action (especially governments prepared to intervene and regulate to protect community health) on the social and economic determinants. Examples provided for the effects of social vaccines are: restoring land ownership to Indigenous peoples, regulating the advertising of harmful products and progressive taxation for universal social protection. Social vaccines require more research to improve understanding of social and political processes that are likely to improve health equity worldwide. The vaccine metaphor should be helpful in arguing for increased action on the social determinants of health.
Wysokinski, Tomasz W.; Chapman, Dean; Adams, Gregg; Renier, Michel; Suortti, Pekka; Thomlinson, William
2015-03-01
The BioMedical Imaging and Therapy (BMIT) facility provides synchrotron-specific imaging and radiation therapy capabilities [1-4]. We describe here the Insertion Device (ID) beamline 05ID-2 with the beam terminated in the SOE-1 (Secondary Optical Enclosure) experimental hutch. This endstation is designed for imaging and therapy research primarily in animals ranging in size from mice to humans to horses, as well as tissue specimens including plants. Core research programs include human and animal reproduction, cancer imaging and therapy, spinal cord injury and repair, cardiovascular and lung imaging and disease, bone and cartilage growth and deterioration, mammography, developmental biology, gene expression research as well as the introduction of new imaging methods. The source for the ID beamline is a multi-pole superconducting 4.3 T wiggler [5]. The high field gives a critical energy over 20 keV. The high critical energy presents shielding challenges and great care must be taken to assess shielding requirements [6-9]. The optics in the POE-1 and POE-3 hutches [4,10] prepare a monochromatic beam that is 22 cm wide in the last experimental hutch SOE-1. The double crystal bent-Laue or Bragg monochromator, or the single-crystal K-edge subtraction (KES) monochromator provide an energy range appropriate for imaging studies in animals (20-100+ keV). SOE-1 (excluding the basement structure 4 m below the experimental floor) is 6 m wide, 5 m tall and 10 m long with a removable back wall to accommodate installation and removal of the Large Animal Positioning System (LAPS) capable of positioning and manipulating animals as large as a horse [11]. This end-station also includes a unique detector positioner with a vertical travel range of 4.9 m which is required for the KES imaging angle range of +12.3° to -7.3°. The detector positioner also includes moveable shielding integrated with the safety shutters. An update on the status of the other two end-stations at BMIT, described in Part 1&2 [3,4] of this article, is included. 1PACS Codes: 07.85.Qe, 07.85.Tt, 87.62.+n, 87.59.-e
Miner, Brooks E.; Stöger, Reinhard J.; Burden, Alice F.; Laird, Charles D.; Hansen, R. Scott
2004-01-01
PCR amplification of limited amounts of DNA template carries an increased risk of product redundancy and contamination. We use molecular barcoding to label each genomic DNA template with an individual sequence tag prior to PCR amplification. In addition, we include molecular ‘batch-stamps’ that effectively label each genomic template with a sample ID and analysis date. This highly sensitive method identifies redundant and contaminant sequences and serves as a reliable method for positive identification of desired sequences; we can therefore capture accurately the genomic template diversity in the sample analyzed. Although our application described here involves the use of hairpin-bisulfite PCR for amplification of double-stranded DNA, the method can readily be adapted to single-strand PCR. Useful applications will include analyses of limited template DNA for biomedical, ancient DNA and forensic purposes. PMID:15459281
A medical intervention is a medical procedure or application intended to relieve or prevent illness or injury. Examples of medical interventions include vaccination and drug administration. After a medical intervention, adverse events (AEs) may occur which lie outside the intended consequences of the intervention. The representation and analysis of AEs are critical to the improvement of public health. The Ontology of Adverse Events (OAE), previously named Adverse Event Ontology (AEO), is a community-driven ontology developed to standardize and integrate data relating to AEs arising subsequent to medical interventions, as well as to support computer-assisted reasoning. OAE has over 3,000 terms with unique identifiers, including terms imported from existing ontologies and more than 1,800 OAE-specific terms. In OAE, the term 'adverse event' denotes a pathological bodily process in a patient that occurs after a medical intervention. Causal adverse events are defined by OAE as those events that are causal consequences of a medical intervention. OAE represents various adverse events based on patient anatomic regions and clinical outcomes, including symptoms, signs, and abnormal processes. OAE has been used in the analysis of several different sorts of vaccine and drug adverse event data. For example, using the data extracted from the Vaccine Adverse Event Reporting System (VAERS), OAE was used to analyse vaccine adverse events associated with the administrations of different types of influenza vaccines. OAE has also been used to represent and classify the vaccine adverse events cited in package inserts of FDA-licensed human vaccines in the USA. OAE is a biomedical ontology that logically defines and classifies various adverse events occurring after medical interventions. OAE has successfully been applied in several adverse event studies. The OAE ontological framework provides a platform for systematic representation and analysis of adverse events and of the factors (e.g., vaccinee age) important for determining their clinical outcomes.
Patient identification (ID) bands are an essential component in patient ID. Quality improvement methodology has been applied as a model to reduce ID band errors although previous studies have not addressed standardization of ID bands. Our specific aim was to decrease ID band errors by 50% in a 12-month period. The Six Sigma DMAIC (define, measure, analyze, improve, and control) quality improvement model was the framework for this study. ID bands at a tertiary care pediatric hospital were audited from January 2011 to January 2012 with continued audits to June 2012 to confirm the new process was in control. After analysis, the major improvement strategy implemented was standardization of styles of ID bands and labels. Additional interventions included educational initiatives regarding the new ID band processes and disseminating institutional and nursing unit data. A total of 4556 ID bands were audited with a preimprovement ID band error average rate of 9.2%. Significant variation in the ID band process was observed, including styles of ID bands. Interventions were focused on standardization of the ID band and labels. The ID band error rate improved to 5.2% in 9 months (95% confidence interval: 2.5-5.5; P < .001) and was maintained for 8 months. Standardization of ID bands and labels in conjunction with other interventions resulted in a statistical decrease in ID band error rates. This decrease in ID band error rates was maintained over the subsequent 8 months.
The sciences of vaccinology and immunology were created only two centuries ago by Jenner's scientific studies of prevention of smallpox through inoculation with cowpox virus. This rudimentary beginning was expanded greatly by the giants of late 19th- and early 20th-century biomedical sciences. The period from 1930 to 1950 was a transitional era, with the introduction of chick embryos and minced tissues for propagating viruses and rickettsiae in vitro for vaccines. Modern vaccinology began about 1950 as a continuum following notable advances made during the 1940s and World War II. Its pursuit has been based largely on breakthroughs in cell culture, bacterial polysaccharide chemistry, molecular biology, and immunology which have yielded many live and killed viral and bacterial vaccines plus the recombinant-expressed hepatitis B vaccine. The present paper was presented as a lecture given at a Meeting of the Institute of Human Virology entitled A Symposium on HIV-AIDS and Cancer Biology, Baltimore, Maryland, on August 30, 1999 and recounts, by invitation, more than 55 years of vaccine research from the venue of personal experience and attainment by the author. The paper is intentionally brief and truncated with focus only on highlights and limited referencing. Detailed recounting and referencing are given elsewhere in text references 1 and 2. This narration will have achieved its purpose if it provides a background of understanding and guidelines that will assist others who seek to engage in creation of new vaccines.
..., ID-4X, Advising of Service/Earnings Requirements for Sickness Benefits, ID-20-1, Advising that Normal..., ID-4K, ID-4Y, ID-20-1, ID-20-2, and ID-204 is required to obtain or retain benefits. One response is... determine (1) the practical utility of the collection; (2) the accuracy of the estimated burden of the...
Armony-Sivan, Rinat; Zhu, Bingquan; Clark, Katy M.; Richards, Blair; Ji, Chai; Kaciroti, Niko; Shao, Jie
2016-01-01
This study considered effects of timing and duration of iron deficiency (ID) on frontal EEG asymmetry in infancy. In healthy term Chinese infants, EEG was recorded at 9 months in three experimental conditions: baseline, peek-a-boo, and stranger approach. Eighty infants provided data for all conditions. Prenatal ID was defined as low cord ferritin or high ZPP/H. Postnatal ID was defined as ≥ two abnormal iron measures at 9 months. Study groups were pre- and postnatal ID, prenatal ID only, postnatal ID only, and not ID. GLM repeated measure analysis showed a main effect for iron group. The pre- and postnatal ID group had negative asymmetry scores, reflecting right frontal EEG asymmetry (mean ±SE: −.18 ±.07) versus prenatal ID only (.00 ±.04), postnatal ID only (.03 ±.04), and not ID (.02 ±.04). Thus, ID at both birth and 9 months was associated with right frontal EEG asymmetry, a neural correlate of behavioral withdrawal and negative emotions. PMID:26668100
Santos, Denise CC; Angulo-Barroso, Rosa M; Li, Ming; Bian, Yang; Sturza, Julie; Richards, Blair; Lozoff, Betsy
2017-01-01
BACKGROUND/OBJECTIVES Poorer motor development is reported in infants with iron deficiency (ID). The role of timing, duration and severity is unclear. We assessed relations between ID timing, duration, and severity and gross motor scores, neurological integrity, and motor behavior quality at 9 months. METHODS Iron status was determined at birth and 9 months in otherwise healthy term Chinese infants. The 9-month motor evaluation included the Peabody Developmental Motor Scale (PDMS-2), Infant Neurological International Battery (INFANIB), and motor quality factor. Motor outcomes were analyzed by ID timing (fetal-neonatal, infancy), duration, and severity. For severity, we also considered maternal iron status. RESULTS Data were available for 1194 infants. Iron status was classified as fetal-neonatal and infancy ID (n=253), fetal-neonatal ID (n=256), infancy ID (n=288), and not ID (n=397). Compared with not ID, infants with fetal-neonatal or infancy ID had lower locomotion scores (effect size ds=0.19, 0.18) and those with ID in both periods (longer duration) had lower locomotion and overall PDMS-2 gross motor scores (ds=0.20, 0.18); ID groups did not differ. More severe ID in late pregnancy was associated with lower INFANIB Vestibular function (p=0.01), and total score (p=0.03). More severe ID in infancy was associated with lower scores for locomotion (p=0.03), overall gross motor (p=0.05). CONCLUSIONS Fetal-neonatal and/or infancy ID was associated with lower overall gross motor development and locomotion test scores at 9 months. Associations with ID severity varied by ID timing: more severe ID in late pregnancy, poorer neurological integrity; more severe ID in infancy, poorer gross motor development. PMID:29235557
Intelligent Design (ID) burst onto the scene in 1996, with the publication of Darwin's Black Box by Michael Behe. Since then, there has been a plethora of articles written about ID, both pro and con. However, most of the articles critical of ID deal with peripheral issues, such as whether ID is just another form of creationism or whether ID qualifies as science or whether ID should be taught in public schools. It is our view that the central issue is whether the basic claim of ID is correct. Our goal is fourfold: (I) to show that most of the proposed refutations of ID are unconvincing and/or incorrect, (II) to describe the single fundamental error of ID, (III) to discuss the historic tradition surrounding the ID controversy, showing that ID is an example of a "god-of-the-gaps" argument, and (IV) to place the ID controversy in the larger context of proposed proofs for the existence of God, with the emphasis on Jewish tradition.
Intelligent Design (ID) burst onto the scene in 1996, with the publication of Darwin’s Black Box by Michael Behe. Since then, there has been a plethora of articles written about ID, both pro and con. However, most of the articles critical of ID deal with peripheral issues, such as whether ID is just another form of creationism or whether ID qualifies as science or whether ID should be taught in public schools. It is our view that the central issue is whether the basic claim of ID is correct. Our goal is fourfold: (I) to show that most of the proposed refutations of ID are unconvincing and/or incorrect, (II) to describe the single fundamental error of ID, (III) to discuss the historic tradition surrounding the ID controversy, showing that ID is an example of a “god-of-the-gaps” argument, and (IV) to place the ID controversy in the larger context of proposed proofs for the existence of God, with the emphasis on Jewish tradition. PMID:23908779
Motivation: Text mining technologies have been shown to reduce the laborious work involved in organizing the vast amount of information hidden in the literature. One challenge in text mining is linking ambiguous word forms to unambiguous biological concepts. This article reports on a comprehensive study on resolving the ambiguity in mentions of biomedical named entities with respect to model organisms and presents an array of approaches, with focus on methods utilizing natural language parsers. Results: We build a corpus for organism disambiguation where every occurrence of protein/gene entity is manually tagged with a species ID, and evaluate a number of methods on it. Promising results are obtained by training a machine learning model on syntactic parse trees, which is then used to decide whether an entity belongs to the model organism denoted by a neighbouring species-indicating word (e.g. yeast). The parser-based approaches are also compared with a supervised classification method and results indicate that the former are a more favorable choice when domain portability is of concern. The best overall performance is obtained by combining the strengths of syntactic features and supervised classification. Availability: The corpus and demo are available at http://www.nactem.ac.uk/deca_details/start.cgi, and the software is freely available as U-Compare components (Kano et al., 2009): NaCTeM Species Word Detector and NaCTeM Species Disambiguator. U-Compare is available at http://-compare.org/ Contact: xinglong.wang@manchester.ac.uk PMID:20053840
Pathogens such as viruses and bacteria are among the greatest threats to human health worldwide. In today's era of population growth and international travel, new technologies are desperately needed to combat the spread of known and emerging pathogens. This book presents a new concept for pathogen inactivation called selective photonic disinfection (SEPHODIS). The SEPHODIS technology inactivates pathogens by mechanical means, a total paradigm shift from traditional chemical and physical methods. The unique strength of SEPHODIS resides in its capability to inactivate pathogens while preserving desirable materials such as human cells and proteins. The technology also avoids the need to use chemicals, drastically reducing the risk of side effects. These properties make SEPHODIS ideal for important biomedical applications such as safeguarding blood products and therapeutics against pathogens, as well as producing effective and safe vaccines to combat infectious disease. Written in a style that is both technically informative and easy to comprehend for the layman reader, this book illustrates the story of SEPHODIS from its initial discovery and bench studies to its real-world applications. EpsteinJ SVostalJ G2003FDA approach to evaluation of pathogen reduction technologyTransfusion 43 134713491347-910.1046/j.1537-2995.2003.00584.xSalunkheVvan der MeerP Fde KorteDSeghatchianJGutierrezL2015Development of blood transfusion product pathogen reduction treatments: a review of methods, current applications and demandsTransfus. Apher. Sci. 52 193419-3410.1016/j.transci.2014.12.016SandersBKoldijkMSchuitemakerH2015Inactivated viral vaccinesVaccine Analysis: Strategies, Principles, and ControlNunnallyB KTurulaV ESitrin RDR DBerlinSpringerpp458045-80GaffneyK JDavisP HPileticI RLevingerN EFayerM D2002Hydrogen bond dissociation and reformation in methanol oligomers following hydroxyl stretch relaxationJ. Phys. Chem. A 106 120121202312012-2310.1021/jp021696gO'ConnellCSherlockRBallM DAszalos-KissBPrendergastUGlynnT J2009Investigation of the hydrophobic recovery of various polymeric biomaterials after 172 nm UV treatment using contact angle, surface free energy and XPS measurementsAppl. Surf. Sci. 255 440544134405-1310.1016/j.apsusc.2008.11.034DykemanE CSankeyO F2010Atomistic modeling of the low-frequency mechanical modes and Raman spectra of icosahedral virus capsidsPhys. Rev. E 81 02191810.1103/PhysRevE.81.021918YanY XGambleE BNelsonK A1985Impulsive stimulated scattering: general importance in femtosecond laser pulse interactions with matter, and spectroscopic applicationsJ. Chem. 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Opt. 22 3406103406-1010.1364/AO.22.003406BornMWolfE1999Principles of OpticsCambridgeCambridge University PressTsenS WKingsleyD HPoweleitCAchilefuSSorokaDWuT CTsenK T2014Studies of inactivation mechanism of non-enveloped icosahedral virus by a visible ultrashort pulsed laserVirol. J. 11 2010.1186/1743-422X-11-20TsenK TTsenS WFuQLindsayS MLiZCopeSVaianaSKiangJ G2011Studies of inactivation of encephalomyocarditis virus, M13 bacteriophage, and Salmonella typhimurium by using a visible femtosecond laser: insight into the possible inactivation mechanismsJ. Biomed. Opt. 16 07800310.1117/1.3600771GaffneyK JDavisP HPileticI RLevingerN EFayerM D2002Hydrogen bond dissociation and reformation in methanol oligomers following hydroxyl stretch relaxationJ. Phys. Chem. A 106 120122312012-2310.1021/jp021696gO'ConnellCSherlockRBallM DAszalos-KissBPrendergastUGlynnT J2009Investigation of the hydrophobic recovery of various polymeric biomaterials after 172 nm UV treatment using contact angle, surface free energy and XPS measurementsAppl. Surf. Sci. 255 4405134405-1310.1016/j.apsusc.2008.11.034YanY XGambleE BNelsonK A1985Impulsive stimulated scattering: general importance in femtosecond laser pulse interactions with matter, and spectroscopic applicationsJ. Chem. Phys. 83 5391995391-9910.1063/1.449708BoustieMBertheLde ResseguierTArrigoniM2008Laser shock waves: fundamentals and applications 1st Int. Symp. On Laser Ultrasonics: Science, Technology and Applications (National Research Council of Canada, Montreal) paper 1 and references thereinwww.optics.rochester.edu/workgroups/boyd/assets/pdf/publications/nlomater.pdfCannonJ LPapafragkouEParkG WOsborneJJaykusL AVinjeJ2006Surrogates for the study of norovirus stability and inactivation in the environment: a comparison of murine norovirus and feline calicivirusJ. Food Prot. 69 276152761-5TsenS WWuT CKiangJ GTsenK T2012Prospects for a novel ultrashort pulsed laser technology for pathogen inactivationJ. Biomed. Sci. 19 6210.1186/1423-0127-19-62TsenS WChapaTBeattyWTsenK TYuDAchilefuS2012Inactivation of enveloped virus by laser-driven protein aggregationJ. Biomed. Opt. 17 12800210.1117/1.JBO.17.12.128002KattenhornL MMillsRWagnerMLomsadzeAMakeevVBorodovskyMPloeghH LKesslerB M2004Identification of proteins associated with murine cytomegalovirus virionsJ. 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Virol. 76 289529012895-90110.1099/0022-1317-76-11-2895UverskyV NFernandezAFinkA L2006Protein Reviews(vol 4)UverskyV NFinkA LNew YorkSpringerTsenS WChapaTBeattyWXuBTsenK TAchilefuS2014Ultrashort pulsed laser treatment inactivates viruses by inhibiting viral replication and transcription in the host nucleusAntiviral Res. 110 707670-610.1016/j.antiviral.2014.07.012ShellanG RRedwoodA JSmithL MGormanS2006 The Mouse in Biomedical Research (New York: Academic)BrittW JAlfordC A1996 Fields Virology (Philadelphia, PA: Lippincott-Raven)PrestonV GMurrayJPrestonC MMcDougallI MStowN D2008The UL25 gene product of herpes simplex virus type 1 is involved in uncoating of the viral genomeJ. Virol. 82 665466666654-6610.1128/JVI.00257-08LuC HLinK HHsuY YTsenK TKuanY S2014Inhibition of Escherichia Coli respiratory enzymes by short visible femtosecond laser irradiationJ. Phys. D: Appl. Phys. 47 31540210.1088/0022-3727/47/31/315402MacleanMMacGregorS JAndersonJ GWoolseyG2008High-intensity narrow-spectrum light inactivation and wavelength sensitivity of Staphylococcus aureus FEMS Microbiol. Lett. 285 227232227-3210.1111/j.1574-6968.2008.01233.xBryantJKleinH G2007Pathogen inactivation: the definitive safeguard for the blood supplyArch. Pathol. Lab. Med. 131 71933719-33SalunkheVvan der MeerP Fde KorteDSeghatchianJGutierrezL2015Development of blood transfusion product pathogen reduction treatments: a review of methods, current applications and demandsTransfus. Apher. Sci. 52 193419-3410.1016/j.transci.2014.12.016AuBuchonJ P2011Update on the status of pathogen inactivation methodsISBT Sci. Series 6 1818181-810.1111/j.1751-2824.2011.01471.xAuBuchonJ P2011Breathing easy with pathogen inactivationBlood 117 74950749-5010.1182/blood-2010-11-313379StramerS LHollingerF BKatzL MKleinmanSMetzelP SGregoryK RDoddR Y2009Emerging infectious disease agents and their potential threat to transfusion safetyTransfusion 49 1S49S1S-49S10.1111/j.1537-2995.2009.02279.xProwseC2009Properties of pathogen-inactivated plasma componentsTransf. Med. Rev 23 124133124-3310.1016/j.tmrv.2008.12.004PelletierJ PTransueSSnyderE L2006Pathogen inactivation techniquesBest Pract. Res. Clin. Haematol. 19 205242205-4210.1016/j.beha.2005.04.001RockG2011A comparison of methods of pathogen inactivation of FFPVox Sang. 100 16978169-7810.1111/j.1423-0410.2010.01374.xHorowitzBBonomoRPrinceA MChinS NBrotmanBShulmanR W1992Solvent/detergent-treated plasma: a virusinactivated substitute for fresh frozen plasmaBlood 79 82633826-33WilliamsonL MCardiganRProwseP V2003Methylene-blue-treated fresh frozen plasma: what is its contribution to blood safety?Transfusion 43 1322291322-2910.1046/j.1537-2995.2003.00483.xLarreaLCalabuigMRoldanVRiveraJTsaiH MVicenteVRoigR2009The influence of riboflavin photochemistry on plasma coagulation factorsTransfus. Apher. 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Literature mining of gene-gene interactions has been enhanced by ontology-based name classifications. However, in biomedical literature mining, interaction keywords have not been carefully studied and used beyond a collection of keywords. In this study, we report the development of a new Interaction Network Ontology (INO) that classifies >800 interaction keywords and incorporates interaction terms from the PSI Molecular Interactions (PSI-MI) and Gene Ontology (GO). Using INO-based literature mining results, a modified Fisher's exact test was established to analyze significantly over- and under-represented enriched gene-gene interaction types within a specific area. Such a strategy was applied to study the vaccine-mediated gene-gene interactions using all PubMed abstracts. The Vaccine Ontology (VO) and INO were used to support the retrieval of vaccine terms and interaction keywords from the literature. INO is aligned with the Basic Formal Ontology (BFO) and imports terms from 10 other existing ontologies. Current INO includes 540 terms. In terms of interaction-related terms, INO imports and aligns PSI-MI and GO interaction terms and includes over 100 newly generated ontology terms with 'INO_' prefix. A new annotation property, 'has literature mining keywords', was generated to allow the listing of different keywords mapping to the interaction types in INO. Using all PubMed documents published as of 12/31/2013, approximately 266,000 vaccine-associated documents were identified, and a total of 6,116 gene-pairs were associated with at least one INO term. Out of 78 INO interaction terms associated with at least five gene-pairs of the vaccine-associated sub-network, 14 terms were significantly over-represented (i.e., more frequently used) and 17 under-represented based on our modified Fisher's exact test. These over-represented and under-represented terms share some common top-level terms but are distinct at the bottom levels of the INO hierarchy. The analysis of these interaction types and their associated gene-gene pairs uncovered many scientific insights. INO provides a novel approach for defining hierarchical interaction types and related keywords for literature mining. The ontology-based literature mining, in combination with an INO-based statistical interaction enrichment test, provides a new platform for efficient mining and analysis of topic-specific gene interaction networks.
Staging and detection of various states of sleep derived from EEG and other biomedical signals have proven to be very helpful in diagnosis, prognosis and remedy of various sleep related disorders. The time consuming and costly process of visual scoring of sleep stages by a specialist has always motivated researchers to develop an automatic sleep scoring system and the first step toward achieving this task is finding discriminating characteristics (or features) for each stage. A vast variety of these features and methods have been investigated in the sleep literature with different degrees of success. In this study, we investigated the performance of a newly introduced measure: the Itakura Distance (ID), as a similarity measure between EEG and EOG signals. This work demonstrated and further confirmed the outcomes of our previous research that the Itakura Distance serves as a valuable similarity measure to differentiate between different sleep stages.
Instructional design (ID) models have been developed to promote understandings of ID reality and guide ID performance. As the number and diversity of ID practices grows, implicit doubts regarding the reliability, validity, and usefulness of ID models suggest the need for methodological guidance that would help to generate ID models that are…
Accumulating evidence reveals that Id-1 is upregulated and functions as a potential tumor promoter in several human cancer types. However, the role of Id-1 in osteosarcoma (OS) is unknown. In present study, we found that Id-1 expression was elevated in OS tissues than adjacent normal bone tissues. More importantly, we demonstrated that overexpression of Id-1 is significantly correlated with tumor progression and poor survival in OS patients. Furthermore, increased expression of Id-1 was observed in OS cell lines and ectopic expression of Id-1 significantly enhanced in vitro cell proliferation and promoted in vivo tumor growth, whereas knockdown of Id-1 suppressed OS cellsmore » growth. Moreover, our experimental data revealed that Id-1 promotes cell proliferation by facilitating cell cycle progression and inhibits cell apoptosis. Mechanistically, the effects of Id-1 in OS cells is at least partly through activation of PI3K/Akt signaling pathway. Therefore, we identified a tumorigenic role of Id-1 in OS and suggested a potential therapeutic target for OS patients. - Highlights: • Id-1 expression is positively correlated in OS patients with poor prognosis. • Overexpression of Id-1 promotes OS cell growth in vitro and in vivo. • Id-1induces cell cycle progression and inhibits cell apoptosis. • PI3K/Akt signaling pathway contributed to the oncogenic effects of Id-1 in OS cells.« less
Moorhouse, Rika; Slack, Catherine; Quayle, Michael; Essack, Zaynab; Lindegger, Graham
2014-06-30
South Africa is a major hub of HIV prevention trials, with plans for a licensure trial to start in 2015. The appropriate standards of care and of prevention in HIV vaccine trials are complex and debated issues and ethical guidelines offer some direction. However, there has been limited empirical exploration of South African stakeholders' perspectives on ethical guidance related to prevention and care in HIV vaccine trials. Site staff, Community Advisory Board members and Research Ethics Committee members involved with current HIV vaccine trials in South Africa were invited to participate in an exploration of their views. A questionnaire listed 10 care and 10 prevention recommendations drawn from two widely available sets of ethical guidelines for biomedical HIV prevention trials. Respondents (n = 98) rated each recommendation on five dimensions: "Familiarity with", "Ease of Understanding", "Ease of Implementing", "Perceived Protection", and "Agreement with" each ethical recommendation. The ratings were used to describe stakeholder perspectives on dimensions for each recommendation. Dimension ratings were averaged across the five dimensions and used as an indication of overall merit for each recommendation. Differences were explored across dimensions, between care-oriented and prevention-oriented recommendations, and between stakeholder groups. Both care and prevention recommendations were rated highly overall, with median ratings well above the scale midpoint. In general, informed consent recommendations were most positively rated. Care-related recommendations were rated significantly more positively than prevention-related recommendations, with the five lowest-rated recommendations being prevention-related. The most problematic dimension across all recommendations was "Ease of Implementing," and the least problematic was "Agreement with," suggesting the most pressing stakeholder concerns are practical rather than theoretical; that is, respondents agree with but see barriers to the attainment of these recommendations. We propose that prevention recommendations be prioritized for refinement, especially those assigned bottom-ranking scores for "Ease of Implementing", and/ or "Ease of Understanding" in order to assist vaccine stakeholders to better comprehend and implement these recommendations. Further qualitative research could also assist to better understand nuances in stakeholder reservations about implementing such recommendations.
This article appeared in a journal published by Elsevier. The attached copy is furnished to the author for internal non-commercial research and education use, including for instruction at the authors institution and sharing with colleagues. Other uses, including reproduction and distribution, or selling or licensing copies, or posting to personal, institutional or third party websites are prohibited. In most cases authors are permitted to post their version of the article (e.g. in Word or Tex form) to their personal website or institutional repository. Authors requiring further information regarding Elsevier's archiving and manuscript policies are encouraged to visit: http://www.elsevier.com/copyright People who inject drugs (PWID) are at high risk of HCV. Limited evidence of the effectiveness of prevention interventions and low uptake of treatment in this group highlight the need for increased investment in biomedical interventions, notably safe and efficacious vaccines. While several candidates are currently in development, field trials in PWID present challenges, including ethical issues associated with trial literacy, informed consent and standards of care. Significant biological and social factors and differences between HIV and HCV suggest that HCV warrants targeted vaccine preparedness research to lay the groundwork for successful implementation of future trials. PMID:20831914
Background South Africa is a major hub of HIV prevention trials, with plans for a licensure trial to start in 2015. The appropriate standards of care and of prevention in HIV vaccine trials are complex and debated issues and ethical guidelines offer some direction. However, there has been limited empirical exploration of South African stakeholders’ perspectives on ethical guidance related to prevention and care in HIV vaccine trials. Methods Site staff, Community Advisory Board members and Research Ethics Committee members involved with current HIV vaccine trials in South Africa were invited to participate in an exploration of their views. A questionnaire listed 10 care and 10 prevention recommendations drawn from two widely available sets of ethical guidelines for biomedical HIV prevention trials. Respondents (n = 98) rated each recommendation on five dimensions: “Familiarity with”, “Ease of Understanding”, “Ease of Implementing”, “Perceived Protection”, and “Agreement with” each ethical recommendation. The ratings were used to describe stakeholder perspectives on dimensions for each recommendation. Dimension ratings were averaged across the five dimensions and used as an indication of overall merit for each recommendation. Differences were explored across dimensions, between care-oriented and prevention-oriented recommendations, and between stakeholder groups. Results Both care and prevention recommendations were rated highly overall, with median ratings well above the scale midpoint. In general, informed consent recommendations were most positively rated. Care-related recommendations were rated significantly more positively than prevention-related recommendations, with the five lowest-rated recommendations being prevention-related. The most problematic dimension across all recommendations was “Ease of Implementing,” and the least problematic was “Agreement with,” suggesting the most pressing stakeholder concerns are practical rather than theoretical; that is, respondents agree with but see barriers to the attainment of these recommendations. Conclusions We propose that prevention recommendations be prioritized for refinement, especially those assigned bottom-ranking scores for “Ease of Implementing”, and/ or “Ease of Understanding” in order to assist vaccine stakeholders to better comprehend and implement these recommendations. Further qualitative research could also assist to better understand nuances in stakeholder reservations about implementing such recommendations. PMID:24981027
The conventional response of governments to protect their populations against the threat of influenza has been to ensure adequate vaccine production and/or access to supplies of vaccines and antiviral medications. This focus has, in turn, shaped the global governance structures around pandemic influenza, with collective efforts centred on facilitating virus sharing, maintaining and increasing vaccine production, and ensuring access to pharmaceuticals - responses that remain unattainable for many low- and middle-income countries (LMICs) in the short to medium term. This paper argues that this emphasis on pharmacological responses reflects a particular view of biomedicine that pays inadequate attention to the weak capacity of many health systems. In more recent years, this dynamic has been further exacerbated by the influence of evidence-based medicine (EBM) that preferences certain types of biomedical knowledge and practice. This paper explores the role that EBM has played in shaping the global governance of pandemic influenza, and how it has served to reinforce and reify the authority of particular groups of actors, including policy-makers, elected officials and the medical community. The paper concludes that only by unpacking these structures and revealing the political authority in play can alternative policy responses more appropriate to LMICs be considered.
A method for treatment and amelioration of breast, cervical, ovarian, endometrial, squamous cells, prostate cancer and melanoma in a patient comprising targeting Id-1 or Id-2 gene expression with a delivery vehicle comprising a product which modulates Id-1 or Id-2 expression.
...The following applicants filed AM or FM proposals to change the community of license: ALEXANDRA COMMUNICATIONS, INC., Station KRKZ- FM, Facility ID 189499, BPH-20120725AHL, From NETARTS, OR, To CHINOOK, WA; ALEXANDRA COMMUNICATIONS, INC., Station KTIL, Facility ID 50554, BMP-20120725AHO, From TILLAMOOK, OR, To NETARTS, OR; BIRACH BROADCASTING CORPORATION, Station NEW, Facility ID 136069, BMP- 20120813ABI, From TERRE HAUTE, IN, To PEOTONE, IN; BRAHMIN BROADCASTING CORPORATION, Station KPAD, Facility ID 166006, BMPH-20111230ABO, From RAWLINS, WY, To WHEATLAND, WY; CITICASTERS LICENSES, INC., Station WOGB, Facility ID 89, BPH-20120720ACQ, From KAUKAUNA, WI, To REEDSVILLE, WI; CLEAR CHANNEL BROADCASTING LICENSES, INC., Station WQNS, Facility ID 41008, BPH-20120807ACK, From WAYNESVILLE, NC, To WOODFIN, NC; CORPORATION FOR NATIVE BROADCASTING, Station KXSW, Facility ID 171940, BPED-20120717AAL, From SISSETON, SD, To AGENCY VILLAGE, SD; CRAIN MEDIA GROUP, LLC, Station KEAZ, Facility ID 48748, BPH-20120716ADV, From HEBER SPRINGS, AR, To KENSETT, AR; DAIJ MEDIA, LLC, Station KJOZ, Facility ID 20625, BP-20120731AAA, From CONROE, TX, To FRIENDSWOOD, TX; ENTERTAINMENT MEDIA TRUST, DENNIS J.WATKINS, TRUSTEE, Station KQQZ, Facility ID 5281, BMP-20120628AAL, From FAIRVIEW HEIGHTS, IL, To DESOTO, MO; GOOD TIDINGS TRUST, INC., Station WAYR, Facility ID 24625, BP-20120724ABN, From ORANGE PARK, FL, To FLEMING ISLAND, FL; IHR EDUCATIONAL BROADCASTING, Station NEW, Facility ID 160745, BMP-20120821AAF, From MERRILL, OR, To ALTAMONT, OR; JER LICENSES, LLC, Station NEW, Facility ID 190382, BNPH-20120529ALR, From GUNNISON, CO, To DOTSERO, CO; KIERTRON, INC., Station KBRT, Facility ID 34588, BMP-20120809AAQ, From AVALON, CA, To COSTA MESA, CA; MALVERN ENTERTAINMENT CORPORATION, Station KHAN, Facility ID 164210, BPH-20120716ADT, From KENSETT, AR, To MAGNESS, AR; SYNERGY BROADCAST NORTH DAKOTA, LLC, Station KLTQ, Facility ID 164305, BPH-20120727AHW, From NEW ENGLAND, ND, To BEULAH, ND; SYNERGY BROADCAST NORTH DAKOTA, LLC, Station KQLZ, Facility ID 166059, BPH-20120727AID, From BEULAH, ND, To NEW ENGLAND, ND; THE OPP BROADCASTING CO., INC., Station WAMI- FM, Facility ID 66211, BPH-20120612ACO, From FORT DEPOSIT, AL, To OPP, AL; TRI STATE RADIO, LLC, Station KYLZ, Facility ID 170181, BPH- 20120807ACF, From PAROWAN, UT, To ENOCH, UT.
Salvador-Carulla, Luis; Martínez-Leal, Rafael; Heyler, Carla; Alvarez-Galvez, Javier; Veenstra, Marja Y.; García-Ibáñez, Jose; Carpenter, Sylvia; Bertelli, Marco; Munir, Kerim; Torr, Jennifer; Van Schrojenstein Lantman-de Valk, Henny M. J.
2015-01-01
Background Intellectual disability (ID) has consequences at all stages of life, requires high service provision and leads to high health and societal costs. However, ID is largely disregarded as a health issue by national and international organisations, as are training in ID and in the health aspects of ID at every level of the education system. Specific aim This paper aims to (1) update the current information about availability of training and education in ID and related health issues in Europe with a particular focus in mental health; and (2) to identify opportunities arising from the initial process of educational harmonization in Europe to include ID contents in health sciences curricula and professional training. Method We carried out a systematic search of scientific databases and websites, as well as policy and research reports from the European Commission, European Council and WHO. Furthermore, we contacted key international organisations related to health education and/or ID in Europe, as well as other regional institutions. Results ID modules and contents are minimal in the revised health sciences curricula and publications on ID training in Europe are equally scarce. European countries report few undergraduate and graduate training modules in ID, even in key specialties such as paediatrics. Within the health sector, ID programmes focus mainly on psychiatry and psychology. Conclusion The poor availability of ID training in health sciences is a matter of concern. However, the current European policy on training provides an opportunity to promote ID in the curricula of programmes at all levels. This strategy should address all professionals working in ID and it should increase the focus on ID relative to other developmental disorders at all stages of life. PMID:25705375
Intellectual disability (ID) has consequences at all stages of life, requires high service provision and leads to high health and societal costs. However, ID is largely disregarded as a health issue by national and international organisations, as are training in ID and in the health aspects of ID at every level of the education system. This paper aims to (1) update the current information about availability of training and education in ID and related health issues in Europe with a particular focus in mental health; and (2) to identify opportunities arising from the initial process of educational harmonization in Europe to include ID contents in health sciences curricula and professional training. We carried out a systematic search of scientific databases and websites, as well as policy and research reports from the European Commission, European Council and WHO. Furthermore, we contacted key international organisations related to health education and/or ID in Europe, as well as other regional institutions. ID modules and contents are minimal in the revised health sciences curricula and publications on ID training in Europe are equally scarce. European countries report few undergraduate and graduate training modules in ID, even in key specialties such as paediatrics. Within the health sector, ID programmes focus mainly on psychiatry and psychology. The poor availability of ID training in health sciences is a matter of concern. However, the current European policy on training provides an opportunity to promote ID in the curricula of programmes at all levels. This strategy should address all professionals working in ID and it should increase the focus on ID relative to other developmental disorders at all stages of life.
Shankar, Rohit; Rowe, Charles; Van Hoorn, Alje; Henley, William; Laugharne, Richard; Cox, David; Pande, Raj; Roy, Ashok; Sander, Josemir W
2018-01-01
One quarter of people with epilepsy have an intellectual disability (ID) and one fifth of people with an ID have epilepsy. Both conditions are associated with higher levels of morbidity, stigma and premature mortality. There have been calls for action to promote more research in this group. We examined if this group are represented adequately in current research. The proportion of research output in epilepsy conferences and publications relevant to ID and the proportion in ID conferences and publications on epilepsy for 2015-2016 were identified. As the percentage of children in the population with epilepsy is 17%, research output of this group was compared with the ID group. Recognised material was classified based on whether it applied to general epilepsy/ID research, children with epilepsy or people with epilepsy and ID. Data was analysed to determine the proportion of presented research specifically identifying people with epilepsy and ID. Fewer than 2% of presentations at epilepsy conferences specifically related to the ID and epilepsy group compared to 15% relating to children with epilepsy. Similarly only 1.4% of the research presented at major ID conferences related to those with people with epilepsy and ID. About 5% of published research in the field of epilepsy related to those with ID as compared with 24% for children with epilepsy. Twelve percent of published research in ID specifically identified epilepsy. Publications and conference presentations, on the population with epilepsy and comorbid ID is under-represented. Increased research in this area might assist in improving the quality of care for this relatively neglected group.
HIV prevention research has been facing increasing ethical and operational challenges. Factors influencing the design and conduct of HIV prevention trials include a rapidly changing evidence base, new biomedical prevention methods and modalities being tested, a large diversity of countries, sites and populations affected by HIV and participating in trials, and challenges of developing and making available products that will be feasible and affordable for at-risk populations. To discuss these challenges, a meeting, Ethical considerations around novel combination prevention modalities in HIV prevention and vaccine trials in resource-limited settings, was convened by NIH/NIAID/Division of AIDS on April 22-23, 2013. Several themes emerged from the meeting: (1) because of both trial design and ethical complexities, choosing prevention packages and designing combination prevention research trials will need to be evaluated on a case by case basis in different clinical trials, countries, and health systems; (2) multilevel stakeholder engagement from the beginning is vital to a fair and transparent process and also to designing ethical and relevant trials; (3) research should generally be responsive to a host country's needs, and sponsors and stakeholders should work together to address potential barriers to future access; and finally, (4) another meeting including a broader group of stakeholders is needed to address many of the outstanding ethical issues raised by this meeting. We offer an overview of the meeting and the key discussion points and recommendations to help guide the design and conduct of future HIV prevention and vaccine research in resource-limited settings.
We present the preparation, resources, results and analysis of three tasks of the BioNLP Shared Task 2011: the main tasks on Infectious Diseases (ID) and Epigenetics and Post-translational Modifications (EPI), and the supporting task on Entity Relations (REL). The two main tasks represent extensions of the event extraction model introduced in the BioNLP Shared Task 2009 (ST'09) to two new areas of biomedical scientific literature, each motivated by the needs of specific biocuration tasks. The ID task concerns the molecular mechanisms of infection, virulence and resistance, focusing in particular on the functions of a class of signaling systems that are ubiquitous in bacteria. The EPI task is dedicated to the extraction of statements regarding chemical modifications of DNA and proteins, with particular emphasis on changes relating to the epigenetic control of gene expression. By contrast to these two application-oriented main tasks, the REL task seeks to support extraction in general by separating challenges relating to part-of relations into a subproblem that can be addressed by independent systems. Seven groups participated in each of the two main tasks and four groups in the supporting task. The participating systems indicated advances in the capability of event extraction methods and demonstrated generalization in many aspects: from abstracts to full texts, from previously considered subdomains to new ones, and from the ST'09 extraction targets to other entities and events. The highest performance achieved in the supporting task REL, 58% F-score, is broadly comparable with levels reported for other relation extraction tasks. For the ID task, the highest-performing system achieved 56% F-score, comparable to the state-of-the-art performance at the established ST'09 task. In the EPI task, the best result was 53% F-score for the full set of extraction targets and 69% F-score for a reduced set of core extraction targets, approaching a level of performance sufficient for user-facing applications. In this study, we extend on previously reported results and perform further analyses of the outputs of the participating systems. We place specific emphasis on aspects of system performance relating to real-world applicability, considering alternate evaluation metrics and performing additional manual analysis of system outputs. We further demonstrate that the strengths of extraction systems can be combined to improve on the performance achieved by any system in isolation. The manually annotated corpora, supporting resources, and evaluation tools for all tasks are available from http://www.bionlp-st.org and the tasks continue as open challenges for all interested parties.
Intellectual disability (ID) occurs in almost 3% of newborns. Despite substantial research, a fundamental question about its origin and links to intelligence (IQ) still remains. ID has been shown to be inherited and has been accepted as the extreme low of the normal IQ distribution. However, ID displays a complex pattern of inheritance. Previously, noninherited rare mutations were shown to contribute to severe ID risk in individual families, but in the majority of cases causes remain unknown. Common variants associated with ID risk in the population have not been systematically established. Here we evaluate the hypothesis, originally proposed almost 1 century ago, that most ID is caused by the same genetic and environmental influences responsible for the normal distribution of IQ, but that severe ID is not. We studied more than 1,000,000 sibling pairs and 9,000 twin pairs assessed for IQ and for the presence of ID. We evaluated whether genetic and environmental influences at the extremes of the distribution are different from those operating in the normal range. Here we show that factors influencing mild ID (lowest 3% of IQ distribution) were similar to those influencing IQ in the normal range. In contrast, the factors influencing severe ID (lowest 0.5% of IQ distribution) differ from those influencing mild ID or IQ scores in the normal range. Taken together, our results suggest that most severe ID is a distinct condition, qualitatively different from the preponderance of ID, which, in turn, represents the low extreme of the normal distribution of intelligence.
Stover, John; Hallett, Timothy B; Wu, Zunyou; Warren, Mitchell; Gopalappa, Chaitra; Pretorius, Carel; Ghys, Peter D; Montaner, Julio; Schwartländer, Bernhard
2014-01-01
In 2011 an Investment Framework was proposed that described how the scale-up of key HIV interventions could dramatically reduce new HIV infections and deaths in low and middle income countries by 2015. This framework included ambitious coverage goals for prevention and treatment services resulting in a reduction of new HIV infections by more than half. However, it also estimated a leveling in the number of new infections at about 1 million annually after 2015. We modeled how the response to AIDS can be further expanded by scaling up antiretroviral treatment (ART) within the framework provided by the 2013 WHO treatment guidelines. We further explored the potential contributions of new prevention technologies: 'Test and Treat', pre-exposure prophylaxis and an HIV vaccine. Immediate aggressive scale up of existing approaches including the 2013 WHO guidelines could reduce new infections by 80%. A 'Test and Treat' approach could further reduce new infections. This could be further enhanced by a future highly effective pre-exposure prophylaxis and an HIV vaccine, so that a combination of all four approaches could reduce new infections to as low as 80,000 per year by 2050 and annual AIDS deaths to 260,000. In a set of ambitious scenarios, we find that immediate implementation of the 2013 WHO antiretroviral therapy guidelines could reduce new HIV infections by 80%. Further reductions may be achieved by moving to a 'Test and Treat' approach, and eventually by adding a highly effective pre-exposure prophylaxis and an HIV vaccine, if they become available.
Azam, Maleeha; Ayub, Humaira; Vissers, Lisenka E. L. M.; Gilissen, Christian; Ali, Syeda Hafiza Benish; Riaz, Moeen; Veltman, Joris A.; Pfundt, Rolph; van Bokhoven, Hans; Qamar, Raheel
2014-01-01
Intellectual disability (ID) is a major health problem mostly with an unknown etiology. Recently exome sequencing of individuals with ID identified novel genes implicated in the disease. Therefore the purpose of the present study was to identify the genetic cause of ID in one syndromic and two non-syndromic Pakistani families. Whole exome of three ID probands was sequenced. Missense variations in two plausible novel genes implicated in autosomal recessive ID were identified: lysine (K)-specific methyltransferase 2B (KMT2B), zinc finger protein 589 (ZNF589), as well as hedgehog acyltransferase (HHAT) with a de novo mutation with autosomal dominant mode of inheritance. The KMT2B recessive variant is the first report of recessive Kleefstra syndrome-like phenotype. Identification of plausible causative mutations for two recessive and a dominant type of ID, in genes not previously implicated in disease, underscores the large genetic heterogeneity of ID. These results also support the viewpoint that large number of ID genes converge on limited number of common networks i.e. ZNF589 belongs to KRAB-domain zinc-finger proteins previously implicated in ID, HHAT is predicted to affect sonic hedgehog, which is involved in several disorders with ID, KMT2B associated with syndromic ID fits the epigenetic module underlying the Kleefstra syndromic spectrum. The association of these novel genes in three different Pakistani ID families highlights the importance of screening these genes in more families with similar phenotypes from different populations to confirm the involvement of these genes in pathogenesis of ID. PMID:25405613
High-throughput genotyping platforms enable simultaneous analysis of multiple polymorphisms for blood group typing. BLOODchip® ID is a genotyping platform based on Luminex® xMAP technology for simultaneous determination of 37 red blood cell (RBC) antigens (ID CORE XT) and 18 human platelet antigens (HPA) (ID HPA XT) using the BIDS XT software. In this international multicentre study, the performance of ID CORE XT and ID HPA XT, using the centres' current genotyping methods as the reference for comparison, and the usability and practicality of these systems, were evaluated under working laboratory conditions. DNA was extracted from whole blood in EDTA with Qiagen methodologies. Ninety-six previously phenotyped/genotyped samples were processed per assay: 87 testing samples plus five positive controls and four negative controls. Results were available for 519 samples: 258 with ID CORE XT and 261 with ID HPA XT. There were three "no calls" that were either caused by human error or resolved after repeating the test. Agreement between the tests and reference methods was 99.94% for ID CORE XT (9,540/9,546 antigens determined) and 100% for ID HPA XT (all 4,698 alleles determined). There were six discrepancies in antigen results in five RBC samples, four of which (in VS, N, S and Do(a)) could not be investigated due to lack of sufficient sample to perform additional tests and two of which (in S and C) were resolved in favour of ID CORE XT (100% accuracy). The total hands-on time was 28-41 minutes for a batch of 16 samples. Compared with the reference platforms, ID CORE XT and ID HPA XT were considered simpler to use and had shorter processing times. ID CORE XT and ID HPA XT genotyping platforms for RBC and platelet systems were accurate and user-friendly in working laboratory settings.
We present the preparation, resources, results and analysis of three tasks of the BioNLP Shared Task 2011: the main tasks on Infectious Diseases (ID) and Epigenetics and Post-translational Modifications (EPI), and the supporting task on Entity Relations (REL). The two main tasks represent extensions of the event extraction model introduced in the BioNLP Shared Task 2009 (ST'09) to two new areas of biomedical scientific literature, each motivated by the needs of specific biocuration tasks. The ID task concerns the molecular mechanisms of infection, virulence and resistance, focusing in particular on the functions of a class of signaling systems that are ubiquitous in bacteria. The EPI task is dedicated to the extraction of statements regarding chemical modifications of DNA and proteins, with particular emphasis on changes relating to the epigenetic control of gene expression. By contrast to these two application-oriented main tasks, the REL task seeks to support extraction in general by separating challenges relating to part-of relations into a subproblem that can be addressed by independent systems. Seven groups participated in each of the two main tasks and four groups in the supporting task. The participating systems indicated advances in the capability of event extraction methods and demonstrated generalization in many aspects: from abstracts to full texts, from previously considered subdomains to new ones, and from the ST'09 extraction targets to other entities and events. The highest performance achieved in the supporting task REL, 58% F-score, is broadly comparable with levels reported for other relation extraction tasks. For the ID task, the highest-performing system achieved 56% F-score, comparable to the state-of-the-art performance at the established ST'09 task. In the EPI task, the best result was 53% F-score for the full set of extraction targets and 69% F-score for a reduced set of core extraction targets, approaching a level of performance sufficient for user-facing applications. In this study, we extend on previously reported results and perform further analyses of the outputs of the participating systems. We place specific emphasis on aspects of system performance relating to real-world applicability, considering alternate evaluation metrics and performing additional manual analysis of system outputs. We further demonstrate that the strengths of extraction systems can be combined to improve on the performance achieved by any system in isolation. The manually annotated corpora, supporting resources, and evaluation tools for all tasks are available from http://www.bionlp-st.org and the tasks continue as open challenges for all interested parties. PMID:22759456
Naaber, Paul; Makoid, Ene; Aus, Anneli; Loivukene, Krista; Poder, Airi
2009-01-01
Laboratory diagnosis of syphilis is usually accomplished by serology. There are currently a large number of different commercial treponemal tests available that vary in format, sensitivity and specificity. To evaluate the ID-PaGIA Syphilis Antibody Test as an alternative to other specific treponemal tests for primary screening or confirmation of diagnosis. Serum samples from healthy adults (n = 100) were used for detection of specificity of ID-PaGIA. To evaluate sensitivity of ID-PaGIA serum samples (n = 101) from patients with confirmed or suspected syphilis were tested for syphilis antibodies with FTA-Abs IgM, ID-PaGIA, ELISA IgM and TPHA tests. No false-positive results were found with ID-PaGIA. Sensitivity of various treponemal tests was the following: FTA-Abs IgM: 95.5%, ID-PaGIA and ELISA IgM: 94%, and TPHA 75%. The positive and negative predictive values of ID-PaGIA were 100 and 89.5%, respectively. Compared with other treponemal tests ID-PaGIA has excellent sensitivity and specificity.
Intellectual disability (ID) occurs in almost 3% of newborns. Despite substantial research, a fundamental question about its origin and links to intelligence (IQ) still remains. ID has been shown to be inherited and has been accepted as the extreme low of the normal IQ distribution. However, ID displays a complex pattern of inheritance. Previously, noninherited rare mutations were shown to contribute to severe ID risk in individual families, but in the majority of cases causes remain unknown. Common variants associated with ID risk in the population have not been systematically established. Here we evaluate the hypothesis, originally proposed almost 1 century ago, that most ID is caused by the same genetic and environmental influences responsible for the normal distribution of IQ, but that severe ID is not. We studied more than 1,000,000 sibling pairs and 9,000 twin pairs assessed for IQ and for the presence of ID. We evaluated whether genetic and environmental influences at the extremes of the distribution are different from those operating in the normal range. Here we show that factors influencing mild ID (lowest 3% of IQ distribution) were similar to those influencing IQ in the normal range. In contrast, the factors influencing severe ID (lowest 0.5% of IQ distribution) differ from those influencing mild ID or IQ scores in the normal range. Taken together, our results suggest that most severe ID is a distinct condition, qualitatively different from the preponderance of ID, which, in turn, represents the low extreme of the normal distribution of intelligence. PMID:26711998
Keeping up with journal articles on a daily basis is an important activity of scientists engaged in biomedical research. Usually, journal articles and papers in the field of biomedicine are accessed through the Medline/PubMed electronic library. In the process of navigating PubMed, researchers unknowingly generate user-specific reading profiles that can be shared within a social networking environment. This paper examines the structure of the social networking environment generated by PubMed users. A web browser plugin was developed to map [in Medical Subject Headings (MeSH) terms] the reading patterns of individual PubMed users. We developed a scientific social network based on the personal research profiles of readers of biomedical articles. A browser plugin is used to record the digital object identifier or PubMed ID of web pages. Recorded items are posted on the activity feed and automatically mapped to PubMed abstract. Within the activity feed a user can trace back previously browsed articles and insert comments. By calculating the frequency with which specific MeSH occur, the research interests of PubMed users can be visually represented with a tag cloud. Finally, research profiles can be searched for matches between network users. A social networking environment was created using MeSH terms to map articles accessed through the Medline/PubMed online library system. In-network social communication is supported by the recommendation of articles and by matching users with similar scientific interests. The system is available at http://bioknol.org/en/.
Studies comparing the sexual attitudes of men and women with intellectual disabilities (ID) have been limited. A mixed-methods approach was employed to explore attitudes toward sexuality among men and women with ID in Taiwan and to ascertain the disparities between attitudes among men and women with ID. First, fifty-six men and forty-four women with mild and moderate ID completed a face-to-face interview survey. After this, focus groups were conducted for men and women with ID. Results indicated that women with ID were more likely to have negative attitudes toward parenting and non-reproductive sexual behavior than their male counterparts. Qualitative data indicated that men and women with ID had different sexual attitudes and experiences and were subject to different expectations from people around them. Both men and women with ID had very limited opportunities to develop romantic relationships and a healthy sexual identity. Sexual rights awareness and practice should be matters of concern for this group of adults and women with ID in particular.
Desprez, Pierre-Yves [El Cerrito, CA; Campisi, Judith [Berkeley, CA
2011-10-04
A method for detection and prognosis of breast cancer and other types of cancer. The method comprises detecting expression, if any, for both an Id-1 and an Id-2 genes, or the ratio thereof, of gene products in samples of breast tissue obtained from a patient. When expressed, Id-1 gene is a prognostic indicator that breast cancer cells are invasive and metastatic, whereas Id-2 gene is a prognostic indicator that breast cancer cells are localized and noninvasive in the breast tissue.
The purpose of this study was to generate insulin dose (ID) percentiles for children and adolescents with type 1 diabetes mellitus (DM1) having the opportunity to assess this important parameter in relation to age and sex. Daily IDs per weight (ID/kg) were recorded in 22,177 patients with DM1 (3-25 years of age, DM1 duration of more than 2 years, 48% female) and ID percentiles (ID-Perc) were created statistically. The ID-Perc were compared between male and female, and between multiple insulin injection therapy (MIT) and continuous s.c. insulin infusion (CSII). A multivariate regression analysis was performed for ID in the third year of DM1 with ID/kg, body weight, age, gender, and insulin delivery regimen as variables. The 50th ID-Perc (P50) varied among 0.67 IU/kg (age 3 years), 0.93 IU/kg (13 years), and 0.70 IU/kg (23 years) increasing from early childhood to adolescence and decreasing toward adulthood. Highest P50 ID was found at 12 years in females (0.94 IU/kg) and at 14 years in males (0.92 IU/kg). Using ICT, the ID was significantly higher compared with CSII (P50: 0.94 IU/kg versus 0.79 IU/kg at 13 years). In multivariate regression analysis, ID was significantly (P>0.001) associated with age, gender, and insulin delivery regime. The ID-Perc were significantly different during various periods of childhood and were influenced by gender, body weight, and insulin injection regimes. Therefore, the presented data 1) provide evidence to interpret individual ID in children and adolescents with DM1 and 2) more specifically identify children with unusually high (insulin resistance and non-compliance) or low (MODY and persistent remission) insulin requirement.
Research findings investigating the sociodemographics of autism spectrum disorder (ASD) have been inconsistent and rarely considered the presence of intellectual disability (ID). We used population data on Western Australian singletons born from 1984 to 1999 (n = 398,353) to examine the sociodemographic characteristics of children diagnosed with ASD with or without ID, or ID without ASD compared with non-affected children. The profiles for the four categories examined, mild-moderate ID, severe ID, ASD without ID and ASD with ID varied considerably and we often identified a gradient effect where the risk factors for mild-moderate ID and ASD without ID were at opposite extremes while those for ASD with ID were intermediary. This was demonstrated clearly with increased odds of ASD without ID amongst older mothers aged 35 years and over (odds ratio (OR) = 1.69 [CI: 1.18, 2.43]), first born infants (OR = 2.78; [CI: 1.67, 4.54]), male infants (OR = 6.57 [CI: 4.87, 8.87]) and increasing socioeconomic advantage. In contrast, mild-moderate ID was associated with younger mothers aged less than 20 years (OR = 1.88 [CI: 1.57, 2.25]), paternal age greater than 40 years (OR = 1.59 [CI: 1.36, 1.86]), Australian-born and Aboriginal mothers (OR = 1.60 [CI: 1.41, 1.82]), increasing birth order and increasing social disadvantage (OR = 2.56 [CI: 2.27, 2.97]). Mothers of infants residing in regional or remote areas had consistently lower risk of ASD or ID and may be linked to reduced access to services or under-ascertainment rather than a protective effect of location. The different risk profiles observed between groups may be related to aetiological differences or ascertainment factors or both. Untangling these pathways is challenging but an urgent public health priority in view of the supposed autism epidemic.
Tabima, Javier F.; Everhart, Sydney E.; Larsen, Meredith M.; Weisberg, Alexandra J.; Kamvar, Zhian N.; Tancos, Matthew A.; Smart, Christine D.; Chang, Jeff H.
2016-01-01
Development of tools to identify species, genotypes, or novel strains of invasive organisms is critical for monitoring emergence and implementing rapid response measures. Molecular markers, although critical to identifying species or genotypes, require bioinformatic tools for analysis. However, user-friendly analytical tools for fast identification are not readily available. To address this need, we created a web-based set of applications called Microbe-ID that allow for customizing a toolbox for rapid species identification and strain genotyping using any genetic markers of choice. Two components of Microbe-ID, named Sequence-ID and Genotype-ID, implement species and genotype identification, respectively. Sequence-ID allows identification of species by using BLAST to query sequences for any locus of interest against a custom reference sequence database. Genotype-ID allows placement of an unknown multilocus marker in either a minimum spanning network or dendrogram with bootstrap support from a user-created reference database. Microbe-ID can be used for identification of any organism based on nucleotide sequences or any molecular marker type and several examples are provided. We created a public website for demonstration purposes called Microbe-ID (microbe-id.org) and provided a working implementation for the genus Phytophthora (phytophthora-id.org). In Phytophthora-ID, the Sequence-ID application allows identification based on ITS or cox spacer sequences. Genotype-ID groups individuals into clonal lineages based on simple sequence repeat (SSR) markers for the two invasive plant pathogen species P. infestans and P. ramorum. All code is open source and available on github and CRAN. Instructions for installation and use are provided at https://github.com/grunwaldlab/Microbe-ID. PMID:27602267
Tabima, Javier F; Everhart, Sydney E; Larsen, Meredith M; Weisberg, Alexandra J; Kamvar, Zhian N; Tancos, Matthew A; Smart, Christine D; Chang, Jeff H; Grünwald, Niklaus J
2016-01-01
Development of tools to identify species, genotypes, or novel strains of invasive organisms is critical for monitoring emergence and implementing rapid response measures. Molecular markers, although critical to identifying species or genotypes, require bioinformatic tools for analysis. However, user-friendly analytical tools for fast identification are not readily available. To address this need, we created a web-based set of applications called Microbe-ID that allow for customizing a toolbox for rapid species identification and strain genotyping using any genetic markers of choice. Two components of Microbe-ID, named Sequence-ID and Genotype-ID, implement species and genotype identification, respectively. Sequence-ID allows identification of species by using BLAST to query sequences for any locus of interest against a custom reference sequence database. Genotype-ID allows placement of an unknown multilocus marker in either a minimum spanning network or dendrogram with bootstrap support from a user-created reference database. Microbe-ID can be used for identification of any organism based on nucleotide sequences or any molecular marker type and several examples are provided. We created a public website for demonstration purposes called Microbe-ID (microbe-id.org) and provided a working implementation for the genus Phytophthora (phytophthora-id.org). In Phytophthora-ID, the Sequence-ID application allows identification based on ITS or cox spacer sequences. Genotype-ID groups individuals into clonal lineages based on simple sequence repeat (SSR) markers for the two invasive plant pathogen species P. infestans and P. ramorum. All code is open source and available on github and CRAN. Instructions for installation and use are provided at https://github.com/grunwaldlab/Microbe-ID.
Attitudes of teachers (N = 96) and paraprofessionals (N = 48) working with students with intellectual disability (ID) towards the new definition of ID (Luckasson et al., 1992, 2002), was examined. The main innovation of the new definition of ID is the cancellation of the four ID levels, suggesting an optimistic view, especially towards individuals…
Desprez, Pierre-Yves [El Cerrito, CA; Campisi, Judith [Berkeley, CA
2008-09-30
A method for detection and prognosis of breast cancer and other types of cancer. The method comprises detecting expression, if any, for both an Id-1 and an Id-2 genes, or the ratio thereof, of gene products in samples of breast tissue obtained from a patient. When expressed, Id-1 gene is a prognostic indicator that breast cancer cells are invasive and metastatic, whereas Id-2 gene is a prognostic indicator that breast cancer cells are localized and noninvasive in the breast tissue.
Yeasts, as Eukaryotes, offer unique features for ease of growth and genetic manipulation possibilities, making it an exceptional microbial host. Areas covered: This review provides general and patent-oriented insights into production of biopharmaceuticals by yeasts. Patents, wherever possible, were correlated to the original or review articles. The review describes applications of major GRAS (generally regarded as safe) yeasts for the production of therapeutic proteins and subunit vaccines; additionally, immunomodulatory properties of yeast cell wall components were reviewed for use of whole yeast cells as a new vaccine platform. The second part of the review will discuss yeast- humanization strategies and innovative applications. Expert opinion: Biomedical applications of yeasts were initiated by utilization of Saccharomyces cerevisiae, for production of leavened (fermented) products, and advanced to serve to produce biopharmaceuticals. Higher biomass production and expression/secretion yields, more similarity of glycosylation patterns to mammals and possibility of host-improvement strategies through application of synthetic biology might enhance selection of Pichia pastoris (instead of S. cerevisiae) as a host for production of biopharmaceutical in future. Immunomodulatory properties of yeast cell wall β-glucans and possibility of intracellular expression of heterologous pathogen/tumor antigens in yeast cells have expanded their application as a new platform, 'Whole Yeast Vaccines'.
The purpose of this research is to elucidate the actual status of Infectious Diseases (ID) Fellowship programs in Japan to improve them further. We conducted qualitative interviews with infectious diseases fellows and his/her faculty consultants from 10 institutions providing ID Fellowships in Japan. We qualitatively analysed the data to delineate the actual status of each program and the fellowship program policies overall, and to identify measures for further improvement. The interviews revealed that there are largely two kinds of ID fellowships; ID programs entirely devoting full time to infectious diseases, and programs that are subordinate concepts of other subspecialties, where only a portion of hours were devoted to ID. Some institutions did not even have an ID department. Time spent by the faculty consultants on fellows also varied among programs. The desire for improvement also varied among interviewees; some being happy with the current system while others demanded radical reform. Even though there are many ID fellowship programs in Japan, the content, quality, and concepts apparently vary among programs. The perceptions by interviewees on the educational system differed, depending on the standpoints they have on ID physicians. There probably needs to be a coherency in the provision of ID fellowship programs so that fellows acquire competency in the subspecialty with sufficient expertise to act as independent ID specialists. Further studies are necessary for the improvement of ID subspecialty training in Japan.
Intellectual disability (ID) is one of the many features manifested in various genetic syndromes leading to deficits in cognitive function among affected individuals. ID is a feature affected by polygenes and multiple environmental factors. It leads to a broad spectrum of affected clinical and behavioral characteristics among patients. Until now, the causative mechanism of ID is unknown and the progression of the condition is poorly understood. Advancement in technology and research had identified various genetic abnormalities and defects as the potential cause of ID. However, the link between these abnormalities with ID is remained inconclusive and the roles of many newly discovered genetic components such as non-coding RNAs have not been thoroughly investigated. In this review, we aim to consolidate and assimilate the latest development and findings on a class of small non-coding RNAs known as microRNAs (miRNAs) involvement in ID development and progression with special focus on Down syndrome (DS) and X-linked ID (XLID) [including Fragile X syndrome (FXS)]. PMID:23596395
Plank-Bazinet, Jennifer L; Sampson, Annie; Kornstein, Susan G; Germino, Gregory G; Robert-Guroff, Marjorie; Gilman, Stephen E; Wetherington, Cora Lee; Cook, Nakela; Cornelison, Terri L; Begg, Lisa; Clayton, Janine Austin
2018-01-01
Sex and gender are critical contributors to overall health and disease, and considering both in research informs the development of prevention strategies and treatment interventions for both men and women. The National Institutes of Health (NIH) Office of Research on Women's Health sponsored a preconference workshop on this topic at the 24th Annual Women's Health Congress, which was held in Crystal City, VA, in April 2016. The workshop featured presentations by NIH intramural and extramural scientists who presented data on a variety of topics including polycystic kidney disease, vaccine protection, depression, drug addiction, and cardiovascular disease. In this publication, we discuss the major points of each presentation and demonstrate the importance of considering sex and gender in biomedical research.
MKK) Daytona Beach, FL (DAB) Boise, ID (BOI) Fort Lauderdale, FL (FLL) Idaho Falls Fanning Field, ID (IDA) Fort Lauderdale Executive, FL (FXE... Lewiston , ID (LWS) Fort Myers Page Field, FL (FMY) Pocatello, ID (PIH) Fort Myers Regional, FL (RSW) Twin Falls, ID (TWF) Fort Pierce, FL (FPR) Alton St... Idaho (SUN) 6. Marion Williamson County, Illinois (MWA) 7. Waukegan, Illinois (UGN) 8. Topeka-Phillip Ballard, Kansas (TOP) 9. Owensboro-Daviees County
Women with intellectual disabilities (ID) have cognitive impairment and communication difficulties; for both caregivers and clinical personnel, discovering the early symptoms of breast cancer among women with ID is challenging. The mammography utilization rate of women with ID was significantly lower than that of women in the general population. This study employed a 2008 database of people with disabilities in Taiwan as a research target and analyzed the mammography utilization rate of women with ID aged 50–69 years. In addition, relevant factors influencing mammography utilization among women with ID were also investigated. A total of 4370 participants were recruited and the majority were illiterate or had elementary-level educations (82.27%). The majority of the participants had ID that was more severe than mild (83.80%). The mammography utilization rate of women with ID was 4.32%, which was significantly lower than that of women in the general population (12%). The mammography utilization rate among women with ID who were married, had higher education levels, and had been diagnosed with cancer, diabetes, or mild ID was significantly higher. However, the mammography utilization rate among women with ID, who had elementary-level educations or were illiterate, was only 4.03%. The utilization rate among women with profound ID was only 2.65%. Women with ID who had undergone pap smears or had utilized adult preventive health services demonstrated a significantly higher mammography utilization rate. This study identified that education level, a diagnosis of diabetes, and the application of pap smears or adult preventive health services were primary factors that influenced the mammography utilization rate among women with ID. This study also observed that in Taiwan, the mammography utilization rate of women with ID was lower than that of pap smears and adult preventive health services, and was only half of that of people with disabilities. An unequal situation existed in regard to the acceptance of breast cancer screening among women with ID, and a different form of strategic planning must be adopted in public health policy. Because ID differs from other disabilities and most women with ID are illiterate, tailored courses are required to train primary caregivers and clinical personnel in providing knowledge and services. The objectives are to diagnose breast cancer at an early stage to decrease the risk of mortality and ensure their rights to health.
Phillips, Shannon Connor; Saysana, Michele; Worley, Sarah; Hain, Paul D
2012-06-01
Accurate and consistent placement of a patient identification (ID) band is used in health care to reduce errors associated with patient misidentification. Multiple safety organizations have devoted time and energy to improving patient ID, but no multicenter improvement collaboratives have shown scalability of previously successful interventions. We hoped to reduce by half the pediatric patient ID band error rate, defined as absent, illegible, or inaccurate ID band, across a quality improvement learning collaborative of hospitals in 1 year. On the basis of a previously successful single-site intervention, we conducted a self-selected 6-site collaborative to reduce ID band errors in heterogeneous pediatric hospital settings. The collaborative had 3 phases: preparatory work and employee survey of current practice and barriers, data collection (ID band failure rate), and intervention driven by data and collaborative learning to accelerate change. The collaborative audited 11377 patients for ID band errors between September 2009 and September 2010. The ID band failure rate decreased from 17% to 4.1% (77% relative reduction). Interventions including education of frontline staff regarding correct ID bands as a safety strategy; a change to softer ID bands, including "luggage tag" type ID bands for some patients; and partnering with families and patients through education were applied at all institutions. Over 13 months, a collaborative of pediatric institutions significantly reduced the ID band failure rate. This quality improvement learning collaborative demonstrates that safety improvements tested in a single institution can be disseminated to improve quality of care across large populations of children.
Background Cell lines have been widely used in biomedical research. The community-based Cell Line Ontology (CLO) is a member of the OBO Foundry library that covers the domain of cell lines. Since its publication two years ago, significant updates have been made, including new groups joining the CLO consortium, new cell line cells, upper level alignment with the Cell Ontology (CL) and the Ontology for Biomedical Investigation, and logical extensions. Construction and content Collaboration among the CLO, CL, and OBI has established consensus definitions of cell line-specific terms such as ‘cell line’, ‘cell line cell’, ‘cell line culturing’, and ‘mortal’ vs. ‘immortal cell line cell’. A cell line is a genetically stable cultured cell population that contains individual cell line cells. The hierarchical structure of the CLO is built based on the hierarchy of the in vivo cell types defined in CL and tissue types (from which cell line cells are derived) defined in the UBERON cross-species anatomy ontology. The new hierarchical structure makes it easier to browse, query, and perform automated classification. We have recently added classes representing more than 2,000 cell line cells from the RIKEN BRC Cell Bank to CLO. Overall, the CLO now contains ~38,000 classes of specific cell line cells derived from over 200 in vivo cell types from various organisms. Utility and discussion The CLO has been applied to different biomedical research studies. Example case studies include annotation and analysis of EBI ArrayExpress data, bioassays, and host-vaccine/pathogen interaction. CLO’s utility goes beyond a catalogue of cell line types. The alignment of the CLO with related ontologies combined with the use of ontological reasoners will support sophisticated inferencing to advance translational informatics development. PMID:25852852
Riazuddin, S; Hussain, M; Razzaq, A; Iqbal, Z; Shahzad, M; Polla, D L; Song, Y; van Beusekom, E; Khan, A A; Tomas-Roca, L; Rashid, M; Zahoor, M Y; Wissink-Lindhout, W M; Basra, M A R; Ansar, M; Agha, Z; van Heeswijk, K; Rasheed, F; Van de Vorst, M; Veltman, J A; Gilissen, C; Akram, J; Kleefstra, T; Assir, M Z; Grozeva, D; Carss, K; Raymond, F L; O'Connor, T D; Riazuddin, S A; Khan, S N; Ahmed, Z M; de Brouwer, A P M; van Bokhoven, H; Riazuddin, S
2017-11-01
Intellectual disability (ID) is a clinically and genetically heterogeneous disorder, affecting 1-3% of the general population. Although research into the genetic causes of ID has recently gained momentum, identification of pathogenic mutations that cause autosomal recessive ID (ARID) has lagged behind, predominantly due to non-availability of sizeable families. Here we present the results of exome sequencing in 121 large consanguineous Pakistani ID families. In 60 families, we identified homozygous or compound heterozygous DNA variants in a single gene, 30 affecting reported ID genes and 30 affecting novel candidate ID genes. Potential pathogenicity of these alleles was supported by co-segregation with the phenotype, low frequency in control populations and the application of stringent bioinformatics analyses. In another eight families segregation of multiple pathogenic variants was observed, affecting 19 genes that were either known or are novel candidates for ID. Transcriptome profiles of normal human brain tissues showed that the novel candidate ID genes formed a network significantly enriched for transcriptional co-expression (P<0.0001) in the frontal cortex during fetal development and in the temporal-parietal and sub-cortex during infancy through adulthood. In addition, proteins encoded by 12 novel ID genes directly interact with previously reported ID proteins in six known pathways essential for cognitive function (P<0.0001). These results suggest that disruptions of temporal parietal and sub-cortical neurogenesis during infancy are critical to the pathophysiology of ID. These findings further expand the existing repertoire of genes involved in ARID, and provide new insights into the molecular mechanisms and the transcriptome map of ID.
Riazuddin, S; Hussain, M; Razzaq, A; Iqbal, Z; Shahzad, M; Polla, D L; Song, Y; van Beusekom, E; Khan, A A; Tomas-Roca, L; Rashid, M; Zahoor, M Y; Wissink-Lindhout, W M; Basra, M A R; Ansar, M; Agha, Z; van Heeswijk, K; Rasheed, F; Van de Vorst, M; Veltman, J A; Gilissen, C; Akram, J; Kleefstra, T; Assir, M Z; Grozeva, D; Carss, K; Raymond, F L; O'Connor, T D; Riazuddin, S A; Khan, S N; Ahmed, Z M; de Brouwer, A P M; van Bokhoven, H; Riazuddin, S
2017-01-01
Intellectual disability (ID) is a clinically and genetically heterogeneous disorder, affecting 1–3% of the general population. Although research into the genetic causes of ID has recently gained momentum, identification of pathogenic mutations that cause autosomal recessive ID (ARID) has lagged behind, predominantly due to non-availability of sizeable families. Here we present the results of exome sequencing in 121 large consanguineous Pakistani ID families. In 60 families, we identified homozygous or compound heterozygous DNA variants in a single gene, 30 affecting reported ID genes and 30 affecting novel candidate ID genes. Potential pathogenicity of these alleles was supported by co-segregation with the phenotype, low frequency in control populations and the application of stringent bioinformatics analyses. In another eight families segregation of multiple pathogenic variants was observed, affecting 19 genes that were either known or are novel candidates for ID. Transcriptome profiles of normal human brain tissues showed that the novel candidate ID genes formed a network significantly enriched for transcriptional co-expression (P<0.0001) in the frontal cortex during fetal development and in the temporal–parietal and sub-cortex during infancy through adulthood. In addition, proteins encoded by 12 novel ID genes directly interact with previously reported ID proteins in six known pathways essential for cognitive function (P<0.0001). These results suggest that disruptions of temporal parietal and sub-cortical neurogenesis during infancy are critical to the pathophysiology of ID. These findings further expand the existing repertoire of genes involved in ARID, and provide new insights into the molecular mechanisms and the transcriptome map of ID. PMID:27457812
The design and preparation of an excellent corrosion protection coating is still a grand challenge and is essential for large-scale practical application. Herein, a novel cationic reduced graphene oxide (denoted as RGO-ID + )-based epoxy coating was fabricated for corrosion protection. RGO-ID + was synthesized by in situ synthesis and salification reaction, which is stable dispersion in water and epoxy latex, and the self-aligned RGO-ID + -reinforced cathodic electrophoretic epoxy nanocomposite coating (denoted as RGO-ID + coating) at the surface of metal was prepared by electrodeposition. The self-alignment of RGO-ID + in the coatings is mainly attributed to the electric field force. The significantly enhanced anticorrosion performance of RGO-ID + coating is proved by a series of electrochemical measurements in different concentrated NaCl solutions and salt spray tests. This superior anticorrosion property benefits from the self-aligned RGO-ID + nanosheets and the quaternary-N groups present in the RGO-ID + nanocomposite coating. Interestingly, the RGO-ID + also exhibits a high antibacterial activity toward Escherichia coli with 83.4 ± 1.3% antibacterial efficiency, which is attributed to the synergetic effects of RGO-ID + and the electrostatic attraction and hydrogen bonding between RGO-ID + and E. coli. This work offers new opportunities for the successful development of effective corrosion protection and self-antibacterial coatings.
Objective To determine whether children with attention deficit hyperactivity disorder (ADHD) and mild intellectual disability (ID) are a clinically distinct ADHD subgroup. Study design This was a cross-sectional study comparing clinical characteristics (ADHD subtypes, total number of symptoms, and rates of common comorbidities) between children with ADHD and mild ID and those with ADHD and IQ test scores >70, and also between children with ADHD and ID and a general population sample of children with ID alone. The sample comprised a clinical sample of children with ADHD with ID (n = 97) and without ID (n = 874) and a general population sample of children with ID and without ADHD (n = 58). Results After correcting for multiple statistical tests, no differences were found between the 2 ADHD groups on any measure except the presence of conduct disorder (CD) symptoms and diagnoses. Children with ADHD and ID had higher rates of both (OR, 2.38; 95% CI, 1.71-3.32 and OR, 2.69; 95% CI, 1.69-4.28, respectively). Furthermore, children with ADHD and ID had significantly higher rates of oppositional defiant disorder (OR, 5.54; 95% CI, 2.86-10.75) and CD (OR, 13.66; 95% CI, 3.25-57.42) symptoms and a higher incidence of oppositional defiant disorder diagnoses (OR, 30.99; 95% CI, 6.38-150.39) compared with children with ID without ADHD. Conclusion Children with ADHD and mild ID appear to be clinically typical of children with ADHD except for more conduct problems. This finding has implications for clinicians treating these children in terms of acknowledging the presence and impact of ADHD symptoms above and beyond ID and dealing with a comorbid CD. PMID:23608559
Baumgartner, Jeannine; Smuts, Cornelius M; Malan, Linda; Arnold, Myrtha; Yee, Benjamin K; Bianco, Laura E; Boekschoten, Mark V; Müller, Michael; Langhans, Wolfgang; Hurrell, Richard F; Zimmermann, Michael B
2012-08-01
Deficiencies of iron (Fe) (ID) and (n-3) fatty acids (FA) [(n-3)FAD] may impair brain development and function through shared mechanisms. However, little is known about the potential interactions between these 2 common deficiencies. We studied the effects of ID and (n-3)FAD, alone and in combination, on brain monoamine pathways (by measuring monoamines and related gene expression) and spatial working and reference memory (by Morris water maze testing). Using a 2 × 2 design, male rats were fed an ID, (n-3)FAD, ID+(n-3)FAD, or control diet for 5 wk postweaning (postnatal d 21-56) after (n-3)FAD had been induced over 2 generations. The (n-3)FAD and ID diets decreased brain (n-3) FA by 70-76% and Fe by 20-32%, respectively. ID and (n-3)FAD significantly increased dopamine (DA) concentrations in the olfactory bulb (OB) and striatum, with an additive 1- to 2-fold increase in ID+(n-3)FAD rats compared with controls (P < 0.05). ID decreased serotonin (5-HT) levels in OB, with a significant decrease in ID+(n-3)FAD rats. Furthermore, norepinephrine concentrations were increased 2-fold in the frontal cortex (FC) of (n-3)FAD rats (P < 0.05). Dopa decarboxylase was downregulated in the hippocampus of ID and ID+(n-3)FAD rats (fold-change = -1.33; P < 0.05). ID and (n-3)FAD significantly impaired working memory performance and the impairment positively correlated with DA concentrations in FC (r = 0.39; P = 0.026). Reference memory was impaired in the ID+(n-3)FAD rats (P < 0.05) and was negatively associated with 5-HT in FC (r = -0.42; P = 0.018). These results suggest that the combined deficiencies of Fe and (n-3) FA disrupt brain monoamine metabolism and produce greater deficits in reference memory than ID or (n-3)FAD alone.
Bonura, Erin M.; Lee, Eun Sul; Ramsey, Katrina; Armstrong, Wendy S.
2016-01-01
Background. Only 49% of infectious diseases (ID) fellowship programs were filled in 2015 through the national match, but little is known about internal medicine (IM) resident perceptions of ID and factors related to IM resident career choice. Methods. We conducted 25 interviews and disseminated a Web-based survey to graduating IM residents in the United States utilizing a 2-stage sampling strategy. Participants were categorized into 3 groups based on interest in ID: (1) applied/intended to apply to ID; (2) interested in ID but did not apply; (3) never interested in ID. We conducted all analysis using poststratification adjustment weights with survey data analysis procedures. Results. Of the 590 participants, 42 (7%) selected category 1, 188 (32%) category 2, and 360 (61%) category 3. Most (65%) developed an interest in their ultimate career before residency. Of those interested in ID, >52% rated their ID medical school curriculum as very good and influential on their interest in ID. Ninety-one percent of category 2 participants felt mentorship was influential on career choice, although 43% identified an ID mentor. Category 2 chose salary as the most dissuading factor and the most likely intervention to increase ID interest. Conclusions. In this nationally representative sample of graduating IM residents, most develop an interest in their ultimate career before residency. Factors influencing this decision reside in both medical school and residency, which is consistent with career decision-making constructs. By identifying career determining factors and understanding how they fit into medical training frameworks, we can develop targeted initiatives to reinvigorate interest in ID. PMID:27126345
The surface modification, functionalization, and conjugation of undoped and 11 at.% Eu3+-doped TbPO4 ·H2O nanowires by using silica, a thyocyanate functional group, and immunoglobulin G, respectively, are described in this paper. For the core layer of obtained conjugated nanowires, the undoped TbPO4 ·H2O exhibited characteristic photoluminescent green emission corresponding to 5 D 4 → 7 F J transitions ( J = 6, 5, 4, 3) while the incorporation of Eu3+ into TbPO4 ·H2O lattice was evidenced by Starks splitting transitions at 590, 615, 693 nm of Eu3+ ions for the case of 11 at.% Eu3+-doped TbPO4 ·H2O. The results also indicated that both immunoglobulin G-conjugated undoped and Eu3+-doped TbPO4 ·H2O nanowires can be used in the fluorescent immune analysis as a biomedical label maker to identify measles viruses in vaccine testing.
Adolescents with intellectual disability (ID) engage in risky behavior and offending. However, little is known on the impact school-related predictors have on engagement in risky behaviors for adolescents with ID. This study analyzed secondary data from the National Longitudinal Transition Study-2 (NLTS2) to determine levels of engagement in risky behaviors and offending for adolescents with mild and moderate/severe ID. School-related predictors of engagement for adolescents with mild ID were also explored. Results indicated adolescents with mild ID engage in risky behaviors and offending at significantly higher rates as compared to adolescents with moderate/severe ID. Participation in a social skills or life skills class was a significant predictor of less engagement in risky behaviors for individuals with mild ID.
von Haehling, Stephan; Gremmler, Uwe; Krumm, Michael; Mibach, Frank; Schön, Norbert; Taggeselle, Jens; Dahm, Johannes B; Angermann, Christiane E
2017-06-01
Iron deficiency (ID) and anaemia are common in heart failure (HF). The prospective, observational PReP registry (Prävalenz des Eisenmangels bei Patienten mit Herzinsuffizienz) studied prevalence and clinical impact of ID and anaemia in HF outpatients attending cardiology practices in Germany. A total of 42 practices enrolled consecutive patients with chronic HF [left ventricular ejection fraction (LVEF) ≤45%]. ID was defined as serum ferritin <100 µg/l, or serum ferritin ≥100 µg/l/<300 µg/l plus transferrin saturation <20%, and anaemia as haemoglobin <13 g/dl (12 g/dl) in men (women). Exercise capacity was assessed using spiroergometry (69.4%) or 6-min walk test (30.4%). Amongst 1198 PReP-participants [69.0 ± 10.6 years, 25.3% female, New York Heart Association (NYHA) class 2.4 ± 0.5, LVEF 35.3 ± 7.2%], ID was found in 42.5% (previously unknown in all), and anaemia in 18.9% (previously known in 4.8%). ID was associated with female gender, lower body weight and haemoglobin, higher NYHA class and natriuretic peptide (NP) levels (all p < 0.05). ID was also more common in anaemic than non-anaemic patients (p < 0.0001), and 9.8% of PrEP-participants had both, ID and anaemia. On spiroergometry, ID independently predicted maximum exercise capacity even after multivariable adjustment, including anaemia (p = 0.0004). In all PrEP-participants, ID predicted reduced physical performance (adjusted for age, gender, anaemia, serum creatinine, C-reactive protein, LVEF, and NP level). Despite high prevalence, ID was previously unknown in all PrEP-participants, and anaemia was often unappreciated. Given the clinical relevance, treatability, and independent association with reduced physical performance, ID should be considered more in real-world ambulatory healthcare settings and ID-screening be advocated to cardiologists in such populations.
Objectives To investigate mortality and its causes in adults over the age of 20 years with intellectual disability (ID). Design, setting and participants Retrospective population-based standardised mortality of the ID and Comparison cohorts. The ID cohort comprised 42 204 individuals who registered for disability services with ID as a primary or secondary diagnosis from 2005 to 2011 in New South Wales (NSW). The Comparison cohort was obtained from published deaths in NSW from the Australian Bureau of Statistics (ABS) from 2005 to 2011. Main outcome measures We measured and compared Age Standardised Mortality Rate (ASMR), Comparative Mortality Figure (CMF), years of productive life lost (YPLL) and proportion of deaths with potentially avoidable causes in an ID cohort with an NSW general population cohort. Results There were 19 362 adults in the ID cohort which experienced 732 (4%) deaths at a median age of 54 years. Age Standardised Mortality Rates increased with age for both cohorts. Overall comparative mortality figure was 1.3, but was substantially higher for the 20–44 (4.0) and 45–64 (2.3) age groups. YPLL was 137/1000 people in the ID cohort and 49 in the comparison cohort. Cause of death in ID cohort was dominated by respiratory, circulatory, neoplasm and nervous system. After recoding deaths previously attributed to the aetiology of the disability, 38% of deaths in the ID cohort and 17% in the comparison cohort were potentially avoidable. Conclusions Adults with ID experience premature mortality and over-representation of potentially avoidable deaths. A national system of reporting of deaths in adults with ID is required. Inclusion in health policy and services development and in health promotion programmes is urgently required to address premature deaths and health inequalities for adults with ID. PMID:28179413
The interpolative decomposition (ID) is combined with the multilevel fast multipole algorithm (MLFMA), denoted by ID-MLFMA, to handle multiscale problems. The ID-MLFMA first generates ID levels by recursively dividing the boxes at the finest MLFMA level into smaller boxes. It is specifically shown that near-field interactions with respect to the MLFMA, in the form of the matrix vector multiplication (MVM), are efficiently approximated at the ID levels. Meanwhile, computations on far-field interactions at the MLFMA levels remain unchanged. Only a small portion of matrix entries are required to approximate coupling among well-separated boxes at the ID levels, and these submatrices can be filled without computing the complete original coupling matrix. It follows that the matrix filling in the ID-MLFMA becomes much less expensive. The memory consumed is thus greatly reduced and the MVM is accelerated as well. Several factors that may influence the accuracy, efficiency and reliability of the proposed ID-MLFMA are investigated by numerical experiments. Complex targets are calculated to demonstrate the capability of the ID-MLFMA algorithm.
Continuous monitoring in daily life is important for the health condition control of the elderly. However, portable or wearable devices need to carry by user on their own will. On the other hand, implantation sensors are not adoptable, because of generic users dislike to insert the any object in the body for monitoring. Therefore, another monitoring system of the health condition to carry it easily is necessary. In addition, ID system is necessary even if the subject live with few families. Furthermore, every measurement system should be wireless system, because not to obstruct the daily life of the user. In this paper, we propose the monitoring system, which is mounted on the body surface. This system will not obstruct the action or behavior of user in daily life, because this system attached the body surface on the back of the user. In addition, this system has wireless communication system, using Bluetooth, and acquired data transfer to the outside of the house via the Internet.
Layered double hydroxide (LDH) nanomaterial has emerged as a novel delivery agent for biomedical applications due to its unique structure and properties. However, in vivo positron emission tomography (PET) imaging with LDH nanoparticles has not been achieved. The aim of this study is to explore chelator-free labeling of LDH nanoparticles with radioisotopes for in vivo PET imaging. Bivalent cation 64Cu2+ and trivalent cation 44Sc3+ were found to readily label LDH nanoparticles with excellent labeling efficiency and stability, whereas tetravalent cation 89Zr4+ could not label LDH since it does not fit into the LDH crystal structure. PET imaging shows that prominent tumor uptake was achieved in 4T1 breast cancer with 64Cu-LDH-BSA via passive targeting alone (7.7 ± 0.1%ID/g at 16 h post-injection; n = 3). These results support that LDH is a versatile platform that can be labeled with various bivalent and trivalent radiometals without comprising the native properties, highly desirable for PET image-guided drug delivery.
The recent rise in unfilled training positions among infectious diseases (ID) fellowship programs nationwide indicates that ID is declining as a career choice among internal medicine residency graduates. Supplementing ID training with training in critical care medicine (CCM) might be a way to regenerate interest in the specialty. Hands-on patient care and higher salaries are obvious attractions. High infection prevalence and antibiotic resistance in intensive care units, expanding immunosuppressed host populations, and public health crises such as the recent Ebola outbreak underscore the potential synergy of CCM-ID training. Most intensivists receive training in pulmonary medicine and only 1% of current board-certified intensivists are trained in ID. While still small, this cohort of CCM-ID certified physicians has continued to rise over the last 2 decades. ID and CCM program leadership nationwide must recognize these trends and the merits of the CCM-ID combination to facilitate creation of formal dual-training opportunities. PMID:25944345
Barnard-Brak, Lucy; Schmidt, Marcelo; Chesnut, Steven; Wei, Tianlan; Richman, David
2014-04-01
Data from the National Longitudinal Transition Study-2 ( SRI International, 2002 ) were analyzed to identify variables that predicted whether individuals with intellectual disability (ID) received sex education in public schools across the United States. Results suggested that individuals receiving special education services without ID were only slightly more likely to receive sex education than students with mild ID (47.5% and 44.1%, respectively), but the percentage of students with moderate to profound ID that received sex education was significantly lower (16.18%). Analysis of teacher opinions and perceptions of the likelihood of the students benefiting from sex education found that most teachers indicated that students without ID or with mild ID would benefit (60% and 68%, respectively), but the percentage dropped to 25% for students with moderate to profound ID. Finally, across all students, the only significant demographic variable that predicted receipt of sex education was more expressive communication skills. Results are discussed in terms of ensuring equal access to sex education for students with ID in public schools.
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A method for treatment of breast cancer and other types of cancer. The method comprises targeting and modulating Id-1 gene expression, if any, for the Id-1 gene, or gene products in breast or other epithelial cancers in a patient by delivering products that modulate Id-1 gene expression. When expressed, Id-1 gene is a prognostic indicator that cancer cells are invasive and metastatic.
Monoamine oxidase A (MAOA) gene polymorphisms resulting in high and low transcription rates are associated with individual differences in reward efficacy and response inhibition. Iron deficiency (ID) is the most frequent single-nutrient deficiency worldwide, and prenatal ID has recently been shown to carry a risk for lower mental development scores in infants. In this study, a potential interaction of MAOA genotype and prenatal ID was studied in young male rhesus monkeys. Cognitive tasks, including problem solving, responsiveness to reward and attention, were used to characterize the potential interaction of these two fetal risks. ID was induced by feeding rhesus monkey dams an iron-deficient (10 ppm, ID) or an iron-sufficient (100 ppm, IS) diet during gestation (n = 10/group). Subgroups of the ID and IS diet offspring had low-MAOA or high-MAOA transcription rate polymorphisms. ID combined with low-MAOA genotype showed distinctive effects on reward preference and problem solving while ID in hi-MAOA juveniles modified response inhibition. Given the incidence of ID and MAOA polymorphisms in humans, this interaction could be a significant determinant of cognitive performance.
Martinez, Julia A; Rutledge, Patricia C; Sher, Kenneth J
2007-06-01
The authors examined the ownership of false identification (fake ID) for the purpose of obtaining alcohol and the relation of fake ID ownership to heavy drinking in a longitudinal sample of college students under 21 years of age. A sample of 3,720 undergraduates was assessed the summer prior to college entrance and during the 4 semesters comprising freshman and sophomore years. Regression analyses were used to estimate bidirectional relations between consumption and fake ID ownership. Sex, Greek membership, and prior drinking were controlled. Results showed that fake ID ownership increased over time (12.5% pre-college to 32.2% fourth semester) and that Greek members were more likely than others to own fake IDs. Fake ID ownership predicted concurrent and next-semester heavy drinking with increasing strength over time. Also, the acquisition (onset) of fake ID ownership at each time point was predicted by previous-semester consumption. When traditional, robust risk factors of consumption are controlled, fake ID ownership meaningfully relates to heavy drinking in college. It thus presents a significant public health problem, addressable through training for alcohol servers and retailers, punitive measures toward fake ID owners, and other possible interventions.
Vaccination is universally considered as the principal measure for the control of influenza, which represents a significant burden worldwide, both from a health-care and a socio-economic viewpoint. Conventional non-adjuvanted trivalent influenza vaccines (TIVs) have been recognized as having some deficiencies, such as suboptimal immunogenicity particularly in the elderly, in patients with severe chronic diseases and immunocompromized, indeed, those groups of the population at higher risk of developing severe complications following influenza infection, when compared to healthy adults. Moreover, the protection offered by conventional vaccines may be reduced by periodic antigenic drifts, resulting in a mismatch between the circulating and vaccinal viral strains. Another gap regarding currently available vaccines is related to the egg-based manufacturing system for their production: not only the length of time involved with the latter but also the limited capacity of this platform technology represent a major limitation for the active prevention of influenza, which is particularly important in the case of a new pandemic strain. New technologies used in vaccine composition, administration and manufacture have led to major advances during the last few years, and clinical researchers have continued to work hard, investigating several different strategies to improve the performance of influenza vaccines: namely, the addition of different adjuvants (i.e., MF59- and AS03-vaccines, virosomal formulations), the use of alternative routes of administration or manufacture (i.e., intradermal, nasal and oral vaccines and cell culture- and reverse genetic-based vaccines) or of high doses of antigen, and the development of DNA-vaccines, or the use of conserved viral epitopes (i.e., the extracellular portion of the M2 protein, the nucleoprotein and some domains of the hemagglutinin), in the attempt to produce a "universal target" antigen vaccine. The knowledge acquired represents a fundamental challenge for the control of influenza. An overview of the most recent and interesting results, some of which gained from our own research experience, particularly concerning two successful approaches, of those outlined above, namely the use of: (i) the oil-in-water MF59-adjuvant, and (ii) the intradermal (ID) route for vaccine administration, through a novel microinjection system, will be reported and discussed, together with the possible implications and perspectives to optimize immunization policies against influenza in the near future.
Summarizes study of curricula of nine graduate programs in instructional development (ID). Comparisons are presented on nine variables--purpose; curriculum development processes; ID courses; where/how ID is learned; synthesizing projects; emphasis of faculty/organization development and performance solutions; orientation to evaluation and ID; and…
. REAL ID LANL Impacts and Solutions The federal government has determined New Mexico is non-compliant Identification Cards whom will also become Non-Compliant. Access through LANL Vehicle Access Portals unaffected alternate ID if they are coming from "non-compliant" REAL-ID states LANS and the Field Office have
Eisenga, Michele F; Minović, Isidor; Berger, Stefan P; Kootstra-Ros, Jenny E; van den Berg, Else; Riphagen, Ineke J; Navis, Gerjan; van der Meer, Peter; Bakker, Stephan J L; Gaillard, Carlo A J M
a run is always the @RUN statement, which can specify user-id, account number, and project-id. The @ PASSWD statement specifies password and security...Every-Page-Label Options PASSWD password for batch; F36 User-id validation chang for demand; comp, nent set for batch LEV change Clearance Level F33...clearance level @@PASS Change password F36 Current valid password must @@ PASSWD be specified @@SEND Display a print file F16 Sym to user-id or site-id that is
Tebas, Pablo; Roberts, Christine C; Muthumani, Kar; Reuschel, Emma; White, Scott; Khan, Amir S; Racine, Trina; Choi, Hyeree; Zaidi, Faraz; Boyer, Jean; Kudchodkar, Sagar; Park, Young K; Trottier, Sylvie; Remigio, Celine; Krieger, Diane; Kobinger, Gary P; Weiner, David; Maslow, Joel
2017-01-01
Abstract Background While Zika virus (ZIKV) infection is typically self-limited, congenital birth defects and Guillain-Barré syndrome are well-described. There are no therapies or vaccines against ZIKV infection. Methods ZIKA-001 is a phase I, open label, clinical trial designed to evaluate the safety, side effect profile, and immunogenicity of a synthetic, DNA vaccine (GLS-5700) targeting the pre-membrane+envelope proteins (prME) of the virus. Two groups of 20 participants received GLS-5700 at one of two dose levels: 1 mg or 2 mg DNA/dose at 0, 4, and 12 weeks. Vaccine was administered as 0.1 or 0.2 ml (1 or 2 mg) intradermal (ID) injection followed by electroporation (EP) with the CELLECTRA®-3P device Results The median age of the 40 participants was 38 (IQR 30–54) years; 60% were female 30% Latino and 78% white. No SAEs have been reported to date. Local minor AEs were injection site pain, redness, swelling and itching that occurred in half of the participants. Systemic adverse events were rare and included headache, myalgias, upper respiratory infections, fatigue/malaise and nausea. Four weeks after the first dose 25% vs. 60% of the participants in the 1 mg and 2 mg dose seroconverted. By week 6, 2 weeks after the second dose, the response was 65 and 84% respectively and 2 weeks after the third dose all participants in both dosing groups developed antibodies. At the end of the vaccination period over 60% of vaccinated person neutralized Zika virus in a vero cell assay and greater than 80% on neuronal cell targets. The protective efficacy of the antibodies generated by the vaccine was evaluated in the lethal IFNAR−/− mouse model. After the intraperitoneal administration of 0.1 ml of either baseline, week 14 serum or PBS the animals were challenged with 106 PFUs of ZIKV PR209 isolate. Whereas animals administered PBS (control) or baseline serum succumbed after a median of 5 days, those pretreated with week 14 serum from study participants survived suggesting that the humoral response generated by the vaccine is protective in this model. Conclusion Our trial shows for the first time in humans the safety and immunogenicity of an engineered DNA encoding consensus viral protein against ZIKV. Future studies will evaluate the effectiveness of the vaccine. Disclosures C. C. Roberts, GeneOne: Member, Salary. S. White, GeneOne: Member, Salary. A. S. Khan, Inovio: Employee and Shareholder, Salary and Stock. J. Boyer, Inovio: Employee and Shareholder, Salary and Stock. Y. K. Park, GeneOne: Board Member, CEO and Employee, Salary and Stock. S. Trottier, Canadian Institutes of Health Research: Investigator, Research grant. C. Remigio, GeneOne: Employee and Shareholder, Salary and Stock. G. P. Kobinger, GeneOne: Grant Investigator and Scientific Advisor, Grant recipient and Research support. D. Weiner, GeneOne: Grant Investigator and Scientific Advisor, Grant recipient, Licensing agreement or royalty and Stock. J. Maslow, GeneOne: Employee, Salary and Stock.
Lakhan, Ram; Bipeta, Rajshekhar; Yerramilli, Srinivasa S R R; Nahar, Vinayak K
2017-01-01
Intellectual disability (ID) can be inherited in families through consanguineous marriage. The ID in an individual can be associated with the ID, epilepsy, and mental illness in their parents. Such connections can be seen more closely among consanguineous marriages in tribal and nontribal population in India. This study shows a few common patterns of the consanguineous relationship in the parents of children with ID in India. This is a case series research design. Extreme or deviant case sampling was applied. Data were collected in homes, camps, and clinical settings in the Barwani district of Madhya Pradesh, India. The patterns of consanguineous marriages and the relationship between children with ID and their relatives with ID, epilepsy, and mental illness were analyzed and reported with pedigree charts. Multiple patterns of consanguineous marriages in tribal and nontribal populations were observed. ID was found to be associated in children with their relatives of the first, second, and third generations. ID may inherit in individuals from their relatives of the first, second, and third generations who have ID, epilepsy, or mental illness and married in the relationship. Appropriate knowledge, guidance, and counseling may be provided to potential couples before planning a consanguineous marriage.
Søndenaa, E; Rasmussen, K; Nøttestad, J A; Lauvrud, C
2010-02-01
Based on national registers, the prevalence of intellectual disability (ID) in Norway is estimated to be 0.44 per 100 inhabitants. This study aimed to examine geographic and urban-rural differences in the prevalence of ID in Norway. Methods A survey based on the national register. Financial transfers intended to provide equal services to people with ID are based on these reports. Results A higher prevalence was found in the North region of Norway. A negative correlation between the population density and the prevalence of ID was also found. Conclusion There was considerable geographic and urban-rural differences in the prevalence of ID, which may be attributable to not only the large diversity of services, but also some other factors. The results were discussed with respect to the deinstitutionalisation progress, resource-intensive services and costs. Differences also reflect some problems in diagnosing ID in people having mild ID.
The explosion of medical applications (apps) in the Apple and Google Play app stores has made it increasingly difficult to find relevant and reliable infectious diseases (ID) apps. Apple created a section called "Apps for Healthcare Professionals"; however, several ID apps are missing. Google Play's ID category has several non-ID apps. Many apps involve diagnosis and patient management, creating a need for regulations and oversight by the US Food and Drug Administration. There are no standards to guide accuracy or reliability of medical apps' content. We searched Apple and Google Play app stores to identify new ID apps. Over 1200 apps were identified. We applied several exclusion criteria to identify adult/pediatric apps with data from trustworthy sources that were not reviewed within the last year. Twelve new ID apps were identified with a comprehensive list of 24 ID apps to assist healthcare professionals at the point of care.
Radke, John C; Kamyszek, Greg J; Kull, Robert S; Velasco, Gerardo R
2017-09-04
The null hypothesis was that mandibular amplitude, velocity, and variability during gum chewing are not altered in subjects with temporomandibular joint (TMJ) internal derangements (ID). Thirty symptomatic subjects with confirmed ID consented to chew gum on their left and right sides while being tracked by an incisor-point jaw tracker. A gender and age matched control group (p > 0.67) volunteered to be likewise recorded. Student's t-test compared the ID group's mean values to the control group. The control group opened wider (p < 0.05) and chewed faster (p < 0.05) than the ID group. The mean cycle time of the ID group (0.929 s) was longer than the control group (0.751 s; p < 0.05) and more variable (p < 0.05). The ID group exhibited reduced amplitude and velocity but increased variability during chewing. The null hypothesis was rejected. Further study of adaptation to ID by patients should be pursued.
points. Figure 4: Linear interpolation Table 1: Wind speed prediction information (ID:0-2 for Albany, ID:3-5 for Pittston, and ID:6-8 for JFK Airport ID...Pittston, and JFK Airport in Table 1, how can we estimate a reasonable wind speed for the current location at the current time? Figure 5: Example
Ailey, Sarah H.; Miller, Arlene Michaels; Fogg, Louis
2014-01-01
Individuals with intellectual disabilities (ID) increasingly live with other individuals with ID in small community homes staffed by paraprofessionals where aggressive/challenging (problem) behaviors occur more frequently then among individuals with ID living with their families. Evidence suggests that individuals with ID are more susceptible to…
Neural crest cells are unique to vertebrates and generate many of the adult structures that differentiate them from their closest invertebrate relatives, the cephalochordates. Id genes are robust markers of neural crest cells at all stages of development. We compared Id gene expression in amphioxus and lamprey to ask if cephalochordates deploy Id genes at the neural plate border and dorsal neural tube in a manner similar to vertebrates. Furthermore, we examined whether Id expression in these cells is a basal vertebrate trait or a derived feature of gnathostomes. We found that while expression of Id genes in the mesoderm and endoderm is conserved between amphioxus and vertebrates, expression in the lateral neural plate border and dorsal neural tube is a vertebrate novelty. Furthermore, expression of lamprey Id implies that recruitment of Id genes to these cells occurred very early in the vertebrate lineage. Based on expression in amphioxus we postulate that Id cooption conferred sensory cell progenitor-like properties upon the lateral neurectoderm, and pharyngeal mesoderm-like properties upon cranial neural crest. Amphioxus Id expression is also consistent with homology between the anterior neurectoderm of amphioxus and the presumptive placodal ectoderm of vertebrates. These observations support the idea that neural crest evolution was driven in large part by cooption of multipurpose transcriptional regulators from other tissues and cell types.
Intellectual disability (ID) is characterized by limitation in intellectual function and adaptive behavior, with onset in childhood. Frequent identifiable causes of ID originate from chromosomal imbalances. During the last years, array-CGH has successfully contributed to improve the diagnostic detection rate of genetic abnormalities in patients with ID. Most array-CGH studies focused on patients with moderate or severe intellectual disability. Studies on genetic etiology in children with mild intellectual disability (ID) are very rare. We performed array-CGH analysis in 66 children with mild intellectual disability assessed in a population-based study and for whom no genetic etiology was identified. We found one or more copy number variations (CNVs) in 20 out of 66 (~30 %) patients with a mild ID. In eight of them (~12 %), the CNVs were certainly responsible for the phenotype and in six they were potentially pathogenic for ID. Altogether, array-CGH helped to determine the etiology of ID in 14 patients (~21 %). Our results underscore the clinical relevance of array-CGH to investigate the etiology of isolated idiopathic mild ID in patients or associated with even subtle dysmorphic features or congenital malformations.
Otero, Gloria A; Pliego-Rivero, F Bernardo; Porcayo-Mercado, Rosario; Mendieta-Alcántara, Gustavo
2008-08-01
Iron is an important oligoelement participating in multiple metabolic processes, including the synthesis of catecholamines, and its deficiency (ID) throughout development is particularly insidious on brain maturation and the emergence of cognitive functions during school age. A working memory (WM) study in 8-10-year-old ID children is presented. It is hypothesized that an impairment in WM exists in ID school-age children and a substantial restoration of this mental ability should occur after iron supplementation. Event-related potentials (ERPs) were recorded during the completion of a Sternberg-type task in control, ID and ID-iron supplemented children. ID children showed less correct answers and diminished ERP amplitude in frontal, central, parietal and temporal regions compared to control children. After iron supplementation and normalizing bodily iron stores, behavioral and ERP differences disappeared between ID and control children. Considering that WM is fundamentally related to attention ability, the results presented here confirm and reinforce previous observations: ID severely diminishes attention [Otero GA, Pliego-Rivero FB, Contreras G, Ricardo J, Fernandez T. Iron supplementation brings up a lacking P300 in iron deficient children. Clin Neurophysiol 2004;115:2259-66] and WM while iron supplementation substantially restores the cognitive capabilities tested. This is one of very few reports using ERP showing a diminished WM capability in ID school-age children.
Lakhan, Ram; Bipeta, Rajshekhar; Yerramilli, Srinivasa S. R. R.; Nahar, Vinayak K.
2017-01-01
Background: Intellectual disability (ID) can be inherited in families through consanguineous marriage. The ID in an individual can be associated with the ID, epilepsy, and mental illness in their parents. Such connections can be seen more closely among consanguineous marriages in tribal and nontribal population in India. Objective: This study shows a few common patterns of the consanguineous relationship in the parents of children with ID in India. Materials and Methods: This is a case series research design. Extreme or deviant case sampling was applied. Data were collected in homes, camps, and clinical settings in the Barwani district of Madhya Pradesh, India. The patterns of consanguineous marriages and the relationship between children with ID and their relatives with ID, epilepsy, and mental illness were analyzed and reported with pedigree charts. Results: Multiple patterns of consanguineous marriages in tribal and nontribal populations were observed. ID was found to be associated in children with their relatives of the first, second, and third generations. Conclusion: ID may inherit in individuals from their relatives of the first, second, and third generations who have ID, epilepsy, or mental illness and married in the relationship. Appropriate knowledge, guidance, and counseling may be provided to potential couples before planning a consanguineous marriage. PMID:29204013
The Interaction Network Ontology (INO) logically represents biological interactions, pathways, and networks. INO has been demonstrated to be valuable in providing a set of structured ontological terms and associated keywords to support literature mining of gene-gene interactions from biomedical literature. However, previous work using INO focused on single keyword matching, while many interactions are represented with two or more interaction keywords used in combination. This paper reports our extension of INO to include combinatory patterns of two or more literature mining keywords co-existing in one sentence to represent specific INO interaction classes. Such keyword combinations and related INO interaction type information could be automatically obtained via SPARQL queries, formatted in Excel format, and used in an INO-supported SciMiner, an in-house literature mining program. We studied the gene interaction sentences from the commonly used benchmark Learning Logic in Language (LLL) dataset and one internally generated vaccine-related dataset to identify and analyze interaction types containing multiple keywords. Patterns obtained from the dependency parse trees of the sentences were used to identify the interaction keywords that are related to each other and collectively represent an interaction type. The INO ontology currently has 575 terms including 202 terms under the interaction branch. The relations between the INO interaction types and associated keywords are represented using the INO annotation relations: 'has literature mining keywords' and 'has keyword dependency pattern'. The keyword dependency patterns were generated via running the Stanford Parser to obtain dependency relation types. Out of the 107 interactions in the LLL dataset represented with two-keyword interaction types, 86 were identified by using the direct dependency relations. The LLL dataset contained 34 gene regulation interaction types, each of which associated with multiple keywords. A hierarchical display of these 34 interaction types and their ancestor terms in INO resulted in the identification of specific gene-gene interaction patterns from the LLL dataset. The phenomenon of having multi-keyword interaction types was also frequently observed in the vaccine dataset. By modeling and representing multiple textual keywords for interaction types, the extended INO enabled the identification of complex biological gene-gene interactions represented with multiple keywords.
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Background Informed consent based on comprehension of potential risks and benefits is fundamental to the ethical conduct of clinical research. We explored mental models of candidate HIV vaccines and clinical trials that may impact on the feasibility and ethics of biomedical HIV prevention trials among men who have sex with men (MSM) in India. Methods A community-based research project was designed and implemented in partnership with community-based organizations serving MSM in Chennai and Mumbai. We conducted 12 focus groups (n = 68) with diverse MSM and 14 key informant interviews with MSM community leaders/service providers using a semi-structured interview guide to explore knowledge and beliefs about HIV vaccines and clinical trials. Focus groups (60–90 minutes) and interviews (45–60 minutes) were conducted in participants’ native language (Tamil in Chennai; Marathi or Hindi in Mumbai), audio-taped, transcribed and translated into English. We explored focus group and interview data using thematic analysis and a constant comparative method, with a focus on mental models of HIV vaccines and clinical trials. Results A mental model of HIV vaccine-induced seropositivity as “having HIV” resulted in fears of vaccine-induced infection and HIV stigma. Some participants feared inactivated vaccines might “drink blood” and “come alive”. Pervasive preventive misconception was based on a mental model of prevention trials as interventions, overestimation of likely efficacy of candidate vaccines and likelihood of being assigned to the experimental group, with expectations of protective benefits and decreased condom use. Widespread misunderstanding and lack of acceptance of placebo and random assignment supported perceptions of clinical trials as “cheating”. Key informants expressed concerns that volunteers from vulnerable Indian communities were being used as “experimental rats” to benefit high-income countries. Conclusions Evidence-informed interventions that engage with shared mental models among potential trial volunteers, along with policies and funding mechanisms that ensure local access to products that demonstrate efficacy in trials, may support the safe and ethical implementation of HIV vaccine trials in India. PMID:23919283
Pagan, Cecile; Botros, Hany Goubran; Poirier, Karine; Dumaine, Anne; Jamain, Stéphane; Moreno, Sarah; de Brouwer, Arjan; Van Esch, Hilde; Delorme, Richard; Launay, Jean-Marie; Tzschach, Andreas; Kalscheuer, Vera; Lacombe, Didier; Briault, Sylvain; Laumonnier, Frédéric; Raynaud, Martine; van Bon, Bregje W; Willemsen, Marjolein H; Leboyer, Marion; Chelly, Jamel; Bourgeron, Thomas
2011-01-20
Intellectual disability (ID) is frequently associated with sleep disorders. Treatment with melatonin demonstrated efficacy, suggesting that, at least in a subgroup of patients, the endogenous melatonin level may not be sufficient to adequately set the sleep-wake cycles. Mutations in ASMT gene, coding the last enzyme of the melatonin pathway have been reported as a risk factor for autism spectrum disorders (ASD), which are often comorbid with ID. Thus the aim of the study was to ascertain the genetic variability of ASMT in a large cohort of patients with ID and controls. Here, we sequenced all exons of ASMT in a sample of 361 patients with ID and 440 controls. We then measured the ASMT activity in B lymphoblastoid cell lines (BLCL) of patients with ID carrying an ASMT variant and compared it to controls. We could identify eleven variations modifying the protein sequence of ASMT (ID only: N13H, N17K, V171M, E288D; controls only: E61Q, D210G, K219R, P243L, C273S, R291Q; ID and controls: L298F) and two deleterious splice site mutations (IVS5+2T>C and IVS7+1G>T) only observed in patients with ID. We then ascertained ASMT activity in B lymphoblastoid cell lines from patients carrying the mutations and showed significantly lower enzyme activity in patients carrying mutations compared to controls (p = 0.004). We could identify patients with deleterious ASMT mutations as well as decreased ASMT activity. However, this study does not support ASMT as a causative gene for ID since we observed no significant enrichment in the frequency of ASMT variants in ID compared to controls. Nevertheless, given the impact of sleep difficulties in patients with ID, melatonin supplementation might be of great benefit for a subgroup of patients with low melatonin synthesis.
Introduction:Iron deficiency has been known to cause significant functional impairment, lower quality of life and higher morbidity and mortality. The aim of this study was to estimate the prevalence and significance of iron deficiency in our patients and medical staff. Material and methods:We performed a prospective cross-sectional study: In July 2016, 383 persons were screened for the presence of iron deficiency (ID): 325 patients and 58 people from the medical staff. Transferrin saturation (TSAT), serum ferritin (SF) and complete blood count were performed. Absolute ID was diagnosed if SF <100 ng/ml and TSAT <20%. Relative ID was defined by SF >100 ng/ml and TSAT <20%. Results:The group of medical staff was younger and had a greater proportion of women. The prevalence of absolute ID was 22.5% in patients and 43.1% in medical staff; relative ID was present in 15% of patients and 1.7% of medical staff. Among patients, the absolute ID was significantly correlated with the female sex (p=0.002) and pre-menopausal status (p=0.01) but did not correlate with diagnosis, age, BMI, nonsteroidal anti-inflammatory drug (NSAID), aspirin or acenocoumarol consumption. The relative ID is associated with advanced age (p=0.03) and diagnosis of cancer and liver cirrhosis (p=0.01). Conclusions:Absolute ID had a high prevalence among patients (22.5%), but there was even a bigger issue among the medical staff (43.1%). Absolute ID was correlated with female sex and pre-menopausal status. Relative ID was related to advanced age, cancer and liver cirrhosis. Abbreviations: serum ferritine- SF, transferrin saturation coefficient- TSAT, iron deficiency- ID, inflammatory bowel diseases- IBD, quality of life- QoL, GI- gastrointestinal PMID:29696062
Introduction: Iron deficiency has been known to cause significant functional impairment, lower quality of life and higher morbidity and mortality. The aim of this study was to estimate the prevalence and significance of iron deficiency in our patients and medical staff. Material and methods: We performed a prospective cross-sectional study: In July 2016, 383 persons were screened for the presence of iron deficiency (ID): 325 patients and 58 people from the medical staff. Transferrin saturation (TSAT), serum ferritin (SF) and complete blood count were performed. Absolute ID was diagnosed if SF <100 ng/ml and TSAT <20%. Relative ID was defined by SF >100 ng/ml and TSAT <20%. Results: The group of medical staff was younger and had a greater proportion of women. The prevalence of absolute ID was 22.5% in patients and 43.1% in medical staff; relative ID was present in 15% of patients and 1.7% of medical staff. Among patients, the absolute ID was significantly correlated with the female sex (p=0.002) and pre-menopausal status (p=0.01) but did not correlate with diagnosis, age, BMI, nonsteroidal anti-inflammatory drug (NSAID), aspirin or acenocoumarol consumption. The relative ID is associated with advanced age (p=0.03) and diagnosis of cancer and liver cirrhosis (p=0.01). Conclusions: Absolute ID had a high prevalence among patients (22.5%), but there was even a bigger issue among the medical staff (43.1%). Absolute ID was correlated with female sex and pre-menopausal status. Relative ID was related to advanced age, cancer and liver cirrhosis. Abbreviations: serum ferritine- SF, transferrin saturation coefficient- TSAT, iron deficiency- ID, inflammatory bowel diseases- IBD, quality of life- QoL, GI- gastrointestinal.
The aging of the population with intellectual disability (ID), with associated conseqences as dementia, creates a need for evidence-based methods to support staff. Dementia Care Mapping (DCM) is perceived to be valuable in dementia care and promising in ID-care. The aim of this study was to evaluate the process of the first use of DCM in ID-care. DCM was used among older people with ID and care-staff in 12 group homes of six organisations. We obtained data on the first use of DCM in ID-care via focus-group discussions and face-to-face interviews with: care-staff (N = 24), managers (N = 10), behavioural specialists (N = 7), DCM-ID mappers (N = 12), and DCM-trainers (N = 2). We used the RE-AIM framework for a thematic process-analysis. All available staff (94%) participated in DCM (reach). Regarding its efficacy, staff considered DCM valuable; it provided them new knowledge and skills. Participants intended to adopt DCM, by continuing and expanding its use in their organisations. DCM was implemented as intended, and strictly monitored and supported by DCM-trainers. As for maintenance, DCM was further tailored to ID-care and a version for individual ID-care settings was developed, both as standards for international use. To sustain the use of DCM in ID-care, a multidisciplinary, interorganisational learning network was established. DCM tailored to ID-care proved to be an appropriate and valuable method to support staff in their work with aging clients, and it allows for further implementation. This is a first step to obtain an evidence-based method in ID-care for older clients.
The purposes of this research are to find out, (1) whether C-ID, R2D2 model is effective to be implemented on learning Reading comprehension, (2) college students' activity during the implementation of C-ID, R2D2 model on learning Reading comprehension, and 3) college students' learning achievement during the implementation of C-ID, R2D2 model on…
Trollor, Julian; Srasuebkul, Preeyaporn; Xu, Han; Howlett, Sophie
2017-02-07
To investigate mortality and its causes in adults over the age of 20 years with intellectual disability (ID). Retrospective population-based standardised mortality of the ID and Comparison cohorts. The ID cohort comprised 42 204 individuals who registered for disability services with ID as a primary or secondary diagnosis from 2005 to 2011 in New South Wales (NSW). The Comparison cohort was obtained from published deaths in NSW from the Australian Bureau of Statistics (ABS) from 2005 to 2011. We measured and compared Age Standardised Mortality Rate (ASMR), Comparative Mortality Figure (CMF), years of productive life lost (YPLL) and proportion of deaths with potentially avoidable causes in an ID cohort with an NSW general population cohort. There were 19 362 adults in the ID cohort which experienced 732 (4%) deaths at a median age of 54 years. Age Standardised Mortality Rates increased with age for both cohorts. Overall comparative mortality figure was 1.3, but was substantially higher for the 20-44 (4.0) and 45-64 (2.3) age groups. YPLL was 137/1000 people in the ID cohort and 49 in the comparison cohort. Cause of death in ID cohort was dominated by respiratory, circulatory, neoplasm and nervous system. After recoding deaths previously attributed to the aetiology of the disability, 38% of deaths in the ID cohort and 17% in the comparison cohort were potentially avoidable. Adults with ID experience premature mortality and over-representation of potentially avoidable deaths. A national system of reporting of deaths in adults with ID is required. Inclusion in health policy and services development and in health promotion programmes is urgently required to address premature deaths and health inequalities for adults with ID. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.
Inclusion of people with intellectual disability (ID) in higher postsecondary academic education is on the rise. However, there are no scientific criteria for determining the eligibility for full inclusion of students with ID in university courses. This study focuses on two models of academic inclusion for students with ID: (a) separate adapted enrichment model: students with ID study in separate enrichment courses adapted to their level; (b) full inclusion model: students with ID are included in undergraduate courses, receive academic credits and are expected to accumulate the amount of credits for a B.A. (a) To examine whether crystallized and fluid intelligence and cognitive tests can serve as screening tests for determining the appropriate placement of students with ID for the adapted enrichment model versus the full inclusion model. (b) To examine the attitudes towards the program of students with ID in the inclusion model. The sample included 31 adults with ID: students with ID who were fully included (N = 10) and students with ID who participated in the adapted enrichment model (N = 21). Crystallized and fluid intelligence were examined (WAIS-III, Wechsler, 1997) and Hebrew abstract verbal tests (Glanz, 1989). Semi-structured interviews were conducted in order to examine the attitudes of students in the inclusion model towards the program. The ANOVAs indicate that the most prominent difference between the groups was in vocabulary, knowledge and working memory. ROC analysis, a fundamental tool for diagnostic test evaluation, was used to determine the students' eligibility for appropriate placement in the two models. Seven tests distinguished between the groups in terms of sensitivity and specificity. The interviews were analyzed according to three phases. The results indicate that students with ID are able to participate in undergraduate courses and achieve academic goals. The general IQ and idioms test seem to be best determiners for appropriate placement of students with ID to one of the two models. The included students with ID are motivated and self-determined in continuing in the program.
It has been realized in the recent years that magnetized disk windsdisk- likely play a decisive role in the global evolution of protoplanetary disksprotoplanetaryevolution (PPDs). Motivated by recent local simulationslocal , we first describe a global magnetized disk wind model, from which wind-driven accretion rate-ratewind-driven and wind mass loss rate can be reliably estimated. Both rates are shown to strongly depend on the amount of magnetic fluxmagnetic threading the disk. Wind kinematics is also affected by thermodynamics in the wind zone (particularly far UV heating/ionization), and the mass loss processloss- can be better termed as "magneto-photoevaporation." We then construct a framework of PPD global evolutionglobal that incorporates wind-driven and viscously driven accretionviscously-driven as well as wind mass loss. For typical PPD accretion rates, the required field strength would lead to wind mass loss rate at least comparable to disk accretion rate, and mass loss is most significant in the outer disk (beyond ˜ 10 AU). Finally, we discuss the transport of magnetic flux in PPDs, which largely governs the long-term evolutionlong-term of PPDs.
In this editorial, we first summarize the 2016 International Conference on Intelligent Biology and Medicine (ICIBM 2016) that was held on December 8-10, 2016 in Houston, Texas, USA, and then briefly introduce the ten research articles included in this supplement issue. ICIBM 2016 included four workshops or tutorials, four keynote lectures, four conference invited talks, eight concurrent scientific sessions and a poster session for 53 accepted abstracts, covering current topics in bioinformatics, systems biology, intelligent computing, and biomedical informatics. Through our call for papers, a total of 77 original manuscripts were submitted to ICIBM 2016. After peer review, 11 articles were selected in this special issue, covering topics such as single cell RNA-seq analysis method, genome sequence and variation analysis, bioinformatics method for vaccine development, and cancer genomics.
Mueller, Steffen; Coleman, J. Robert; Papamichail, Dimitris; Ward, Charles B.; Nimnual, Anjaruwee; Futcher, Bruce; Skiena, Steven; Wimmer, Eckard
2010-01-01
Influenza claims 250,000 - 500,000 lives annually worldwide. Despite existing vaccines and enormous efforts in biomedical research, these staggering numbers have not changed significantly over the last two decades1, motivating the search for new, more effective, vaccines that can be rapidly designed and easily produced. Using influenza virus strain A/PR/8/34, we describe a systematic, rational approach, termed Synthetic Attenuated Virus Engineering (SAVE), to develop new, efficacious live attenuated influenza virus vaccine candidates through genome-scale changes in codon pair bias. Attenuation is based on many hundreds of nucleotide changes across the viral genome, offering high genetic stability and a wide margin of safety. The method can be applied rapidly to any emerging influenza virus in its entirety, an advantage that is significant for dealing with seasonal epidemics and pandemic threats, such as H5N1- or 2009-H1N1 influenza. PMID:20543832
Kancherla, Vijaya; Van Naarden Braun, Kim; Yeargin-Allsopp, Marshalyn
2015-01-01
Dental care among young adults with intellectual disability (ID) is poorly documented and largely unmet. By using population-based data from the Metropolitan Atlanta Developmental Disabilities Follow-Up Study, we assessed factors associated with at least one or two dental visits per year among young adults with and without ID. Significantly fewer young adults with ID (45%) visited a dentist at least once per year, compared with those without ID (58%). ID severity and the presence of co-occurring developmental disabilities predicted dental care use. Sociodemographics, daily functioning, societal participation, dental services, and dental health factors were examined as predictors of dental care frequency. Our findings can help focus efforts toward improving the frequency of dental care visits among young adults with ID. PMID:23501584
Nationally, there is a drive to rotate more Foundation and GP Trainee Doctors through Psychiatry posts. In East London Foundation Trust (ELFT) in Bedfordshire, doctors from Core Psychiatry, Foundation and GP training programmes come to train in Psychiatry. Many will not have worked in Psychiatry before and have little experience of patients with ID. The prevalence of people with ID is increasing with improved life expectancy. They are a complex and vulnerable group with considerable wider legal, ethical and social issues. Recent national reports including the Confidential Inquiry in to Premature Deaths in People with Learning Disability 3 and Transforming Care 4 have recommended increased training and awareness of the roles and responsibilities for all health staff who provide care to people with ID. To survey the knowledge level and expectations of junior doctors on Psychiatry placements in Bedfordshire in relation to ID and local logistical arrangements of services and on call duties. The local ID governance committee together with the Postgraduate Medical Education Department created a questionnaire which was circulated to new trainee Doctors on placements with ELFT. The questionnaire was distributed to new trainees after 3 different inductions throughout the year. This combined self-rating questions using Likert scales, multiple choice answers and others allowing for expanded free text answers. The results show the self-rated knowledge levels of ID psychiatry in general and with regard to local services and on call arrangements amongst new trainees was low. The majority of trainees indicated they would have liked to have received information on the suggested areas at the start of the placement. When given the option of themes of information the psychiatric and medical presentation was most sought, although general and on call specific information was also indicated to be useful. The most popular delivery of information was found to be oral presentation and hand out at induction, followed by an electronic document. 8 trainees were interested in attending clinical sessions in ID and most felt it would be feasible in their posts to get to these. This survey shows that Junior Doctors from different training programmes rate their knowledge of ID psychiatry to be low. This has implications during their rotation in a mental health trust as they are expected to cover an ID ward whilst on call, but also going forward in their careers as all specialties will encounter patients with ID. It is known that awareness of patients with ID is lacking in many healthcare professionals and we know that people with ID are living longer, however continue to have worse health than the general population. The results show trainees would like more education on ID and would be interested in attending clinical sessions in ID psychiatry. The results will enable clinicians in ID services how best to improve the local induction experience for trainees. It also will guide how to educate colleagues outside of the specialty to improve their practice with people with ID, which will improve standards in the quality of care people with ID receive from doctors who treat them.
Background Inclusion of people with intellectual disability (ID) in higher postsecondary academic education is on the rise. However, there are no scientific criteria for determining the eligibility for full inclusion of students with ID in university courses. This study focuses on two models of academic inclusion for students with ID: (a) separate adapted enrichment model: students with ID study in separate enrichment courses adapted to their level; (b) full inclusion model: students with ID are included in undergraduate courses, receive academic credits and are expected to accumulate the amount of credits for a B.A. Aim (a) To examine whether crystallized and fluid intelligence and cognitive tests can serve as screening tests for determining the appropriate placement of students with ID for the adapted enrichment model versus the full inclusion model. (b) To examine the attitudes towards the program of students with ID in the inclusion model. Method/Procedure The sample included 31 adults with ID: students with ID who were fully included (N = 10) and students with ID who participated in the adapted enrichment model (N = 21). Crystallized and fluid intelligence were examined (WAIS-III, Wechsler, 1997) and Hebrew abstract verbal tests (Glanz, 1989). Semi-structured interviews were conducted in order to examine the attitudes of students in the inclusion model towards the program. Outcomes and results The ANOVAs indicate that the most prominent difference between the groups was in vocabulary, knowledge and working memory. ROC analysis, a fundamental tool for diagnostic test evaluation, was used to determine the students’ eligibility for appropriate placement in the two models. Seven tests distinguished between the groups in terms of sensitivity and specificity. The interviews were analyzed according to three phases. Conclusions/Implications The results indicate that students with ID are able to participate in undergraduate courses and achieve academic goals. The general IQ and idioms test seem to be best determiners for appropriate placement of students with ID to one of the two models. The included students with ID are motivated and self-determined in continuing in the program. PMID:29684024
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... compliant on or before May 11, 2011. Id. At the time DHS promulgated the REAL ID final rule, DHS recognized... time to ensure that the documents they issue meet the security requirements of the REAL ID Act. Without.... SUMMARY: Pursuant to the Department of Homeland Security's REAL ID regulations, States must be in full...
Background: The role of gender has been a neglected issue in research on intellectual disability (ID). People with ID are generally treated as a homogenous group that are largely categorized by their level of ID. This study compared living conditions of women and men with ID and related the results to similarities and differences among the general…
Most school districts do not have an ID card policy that everyone knows and follows, yet. many school districts are implementing ID card programs to address concerns about safety, efficiency, and convenience. A well-thought-out ID card program leads to greater security and smoother operations throughout the school and should thus be a priority.…
Mullen, Saul A.; Carvill, Gemma L.; Bellows, Susannah; Bayly, Marta A.; Berkovic, Samuel F.; Dibbens, Leanne M.
2013-01-01
Objective: We examined whether copy number variants (CNVs) were more common in those with a combination of intellectual disability (ID) and genetic generalized epilepsy (GGE) than in those with either phenotype alone via a case-control study. Methods: CNVs contribute to the genetics of multiple neurodevelopmental disorders with complex inheritance, including GGE and ID. Three hundred fifty-nine probands with GGE and 60 probands with ID-GGE were screened for GGE-associated recurrent microdeletions at 15q13.3, 15q11.2, and 16p13.11 via quantitative PCR or loss of heterozygosity. Deletions were confirmed by comparative genomic hybridization (CGH). ID-GGE probands also had genome-wide CGH. Results: ID-GGE probands showed a significantly higher rate of CNVs compared with probands with GGE alone, with 17 of 60 (28%) ID-GGE probands having one or more potentially causative CNVs. The patients with ID-GGE had a 3-fold-higher rate of the 3 GGE-associated recurrent microdeletions than probands with GGE alone (10% vs 3%, p = 0.02). They also showed a high rate (13/60, 22%) of rare CNVs identified using genome-wide CGH. Conclusions: This study shows that CNVs are common in those with ID-GGE with recurrent deletions at 15q13.3, 15q11.2, and 16p13.11, particularly enriched compared with individuals with GGE or ID alone. Recurrent CNVs are likely to act as risk factors for multiple phenotypes not just at the population level, but also in any given individual. Testing for CNVs in ID-GGE will have a high diagnostic yield in a clinical setting and will inform genetic counseling. PMID:24068782
Saunders, Barbara S; Tilford, J Mick; Fussell, Jill J; Schulz, Eldon G; Casey, Patrick H; Kuo, Dennis Z
2015-03-01
Families of children with autism spectrum disorder (ASD) endure significant financial and employment burden because of their children's numerous needed services. The study objective is to describe additional impact on families of children with intellectual disability (ID) in addition to ASD. The study is a secondary data analysis of the 2009-2010 National Survey of Children with Special Health Care Needs. Children whose parents answered "yes" when asked whether their child had ASD or ID were classified as having ASD alone (unweighted n = 2,406), ID alone (unweighted n = 1,363), or both ASD/ID (unweighted n = 620). Bivariate and multivariate analyses compared study outcomes of family financial and caregiver burden using ASD as the reference group. All analyses were weighted using person-level estimates. Of children with ASD, 24% also had ID. More than half of caregivers of children with ASD/ID reported financial difficulty (52%) and having to stop work to care for their child (51%). Compared with ASD alone, caregivers of children with both ASD/ID were more likely to report financial difficulty (aOR 1.65, 95% CI 1.10-2.46), cutting work hours (aOR 1.43, 95% CI .98-2.08), and stop working (aOR 2.32, 95% CI 1.57-3.43). No differences were found between caregivers of children with ASD only and ID only. We conclude that having ID in addition to ASD may be associated with greater negative impact on family financial and employment burden. Recognition of ID in addition to ASD is important to tailor the clinical approach and sufficiently support families. (PsycINFO Database Record (c) 2015 APA, all rights reserved).
Schmitt, Steven; MacIntyre, Ann T; Bleasdale, Susan C; Ritter, J Trees; Nelson, Sandra B; Berbari, Elie F; Burdette, Steven D; Hewlett, Angela; Miles, Matthew; Robinson, Philip A; Siddiqui, Javeed; Trotman, Robin; Martinelli, Lawrence; Zeitlin, Gary; Rodriguez, Andrés; Smith, Mark W; McQuillen, Daniel P
2018-06-13
Intervention by infectious diseases (ID) physicians improves outcomes for inpatients in Medicare, but patients with other insurance types could fare differently. We assessed whether ID involvement leads to better outcomes among privately insured patients under age 65 hospitalized with common infections. We performed a retrospective analysis of administrative claims data from community hospital and post-discharge ambulatory care. Patients were privately insured individuals under 65 years old with an acute-care stay in 2014 for selected infections, classed as having early (by day 3) or late (after day 3) ID intervention, or none. Key outcomes were mortality, cost, length of the index stay; readmission rate, mortality and total cost of care over the first 30 days after discharge. Patients managed with early ID involvement had shorter length of stay, lower spending, and lower mortality in the index stay than those patients managed without ID involvement. Relative to late, early ID involvement was associated with shorter length of stay and lower cost. Individuals with early ID intervention during hospitalization had fewer readmissions and lower healthcare payments after discharge. Relative to late, those with early ID intervention experienced lower readmission, lower spending, and lower mortality. Among privately insured patients under 65 years old, treated in a hospital, early intervention with an ID physician was associated with lower mortality rate and shorter length of stay. Patients who received early ID intervention during their hospital stay were less likely to be readmitted after discharge and had lower total healthcare spending.
Santesso, Diane L.; Schmidt, Louis A.; Trainor, Laurel J.
2007-01-01
Many studies have shown that infants prefer infant-directed (ID) speech to adult-directed (AD) speech. ID speech functions to aid language learning, obtain and/or maintain an infant's attention, and create emotional communication between the infant and caregiver. We examined psychophysiological responses to ID speech that varied in affective…
This study investigates the use of inquiry learning (IL) approach for intellectually disabled (ID) students. It draws on findings from the trial lessons of 6 classes of ID students in a project developing an adapted General Studies Curriculum for ID students at primary level. Data analysis focuses on examining how IL was employed for ID students.…
Farias, Sarah Tomaszewski; Chand, Vineeta; Bonnici, Lisa; Baynes, Kathleen; Harvey, Danielle; Mungas, Dan; Simon, Christa; Reed, Bruce
2012-11-01
The Nun Study showed that lower linguistic ability in young adulthood, measured by idea density (ID), increased the risk of dementia in late life. The present study examined whether ID measured in late life continues to predict the trajectory of cognitive change. ID was measured in 81 older adults who were followed longitudinally for an average of 4.3 years. Changes in global cognition and 4 specific neuropsychological domains (episodic memory, semantic memory, spatial abilities, and executive function) were examined as outcomes. Separate random effects models tested the effect of ID on longitudinal change in outcomes, adjusted for age and education. Lower ID was associated with greater subsequent decline in global cognition, semantic memory, episodic memory, and spatial abilities. When analysis was restricted to only participants without dementia at the time ID was collected, results were similar. Linguistic ability in young adulthood, as measured by ID, has been previously proposed as an index of neurocognitive development and/or cognitive reserve. The present study provides evidence that even when ID is measured in old age, it continues to be associated with subsequent cognitive decline and as such may continue to provide a marker of cognitive reserve.
The recent rise in unfilled training positions among infectious diseases (ID) fellowship programs nationwide indicates that ID is declining as a career choice among internal medicine residency graduates. Supplementing ID training with training in critical care medicine (CCM) might be a way to regenerate interest in the specialty. Hands-on patient care and higher salaries are obvious attractions. High infection prevalence and antibiotic resistance in intensive care units, expanding immunosuppressed host populations, and public health crises such as the recent Ebola outbreak underscore the potential synergy of CCM-ID training. Most intensivists receive training in pulmonary medicine and only 1% of current board-certified intensivists are trained in ID. While still small, this cohort of CCM-ID certified physicians has continued to rise over the last 2 decades. ID and CCM program leadership nationwide must recognize these trends and the merits of the CCM-ID combination to facilitate creation of formal dual-training opportunities. Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.
Many association studies provide the relationship between single nucleotide polymorphisms (SNPs), diseases and cancers, without giving a SNP ID, however. Here, we developed the SNP ID-info freeware to provide the SNP IDs within inputting genetic and physical information of genomes. The program provides an "SNP-ePCR" function to generate the full-sequence using primers and template inputs. In "SNPosition," sequence from SNP-ePCR or direct input is fed to match the SNP IDs from SNP fasta-sequence. In "SNP search" and "SNP fasta" function, information of SNPs within the cytogenetic band, contig position, and keyword input are acceptable. Finally, the SNP ID neighboring environment for inputs is completely visualized in the order of contig position and marked with SNP and flanking hits. The SNP identification problems inherent in NCBI SNP BLAST are also avoided. In conclusion, the SNP ID-info provides a visualized SNP ID environment for multiple inputs and assists systematic SNP association studies. The server and user manual are available at http://bio.kuas.edu.tw/snpid-info.
The tumour-associated antigen, Ep-CAM, is over-expressed in colorectal carcinoma (CRC). In the present study, a recombinant Ep-CAM protein or a human anti-idiotypic antibody (anti-Id) mimicking Ep-CAM, either alone or in combination, was used for vaccination of CRC patients (n=9). GM-CSF was given as an adjuvant cytokine. A cellular immune response was assessed by measuring anti-Ep-CAM lymphoproliferation, IFN-gamma production (ELISPOT) and by analysing the TCR BV gene usage within the CD4+ and CD8+ T-cell subsets followed by CDR3 fragment analysis. A proliferative and/or IFN-gamma T-cell response was induced against the Ep-CAM protein in eight out of nine patients, and against Ep-CAM-derived peptides in nine out of nine patients. Analysis of the TCR BV gene usage showed a significantly higher usage of BV12 family in CD4+ T cells of patients both before and after immunisation than in those of healthy control donors (p<0.05). In the CD8+ T-cell subset, a significant (p<0.05) increase in the BV19 usage was noted in patients after immunisation. In individual patients, a number of TCR BV gene families in both CD4+ and CD8+ T cells were over-expressed mainly in post-immunisation samples. Analysis of the CDR3 length polymorphism revealed a higher degree of clonality in post-immunisation samples than in pre-immunisation samples. In vitro stimulation with Ep-CAM protein confirmed the expansion of anti-Ep-CAM T-cell clones. The results indicate that immunisation with the Ep-CAM protein and/or anti-Id entails the induction of an anti-Ep-CAM T-cell response in CRC patients, and suggest that BV19+ CD8+ T cells might be involved in a vaccine-induced immune response.
...In this Report and Order (Order), the Commission adopts rules to implement the Truth in Caller ID Act of 2009 (Truth in Caller ID Act, or Act). The Truth in Caller ID Act, and the Commission's implementing rules, prohibit any person or entity from knowingly altering or manipulating caller identification information with the intent to defraud, cause harm, or wrongfully obtain anything of value.
Family impact (or family burden) is a concept born in the field of mental health that has successfully been exported to the ambit of intellectual disability (ID). However, differences in family impact associated with severe mental health disorders (schizophrenia), to ID or to mental health problems in ID should be expected. Seventy-two adults with…
ETR BASEMENT, TRA-642, INTERIOR. BASEMENT. CUBICLE INTERIOR (SEE PHOTOS ID-33-G-101 AND ID-33-G-102) WITH TANK AND SODIUM-RELATED APPARATUS. CAMERA STANDS BEFORE ROLL-UP DOOR SHOWN IN PHOTO ID-33-G-101. INL NEGATIVE NO. HD24-3-3. Mike Crane, Photographer, 11/2000 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID
While studies report associations between perinatal outcomes and both autism spectrum disorder (ASD) and intellectual disability (ID), there has been little study of ASD with versus without co-occurring ID. We compared perinatal risk factors among 7547 children in the 2006-2010 Autism and Developmental Disability Monitoring Network classified as…
... to the INL Research Library at 1776 Science Center Drive, Idaho Falls, ID 83401, beginning September... Library, 1776 Science Center Drive, Idaho Falls, ID 83401. FOR FURTHER INFORMATION CONTACT: Clayton...
Evenhuis, H M; Sjoukes, L; Koot, H M; Kooijman, A C
2009-01-01
This study addresses the question to what extent visual impairment leads to additional disability in adults with intellectual disabilities (ID). In a multi-centre cross-sectional study of 269 adults with mild to profound ID, social and behavioural functioning was assessed with observant-based questionnaires, prior to expert assessment of visual function. With linear regression analysis the percentage of variance, explained by levels of visual function, was calculated for the total population and per ID level. A total of 107/269 participants were visually impaired or blind (WHO criteria). On top of the decrease by ID visual impairment significantly decreased daily living skills, communication & language, recognition/communication. Visual impairment did not cause more self-absorbed and withdrawn behaviour or anxiety. Peculiar looking habits correlated with visual impairment and not with ID. In the groups with moderate and severe ID this effect seems stronger than in the group with profound ID. Although ID alone impairs daily functioning, visual impairment diminishes the daily functioning even more. Timely detection and treatment or rehabilitation of visual impairment may positively influence daily functioning, language development, initiative and persistence, social skills, communication skills and insecure movement.
Pescatello, Linda S; Kostek, Matthew A; Gordish-Dressman, Heather; Thompson, Paul D; Seip, Richard L; Price, Thomas B; Angelopoulos, Theodore J; Clarkson, Priscilla M; Gordon, Paul M; Moyna, Niall M; Visich, Paul S; Zoeller, Robert F; Devaney, Joseph M; Hoffman, Eric P
2006-06-01
To examine associations among the angiotensin I-converting enzyme (ACE) insertion (I)/deletion (D) polymorphism and the response to a 12-wk (2 d.wk) unilateral, upper-arm resistance training (RT) program in the trained (T, nondominant) and untrained (UT, dominant) arms. Subjects were 631 (mean+/-SEM, 24.2+/-0.2 yr) white (80%) men (42%) and women (58%). The ACE ID genotype was in Hardy-Weinberg equilibrium with frequencies of 23.1, 46.1, and 30.8% for ACE II, ID, and DD, respectively (chi=1.688, P=0.430). Maximum voluntary contraction (MVC) and one-repetition maximum (1RM) assessed peak elbow flexor muscle strength. Magnetic resonance imaging measured biceps muscle cross-sectional area (CSA). Multiple variable and repeated-measures ANCOVA tested whether muscle strength and size differed at baseline and pre- to post-RT among T and UT and ACE ID genotype. Baseline muscle strength and size were greater in UT than T (P<0.001) and did not differ among ACE ID genotype in either arm (P >or= 0.05). In T, MVC increases were greater for ACE II/ID (22%) than DD (17%) (P<0.05), whereas 1RM (51%) and CSA (19%) gains were not different among ACE ID genotype pre- to post-RT (P >or= 0.05). In UT, MVC increased among ACE II/ID (7%) (P<0.001) but was similar among ACE DD (2%) pre- to post-RT (P >or= 0.05). In UT, 1RM (11%) and CSA (2%) increases were greater for ACE DD/ID than ACE II (1RM, 7%; CSA, -0.1%) (P<0.05). ACE ID genotype explained approximately 1% of the MVC response to RT in T and approximately 2% of MVC, 2% of 1RM, and 4% of CSA response in UT (P<0.05). ACE ID genotype is associated with the contralateral effects of unilateral RT, perhaps more so than with the muscle strength and size adaptations that result from RT.
There is limited experimental evidence to support the view that individuals with intellectual disabilities (ID) have a deficit in motor control. This work is a first attempt to evaluate their motor coordination. The study assessed the relationship between cognitive ability and sensorimotor integration. The clinical hypothesis is that adults with ID fall below non-ID adults in motor skills that involve hand-eye coordination. A group of 42 adults with ID (ID group) was compared to 48 age-matched typical adults (TA) using a mixed experimental design ('Task' as the within-subjects factor and 'Group' as the between-subjects factor). Participants performed the following tests twice: Box-and-Blocks, 25-Grooved-Pegboard, Stick Catching and overhead Beanbag-Throw. Pearson correlations and ANOVAs were used to test the hypothesis (p < or = 0.05). As expected, TA outperformed the ID group in all tests regardless of the hand used during for the assessment. However, TA individuals scored significantly better with one hand (i.e., the preferred and dominant hand) as opposed to persons with ID, who exhibited no hand preference. Test-retest correlations among the first and second assessment scores yielded moderate-strong coefficients, depending on the type of test (Box-and-Blocks = 0.92 and 0.96, 25-Grooved-Pegboard = 0.69 and 0.83, Stick-Catching = 0.88 and 0.94, Beanbag-Throw = 0.58 and 0.91 for ID and TA, respectively). Difficulties in the integration of perceptual information into motor action may result in inadequate solutions to daily motor problems. As it stems from our results, intellectual disability relates to inability to integrate visual inputs and hand movements. In people with mild ID such inability is observed using both hands (i.e., they show no hand preferences). Poor perceptual-motor coordination might have a functional significance in that it may lead to exclusion from vocational and recreational activities, and a decreasing competence of ADL. Assessing coordination in adults with ID may contribute to understanding the nature of the ID condition and may encourage an early rehabilitation.
This study aimed to understand and describe the views of family members and direct support staff regarding the use of Facebook by persons with intellectual disability (ID) within the context of social capital. In-depth, semistructured interviews conducted with 16 family members and direct support staff of persons with ID who use Facebook revealed that most participants favored Facebook use by persons with ID for bonding and bridging social capital and for normalization. Most participants noted the empowering effect of online activity on persons with ID, yet some reported risks and usage difficulties. Although Facebook use enhances the well-being of persons with ID, findings highlighted the participants' need for formal guidelines regarding social media best-practices for people with ID.
People with intellectual disability (ID), are some of the most stigmatized and marginalized social groups. Ongoing global initiatives such as the United Nations Convention on the Rights of Persons with Disabilities (UNCPD) and Strategic Development Goals (SDGs) aim to accelerate their inclusion into the society. In many high-income countries, deinstitutionalization of care for people with ID forms part of the broader social inclusion agenda for people with ID into the society. Access to appropriate assistive technology (AT) can mediate the ongoing normalization/inclusion efforts for people with ID. AT can enable users with ID to access societal processes such as education, employment, socialization or independent living. Effective use of AT can also enhance the formation and/or maintenance of interpersonal relationships by people with ID, thus promote their social support.
...) Global Positioning System (GPS) and the Instrument Landing System (ILS) or Localizer (LOC) standard... the earth. * * * * * ANM ID E5 Twin Falls, ID [Modified] Twin Falls Joslin Field-Magic Valley Regional...
There is a growing recognition for the importance of proteins with large intrinsically disordered (ID) segments in cell signaling and regulation. ID segments in these proteins often harbor regions that mediate molecular recognition. Coupled folding and binding of the recognition regions has been proposed to confer high specificity to interactions involving ID segments. However, researchers recently questioned the origin of the interaction specificity of ID proteins because of the overrepresentation of hydrophobic residues in their interaction interfaces. Here, we focused on the role of polar and charged residues in interactions mediated by ID segments. Making use of the extended nature of most ID segments when in complex with globular proteins, we first identified large numbers of complexes between globular proteins and ID segments by using radius-of-gyration-based selection criteria. Consistent with previous studies, we found the interfaces of these complexes to be enriched in hydrophobic residues, and that these residues contribute significantly to the stability of the interaction interface. However, our analyses also show that polar interactions play a larger role in these complexes than in structured protein complexes. Computational alanine scanning and salt-bridge analysis indicate that interfaces in ID complexes are highly complementary with respect to electrostatics, more so than interfaces of globular proteins. Follow-up calculations of the electrostatic contributions to the free energy of binding uncovered significantly stronger Coulombic interactions in complexes harbouring ID segments than in structured protein complexes. However, they are counter-balanced by even higher polar-desolvation penalties. We propose that polar interactions are a key contributing factor to the observed high specificity of ID segment-mediated interactions. PMID:23990768
The use of midazolam for dental care in patients with intellectual disability is poorly documented. This study aimed to evaluate the effectiveness and safety of conscious sedation procedures using intravenous midazolam in adults and children with intellectual disability (ID) compared to dentally anxious patients (DA). Ninety-eight patients with ID and 44 patients with DA programmed for intravenous midazolam participated in the study over 187 and 133 sessions, respectively. Evaluation criteria were success of dental treatment, cooperation level (modified Venham scale), and occurrence of adverse effects. The mean intravenous dose administered was 8.8±4.9 mg and 9.8±4.1 mg in ID and DA sessions respectively (t-test, NS). 50% N2O/O2 was administered during cannulation in 51% of ID sessions and 61% of DA sessions (NS, Fisher exact test). Oral or rectal midazolam premedication was administered for cannulation in 31% of ID sessions and 3% of DA sessions (p<0,001, Fisher exact test). Dental treatment was successful in 9 out of 10 sessions for both groups. Minor adverse effects occurred in 16.6% and 6.8% of ID and DA sessions respectively (p = 0.01, Fisher exact test). Patients with ID were more often very disturbed during cannulation (25.4% ID vs. 3.9% DA sessions) and were less often relaxed after induction (58.9% ID vs. 90.3% DA) and during dental treatment (39.5% ID vs. 59.7% DA) (p<0.001, Fisher exact test) than patients with DA. When midazolam sedation was repeated, cooperation improved for both groups. Conscious sedation procedures using intravenous midazolam, with or without premedication and/or inhalation sedation (50% N2O/O2), were shown to be safe and effective in patients with intellectual disability when administered by dentists. PMID:23940729
"Intelligent Design" (ID) is a new form of creationism that emerged after legal decisions in the 1980s hampered the inclusion of "creation science" in the public school curriculum. To avoid legal challenge, proponents claim agnosticism regarding the identity of the intelligent agent, which could be material (such as highly intelligent terrestrials) or transcendental (God). ID consists of a scientific/scholarly effort, and a politico-religious movement of "cultural renewal." Intelligent design is supposedly detectable through the application of Michael Behe's "irreducible complexity" concept and/or William Dembski's concept of "complex specified information". ID's claims amount to, first, that "Darwinism" (vaguely defined) is incapable of providing an adequate mechanism for evolution, and second (subsequently), that evolution did not occur. Although scientific ideas not infrequently are slow to be accepted, in the 20 years since ID appeared, there is no evidence of it being used to solve problems in biology. Even if the scientific/scholarly part of ID has been a failure, the "cultural renewal" part of ID has been a success. This social and political aspect of ID seeks "restoration" of a theistic sensibility in American culture to replace what supporters consider an overemphasis on secularism. In the last few years, in several states, legislators have introduced legislation promoting ID (to date, unsuccessfully) and an addendum to the 2001 federal education bill conference committee report (the "Santorum amendment") is being used to promote the teaching of ID in public schools. Perhaps because ID has no actual content other than antievolutionism, ID proponents contend that pre-college teachers should teach wweaknesses of evolutionw or "evidence against evolutionw - largely warmed-over arguments from creation science - even though professional scientists do not recognize these as valid scientific claims.
... Login ID and FIX Login ID to $500 per month for regular access and $1000 per month for Sponsored User... a FIX fee of $1200 for a minimum of two monthly login IDs (so, $600 for one), or a fee of $2,400 for... to increase the fees charged for a CMI Login ID and FIX Login ID to $500 per month for regular access...
Strelnikov, N.; Budker Institute of Nuclear Physics, Novosibirsk 630090; Trakhtenberg, E.
2014-11-15
A short prototype (847-mm-long) of an Insertion Device (ID) with the dynamic compensation of ID magnetic forces has been designed, built, and tested at the Advanced Photon Source (APS) of the Argonne National Laboratory. The ID magnetic forces were compensated by the set of conical springs placed along the ID strongback. Well-controlled exponential characteristics of conical springs permitted a very close fit to the ID magnetic forces. Several effects related to the imperfections of actual springs, their mounting and tuning, and how these factors affect the prototype performance has been studied. Finally, series of tests to determine the accuracy andmore » reproducibility of the ID magnetic gap settings have been carried out. Based on the magnetic measurements of the ID B{sub eff}, it has been demonstrated that the magnetic gaps within an operating range were controlled accurately and reproducibly within ±1 μm. Successful tests of this ID prototype led to the design of a 3-m long device based on the same concept. The 3-m long prototype is currently under construction. It represents R and D efforts by the APS toward APS Upgrade Project goals as well as the future generation of IDs for the Linac Coherent Light Source (LCLS)« less
Lunsky, Y; White, S E; Palucka, A M; Weiss, J; Bockus, S; Gofine, T
2010-01-01
Limitations of general psychiatric services have led to the development of specialised psychiatric programmes for patients with intellectual disability (ID) and mental health needs. Few studies have examined treatment outcomes of specialised inpatient units, and no studies have explored how the effects of intervention may differ for individuals at varying levels of cognitive ability. The present study examined clinical outcomes of inpatients with mild ID in contrast to inpatients with moderate to severe ID within the same service. Thirty-three patients (17 with mild ID and 16 with moderate to severe ID) discharged between 2006 and 2008 from a specialised inpatient unit in Canada for adults with ID and mental illness were studied. In addition to examining change in scores on clinical measures, outcomes with regard to length of stay, diagnostic change, residential change and re-admission to hospital were explored. Both groups demonstrated clinical improvement from admission to discharge. However, only patients with mild ID demonstrated improvements on the Global Assessment of Functioning. This study is one of the first to consider outcomes of higher and lower functioning individuals with ID on a specialised inpatient unit. Results suggest that outcomes may be different for these groups, and some clinical measures may be more sensitive to changes in patients with more severe disabilities.
... notification and a valid government- issued photo ID (such as driver's license, passport, U.S. government or... number/state, passport number/country, or U.S. government ID number/agency or military ID number/branch...
Ditchman, Nicole; Werner, Shirli; Kosyluk, Kristin; Jones, Nev; Elg, Brianna; Corrigan, Patrick W
2013-05-01
Individuals with intellectual disabilities (ID) and individuals with mental illness are consistently found to be among the most socially excluded populations and continue to face substantial health, housing, and employment disparities due to stigma. Although this has spurred extensive research efforts and theoretical advancements in the study of stigma toward mental illness, the stigma of ID has received only limited attention. In this article we explore the application of mental illness stigma research for ID. We carefully reviewed the existing research on mental illness stigma as a foundation for a parallel summary of the empirical literature on attitudes and stigma related to ID. Based on our review, there has not been a systematic approach to the study of stigma toward ID. However, multilevel conceptual models of stigma have received much attention in the mental illness literature. These models have been used to inform targeted interventions and have application to the study of the stigma process for individuals with ID. Nonetheless, there are indeed key differences between-as well as substantial variability within-the ID and mental illness populations that must be considered. Stigma is an issue of social justice impacting the lives of individuals with ID, yet there remains virtually no systematic framework applied to the understanding of the stigma process for this group. Future research can draw on the stigma models developed in the mental illness literature to guide more rigorous research efforts and ultimately the development of effective, multilevel stigma-change strategies for ID.
Iodine deficiency (ID)-induced thyroid hormone (TH) insufficient during development leads to impairments of brain function, such as learning and memory. Marginal ID has been defined as subtle insufficiency of TH, characterized as low thyroxine (T 4 ) levels, whether marginal ID potentially had adverse effects on the development of hippocampus and the underlying mechanisms remain unclear. Thus, in the present study, we established Wistar rat models with ID diet during pregnancy and lactation. The effects of marginal ID on long-term potentiation (LTP) were investigated in the hippocampal CA1 region. To study the development of dendritic spines in pyramidal cells, Golgi-Cox staining was conducted on postnatal day (PN) 7, PN14, PN21, and PN28. The activation of Rac1 signaling pathway, which is essential for dendritic spine development by regulating actin cytoskeleton, was also investigated. Our results showed that marginal ID slightly reduced the field-excitatory postsynaptic potential (f-EPSP) slope and the population spike (PS) amplitude. Besides, the density of dendritic spines during the critical period of rat postnatal development was mildly decreased, and we found no significant change of spine morphology in marginal ID group. We also observed decreased activation of the Rac1 signaling pathway in pups subjected to maternal marginal ID. Our study may support the hypothesis that decreased T 4 induced by marginal ID results in slight impairments of LTP and leads to mild damage of dendritic spine development, which may be due to abnormal regulation of Rac1 signaling pathway on cytoskeleton.
Yaqoob, M; Bashir, A; Zaman, S; Ferngren, H; Von Dobeln, U; Gustavson, K-H
2004-10-01
One of the main objectives of studying intellectual disability (ID) in children is to explore its causes. A specific aetiological diagnosis is important in determining the prognosis, nature and extent of services needed to support affected children. Aetiology and risk factors in mild ID were studied in a cohort of longitudinally followed children (6-10 years of age, n = 40) in four population groups in and around Lahore, Pakistan. The overall prevalence of mild ID was 6.2%. In 22% of the cases the onset of mild ID was prenatal with small for gestational age and multifactorial inheritance as the main underlying factors. During the postnatal period (28% of the cases), social deprivation and malnutrition were the major causes of ID. In a substantial proportion of the cases (50%), the cause of ID could not be traced. The present study indicates a clear relationship of mild ID with prenatal and postnatal malnutrition and social deprivation. Two independent variables, maternal illiteracy and small head circumference at birth, showed a clear association with the development of mild mental disability among children in the study population.
Polgreen, Philip M.; Beekmann, Susan E.; Cairns, Catherine; Filice, Gregory A.; Layton, Marcelle; Hughes, James M.
2016-01-01
Strong working relationships between infectious disease (ID) physicians and public health have resulted in the early detection of emerging infectious threats. From May 6 through June 5, 2015, we surveyed ID physicians in the Infectious Diseases Society of America’s Emerging Infections Network about communications with public health. A total of 688 of 1491 (46%) members completed the survey, 624 (91%) of whom knew how to reach their health department directly for an urgent issue. Only 38 (6%) described communications with their health department as poor. Interest in newer technologies (eg, mobile smartphone applications) showed mixed results. Interest in a smartphone application differed significantly by years of ID experience, with 81 of 146 (55%) respondents with <5 years of ID experience, 172 of 359 (48%) respondents with 5 to 24 years of ID experience, and 61 of 183 (33%) respondents with ≥25 years of ID experience in favor of a smartphone application (P < .001). As more physicians adopt newer communication technologies, health departments should be prepared to incorporate these tools to communicate with ID physicians. PMID:28123206
the wild type T peak. 12 Table 1. Sonic ntations dected by SINtA Individual Cell Sequence Amino Acid Species Conservation 3 ID’ ID Change2 Change... differences in the content of toxic substances in the diet (Biggs et al., 1993; Blaszyk et al., 1996). The development of this p53 mutation load...Changes in the P53 Gene in Single Cells Individual Sequence Amino acid Species conservation ’ ID’ Cell ID change’ change Monkey Mouse Rat Chicken
The present invention provides a novel endoglucanase nucleic acid sequence, designated egl6 (SEQ ID NO:1 encodes the full length endoglucanase; SEQ ID NO:4 encodes the mature form), and the corresponding endoglucanase VI amino acid sequence ("EGVI"; SEQ ID NO:3 is the signal sequence; SEQ ID NO:2 is the mature sequence). The invention also provides expression vectors and host cells comprising a nucleic acid sequence encoding EGVI, recombinant EGVI proteins and methods for producing the same.
... notification and a valid government-issued photo ID (such as driver's license, passport, U. S. government or... license number/State, passport number/country, or US government ID number/agency or military ID number...
... notification and a valid government- issued photo ID (such as driver's license, passport, U.S. government or.../state, passport number/country, or U.S. government ID number/agency or military ID number/branch), and...
... notification and a valid government-issued photo ID (such as driver's license, passport, U.S. government or... number/state, passport number/country, or U.S. government ID number/agency or military ID number/branch...
An increasing number of physicians are seeking dual training in critical care medicine (CCM) and infectious diseases (ID). Understanding experiences and perceptions of CCM-ID physicians could inform career choices and programmatic innovation. All physicians trained and/or certified in both CCM and ID to date in the United States were sent a Web-based questionnaire in 2015. Responses enabled a cross-sectional analysis of physician demographics and training and practice characteristics and satisfaction. Of 202 CCM-ID physicians, 196 were alive and reachable. The response rate was 79%. Forty-six percent trained and 34% practice in the northeastern United States. Only 40% received dual training at the same institution. Eighty-three percent identified as either an intensivist with ID expertise (44%) or as equally an intensivist and ID physician (38%). Median salary was $265 000 (interquartile range [IQR], $215 000-$350 000). Practice settings were split between academic (45%) and community settings (42%). Two-thirds are clinicians but 62% conduct some research and 26% practice outpatient ID. Top reasons to dually specialize included clinical synergy (70%), procedural activity (50%), and less interest in pulmonology (49%). Although 38% cited less proficiency with bronchoscopy as a disadvantage, 87% seldom need pulmonary consultation in the intensive care unit. Median career satisfaction was 4 (IQR, 4-5) out of 5, and 76% would dually train again. CCM-ID graduates prefer the acute care setting, predominantly CCM or a combination of CCM and ID. They find combination training and practice to be synergistic and satisfying, but most have had to seek CCM and ID training independently at separate institutions. Given these findings, avenues for combined training in CCM-ID should be considered. Published by Oxford University Press for the Infectious Diseases Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.
... be unsuitable for children. Viewing discretion is advised. Photos of the Disease and Images of People Affected by the Disease This micrograph ... Photo ID# 2857 PHIL Photo ID# 1657 PHIL Photo ID# 6373 Additional Images and Regulations Be sure to see the regulations ...
Li, Bin; Cheung, Pak Yan; Wang, Xianghong; Tsao, Sai Wah; Ling, Ming Tat; Wong, Yong Chuan; Cheung, Annie L M
2007-11-01
Inhibitor of differentiation or DNA binding (Id-1) is a helix-loop-helix protein that is over-expressed in many types of cancer including esophageal cancer. This study aims to investigate its effects on the phosphatidylinositol-3-kinase (PI3K)/Akt/ nuclear factor kappa B (NFkappaB) signaling pathway and the significance in protecting esophageal cancer cells against apoptosis. We found elevated expression of phosphorylated forms of Akt, glycogen synthase kinase 3beta and inhibitor of kappa B, as well as increased nuclear translocation of NFkappaB subunit p65 and NFkappaB DNA-binding activity, in esophageal cancer cells with stable ectopic Id-1 expression. Transient transfection of Id-1 into HEK293 cells confirmed activation of PI3K/Akt/NFkappaB signaling and the effects were counteracted by the PI3K inhibitor LY294002. Treatment with tumor necrosis factor-alpha (TNF-alpha) elicited a significantly weaker apoptotic response, following a marked and sustained activation of Akt and NFkappaB in the Id-1-over-expressing cells, compared with the vector control. The effects of Id-1 on the PI3K/Akt/NFkappaB signaling pathway and apoptosis were reversed in esophageal cancer cells transfected with siRNA against Id-1. In addition, inhibition of PI3K or NFkappaB signaling using the PI3K inhibitor LY294002 or the NFkappaB inhibitor Bay11-7082 increased the sensitivity of Id-1-over-expressing esophageal cancer cells to TNF-alpha-induced apoptosis. Our results provide the first evidence that Id-1 induces the activation of PI3K/Akt/NFkappaB signaling pathway, and protects esophageal cancer cells from TNF-alpha-induced apoptosis in vitro. Inactivation of Id-1 may provide us with a novel strategy to improve the treatment and survival of patients with esophageal cancer.
Autosomal recessive (AR) gene defects are the leading genetic cause of intellectual disability (ID) in countries with frequent parental consanguinity, which account for about 1/7th of the world population. Yet, compared to autosomal dominant de novo mutations, which are the predominant cause of ID in Western countries, the identification of AR-ID genes has lagged behind. Here, we report on whole exome and whole genome sequencing in 404 consanguineous predominantly Iranian families with two or more affected offspring. In 219 of these, we found likely causative variants, involving 77 known and 77 novel AR-ID (candidate) genes, 21 X-linked genes, as well as 9 genes previously implicated in diseases other than ID. This study, the largest of its kind published to date, illustrates that high-throughput DNA sequencing in consanguineous families is a superior strategy for elucidating the thousands of hitherto unknown gene defects underlying AR-ID, and it sheds light on their prevalence.
Despite some changes to the way that people with intellectual disabilities (ID) are viewed in society, negative attitudes prevail. One of the aspirations of the 2012 Paralympic games was to influence the public's attitudes toward people with disabilities. The aim of this study was to investigate whether stimuli depicting people with ID performing at Paralympic level of competition change attitudes toward ID. A mixed randomized comparison design was employed comparing 2 groups: those who viewed Paralympic-level ID sport footage and information and those who viewed Olympic footage and information. One hundred fourteen students, mean age 25 yr, were administered measures of implicit (subconscious) attitudes toward disability and explicit (belief-based) attitudes toward ID. Implicit attitudes significantly changed in a positive direction for both groups. The findings provide evidence that both Paralympic (ID) and Olympic media coverage may have at least a short-term effect on attitudes toward people with disabilities.
Santibañez, Scott; Polgreen, Philip M; Beekmann, Susan E; Cairns, Catherine; Filice, Gregory A; Layton, Marcelle; Hughes, James M
2016-09-01
Strong working relationships between infectious disease (ID) physicians and public health have resulted in the early detection of emerging infectious threats. From May 6 through June 5, 2015, we surveyed ID physicians in the Infectious Diseases Society of America's Emerging Infections Network about communications with public health. A total of 688 of 1491 (46%) members completed the survey, 624 (91%) of whom knew how to reach their health department directly for an urgent issue. Only 38 (6%) described communications with their health department as poor. Interest in newer technologies (eg, mobile smartphone applications) showed mixed results. Interest in a smartphone application differed significantly by years of ID experience, with 81 of 146 (55%) respondents with <5 years of ID experience, 172 of 359 (48%) respondents with 5 to 24 years of ID experience, and 61 of 183 (33%) respondents with ≥25 years of ID experience in favor of a smartphone application ( P < .001). As more physicians adopt newer communication technologies, health departments should be prepared to incorporate these tools to communicate with ID physicians.
Downing, Christopher; Howard, E Henry; Goodwin, Christina; Geller, E Scott
2016-01-01
Two studies examined factors influencing cashiers' identification (ID)-checking behavior in order to inform the development of interventions to prevent credit-card fraud. In both studies, research assistants made credit purchases in various stores and noted the cashiers' ID-checking behavior. In the first study, the store type, whether the cashier swiped the credit/debit card, the amount of the purchase, and whether the credit/debit card was signed significantly influenced ID-checking behavior. In the second study, an A-B-A design was used to evaluate the impact of a "Check my ID" prompt placed on the credit/debit card. The prompt increased cashiers' ID-checking behavior from 5.9% at Baseline to 10.3% during the Intervention. When the prompt was removed, the cashiers' ID-checking behavior decreased to 7.2%. Implications for further intervention research to prevent credit-card fraud are discussed.
To describe de prevalence of iron deficiency (ID) and anemia in a sample of Mexican elderly population from the National Health and Nutrition Survey (Ensanut) 2012. 1 920 subjects ≥60 years of age were included. Hemoglobin, serum concentrations of ferritin and CRP were measured. The risk for ID and anemia adjusted for potential confounders was assessed in logistic regression models. The overall prevalence of anemia was 13.9%, 15.2% in males and 12.8% females. For ID, overall it was 4.2%, males 4.0% and females 4.3%. The greatest prevalence of ID was found in males and females over 80 years old (6.9 and 7.0%, respectively). ID was present in 1.5 of 10 Mexican elders with anemia. The prevalence of anemia was high in the elderly, however the prevalence of ID was low; there is a need to further investigate the causes of anemia in this age group.
Id-1 (inhibitor of differentiation or DNA binding-1) has been positively associated with cell proliferation, cell cycle progression, and invasiveness during tumorigenesis. In addition, Id-1 has been shown to modulate cellular sensitivity to TGF-{beta}1 (transforming growth factor {beta}1). Here we demonstrate a novel role of Id-1 in promoting TGF-{beta}1-induced cell motility in a non-malignant prostate epithelial cell line, NPTX. We found that Id-1 promoted F-actin stress fiber formation in response to TGF-{beta}1, which was associated with increased cell-substrate adhesion and cell migration in NPTX cells. In addition, this positive effect of Id-1 on TGF-{beta}1-induced cell motility was mediated through activation ofmore » MEK-ERK signaling pathway and subsequent phosphorylation of HSP27 (heat shock protein 27). Furthermore, Id-1 disrupted the adherens junction complex in TGF-{beta}1-treated cells through down-regulation of E-cadherin, redistribution of {beta}-catenin, along with up-regulation of N-cadherin. These lines of evidence reveal a novel tumorigenic role of Id-1 through reorganization of actin cytoskeleton and disassembly of cell-cell adhesion in response to TGF-{beta}1 in human prostate epithelial cells, and suggest that intracellular Id-1 levels might be a determining factor for switching TGF-{beta}1 from a growth inhibitor to a tumor promoter during prostate carcinogenesis.« less
Stanish, Heidi I; Curtin, Carol; Must, Aviva; Phillips, Sarah; Maslin, Melissa; Bandini, Linda G
2016-01-01
Youths with intellectual disabilities (ID) exhibit low levels of physical activity, but the underlying contributors to behavior are unclear. We compared physical activity enjoyment, perceived barriers, beliefs, and self-efficacy among adolescents with ID and typically developing (TD) adolescents. A questionnaire was administered to 38 adolescents with ID (mean age, 16.8 years) and 60 TD adolescents (mean age, 15.3 years). Of the original 33 questionnaire items, 23 met the test-retest reliability criteria and were included in the group comparisons. Fewer adolescents with ID reported that they have someone with whom to do physical activity (64% vs 93%: P < .001), and a greater percentage of adolescents with ID perceived that physical activities were too hard to learn (41% vs 0%; P < .001). Fewer adolescents with ID believed that physical activity would be good for their health (92% vs 100%; P = .05). More adolescents with ID reported a dislike of individual physical activities (P = .02). A large percentage of adolescents with ID (84%) responded that they were good at doing physical activities, but the difference between groups was only of borderline significance (95% of TD adolescents, P = .06). Adolescents shared many of the same perceptions about physical activity, but some important differences between groups were identified.
Dorier, Julien; Goundaroulis, Dimos; Benedetti, Fabrizio; Stasiak, Andrzej
2018-05-02
The backbone of most proteins forms an open curve. To study their entanglement, a common strategy consists in searching for the presence of knots in their backbones using topological invariants. However, this approach requires to close the curve into a loop, which alters the geometry of curve. Knoto-ID allows evaluating the entanglement of open curves without the need to close them, using the recent concept of knotoids which is a generalization of the classical knot theory to open curves. Knoto-ID can analyse the global topology of the full chain as well as the local topology by exhaustively studying all subchains or only determining the knotted core. Knoto-ID permits to localize topologically non-trivial protein folds that are not detected by informatics tools detecting knotted protein folds. Knoto-ID is written in C ++ and includes R (www.R-project.org) scripts to generate plots of projections maps, fingerprint matrices and disk matrices. Knoto-ID is distributed under the GNU General Public License (GPL), version 2 or any later version and is available at https://github.com/sib-swiss/Knoto-ID. A binary distribution for Mac OS X, Linux and Windows with detailed user guide and examples can be obtained from https://www.vital-it.ch/software/Knoto-ID. julien.dorier@sib.swiss.
Objective. The Nun Study showed that lower linguistic ability in young adulthood, measured by idea density (ID), increased the risk of dementia in late life. The present study examined whether ID measured in late life continues to predict the trajectory of cognitive change. Method. ID was measured in 81 older adults who were followed longitudinally for an average of 4.3 years. Changes in global cognition and 4 specific neuropsychological domains (episodic memory, semantic memory, spatial abilities, and executive function) were examined as outcomes. Separate random effects models tested the effect of ID on longitudinal change in outcomes, adjusted for age and education. Results. Lower ID was associated with greater subsequent decline in global cognition, semantic memory, episodic memory, and spatial abilities. When analysis was restricted to only participants without dementia at the time ID was collected, results were similar. Discussion. Linguistic ability in young adulthood, as measured by ID, has been previously proposed as an index of neurocognitive development and/or cognitive reserve. The present study provides evidence that even when ID is measured in old age, it continues to be associated with subsequent cognitive decline and as such may continue to provide a marker of cognitive reserve. PMID:22357642
This article reviews some of the recent biological applications of gold nanoparticles (GNPs) which have been discovered lately by individual studies all around the world. GNPs have emerged as a promising candidates for various biological applications due to their unique physical properties (size and shape dependent), excellent biocompatibility, facile synthesis, ease of bioconjugation, etc. This review starts with a brief introduction about nanotechnology followed by an insight into the history, emergence, and enhanced properties of various gold nanostructures, which form the basis for their numerous biomedical applications. In addition, a brief overview on some of the commonly used fabrication techniques for synthesizing GNPs is also discussed. Finally, a miscellany of the latest biological applications of GNPs, such as cancer diagnostics and therapy, biological probes, drug delivery, gene delivery, vaccine preparation, brain implants, artificial skin, sterilization system, and improving electrical signaling in the heart, published in different articles in reputed journals are highlighted.
... notification and a valid government-issued photo ID (such as driver's license, passport, U.S. government or... number/state, passport number/country, or US government ID number/agency or military ID number/branch...
... notification and a valid government-issued photo ID (such as driver's license, passport, U.S. government or... license number/ state, passport number/country, or U.S. government ID number/agency or military ID number...
... Measuring Equipment (VOR/ DME), and the Lewiston-Nez Perce Instrument Landing System (ILS) Localizer... feet or more above the surface of the earth. * * * * * ANM ID E5 Lewiston, ID [Modified] Lewiston-Nez...
Dongfang Zhao (ORCID ID 0000-0002-5424-9915); Xiaopeng (Shaw) Li (ORCID ID 0000-0002-5264-3775); Yu Zhang (ORCID ID 0000-0003-1202-626X) This project includes literature review and proposing a model for EV planning and operations. We first conducted ...
In current controversies regarding Intelligent Design (ID), critics of ID often claim that naturalisitc science (i.e., science that attempts to explain natural phenomena in terms of strictly non-supernatural processes) has such a good track record that there is no need to introduce supernatural design hypotheses into our thinking. Since ID is not a new idea, we can search through the history of science and look also at ID's track record. In this talk, we focus on the ID thinking of Maupertuis and Leibniz when the former developed the Principle of Least Action and when both of them applied the principle to Snell's law of refraction. In this case, we find that ID did no harm and made no lasting contribution.
Abstract Intrinsic disorder (ID) in proteins has been extensively described for the last decade; a large‐scale classification of ID in proteins is mostly missing. Here, we provide an extensive analysis of ID in the protein universe on the UniProt database derived from sequence‐based predictions in MobiDB. Almost half the sequences contain an ID region of at least five residues. About 9% of proteins have a long ID region of over 20 residues which are more abundant in Eukaryotic organisms and most frequently cover less than 20% of the sequence. A small subset of about 67,000 (out of over 80 million) proteins is fully disordered and mostly found in Viruses. Most proteins have only one ID, with short ID evenly distributed along the sequence and long ID overrepresented in the center. The charged residue composition of Das and Pappu was used to classify ID proteins by structural propensities and corresponding functional enrichment. Swollen Coils seem to be used mainly as structural components and in biosynthesis in both Prokaryotes and Eukaryotes. In Bacteria, they are confined in the nucleoid and in Viruses provide DNA binding function. Coils & Hairpins seem to be specialized in ribosome binding and methylation activities. Globules & Tadpoles bind antigens in Eukaryotes but are involved in killing other organisms and cytolysis in Bacteria. The Undefined class is used by Bacteria to bind toxic substances and mediate transport and movement between and within organisms in Viruses. Fully disordered proteins behave similarly, but are enriched for glycine residues and extracellular structures. PMID:27636733
This study compared insulin lispro (IL) pharmacokinetics (PK) and pharmacodynamics (PD) delivered via microneedle intradermal (ID) injection with subcutaneous (SC) injection under euglycemic glucose clamp conditions. Ten healthy male volunteers were administered 10 international units (IU) of IL at 3 microneedle lengths (1.25, 1.50, or 1.75 mm) in a randomized, crossover fashion on Days 1-3 followed by a repetitive ID 1.5-mm microneedle dose (Day 4) and an SC dose (Day 5). Microneedle ID delivery resulted in more rapid absorption of IL, with decreased time to maximum insulin concentration (ID vs. SC: 36.0-46.4 vs. 64.3 min, P < 0.05) and higher fractional availability at early postinjection times. ID produced more rapid effects on glucose uptake with shorter times to maximal and early half-maximal glucose infusion rates (GIRs) (ID vs. SC: time to maximum GIR, 106-112 vs. 130 min, P < 0.05; early half-maximal GIR, 29-35 vs. 42 min), increased early GIR area under the curve (AUC), and faster offset of insulin action (shorter time to late half-maximal GIR: 271-287 vs. 309 min). Relative total insulin bioavailability (AUC to 360 min and AUC to infinite measurement) did not significantly differ between administration routes. ID PK/PD parameters showed some variation as a function of needle length. Delivery of ID IL was generally well tolerated, although transient, localized wheal formation and redness were observed at injection sites. Microneedle ID insulin lispro delivery enables more rapid onset and offset of metabolic effect than SC therapy and is safe and well tolerated; further study for insulin therapy is warranted.
Self-illuminating fluorescence imaging without autofluorescence background interference has recently aroused more research interests in molecular imaging. Currently, only a few self-illuminating probes were developed, based mainly on toxic quantum dots such as CdSe, CdTe. Herein, we report a novel design of nontoxic self-illuminating gold nanocluster (64Cu-doped AuNCs) for dual-modality positron emission tomography (PET) and near-infrared (NIR) fluorescence imaging based on Cerenkov resonance energy transfer (CRET). PET radionuclide 64Cu was introduced by a chelator-free doping method, which played dual roles as the energy donor and the PET imaging source. Meanwhile, AuNCs acted as the energy acceptor for NIR fluorescence imaging. 64Cu-doped AuNCs exhibited efficient CRET-NIR and PET imaging both in vitro and in vivo. In a U87MG glioblastoma xenograft model, 64Cu-doped AuNCs showed high tumor uptake (14.9%ID/g at 18 h) and produced satisfactory tumor self-illuminating NIR images in the absence of external excitation. This self-illuminating nanocluster with non-toxicity and good biocompatibility can be employed as a novel imaging contrast agent for biomedical applications, especially for molecular imaging. PMID:25224367
Chitin is the most abundant aminopolysaccharide polymer occurring in nature, and is the building material that gives strength to the exoskeletons of crustaceans, insects, and the cell walls of fungi. Through enzymatic or chemical deacetylation, chitin can be converted to its most well-known derivative, chitosan. The main natural sources of chitin are shrimp and crab shells, which are an abundant byproduct of the food-processing industry, that provides large quantities of this biopolymer to be used in biomedical applications. In living chitin-synthesizing organisms, the synthesis and degradation of chitin require strict enzymatic control to maintain homeostasis. Chitin synthase, the pivotal enzyme in the chitin synthesis pathway, uses UDP-N-acetylglucosamine (UDPGlcNAc), produce the chitin polymer, whereas, chitinase enzymes degrade chitin. Bacteria are considered as the major mediators of chitin degradation in nature. Chitin and chitosan, owing to their unique biochemical properties such as biocompatibility, biodegradability, non-toxicity, ability to form films, etc, have found many promising biomedical applications. Nanotechnology has also increasingly applied chitin and chitosan-based materials in its most recent achievements. Chitin and chitosan have been widely employed to fabricate polymer scaffolds. Moreover, the use of chitosan to produce designed-nanocarriers and to enable microencapsulation techniques is under increasing investigation for the delivery of drugs, biologics and vaccines. Each application is likely to require uniquely designed chitosan-based nano/micro-particles with specific dimensions and cargo-release characteristics. The ability to reproducibly manufacture chitosan nano/microparticles that can encapsulate protein cargos with high loading efficiencies remains a challenge. Chitosan can be successfully used in solution, as hydrogels and/or nano/microparticles, and (with different degrees of deacetylation) an endless array of derivatives with customized biochemical properties can be prepared. As a result, chitosan is one of the most well-studied biomaterials. The purpose of this review is to survey the biosynthesis and isolation, and summarize nanotechnology applications of chitin and chitosan ranging from tissue engineering, wound dressings, antimicrobial agents, antiaging cosmetics, and vaccine adjuvants. PMID:27819009
As socio-medical phenomena, epidemics are revealing of the cultures in which they are experienced. The HIV/AIDS epidemic in Africa exposes antecedent tensions between state and society, and, on a broader canvas, between the global north and south. As a contribution to the emerging literature on the social ramifications of HIV/AIDS, this article examines the saga of the Nigerian physician and immunologist, Dr Jeremiah Abalaka, who like other innovators in sub-Saharan Africa claims to have developed a curative HIV vaccine. Whilst articulating the social conditions that enabled Abalaka to thrive, the article explores the marked differences in the reaction to his "discovery" among state representatives, the scientific establishment, the general public, people living with HIV, and the media. Finally, the article valorizes the emergence of new actors in the African health sector, and the diversity of strategies used by ordinary people to achieve and maintain wellness.
Taanila, A; Rantakallio, P; Koiranen, M; von Wendt, L; Järvelin, M-R
2005-03-01
The aim was to study how many of the individuals with intellectual disability (ID; IQ < or = 70) in an age cohort were not receiving a disability pension by the age of 34 years and what their life situation was like in terms of employment, education and morbidity. In 2000, the Northern Finland 1966 Birth Cohort (n=12,058 live-born) included 129 individuals with ID. The outcome data on employment, education, pensions and morbidity were obtained from national registers. A total of 85.3% (n=110) of all the individuals with ID were on pension, and 66 of them had severe ID (IQ <50) and 44 had mild ID (IQ 50-70). Altogether 99 were drawing a pension because of ID, and 11 had a main diagnosis other than ID in the register of Social Insurance Institution. Nineteen individuals with mild ID were not on disability pension. The educational level of those without pension was low, and all whose occupation was known worked in low-level manual trades in the open labour market. During the past 8 years (1993-2000), their employment rate had been lower and unemployment rate correspondingly higher and unemployment periods longer than those of the reference group (IQ >85 or not measured). As to the morbidity, they had been hospitalized twice more often than those in the reference group and the mean of their hospitalization days was over fourfold. More attention should be paid to the vocational education and supported employment services of individuals with ID to help them to manage as independently as possible.
Oortveld, Merel A W; Keerthikumar, Shivakumar; Oti, Martin; Nijhof, Bonnie; Fernandes, Ana Clara; Kochinke, Korinna; Castells-Nobau, Anna; van Engelen, Eva; Ellenkamp, Thijs; Eshuis, Lilian; Galy, Anne; van Bokhoven, Hans; Habermann, Bianca; Brunner, Han G; Zweier, Christiane; Verstreken, Patrik; Huynen, Martijn A; Schenck, Annette
2013-10-01
Intellectual Disability (ID) disorders, defined by an IQ below 70, are genetically and phenotypically highly heterogeneous. Identification of common molecular pathways underlying these disorders is crucial for understanding the molecular basis of cognition and for the development of therapeutic intervention strategies. To systematically establish their functional connectivity, we used transgenic RNAi to target 270 ID gene orthologs in the Drosophila eye. Assessment of neuronal function in behavioral and electrophysiological assays and multiparametric morphological analysis identified phenotypes associated with knockdown of 180 ID gene orthologs. Most of these genotype-phenotype associations were novel. For example, we uncovered 16 genes that are required for basal neurotransmission and have not previously been implicated in this process in any system or organism. ID gene orthologs with morphological eye phenotypes, in contrast to genes without phenotypes, are relatively highly expressed in the human nervous system and are enriched for neuronal functions, suggesting that eye phenotyping can distinguish different classes of ID genes. Indeed, grouping genes by Drosophila phenotype uncovered 26 connected functional modules. Novel links between ID genes successfully predicted that MYCN, PIGV and UPF3B regulate synapse development. Drosophila phenotype groups show, in addition to ID, significant phenotypic similarity also in humans, indicating that functional modules are conserved. The combined data indicate that ID disorders, despite their extreme genetic diversity, are caused by disruption of a limited number of highly connected functional modules.
Atherosclerosis represents a serious global health problem that demands new therapeutic and prophylactic interventions. Considering that atherosclerosis has autoimmune and inflammatory components, immunotherapy is a possible focus to treat this disease. Areas covered: Based on the analysis of the current biomedical literature, this review describes the status on the development of vaccines against atherosclerosis. Several targets have been identified including sequences of apolipoprotein B100 (ApoB100), cholesteryl ester transfer protein (CETP), heat shock proteins (HSP), extracellular matrix proteins, T cell receptor β chain variable region 31 (TRBV31), the major outer membrane protein (MOMP), and the outer membrane protein 5 (Pomp5) from Chlamydia pneumoniae. Humoral and cellular immunities to these targets have been associated with therapeutic effects in murine models and humans. The evaluation of some candidates in clinical trials is ongoing. Expert commentary: New research paths based on the use of next generation vaccine production platforms are envisioned.
In all languages studied to date, distinct prosodic contours characterize different intention categories of infant-directed (ID) speech. This vocal behavior likely exists universally as a species-typical trait, but little research has examined whether listeners can accurately recognize intentions in ID speech using only vocal cues, without access to semantic information. We recorded native-English-speaking mothers producing four intention categories of utterances (prohibition, approval, comfort, and attention) as both ID and adult-directed (AD) speech, and we then presented the utterances to Shuar adults (South American hunter-horticulturalists). Shuar subjects were able to reliably distinguish ID from AD speech and were able to reliably recognize the intention categories in both types of speech, although performance was significantly better with ID speech. This is the first demonstration that adult listeners in an indigenous, nonindustrialized, and nonliterate culture can accurately infer intentions from both ID speech and AD speech in a language they do not speak.
Prevalence of iron deficiency (ID) at intensive care (ICU) admission is around 25 to 40%. Blood losses are important during ICU stay, leading to iron losses, but prevalence of ID at ICU discharge is unknown. ID has been associated with fatigue and muscular weakness, and may thus impair post-ICU rehabilitation. This study assessed ID prevalence at ICU discharge, day 28 (D28) and six months (M6) after and its relation with fatigue. We conducted this prospective, multicenter observational study at four University hospitals ICUs. Anemic (hemoglobin (Hb) less than 13 g/dL in male and less than 12 g/dL in female) critically ill adult patients hospitalized for at least five days had an iron profile taken at discharge, D28 and M6. ID was defined as ferritin less than 100 ng/L or less than 300 ng/L together with a transferrin saturation less than 20%. Fatigue was assessed by numerical scale and the Multidimensional Fatigue Inventory-20 questionnaire at D28 and M6 and muscular weakness by a hand grip test at ICU discharge. Among 107 patients (men 77%, median (IQR) age 63 (48 to 73) years) who had a complete iron profile at ICU discharge, 9 (8.4%) had ID. At ICU discharge, their hemoglobin concentration (9.5 (87.7 to 10.3) versus 10.2 (92.2 to 11.7) g/dL, P =0.09), hand grip strength (52.5 (30 to 65) versus 49.5 (15.5 to 67.7)% of normal value, P =0.61) and visual analog scale fatigue scale (57 (40 to 80) versus 60 (47.5 to 80)/100, P =0.82) were not different from non-ID patients. At D28 (n =80 patients) and M6 (n =78 patients), ID prevalence increased (to 25 and 35% respectively) while anemia prevalence decreased (from 100% to 80 and 25% respectively, P <0.0001). ID was associated with increased fatigue at D28, after adjustment for main confounding factors, including anemia (regression coefficient (95%CI), 3.19 (0.74 to 5.64), P =0.012). At M6, this association disappeared. The prevalence of ID increases from 8% at discharge to 35% six months after prolonged ICU stay (more than five days). ID was associated with increased fatigue, independently of anemia, at D28.
van der Eijk, Annemiek A; Tintu, Andrei N; Hays, John P
2017-01-01
Infectious disease point-of-care test (ID-POCT) devices are becoming widely available, and in this respect, international quality standards and guidelines are available for consultation once ID-POCT has been implemented into medical institutions. However, specific guidelines for consultation during the initial pre-implementation decision-making process are currently lacking. Further, there exist pre-implementation issues specific to ID-POCT. Here we present pre-implementation guidelines for consultation when considering the implementation of ID-POCT in medical institutions.
A U.S. Geological Survey report detailing the analytical results and sample locality maps of stream-sediment, heavy-mineral-concentrate, and rock samples from the Little Jacks Creek, Big Jacks Creek, Duncan Creek, and Upper Deep Creek Wilderness Study Areas, Owyhee County, Idaho
As well as being highly comorbid conditions, autism spectrum disorders (ASD) and intellectual disability (ID) share a number of clinically-relevant phenomena. This raises questions about similarities and overlap in diagnosis and aetiological pathways that may exist for both conditions. To examine maternal conditions and perinatal factors for children diagnosed with an ASD, with or without ID, and children with ID of unknown cause, compared with unaffected children. The study population comprised all live singleton births in Western Australia (WA) between January 1984 and December 1999 (N = 383,153). Univariate and multivariate multinomial logistic regression models were applied using a blocked modelling approach to assess the effect of maternal conditions, sociodemographic factors, labour and delivery characteristics and neonatal outcomes. In univariate analyses mild-moderate ID was associated with pregnancy hypertension, asthma, urinary tract infection, some types of ante-partum haemorrhage, any type of preterm birth, elective C-sections, breech presentation, poor fetal growth and need for resuscitation at birth, with all factors showing an increased risk. Severe ID was positively associated with poor fetal growth and need for resuscitation, as well as any labour or delivery complication. In the multivariate analysis no maternal conditions or perinatal factors were associated with an increased risk of ASD without ID. However, pregnancy hypertension and small head circumference were associated with a reduced risk (OR = 0.64, 95% CI: 0.43, 0.94; OR = 0.58, 95% CI: 0.34, 0.96, respectively). For ASD with ID, threatened abortion before 20 weeks gestation and poor fetal growth were associated with an increased risk. Findings show that indicators of a poor intrauterine environment are associated with an elevated risk of ID, while for ASD, and particularly ASD without ID, the associations are much weaker. As such, these findings highlight the importance of accounting for the absence or presence of ID when examining ASD, if we are to improve our understanding of the causal pathways associated with these conditions.
The REAL ID Act specifies the minimum standards that must be used to produce and issue drivers license and : identification cards that are REAL ID compliant. Beginning in 2020, if a person does not possess a form of : identification that meets REA...
Syed, Sana; Addo, O Yaw; De la Cruz-Góngora, Vanessa; Ashour, Fayrouz A Sakr; Ziegler, Thomas R; Suchdev, Parminder S
2016-06-23
Anemia affects approximately 25% of school-aged children (SAC-aged 5.00-14.99 years) globally. We determined in three countries the prevalence and determinants of anemia in SAC. Data on sociodemographics, inflammation and nutrition status were obtained from the 2006 Mexican National Nutrition Survey, the 2003-6 US National Health and Nutrition Examination Surveys, and the 2010 Encuesta Nacional de Nutrición Situación Colombia. In the US, vitamin A and iron deficiency (ID) were available only for girls aged 12.00-14.99 years to which our analysis was limited. Associations were evaluated by country using multivariable logistic regression adjusting for confounders and complex survey design. The prevalence of anemia and ID were: Mexico 12% (ID 18%), n = 3660; US 4% (ID 10%), n = 733; and Colombia 4% (ID 9%), n = 8573. The percentage of anemia associated with ID was 22.4% in Mexico, 38.9% in the US and 16.7% in Colombia. In Mexico, anemia was associated with ID (adjusted OR: 1.5, p = 0.02) and overweight (aOR 0.4, p = 0.007). In the US, anemia was associated with black race/ethnicity (aOR: 14.1, p < 0.0001) and ID (aOR: 8.0, p < 0.0001). In Colombia, anemia was associated with black race/ethnicity (aOR: 1.6, p = 0.005), lowest socio-economic status quintile (aOR: 1.8, p = 0.0005), ID (aOR: 2.7, p < 0.0001), and being stunted (aOR: 1.6, p = 0.02). While anemia was uniformly associated with iron deficiency in Mexico, Columbia, and the United States, other measured factors showed inconsistent associations with anemia. Additional data on anemia determinants in SAC are needed to guide interventions.
Syed, Sana; Addo, O. Yaw; De la Cruz-Góngora, Vanessa; Ashour, Fayrouz A. Sakr; Ziegler, Thomas R.; Suchdev, Parminder S.
2016-01-01
Anemia affects approximately 25% of school-aged children (SAC—aged 5.00–14.99 years) globally. We determined in three countries the prevalence and determinants of anemia in SAC. Data on sociodemographics, inflammation and nutrition status were obtained from the 2006 Mexican National Nutrition Survey, the 2003-6 US National Health and Nutrition Examination Surveys, and the 2010 Encuesta Nacional de Nutrición Situación Colombia. In the US, vitamin A and iron deficiency (ID) were available only for girls aged 12.00–14.99 years to which our analysis was limited. Associations were evaluated by country using multivariable logistic regression adjusting for confounders and complex survey design. The prevalence of anemia and ID were: Mexico 12% (ID 18%), n = 3660; US 4% (ID 10%), n = 733; and Colombia 4% (ID 9%), n = 8573. The percentage of anemia associated with ID was 22.4% in Mexico, 38.9% in the US and 16.7% in Colombia. In Mexico, anemia was associated with ID (adjusted OR: 1.5, p = 0.02) and overweight (aOR 0.4, p = 0.007). In the US, anemia was associated with black race/ethnicity (aOR: 14.1, p < 0.0001) and ID (aOR: 8.0, p < 0.0001). In Colombia, anemia was associated with black race/ethnicity (aOR: 1.6, p = 0.005), lowest socio-economic status quintile (aOR: 1.8, p = 0.0005), ID (aOR: 2.7, p < 0.0001), and being stunted (aOR: 1.6, p = 0.02). While anemia was uniformly associated with iron deficiency in Mexico, Columbia, and the United States, other measured factors showed inconsistent associations with anemia. Additional data on anemia determinants in SAC are needed to guide interventions. PMID:27347992
Background As well as being highly comorbid conditions, autism spectrum disorders (ASD) and intellectual disability (ID) share a number of clinically-relevant phenomena. This raises questions about similarities and overlap in diagnosis and aetiological pathways that may exist for both conditions. Aims To examine maternal conditions and perinatal factors for children diagnosed with an ASD, with or without ID, and children with ID of unknown cause, compared with unaffected children. Methods The study population comprised all live singleton births in Western Australia (WA) between January 1984 and December 1999 (N = 383,153). Univariate and multivariate multinomial logistic regression models were applied using a blocked modelling approach to assess the effect of maternal conditions, sociodemographic factors, labour and delivery characteristics and neonatal outcomes. Results In univariate analyses mild-moderate ID was associated with pregnancy hypertension, asthma, urinary tract infection, some types of ante-partum haemorrhage, any type of preterm birth, elective C-sections, breech presentation, poor fetal growth and need for resuscitation at birth, with all factors showing an increased risk. Severe ID was positively associated with poor fetal growth and need for resuscitation, as well as any labour or delivery complication. In the multivariate analysis no maternal conditions or perinatal factors were associated with an increased risk of ASD without ID. However, pregnancy hypertension and small head circumference were associated with a reduced risk (OR = 0.64, 95% CI: 0.43, 0.94; OR = 0.58, 95% CI: 0.34, 0.96, respectively). For ASD with ID, threatened abortion before 20 weeks gestation and poor fetal growth were associated with an increased risk. Conclusion Findings show that indicators of a poor intrauterine environment are associated with an elevated risk of ID, while for ASD, and particularly ASD without ID, the associations are much weaker. As such, these findings highlight the importance of accounting for the absence or presence of ID when examining ASD, if we are to improve our understanding of the causal pathways associated with these conditions. PMID:23308096
Wafer identifications (wafer ID) can be used to identify wafers from each other so that wafer processing can be traced easily. Wafer ID recognition is one of the problems of optical character recognition. The process to recognize wafer IDs is similar to that used in recognizing car license-plate characters. However, due to some unique characteristics, such as the irregular space between two characters and the unsuccessive strokes of wafer ID, it will not get a good result to recognize wafer ID by directly utilizing the approaches used in car license-plate character recognition. Wafer ID scratches are engraved by a laser scribe almost along the following four fixed directions: horizontal, vertical, plus 45 degrees , and minus 45 degrees orientations. The closer to the center line of a wafer ID scratch, the higher the gray level will be. These and other characteristics increase the difficulty to recognize the wafer ID. In this paper a wafer ID recognition scheme based on an asterisk-shape filter and a high-low score comparison method is proposed to cope with the serious influence of uneven luminance and make recognition more efficiently. Our proposed approach consists of some processing stages. Especially in the final recognition stage, a template-matching method combined with stroke analysis is used as a recognizing scheme. This is because wafer IDs are composed of Semiconductor Equipment and Materials International (SEMI) standard Arabic numbers and English alphabets, and thus the template ID images are easy to obtain. Furthermore, compared with the approach that requires prior training, such as a support vector machine, which often needs a large amount of training image samples, no prior training is required for our approach. The testing results show that our proposed scheme can efficiently and correctly segment out and recognize the wafer ID with high performance.
ID (BOI) Fort Lauderdale Executive, FL (FXE) Idaho Falls Fanning Field, ID (IDA) Fort Myers Page Field, FL (FMY) Lewiston , ID (LWS) Fort Myers...Pacoima/Whitman, California (WHP) 3. Lakeland, Florida (LAL) 4. Valdosta Municipal, Georgia (VLD) 5. Halley, Idaho (SUN) 6. Marion Williamson County
Davis, J P; Schell, W L; Amundson, T E; Godsey, M S; Spielman, A; Burgdorfer, W; Barbour, A G; LaVenture, M; Kaslow, R A
1984-01-01
In 1980-82, 80 individuals (71 Wisconsin residents) had confirmed Lyme disease (LD-c) reported; 39 additional patients had probable or possible LD. All cases of LD-c occurred during May-November; 73 percent occurred during June-July; 54 (68 percent) occurred in males. The mean age was 38.7 years (range, 7-77 years). Among LD-c patients, likely exposure to the presumed vector Ixodes dammini (ID) occurred in 22 different Wisconsin counties. Antibodies to the ID spirochete that causes LD occurred in 33 of 49 LD-c cases versus 0 of 18 in ill controls (p less than .001) and in 13 of 26 LD-c cases treated with penicillin or tetracycline versus 16 of 19 LD-c cases not treated. Early antibiotic therapy appears to blunt the antibody response to the ID spirochete. Regional tick surveys conducted in Wisconsin during each November in 1979-82 have demonstrated regions of greater density of ID. Utilizing comparable tick collection in these surveys, increases were noted in the percentage of deer with ID from 24 percent (31/128) in 1979 to 38 percent (58/152) in 1981, in the standardized mean value of ID/deer from 1.0 in 1979 to 2.2 in 1981, in the percentage of ID of the total ticks collected from 13 percent in 1979 to 71 percent in 1981, or in the ratio of ID to Dermacentor albipictus ticks from 0.14 in 1979 to 2.44 in 1981. However, a reduction in the density of ID/deer was noted generally throughout Wisconsin in 1982 when compared to 1981. LD is widespread in Wisconsin, with ecologic and clinical features similar to those occurring along the eastern seaboard.
Brown, Alyse C.; Chouinard, Philippe A.; Crewther, Sheila G.
2017-01-01
Sensory, in particular visual processing is recognized as often perturbed in individuals with Autism Spectrum Disorder (ASD). However, in terms of the literature pertaining to visual processing, individuals in the normal intelligence range (IQ = 90–110) and above, are more frequently represented in study samples than individuals who score below normal in the borderline intellectual disability (ID) (IQ = 71–85) to ID (IQ < 70) ranges. This raises concerns as to whether or not current research is generalizable to a disorder that is often co-morbid with ID. Thus, the aim of this review is to better understand to what extent the current ASD visual processing literature is representative of the entire ASD population as either diagnosed or recognized under DSM-5. Our recalculation of ASD prevalence figures, using the criteria of DSM-5, indicates approximately 40% of the ASD population are likely to be ID although searching of the visual processing literature in ASD up to July 2016 showed that only 20% of papers included the ASD with-ID population. In the published literature, the mean IQ sampled was found to be 104, with about 80% of studies sampling from the 96–115 of the IQ range, highlighting the marked under-representation of the ID and borderline ID sections of the ASD population. We conclude that current understanding of visual processing and perception in ASD is not based on the mean IQ profile of the DSM-5 defined ASD population that now appears to lie within the borderline ID to ID range. Give the importance of the role of vision for the social and cognitive processing in ASD, we recommend accurately representing ASD via greater inclusion of individuals with IQ below 80, in future ASD research. PMID:28261072
The aim of this study was to assess the infectious diseases (ID) wards of tertiary hospitals in France and Turkey for technical capacity, infection control, characteristics of patients, infections, infecting organisms, and therapeutic approaches. This cross-sectional study was carried out on a single day on one of the weekdays of June 17-21, 2013. Overall, 36 ID departments from Turkey (n = 21) and France (n = 15) were involved. On the study day, 273 patients were hospitalized in Turkish and 324 patients were followed in French ID departments. The numbers of patients and beds in the hospitals, and presence of an intensive care unit (ICU) room in the ID ward was not different in both France and Turkey. Bed occupancy in the ID ward, single rooms, and negative pressure rooms were significantly higher in France. The presence of a laboratory inside the ID ward was more common in Turkish ID wards. The configuration of infection control committees, and their qualifications and surveillance types were quite similar in both countries. Although differences existed based on epidemiology, the distribution of infections were uniform on both sides. In Turkey, anti-Gram-positive agents, carbapenems, and tigecycline, and in France, cephalosporins, penicillins, aminoglycosides, and metronidazole were more frequently preferred. Enteric Gram-negatives and hepatitis B and C were more frequent in Turkey, while human immunodeficiency virus (HIV) and streptococci were more common in France (p < 0.05 for all significances). Various differences and similarities existed in France and Turkey in the ID wards. However, the current scene is that ID are managed with high standards in both countries.
In the last fifteen years a controversial new theory of the origins of biological complexity and the nature of the universe has been fomenting bitter debates in education and science policy across North America, Europe, and Australia. Backed by intellectuals at respectable universities, Intelligent Design theory (ID) proposes an alternative to accepted accounts of evolutionary theory: that life is so complex, and that the universe is so fine-tuned for the appearance of life, that the only plausible explanation is the existence of an intelligent designer. For many ID theorists, the designer is taken to be the god of Christianity. Niall Shanks has written the first accessible introduction to, and critique of, this controversial new intellectual movement. Shanks locates the growth of ID in the last two decades of the twentieth century in the growing influence of the American religious right. But as he shows, its roots go back beyond Aquinas to Ancient Greece. After looking at the historical roots of ID, Shanks takes a hard look at its intellectual underpinnings, discussing modern understandings of thermodynamics, and how self-organizing processes lead to complex physical, chemical, and biological systems. He considers cosmological arguments for ID rooted in so-called "anthropic coincidences" and also tackles new biochemical arguments for ID based on "irreducible biological complexity." Throughout he shows how arguments for ID lack cohesion, rest on errors and unfounded suppositions, and generally are grossly inferior to evolutionary explanations. While ID has been proposed as a scientific alternative to evolutionary biology, Shanks argues that ID is in fact "old creationist wine in new designer label bottles" and moreover is a serious threat to the scientific and democratic values that are our cultural and intellectual inheritance from the Enlightenment.
Holman, Robert C.; Seeman, Sara M.; Rarig, Alice J.; McEwen, Mary; Steiner, Claudia A.; Bartholomew, Michael L.; Hennessy, Thomas W.
2016-01-01
Objective: Reports about infectious disease (ID) hospitalization rates among American Indian/Alaska Native (AI/AN) persons have been constrained by data limited to the tribal health care system and by comparisons with the general US population. We used a merged state database to determine ID hospitalization rates in Alaska. Methods: We combined 2010 and 2011 hospital discharge data from the Indian Health Service and the Alaska State Inpatient Database. We used the merged data set to calculate average annual age-adjusted and age-specific ID hospitalization rates for AI/AN and non-AI/AN persons in Alaska. We stratified the ID hospitalization rates by sex, age, and ID diagnosis. Results: ID diagnoses accounted for 19% (6501 of 34 160) of AI/AN hospitalizations, compared with 12% (7397 of 62 059) of non-AI/AN hospitalizations. The average annual age-adjusted hospitalization rate was >3 times higher for AI/AN persons (2697 per 100 000 population) than for non-AI/AN persons (730 per 100 000 population; rate ratio = 3.7, P < .001). Lower respiratory tract infection (LRTI), which occurred in 38% (2486 of 6501) of AI/AN persons, was the most common reason for ID hospitalization. AI/AN persons were significantly more likely than non-AI/AN persons to be hospitalized for LRTI (rate ratio = 5.2, P < .001). Conclusions: A substantial disparity in ID hospitalization rates exists between AI/AN and non-AI/AN persons, and the most common reason for ID hospitalization among AI/AN persons was LRTI. Public health programs and policies that address the risk factors for LRTI are likely to benefit AI/AN persons. PMID:28005485
McVey, Elaine; Keith, Steven; Herr, Joshua K.; Sutter, Diane; Pettis, Ronald J.
2015-01-01
Background: This study sought to assess the function and delivery reliability of intradermal (ID) infusion sets used with commercial insulin pumps. Method: Healthy subjects (n = 43) were randomized to either ID or subcutaneous (SC) arms, and received basal/bolus placebo delivery for 24 hours. Subjects received 4 of 8 infusion set combinations (ID: microneedle design A or B, with 2 pump brands [Animas or MiniMed]; SC: Teflon Quickset or steel Rapid-D, Animas pump only, with or without overtaping) and were evaluated for pump occlusion alarms, fluid leakage, pain, and tissue tolerability. A novel algorithm was developed to determine flow consistency based on fluid pressure, and the duration and occurrence rate for periods of unalarmed but interrupted flow (“silent occlusions’”) were compared. Results: ID delivery was successfully maintained over the 24-hour infusion period. The number of silent occlusions was lower for ID microneedle cannula design B than A (P < .01) and lower for Rapid-D SC device compared to Quick-set (P = .03). There was no significant difference in the number of occlusion alarms between the ID and SC devices with the Animas pump. However, the pumps tested with ID devices had significantly different alarm rates (MiniMed 29.5%, Animas 0%, P < .001). Leakage and tissue tolerability were comparable across devices. Conclusion: The ID infusion set reliably delivered diluent for an extended 24-hour period in healthy subjects and was well tolerated. Silent occlusion flow interruptions could be detected in both ID and SC infusion sets using a proprietary algorithm. This algorithm is a promising method for quantitatively evaluating infusion set flow performance. PMID:26319228
An automatic ID identification system for gas cylinders' online production was developed based on the production conditions and requirements of the Technical Committee for Standardization of Gas Cylinders. A cylinder ID image acquisition system was designed to improve the image contrast of ID regions on gas cylinders against the background. Then the ID digits region was located by the CNN template matching algorithm. Following that, an adaptive threshold method based on the analysis of local average grey value and standard deviation was proposed to overcome defects of non-uniform background in the segmentation results. To improve the single digit identification accuracy, two BP neural networks were trained respectively for the identification of all digits and the easily confusable digits. If the single digit was classified as one of confusable digits by the former BP neural network, it was further tested by the later one, and the later result was taken as the final identification result of this single digit. At last, the majority voting was adopted to decide the final identification result for the 6-digit cylinder ID. The developed system was installed on a production line of a liquefied-petroleum-gas cylinder plant and worked in parallel with the existing weighing step on the line. Through the field test, the correct identification rate for single ID digit was 94.73%, and none of the tested 2000 cylinder ID was misclassified through the majority voting.
Oortveld, Merel A. W.; Keerthikumar, Shivakumar; Oti, Martin; Nijhof, Bonnie; Fernandes, Ana Clara; Kochinke, Korinna; Castells-Nobau, Anna; van Engelen, Eva; Ellenkamp, Thijs; Eshuis, Lilian; Galy, Anne; van Bokhoven, Hans; Habermann, Bianca; Brunner, Han G.; Zweier, Christiane; Verstreken, Patrik; Huynen, Martijn A.; Schenck, Annette
2013-01-01
Intellectual Disability (ID) disorders, defined by an IQ below 70, are genetically and phenotypically highly heterogeneous. Identification of common molecular pathways underlying these disorders is crucial for understanding the molecular basis of cognition and for the development of therapeutic intervention strategies. To systematically establish their functional connectivity, we used transgenic RNAi to target 270 ID gene orthologs in the Drosophila eye. Assessment of neuronal function in behavioral and electrophysiological assays and multiparametric morphological analysis identified phenotypes associated with knockdown of 180 ID gene orthologs. Most of these genotype-phenotype associations were novel. For example, we uncovered 16 genes that are required for basal neurotransmission and have not previously been implicated in this process in any system or organism. ID gene orthologs with morphological eye phenotypes, in contrast to genes without phenotypes, are relatively highly expressed in the human nervous system and are enriched for neuronal functions, suggesting that eye phenotyping can distinguish different classes of ID genes. Indeed, grouping genes by Drosophila phenotype uncovered 26 connected functional modules. Novel links between ID genes successfully predicted that MYCN, PIGV and UPF3B regulate synapse development. Drosophila phenotype groups show, in addition to ID, significant phenotypic similarity also in humans, indicating that functional modules are conserved. The combined data indicate that ID disorders, despite their extreme genetic diversity, are caused by disruption of a limited number of highly connected functional modules. PMID:24204314
People with intellectual disability (ID) are living longer than ever before, raising concerns about old-age associated disorders. Dementia is among the most serious of these disorders, and theories relating cognitive reserve to risk predict that older adults with ID should be particularly vulnerable. Previous estimates of relative risk for dementia associated with ID have been inconsistent, and the present analyses examined the possible influence of variation in diagnostic criteria on findings. As expected, relaxation in the stringency of case definition for adults with ID increased relative risk, underscoring the importance of developing valid criteria for defining mild cognitive impairment, early dementia, and distinguishing between the two in adults with ID. Once available, these standards will contribute to more effective evidence-based planning. PMID:24273589
After a quarter century of discoveries that rattled the foundations of classical mechanics and electrodynamics, the year 1926 saw the publication of two works intended to provide a theoretical structure to support new quantum explanations of the subatomic world. Heisenberg's matrix mechanics and Schrödinger's wave mechanics provided compatible but mathematically disparate ways of unifying the discoveries of Planck, Einstein, Bohr and many others. Efforts began immediately to prove the equivalence of these two structures, culminated successfully by John von Neumann's 1932 volume Mathematical Foundations of Quantum Mechanics. This forms the springboard for the current effort. We begin with a presentation of a minimal set of von Neumann postulates while introducing language and notation to facilitate subsequent discussion of quantum calculations based in finite dimensional Hilbert spaces. 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The impact of immunosuppression despite virological suppression (immuno-virological discordance, ID) on the risk of developing fatal and non-fatal AIDS/non-AIDS events is unclear and remains to be elucidated. Patients in EuroSIDA starting at least 1 new antiretroviral drug with CD4<350 cells/µl and viral load (VL)>500 copies/mL were followed-up from the first day of VL< = 50 copies/ml until a new fatal/non-fatal non-AIDS/AIDS event. Considered non-AIDS events included non-AIDS malignancies, pancreatitis, severe liver disease with hepatic encephalopathy (>grade 3), cardio- and cerebrovascular events, and end-stage renal disease. Patients were classified over time according to whether current CD4 count was above (non-ID) or below (ID) baseline level. Relative rates (RR) of events were calculated for ID vs. non-ID using adjusted Poisson regression models. 2,913 patients contributed 11,491 person-years for the analysis of non-AIDS. 241 pre-specified non-AIDS events (including 84 deaths) and 89 AIDS events (including 10 deaths) occurred. The RR of developing pre-specified non-AIDS events for ID vs. non-ID was 1.96 (95% CI 1.37-2.81, p<0.001) in unadjusted analysis and 1.43 (0.94-2.17, p = 0.095) after controlling for current CD4 count. ID was not associated with the risk of AIDS events (aRR 0.76, 95% CI 0.41-1.38, p = 0.361). Compared to CD4 responders, patients with immuno-virological discordance may be at increased risk of developing non-AIDS events. Further studies are warranted to establish whether in patients with ID, strategies to directly modify CD4 count response may be needed besides the use of ART.
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The article highlights the career of Professor Mansour Ali Haseeb (1910 - 1973; DKSM, Dip Bact, FRCPath, FRCP [Lond]), a pioneer worker in health, medical services, biomedical research and medical education in the Sudan. After his graduation from the Kitchener School of Medicine (renamed, Faculty of Medicine, University of Khartoum [U of K]) in 1934, he devoted his life for the development of laboratory medicine. He became the first Sudanese Director of Stack Medical Research Laboratories (1952 - 1962). He made valuable contributions by his services in the vaccine production and implementation programs, most notably in combating small pox, rabies and epidemic meningitis. In 1963 he became the first Sudanese Professor of Microbiology and Parasitology and served as the first Sudanese Dean of the Faculty of Medicine, U of K (1963-1969). He was an active loyal citizen in public life and served in various fields outside the medical profession. As Mayor of Omdurman, he was invited to visit Berlin in 1963 by Willy Brandt, Mayor of West Berlin (1957-1966) and Chancellor of the Federal Republic of Germany (1969 to 1974). Also as Mayor of Omdurman, he represented the City in welcoming Queen Elizabeth II during her visit to Sudan in February 1965. He also received State Medals from Egypt and Ethiopia. In 1973 he was appointed Chairman of the Sudan Medical Research Council, and was awarded the international Dr. Shousha Foundation Prize and Medal by the WHO for his contribution in the advancement of health, research and medical services.
Hartley, Sigan L; Esbensen, Anna J; Shalev, Rebecca; Vincent, Lori B; Mihaila, Iulia; Bussanich, Paige
2015-01-01
Background There is a paucity of research on psychosocial treatments for depression in adults with intellectual disability (ID). In this pilot study, we explored the efficacy of a group CBT treatment that involved a caregiver component in adults with mild ID with a depressive disorder. Method Sixteen adults with mild ID and a depressive disorder participated in a 10-week group CBT treatment and 8 adults with mild ID with a depressive disorder served as a treatment as usual (TAU) control group. Adults with mild ID and caregivers completed measures of depressive symptoms, behavior problems, and social skills at pre-treatment, post-treatment, and a 3-month follow-up. Adults with mild ID also completed a series of tasks to measure their understanding of the principles of cognitive therapy pre- and post-treatment. Results The CBT group demonstrated significant decreases in depressive symptoms and behavior problems from pre-treatment to post-treatment and these effects were maintained at a 3-month follow-up. The CBT group demonstrated significant improvements in their ability to infer emotions and thoughts based on various situation-thought-emotion pairings from pre-treatment to post-treatment. Conclusions Findings indicate that adults with mild ID with a depressive disorder benefitted from a group CBT treatment with a caregiver component. Moreover, adults with mild ID appeared to benefit, at least in part, from the cognitive therapy components of the treatment, in addition to the behavior therapy components. PMID:26925187
Lugtenberg, Dorien; Reijnders, Margot R F; Fenckova, Michaela; Bijlsma, Emilia K; Bernier, Raphael; van Bon, Bregje W M; Smeets, Eric; Vulto-van Silfhout, Anneke T; Bosch, Danielle; Eichler, Evan E; Mefford, Heather C; Carvill, Gemma L; Bongers, Ernie M H F; Schuurs-Hoeijmakers, Janneke Hm; Ruivenkamp, Claudia A; Santen, Gijs W E; van den Maagdenberg, Arn M J M; Peeters-Scholte, Cacha M P C D; Kuenen, Sabine; Verstreken, Patrik; Pfundt, Rolph; Yntema, Helger G; de Vries, Petra F; Veltman, Joris A; Hoischen, Alexander; Gilissen, Christian; de Vries, Bert B A; Schenck, Annette; Kleefstra, Tjitske; Vissers, Lisenka E L M
2016-08-01
Recently WAC was reported as a candidate gene for intellectual disability (ID) based on the identification of a de novo mutation in an individual with severe ID. WAC regulates transcription-coupled histone H2B ubiquitination and has previously been implicated in the 10p12p11 contiguous gene deletion syndrome. In this study, we report on 10 individuals with de novo WAC mutations which we identified through routine (diagnostic) exome sequencing and targeted resequencing of WAC in 2326 individuals with unexplained ID. All but one mutation was expected to lead to a loss-of-function of WAC. Clinical evaluation of all individuals revealed phenotypic overlap for mild ID, hypotonia, behavioral problems and distinctive facial dysmorphisms, including a square-shaped face, deep set eyes, long palpebral fissures, and a broad mouth and chin. These clinical features were also previously reported in individuals with 10p12p11 microdeletion syndrome. To investigate the role of WAC in ID, we studied the importance of the Drosophila WAC orthologue (CG8949) in habituation, a non-associative learning paradigm. Neuronal knockdown of Drosophila CG8949 resulted in impaired learning, suggesting that WAC is required in neurons for normal cognitive performance. In conclusion, we defined a clinically recognizable ID syndrome, caused by de novo loss-of-function mutations in WAC. Independent functional evidence in Drosophila further supported the role of WAC in ID. On the basis of our data WAC can be added to the list of ID genes with a role in transcription regulation through histone modification.
Wagner, Adam P; Croudace, Tim J; Bateman, Naomi; Pennington, Mark W; Prince, Elizabeth; Redley, Marcus; White, Simon R; Ring, Howard
2017-01-01
Intellectual disability (ID) is relatively common in people with epilepsy, with prevalence estimated to be around 25%. Surprisingly, given this relatively high frequency, along with higher rates of refractory epilepsy than in those without ID, little is known about outcomes of different management approaches/clinical services treating epilepsy in adults with ID-we investigate this area. We undertook a naturalistic observational cohort study measuring outcomes in n = 91 adults with ID over a 7-month period (recruited within the period March 2008 to April 2010). Participants were receiving treatment for refractory epilepsy (primarily) in one of two clinical service settings: community ID teams (CIDTs) or hospital Neurology services. The pattern of comorbidities appeared important in predicting clinical service, with Neurologists managing the epilepsy of relatively more of those with neurological comorbidities whilst CIDTs managed the epilepsy of relatively more of those with psychiatric comorbidities. Epilepsy-related outcomes, as measured by the Glasgow Epilepsy Outcome Scale 35 (GEOS-35) and the Epilepsy and Learning Disabilities Quality of Life Scale (ELDQoL) did not differ significantly between Neurology services and CIDTs. In the context of this study, the absence of evidence for differences in epilepsy-related outcomes amongst adults with ID and refractory epilepsy between mainstream neurology and specialist ID clinical services is considered. Determining the selection of the service managing the epilepsy of adults with an ID on the basis of the skill sets also required to treat associated comorbidities may hence be a reasonable heuristic.
Kemmer, Teresa M; Bovill, Maria E; Kongsomboon, Wantanee; Hansch, Steven J; Geisler, Karen L; Cheney, Carrie; Shell-Duncan, Bettina K; Drewnowski, Adam
2003-12-01
Iron-deficiency anemia (IDA) in refugees is reported to be among the major medical problems worldwide. Because food rations are typically inadequate in iron, long-term reliance is a key predictor of anemia among displaced people. Comprehensive nutritional assessments of refugee children from Burma have not previously been completed. Refugee children aged 6-59 mo were studied to determine 1) the prevalences of anemia, iron deficiency (ID) and IDA and 2) the factors associated with anemia and ID. Cluster sampling in three camps and convenience sampling in two additional camps were used. Hemoglobin (Hb) levels were measured and micro mol zinc protoporphyrin/mol heme were determined in 975 children. Logistic regression analyses (95% CI) determined predictors of anemia and ID. The prevalences of IDA, anemia and ID in these refugee children were 64.9, 72.0 and 85.4%, respectively. Predictors of anemia included young age (P < 0.001), food ration lasting <1 mo (P = 0.001), daily consumption of dietary iron inhibitors (P < 0.05), weight-for-height Z-score of <-2 (P < 0.05), male gender (P < 0.05) and uneducated father (P < 0.001). Predictors of ID were young age (P < 0.001) and recently reported illness (P < 0.05). Laboratory tests confirmed that anemia and ID are major health problems among these refugee children and that ID is the leading cause of anemia. A comprehensive nutrition and public health-focused approach to combating anemia and ID is essential. Following the presentation of results to policy makers, the improvement of the micronutrient content of rations has been initiated.
Background: The association between poverty and intellectual disability (ID) has been well documented. However, little is known about persons with ID who face circumstances of extreme poverty, such as homelessness. This paper describes the situation of persons with ID who were or are homeless in Montreal and are currently receiving services from a…
... recipient's signature on the authorization document matches the signature on the ID card. In a Photo ID area... matches the serial number on the recipient's ID card; (3) Issue a replacement in accordance with... other action, such as correcting the address on the master issuance file, warranted by the reported...
...-0531; Airspace Docket No. 13-ANM-20] Establishment of Class E Airspace; Salmon, ID AGENCY: Federal... at the Salmon VHF Omni-Directional Radio Range/Distance Measuring Equipment (VOR/DME) navigation aid, Salmon, ID, to facilitate vectoring of Instrument Flight Rules (IFR) aircraft under control of Salt Lake...
Advocates of Intelligent Design (ID) theory argue that evolution is a theory in crisis, ID is a legitimate scientific theory, and biology teachers should teach the controversy. Supporters of evolutionary theory testify that ID is a religious, not scientific, concept, and evolution is in no danger of bankruptcy, having survived 140 years of…
Research has found staff attitudes regarding the sexuality of people with intellectual disability (ID) to be negative but influenced by several factors. The current study aimed to examine whether gender of people with ID affects such attitudes. Semistructured interviews were completed with 10 staff members and analysed using thematic analysis. Results indicated 3 themes: Women are perceived as sexually innocent, men as more sexually motivated, and motivations for sexual relationships are perceived to differ between men and women with ID. The study indicates unfavourable attitudes towards sexuality in individuals with ID that correlate with traditional, restricted gender stereotypes. The identification of these themes highlights the importance of considering gender when supporting the sexuality of people with ID.
Patients with autism spectrum disorders (ASDs) and intellectual disability (ID) can be clinically complex and often have limited access to psychiatric care. Because little is known about post-graduate clinical education in ASD and ID, we surveyed training directors of child and adolescent psychiatry (CAP) fellowship programs. On average, CAP directors reported 3 and 4 hours per year, respectively, of lectures in ASD and ID. Training directors commonly reported that trainees see 1–5 patients with ASD or ID per year for outpatient pharmacological management and inpatient treatment. Forty five percent of directors endorsed needing additional resources for training in ASD and ID, which, coupled with low didactic and clinical exposure, suggests that current training is inadequate. PMID:24113341
Oesch, Sibylle; Degen, Lukas; Beglinger, Christoph
2005-10-01
The control of food intake and satiety requires a coordinated interplay. Oral protein and duodenal fat inhibit food intake and induce satiety, but their interactive potential is unclear. Our aim was therefore to investigate the interactions between an oral protein preload and intraduodenal (ID) fat on food intake and satiety feelings. Twenty healthy male volunteers were studied in a randomized, double-blind, four-period crossover design. On each study day, subjects underwent one of the following treatments: 1) water preload plus ID saline perfusion, 2) water preload plus ID fat perfusion, 3) protein preload plus ID saline perfusion, or 4) protein preload plus ID fat perfusion. Subjects were free to eat and drink as much as they wished. An oral protein preload significantly reduced caloric intake (19%, P < 0.01). Simultaneous administration of an oral protein preload and ID fat did not result in a positive synergistic effect with respect to caloric consumption, rejecting the initial hypothesis that the two nutrients exert a positive synergistic effect on food intake. An oral protein preload but not ID fat altered the feelings of hunger and fullness. These data indicate that the satiety effect of an oral protein preload is not amplified by ID fat; indeed, the effect of a protein preload does not seem to be mediated by cholecystokinin, glucagon-like peptide-1, or peptide YY. Much more information is necessary to understand the basic physiological mechanisms that control food intake and satiety.
The present invention provides an isolated polynucleotide encoding a c-Jun peptide consisting of about amino acid residues 33 to 79 as set fort in SEQ ID NO: 10 or conservative variations thereof. The invention also provides a method for producing a peptide of SEQ ID NO:1 comprising (a) culturing a host cell containing a polynucleotide encoding a c-Jun peptide consisting of about amino acid residues 33 to 79 as set forth in SEQ ID NO: 10 under conditions which allow expression of the polynucleotide; and (b) obtaining the peptide of SEQ ID NO:1.
Essack, Zaynab; Koen, Jennifer; Slack, Catherine; Lindegger, Graham; Newman, Peter A
2012-01-01
Community engagement is crucial to ongoing development and testing of sorely needed new biomedical HIV prevention technologies. Yet, negative trial results raise significant challenges for community engagement in HIV prevention trials, including the early termination of the Cellulose Sulfate microbicide trial and two Phase IIb HIV vaccine trials (STEP and Phambili). The present study aimed to explore the perspectives and experiences of civil society organization (CSO) representatives regarding negative HIV prevention trial results and perceived implications for future trials. We conducted in-depth interviews with 14 respondents from a broad range of South African and international CSOs, and analyzed data using thematic analysis. CSO representatives reported disappointment in response to negative trial results, but acknowledged such outcomes as inherent to clinical research. Respondents indicated that in theory negative trial results seem likely to impact on willingness to participate in future trials, but that in practice people in South Africa have continued to volunteer. Negative trial results were described as having contributed to improving ethical standards, and to a re-evaluation of the scientific agenda. Such negative results were identified as potentially impacting on funding for trials and engagement activities. Our findings indicate that trial closures may be used constructively to support opportunities for reflection and renewed vigilance in strategies for stakeholder engagement, communicating trial outcomes, and building research literacy among communities; however, these strategies require sustained resources for community engagement and capacity-building.
... ``as the `Pharmacy.''' Id. The Pharmacy had a ``teller like window where the prescription drug products... inventory.'' Id. She then stated that ``no prior inventories or logs were made available to'' her. Id... dispensing log. The Government also alleges that ``Respondent failed to store [the] controlled substances in...
..., to request (1) a digital ID certificate, which allows the participant (or its counsel or... NRC- issued digital ID certificate). Based upon this information, the Secretary will establish an... electronic docket. Information about applying for a digital ID certificate is available on NRC's public Web...
Nodin, N; Carballo-Diéguez, A; Ventuneac, A M; Balan, I C; Remien, R
2008-01-01
Condom use is the best available strategy to prevent HIV infection during sexual intercourse. However, since many people choose not to use condoms in circumstances in which HIV risk exists, alternatives to condom use for HIV prevention are needed. Currently there are several alternative bio-medical HIV-prevention products in different stages of development: microbicides, vaccines, post-exposure prophylaxis (PEP) and pre-exposure prophylaxis (PrEP). Seventy-two men who have sex with men (MSM) who took part in a study on Internet use and intentional condomless anal intercourse were asked about these four products during a semi-structured interview. The questions explored knowledge and acceptability of all the products and willingness to participate in microbicide and vaccine trials. Qualitative analysis of the data suggests that these men had virtually no knowledge of PrEP, very limited knowledge of microbicides, some information about PEP and considerably more knowledge about vaccines. Reactions towards the products were generally positive except for PrEP, for which reactions were polarized as either enthusiastic or negative. With the exception of PrEP, many men expressed willingness to use the products in the future. Most men would be willing to participate in trials for microbicides and vaccines if given basic reassurances. Concerns over negative side effects and preoccupation with possible infection were some of the motives given for non-willingness to participate in a vaccine trial. These results should inform the development of future trials of biomedical prevention products.
We have had recent reminders of the threats posed by naturally occurring and bioengineered pandemic respiratory infections. It is estimated that if a pandemic infection were to arise anywhere in the world, such an infection would become widespread within 3 months and would have its maximum effect within 6 months. At present, the fastest that a vaccine effective against a new combination of antigens can be developed, purified, and produced is 9–12 months, not counting time for mass production. The current rate at which the production of influenza vaccines can be accelerated is limited by the fact that production is carried out in eggs. Therefore, there is urgent need for cell-based vaccine technologies. These are under way in several centers, yet attainment of a safe product remains several years away. Furthermore, there is need for public and private investment in manufacturing surge capacity and/or dedicated National Institutes of Health facilities to enable accelerated production. We must support efforts to shorten development time by developing and approving subunit antigens and immunogens that anticipate the most virulent viral mutations. Surveillance sites and their electronic interconnections must be expanded. Another component still lacking is funding for laboratories with high throughput screening and strong informatics capabilities to enable the fingerprinting and cataloguing of all known specimens of influenza and other pathogenic organisms for rapid identification of emerging or bioengineered pathogens. In all these efforts, we look to the federal government and to the biomedical research community in both public and private sectors. PMID:15061626
Biomedical ontologies are representations of classes of entities in the biomedical domain and how these classes are related in computer- and human-interpretable formats. Ontologies support data standardization and exchange and provide a basis for computer-assisted automated reasoning. IDOBRU is an ontology in the domain of Brucella and brucellosis. Brucella is a Gram-negative intracellular bacterium that causes brucellosis, the most common zoonotic disease in the world. In this study, IDOBRU is used as a platform to model and analyze how the hosts, especially host macrophages, interact with virulent Brucella strains or live attenuated Brucella vaccine strains. Such a study allows us to better integrate and understand intricate Brucella pathogenesis and host immunity mechanisms. Different levels of host-Brucella interactions based on different host cell types and Brucella strains were first defined ontologically. Three important processes of virulent Brucella interacting with host macrophages were represented: Brucella entry into macrophage, intracellular trafficking, and intracellular replication. Two Brucella pathogenesis mechanisms were ontologically represented: Brucella Type IV secretion system that supports intracellular trafficking and replication, and Brucella erythritol metabolism that participates in Brucella intracellular survival and pathogenesis. The host cell death pathway is critical to the outcome of host-Brucella interactions. For better survival and replication, virulent Brucella prevents macrophage cell death. However, live attenuated B. abortus vaccine strain RB51 induces caspase-2-mediated proinflammatory cell death. Brucella-associated cell death processes are represented in IDOBRU. The gene and protein information of 432 manually annotated Brucella virulence factors were represented using the Ontology of Genes and Genomes (OGG) and Protein Ontology (PRO), respectively. Seven inference rules were defined to capture the knowledge of host-Brucella interactions and implemented in IDOBRU. Current IDOBRU includes 3611 ontology terms. SPARQL queries identified many results that are critical to the host-Brucella interactions. For example, out of 269 protein virulence factors related to macrophage-Brucella interactions, 81 are critical to Brucella intracellular replication inside macrophages. A SPARQL query also identified 11 biological processes important for Brucella virulence. To systematically represent and analyze fundamental host-pathogen interaction mechanisms, we provided for the first time comprehensive ontological modeling of host-pathogen interactions using Brucella as the pathogen model. The methods and ontology representations used in our study are generic and can be broadened to study the interactions between hosts and other pathogens.
Voronin, Yegor; Myrzahmetov, Askar; Bernstein, Alan
2011-01-01
Scientific publishing is undergoing significant changes due to the growth of online publications, increases in the number of open access journals, and policies of funders and universities requiring authors to ensure that their publications become publicly accessible. Most studies of the impact of these changes have focused on the growth of articles available through open access or the number of open-access journals. Here, we investigated access to publications at a number of institutes and universities around the world, focusing on publications in HIV vaccine research--an area of biomedical research with special importance to the developing world. We selected research papers in HIV vaccine research field, creating: 1) a first set of 50 most recently published papers with keywords "HIV vaccine" and 2) a second set of 200 articles randomly selected from those cited in the first set. Access to the majority (80%) of the recently published articles required subscription, while cited literature was much more accessible (67% freely available online). Subscriptions at a number of institutions around the world were assessed for providing access to subscription-only articles from the two sets. The access levels varied widely, ranging among institutions from 20% to 90%. Through the WHO-supported HINARI program, institutes in low-income countries had access comparable to that of institutes in the North. Finally, we examined the response rates for reprint requests sent to corresponding authors, a method commonly used before internet access became widespread. Contacting corresponding authors with requests for electronic copies of articles by email resulted in a 55-60% success rate, although in some cases it took up to 1.5 months to get a response. While research articles are increasingly available on the internet in open access format, institutional subscriptions continue to play an important role. However, subscriptions do not provide access to the full range of HIV vaccine research literature. Access to papers through subscriptions is complemented by a variety of other means, including emailing corresponding authors, joint affiliations, use of someone else's login information and posting requests on message boards. This complex picture makes it difficult to assess the real ability of scientists to access literature, but the observed differences in access levels between institutions suggest an unlevel playing field, in which some researchers have to spend more efforts than others to obtain the same information.
The 2010 earthquake resulted in the breakdown of Haiti's social, economic and health infrastructure. Over one-quarter of a million people remain internally displaced (ID). ID women experience heightened vulnerability to intimate partner violence (IPV) due to increased poverty and reduced community networks. Scant research has examined experiences of IPV among ID women in post-earthquake Haiti. We conducted a qualitative study to explore the impact of participating in Famn an Aksyon Pou Santé Yo (FASY), a small-group HIV prevention intervention, on ID women's agency in Leogane, Haiti. We conducted four focus groups with ID women, FASY participants (n = 40) and in-depth individual interviews with peer health workers (n = 7). Our study was guided by critical ethnography and paid particular attention to power relations. Findings highlighted multiple forms of IPV (e.g., physical, sexual). Participants discussed processes of intrapersonal (confidence), interpersonal (communication), relational (support) and collective (women's rights) agency. Yet structural factors, including patriarchal gender norms and poverty, silenced IPV discussions and constrained women's agency. Findings suggest that agency among ID women is a multi-level, non-linear and incremental process. To effectively address IPV among ID women in Haiti, interventions should address structural contexts of gender inequity and poverty and concurrently facilitate multi-level processes of agency.
Santesso, Diane L; Schmidt, Louis A; Trainor, Laurel J
2007-10-01
Many studies have shown that infants prefer infant-directed (ID) speech to adult-directed (AD) speech. ID speech functions to aid language learning, obtain and/or maintain an infant's attention, and create emotional communication between the infant and caregiver. We examined psychophysiological responses to ID speech that varied in affective content (i.e., love/comfort, surprise, fear) in a group of typically developing 9-month-old infants. Regional EEG and heart rate were collected continuously during stimulus presentation. We found the pattern of overall frontal EEG power was linearly related to affective intensity of the ID speech, such that EEG power was greatest in response to fear, than surprise than love/comfort; this linear pattern was specific to the frontal region. We also noted that heart rate decelerated to ID speech independent of affective content. As well, infants who were reported by their mothers as temperamentally distressed tended to exhibit greater relative right frontal EEG activity during baseline and in response to affective ID speech, consistent with previous work with visual stimuli and extending it to the auditory modality. Findings are discussed in terms of how increases in frontal EEG power in response to different affective intensity may reflect the cognitive aspects of emotional processing across sensory domains in infancy.
In addition to having prosodic characteristics that are attractive to infant listeners, infant-directed (ID) speech shares certain characteristics of adult-directed (AD) clear speech, such as increased acoustic distance between vowels, that might be expected to make ID speech easier for adults to perceive in noise than AD conversational speech. However, perceptual tests of two women's ID productions by Andruski and Bessega [J. Acoust. Soc. Am. 112, 2355] showed that is not always the case. In a word identification task that compared ID speech with AD clear and conversational speech, one speaker's ID productions were less well-identified than AD clear speech, but better identified than AD conversational speech. For the second woman, ID speech was the least accurately identified of the three speech registers. For both speakers, hard words (infrequent words with many lexical neighbors) were also at an increased disadvantage relative to easy words (frequent words with few lexical neighbors) in speech registers that were less accurately perceived. This study will compare several acoustic properties of these women's productions, including pitch and formant-frequency characteristics. Results of the acoustic analyses will be examined with the original perceptual results to suggest reasons for differences in listener's accuracy in identifying these two women's ID speech in noise.
Background: Epilepsy is a disorder that is commonly found in people with intellectual disability (ID). The prevalence of epilepsy increases with the severity of ID. The objective of this study was to determine if there is an association between intelligence quotient (IQ) and epilepsy in children with ID. Materials and Methods: A total of 262 children, aged 3-18 years, with ID were identified as part of a community-based rehabilitation project. These children were examined for epilepsy and diagnosed by a psychiatrist and physicians based on results of electroencephalogram tests. A Spearman's correlation (ρ) was used to determine if there was an association between IQ scores and the occurrence of epilepsy. X2 statistics used to examine the relationship of epilepsy with gender, socioeconomic status, population type, severity of ID, family history of mental illness, mental retardation, epilepsy, and coexisting disorder. Results: Spearman's rho –0.605 demonstrates inverse association of IQ with epilepsy. X2 demonstrates statistically significant association (P < 0.05) with gender, severity of ID, cerebral palsy, behavior problems, and family history of mental illness, mental retardation, and epilepsy. Conclusions: Lower IQ score in children with ID has association with occurrence of epilepsy. Epilepsy is also found highly associated with male gender and lower age. PMID:24347947
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Yang, Hua; Li, Tao; Hu, Xinlei; Wang, Feng; Zou, Yang
2014-01-01
In the area of computer security, Intrusion Detection (ID) is a mechanism that attempts to discover abnormal access to computers by analyzing various interactions. There is a lot of literature about ID, but this study only surveys the approaches based on Artificial Immune System (AIS). The use of AIS in ID is an appealing concept in current techniques. This paper summarizes AIS based ID methods from a new view point; moreover, a framework is proposed for the design of AIS based ID Systems (IDSs). This framework is analyzed and discussed based on three core aspects: antibody/antigen encoding, generation algorithm, and evolution mode. Then we collate the commonly used algorithms, their implementation characteristics, and the development of IDSs into this framework. Finally, some of the future challenges in this area are also highlighted.
In sickle cell anemia (SS), some red blood cells dehydrate, forming a hyperdense (HD) cell fraction (>1.114 g/mL; mean corpuscular hemoglobin concentration [MCHC], >46 g/dL) that contains many irreversibly sickled cells (ISCs), whereas other SS red blood cells dehydrate to an intermediate density (ID; 1.090 to 1.114 g/mL; MCHC, 36 to 46 g/dL). This study asks if the potassium-chloride cotransporter (K:Cl) and the calcium-dependent potassium channel [K(Ca2+)] are participants in the formation of one or both types of dense SS red blood cells. We induced sickling by exposing normal density (ND; 1.080 to 1.090 g/mL; MCHC, 32 to 36 g/dL) SS discocytes to repetitive oxygenation-deoxygenation (O-D) cycles in vitro. At physiologic Na+, K+, and Cl-, and 0.5 to 2 mmol/L Ca2+, the appearance of dense cells was time- and pH-dependent. O-D cycling at pH 7.4 in 5% CO2-equilibrated buffer generated only ID cells, whereas O-D cycling at pH 6.8 in 5% CO2-equilibrated buffer generated both ID and HD cells, the latter taking more than 8 hours to form. At 22 hours, 35% +/- 17% of the parent ND cells were recovered in the ID fraction and 18% +/- 11% in the HD fraction. Continuous deoxygenation (N2/5% CO2) at pH 6.8 generated both ID and HD cells, but many of these cells had multiple projections, clearly different from the morphology of endogenous dense cells and ISCs. Continuous oxygenation (air/5% CO2) at pH 6.8 resulted in less than 10% dense cell (ID + HD) formation. ATP depletion substantially increased HD cell formation and moderately decreased ID cell formation. HD cells formed after 22 hours of O-D cycling at pH 6.8 contained fewer F cells than did ID cells, suggesting that HD cell formation is particularly dependent on HbS polymerization. EGTA chelation of buffer Ca2+ inhibited HD but not ID cell formation, and increasing buffer Ca2+ from 0.5 to 2 mmol/L promoted HD but not ID cell formation in some SS patients. Substitution of nitrate for Cl- inhibited ID cell formation, as did inhibitors of the K:Cl cotransporter, okadaic acid, and [(dihydroindenyl) oxy]alkanoic acid (DIOA). Conversely, inhibitors of K(Ca2+), charybdotoxin and clotrimazole, inhibited HD cell formation. The combined use of K(Ca2+) and K:Cl inhibitors nearly eliminated dense cell (ID + HD cell) formation. In summary, dense cells formed by O-D cycling for 22 hours at pH 7.4 cycling are predominately the ID type, whereas dense cells formed by O-D cycling for 22 hours at pH 6.8 are both the ID and HD type, with the latter low in HbF, suggesting that HD cell formation has a greater dependency on HbS polymerization. A combination of K:Cl cotransport and the K(Ca2+) activities account for the majority of dense cells formed, and these pathways can be driven independently. We propose a model in which reversible sickling-induced K+ loss by K:Cl primarily generates ID cells and K+ loss by the K(Ca2+) channel primarily generates HD cells. These results imply that both pathways must be inhibited to completely prevent dense SS cell formation and have potential therapeutic implications.
Atypical laterality (i.e. the lack of a clear pattern of lateralization) has been found to be a characteristic feature of individuals with intellectual disability (ID). The evidence for this has been based on 'handedness' studies which have contained little information about the ability of people with ID to carry out interhemispheric tasks reflecting bilateral transfer or interference. The present study examined this capacity in individuals with ID by utilizing bilateral transfer and interference paradigms. Right-handed subjects with ID (IQ = 55-76) and controls matched for age and sex were tested for bilateral transfer of motor skill in contralateral hands with a mirror-drawing task. The subjects were also tested for their ability to perform a finger-tapping task while processing verbal and non-verbal stimuli. The findings indicated that people with ID are significantly deficient relative to matched controls in bilateral transfer of motor skills from their non-preferred (left) hand to their preferred (right) one. The effect of interference during performance of the dual task was significantly greater in individuals with ID. Subjects with ID were found to perform better with their non-preferred than with their preferred hand. A within-group comparison revealed that right-handed performance was more affected by interference than left in these subjects.
Su, C. Y.; Chen, C. C.; Wuang, Y. P.; Lin, Y. H.; Wu, Y. Y.
2008-01-01
Background: Very little is known about the neuropsychological correlates of adaptive functioning in people with intellectual disabilities (ID). This study examined whether specific cognitive deficits and demographic variables predicted everyday functioning in adults with ID. Method: People with ID (n = 101; ages 19-41 years; mean education = 11…
...-0531; Airspace Docket No. 13-ANM-20] Proposed Establishment of Class E Airspace; Salmon, ID AGENCY... action proposes to establish Class E airspace at the Salmon VHF Omni-Directional Radio Range/Distance Measuring Equipment (VOR/DME) navigation aid, Salmon, ID, to facilitate vectoring of Instrument Flight Rules...
... DEPARTMENT OF DEFENSE Office of the Secretary [Docket ID: DoD-2013-HA-0180] Proposed Collection... DoD-2008-HA-0180. The Docket ID is corrected to read as set forth in this notice. The corrected Docket ID should read DoD-2013-HA-0180. DATES: This notice is effective on August 27, 2013. FOR FURTHER...
Individuals with intellectual disability (ID) have complex mental health needs and may seek specialized ID psychiatric services. This study reports on predictors of specialized inpatient admissions for 234 individuals with ID who received outpatient services at a psychiatric hospital. Overall, from 2007-2012, 55 of the 234 outpatients were triaged…
..., to request (1) a digital ID certificate, which allows the participant (or its counsel or... NRC- issued digital ID certificate). Based upon this information, the Secretary will establish an... electronic docket. Information about applying for a digital ID certificate is available on NRC's public Web...
... methodological changes approved in Proposal Twelve. Id. at 14. These methodological changes include the use of... study and models for Return Receipt service were developed in 1976 and updated in Docket Nos. MC96-3, R2000-1, and R2001-1. Id. \\7\\ Id. at 21; Docket No. ACR2010, USPS-FY10-28, FY 2010 Special Cost Studies...
..., NY; CUMULUS LICENSING LLC, Station KRRF, Facility ID 10329, BPH-20110218ABV, From GOLETA, CA, To OAK VIEW, CA; CUMULUS LICENSING LLC, Station KRUZ, Facility ID 3159, BPH-20110218ABW, From SANTA BARBARA..., BPH-20091211AFR, From MEXIA, TX, To BELLMEAD, TX; MICHAEL GREENE, Station KOYD, Facility ID 166015...
The voice of people with intellectual disabilities (ID) is needed in the literature to best understand their unique experiences and perspectives. Researchers face challenges in conducting interviews with people with ID who are limited in conceptual and verbal language skills. It can also be difficult to obtain participants with ID because of…
Tonnsen, Bridgette L.; Boan, Andrea D.; Bradley, Catherine C.; Charlest, Jane; Cohen, Amy; Carpenter, Laura A.
2016-01-01
Autism spectrum disorders (ASD) often co-occur with intellectual disability (ID) and are associated with poorer psychosocial and family-related outcomes than ID alone. The present study examined the prevalence, stability, and characteristics of ASD estimates in 2,208 children with ASD and ID identified through the South Carolina Autism and…
Eisenman, Laura T.; Farley-Ripple, Elizabeth; Culnane, Mary; Freedman, Brian
2013-01-01
Social networks of persons with intellectual disabilities (ID) have been characterized as smaller and less diverse than those of typical peers. Advocates have focused on strengthening those social networks by expanding circles of social support, protection, and friendship. As young adults with ID experience increasing levels of community…
..., Station NEW, Facility ID 189518, BNPH- 20110629BVH, From ROTAN, TX, To ROSCOE, TX; HI-LINE RADIO...; OHANA BROADCAST COMPANY LLC, Station KSHK, Facility ID 62228, BPH- 20120822AAH, From KEKAHA, HI, To HANAMAULU, HI; OHANA BROADCAST COMPANY LLC, Station KUAI, Facility ID 1752, BP-20120822AAO, From ELEELE, HI...
Background: Children with intellectual disability (ID) are at heightened risk for behaviour problems and diagnosed mental disorder. Likewise, mothers of children with ID are more stressed than mothers of typically developing children. Research on behavioural phenotypes suggests that different syndromes of ID may be associated with distinct child…
Horovitz, Max; Matson, Johnny L.; Sipes, Megan; Shoemaker, Mary; Belva, Brian; Bamburg, Jay W.
2011-01-01
Individuals with intellectual disability (ID) have a high risk for developing comorbid psychopathology. While researchers have shown that symptoms of psychopathology remain relatively stable in children with ID over time, little research has been conducted to demonstrate symptom stability for adults with ID. Incidence of psychopathology symptoms…
Few instructional design (ID) models exist which are specific for developing educational games. Moreover, those extant ID models have not been rigorously evaluated. No ID models were found which focus on educational games with complex learning objectives. "Ten Steps to Complex Learning" (TSCL) is based on the four component instructional…
People with intellectual disability (ID) comprise 2-3% of the Australian population. They mostly rely on their GP for primary health care. In rural areas where there are issues with health workforce shortages, there is a risk that people with ID may not get timely access to primary care or may not be aware of the range of healthcare services available to support them. Internationally, research has shown that regular health assessments are beneficial for people with ID. Annual comprehensive health assessments (ACHAs) have been shown to result in increased detection of medical conditions and could assist in reducing the gap in mortality between people with ID and the broader population. In Australia, people with ID have been eligible to access ACHAs under Medicare since 2007. These provide for a regular review of the person's physical, psychological and social functioning. This study explored the extent to which rural people with ID were accessing these ACHAs, and factors which affected their access to ACHAs. In this qualitative study in-depth interviews were conducted with 18 participants including people with ID, carers/support workers and rural doctors. Interviews were then coded and analysed for themes. Seven themes were identified: (1) healthcare barriers in rural areas; (2) cohesion of rural communities; (3) the way rural doctors practice; (4) lack of knowledge/understanding; (5) venturing into new territory; (6) the role of the practice nurse; and (7) the health communication triangle. Despite the well-known problems of lack of services and distance to specialists in rural Australia, there are compensatory factors which were perceived as improving the wellbeing of people with ID, such as increased social cohesion and community connectedness. More education is needed to ensure that the rationale for ACHAs for people with ID is understood and that doctors feel confident to use them. The number of Medicare reforms implemented in a relatively short period presented change-management challenges for rural practices with rural workforce pressures. The role of the carer/support worker is crucial in the health assessment process and can improve the transfer of information about a client with ID between the disability and health sectors and within the health sector.
Davis, Sharon R; Durvasula, Seeta; Merhi, Diana; Young, Paul M; Traini, Daniela; Bosnic Anticevich, Sinthia Z
2016-02-01
Fifteen percent of Australians with intellectual disability (ID) are reported to have asthma. People with ID are at risk of poor health knowledge due to deficits in intellectual and adaptive functioning, but their medication knowledge has largely been ignored in research to date. To explore the level of understanding of asthma medication use of people with ID who self-administer their inhaled medications, in order to inform future educational support. Setting The research was conducted in NSW, Australia, at the participants' homes, the point of health care access, or the offices of relevant support organisations. In this qualitative study face-to-face interviews were conducted with people with ID using a semi-structured interview guide. The interviews were recorded, transcribed and thematically analysed. Main outcome Identification of barriers to asthma medication self-management by people with ID. Seventeen people with ID who self-administer their asthma medications were interviewed. Factors influencing their asthma medication knowledge and use included understanding of their illness and the need for medication; aspects of self-management and autonomy versus dependence. This sample of people with ID had a good understanding of the importance of using their inhaled asthma medications, as well as asthma triggers, and the difference between use of preventer and reliever medications. Both enablers and barriers to asthma medication self-management were identified in the domains of managing attacks, adherence, knowledge of side effects and sources of information on correct use of inhalers. The level of autonomy for medication use varied, with motivation to self-manage asthma influenced by the level of support that was practically available to individual participants. This research investigated aspects of asthma medication self-management of people with ID. Based on the barriers identified, pharmacists should promote use of spacers and written asthma action plans as well as counsel people with ID about how to recognise and minimise side effects of asthma medications. Specific strategies for pharmacists when educating people with ID and their caregivers include active listening to determine understanding of concepts, exercising care with language, and working with the person's known routines to maximise adherence with preventer medications.
Brehmer-Rinderer, Barbara; Zeilinger, Elisabeth Lucia; Radaljevic, Ana; Weber, Germain
2013-01-01
Frailty is a theoretical concept used to track individual age-related declines. Persons with intellectual disabilities (ID) often present with pre-existing deficits that would be considered frailty markers in the general population. The previously developed Vienna Frailty Questionnaire for Persons with ID (VFQ-ID) was aimed at assessing frailty in…
Describes the development and advantages of LEGUME ID, a multimedia module for agricultural education. LEGUME ID is an example of how teachers, given the opportunity through accessible computer software programs, can create powerful teaching tools. Summarized is a student response to the use of this teacher-produced software program. (MCO)
Papazoglou, Aimilia; Jacobson, Lisa A.; McCabe, Marie; Kaufmann, Walter; Zabel, T. Andrew
2014-01-01
The "Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition" ("DSM-5") diagnostic criteria for intellectual disability (ID) include a change to the definition of adaptive impairment. New criteria require impairment in one adaptive domain rather than two or more skill areas. The authors examined the diagnostic…
Sermier Dessemontet, Rachel; Morin, Diane; Crocker, Anne G.
2014-01-01
This study investigates the relations between teachers' attitudes towards persons with intellectual disability (ID), in-service training on ID, and prior contacts with persons with ID. A sample of Canadian elementary school teachers (N?=?118) completed the Attitudes Toward Intellectual Disability Questionnaire, which measures cognitive, affective…
Background: There are no validated risk assessment tools for intellectually disabled (ID) sex offenders, with the exception of the work of Lindsay et al. ["Journal of Applied Research in Intellectual Disabilities" (2004) 17: 267] regarding the prediction of risk for aggressive behaviour of ID offenders in residential settings. ID sex offenders…
Diagnosis of neuropathic pain (NP) can be challenging. The ID Pain (ID-P) questionnaire, a screening tool for NP, has been used widely both in the original version and translated forms. The aim of this study was to develop an Arabic version of ID-P and assess its validity and reliability in detecting neuropathic pain. The original ID-P was translated in Arabic language and administered to the study population. Reliability of the Arabic version was evaluated by percentage observed agreement, and Cohen's kappa; and validity by sensitivity, specificity, correctly classified, and receiver operating characteristic (ROC) curve. Physician diagnosis was considered as the gold standard for comparing the diagnostic accuracy. The study included 375 adult patients (153 [40.8%] with NP; 222 [59.2%] with nociceptive pain). Overall observed percentage agreement and Cohen's kappa were >90% and >0.80, respectively. Median (range) score of ID-P scale was 3 (2-4) and 1 (0-2) in the NP group and NocP group, respectively (p<0.001). Area under the ROC curve was 0.808 (95% CI, 0.764-0.851). For the cut-off value of ≥2, sensitivity was 84.3%, specificity was 66.7%, and correct classification was 73.9%. Thus, the Arabic version of ID-P showed moderate reliability and validity as a pain assessment tool. This article presents the psychometric properties of the Arabic version of ID Pain questionnaire. This Arabic version may serve as a simple yet important screening tool, and help in appropriate management of neuropathic pain, specifically in primary care centers in the Kingdom of Saudi Arabia.
Objective. To study mode of birth, perinatal health and death in children born to mothers with intellectual disability (ID) in Sweden. Design. Population-based register study. Setting. National registers; the National Patient Register linked to the Medical Birth Register. Sample. Children of first-time mothers with ID (n = 326; classified in the International Classification of Diseases 8–10) were identified and compared with 340 624 children of first-time mothers without ID or any other psychiatric diagnosis between 1999 and 2007. Methods. Population-based data were extracted from the National Patient Register and the Medical Birth Register. Main outcome measures. Mode of birth, preterm birth, small for gestational age, Apgar score, stillbirth and perinatal death. Results. Children born to mothers with ID were more often stillborn (1.2 vs. 0.3%) or died perinatally (1.8 vs. 0.4%) than children born to mothers without ID. They had a higher proportion of cesarean section birth (24.5 vs. 17.7%) and preterm birth (12.2 vs. 6.1%), were small for gestational age (8.4 vs. 3.1%) and had lower Apgar scores (<7 points at five minutes; 3.7 vs 1.5%) compared with children born to mothers without ID. Logistic regression adjusted for maternal characteristics confirmed an increased risk of small for gestational age (odds ratio 2.25), stillbirth (odds ratio 4.53) and perinatal death (odds ratio 4.25) in children born to mothers with ID. Conclusions. Unborn and newborn children of mothers with ID should be considered a risk group, and their mothers may need better individual-based care and support. PMID:22924821
Lugtenberg, Dorien; Reijnders, Margot R F; Fenckova, Michaela; Bijlsma, Emilia K; Bernier, Raphael; van Bon, Bregje W M; Smeets, Eric; Vulto-van Silfhout, Anneke T; Bosch, Danielle; Eichler, Evan E; Mefford, Heather C; Carvill, Gemma L; Bongers, Ernie M H F; Schuurs-Hoeijmakers, Janneke HM; Ruivenkamp, Claudia A; Santen, Gijs W E; van den Maagdenberg, Arn M J M; Peeters-Scholte, Cacha M P C D; Kuenen, Sabine; Verstreken, Patrik; Pfundt, Rolph; Yntema, Helger G; de Vries, Petra F; Veltman, Joris A; Hoischen, Alexander; Gilissen, Christian; de Vries, Bert B A; Schenck, Annette; Kleefstra, Tjitske; Vissers, Lisenka E L M
2016-01-01
Recently WAC was reported as a candidate gene for intellectual disability (ID) based on the identification of a de novo mutation in an individual with severe ID. WAC regulates transcription-coupled histone H2B ubiquitination and has previously been implicated in the 10p12p11 contiguous gene deletion syndrome. In this study, we report on 10 individuals with de novo WAC mutations which we identified through routine (diagnostic) exome sequencing and targeted resequencing of WAC in 2326 individuals with unexplained ID. All but one mutation was expected to lead to a loss-of-function of WAC. Clinical evaluation of all individuals revealed phenotypic overlap for mild ID, hypotonia, behavioral problems and distinctive facial dysmorphisms, including a square-shaped face, deep set eyes, long palpebral fissures, and a broad mouth and chin. These clinical features were also previously reported in individuals with 10p12p11 microdeletion syndrome. To investigate the role of WAC in ID, we studied the importance of the Drosophila WAC orthologue (CG8949) in habituation, a non-associative learning paradigm. Neuronal knockdown of Drosophila CG8949 resulted in impaired learning, suggesting that WAC is required in neurons for normal cognitive performance. In conclusion, we defined a clinically recognizable ID syndrome, caused by de novo loss-of-function mutations in WAC. Independent functional evidence in Drosophila further supported the role of WAC in ID. On the basis of our data WAC can be added to the list of ID genes with a role in transcription regulation through histone modification. PMID:26757981
Bereavement and loss have significant impact on the lives of individuals with intellectual disability (ID). Although there is a growing impetus to define the symptoms of grief that predict long-term functional impairment, little is known about maladaptive grieving among individuals with ID. We examine the literature concerning the phenomenology of traumatic grief (TG) in the general population, along with what is known about the manifestations of grief in individuals with ID. We then apply modern theories of grief and grief resolution to individuals with ID in order to highlight potential areas of vulnerability in this population and to lay the groundwork for interventions that will facilitate their adaptation to loss. We provide a theoretical framework for the proposition that individuals (including children and adults) with ID are more susceptible to TG, based on an increased risk of secondary loss, barriers to communicating about the loss, and difficulty finding meaning in the loss. We conclude that individuals with ID should be considered as potential candidates for targeted bereavement interventions. Further research is required, however, in order to develop population-appropriate measurement scales for testing these hypotheses. PMID:18306095
Ludi, Erica; Ballard, Elizabeth D; Greenbaum, Rachel; Pao, Maryland; Bridge, Jeffrey; Reynolds, William; Horowitz, Lisa
2012-06-01
Children and adolescents with intellectual disabilities (IDs), often diagnosed with comorbid psychiatric disorders, are a vulnerable population who may be at risk for developing suicidal thoughts and behaviors. Previous research has demonstrated that direct suicide screening can rapidly and effectively detect suicide risk and facilitate further clinical evaluation and management. Currently, there are no measures that screen for suicide risk designed specifically for individuals with ID. A review of the literature was conducted to (1) estimate the prevalence of suicidal thoughts, behaviors, and deaths by suicide in children and adolescents with ID; (2) describe associations between youth with ID and suicide risk; and (3) identify the limitations of commonly used suicide screening measures developed for non-ID youth. The literature review confirms that suicide risk exists in this population; youth with ID think about, attempt, and die by suicide. Standardized suicide risk screening is challenged by the lack of measures developed for this population. A summary of the findings is followed by a discussion of the practical clinical considerations surrounding the assessment of suicide risk in youth with ID.
Background Training of infectious disease (ID) specialists is structured on classical clinical microbiology training in Turkey and ID specialists work as clinical microbiologists at the same time. Hence, this study aimed to determine the clinical skills and knowledge required by clinical microbiologists. Methods A cross-sectional study was carried out between June 1, 2010 and September 15, 2010 in 32 ID departments in Turkey. Only patients hospitalized and followed up in the ID departments between January-June 2010 who required consultation with other disciplines were included. Results A total of 605 patients undergoing 1343 consultations were included, with pulmonology, neurology, cardiology, gastroenterology, nephrology, dermatology, haematology, and endocrinology being the most frequent consultation specialties. The consultation patterns were quite similar and were not affected by either the nature of infections or the critical clinical status of ID patients. Conclusions The results of our study show that certain internal medicine subdisciplines such as pulmonology, neurology and dermatology appear to be the principal clinical requisites in the training of ID specialists, rather than internal medicine as a whole. PMID:22177310
The aim of this study was to identify the contribution of Irish intellectual disability clinical nurse specialists (ID CNSs) to service delivery. A nonexperimental descriptive design was selected to survey ID CNSs presently working in Ireland. The questionnaire was developed based on focus group interviews, available literature, and expert panel views. Ethical approval and access were granted to all ID CNSs in Ireland. Thirty-two responded (33.68% response rate) from all work areas (voluntary organizations or health service executive) practicing within residential, community, or school services. Respondents were surveyed across a range of areas (demographic details and support to client, staff, family, organization, community, other agencies, and professional development). Findings identify that ID CNSs are active in all aspects of their roles as clinical specialist, educator, communicator, researcher, change agent, and leader, thus supporting person-centered care and improving service delivery. To meet changing healthcare demands, promote person-centered care, and improve service delivery, the CNS role in ID should be developed and supported. The findings merit a further study on ID CNS role activity, possible variables influencing role activity, and team members' views.
We propose the Josephson junctions linked by a normal metal between a d + id superconductor and another d + id superconductor, a d-wave superconductor, or a s-wave superconductor for identifying the chiral d + id superconductivity. The time-reversal breaking in the chiral d-wave superconducting state is shown to result in a Josephson φ 0 -junction state where the current-phase relation is shifted by a phase φ 0 from the sinusoidal relation, other than 0 and π. The ground-state phase difference φ 0 and the critical current can be used to definitely confirm and read the information about the d + id superconductivity. A smooth evolution from conventional 0-π transitions to tunable φ 0 -states can be observed by changing the relative magnitude of two types of d-wave components in the d + id pairing. On the other hand, the Josephson junction involving the d + id superconductor is also the simplest model to realize a φ 0 - junction, which is useful in superconducting electronics and superconducting quantum computation.
We propose the Josephson junctions linked by a normal metal between a d + id superconductor and another d + id superconductor, a d-wave superconductor, or a s-wave superconductor for identifying the chiral d + id superconductivity. The time-reversal breaking in the chiral d-wave superconducting state is shown to result in a Josephson φ0-junction state where the current-phase relation is shifted by a phase φ0 from the sinusoidal relation, other than 0 and π. The ground-state phase difference φ0 and the critical current can be used to definitely confirm and read the information about the d + id superconductivity. A smooth evolution from conventional 0-π transitions to tunable φ0-states can be observed by changing the relative magnitude of two types of d-wave components in the d + id pairing. On the other hand, the Josephson junction involving the d + id superconductor is also the simplest model to realize a φ0- junction, which is useful in superconducting electronics and superconducting quantum computation. PMID:28266582
Infundibular dilatation (ID) is a funnel-shaped enlargement of the origin of cerebral arteries. The coexistence of an aneurysm and ID is relatively rare. Patients with IDs are rarely followed up. However, some IDs have been reported to develop into aneurysms with subsequent rupture. Here we report on a case of an aneurysm that coexisted with ID of the posterior communicating artery. A 51-year-old woman underwent magnetic resonance imaging (MRI) to check for aneurysms and other problems. MRI revealed an unruptured aneurysm of the right internal carotid artery, for which the patient was admitted to our hospital. Three-dimensional computed tomographic angiography revealed an aneurysm, which protruded outward, and ID of the posterior communicating artery, which protruded inward. A right pterional craniotomy was performed with aneurysm clipping. The postoperative course was uneventful. In this report, we demonstrate operative views of the aneurysm and ID with the use of neuroendoscopy. ID can develop into a true arterial aneurysm and potentially rupture. Therefore, we need to observe the patients with IDs carefully, particularly in young women.
Although evolutionary biology is replete with explanations for complex biological structures, scientists concerned about evolution education have been forced to confront “intelligent design” (ID), which rejects a natural origin for biological complexity. The content of ID is a subset of the claims made by the older “creation science” movement. Both creationist views contend that highly complex biological adaptations and even organisms categorically cannot result from natural causes but require a supernatural creative agent. Historically, ID arose from efforts to produce a form of creationism that would be less vulnerable to legal challenges and that would not overtly rely upon biblical literalism. Scientists do not use ID to explain nature, but because it has support from outside the scientific community, ID is nonetheless contributing substantially to a long-standing assault on the integrity of science education. PMID:17494747
Environmental stress generally exacerbates the harmful effects of inbreeding and it has been proposed that this could be exploited in purging deleterious alleles from threatened inbred populations. However, understanding what factors contribute to variability in the strength of inbreeding depression (ID) observed across adverse environmental conditions remains a challenge. Here, we examined how the nature and timing of stress affects ID and the potential for purging using inbred and outbred Drosophila melanogaster larvae exposed to biotic (larval competition, bacteria infection) and abiotic (ethanol, heat) stressors compared with unstressed controls. ID was measured during (larval survival) and after (male mating success) stress exposure. The level of stress imposed by each stressor was approximately equal, averaging a 42% reduction in outbred larval survival relative to controls. All stressors induced on average the same ID, causing a threefold increase in lethal equivalents for larval survival relative to controls. However, stress-induced ID in larval success was followed by a 30% reduction in ID in mating success of surviving males. We propose that this fitness recovery is due to ‘intragenerational purging' whereby fitness correlations facilitate stress-induced purging that increases the average fitness of survivors in later life history stages. For biotic stressors, post-stress reductions in ID are consistent with intragenerational purging, whereas for abiotic stressors, there appeared to be an interaction between purging and stress-induced physiological damage. For all stressors, there was no net effect of stress on lifetime ID compared with unstressed controls, undermining the prediction that stress enhances the effectiveness of population-level purging across generations. PMID:26604190
Intellectual disability (ID) is a clinically and genetically heterogeneous common condition that remains etiologically unresolved in the majority of cases. Although several hundred diseased genes have been identified in X-linked, autosomal-recessive, or syndromic types of ID, the establishment of an etiological basis remains a difficult task in unspecific, sporadic cases. Just recently, de novo mutations in SYNGAP1, STXBP1, MEF2C, and GRIN2B were reported as relatively common causes of ID in such individuals. On the basis of a patient with severe ID and a 2.5 Mb microdeletion including ARID1B in chromosomal region 6q25, we performed mutational analysis in 887 unselected patients with unexplained ID. In this cohort, we found eight (0.9%) additional de novo nonsense or frameshift mutations predicted to cause haploinsufficiency. Our findings indicate that haploinsufficiency of ARID1B, a member of the SWI/SNF-A chromatin-remodeling complex, is a common cause of ID, and they add to the growing evidence that chromatin-remodeling defects are an important contributor to neurodevelopmental disorders. PMID:22405089
Watchman, Karen; Janicki, Matthew P; Splaine, Michael; Larsen, Frode K; Gomiero, Tiziano; Lucchino, Ronald
2017-06-01
The World Health Organization (WHO) has called for the development and adoption of national plans or strategies to guide public policy and set goals for services, supports, and research related to dementia. It called for distinct populations to be included within national plans, including adults with intellectual disability (ID). Inclusion of this group is important as having Down's syndrome is a significant risk factor for early-onset dementia. Adults with other ID may have specific needs for dementia-related care that, if unmet, can lead to diminished quality of old age. An International Summit on Intellectual Disability and Dementia, held in Scotland, reviewed the inclusion of ID in national plans and recommended that inclusion goes beyond just description and relevance of ID. Reviews of national plans and reports on dementia show minimal consideration of ID and the challenges that carers face. The Summit recommended that persons with ID, as well as family carers, should be included in consultation processes, and greater advocacy is required from national organizations on behalf of families, with need for an infrastructure in health and social care that supports quality care for dementia.
Cardol, M.; Rijken, M.; van Schrojenstein Lantman-de Valk, H.
2012-01-01
Background: The prevalence of diabetes is relatively high in people with intellectual disability (ID). However, little is known about how people with ID experience having diabetes and how they manage the condition. Method: Seventeen people with mild to moderate ID who have diabetes were interviewed. A framework on illness perceptions having an…
Individuals with significant intellectual disabilities (ID) are more likely to engage in problem behaviors than are people with milder disabilities or with no disability. It is widely considered that behavior problems serve a communicative function for individuals with severe ID and limited communication skills. Among people with significant ID,…
This study examined sleep, sleepiness, and daytime performance in 68 children with autism, 57 children with intellectual disability (ID), and 69 typically developing preschool children. Children in the autism and ID groups had poorer daytime performance and behaviors than the typically developing children. Children in the ID group also were…
[email protected] , or by telephone at (301) 415-1677, to request (1) a digital ID certificate, which allows the... its counsel or representative, already holds an NRC- issued digital ID certificate). Based upon this... Secretary has not already established an electronic docket. Information about applying for a digital ID...
Xenitidis, K.; Paliokosta, E.; Rose, E.; Maltezos, S.; Bramham, J.
2010-01-01
Background: This study examined symptoms and lifetime course of Attention Deficit Hyperactivity Disorder (ADHD) in adults with borderline and mild Intellectual Disability (ID). Method: A total of 48 adults with ID and ADHD were compared with 221 adults with ADHD without ID using the informant Barkley scale for childhood and adulthood symptoms.…
...-0023; Airspace Docket No. 11-ANM-2] Amendment of Class D and Class E Airspace; Idaho Falls, ID AGENCY... D and Class E airspace at Idaho Falls, ID, by changing the name of the airport to Idaho Falls... Performance (RNP) standard instrument approach procedures at Idaho Falls Regional Airport. This improves the...
... DEPARTMENT OF COMMERCE Foreign-Trade Zones Board [B-68-2012] Foreign-Trade Zone 242--Boundary County, ID; Application for Subzone AREVA Enrichment Services, LLC; Bonneville County, ID An application... FTZ 242, requesting special-purpose subzone status for the facility of AREVA Enrichment Services, LLC...
Weiss, Jonathan A.; Lunsky, Yona; Gracey, Carolyn; Canrinus, Maaike; Morris, Susan
2009-01-01
Background: Strains on the mental health system and inaccessible services for individuals with intellectual disabilities (ID) often force caregivers to bring individuals with ID to the emergency department (ED) when in psychiatric crisis. The purpose of this study was to understand the experience of caregivers and adults with ID and mental health…
...-Challis National Forest, ID; Upper North Fork HFRA Ecosystem Restoration Project Environmental Impact... improve the health of the ecosystem and reach the desired future condition. DATES: Comments concerning the... Ecosystem Restoration Project EIS, P.O. Box 180, 11 Casey Rd., North Fork, ID 83466. Comments may also be...
Holwerda, Anja; van der Klink, Jac J. L.; de Boer, Michiel R.; Groothoff, Johan W.; Brouwer, Sandra
2013-01-01
Individuals with intellectual disabilities (ID) are three to four times less often employed compared to their non-disabled peers. Evidence for factors associated with work participation of young adults with ID is limited. Furthermore, studies on predictors for sustainable work participation among young adults with ID is lacking altogether.…
... precursor of PM2.5. Table 2a to Appendix A of Subpart A—Data Elements for Reporting on Emissions From Point Sources, Where Required by 40 CFR 51.30 Data elements Every-yearreporting Three-yearreporting (1... phone number ✓ ✓ (6) FIPS code ✓ ✓ (7) Facility ID codes ✓ ✓ (8) Unit ID code ✓ ✓ (9) Process ID code...
Background: Individuals with intellectual disability (ID) and legal involvement are a unique population with complex needs. To date, there has been limited research exploring the demographic and clinical profiles of individuals with ID and legal involvement that are in crisis and how they differ to individuals with ID without legal involvement.…
[email protected] , or by telephone at 301-415-1677, to request (1) a digital identification (ID... which the participant, or its counsel or representative, already holds an NRC-issued digital ID... about applying for a digital ID certificate is available on the NRC's public Web site at http://www.nrc...
... for access codes to file on EDGAR. 239.63 Section 239.63 Commodity and Securities Exchanges SECURITIES... Statements § 239.63 Form ID, uniform application for access codes to file on EDGAR. Form ID must be filed by... log on to the EDGAR system, submit filings, and change its CCC. (d) Password Modification...
