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
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
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
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.
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.
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
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.
The suppression of viral loads and identification of selection signatures in non-human primates after challenge are indicators for effective human immunodeficiency virus (HIV)/simian immunodeficiency virus (SIV) vaccines. To mimic the protective immunity elicited by attenuated SIV vaccines, we developed an integration-defective SIV (idSIV) vaccine by inactivating integrase, mutating sequence motifs critical for integration, and inserting the cytomegalovirus (CMV) promoter for more efficient expression in the SIVmac239 genome. Chinese rhesus macaques were immunized with idSIV DNA and idSIV particles, and the cellular and humoral immune responses were measured. After the intravenous SIVmac239 challenge, viral loads were monitored and selection signatures in viral genomes from vaccinated monkeys were identified by single genome sequencing. T cell responses, heterologous neutralization against tier-1 viruses, and antibody-dependent cellular cytotoxicity (ADCC) were detected in idSIV-vaccinated macaques post immunization. After challenge, the median peak viral load in the vaccine group was significantly lower than that in the control group. However, this initial viral control did not last as viral set-points were similar between vaccinated and control animals. Selection signatures were identified in Nef, Gag, and Env proteins in vaccinated and control macaques, but these signatures were different, suggesting selection pressure on viruses from vaccine-induced immunity in the vaccinated animals. Our results showed that the idSIV vaccine exerted some pressure on the virus population early during the infection but future modifications are needed in order to induce more potent immune responses. PMID:28574482
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.
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
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
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.
There is little information of hepatitis B vaccination coverage for people with intellectual disabilities (ID). The present paper aims to examine the completed hepatitis B vaccination coverage rate and its determinants of children and adolescents with ID in Taiwan. A cross-sectional questionnaire survey, with the entire response participants was…
Immunization with radiation-attenuated sporozoites (RAS) via mosquito bites has been shown to induce sterile immunity against malaria in humans, but this route of vaccination is neither practical nor ethical. The importance of delivering RAS to the liver through circulation in eliciting immunity against this parasite has been recently verified by human studies showing that high-level protection was achieved only by intravenous (IV) administration of RAS, but not by intradermal (ID) or subcutaneous (SC) vaccination. Here, we report in a murine model that ID inoculation of RAS into laser-illuminated skin confers immune protection against malarial infection almost as effectively as IV immunization. Brief illumination of the inoculation site with a low power 532 nm Nd:YAG laser enhanced the permeability of the capillary beneath the skin, owing to hemoglobin-specific absorbance of the light. The increased blood vessel permeability appeared to facilitate an association of RAS with blood vessel walls by an as-yet-unknown mechanism, ultimately promoting a 7-fold increase in RAS entering circulation and reaching the liver over ID administration. Accordingly, ID immunization of RAS at a laser-treated site stimulated much stronger sporozoite-specific antibody and CD8+IFN-γ+ T cell responses than ID vaccination and provided nearly full protection against malarial infection, whereas ID immunization alone was ineffective. This novel, safe, and convenient strategy to augment efficacy of ID sporozoite-based vaccines warrants further investigation in big animals and in humans. PMID:25725360
Vaccination against hepatitis A virus (HAV) is unaffordable to many developing countries. Substantial reductions in cost occur when vaccines are administered intradermally at low doses. Aluminum-free HAV vaccines are considered more suitable for intradermal use than traditional vaccines which can cause long-lasting local reactions. Thus, we compared the immunogenicity and safety of an aluminum-free virosomal HAV vaccine (Epaxal) administered by different routes: intradermal (i.d.), subcutaneous (s.c.), and intramuscular (i.m.). Two open pilot studies were conducted as sub-studies of a large lot consistency trial. Healthy subjects aged 18 to 45 were enrolled. Study 1 compared two i.d. regimens of a lower dose of Epaxal [0.1 mL (4.8 IU), one or two injection sites] with i.m. administration of the standard dose [0.5 mL (24 IU)]. Study 2 compared the s.c. with the i.m. administration of the standard dose. At month 12, subjects in study 1 received a booster dose of 0.1 mL i.d. or 0.5 mL i.m.; subjects in study 2 received 0.5 mL via the respective route (s.c. or i.m.). Serum was tested for antibodies at baseline, 2 weeks (study 1), and 1 and 6 months after the primary vaccination as well as prior and 1 month after the booster dose. Incidences of solicited and unsolicited adverse events were recorded. Seroprotection rates (anti-HAV geometric mean concentration of > or =20 mIU/mL) after 1 month ranged from 93.2% to 100% in all groups and remained high until month 12 (range 85.2&-90.2%). Complete (100%) seroprotection was achieved by all subjects in all groups after booster vaccination. All routes of administration were well tolerated. Local reactions were more common in subjects vaccinated i.d. and s.c. than i.m. The aluminum-free virosomal HAV vaccine Epaxal is highly immunogenic and well tolerated when administered either via i.d., s.c., or i.m. Vaccination via the i.d. route may confer significant cost savings over the conventional i.m. route.
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…
Pathogen-derived molecules are danger signals and are able to activate innate immunity that in turn controls and regulates generation of adaptive immune responses. Mycobacterium tuberculosis heat shock protein 70 (myc HSP70) has been shown to exert a potent adjuvant effect in vaccination against both infectious agents and solid tumors. Here we explore the use of myc HSP70, as an adjuvant, in DNA vaccination against lymphoma. We describe the effects of vaccination using myc HSP70 encoding plasmid (pHSP70) co-injected with idiotype encoding plasmid (pId), in the 38C13 murine lymphoma model. We dissect mechanisms of anti-tumor immune response and compared efficacy with that of other DNA vaccination strategies. We show that myc HSP70 plasmid prolongs survival of immunized mice challenged with a high number (2000) of tumor cells. The magnitude of the anti-tumor effect is comparable to that obtained using granulocyte-macrophage colony-stimulating factor (GM-CSF) in the same setting. Moreover, HSP-induced protection is independent from the generation of IgG1 and IgG2a antibodies. Instead, anti-idiotype antibodies of IgG2b subclass develop after vaccination with pHSP as well as with pId and Id-GM-CSF fusion plasmid (pId-GM). Co-injection of HSP70 and Id plasmids induces a specific pattern of anti-idiotype immune response able to improve survival of immunized mice.
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
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.
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.
Hydrogels have been widely studied in various biomedical applications, such as tissue engineering, cell culture, immunotherapy and vaccines, and drug delivery. Peptide-based nanofibers represent a promising new strategy for current drug delivery approaches and cell carriers for tissue engineering. This review focuses on the recent advances in the use of self-assembling engineered β-sheet peptide assemblies for biomedical applications. The applications of peptide nanofibers in biomedical fields, such as drug delivery, tissue engineering, immunotherapy, and vaccines, are highlighted. The current challenges and future perspectives for self-assembling peptide nanofibers in biomedical applications are discussed.
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.
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
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.
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
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.
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.
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.
Heine, Shannon J.; Diaz-McNair, Jovita; Andar, Abhay U.; Drachenberg, Cinthia B.; van de Verg, Lillian; Walker, Richard; Picking, Wendy L.; Pasetti, Marcela F.
2014-01-01
Shigella is one of the leading pathogens contributing to the vast pediatric diarrheal disease burden in low-income countries. No licensed vaccine is available and the existing candidates are only partially effective and serotype-specific. Shigella type III secretion system proteins IpaB and IpaD, which are conserved across Shigella spp., are candidates for a broadly protective, subunit-based vaccine. Herein, we investigated the immunogenicity and protective efficacy of IpaB and IpaD administered intradermally (i.d.) with a double-mutant of the E. coli heat-labile enterotoxin (dmLT) adjuvant using microneedles. Different dosage levels of IpaB and IpaD with or without dmLT were tested in mice. Vaccine delivery into the dermis, recruitment of neutrophils, macrophages, dendritic cells (DC) and Langerhans cells (LC), and colocalization of vaccine antigens within skin-activated antigen presenting cells (APC) was demonstrated through histology and immunofluorescence microscopy. Ag-loaded neutrophils, macrophages, DC and LC remained in the tissue at least one week. IpaB, IpaD and dmLT-specific serum IgG and IgG secreting cells were produced following i.d. immunization. The protective efficacy was 70% against S. flexneri and 50% against S. sonnei. Similar results were obtained when the vaccine was administered intranasally, with the i.d. route requiring 25-40 times lower doses. Distinctively, IgG was detected in mucosal secretions; sIgA as well as mucosal and systemic IgA antibody secreting cells (ASC) were seemingly absent. Vaccine-induced T cells produced IFN-γ, IL-2, TNF-α, IL-17, IL-4, IL-5 and IL-10. These results demonstrate the potential of i.d. vaccination with IpaB and IpaD to prevent Shigella infection and support further studies in humans. PMID:24453241
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
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.
Rabies is a virtually 100% fatal acute viral encephalitis caused by an RNA virus belonging to family Rhabdoviridae and genus Lyssavirus. The virus can infect all warm blooded animals. The disease is transmitted to humans by the bite, lick or scratch of an infected animal. More than 99% of all human rabies deaths occur in the developing world. It is preventable with timely and proper usage of modern immunobiologicals (vaccines and immunoglobulins). Once exposure occurs, modern prophylaxis entails immediate wound care, local infiltration of rabies immune globulin and parenteral administration of modern cell culture vaccines in multiple doses. The annual medicinal (vaccines and other drugs) cost for animal bite treatment is Rs. 2 billion approximately (2004). The objective of the present study is to evaluate the performance of the Intradermal (i.d.) route visa vis the Intramuscular (i.m.) route in our clinical setting the Antirabies Vaccination (ARV) OPD, Sir J.J. Hospital, Mumbai. A total of 1460 patients were administered the Antirabies vaccine by the Intradermal route over the 1 year period as compared to 1075 patients who were administered the Antirabies vaccine by the Intramuscular route in the previous year. 1230 (84.2) of the patients who were administered the vaccine by the i.d. route completed the schedule and 230 (15.8%) partially completed the schedule. Four hundred thirty two (40%) of the patients who were administered the vaccine by the Intramuscular route completed the schedule and 643 (59.8%) partially completed the schedule. The vaccine cost for i.d. was Rs. 2,80,600. The vaccine cost for the intramuscular (i.m.) assuming 84% compliance was estimated as Rs. 15, 64, 000. Assuming 40% compliance the cost was estimated as Rs. 7, 82, 230. Thus a saving of Rs. 5, 01, 630 to Rs. 12, 83, 400 was effected. In our setting, the Intradermal regime was cost effective and increased patient adherence and enrolment. It has now been routinely adopted at the clinic.
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
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
Schwartz, Michael D; Macias-Moriarity, Lilia Z; Schelling, Joerg
2012-12-01
Air carrier and professional corporate aircrews provide a unique and highly distinct population in which to examine potential transport and transmission of infectious diseases (ID). This study sought to assess frequency of flying while acutely ill, identify clinical triggers in self-grounding, determine employer support for self-grounding, examine rates of influenza vaccination, and identify unmet needs for current information on ID issues related to extensive travel required of professional aircrews. Anonymous questionnaires were completed by select European mainline, U.S. regional airline, and professional corporate aircrews on ID topics such as flying while ill, flying with ill crewmembers, receipt of influenza vaccination, disinfection, and other aviation medical issues. Data were analyzed and reported as composite and stratified by airline vs. corporate aviation respondents. Aircrews often flew while ill (or with ill crewmembers); 52% flew until fever reached 38 degrees C (100.4 degrees F) and an additional 37% flew up to 38.89 degrees C (102 degrees F). Rate of annual influenza vaccination was quite low for all groups, but especially so for airline crews (21-27%), even given potential occupational exposure risk. Crews also had strongly differing perceptions of employer views on self-grounding, depending upon employment setting. There were sizable disparities between aircrew flying for U.S. regional, European mainline, and large corporate aviation departments with respect to self-grounding when ill and routinely receiving a seasonal influenza vaccination. All study groups reported a pressing need for enhanced anonymous access to current ID and medical information.
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
Babakhanyan, Anna; Leke, Rose G. F.; Salanti, Ali; Bobbili, Naveen; Gwanmesia, Philomina; Leke, Robert J. I.; Quakyi, Isabella A.; Chen, John J.; Taylor, Diane Wallace
2014-01-01
In pregnant women, Plasmodium falciparum-infected erythrocytes expressing the VAR2CSA antigen bind to chondroitin sulfate A in the placenta causing placental malaria. The binding site of VAR2CSA is present in the ID1-ID2a region. This study sought to determine if pregnant Cameroonian women naturally acquire antibodies to ID1-ID2a and if antibodies to ID1-ID2a correlate with absence of placental malaria at delivery. Antibody levels to full-length VAR2CSA and ID1-ID2a were measured in plasma samples from 745 pregnant Cameroonian women, 144 Cameroonian men, and 66 US subjects. IgM levels and IgG avidity to ID1-ID2a were also determined. As expected, antibodies to ID1-ID2a were absent in US controls. Although pregnant Cameroonian women developed increasing levels of antibodies to full-length VAR2CSA during pregnancy, no increase in either IgM or IgG to ID1-ID2a was observed. Surprisingly, no differences in antibody levels to ID1-ID2a were detected between Cameroonian men and pregnant women. For example, in rural settings only 8–9% of males had antibodies to full-length VAR2CSA, but 90–96% had antibodies to ID1-ID2a. In addition, no significant difference in the avidity of IgG to ID1-ID2a was found between pregnant women and Cameroonian men, and no correlation between antibody levels at delivery and absence of placental malaria was found. Thus, the response to ID1-ID2a was not pregnancy specific, but predominantly against cross-reactivity epitopes, which may have been induced by other PfEMP1 antigens, malarial antigens, or microbes. Currently, ID1-ID2a is a leading vaccine candidate, since it binds to the CSA with the same affinity as the full-length molecule and elicits binding-inhibitory antibodies in animals. Further studies are needed to determine if the presence of naturally acquired cross-reactive antibodies in women living in malaria endemic countries will alter the response to ID1-ID2a following vaccination with ID1-ID2a. PMID:24505415
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.
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
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.
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
shock were biocompatible in vivo, retained potent antibody responses, and were well tolerated by rhesus macaques. Vaccinated primates were completely...results indicate that the vaccines were biocompatible by i.d. administration and physical separation. Seroconversion also occurred after the primary...the vaccinated animals, suggesting that the potency of this vaccine was maintained. Cellular immu- nity , not addressed in our study, may also be
Dhaduk, Kishor M; Unadkat, Sumit V; Katharotiya, Pooja R; Mer, Ankit R; Chaudhary, Monika C; Prajapati, Mrudul M
2016-01-01
Rabies is a preventable neglected public health problem and associated with multiple cultural, religious, and social practices, myths in our country. There is a lack of organized surveillance system to measure the incidence of animal bite and human rabies as well as to evaluate cost-saving of different routes, regimen, and types of antirabies vaccines (ARV)/immunoglobulin available in India. The objective of this study is to know dropout rate in intradermal (i.d.) ARV regimen among animal bite and to analyze the utilized volume of ARV by a different route of vaccine administration. A total of 250 animal bite victims were followed up at ARV Clinic (ARVC). Volume utilization of i.d. route over intramuscular (i.m.) route was analyzed among the patients who attended ARVC during the past 2 years. Total dropout and delayed compliance rates of ARV regimen among different group were compared by Chi-square test. The i.d. route was about five times more volume and cost-saving than i.m. route. The majority of victims belonged to 15-30 years (27.60%) and children <15 years (26.40%) and had wound at their lower limbs (85%) mainly bitten by dogs (98%). Thirty-four percent total dropout and 31.5% delayed compliance observed particularly during the last dose of i.d. regimen. There was no significant difference in dropout rates among different demographic groups. Half of the victims practiced wound toilet on the same day of bite. Only 68% received the first dose of ARV within 24 h of the exposure. Children and young adults are at higher risk of having dog bite. I.d. ARV regimen is more volume and cost-saving than i.m. one and proper counseling and follow-up should be arranged to complete the vaccination schedule.
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
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.
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
The VAR2CSA protein of Plasmodium falciparum is transported to and expressed on the infected erythrocyte surface where it plays a key role in placental malaria (PM). It is the current leading candidate for a vaccine to prevent PM. However, the antigenic polymorphism integral to VAR2CSA poses a challenge for vaccine development. Based on detailed analysis of polymorphisms in the sequence of its ligand-binding N-terminal region, currently the main focus for vaccine development, we assessed var2csa from parasite isolates infecting pregnant women. The results reveal for the first time the presence of a major dimorphic region in the functionally critical N-terminal ID1 domain. Parasite isolates expressing VAR2CSA with particular motifs present within this domain are associated with gravidity- and parasite density-related effects. These observations are of particular interest in guiding efforts with respect to optimization of the VAR2CSA-based vaccines currently under development. PMID:26393516
Barucca, A; Capitani, M; Cesca, M; Tomassoni, D; Kazmi, U; Concetti, F; Vincenzetti, L; Concetti, A; Venanzi, F M
2014-11-01
Anti-idiotypic MK2-23 monoclonal antibody (anti-Id MK2-23 mAb), which mimics the high molecular weight melanoma-associated antigen (HMW-MAA), has been used to implement active immunotherapy against melanoma. However, due to safety and standardization issues, this approach never entered extensive clinical trials. In the present study, we investigated the usage of DNA vaccines as an alternative to MK2-23 mAb immunization. MK2-23 DNA plasmids coding for single chain (scFv) MK2-23 antibody were constructed via the insertion of variable heavy (V H) and light (V L) chains of MK2-23 into the pVAC-1mcs plasmids. Two alternative MK2-23 plasmids format V H/V L, and V L/V H were assembled. We demonstrate that both polypeptides expressed by scFv plasmids in vitro retained the ability to mimic HMW-MAA antigen, and to elicit specific anti-HMW-MAA humoral and cellular immunoresponses in immunized mice. Notably, MK2-23 scFv DNA vaccines impaired the onset and growth of transplantable B16 melanoma cells not engineered to express HMW-MAA. This pilot study suggests that optimized MK2-23 scFv DNA vaccines could potentially provide a safer and cost-effective alternative to anti-Id antibody immunization, for melanoma immunotherapy.
Asplenic or hyposplenic (AH) individuals are particularly vulnerable to invasive infections caused by encapsulated bacteria. Such infections have often a sudden onset and a fulminant course. Infectious diseases (IDs) incidence in AH subjects can be reduced by preventive measures such as vaccination. The aim of our work is to provide updated recommendations on prevention of infectious diseases in AH adult patients, and to supply a useful and practical tool to healthcare workers for the management of these subjects, in hospital setting and in outpatients consultation. A systematic literature review on evidence based measures for the prevention of IDs in adult AH patients was performed in 2015. Updated recommendations on available vaccines were consequently provided. Vaccinations against S. pneumoniae, N. meningitidis, H. influenzae type b and influenza virus are strongly recommended and should be administered at least 2 weeks before surgery in elective cases or at least 2 weeks after the surgical intervention in emergency cases. In subjects without evidence of immunity, 2 doses of live attenuated vaccines against measles-mumps-rubella and varicella should be administered 4-8 weeks apart from each other; a booster dose of tetanus, diphtheria and pertussis vaccine should be administered also to subjects fully vaccinated, and a 3-dose primary vaccination series is recommended in AH subjects with unknown or incomplete vaccination series (as in healthy people). Evidence based prevention data support the above recommendations to reduce the risk of infection in AH individuals.
ABSTRACT Asplenic or hyposplenic (AH) individuals are particularly vulnerable to invasive infections caused by encapsulated bacteria. Such infections have often a sudden onset and a fulminant course. Infectious diseases (IDs) incidence in AH subjects can be reduced by preventive measures such as vaccination. The aim of our work is to provide updated recommendations on prevention of infectious diseases in AH adult patients, and to supply a useful and practical tool to healthcare workers for the management of these subjects, in hospital setting and in outpatients consultation. A systematic literature review on evidence based measures for the prevention of IDs in adult AH patients was performed in 2015. Updated recommendations on available vaccines were consequently provided. Vaccinations against S. pneumoniae, N. meningitidis, H. influenzae type b and influenza virus are strongly recommended and should be administered at least 2 weeks before surgery in elective cases or at least 2 weeks after the surgical intervention in emergency cases. In subjects without evidence of immunity, 2 doses of live attenuated vaccines against measles-mumps-rubella and varicella should be administered 4–8 weeks apart from each other; a booster dose of tetanus, diphtheria and pertussis vaccine should be administered also to subjects fully vaccinated, and a 3-dose primary vaccination series is recommended in AH subjects with unknown or incomplete vaccination series (as in healthy people). Evidence based prevention data support the above recommendations to reduce the risk of infection in AH individuals. PMID:27929751
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.
Scheuermann, Richard H; Sinkovits, Robert S; Schenkelberg, Theodore; Koff, Wayne C
2017-06-01
Biomedical research has become a data intensive science in which high throughput experimentation is producing comprehensive data about biological systems at an ever-increasing pace. The Human Vaccines Project is a new public-private partnership, with the goal of accelerating development of improved vaccines and immunotherapies for global infectious diseases and cancers by decoding the human immune system. To achieve its mission, the Project is developing a Bioinformatics Hub as an open-source, multidisciplinary effort with the overarching goal of providing an enabling infrastructure to support the data processing, analysis and knowledge extraction procedures required to translate high throughput, high complexity human immunology research data into biomedical knowledge, to determine the core principles driving specific and durable protective immune responses.
Donzelli, Mattia, E-mail: donzelli@esrf.fr; Bräuer-Krisch, Elke; Nemoz, Christian
Purpose: Upcoming veterinary trials in microbeam radiation therapy (MRT) demand for more advanced irradiation techniques than in preclinical research with small animals. The treatment of deep-seated tumors in cats and dogs with MRT requires sophisticated irradiation geometries from multiple ports, which impose further efforts to spare the normal tissue surrounding the target. Methods: This work presents the development and benchmarking of a precise patient alignment protocol for MRT at the biomedical beamline ID17 of the European Synchrotron Radiation Facility (ESRF). The positioning of the patient prior to irradiation is verified by taking x-ray projection images from different angles. Results: Usingmore » four external fiducial markers of 1.7 mm diameter and computed tomography-based treatment planning, a target alignment error of less than 2 mm can be achieved with an angular deviation of less than 2{sup ∘}. Minor improvements on the protocol and the use of smaller markers indicate that even a precision better than 1 mm is technically feasible. Detailed investigations concerning the imaging dose lead to the conclusion that doses for skull radiographs lie in the same range as dose reference levels for human head radiographs. A currently used online dose monitor for MRT has been proven to give reliable results for the imaging beam. Conclusions: The ESRF biomedical beamline ID17 is technically ready to apply conformal image-guided MRT from multiple ports to large animals during future veterinary trials.« less
We introduce the first meta-service for information extraction in molecular biology, the BioCreative MetaServer (BCMS; ). This prototype platform is a joint effort of 13 research groups and provides automatically generated annotations for PubMed/Medline abstracts. Annotation types cover gene names, gene IDs, species, and protein-protein interactions. The annotations are distributed by the meta-server in both human and machine readable formats (HTML/XML). This service is intended to be used by biomedical researchers and database annotators, and in biomedical language processing. The platform allows direct comparison, unified access, and result aggregation of the annotations. PMID:18834497
Okwesili, A N; Onuigwe, F U; Ibrahim, K; Buhari, H; Ibrahim, A; Jafaru, H; Erhabor, O; Onuigwe, F U; Isaac, Z; Ahmed, M H; Mainasara, M Y; Adias, T C; Yeldu, M H; Uko, E K; Udoma, F
2015-12-23
Hepatitis B (HB) is a serious global public health problem that put health professionals particularly at risk. The aim of this study was to investigate the prevalence of Hepatitis B surface antigen (HBsAg) among Biomedical Students of African descent attending Usmanu Danfodiyo University Sokoto in North-Western Nigeria. The Onsite HBsAg (CTK Biotech, USA) was used to detect the presence of hepatitis B surface antigen. We tested 186 consecutively-recruited students consisting of 147 males and 39 females aged 18-35 years (mean age 26 ± 2.0 years). Of the 186 students tested, 25 (13.4%) were positive for HBsAg. The prevalence of HBsAg was significantly higher among students in the 21-25 years age group. Hepatitis B vaccination uptake among students was 7%. Majority of subjects were single 173(93.1%) compared to married 13 (6.9%). Ethnic distribution of the subjects indicated that 104(55.9%) were Hausa compared to Yoruba 32 (17.2%), other ethnic groups 21(11.3%), Fulani 20(10.8%) and Igbo 9(4.8%). This study indicates a high prevalence of hepatitis B virus infection among Biomedical students in Sokoto, North Western, Nigeria. Finding from this study is enough justification for the implementation of a policy to routinely test students entering into the biomedical professions for Hepatitis B virus infection. There is the need to provide hepatitis B vaccination universally to all those who are found negative prior to commencement of their biomedical training. There is also need to educate students entering biomedical professions and healthcare workers on the modes of transmission and prevention, importance of being compliant with protective vaccination as well as the need to observe universal precaution and infection control guidelines during their training and future professional practice.
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.
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
In the fight against the HIV/AIDS pandemic different approaches can be distinguished, reflecting professional backgrounds, world views and political interests. One important distinction is between the biomedical and the development paradigms. The biomedical paradigm is characterized by individualization and the concept of "risk". This again is related to the concept of the market where health is a product of services and progress a series of new discoveries that can be marketed. The development paradigm is characterized by participation of the different stakeholders and by community work. The concept "vulnerability" is important in the development paradigm and emphasis is placed on efforts to decrease this vulnerability in a variety of sustainable ways. Biomedical technology is definitely one of the tools in these efforts. In the beginning of the pandemic the biomedical approach was important for the discovery of the virus and understanding its epidemiology. Later, stakeholders became involved. In the light of absence of treatment or vaccines, the development paradigm became more important and the two approaches were more in balance. However, since the reports about effective treatment of AIDS and hope of development of vaccines, the biomedical paradigm has become a leading principle in many HIV/AIDS prevention programmes. There is a need for a better balance between the two paradigms. Especially in developing countries, where it is not realistic to think that sustainable biomedical interventions can be organized on a short-term basis, it would be counterproductive to base our efforts to deal with HIV/AIDS exclusively on the biomedical approach. PMID:10743300
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
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.
Dogs were immunized i.m. with attenuated poxvirus vaccines (vaccinia virus, Orf-virus) and a bovine herpesvirus-1 (BHV-1) vaccine. After intradermal (i.d.) application of the vaccine viruses a specific delayed type hypersensitivity (DTH) reaction of the skin occurred only with vaccinia virus. The i.d. application of Orf-virus caused a short-term, non-specific inflammatory reaction of the skin, even in dogs not immunized with Orf-virus. Out of 30 sera from Orf-virus immunized beagles (n = 4) only eight were found reactive to Orf-virus in a competition ELISA. Three sera from dogs not Orf-virus immunized but skin-tested with the virus contained low antibody titers. Using indirect immunofluorescence (IIF) in flow cytometry, the existence of Orf-virus antigens was examined on the surface and in the cytoplasm of permissive (BFK and Vero)- and questionable permissive MDCK cells. The canine kidney MDCK cell line was found to be non-permissive for Orf-virus replication; the occurrence of an Orf-(ecthyma contagiosum) like disease in dogs is unlikely.
BARBIERI, M.; CAPRI, S.; WAURE, C. DE; BOCCALINI, S.; PANATTO, D.
2017-01-01
Summary Introduction Nowadays, four different types of influenza vaccines are available in Italy: trivalent (TIV), quadrivalent (QIV), MF59-adjuvanted (aTIV) and intradermal TIV (idTIV) inactivated vaccines. Recently, a concept of the appropriateness (i.e. according to the age and risk factors) of the use of different vaccines has been established in Italy. We conducted a budget impact analysis of switching to a policy, in which the Italian elderly (who carry the major disease burden) received the available vaccines according to their age and risk profile. Methods A novel budget impact model was constructed with a time horizon of one influenza season. In the reference scenario the cohort of Italian elderly individuals could receive either available vaccine according to 2017/18 season market share. The alternative scenario envisaged the administration of TIV/QIV to people aged 65-74 years and at low risk of developing influenza-related complications, while aTIV/idTIV were allocated to high-risk 65-74-year-olds and all subjects aged ≥ 75 years. Results Switching to the alternative scenario would result in both significant health benefits and net budget savings. Particularly, it would be possible to prevent an additional 8201 cases of laboratory-confirmed influenza, 988 complications, 355 hospitalizations and 14 deaths. Despite the alternative strategy being associated with slightly higher vaccination costs, the total savings derived from fewer influenza events completely resets this increase with net budget savings of € 0.13 million. Conclusions An immunization policy in which influenza vaccines are administered according to the age and risk profile of Italian elderly individuals is advisable. PMID:29707658
Barbieri, M; Capri, S; Waure, C DE; Boccalini, S; Panatto, D
2017-12-01
Nowadays, four different types of influenza vaccines are available in Italy: trivalent (TIV), quadrivalent (QIV), MF59-adjuvanted (aTIV) and intradermal TIV (idTIV) inactivated vaccines. Recently, a concept of the appropriateness (i.e. according to the age and risk factors) of the use of different vaccines has been established in Italy. We conducted a budget impact analysis of switching to a policy, in which the Italian elderly (who carry the major disease burden) received the available vaccines according to their age and risk profile. A novel budget impact model was constructed with a time horizon of one influenza season. In the reference scenario the cohort of Italian elderly individuals could receive either available vaccine according to 2017/18 season market share. The alternative scenario envisaged the administration of TIV/QIV to people aged 65-74 years and at low risk of developing influenza-related complications, while aTIV/idTIV were allocated to high-risk 65-74-year-olds and all subjects aged ≥ 75 years. Switching to the alternative scenario would result in both significant health benefits and net budget savings. Particularly, it would be possible to prevent an additional 8201 cases of laboratory-confirmed influenza, 988 complications, 355 hospitalizations and 14 deaths. Despite the alternative strategy being associated with slightly higher vaccination costs, the total savings derived from fewer influenza events completely resets this increase with net budget savings of € 0.13 million. An immunization policy in which influenza vaccines are administered according to the age and risk profile of Italian elderly individuals is advisable.
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.
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.
... advised. Click on any image to enlarge it. Images of People Affected by the Disease Chickenpox in ... vaccinated child. Courtesy of Varicella Active Surveillance Project Images of Varicella Zoster Virus PHIL Photo ID# 2791 ...
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
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.
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
Background Speed Leish K® is used as a serological screening test for Leishmania infection prior to vaccination. Limited comparative serological studies with Speed Leish K® have been performed. The aim of this study was to evaluate the diagnostic performance of four commercially available serologic tests including ELISAs (Leiscan®, ID Screen® and Leishmania 96®), a rapid test (Speed Leish K®) and an in-house IFAT for the detection of specific antibodies against Leishmania infantum antigen in dogs in different states of infection. Methods Sick infected dogs (n = 36), healthy infected dogs (n = 18), L. infantum seropositive dogs with low to high levels of antibodies (n = 53), dogs seropositive to other pathogens (to evaluate cross reaction) (n = 14) and uninfected dogs from a non-endemic area (n = 50) and from an endemic area (n = 32) were analysed by the serological methods mentioned above. Results The sensitivity was as follows: ID Screen® (0.953), Leiscan® and Leishmania 96® (0.925), IFAT (0.869) and Speed Leish K® (0.636). The maximum specificity (1.000) was attained for all diagnostic tests except the Leishmania 96® (0.896) and IFAT (0.917). The accuracy was as follows: ID Screen® (0.975), Leiscan® (0.961), Leishmania 96® (0.911), IFAT (0.892) and Speed Leish K® (0.808). In relation to the area under the ROC curve (AUC-ROC), the maximum value was attained with the ID Screen® (0.993) closely followed by Leiscan® (0.990), then, Leishmania 96® (0.962), IFAT (0.926) and Speed Leish K® (0.818). For the Kappa index, the best result was obtained by the ID Screen® (0.951) followed by Leiscan® (0.921), Leishmania 96® (0.822), IFAT (0.783) and Speed Leish K® (0.622). Statistically significant differences were found between the AUC-ROC of quantitative serological tests and the only qualitative rapid test evaluated. There were also statistically significant differences between AUC-ROC of the ELISAs (ID Screen® and Leiscan®) and IFAT. Conclusions Leiscan® and ID Screen® had superior diagnostic performance measures than IFAT and all quantitative serological tests were superior when compared to Speed Leish K®. Thus, Speed Leish K® may be considered a less valuable screening test prior to vaccination as it may result in vaccination of seropositive dogs and in some cases seropositive sick dogs. PMID:24655335
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
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.
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
cancer cell line ID8-T. Using an orthotopic ID8-T tumor model in syngeneic mice, we have demonstrated that intraperitoneal delivery of a CXCR4...infiltration of CD8+ T cells and IL-12 cytokine-expressing tumor associated macrophages with concomitant inhibition of the immunosuppressive network. We...vaccines and adoptively-transferred T cells . 15. SUBJECT TERMS 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES 19a
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.
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.
Vaccines for early-life immunization are a crucial biomedical intervention to reduce global morbidity and mortality, yet their developmental path has been largely ad hoc, empiric, and inconsistent. Immune responses of human newborns and infants are distinct and cannot be predicted from those of human adults or animal models. Therefore, understanding and modeling age-specific human immune responses will be vital to the rational design and development of safe and effective vaccines for newborns and infants. PMID:21734174
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…
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.
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
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).
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.
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
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.
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).
Simmons, Jonathan; Marston, Jeremy; Fisher, Paul; Broderick, Kate
2017-11-01
Needle-free methods of drug delivery circumvent the drawbacks associated with the use of hypodermic needles such as needle-stick injuries, needle-phobia, cross contamination and disposal. Furthermore, pioneering DNA-based vaccines that aim to treat cancer and fight infectious diseases, such as HIV, Ebola and Zika, require precise deposition into the skin to target the immune response producing cells found only in the epidermis and dermis. Intradermal (ID) delivery can be achieved using a needle and the Mantoux technique but this requires a highly skilled technician and so extensive use of DNA vaccines calls for an alternative method of delivery. One option is jet injection which has been employed in mass vaccination programs for intramuscular or subcutaneous delivery and is used by some diabetic patients to inject insulin. In this talk I will present results from our ongoing ex-vivo experimental study into ID jet injection. Ultra-high-speed imaging is used to visualize the process of the jet exiting the nozzle and striking excised skin. A skin bleb grows as liquid is deposited within the skin. I will discuss how the control parameters, such as the rheological profile of the liquid and the stand-off distance, influence the volume of liquid successfully delivered intradermally.
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
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.
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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
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'.
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
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.
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.
Firbas, Christa; Boehm, Thomas; Buerger, Vera; Schuller, Elisabeth; Sabarth, Nicolas; Jilma, Bernd; Klade, Christoph S
2010-03-11
An effective vaccine would be a significant progress in the management of chronic HCV infections. This study was designed to examine whether different application schedules and injection routes may enhance the immunogenicity of the HCV peptide vaccine IC41. In this randomized trial 54 healthy subjects received either subcutaneous (s.c.) or intradermal (i.d.) vaccinations weekly (16 injections) or every other week (8 injections). One group additionally received imiquimod, an activator of the toll-like receptor (TLR) 7. The T cell epitope-specific immune response to IC41 was assessed using [(3)H]-thymidine CD4+ T cell proliferation, interferon-gamma (IFN-gamma) CD8+ and CD4+ ELIspot and HLA-A*0201 fluorescence-activated cell sorting (FACS) tetramer-binding assays. More than 60% of vaccinees responded in the CD4+ T cell proliferation assay in all groups. An HLA-A*0201 FACS tetramer-binding assay and IFN-gamma CD8+ ELIspot class I response of more than 70% was induced in four and three groups, respectively. IC41 induced significant immunological responses in all groups with responder rates of up to 100%. Interestingly, topical imiquimod was not able to enhance immunogenicity but was associated with a lower immune response. Local injection site reactions were mostly transient. Intradermal injections caused more pronounced reactions compared to s.c., especially erythema and edema. Compared to a previous study intensified dosing and/or i.d. injections enhanced the response rates to the vaccine IC41 in three assays measuring T cell function. Immunization with IC41 was generally safe in this study. These results justify testing IC41 in further clinical trials with HCV-infected individuals.
Piedrafita, David; Preston, Sarah; Kemp, Joanna; de Veer, Michael; Sherrard, Jayne; Kraska, Troy; Elhay, Martin; Meeusen, Els
2013-01-01
It has recently been recognised that vaccine adjuvants play a critical role in directing the nature of a vaccine induced effector response. In the present study, several adjuvants were evaluated for their ability to protect sheep after field vaccination with the larval-specific Haemonchus contortus antigen, HcsL3. Using a suboptimal antigen dose, aluminium adjuvant was shown to reduce the cumulative faecal egg counts (cFEC) and worm burden by 23% and 25% respectively, in agreement with a previous study. The addition of Quil A to the aluminium-adjuvanted vaccine brought cFEC back to control levels. Vaccination with the adjuvant DEAE-dextran almost doubled the protection compared to the aluminium-adjuvanted vaccine resulting in 40% and 41% reduction in cFEC and worm counts compared to controls. Examination of skin responses following i.d. injection of exsheathed L3, revealed that cFEC was negatively correlated with wheal size and tissue eosinophils for the DEAE-dextran and aluminium-adjuvanted groups respectively. These studies have for the first time shown the potential of DEAE-dextran adjuvant for helminth vaccines, and discovered significant cellular correlates of vaccine-induced protection.
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
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.
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.
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
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.
Bryan, J P; Sjogren, M H; Macarthy, P; Cox, E; Legters, L J; Perine, P L
1992-01-01
To determine the duration of antibody after low-dose, intradermal (i.d.), plasma-derived hepatitis B vaccination and the response to a booster dose, we studied two classes of medical students who were immunized with 2 micrograms doses i.d. In one class, 73/88 (85%) who had been immunized by skilled personnel at 0, 1 and 6 months, had protective concentrations (greater than or equal to 10 mIU ml-1) of anti-HBs at 20 months after the first dose. Twelve (92%) out of 13 students who received only two doses at 0 and 1 months also had protective concentrations at month 20. At month 27, 11/16 (69%) with antibody less than or equal to 10 mIU ml-1 responded to a fourth dose of 2 micrograms i.d. with protective concentrations of anti-HBs. In the second class, after three doses of vaccine at 0, 1, and 6 months, protective concentrations of anti-HBs were present in 90/93 (97%) at 14 months and in 71/80 (89%) at 25 months. In those who received only two doses, protective concentrations were found in 24/31 (74%) at 14 months and 9/16 (56%) at 25 months. After a booster dose of 2 micrograms i.d. at month 25, anti-HBs concentrations rose from a geometric mean of 78 to 1198 mIU ml-1 in 60 subjects previously immunized with three doses and from 18 to 1054 mIU ml-1 in 16 students previously immunized with only two doses. Overall, 73/76 (96%) of students in the second group had protective concentrations of antibody after the booster dose.(ABSTRACT TRUNCATED AT 250 WORDS)
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
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.
Within the framework of the ESRF Phase I Upgrade Programme, a new state-of-the-art synchrotron beamline ID16B has been recently developed for hard X-ray nano-analysis. The construction of ID16B was driven by research areas with major scientific and societal impact such as nanotechnology, earth and environmental sciences, and bio-medical research. Based on a canted undulator source, this long beamline provides hard X-ray nanobeams optimized mainly for spectroscopic applications, including the combination of X-ray fluorescence, X-ray diffraction, X-ray excited optical luminescence, X-ray absorption spectroscopy and 2D/3D X-ray imaging techniques. Its end-station re-uses part of the apparatus of the earlier ID22 beamline, while improving and enlarging the spectroscopic capabilities: for example, the experimental arrangement offers improved lateral spatial resolution (∼50 nm), a larger and more flexible capability for in situ experiments, and monochromatic nanobeams tunable over a wider energy range which now includes the hard X-ray regime (5–70 keV). This paper describes the characteristics of this new facility, short-term technical developments and the first scientific results. PMID:26698084
Piedrafita, David; Preston, Sarah; Kemp, Joanna; de Veer, Michael; Sherrard, Jayne; Kraska, Troy; Elhay, Martin; Meeusen, Els
2013-01-01
It has recently been recognised that vaccine adjuvants play a critical role in directing the nature of a vaccine induced effector response. In the present study, several adjuvants were evaluated for their ability to protect sheep after field vaccination with the larval-specific Haemonchus contortus antigen, HcsL3. Using a suboptimal antigen dose, aluminium adjuvant was shown to reduce the cumulative faecal egg counts (cFEC) and worm burden by 23% and 25% respectively, in agreement with a previous study. The addition of Quil A to the aluminium-adjuvanted vaccine brought cFEC back to control levels. Vaccination with the adjuvant DEAE-dextran almost doubled the protection compared to the aluminium-adjuvanted vaccine resulting in 40% and 41% reduction in cFEC and worm counts compared to controls. Examination of skin responses following i.d. injection of exsheathed L3, revealed that cFEC was negatively correlated with wheal size and tissue eosinophils for the DEAE-dextran and aluminium-adjuvanted groups respectively. These studies have for the first time shown the potential of DEAE-dextran adjuvant for helminth vaccines, and discovered significant cellular correlates of vaccine-induced protection. PMID:24205209
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.
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
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.
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
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.
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
This review will summarize advances in swine genomics and how it has altered approaches for swine disease and vaccination research. The swine has been a major biomedical model species, for transplantation, heart disease, allergies and asthma, as well as normal neonatal development and reproductive p...
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/.
vaccines and the prevention of myriad diseases to the most recent advances in molecular medicine, federally funded biomedical research saves lives...affecting the study of autism , asthma and cancer research.” — Assistant Professor from the Public Health Research Institute in New Jersey “The poor
Parents of children with autism have played a prominent role in controversies surrounding this condition. Parental voices were critical in challenging the "refrigerator mother" theory and more recently have attracted public attention for claims that autism may be caused by childhood vaccinations and that "unorthodox biomedical" treatments may…
Vaccination is considered one of the most efficient and cost-effective public health policies most used in the control and prevention of disease. However, it is also one of the most polemic and controversial biomedical techniques, making it difficult to avoid an ethical dilemma, especially when vaccination is compulsory for the entire population. Indeed, since vaccines are not totally effective and safe, there is an ethical conflict between the individual and the collective interest, because children effectively carry the burden of vaccination for the benefit of public health when they are affected with serious adverse reactions and do not benefit from the care that should be offered by the government. The objective of this article was to demonstrate that the tools of bioethics are relevant in this discussion to understand and analyze these dilemmas critically by providing convincing arguments to underpin the development of biopolitics that consider prevention not only rigorously, but also the joint responsibility of all as fundamental for individual and collective protection.
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
The growing evidence base for biomedical HIV prevention interventions – such as oral pre-exposure prophylaxis, microbicides, male circumcision, treatment as prevention, and eventually prevention vaccines – has given rise to concerns about the ways in which users of these biomedical products may adjust their HIV risk behaviors based on the perception that they are prevented from infection. Known as risk compensation, this behavioral adjustment draws on the theory of “risk homeostasis,” which has previously been applied to phenomena as diverse as Lyme disease vaccination, insurance mandates, and automobile safety. Little rigorous evidence exists to answer risk compensation concerns in the biomedical HIV prevention literature, in part because the field has not systematically evaluated the study designs available for testing these behaviors. The goals of this Commentary are to explain the origins of risk compensation behavior in risk homeostasis theory, to reframe risk compensation as a testable response to the perception of reduced risk, and to assess the methodological rigor and ethical justification of study designs aiming to isolate risk compensation responses. Although the most rigorous methodological designs for assessing risk compensation behavior may be unavailable due to ethical flaws, several strategies can help investigators identify potential risk compensation behavior during Phase II, Phase III, and Phase IV testing of new technologies. Where concerns arise regarding risk compensation behavior, empirical evidence about the incidence, types, and extent of these behavioral changes can illuminate opportunities to better support the users of new HIV prevention strategies. This Commentary concludes by suggesting a new way to conceptualize risk compensation behavior in the HIV prevention context. PMID:23597916
Peripheral blood CD14+ monocytes from multiple myeloma (MM) patients can be induced to differentiate into fully functional, mature, CD83+ dendritic cells (DCs) which are highly efficient in priming autologous T lymphocytes in response to the patient-specific tumor idiotype (Id). We have recently scaled up our manufacturing protocol for application in a phase I-II clinical trial of anti-Id vaccination with DCs in MM patients. Elegible patients received a series of by-monthly immunizations consisting of three subcutaneous and two intravenous injections of Id-keyhole limpet hemocyanin (KLH)-pulsed DCs (5 x -, 10 x -, 50 x 10(6) cells and 10 x -, 50 x 10(6) cells, respectively). To generate DCs, monocytes were labeled with clinical grade anti-CD14 conjugates and positively selected by immunomagnetic separation. Cells were then cultured, according to Good Manufacturing Practice guidelines, in FCS-free medium in cell culture bags, and differentiated to DCs with GM-CSF plus IL-4 followed by TNF-alpha or, more recently, by a cocktail of IL-1beta, IL-6, TNF-alpha and prostaglandin-E2. Before maturation, Mo-DCs were pulsed with the autologous Id as whole protein or Id (VDJ)-derived HLA class I restricted peptides. Ten MM patients, who had been treated with two courses of high-dose chemotherapy with peripheral blood stem cell support, entered into the clinical study. CD14+ monocytes were enriched from 16.1+/-5.7% to 95.5+/-3.2% (recovery 67.9+/-15%, viability > 97%). After cell culture, phenotypic analysis showed that 89.6+/-6.6% of the cells were mature DCs. We obtained 2.89+/-1 x 10(8) DCs/leukapheresis which represented 24.5+/-9% of the initial number of CD14+ cells. Notably, the cytokine cocktail induced a significantly higher percentage and yield (31+/-10.9 of initial CD14+ cells) of DCs than TNF-alpha alone, secretion of larger amounts of IL-12, potent stimulatory activity on allogeneic and autologous T cells. Storage in liquid nitrogen did not modify the phenotype or functional characteristics of pre-loaded DCs. The recovery of thawed, viable DCs, was 78+/-10%. Thus, positive selection of CD14+ monocytes allows the generation of a uniform population of mature pre-loaded DCs which can be cryopreserved with no effects on phenotype and function and are suitable for clinical trials. Based on these results, a DCs-based phase II trial of anti-Id vaccination with VDJ-derived HLA class I-restricted peptides and KLH is underway for lymphoma patients.
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.
Funding for biomedical research has shifted from government to the private sector. One reason is rapid expansion in the number and strength of U.S. biotechnology companies, which collectively spend more than $6 billion a year on biomedical research. Most of these companies are not yet profitable and therefore depend on flows of capital from private investors, Wall Street, and large pharmaceutical company collaborations. Investment in the new drugs, devices, and vaccines in this pipeline is sensitive to signals emanating from the debate on health care reform, suggesting that new federal policy will have a major impact on steering the type of innovation to emerge in the future.
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
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.
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.
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.
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
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.
2011-01-01
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
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.
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.
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
In this study, we constructed recombinant plasmid pcDNA3.1/P12X3C3D including P1, 2A, 3C, 3D and part of 2B gene of FMDV and pcDNA3.1/IFN containing the gene encoding bovine IFN-alpha. We inoculated the DNA vaccine pcDNA3.1/P12X3C3D with or without pcDNA3.1/IFN to evaluate the efficiency of this DNA vaccine and the immunogenicity of DNA vaccine enhanced by the co-delivery with pcDNA3.1/IFN. After two times of vaccination with DNA vaccine, all of guinea pigs were challenged with 103 ID50 FMDV type O. Anti-FMDV antibody levels were detected by ELISA and T lymphocyte proliferation response was tested by MTT assay. The result shows that guinea pigs inoculated by pcDNA3.1/P12X3C3D alone or with pcDNA3.1/IFN generated specific antibodies and induced an FMDV-specific T lymphocyte proliferation response. FMDV challenge tests showed that one in four guinea pigs immunized by pcDNA3.1/P12X3C3D with pcDNA3.1/IFN was protected from the FMDV serotype O infection. This result indicated that the efficiency of the DNA vaccine was enhanced by co-delivery with pcDNA3.1/IFN. However, the protection rate was considerably lower than that immunized with conventional FMD vaccine.
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).
A project for the production of radiovaccines and other bio-medical products is presented which includes a radiation facility provided with a gamma ray source equivalent to 100,000 Ci of Co-60. The whole process incorporates novel basic features in virus production and inactivation steps. The former is carried out in animals previously subjected to immunodepression through electromagnetic radiation. The later is obtained at low temperatures by using either electromagnetic or particle radiations. A vaccine manufacture process is shown to illustrate the utilization of ionizing radiations to obtain a foot and mouth disease virus (FMDV) vaccine with good antigenic quality and low cost.
Pfister, G; Herndler-Brandstetter, D; Grubeck-Loebenstein, B
2006-06-01
The public health of our society is challenged by a continuous increase in life expectancy. Hence, biomedical aging research is enjoying a steadily increasing popularity but also enlightens our understanding of age-related diseases by a number of striking results from basic research. One of the most striking changes that occurs during normal human aging is an overall diminution of immune functions, a phenomenon often termed immunosenescence. Starting from some highly exciting examples from basic immunological research, this article sheds light on which impact normal human aging has on several immune defence mechanisms. In addition, clinical consequences in view of Alzheimer's disease, immunogenicity of vaccines and autoimmune diseases are discussed.
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
To measure parent knowledge levels and opinions related to the human papillomavirus (HPV) and the two vaccines used to prevent it. To measure parent behavior in terms of whether or not to have their children vaccinated. Between June 19, 2012, and August 24, 2012, questionnaires were distributed to parents while waiting for their child to see their pediatrician at a local group practice. The survey was reviewed for face validity by College of Pharmacy social science and clinical faculty members, and an earlier version of it had been used successfully in a published study of biomedical students' knowledge of and attitudes toward the HPV vaccine. 129 usable surveys were obtained. 48.1% of subjects said they learned about the HPV vaccines from the media, while 47.3% identified health care practitioner(s) as a source of knowledge. The mean score on a 20-item knowledge test regarding the infection and vaccines was 36% (range 0-80%). Opinions on the subject varied widely. For example, 22.4% of subjects agreed that schools should require that students be vaccinated before enrolling, while 3.2% agreed that vaccination causes patients to become sexually active. Subjects reported vaccination status for 253 children (mean age 13) as follows: 33% vaccinated; 28% not vaccinated but will be; 11% will never be vaccinated; and 28% not decided. These results are somewhat encouraging, because many parents are hearing about the vaccines from their providers. Although not an equally valid source, the media are also raising awareness. Based on the knowledge and opinion results of this study, there is a need for pharmacists and other providers to educate their patients about the vaccines and the virus and to converse with them regarding the moral and psychological implications of vaccination. Still, it is encouraging that these subjects had or plan to have over half (61%) of their children vaccinated.
peptides, anti-idiotypes, vaccines, 06 03 human immunodeficiency virus, chimpanzees, RAI, Virology, 06 13 HTLV III, Immunology 19. ABSTRACT (Continue on...idiotypes (anti-Id for con- trolling HIV infection. We have identified four regions of the human immunodeficiency virus type I HIV-1 envelope glycoprotein...analogous to amino acid sequences from the feline leukemia virus / transmembrane glycoprotein. Studies have utilized an affinity purified chimpanzee anti
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
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
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
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.
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.
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
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.
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.
Rotheram-Borus, Mary Jane; Swendeman, Dallas; Chovnick, Gary
2010-01-01
In the past 25 years, the field of HIV prevention research has been transformed repeatedly. Today, effective HIV prevention requires a combination of behavioral, biomedical, and structural intervention strategies. Risk of transmitting or acquiring HIV is reduced by consistent male and female-condom use, reductions in concurrent and/or sequential sexual and needle-sharing partners, male circumcision, and treatment with antiretroviral medications. At least 144 behavioral prevention programs have been found effective in reducing HIV transmission acts; however, scale up of these programs has not occurred outside of the United States. A series of recent failures of HIV-prevention efficacy trials for biomedical innovations such as HIV vaccines, treating herpes simplex 2 and other sexually transmitted infections, and diaphragm and microbicide barriers highlights the need for behavioral strategies to accompany biomedical strategies. This challenges prevention researchers to reconceptualize how cost-effective, useful, realistic, and sustainable prevention programs will be designed, delivered, tested, and diffused. The next generation of HIV prevention science must draw from the successes of existing evidence-based interventions and the expertise of the market sector to integrate preventive innovations and behaviors into everyday routines. PMID:19327028
The NASA Lewis Research Center in cooperation with the World Health Organization, U.S.A. I.D., the Pan American Health Organization and national government agencies in some developing countries sponsored the installation of twenty photovoltaic powered medical vaccine storage refrigerator-freezer (R/F) systems. The Solar Power Corporation was selected as the contractor to perform the design, development and installation of these twenty units. Solar Power's experiences are described herein.
A major branch of glycobiology and glycan-focused biomedicine studies the interaction between carbohydrates and other biopolymers, most importantly, glycan-binding proteins. Today, this research into glycan-biopolymer interaction is unthinkable without glycan arrays, tools that enable high-throughput analysis of carbohydrate interaction partners. Glycan arrays offer many applications in basic biochemical research, for example, defining the specificity of glycosyltransferases and lectins such as immune receptors. Biomedical applications include the characterization and surveillance of influenza strains, identification of biomarkers for cancer and infection, and profiling of immune responses to vaccines. Here, we review major applications of glycan arrays both in basic and applied research. Given the dynamic nature of this rapidly developing field, we focus on recent findings.
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
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.
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
HIV-1 DNA vaccines have many advantageous features. Evaluation of HIV-1 vaccine candidates often starts in small animal models before macaque and human trials. Here, we selected and optimized DNA vaccine candidates through systematic testing in rabbits for the induction of broadly neutralizing antibodies (bNAb). We compared three different animal models: guinea pigs, rabbits and cynomolgus macaques. Envelope genes from the prototype isolate HIV-1 Bx08 and two elite neutralizers were included. Codon-optimized genes, encoded secreted gp140 or membrane bound gp150, were modified for expression of stabilized soluble trimer gene products, and delivered individually or mixed. Specific IgG after repeated i.d. inoculations with electroporation confirmed in vivo expression and immunogenicity. Evaluations of rabbits and guinea pigs displayed similar results. The superior DNA construct in rabbits was a trivalent mix of non-modified codon-optimized gp140 envelope genes. Despite NAb responses with some potency and breadth in guinea pigs and rabbits, the DNA vaccinated macaques displayed less bNAb activity. It was concluded that a trivalent mix of non-modified gp140 genes from rationally selected clinical isolates was, in this study, the best option to induce high and broad NAb in the rabbit model, but this optimization does not directly translate into similar responses in cynomolgus macaques.
HIV-1 DNA vaccines have many advantageous features. Evaluation of HIV-1 vaccine candidates often starts in small animal models before macaque and human trials. Here, we selected and optimized DNA vaccine candidates through systematic testing in rabbits for the induction of broadly neutralizing antibodies (bNAb). We compared three different animal models: guinea pigs, rabbits and cynomolgus macaques. Envelope genes from the prototype isolate HIV-1 Bx08 and two elite neutralizers were included. Codon-optimized genes, encoded secreted gp140 or membrane bound gp150, were modified for expression of stabilized soluble trimer gene products, and delivered individually or mixed. Specific IgG after repeated i.d. inoculations with electroporation confirmed in vivo expression and immunogenicity. Evaluations of rabbits and guinea pigs displayed similar results. The superior DNA construct in rabbits was a trivalent mix of non-modified codon-optimized gp140 envelope genes. Despite NAb responses with some potency and breadth in guinea pigs and rabbits, the DNA vaccinated macaques displayed less bNAb activity. It was concluded that a trivalent mix of non-modified gp140 genes from rationally selected clinical isolates was, in this study, the best option to induce high and broad NAb in the rabbit model, but this optimization does not directly translate into similar responses in cynomolgus macaques. PMID:26344115
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.
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.
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.
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
In this paper, we describe a histological ontology of the human cardiovascular system developed in collaboration among histology experts and computer scientists. The histological ontology is developed following an existing methodology using Conceptual Models (CMs) and validated using OOPS!, expert evaluation with CMs, and how accurately the ontology can answer the Competency Questions (CQ). It is publicly available at http://bioportal.bioontology.org/ontologies/HO and https://w3id.org/def/System . The histological ontology is developed to support complex tasks, such as supporting teaching activities, medical practices, and bio-medical research or having natural language interactions.
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.
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
biodefense. For example, USAMRIID researchers are using Dovis to initiate drug discovery efforts against the ricin A-chain toxin and the Ebola virus...in host cell invasion and bacterial toxin production). Traditional experimental methods to determine the functions of proteins encoded in genomic...readily modeled. A second study involved determining the pro- tein structure of VP24, the smallest protein in the Ebola and Marburg virus genomes.9
Biomedical globalization is a reality in the presence of local worlds with growing human sufferance and inequalities. In this structural and cultural context, characterised by the new communication by Internet and social media, polarisation of medical and scientific debate is enhancing. Based on episodes related to public health issues like vaccines, the quest for better access of Italian professionals and public opinion to an open scientific debate on health research and practice is discussed.
Douglas Lowy, M.D., and John Schiller, Ph.D., of CCR’s Laboratory of Cellular Oncology have received the 2017 Lasker~DeBakey Clinical Medical Research Award for their groundbreaking research leading to the development of human papillomavirus (HPV) vaccines. The Lasker Awards are widely regarded as the country’s most prestigious biomedical research prizes.
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.
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.
In Bolivia, workshops serve as a means for biomedical practitioners and Aymara and Quechua ethnomedical practitioners from the Andes to share information about illnesses. The traditional practitioners demonstrate and biomedical personnel participate in curing rituals. Joint therapy sessions and development of joint strategies to improve health are included. Participants list the names, symptoms, causes, and treatments of diarrhea in a column for ethnomedicine and another for biomedicine. Biomedical and ethnomedical practitioners work together to persuade indigenous peoples to overcome their fear of and resistance to vaccination. One way to achieve this is by having people examine unsterilized knives under the microscope to see the tetanus toxoid. Physicians tend not to respect midwives and traditional birth attendants (TBAs). Biomedical trainers are not trained in and/or undervalue ethnomedicine, and can introduce midwives and TBAs to unhealthy practices. For example, they insist on scissors to cut the umbilical cord, but scissors are hard to sterilize, resulting in increased rates of neonatal tetanus. Women trained in medical anthropology, cross-cultural communication, and public health are the best trainers of TBAs and midwives. Supervision is needed to integrate TBAs and midwives into health programs and to improve their skills. Herbalism and ritual healing are more popular than the rural health care delivery system. Integrated clinics attract more clients than standard clinics. Recommended guidelines on collaboration revolve around recognition and respect of traditional healers, rewards for biomedical and ethnomedical personnel who collaborate, and issuance of health cards so both sets of practitioners can view patients' medical histories.
The risk to die from an infectious disease in Germany has been continuously decreasing over the last century. Since infections are, however, not only causes of death but risk factors for diseases like cardiovascular diseases, it is essential to monitor and analyze their prevalence and frequency, especially in consideration of the increased life expectancy. To gain more knowledge about infectious diseases as risk factors and their implications on the condition and change of the immune status, the German National Cohort (GNC), a population-based prospective cohort study, will recruit 200,000 subjects between 2014 and 2017. In Pretest 1, a feasibility study for the GNC, we evaluated a self-administered and self-report questionnaire on infectious diseases and on the use of health care facilities (hereinafter called "ID Screen") for feasibility and validity. From August-November 2011, 435 participants between the ages of 20-69 completed the ID Screen. All subjects had been recruited via a random sample from the local residents' registration offices by 4 of the 18 participating study centers. The questionnaire encompasses 77 variables in six sections assessing items such as 12-month prevalence of infections, cumulative prevalence of infectious diseases, visit of health care facilities and vaccination. The feasibility was amongst others evaluated by assessing the completeness and comprehensiveness of the questionnaire. To assess the questionnaires ability to measure "immune status" and "susceptibility to infections", multivariate analysis was used. The overall practicability was good and most items were well understood, demonstrated by < 2/33 missing questions per questionnaire and only three variables: vaccination for influenza and pneumococci and infection with chickenpox had a frequency > 5 % of missing values. However, direct comparison of the items 12-month prevalence and lifetime prevalence of nephritis/pyelitis showed poor agreement and thereby poor understanding by 80 % of the participants, illustrating the necessity for a clear, lay person appropriate description of rare diseases to increase comprehensibility. The questionnaire will be used to support the assessment of immune dysfunction and frequency of infection. An analysis of these constructs in an exploratory factor analysis revealed limited applicability due to low interitem correlation (Cronbach's α < 0.5). This is corroborated by the extraction of more than one factor with a Kaiser-Meyer-Olkin measure of 0.6 instead of a unidimensional latent construct for "immune status". All in all, the ID Screen is a good and reliable tool to measure infectious diseases as risk factors and outcome in general, but requires a better translation of infection specific terms into lay person terms. For the assessment of the overall immune status, the tool has strong limitations. Vaccinations status should also rather be assessed based on vaccination certificates than on participants' recall.
An important influence on parents' decisions about pediatric vaccination (children under 6 years of age) is the attitude of their health care providers, including complementary and alternative medicine (CAM) providers. Very limited qualitative research exists, however, on how attitudes towards vaccination develop among healthcare professionals in-training. We explored perspective development among three groups of students: medical, chiropractic, and naturopathic. We conducted focus group sessions with participants from each year of study at three different healthcare training programs in Ontario, Canada. Semi-structured and open-ended questions were used to elicit dynamic interaction among participants and explore how they constructed their attitudes toward vaccination at the beginning and part way through their professional training. Analyses of verbatim transcripts of audiotaped interviews were conducted both inductively and deductively using questions structured by existing literature on learning, professional socialization and interprofessional relations. We found five major themes and each theme was illustrated with representative quotes. Numerous unexpected insights emerged within these themes, including students' general open-mindedness towards pediatric vaccination at the beginning of their training; the powerful influence of both formal education and informal socialization; uncritical acceptance of the vaccination views of senior or respected professionals; students' preference for multiple perspectives rather than one-sided, didactic instruction; the absence of explicit socio-cultural tensions among professions; and how divergences among professional students' perspectives result from differing emphases with respect to lifestyle, individual choice, public health and epidemiological factors-rather than disagreement concerning the biomedical evidence. This last finding implies that their different perspectives on pediatric vaccination may be complementary rather than irreconcilable. Our findings should be considered by developers of professional and interprofessional educational curricula and public health officials formulating policy on pediatric vaccination.
over the quality of combined feeds and the microclimate parameters, appropriate preparations of the production sectors, prevention of the " mastitis ...fact, still incomprehensible to us: We formed ah isolated farm out of young animals vaccinated when 5 months old. A year later, four cows aborted...had 27 unfavorable areas left, in which we hope to achieve recovery this year. The fact that up to 23 percent non-calving young cows are introduced
To investigate the association between the gene polymorphisms of angiotensin-converting enzyme (ACE) and digestive system cancer risk. A search was performed in Pubmed, Medline, ISI Web of Science and Chinese Biomedical (CBM) databases, covering all studies until Sep 1st, 2013. Statistical analysis was performed by using Revman5.2 and STATA 12.0. A total of 15 case-control studies comprising 2,390 digestive system cancer patients and 9,706 controls were identified. No significant association was found between the I/D polymorphism and digestive cancer risk (OR =0.93, 95%CI = (0.75, 1.16), P =0.53 for DD+DI vs. II). In the subgroup analysis by ethnicity and cancer type, no significant associations were found for the comparison of DD+DI vs. II. Results from other comparative genetic models also indicated a lack of associations between this polymorphism and digestive system cancer risks. This meta-analysis suggested that the ACE D/I polymorphism might not contribute to the risk of digestive system cancer.
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/).
Chitosan is a versatile polysaccharide of biological origin. Due to the biocompatible and biodegradable nature of chitosan, it is intensively utilized in biomedical applications in scaffold engineering as an absorption enhancer, and for bioactive and controlled drug release. In cancer therapy, chitosan has multifaceted applications, such as assisting in gene delivery and chemotherapeutic delivery, and as an immunoadjuvant for vaccines. The present review highlights the recent applications of chitosan and chitosan derivatives in cancer therapy.
Chitosan is a versatile polysaccharide of biological origin. Due to the biocompatible and biodegradable nature of chitosan, it is intensively utilized in biomedical applications in scaffold engineering as an absorption enhancer, and for bioactive and controlled drug release. In cancer therapy, chitosan has multifaceted applications, such as assisting in gene delivery and chemotherapeutic delivery, and as an immunoadjuvant for vaccines. The present review highlights the recent applications of chitosan and chitosan derivatives in cancer therapy. PMID:28346381
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.
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
Fry, Norman K; Campbell, Helen; Amirthalingam, Gayatri; Harrison, Timothy G; Mant, David; Harnden, Anthony
2014-01-01
Objective To estimate the prevalence and clinical severity of whooping cough (pertussis) in school age children presenting with persistent cough in primary care since the introduction and implementation of the preschool pertussis booster vaccination. Design Prospective cohort study (November 2010 to December 2012). Setting General practices in Thames Valley, UK. Participants 279 children aged 5 to 15 years who presented in primary care with a persistent cough of two to eight weeks’ duration. Exclusion criteria were cough likely to be caused by a serious underlying medical condition, known immunodeficiency or immunocompromise, participation in another clinical research study, and preschool pertussis booster vaccination received less than one year previously. Main outcome measures Evidence of recent pertussis infection based on an oral fluid anti-pertussis toxin IgG titre of at least 70 arbitrary units. Cough frequency was measured in six children with laboratory confirmed pertussis. Results 56 (20%, 95% confidence interval 16% to 25%) children had evidence of recent pertussis infection, including 39 (18%, 13% to 24%) of 215 children who had been fully vaccinated. The risk of pertussis was more than three times higher (21/53; 40%, 26% to 54%) in children who had received the preschool pertussis booster vaccination seven years or more previously than in those who had received it less than seven years previously (20/171; 12%, 7% to 17%). The risk of pertussis was similar between children who received five and three component preschool pertussis booster vaccines (risk ratio for five component vaccine 1.14, 0.64 to 2.03). Four of six children in whom cough frequency was measured coughed more than 400 times in 24 hours. Conclusions Pertussis can still be found in a fifth of school age children who present in primary care with persistent cough and can cause clinically significant cough in fully vaccinated children. These findings will help to inform consideration of the need for an adolescent pertussis booster vaccination in the United Kingdom. Study registration UK Clinical Research Network portfolio ID 8361. PMID:24961836
Bachelder, Eric M.; Beaudette, Tristan T.; Broaders, Kyle E.; Paramonov, Sergey E.; Dashe, Jesse; Fréchet, Jean M. J.
2009-01-01
Acid-degradable particles containing a model protein antigen, ovalbumin, were prepared from a polyurethane with acetal moieties embedded throughout the polymer, and characterized by dynamic light scattering and transmission electron microscopy. The small molecule degradation by-product of the particles was synthesized and tested in vitro for toxicity indicating an LC50 of 12,500 μg/ml. A new liquid chromatography-mass spectrometry technique was developed to monitor the in vitro degradation of these particles. The degradation by-product inside RAW macrophages was at its highest level after 24 hours of culture and was efficiently exocytosed until it was no longer detectable after four days. When tested in vitro, these particles induced a substantial increase in the presentation of the immunodominant ovalbumin-derived peptide SIINFEKL in both macrophages and dendritic cells. In addition, vaccination with these particles generated a cytotoxic T-lymphocyte response that was superior to both free ovalbumin and particles made from an analogous but slower-degrading acid-labile polyurethane polymer. Overall, we present a fully degradable polymer system with non-toxic by-products, which may find use in various biomedical applications including protein-based vaccines. PMID:18710254
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.
Varicella-zoster virus (VZV) causes chickenpox and reactivation of latent VZV causes herpes zoster (HZ). VZV reactivation is subject to the opposing mechanisms of declining and boosted VZV-specific cellular mediated immunity (CMI). A reduction in exogenous re-exposure ‘opportunities’ through universal chickenpox vaccination could therefore lead to an increase in HZ incidence. We present the first individual-based model that integrates within-host data on VZV-CMI and between-host transmission data to simulate HZ incidence. This model allows estimating currently unknown pivotal biomedical parameters, including the duration of exogenous boosting at 2 years, with a peak threefold to fourfold increase of VZV-CMI; the VZV weekly reactivation probability at 5% and VZV subclinical reactivation having no effect on VZV-CMI. A 100% effective chickenpox vaccine given to 1 year olds would cause a 1.75 times peak increase in HZ 31 years after implementation. This increase is predicted to occur mainly in younger age groups than is currently assumed. DOI: http://dx.doi.org/10.7554/eLife.07116.001 PMID:26259874
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
Increasing attention is being given to lipid nanocarriers (LNs) as drug delivery systems, due to the advantages offered of a higher biocompatibility and lower toxicity compared with polymeric nanoparticles. Many administration routes are being investigated for LNs, including topical, oral and parenteral ones. LNs are also proposed for specific applications such as cancer treatment, gene therapy, diagnosis and medical devices production. However, the high number of published research articles does not match an equal amount of patents. A recent Review of ours, published in Pharmaceutical Patent Analyst, reported the patents proposing novel methods for the production of LNs. This review work discusses recent patents, filed in 2007-2013 and dealing with the industrial applications of lipid-based nanocarriers for the vectorization of therapeutically relevant molecules, as well as biotech products such as proteins, gene material and vaccines, in the pharmaceutical, diagnostic and biomedical areas.
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
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.
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.
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
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.
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`).
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
Hotaling, Nathan A.; Tang, Li; Irvine, Darrell J.; Babensee, Julia E.
2016-01-01
Strategies to enhance, suppress, or qualitatively shape the immune response are of importance for diverse biomedical applications, such as the development of new vaccines, treatments for autoimmune diseases and allergies, strategies for regenerative medicine, and immunotherapies for cancer. However, the intricate cellular and molecular signals regulating the immune system are major hurdles to predictably manipulating the immune response and developing safe and effective therapies. To meet this challenge, biomaterials are being developed that control how, where, and when immune cells are stimulated in vivo, and that can finely control their differentiation in vitro. We review recent advances in the field of biomaterials for immunomodulation, focusing particularly on designing biomaterials to provide controlled immunostimulation, targeting drugs and vaccines to lymphoid organs, and serving as scaffolds to organize immune cells and emulate lymphoid tissues. These ongoing efforts highlight the many ways in which biomaterials can be brought to bear to engineer the immune system. PMID:26421896
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
Each year millions of nonhuman animals suffer in biomedical experiments for human health benefits. Clinical ethics demand that nonhuman animals are used in the development of pharmaceuticals and vaccines. Nonhuman animals are also used for fundamental biomedical research. Biomedical research that uses nonhuman animals is big business but the financial gains are generally occluded. This paper explores how such research generates profits and gains for those associated with the industry. Research establishments, scientists, laboratories, companies that sell nonhuman animal subjects, that supply equipment for the research, and corporations that market the resulting products are among those that benefit financially. Given the complex articulation of ethical codes, enormous corporate profits that are secured and personal returns that are made, the accepted moral legitimacy of such experiments is compromised. In order to address this, within the confines of the moral orthodoxy, more could to be done to ensure transparency and to extricate the vested financial interests from the human health benefits. But such a determination would not address the fundamental issues that should be at the heart of human actions in respect of the nonhuman animals who are used in experiments. The paper concludes with such an address by calling for an end to the denigration of nonhuman animals as experimental subjects who can be used as commodities for profit-maximisation and as tools in experiments for human health benefits, and the implementation of a more inclusive ethic that is informed by universal concern about the suffering of and compassion for all oppressed beings.
Bassey, Bassey; Abueidda, Abdallah; Cubbon, Grant; Street, Darin; Sabbir Ahmed, Asm; Wysokinski, Tomasz W.; Belev, George; Chapman, Dean
2014-07-01
High field superconducting wiggler beamlines present shielding challenges due to the high critical energy of the synchrotron spectrum. An unexpected, but predictable, weakness in the secondary optical enclosure (SOE-1) was discovered on the BioMedical Imaging and Therapy (BMIT) insertion device (ID) beamline 05ID-2 at the Canadian Light Source (CLS). SOE-1 is a monochromatic beam hutch; the beam in it is supplied by three monochromators housed in an upstream primary optical enclosure (POE-3). The initial shielding of SOE-1 was based on a shielding calculation against target scattered and direct monochromatic (fundamental and harmonics) beams from the monochromators in POE-3. During a radiation survey of the hutch, radiation above the expected level was measured at the downstream end of SOE-1. This increment in radiation level is attributed to scattered white beam into SOE-1 by a K-Edge subtraction (KES) monochromator's crystal (a single crystal monochromator) in POE-3. Though this is peculiar to the BMIT beamline 05ID-2, it may not be uncommon for other beamlines that use single crystal monochromators. Calculations of the level of expected leakage radiation due to the scattered white beam arriving on the downstream wall of the SOE-1 are presented, as well as the supplemental shielding that will reduce the leakage to less than 1 μSv/h as required at the CLS. Also presented are the installed supplemental shielding, and a comparison of the calculations and measurements of the dose rates on the back wall of SOE-1 End Wall, before and after installation of the supplemental shielding.
Bräuer-Krisch, E.; Nemoz, C.; Brochard, Th; Berruyer, G.; Renier, M.; Pouyatos, B.; Serduc, R.
2013-03-01
Microbeam Radiation Therapy (MRT) uses spatially a fractionated "white beam" (energies 50-350 keV) irradiation from a Synchrotron Source. The typical microbeams used at ID17 are 25-100μm-thick, spaced by 200-400μm, and carry extremely high dose rates (up to about 16 kGy/s). These microbeams are well tolerated by biological tissue, i.e. up to several hundred of Gy in the peaks. When valley doses, caused by Compton scattering in between two microbeams, remain within a dose regime similar to conventional RT, a superior tumour control can be achieved with MRT than with conventional RT. The normal tissue tolerance of these microscopically small beams is outstanding and well documented in the literature. The hypothesis of a differential effect in particular on the vasculature of normal versus tumoral tissue might best be proven by using large animal models with spontaneous tumors instead of small laboratory animals with transplantable tumors, an ongoing project on ID17. An alternative approach to deposit a high dose, while preserving the feature of the spatial separation of these microbeams outside the target has opened up new applications in preclinical research. The instrumentation of this method to produce such interlaced beams is presented with an outlook on the challenges to build a treatment platform for human patients. Dose measurements using Gafchromic films exposed in interlaced geometries with their steep profiles highlight the potential to deposit radiotoxic doses in the vicinity of radiosensitive tissues.
Tsunamis are caused by rapid sea floor displacement during earthquakes, landslides and large explosive eruptions in marine environment setting. Massive amounts of sea water in the form of devastating surface waves travelling hundreds of kilometers per hour have the potential to cause extensive damage to coastal infrastructures, considerable loss of life and injury and emergence of infectious diseases (ID). This study involved an extensive and systematic literature review of 50 research publications related to public health impact of the three most devastating tsunamis of the last 12 years induced by great earthquakes, namely the 2004 Sumatra-Andaman earthquake (moment magnitude Mw 9.2), the 2009 Samoa earthquake (Mw 8.1) and the 2011 Tōhoku (Japan) earthquake (Mw 9.0) in the Indian, Western Pacific and South Pacific Oceans respectively. The inclusion criteria were literature type comprising journal articles and official reports, natural disaster type including tsunamis induced only by earthquakes, population type including humans, and outcome measure characterized by disease incidence increase. The potential post-tsunami ID are classified into 11 groups including respiratory, pulmonary, wound-related, water-borne, skin, vector-borne, eye, fecal-oral, food-borne, fungal and mite-borne ID. Respiratory infections were detected after all the above mentioned tsunamis. Wound-related, skin and water-borne ID were observed after the 2004 and 2011 tsunamis, while vector-borne, fecal-oral and eye ID were observed only after the 2004 tsunami and pulmonary, food-borne and mite-borne ID were diagnosed only after the 2011 tsunami. Based on available age and genre data, it is concluded that the most vulnerable population groups are males, children (age ≤ 15 years) and adults (age ≥ 65 years). Tetanus and pneumonia are the deadliest post-tsunami ID. The detected risk factors include (1) lowest socioeconomic conditions, poorly constructed buildings and lack of prevention measures, (2) lack of awareness and prior warning resulting in little time for preparedness or evacuation, (3) severely injured tsunami survivors exposed to high pathogen densities in soil and water, (4) destruction of critical infrastructures including health care systems causing delayed management and treatment of severe cases, (5) aggravating post-tsunami weather conditions, (6) formation of extensive potential vector breeding sites due to flooding, (7) overcrowded conditions in evacuation shelters characterized by small places, inadequate air ventilation, poor hand hygiene and dysfunction of the public health system, (8) low vaccination coverage, (9) poor personal hygiene, (10) minimum precautions against food contamination and (11) dependency of young children and weaker physical strength and resilience of elders needing assistance with daily activities. In conclusion, our study referred to potential ID following tsunamis induced after great earthquakes during the last 12 years. The establishment of strong disaster preparedness plans characterized by adequate environmental planning, resistant infrastructures and resilient health facilities is significant for the early detection, surveillance and control of emerging ID. Moreover, the establishment and the unceasing function of reliable early warning systems may help mitigate tsunami-related impact on public health.
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
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.
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
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 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.
The growing interest of modeling human diseases using genetically modified (transgenic) nonhuman primates (NHPs) is a direct result of NHPs (rhesus macaque, etc.) close relation to humans. NHPs share similar developmental paths with humans in their anatomy, physiology, genetics, and neural functions; and in their cognition, emotion, and social behavior. The NHP model within biomedical research has played an important role in the development of vaccines, assisted reproductive technologies, and new therapies for many diseases. Biomedical research has not been the primary role of NHPs. They have mainly been used for safety evaluation and pharmacokinetics studies, rather than determining therapeutic efficacy. The development of the first transgenic rhesus macaque (2001) revolutionized the role of NHP models in biomedicine. Development of the transgenic NHP model of Huntington's disease (2008), with distinctive clinical features, further suggested the uniqueness of the model system; and the potential role of the NHP model for human genetic disorders. Modeling human genetic diseases using NHPs will continue to thrive because of the latest advances in molecular, genetic, and embryo technologies. NHPs rising role in biomedical research, specifically pre-clinical studies, is foreseeable. The path toward the development of transgenic NHPs and the prospect of transgenic NHPs in their new role in future biomedicine needs to be reviewed. This article will focus on the advancement of transgenic NHPs in the past decade, including transgenic technologies and disease modeling. It will outline new technologies that may have significant impact in future NHP modeling and will conclude with a discussion of the future prospects of the transgenic NHP model. PMID:24174443
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
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.
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
The aims of this research were to identify management practices that sheep farmers currently use to treat and prevent footrot in sheep and whether they consider that these are successful management tools and to find out how sheep farmers would ideally like to manage footrot in their flock. Over 90% of lameness in sheep in the UK is caused by Dichelobacter nodosus, which presents clinically as interdigital dermatitis (ID) alone or with separation of hoof horn (FR). A questionnaire was sent to 265 farmers to investigate their current management and their satisfaction with current management of the spectrum of clinical presentations of footrot. Farmers were also asked their ideal management of footrot and their interest in, and sources of information for, change. Approximately 160 farmers responded. Farmers satisfied with current management reported a prevalence of lameness < or = 5%. These farmers caught and treated lame sheep within 3 days of first seeing them lame, and treated sheep with FR and ID with parenteral antibacterials. Farmers dissatisfied with their management reported a prevalence of lameness >5%. These farmers practised routine foot trimming, footbathing and vaccination against footrot. Whilst 89% of farmers said they were satisfied with their management of FR over 34% were interested in changing management. Farmers identified veterinarians as the most influential source for new information. Farmers reported that ideally they would control FR by culling/isolating lame sheep, sourcing replacements from non-lame parents, trimming feet less, using antibacterial treatments less and using vaccination more. Footbathing was a commonly used management that was linked with dissatisfaction and that also was listed highly as an ideal management. Consequently, some of the ideal managements are in agreement with our understanding of disease control (culling and isolation, sourcing healthy replacements) but others are in contrast with our current knowledge of management and farmers self-reporting of satisfaction of management of footrot (less use of antibacterial treatment, more footbathing and vaccination). One explanation for this is the theory of cognitive dissonance where belief follows behaviour, i.e. farmers report that they believe an ideal which is what they are currently doing, even if the management is sub-optimal. Copyright 2010 Elsevier B.V. All rights reserved.
Following the highly successful inaugural meeting in 2012, the second installment of Virus-Like Particles and Nano-Particle Vaccines (VLPNPV), proved to be a worthy follow-up in an outstanding conference series. VLPNPV is a forum for academics and industry to address one of the major areas of need in biomedical sciences, the development of novel prophylactic and therapeutic vaccines. The conference was opened by Professor Marianne Manchester of the University of California, San Diego who pointed to the significance of the site chosen for the conference, the Salk Institute. Founded by Jonas Salk, the Salk Institute for Biological Studies is a non-profit, independent research institute with focuses in molecular biology and genetics, neurosciences, and plant biology. This diversity in research themes reflects the wishes of the institute's founder who saw value in using interdisciplinary approaches to understanding the basic principles in life, aimed at generating new therapies and treatments for human disease. Likewise, interdisciplinarity was reflected in the main themes of the meeting, which also highlight some of the potential advantages of virus-like particle (VLP) and nanoparticle vaccines, including novel formulations/adjuvanting effects, structurally accurate/designed antigens, production systems and capacity, and tailoring the immune response. These themes were covered by the 2 plenary sessions that opened the conference and are described in this report.
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
The aim of this study was to estimate the diagnostic value of different commercially available ELISA kits for the detection of bluetongue virus (BTV) antibodies in infected and vaccinated animals. The relative specificity of ELISA kits was evaluated using a panel of sera originating from healthy cattle, never vaccinated nor exposed to BTV. All ELISA kits applied had a high relative specificity (99.3 - 100%). The relative sensitivity of ELISA kits assessed using a panel of sera collected from BTV infected cattle was also high and similar for all the kits (97.3 - 100%). However, the relative sensitivity evaluated on the basis of testing vaccinated animals was different: the highest sensitivity was found for Ingenasa, PrioCHECK and ID VET ELISAs (96.5 - 98.3%). Slightly lower sensitivity was calculated for Pourquier and LSI kits (82.8% and 85.4%, respectively) and much lower sensitivity was found for VMRD ELISA kit (69.5%). The repeatability of BTV ELISA kits was expressed as a coefficient of variation (CV) of results of sera tested 5 times in the same day and in different days by the period of 2 months, by the same person, in the same conditions, and by using the same equipment. The CVs of sera tested in all ELISA kits ranged from 6.1 to 9.8% and were below 10% threshold adopted as a maximum for the acceptable repeatability of the method. In conclusion, it can be stated that the applied ELISA kits can be a valuable diagnostic tool for the serological monitoring studies in the BTV contaminated premises. All the methods are very specific and sensitive when testing BTV infected animals. Nevertheless, the Ingenasa and PrioCHECK can be the most useful in sero-surveillance of livestock following vaccination.
van Aalst, Mariëlle; Lötsch, Felix; Spijker, René; van der Meer, Jan T M; Langendam, Miranda W; Goorhuis, Abraham; Grobusch, Martin P; de Bree, Godelieve J
One quarter of HIV infections globally occur among young people 15-24 years of age and more than half of all new infections are to people younger than 25 years. Clearly, there is a need to identify and implement effective HIV prevention strategies among at-risk teens. Some of the most effective options for slowing the epidemic are biomedical and several promising methods are in development, including microbicides, vaccines, and pre-exposure prophylaxis (PREP) or the daily use of antiretrovirals to prevent the acquisition of HIV. There is widespread reluctance to enroll minors in such biomedical prevention trials due to concerns about vulnerability related to physical maturity, experiential maturity, and diminished autonomy as well as legal and social challenges that vary across and within nations. However, excluding minors from trials misses an important opportunity to evaluate the effectiveness, acceptability, and safety of innovative interventions under the best conditions for identifying and resolving potential problems. The challenges of including minors in HIV prevention trials are highlighted via the example of one rural South African community that has been particularly devastated by the HIV epidemic. PMID:17403499
One quarter of HIV infections globally occur among young people 15 to 24 years of age, and more than half of all new infections are in people younger than 25 years. Clearly, there is a need to identify and implement effective HIV prevention strategies among at-risk teens. Some of the most effective options for slowing the epidemic are biomedical, and several promising methods are in development, including microbicides, vaccines, and preexposure prophylaxis (PREP, or the daily use of antiretrovirals to prevent the acquisition of HIV). There is widespread reluctance to enroll minors in such biomedical prevention trials because of concerns about vulnerability related to physical maturity, experiential maturity, and diminished autonomy as well as legal and social challenges that vary across and within nations. However, excluding minors from trials misses an important opportunity to evaluate the effectiveness, acceptability, and safety of innovative interventions under the best conditions for identifying and resolving potential problems. The challenges of including minors in HIV prevention trials are highlighted through the example of one rural South African community that has been particularly devastated by the HIV epidemic.
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.
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
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.
The neuroendocrine and autonomic nervous systems are known regulators of brain-immune interaction. However, the functional significance of this interaction under stress is not fully understood. We investigated the effect of a stress paradigm by applying electric foot shock followed by three reminders, on behavior, immune parameters, and lymphoma tumor growth. Male C3H mice were divided into two groups: Group 1-exposed to electric foot shock followed by three reminders, and Group 2-untreated (controls). Sets of mice underwent the elevated plus maze, staircase, and hot plate tests. After foot shock, natural killer (NK) cell activity, and lymphocyte proliferation were measured. In addition, sets of mice were either vaccinated twice with B-cell lymphoma 38C-13 immunoglobulin for determination of anti-idiotype (Id) antibodies in sera, or inoculated with tumor cells and monitored for tumor development and survival time. Mice exposed to electric foot shock followed by the three reminders had higher NK cell activity, levels of anti-Id antibodies, and a higher proliferation rate of splenocytes in response to mitogens, than the control mice. The exposed mice also showed attenuated tumor growth. Thus, the stress paradigm inhibited tumor development and lead to some immune changes that were not accompanied by behavioral changes.
Salazar-Onfray, Flavio; Pereda, Cristián; Reyes, Diego; López, Mercedes N
2013-01-01
Here we summarize 10 years of effort in the development of a biomedical innovation with global projections. This innovation consists of a novel method for the production of therapeutic dendritic-like cells called Tumor Antigen Presenting Cells (TAPCells®). TAPCells-based immunotherapy was tested in more than 120 stage III and IV melanoma patients and 20 castration-resistant prostate cancer patients in a series of phase I and I/II clinical trials. TAPCells vaccines induced T cell-mediated memory immune responses that correlated with increased survival in melanoma patients and prolonged prostate-specific antigen doubling time in prostate cancer patients. Importantly, more than 60% of tested patients showed a Delayed Type Hypersensitivity (DTH) reaction against the lysates, indicating the development of anti-tumor immunological memory that correlates with clinical benefits. The in vitro analysis of the lysate mix showed that it contains damage-associated molecular patterns such as HMBG-1 protein which are capable to improve, through Toll-like receptor-4, maturation and antigen cross-presentation of the dendritic cells (DC). In fact, a Toll-like receptor-4 polymorphism correlates with patient clinical outcomes. Moreover, Concholepas concholepas hemocyanin (CCH) used as adjuvant proved to be safe and capable of enhancing the immunological response. Furthermore, we observed that DC vaccination resulted in a three-fold increase of T helper-1 lymphocytes releasing IFN-γ and a two-fold increase of T helper-17 lymphocytes capable of producing IL-17 in DTH+ with respect to DTH- patients. Important steps have been accomplished for TAPCells technology transfer, including patenting, packaging and technology assessment. Altogether, our results indicate that TAPCells vaccines constitute an exceptional Chilean national innovation of international value.
In this phase III, open-label, multicenter, and descriptive study in India, children primed with 3 doses (at ages 6, 10, and 14 weeks) of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) were randomized (1:1) to receive a booster dose at 9 to 12 (early booster) or 15 to 18 months old (late booster) in order to evaluate impact of age at booster. We also evaluated a 2-dose catch-up vaccination plus an experimental booster dose in unprimed children age 12 to 18 months. The early booster, late booster, and catch-up vaccinations were administered to 74, 95, and 87 children, respectively; 66, 71, and 81 children, respectively, were included in the immunogenicity according-to-protocol cohort. One month postbooster, for each PHiD-CV serotype, ≥95.2% (early booster) and ≥93.8% (late booster) of the children had antibody concentrations of ≥0.2 μg/ml; ≥96.7% and ≥93.0%, respectively, had opsonophagocytic activity (OPA) titers of ≥8. The postbooster antibody geometric mean concentrations (GMCs) were in similar ranges for early and late boosters; the OPA titers appeared to be lower for most PHiD-CV serotypes (except 6B and 19F) after the early booster. After dose 2 and postbooster, for each PHiD-CV serotype, ≥88.6% and ≥96.3%, respectively, of the catch-up immunogenicity according-to-protocol cohort had antibody concentrations of ≥0.2 μg/ml; ≥71.4% and ≥90.6%, respectively, had OPA titers of ≥8. At least 1 serious adverse event was reported by 2 children in the early booster (skin infection and gastroenteritis) and 1 child in the catch-up group (febrile convulsion and urinary tract infection); all were resolved, and none were considered by the investigators to be vaccine related. PHiD-CV induced robust immune responses regardless of age at booster. Booster vaccination following 2 catch-up doses induced robust immune responses indicative of effective priming and immunological memory. (These studies have been registered at www.clinicaltrials.gov under registration no. NCT01030822 and NCT00814710; a protocol summary is available at www.gsk-clinicalstudyregister.com [study ID 112909]). PMID:25008901
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.
Schmid, Esther F; Ashkenazy, Rebecca; Merson, James; Smith, Dennis A
2009-11-01
Healthcare costs in all industrial nations have increased and payors are starting to look at new ways to contain costs and at new funding models. The business model of pharmaceutical companies is also undergoing rapid changes - potentially disruptive new modalities, such as RNAi, therapeutic vaccines, and cell therapy are emerging, R&D costs have increased year on year, pressures on drug pricing and the efficacy and safety of medicines are mounting. Change is therefore inevitable and already ongoing in healthcare systems and pharmaceutical companies alike. This paper presents several major forces which could drive different future scenarios including: R&D costs, the source of payments for medicines and the emergence of new modalities.
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. 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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
Clemente, Wanessa Trindade; Pierrotti, Lígia Camera; Abdala, Edson; Morris, Michele I; Azevedo, Luiz S; López-Vélez, Rogelio; Cuenca-Estrella, Manuel; Torre-Cisneros, Julian; Petersen, Eskild; Camargo, Luis Fernando A; Wright, Alissa Jade; Beeching, Nicholas J; Vilela, Eduardo Garcia; Santoro-Lopes, Guilherme; Len, Oscar; Stucchi, Raquel S B; Manuel, Oriol; Faria, Luciana Costa; Leblebicioglu, Hakan; Huprikar, Shirish; Molina, Israel; Mourão, Paulo Henrique Orlandi; Kotton, Camille N; Aguado, José María
2018-02-01
The Recommendations for Management of Endemic Diseases and Travel Medicine in Solid-Organ Transplant Recipients and Donors: Latin America clinical practice guideline is intended to guide clinicians caring for solid-organ transplant (SOT) donors, candidates and recipients regarding infectious diseases (ID) issues related to this geographical region, mostly located in the tropics. These recommendations are based on both systematic reviews of relevant literature and expert opinion from both transplant ID and travel medicine specialists. The guidelines provide recommendations for risk evaluation and laboratory investigation, as well as management and prevention of infection of the most relevant endemic diseases of Latin America. This summary includes a brief description of the guideline recommendations but does not include the complete rationale and references for each recommendation, which is available in the online version of the article, published in this journal as a supplement. The supplement contains 10 reviews referring to endemic or travel diseases (eg, tuberculosis, Chagas disease [ChD], leishmaniasis, malaria, strongyloidiasis and schistosomiasis, travelers diarrhea, arboviruses, endemic fungal infections, viral hepatitis, and vaccines) and an illustrative section with maps (http://www.pmourao.com/map/). Contributors included experts from 13 countries (Brazil, Canada, Chile, Denmark, France, Italy, Peru, Spain, Switzerland, Turkey, United Kingdom, United States, and Uruguay) representing four continents (Asia, the Americas and Europe), along with scientific and medical societies.
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
The sciences of vaccinology and of immunology were created just two centuries ago by Jenner's studies of prevention of smallpox by inoculation with cowpox virus. This rudimentary beginning was expanded greatly by the giants of late 19th and early 20th 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 of notable advances made during the 1940s and World War II. Present vaccinology is based largely on breakthroughs in cell culture, bacterial polysaccharide chemistry, molecular biology, and immunology. By invitation, the author, who is a microbe hunter in fact, was asked to chronicle his six decades of pioneering achievements in basic and applied virology, bacteriology, immunology, molecular biology, epidemiology, and cancer, with special reference to the pioneering creation of most of the present day vaccines. Knowledge of the past may guide the present and future. This chronicle will have achieved its legacy if it helps others to understand the why and how of the past that may help to create the substance of the future.
I review the history and politics of Medicare disease prevention policy and identify factors associated with the success or failure of legislative initiatives to add preventive services benefits to Medicare. Between 1965 and 1990, 453 bills for Medicare preventive services were introduced in the U.S. Congress, but not until 1980, after 350 bills had failed, was the first preventive service added to the Medicare program. Medicare currently pays for only four of the 44 preventive services recommended for the elderly by the U.S. Preventive Services Task Force (pneumococcal and hepatitis B vaccinations, Pap smears, and mammography). In addition, Congress has funded demonstration programs for the influenza vaccine and comprehensive preventive services. The preventive services added to Medicare reflect the bias of the biomedical model toward screening and immunizations. Counseling services have received the least legislative attention. Factors associated with successful enactment include single-benefit bills, incorporation into budget-deficit reduction legislation, documented evidence of cost-effectiveness, public hearings, sponsorship by chairs of key congressional committees, and persistent congressional leadership. Factors associated with failure include lack of support from Medicare beneficiaries, lack of professional support, impact on total Medicare expenditures, disagreement over or failure to address payment and financing mechanisms, and competing congressional priorities.
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.
Simple Summary This paper explores the ways in which biomedical research that uses nonhuman animal subjects generates financial profits and gains for humans who are associated with the industry. Research establishments, scientists, regulators and persons that inspect laboratories for compliance, those associated with granting licences, companies that sell nonhuman animal subjects and that supply equipment for the research, and corporations that market the resulting products are among those that benefit financially. These profits are rarely discussed—they seem to be camouflaged by the focus of the moral convention that assumes that human health-related needs prevail over those of the nonhuman animals who are so used. The paper concludes by calling for an end to the denigration of nonhuman animals as experimental subjects who can be used as commodities for profit-maximisation and as tools in experiments for human health benefits. Abstract Each year millions of nonhuman animals suffer in biomedical experiments for human health benefits. Clinical ethics demand that nonhuman animals are used in the development of pharmaceuticals and vaccines. Nonhuman animals are also used for fundamental biomedical research. Biomedical research that uses nonhuman animals is big business but the financial gains are generally occluded. This paper explores how such research generates profits and gains for those associated with the industry. Research establishments, scientists, laboratories, companies that sell nonhuman animal subjects, that supply equipment for the research, and corporations that market the resulting products are among those that benefit financially. Given the complex articulation of ethical codes, enormous corporate profits that are secured and personal returns that are made, the accepted moral legitimacy of such experiments is compromised. In order to address this, within the confines of the moral orthodoxy, more could to be done to ensure transparency and to extricate the vested financial interests from the human health benefits. But such a determination would not address the fundamental issues that should be at the heart of human actions in respect of the nonhuman animals who are used in experiments. The paper concludes with such an address by calling for an end to the denigration of nonhuman animals as experimental subjects who can be used as commodities for profit-maximisation and as tools in experiments for human health benefits, and the implementation of a more inclusive ethic that is informed by universal concern about the suffering of and compassion for all oppressed beings. PMID:26479378
Kosik, Ivan; Ince, William L; Gentles, Lauren E; Oler, Andrew J; Kosikova, Martina; Angel, Matthew; Magadán, Javier G; Xie, Hang; Brooke, Christopher B; Yewdell, Jonathan W
2018-01-01
Rapid antigenic evolution enables the persistence of seasonal influenza A and B viruses in human populations despite widespread herd immunity. Understanding viral mechanisms that enable antigenic evolution is critical for designing durable vaccines and therapeutics. Here, we utilize the primerID method of error-correcting viral population sequencing to reveal an unexpected role for hemagglutinin (HA) glycosylation in compensating for fitness defects resulting from escape from anti-HA neutralizing antibodies. Antibody-free propagation following antigenic escape rapidly selected viruses with mutations that modulated receptor binding avidity through the addition of N-linked glycans to the HA globular domain. These findings expand our understanding of the viral mechanisms that maintain fitness during antigenic evolution to include glycan addition, and highlight the immense power of high-definition virus population sequencing to reveal novel viral adaptive mechanisms.
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.
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
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.
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
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
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.
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.
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.
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.
Smaller health care facilities especially clinics though believed to generate lesser quantum/categories of medical waste, the number of clinics/small health care settings are considerable. The movement to manage biomedical waste in a safe and scientific manner has gathered momentum among the medium and large hospitals in Bangalore, but there has been a little understanding and focus on the smaller health care facilities/clinics in this aspect. It is important to gather evidence regarding the current situation of bio-medical waste (BMW) management and issues in smaller health care settings, so as to expand the safe management to all points of generation in Bangalore and will also help to plan relevant interventional strategies for the same. Hence an exploratory study was conducted to assess the current situation and issues in management of BMW among small health care facilities (sHCF). This cross sectional study was conducted in T. Dasarahalli (ward number 15) under Bruhat Bengaluru Mahanagar Palike (BBMP) of Bangalore. Data was collected from a convenient sample of 35 nursing homes (<50 beds) and clinics in December 2011. The results of this study indicate that 3 (20 %) of nursing homes had a Policy for Health Care Waste Management, though committees for Infection control and Hospital waste management were absent. Recording system like injury and waste management registers were non-existent. In our study the Common Bio-medical Waste Treatment Facility operator collected waste from 28 (80 %) of the sHCF. Segregation at the point of generation was present in 22 (62.9 %) of the sHCF. Segregation process was compliant as per BMW rules 1998 among 5 (16.1 %) of the sHCF. 18 sHCF workers were vaccinated with hepatitis B and tetanus. Deficiencies were observed in areas of containment, sharps management and disinfection. It was observed that though the quantum and category of waste generated was limited there exist deficiencies which warrant initiation of system development measures including capacity building.
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
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.
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/.
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.
..., 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...
Henderson, Carl S; Madison, Andrew C; Shah, Ankoor
2014-01-01
Nanotechnology, or the use of technology at the submicron scale, and its application to medicine (nanomedicine) draws from many ideas and technological advancements across myriad fields of materials technology and has improved biomedical understanding. Nanotechnology puts current materials science on the same physical scale as classic immune mediating substances, including viruses, moieties found on prokaryotic bacteria, and antigen presenting cells. Functionalized nanoparticles, fullerenes, liposomes, nanogels, and virus-like particles, are several examples of nanotechnology that are currently being applied to the treatment of oncologic and infectious diseases. However, the majority of the current commercial utilization of nanomedicine has been directed towards creating improved vaccines in order to prevent infectious diseases. These processes may have direct applications toward the creation of vaccines used to treat autoimmune disease as well. Current therapeutics utilizing nanotechnology, are gaining traction in treatments for gout and rheumatoid arthritis, and experimental animal models have demonstrated success in using the above technologies to improve the effectiveness and safety of current standard treatment of rheumatologic illnesses. Here we review many of the common forms of nanoparticles used in medical applications as well as where they have found a role in rheumatology. Continued technical feasibility, ongoing safety studies, and lingering questions on cost are all issues that have not yet been resolved in regards to widespread application in rheumatology and immunology.
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. PMID:23908779
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.
... reference price Data record 1 CCO_ID_1 CM_ID_2 CP_04 9/27/2010 C Nov-10 NYMEX NY Harbor No.2. Data record 2 CCO_ID_1 CM_ID_2 CP_04 9/27/2010 C Oct-10 NYMEX NY Harbor No.2. Data record 3 CCO_ID_1 CM_ID_2 CP_02 9/27/2010 C Nov-10 NYMEX Henry Hub. Data record 4 CCO_ID_1 CM_ID_2 CP_02 9/27/2010 C Oct-10 NYMEX Henry...
... reference price Data record 1 CCO_ID_1 CM_ID_2 CP_04 9/27/2010 C Nov-10 NYMEX NY Harbor No.2. Data record 2 CCO_ID_1 CM_ID_2 CP_04 9/27/2010 C Oct-10 NYMEX NY Harbor No.2. Data record 3 CCO_ID_1 CM_ID_2 CP_02 9/27/2010 C Nov-10 NYMEX Henry Hub. Data record 4 CCO_ID_1 CM_ID_2 CP_02 9/27/2010 C Oct-10 NYMEX Henry...
... reference price Data record 1 CCO_ID_1 CM_ID_2 CP_04 9/27/2010 C Nov-10 NYMEX NY Harbor No.2. Data record 2 CCO_ID_1 CM_ID_2 CP_04 9/27/2010 C Oct-10 NYMEX NY Harbor No.2. Data record 3 CCO_ID_1 CM_ID_2 CP_02 9/27/2010 C Nov-10 NYMEX Henry Hub. Data record 4 CCO_ID_1 CM_ID_2 CP_02 9/27/2010 C Oct-10 NYMEX Henry...
We have examined the role of an Id-like protein, Id3 (also known as HLH462), in the regulation of muscle-specific gene expression. Id proteins are believed to block expression of muscle-specific genes by preventing the dimerization between ubiquitous bHLH proteins (E proteins) and myogenic bHLH proteins such as MyoD. Consistent with its putative role as an inhibitor of differentiation, Id3 mRNA was detected in proliferating skeletal muscle cells, was further induced by basic fibroblast growth factor (bFGF) and was down-regulated in differentiated muscle cultures. Overexpression of Id3 efficiently inhibited the MyoD-mediated activation of the muscle-specific creatine kinase (MCK) reporter gene. Deletion analysis indicated that the C-terminal 15 amino acids of Id3 are critical for the full inhibitory activity while deleting up to 42 residues from the C-terminus of the related protein, Id2, did not affect its ability to inhibit the MCK reporter gene. Chimeric protein containing the N-terminal region of Id3 and the C-terminus of Id2 was also non-functional in transfected cells. In contrast, wild-type Id3, the C-terminal mutants, and the Id3/Id2 chimera could all interact with the E-protein E47in vitro. Additional studies indicated that truncation of the Id3 C-terminus might have adversely affected the expression level of the mutant proteins but the Id3/Id2 chimera was stably expressed. Taken together, our results revealed a more complex requirement for the expression and proper function of the Id family proteins than was hitherto expected.
We have examined the role of an Id-like protein, Id3 (also known as HLH462), in the regulation of muscle-specific gene expression. Id proteins are believed to block expression of muscle-specific genes by preventing the dimerization between ubiquitous bHLH proteins (E proteins) and myogenic bHLH proteins such as MyoD. Consistent with its putative role as an inhibitor of differentiation, Id3 mRNA was detected in proliferating skeletal muscle cells, was further induced by basic fibroblast growth factor (bFGF) and was down-regulated in differentiated muscle cultures. Overexpression of Id3 efficiently inhibited the MyoD-mediated activation of the muscle-specific creatine kinase (MCK) reporter gene. Deletion analysis indicated that the C-terminal 15 amino acids of Id3 are critical for the full inhibitory activity while deleting up to 42 residues from the C-terminus of the related protein, Id2, did not affect its ability to inhibit the MCK reporter gene. Chimeric protein containing the N-terminal region of Id3 and the C-terminus of Id2 was also non-functional in transfected cells. In contrast, wild-type Id3, the C-terminal mutants, and the Id3/Id2 chimera could all interact with the E-protein E47in vitro. Additional studies indicated that truncation of the Id3 C-terminus might have adversely affected the expression level of the mutant proteins but the Id3/Id2 chimera was stably expressed. Taken together, our results revealed a more complex requirement for the expression and proper function of the Id family proteins than was hitherto expected. PMID:9016574
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.
Statistics play a critical role in biological and clinical research. However, most reports of scientific results in the published literature make it difficult for the reader to reproduce the statistical analyses performed in achieving those results because they provide inadequate documentation of the statistical tests and algorithms applied. The Ontology of Biological and Clinical Statistics (OBCS) is put forward here as a step towards solving this problem. The terms in OBCS including 'data collection', 'data transformation in statistics', 'data visualization', 'statistical data analysis', and 'drawing a conclusion based on data', cover the major types of statistical processes used in basic biological research and clinical outcome studies. OBCS is aligned with the Basic Formal Ontology (BFO) and extends the Ontology of Biomedical Investigations (OBI), an OBO (Open Biological and Biomedical Ontologies) Foundry ontology supported by over 20 research communities. Currently, OBCS comprehends 878 terms, representing 20 BFO classes, 403 OBI classes, 229 OBCS specific classes, and 122 classes imported from ten other OBO ontologies. We discuss two examples illustrating how the ontology is being applied. In the first (biological) use case, we describe how OBCS was applied to represent the high throughput microarray data analysis of immunological transcriptional profiles in human subjects vaccinated with an influenza vaccine. In the second (clinical outcomes) use case, we applied OBCS to represent the processing of electronic health care data to determine the associations between hospital staffing levels and patient mortality. Our case studies were designed to show how OBCS can be used for the consistent representation of statistical analysis pipelines under two different research paradigms. Other ongoing projects using OBCS for statistical data processing are also discussed. The OBCS source code and documentation are available at: https://github.com/obcs/obcs . The Ontology of Biological and Clinical Statistics (OBCS) is a community-based open source ontology in the domain of biological and clinical statistics. OBCS is a timely ontology that represents statistics-related terms and their relations in a rigorous fashion, facilitates standard data analysis and integration, and supports reproducible biological and clinical research.
Farran, Lama K; Lee, Chia-Cheng; Yoo, Hyunjoo; Oller, D Kimbrough
2016-01-01
Infant-directed speech (IDS) provides an environment that appears to play a significant role in the origins of language in the human infant. Differences have been reported in the use of IDS across cultures, suggesting different styles of infant language-learning. Importantly, both cross-cultural and intra-cultural research suggest there may be a positive relationship between the use of IDS and rates of language development, underscoring the need to investigate cultural differences more deeply. The majority of studies, however, have conceptualized IDS monolithically, granting little attention to a potentially key distinction in how IDS manifests across cultures during the first two years. This study examines and quantifies for the first time differences within IDS in the use of baby register (IDS/BR), an acoustically identifiable type of IDS that includes features such as high pitch, long duration, and smooth intonation (the register that is usually assumed to occur in IDS), and adult register (IDS/AR), the type of IDS that does not include such features and thus sounds as if it could have been addressed to an adult. We studied IDS across 19 American and 19 Lebanese mother-infant dyads, with particular focus on the differential use of registers within IDS as mothers interacted with their infants ages 0-24 months. Our results showed considerable usage of IDS/AR (>30% of utterances) and a tendency for Lebanese mothers to use more IDS than American mothers. Implications for future research on IDS and its role in elucidating how language evolves across cultures are explored.
Farran, Lama K.; Lee, Chia-Cheng; Yoo, Hyunjoo; Oller, D. Kimbrough
2016-01-01
Infant-directed speech (IDS) provides an environment that appears to play a significant role in the origins of language in the human infant. Differences have been reported in the use of IDS across cultures, suggesting different styles of infant language-learning. Importantly, both cross-cultural and intra-cultural research suggest there may be a positive relationship between the use of IDS and rates of language development, underscoring the need to investigate cultural differences more deeply. The majority of studies, however, have conceptualized IDS monolithically, granting little attention to a potentially key distinction in how IDS manifests across cultures during the first two years. This study examines and quantifies for the first time differences within IDS in the use of baby register (IDS/BR), an acoustically identifiable type of IDS that includes features such as high pitch, long duration, and smooth intonation (the register that is usually assumed to occur in IDS), and adult register (IDS/AR), the type of IDS that does not include such features and thus sounds as if it could have been addressed to an adult. We studied IDS across 19 American and 19 Lebanese mother-infant dyads, with particular focus on the differential use of registers within IDS as mothers interacted with their infants ages 0–24 months. Our results showed considerable usage of IDS/AR (>30% of utterances) and a tendency for Lebanese mothers to use more IDS than American mothers. Implications for future research on IDS and its role in elucidating how language evolves across cultures are explored. PMID:26981626
To investigate the expression of inhibitor of DNA differentiation/DNA binding 1 (Id1) and Id3 in endometrial carcinoma and explore their roles in regulating the proliferation, invasion, migration and adhesion of endometrial carcinoma cells in vitro. Id1 and Id3 expression in 4 fresh endometrial cancer tissue specimens and matched adjacent tissues were detected using Western blotting. Two endometrial cancer cell lines, HEC-1-B and RL-952, were both divided into 4 groups, namely the untreated group, blank virus group, promoter group and Id1/Id3 double-knockdown group, and their expressions of MMP2, CXCR4 and P21 were detected by qRT-PCR and Western blotting. The proliferation, invasion, migration and adhesion of the cells were evaluated with MTT, Transwell, wound-healing, and adhesion assays. Endometrial carcinoma tissues showed significantly higher Id1 and Id3 expression than the adjacent tissues (P<0.05). In the two endometrial carcinoma cell lines, Id1/Id3 double-knockdown significantly decreased MMP2 and CXCR4 expression and increased P21 expression at both mRNA and protein levels (P<0.05), and resulted in suppressed cell proliferation, invasion, migration and adhesion. Id1 and Id3 expressions are up-regulated in endometrial carcinoma to promote the proliferation, invasion, migration and adhesion of the tumor cells by increasing MMP2 and CXCR4 expression and reducing P21 expression. Therapies targeting Id1/Id3 can be a novel strategy for treatment of endometrial carcinoma.
The NPO Biomedical Science Association provided telephone consultation, including contacts by fax and email, targeting the general public within the framework of influenza control measures worked out by the Japanese Ministry of Health, Labor and Welfare (MHLW). We received 2,813 inquiries during the 2003-2004 flu season and 2,444 inquiries during the 2004-2005 season. By month, the highest number was in October-November, accounting for 42.6%. The preceding season showed a similar trend. By gender, 72.5% of those seeking advice were women. By area of residence, the highest number was living in metropolitan Tokyo, and the remainder lived in the prefectures of Kanagawa, Chiba, Saitama, Nagano, Shizuoka, and Ibaraki in this order. We received no inquiries from the prefectures of Shimane or Saga. By occupation, housewives accounted for 1,114 inquiries (45.6%), followed by private companies with 447 inquiries (18.3%) and health-care providers with 227 inquiries (9.3%), similar to the 2003-2004 flu season. By subject, 1,545 inquiries concerned vaccines (62.2%) mainly, the pros and cons of vaccination, adverse reactions, and the number of inoculations required. Inquiries about pregnancy, infants and young children, and breast-feeding accounted for 19.2%. Inquiries on vaccine shortages during the 2004-2005 flu season (7), SARS (22), and bird flu (22) decreased compared to the previous season, while the number of consultations on antiviral agents increased (209). In discussing how information on influenza should be communicated to the public, we propose that "Influenza Q & A" provided by the Infectious Diseases Surveillance Center of the NIID, MHLW, should include information on influenza specifically addressing pregnant woman and breast-feeding or child-rearing mothers.
Weigler, Benjamin J; Cooper, Donna R; Hankenson, F Claire
2012-01-01
A national survey was conducted to assess immunization practices and tuberculosis screening methods for animal care and research workers in biomedical settings throughout the United States. Veterinarians (n = 953) were surveyed via a web-based mechanism; completed surveys (n = 308) were analyzed. Results showed that occupational health and safety programs were well-developed, enrolling veterinary, husbandry, and research staff at rates exceeding 90% and involving multiple modalities of health assessments and risk communication for vaccine-preventable diseases. Most (72.7%) institutions did not store serum samples from animal research personnel. More than half of the institutions housed nonhuman primates and maintained tuberculosis screening programs, although screening methods varied. Immunization protocols included various recommended or required vaccines that differed depending on job duties, type of institution, and nature of scientific programs. A single case of an identified vaccine–preventable illness in a laboratory worker was noted. Tetanus toxoid was the predominant vaccine administered (91.7%) to animal care and research workers, followed by hepatitis B (54.8%), influenza (39.9%), and rabies (38.3%). For some immunization protocols, an inconsistent rationale for administration was evident. Indications that animal care and research workers are unprotected from work-related etiologic agents did not emerge from this survey; rather, existing guidelines from the Advisory Committee on Immunization Practices and available biologics seem sufficient to address most needs of the laboratory animal research community. Institutions should commit to performance-based standards in parallel with context-specific risk assessment methods to maintain occupational health and safety programs and practices appropriate to their needs. PMID:23312084
ID4, a helix loop helix transcriptional regulator has emerged as a tumor suppressor in prostate cancer. Epigenetic silencing of ID4 promotes prostate cancer whereas ectopic expression in prostate cancer cell lines blocks cancer phenotype. To directly investigate the anti-tumor property, full length human recombinant ID4 encapsulated in biodegradable Polycaprolactone/Maltodextrin (PCL-MD) nano-carrier was delivered to LNCaP cells in which the native ID4 was stably silenced (LNCaP(-)ID4). The cellular uptake of ID4 resulted in increased apoptosis, decreased proliferation and colony formation. Intratumoral delivery of PCL-MD ID4 into growing LNCaP(-)ID4 tumors in SCID mice significantly reduced the tumor volume compared to the tumors treated with chemotherapeutic Docetaxel. The study supports the feasibility of using nano-carrier encapsulated ID4 protein as a therapeutic. Mechanistically, ID4 may assimilate multiple regulatory pathways for example epigenetic re-programming, integration of multiple AR co-regulators or signaling pathways resulting in tumor suppressor activity of ID4. PMID:27487149
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
Mody, Avani A; Wordinger, Robert J; Clark, Abbot F
2017-02-01
Increased expression of TGF-β2 in primary open-angle glaucoma (POAG) aqueous humor (AH) and trabecular meshwork (TM) causes deposition of extracellular matrix (ECM) in the TM and elevated IOP. Bone morphogenetic proteins (BMPs) regulate TGF-β2-induced ECM production. The underlying mechanism for BMP4 inhibition of TGF-β2-induced fibrosis remains undetermined. Bone morphogenic protein 4 induces inhibitor of DNA binding proteins (ID1, ID3), which suppress transcription factor activities to regulate gene expression. Our study will determine whether ID1and ID3 proteins are downstream targets of BMP4, which attenuates TGF-β2 induction of ECM proteins in TM cells. Primary human TM cells were treated with BMP4, and ID1 and ID3 mRNA, and protein expression was determined by quantitative PCR (Q-PCR) and Western immunoblotting. Intracellular ID1 and ID3 protein localization was studied by immunocytochemistry. Transformed human TM cells (GTM3 cells) were transfected with ID1 or ID3 expression vectors to determine their potential inhibitory effects on TGF-β2-induced fibronectin and plasminogen activator inhibitor-I (PAI-1) protein expression. Basal expression of ID1-3 was detected in primary human TM cells. Bone morphogenic protein 4 significantly induced early expression of ID1 and ID3 mRNA (P < 0.05) and protein in primary TM cells, and a BMP receptor inhibitor blocked this induction. Overexpression of ID1 and ID3 significantly inhibited TGF-β2-induced expression of fibronectin and PAI-1 in TM cells (P < 0.01). Bone morphogenic protein 4 induced ID1 and ID3 expression suppresses TGF-β2 profibrotic activity in human TM cells. In the future, targeting specific regulators may control the TGF-β2 profibrotic effects on the TM, leading to disease modifying IOP lowering therapies.
ABSTRACT Proteus mirabilis is a social bacterium that is capable of self (kin) versus nonself recognition. Swarming colonies of this bacterium expand outward on surfaces to centimeter-scale distances due to the collective motility of individual cells. Colonies of genetically distinct populations remain separate, while those of identical populations merge. Ids proteins are essential for this recognition behavior. Two of these proteins, IdsD and IdsE, encode identity information for each strain. These two proteins bind in vitro in an allele-restrictive manner. IdsD-IdsE binding is correlated with the merging of populations, whereas a lack of binding is correlated with the separation of populations. Key questions remained about the in vivo interactions of IdsD and IdsE, specifically, whether IdsD and IdsE bind within single cells or whether IdsD-IdsE interactions occur across neighboring cells and, if so, which of the two proteins is exchanged. Here we demonstrate that IdsD must originate from another cell to communicate identity and that this nonresident IdsD interacts with IdsE resident in the recipient cell. Furthermore, we show that unbound IdsD in recipient cells does not cause cell death and instead appears to contribute to a restriction in the expansion radius of the swarming colony. We conclude that P. mirabilis communicates IdsD between neighboring cells for nonlethal kin recognition, which suggests that the Ids proteins constitute a type of cell-cell communication. IMPORTANCE We demonstrate that self (kin) versus nonself recognition in P. mirabilis entails the cell-cell communication of an identity-encoding protein that is exported from one cell and received by another. We further show that this intercellular exchange affects swarm colony expansion in a nonlethal manner, which adds social communication to the list of potential swarm-related regulatory factors. PMID:27672195
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…
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 significant contribution of medicines in the introduction and spread of ‘modern’ medicine has, with the exception of vaccination, been neglected in historical studies, yet medicines have been a significant factor in people’s experiences of sickness and in their use and non-use of health services. Although medicines are implicitly acknowledged in the literature as important in the provision of healthcare, this article uses a case study of the Mt Everest region of Nepal during the second half of the twentieth century to argue that medicines have had an explicit and central role in the introduction and spread of modern medicine in this region. It also highlights the importance of travellers in the process. While this article focuses on biomedical products, modern medicine, as elsewhere in the wider Himalayan region, continued to be practised within a changing but plural medical environment. The first part of the article discusses medicines and travellers who, in the absence of biomedical services, were the main source of medicines prior to the mid-1960s, while the second part considers medicines and Khunde Hospital, which was built in 1966 by the area’s most famous overseas traveller and became not only the area’s main provider of modern health services but also the main source of medicines. PMID:22025798
The nature of some potential benefits and risks associated with genetic research is different from the types of potential benefits and risks associated with other types of health research such as clinical trials and biomedical research involving humans. Whereas most potential risks associated with biomedical research or clinical trials are mainly biological in nature, potential risks associated with genetic research are mainly of socioeconomic nature. Although the peculiarity of some of the aspects of genetic research and the complexity of the science involved are acknowledged, the extent to which these characteristics hinder firstly disclosure of information to participants and their communities and secondly comprehension of the disclosed information is a practical challenge that tends to be exaggerated in some cases. In this article, a brief overview of the various types of genetic research will be given in order to set the scene for some ethical and practical issues surrounding the research in developing countries that will be discussed subsequently. Case studies that illustrate some of the ethical and practical issues flagged will be given, followed by suggestions on possible ways of tackling some of the challenges in developing country settings. Nevertheless, genetic and genomic research could go a long way in providing knowledge that could be useful in the development of drugs and vaccines for many diseases affecting the developing countries.
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.
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.
We clarified in this study how plasma-induced charging damage (PCD) affects the so-called “random telegraph noise (RTN)” — a principal concern in designing ultimately scaled large-scale integrated circuits (LSIs). Metal-oxide-semiconductor field-effect transistors (MOSFETs) with SiO2 and high-k gate dielectric were exposed to an inductively coupled plasma (ICP) with Ar gas. Drain current vs gate voltage (Ids-Vg) characteristics were obtained before and after the ICP plasma exposure for the same device. Then, the time evolution of Ids fluctuation defined as Ids/μIds was measured, where μIds is the mean Ids. This value corresponds to an RTN feature, and RTN was obtained under various gate voltages (Vg) by a customized measurement technique. We focused on the statistical distribution width of (Ids/μIds), δ(Ids/μIds), in order to clarify the effects of PCD on RTN. δ(Ids/μIds) was increased by PCD for both MOSFETs with the SiO2 and high-k gate dielectrics, suggesting that RTN can be used as a measure of PCD, i.e., a distribution width increase directly indicates the presence of PCD. The dependence of δ(Ids/μIds) on the overdrive voltage Vg-Vth, where Vth is the threshold voltage, was investigated by the present technique. It was confirmed that δ(Ids/μIds) increased with a decrease in the overdrive voltage for MOSFETs with the SiO2 and high-k gate dielectrics. The presence of created carrier trap sites with PCD was characterized by the time constants for carrier capture and emission. The threshold voltage shift (ΔVth) induced by PCD was also evaluated and compared with the RTN change, to correlate the RTN increase with ΔVth induced by PCD. Although the estimated time constants exhibited complex behaviors due to the nature of trap sites created by PCD, δ(Ids/μIds) showed a straightforward tendency in accordance with the amount of PCD. These findings provide an in-depth understanding of plasma-induced RTN characteristic changes in future MOSFETs.
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.
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
Komaragiri, Shravan Kumar; Bostanthirige, Dhanushka H.; Morton, Derrick J.
Deregulation of tumor suppressor genes is associated with tumorigenesis and the development of cancer. In prostate cancer, ID4 is epigenetically silenced and acts as a tumor suppressor. In normal prostate epithelial cells, ID4 collaborates with androgen receptor (AR) and p53 to exert its tumor suppressor activity. Previous studies have shown that ID4 promotes tumor suppressive function of AR whereas loss of ID4 results in tumor promoter activity of AR. Previous study from our lab showed that ectopic ID4 expression in DU145 attenuates proliferation and promotes AR expression suggesting that ID4 dependent AR activity is tumor suppressive. In this study, wemore » examined the effect of ectopic expression of ID4 on highly malignant prostate cancer cell, PC3. Here we show that stable overexpression of ID4 in PC3 cells leads to increased apoptosis and decreased cell proliferation and migration. In addition, in vivo studies showed a decrease in tumor size and volume of ID4 overexpressing PC3 cells, in nude mice. At the molecular level, these changes were associated with increased androgen receptor (AR), p21, and AR dependent FKBP51 expression. At the mechanistic level, ID4 may regulate the expression or function of AR through specific but yet unknown AR co-regulators that may determine the final outcome of AR function. - Highlights: • ID4 expression induces AR expression in PC3 cells, which generally lack AR. • ID4 expression increased apoptosis and decreased cell proliferation and invasion. • Overexpression of ID4 reduces tumor growth of subcutaneous xenografts in vivo. • ID4 induces p21 and FKBP51 expression- co-factors of AR tumor suppressor activity.« less
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
...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.
Routine immunization (RI) is a key child survival intervention. Ensuring acceptable standards of RI service delivery is critical for optimal outcomes. Accumulated evidences suggest that 'supportive supervision' improves the quality of health care services in general. During 2009-2010, the Government of Odisha and UNICEF jointly piloted this strategy in four districts to improve RI program outcomes. The present study aims to assess the effect of this strategy on improvement of skills and practices at immunization session sites. A quasi-experimental 'post-test only' study design was adopted to compare the opinion and practices of frontline health workers and their supervisors in four intervention districts (IDs) with two control districts (CDs). Altogether, we interviewed 111 supervisor-supervisee (health worker) pairs using semi-structured interview schedules and case vignettes. We also directly observed health workers' practices during immunization sessions at 111 sites. Data were analyzed with SPSS version 16.0. The mean knowledge score of supervisors in CDs was significantly higher than in intervention groups. Variegated responses were obtained on case vignettes. The control group performed better in solving certain hypothetically asked problems, whereas the intervention group scored better in others. Health workers in IDs gave a lower rating to their respective supervisors' knowledge, skill, and frequency of supervision. Logistics and vaccine availability were better in CDs. Notwithstanding other limitations, supportive supervision may not have independent effects on improving the quality of immunization services. Addressing systemic issues, such as the availability of essential logistics, supply chain management, timely indenting, and financial resources, could complement the supportive supervision strategy in improving immunization service delivery.
Wyatt, Linda S.; Belyakov, Igor M.; Earl, Patricia L.
2008-03-15
During propagation of modified vaccinia virus Ankara (MVA) encoding HIV 89.6 Env, a few viral foci stained very prominently. Virus cloned from such foci replicated to higher titers than the parent and displayed enhanced genetic stability on passage. Sequence analysis showed a single nucleotide deletion in the 89.6 env gene of the mutant that caused a frame shift and truncation of 115 amino acids from the cytoplasmic domain. The truncated Env was more highly expressed on the cell surface, induced higher antibody responses than the full-length Env, reacted with HIV neutralizing monoclonal antibodies and mediated CD4/co-receptor-dependent fusion. Intramuscular (IM), intradermalmore » (ID) needleless, and intrarectal (IR) catheter inoculations gave comparable serum IgG responses. However, intraoral (IO) needleless injector route gave the highest IgA in lung washings and IR gave the highest IgA and IgG responses in fecal extracts. Induction of CTL responses in the spleens of individual mice as assayed by intracellular cytokine staining was similar with both the full-length and truncated Env constructs. Induction of acute and memory CTL in the spleens of mice immunized with the truncated Env construct by ID, IO, and IR routes was comparable and higher than by the IM route, but only the IR route induced CTL in the gut-associated lymphoid tissue. Thus, truncation of Env enhanced genetic stability as well as serum and mucosal antibody responses, suggesting the desirability of a similar modification in MVA-based candidate HIV vaccines.« less
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.
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.
In this work, an intrusion detection system (IDS) framework based on multi-level clustering for hierarchical wireless sensor networks is proposed. The framework employs two types of intrusion detection approaches: (1) “downward-IDS (D-IDS)” to detect the abnormal behavior (intrusion) of the subordinate (member) nodes; and (2) “upward-IDS (U-IDS)” to detect the abnormal behavior of the cluster heads. By using analytical calculations, the optimum parameters for the D-IDS (number of maximum hops) and U-IDS (monitoring group size) of the framework are evaluated and presented. PMID:26593915
Context Alzheimer disease (AD) is a major public health issue with a prediction of 12 million Americans being affected by 2025 from the present 4 million. Molecular and genetic findings have provided significant insights into the roles that amyloid, tau, and apolipoprotein E isoforms have in the causation of AD. A central issue in AD pathogenesis is the amyloid cascade hypothesis. It states that abnormal amyloid processing and accumulation is the primary causative factor of AD and other associated neuropathologic abnormalities are of secondary consequence. It is presented to provide the rationale for novel drug and vaccination therapeutic strategies. Future research directed at prediction and prevention of AD through a genomic and proteomic analysis with identification of multiple polymorphic genes that interact, resulting in increased risk for late-onset AD, are the realistic and ultimate goals. A new approach for drug development is required, one that will emphasize a genomic and proteomic analysis to identify at-risk gene sets whose genetic expression is sufficient to cause late onset, sporadic AD. Prediction and prevention of disease prior to clinical signs and symptoms are the goals. Objective A review and analysis from electronic literature databases and subsequent reference searches of the molecular genetic data including pertinent genetic mutations and abnormal biochemical findings causal of AD, are cited. The amyloid cascade hypothesis, the contributions of apolipoprotein E, and hyperphosphorylated tau are discussed as to their roles in pathogenesis. Molecular targets for potential drug and vaccination therapies are cited from a critical assessment of the molecular and biomedical data. These data form the basis for rational, target-specific drug and vaccination therapies currently employed and planned for the near future. Phase 2 and 3 clinical trial results of drug and vaccination therapies are cited. Conclusions A new approach is needed as current pharmacologic therapy directed at symptomatic relief has proved to be marginally effective. The genomic and proteomic basis of AD will be defined in the near future, and corresponding molecular therapeutic targets will be identified. Genomic neurology has arrived and its application to resolving AD is our best hope. PMID:16275806
Alzheimer disease (AD) is a major public health issue with a prediction of 12 million Americans being affected by 2025 from the present 4 million. Molecular and genetic findings have provided significant insights into the roles that amyloid, tau, and apolipoprotein E isoforms have in the causation of AD. A central issue in AD pathogenesis is the amyloid cascade hypothesis. It states that abnormal amyloid processing and accumulation is the primary causative factor of AD and other associated neuropathologic abnormalities are of secondary consequence. It is presented to provide the rationale for novel drug and vaccination therapeutic strategies. Future research directed at prediction and prevention of AD through a genomic and proteomic analysis with identification of multiple polymorphic genes that interact, resulting in increased risk for late-onset AD, are the realistic and ultimate goals. A new approach for drug development is required, one that will emphasize a genomic and proteomic analysis to identify at-risk gene sets whose genetic expression is sufficient to cause late onset, sporadic AD. Prediction and prevention of disease prior to clinical signs and symptoms are the goals. A review and analysis from electronic literature databases and subsequent reference searches of the molecular genetic data. including pertinent genetic mutations and abnormal biochemical findings causal of AD, are cited. The amyloid cascade hypothesis, the contributions of apolipoprotein E, and hyperphosphorylated tau are discussed as to their roles in pathogenesis. Molecular targets for potential drug and vaccination therapies are cited from a critical assessment of the molecular and biomedical data. These data form the basis for rational, target-specific drug and vaccination therapies currently employed and planned for the near future. Phase 2 and 3 clinical trial results of drug and vaccination therapies are cited. A new approach is needed as current pharmacologic therapy directed at symptomatic relief has proved to be marginally effective. The genomic and proteomic basis of AD will be defined in the near future, and corresponding molecular therapeutic targets will be identified. Genomic neurology has arrived and its application to resolving AD is our best hope.
Highlights: Black-Right-Pointing-Pointer Expression of Id3 but not Id1 is induced by Wnt3a stimulation in C2C12 cells. Black-Right-Pointing-Pointer Wnt3a induces Id3 expression via canonical Wnt/{beta}-catenin pathway. Black-Right-Pointing-Pointer Wnt3a-induced Id3 expression does not depend on BMP signaling activation. Black-Right-Pointing-Pointer Induction of Id3 expression is critical determinant in Wnt3a-induced cell proliferation and differentiation. -- Abstract: Canonical Wnt signaling plays important roles in regulating cell proliferation and differentiation. In this study, we report that inhibitor of differentiation (Id)3 is a Wnt-inducible gene in mouse C2C12 myoblasts. Wnt3a induced Id3 expression in a {beta}-catenin-dependent manner. Bone morphogenetic protein (BMP) also potently induced Id3 expression. However,more » Wnt-induced Id3 expression occurred independent of the BMP/Smad pathway. Functional studies showed that Id3 depletion in C2C12 cells impaired Wnt3a-induced cell proliferation and alkaline phosphatase activity, an early marker of osteoblast cells. Id3 depletion elevated myogenin induction during myogenic differentiation and partially impaired Wnt3a suppressed myogenin expression in C2C12 cells. These results suggest that Id3 is an important Wnt/{beta}-catenin induced gene in myoblast cell fate determination.« less
Chen, Ching-Jen; Moosa, Shayan; Ding, Dale; Raper, Daniel M; Burke, Rebecca M; Lee, Cheng-Chia; Chivukula, Srinivas; Wang, Tony R; Starke, Robert M; Crowley, R Webster; Liu, Kenneth C
2016-08-01
Cerebrovascular infundibular dilations (IDs) are triangular-shaped widenings less than 3 mm in diameter, which are most commonly found at the posterior communicating artery (PCoA). The aims of this systematic review are to elucidate the natural histories of IDs, determine their risk of progression to significant pathology, and discuss potential management options. A comprehensive literature search of PubMed was used to find all case reports and series relating to cerebral IDs. IDs were classified into three types: type I IDs do not exhibit morphological change over a long follow-up period, type II IDs evolve into saccular aneurysms, while type III IDs are those that result in subarachnoid hemorrhage without prior aneurysmal progression. Data were extracted from studies that demonstrated type II or III IDs. We reviewed 16 cases of type II and seven cases of type III IDs. For type II IDs, 81.3% of patients were female with a median age at diagnosis of 38. All type II IDs were located at the PCoA without a clear predilection for sidedness. Median time to aneurysm progression was 7.5 years. For type III IDs there was no clear gender preponderance and the median age at diagnosis was 51. The PCoA was involved in 85.7% of cases, with 57.1% of IDs occurring on the left. Most patients were treated with clipping. Risk factors for aneurysm formation appear to be female gender, young age, left-sided localization, coexisting aneurysms, and hypertension. IDs can rarely progress to aneurysms or rupture. Young patients with type II or III IDs with coexisting aneurysms or hypertension may benefit from long-term imaging surveillance. 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/
Abstract HIV Research for Prevention: AIDS Vaccine, Microbicide, and ARV-based Prevention Science (HIVR4P) was built on a growing consensus that effective HIV prevention requires a combination of approaches and that understanding, analyzing, and debating the cross-cutting issues that impact prevention research are all essential to combat the global HIV/AIDS epidemic. To that end, the biennial HIVR4P conference is dedicated to all biomedical HIV prevention research approaches, including HIV vaccines, microbicides, pre-exposure prophylaxis, and treatment as prevention. The HIVR4P 2016 conference was held in Chicago, Illinois (USA), on October 17–21, and included more than 700 scientific presentations and 21 satellite sessions covering the latest and most promising advances across the HIV prevention research field. The theme “Partnering for Prevention” represented the conference's commitment to breaking down silos between research disciplines as well as between researchers, program developers, care providers, advocates, communities, and funders. Delegates spanning 42 countries attended the conference. One-third of those in attendance were early career investigators, which reflects a firm commitment to emerging researchers and ultimately to the goal of developing a sustainable scientific enterprise well into the future. This article presents a concise summary of highlights from the conference. For a more detailed account, one may find full abstracts, daily summaries, and webcasts on the conference website at hivr4p.org. PMID:28649869
HIV Research for Prevention: AIDS Vaccine, Microbicide, and ARV-based Prevention Science (HIVR4P) was built on a growing consensus that effective HIV prevention requires a combination of approaches and that understanding, analyzing, and debating the cross-cutting issues that impact prevention research are all essential to combat the global HIV/AIDS epidemic. To that end, the biennial HIVR4P conference is dedicated to all biomedical HIV prevention research approaches, including HIV vaccines, microbicides, pre-exposure prophylaxis, and treatment as prevention. The HIVR4P 2016 conference was held in Chicago, Illinois (USA), on October 17-21, and included more than 700 scientific presentations and 21 satellite sessions covering the latest and most promising advances across the HIV prevention research field. The theme "Partnering for Prevention" represented the conference's commitment to breaking down silos between research disciplines as well as between researchers, program developers, care providers, advocates, communities, and funders. Delegates spanning 42 countries attended the conference. One-third of those in attendance were early career investigators, which reflects a firm commitment to emerging researchers and ultimately to the goal of developing a sustainable scientific enterprise well into the future. This article presents a concise summary of highlights from the conference. For a more detailed account, one may find full abstracts, daily summaries, and webcasts on the conference website at hivr4p.org.
Huang, Yunda; Huang, Ying; Moodie, Zoe; Li, Sue; Self, Steve
2014-01-01
Summary In biomedical research such as the development of vaccines for infectious diseases or cancer, measures from the same assay are often collected from multiple sources or laboratories. Measurement error that may vary between laboratories needs to be adjusted for when combining samples across laboratories. We incorporate such adjustment in comparing and combining independent samples from different labs via integration of external data, collected on paired samples from the same two laboratories. We propose: 1) normalization of individual level data from two laboratories to the same scale via the expectation of true measurements conditioning on the observed; 2) comparison of mean assay values between two independent samples in the Main study accounting for inter-source measurement error; and 3) sample size calculations of the paired-sample study so that hypothesis testing error rates are appropriately controlled in the Main study comparison. Because the goal is not to estimate the true underlying measurements but to combine data on the same scale, our proposed methods do not require that the true values for the errorprone measurements are known in the external data. Simulation results under a variety of scenarios demonstrate satisfactory finite sample performance of our proposed methods when measurement errors vary. We illustrate our methods using real ELISpot assay data generated by two HIV vaccine laboratories. PMID:22764070
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
In previous studies, we have shown that overexpression of growth hormone (GH) in cells of the immune system upregulates proteins involved in cell growth and protects from apoptosis. Here, we report that overexpression of GH in EL4 T lymphoma cells (GHo) also significantly increased levels of the inhibitor of differentiation-2 (Id2). The increase in Id2 was suggested in both Id2 promoter luciferase assays and by Western analysis for Id2 protein. To identify the regulatory elements that mediate transcriptional activation by GH in the Id2 promoter, promoter deletion analysis was performed. Deletion analysis revealed that transactivation involved a 301-132bp region upstream to the Id2 transcriptional start site. The pattern in the human GHo Jurkat T lymphoma cell line paralleled that found in the mouse GHo EL4 T lymphoma cell line. Significantly less Id2 was detected in the nucleus of GHo EL4 T lymphoma cells compared to vector alone controls. Although serum increased the levels of Id2 in control vector alone cells, no difference was found in the total levels of Id2 in GHo EL4 T lymphoma cells treated with or without serum. The increase in Id2 expression in GHo EL4 T lymphoma cells measured by Id2 promoter luciferase expression and Western blot analysis was blocked by the overexpression of a dominant-negative mutant of STAT5. The results suggest that in EL4 T lymphoma cells overexpressing GH, there is an upregulation of Id2 protein that appears to involve STAT protein activity.
Konishi, H; Ogawa, T; Nakagomi, S; Inoue, K; Tohyama, M; Kiyama, H
2010-09-15
In rats under continuous stress (CS) there is decreased hypothalamic dopaminergic innervation to the intermediate lobe (IL) of the pituitary gland, which causes hyperactivation and subsequent degeneration of melanotrophs in the IL. In this study, we investigated the molecular basis for the changes that occur in melanotrophs during CS. Using microarray analysis, we identified several genes differentially expressed in the IL under CS conditions. Among the genes up-regulated under CS conditions, we focused on the inhibitor of DNA binding/differentiation (Id) family of dominant negative basic helix-loop-helix (bHLH) transcription factors. RT-PCR, Western blotting and in situ hybridization confirmed the significant inductions of Id1, Id2 and Id3 in the IL of CS rats. Administration of the dopamine D2 receptor agonist bromocriptine prevented the inductions of Id1-3 in the IL of CS rats, whereas application of the dopamine D2 antagonist sulpiride induced significant expressions of Id1-3 in the IL of normal rats. Moreover, an in vitro study using primary cultured melanotrophs demonstrated a direct effect on Id1-3 inductions by dopamine suppression. These results suggest that the decreased dopamine levels in the IL during CS induce Id1-3 expressions in melanotrophs. Because Id family members inhibit various bHLH transcription factors, it is conceivable that the induced Id1-3 would cooperatively modulate gene expressions in melanotrophs under CS conditions to induce hormone secretion. (c) 2010 IBRO. Published by Elsevier Ltd. All rights reserved.
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.
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
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.
Gleitz, Hélène Fe; Liao, Ai Yin; Cook, James R; Rowlston, Samuel F; Forte, Gabriella Ma; D'Souza, Zelpha; O'Leary, Claire; Holley, Rebecca J; Bigger, Brian W
Channel networks are critical components of drainage basins and delta regions. Despite the important role played by these systems in hydrology and geomorphology, there are at present no well-defined methods to evaluate numerically how two complex channel networks are geometrically far apart. The present study introduces new metrics for evaluating numerically channel networks extracted in grid digital elevation models with respect to a reference channel network (see the figure below). Streams of the evaluated network (EN) are delineated as in the Horton ordering system and examined through a priority climbing algorithm based on the triple index (ID1,ID2,ID3), where ID1 is a stream identifier that increases as the elevation of lower end of the stream increases, ID2 indicates the ID1 of the draining stream, and ID3 is the ID1 of the corresponding stream in the reference network (RN). Streams of the RN are identified by the double index (ID1,ID2). Streams of the EN are processed in the order of increasing ID1 (plots a-l in the figure below). For each processed stream of the EN, the closest stream of the RN is sought by considering all the streams of the RN sharing the same ID2. This ID2 in the RN is equal in the EN to the ID3 of the stream draining the processed stream, the one having ID1 equal to the ID2 of the processed stream. The mean stream planar distance (MSPD) and the mean stream elevation drop (MSED) are computed as the mean distance and drop, respectively, between corresponding streams. The MSPD is shown to be useful for evaluating slope direction methods and thresholds for channel initiation, whereas the MSED is shown to indicate the ability of grid coarsening strategies to retain the profiles of observed channels. The developed metrics fill a gap in the existing literature by allowing hydrologists and geomorphologists to compare descriptions of a fixed physical system obtained by using different terrain analysis methods, or different physical systems described by using the same methods.
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.
Stankic, Marko; Pavlovic, Svetlana; Chin, Yvette; Brogi, Edi; Padua, David; Norton, Larry; Massague, Joan; Benezra, Robert
2014-01-01
SUMMARY ID genes are required for breast cancer colonization of the lungs, but the mechanism remains poorly understood. Here, we show that Id1 expression induces a stem-like phenotype in breast cancer cells, while retaining epithelial properties, contrary to the notion that cancer stem-like properties are inextricably linked to the mesenchymal state. During metastatic colonization, Id1 induces a mesenchymal-to-epithelial transition (MET), specifically in cells whose mesenchymal state is dependent on the Id1 target protein Twist1 but not at the primary site, where this state is controlled by the zinc-finger protein Snail1. Knockdown of Id expression in metastasizing cells prevents MET and dramatically reduces lung colonization. Furthermore, Id1 is induced by TGFβ only in cells that have first undergone EMT, demonstrating that EMT is a pre-requisite for subsequent Id1-induced MET during lung colonization. Collectively, these studies underscore the importance of Id-mediated phenotypic switching during distinct stages of breast cancer metastasis. PMID:24332369
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.
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
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.
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.
In bilateria, positioning and looping of visceral organs requires proper left-right (L/R) asymmetry establishment. Recent work in Drosophila has identified a novel situs inversus gene encoding the unconventional type ID myosin (MyoID). In myoID mutant flies, the L/R axis is inverted, causing reversed looping of organs, such as the gut, spermiduct and genitalia. We have previously shown that MyoID interacts physically with β-Catenin, suggesting a role of the adherens junction in Drosophila L/R asymmetry. Here, we show that DE-Cadherin co-immunoprecipitates with MyoID and is required for MyoID L/R activity. We further demonstrate that MyoIC, a closely related unconventional type I myosin, can antagonize MyoID L/R activity by preventing its binding to adherens junction components, both in vitro and in vivo. Interestingly, DE-Cadherin inhibits MyoIC, providing a protective mechanism to MyoID function. Conditional genetic experiments indicate that DE-Cadherin, MyoIC and MyoID show temporal synchronicity for their function in L/R asymmetry. These data suggest that following MyoID recruitment by β-Catenin at the adherens junction, DE-Cadherin has a twofold effect on Drosophila L/R asymmetry by promoting MyoID activity and repressing that of MyoIC. Interestingly, the product of the vertebrate situs inversus gene inversin also physically interacts with β-Catenin, suggesting that the adherens junction might serve as a conserved platform for determinants to establish L/R asymmetry both in vertebrates and invertebrates.
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.
Satyanarayana, Ande; Klarmann, Kimberly D.; Gavrilova, Oksana; Keller, Jonathan R.
2012-01-01
Obesity is a major health concern that contributes to the development of diabetes, hyperlipidemia, coronary artery disease, and cancer. Id proteins are helix-loop-helix transcription factors that regulate the proliferation and differentiation of cells from multiple tissues, including adipocytes. We screened mouse tissues for the expression of Id1 and found that Id1 protein is highly expressed in brown adipose tissue (BAT) and white adipose tissue (WAT), suggesting a role for Id1 in adipogenesis and cell metabolism. Id1−/− mice are viable but show a significant reduction in fat mass (P<0.005) over the life of the animal that was not due to decreased number of adipocytes. Analysis of Id1−/− mice revealed higher energy expenditure, increased lipolysis, and fatty acid oxidation, resulting in reduced triglyceride accumulation in WAT compared to Id1+/+ mice. Serum levels of triglycerides (193.9±32.2 vs. 86.5±33.8, P<0.0005), cholesterol (189.4±33.8 vs. 110.6±8.23, P<0.0005) and leptin (1263±835 vs. 222±260, P<0.005) were significantly lower in aged Id1−/− mice compared to Id1+/+ mice. Id1-deficient mice have higher resting (P<0.005) and total (P<0.05) O2 consumption and lower respiratory exchange ratio (P<0.005), confirming that Id1−/− mice use a higher proportion of lipid as an energy source for the increased energy expenditure. The expression of PGC1α and UCP1 were 2- to 3-fold up-regulated in Id1−/− BAT, suggesting that loss of Id1 increases thermogenesis. As a consequence of higher energy expenditure and reduced fat mass, Id1−/− mice displayed enhanced insulin sensitivity. Id1 deficiency protected mice against age- and high-fat-diet-induced adiposity, insulin resistance, and hepatosteatosis. Our findings suggest that Id1 plays a critical role in the regulation of energy homeostasis and could be a potential target in the treatment of insulin resistance and fatty liver disease.—Satyanarayana, A., Klarmann, K. D., Gavrilova, l O., Keller, J. R. Ablation of the transcriptional regulator Id1 enhances energy expenditure, increases insulin sensitivity, and protects against age and diet-induced insulin resistance and hepatosteatosis. PMID:21990377
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.
Various aspects of motherese also known as infant-directed speech (IDS) have been studied for many years. As it is a widespread phenomenon, it is suspected to play some important roles in infant development. Therefore, our purpose was to provide an update of the evidence accumulated by reviewing all of the empirical or experimental studies that have been published since 1966 on IDS driving factors and impacts. Two databases were screened and 144 relevant studies were retained. General linguistic and prosodic characteristics of IDS were found in a variety of languages, and IDS was not restricted to mothers. IDS varied with factors associated with the caregiver (e.g., cultural, psychological and physiological) and the infant (e.g., reactivity and interactive feedback). IDS promoted infants’ affect, attention and language learning. Cognitive aspects of IDS have been widely studied whereas affective ones still need to be developed. However, during interactions, the following two observations were notable: (1) IDS prosody reflects emotional charges and meets infants’ preferences, and (2) mother-infant contingency and synchrony are crucial for IDS production and prolongation. Thus, IDS is part of an interactive loop that may play an important role in infants’ cognitive and social development. PMID:24205112
Mulmule, Manoj D.; Shimmy, Shankar M.; Bambole, Vaishali; Jamdar, Sahayog N.; Rawat, K. P.; Sarma, K. S. S.
2017-02-01
Idli, a steam-cooked breakfast food item consumed in India, is famous as a staple food for its spongy texture and unique fermented taste. Idli preparation is a time consuming process; although instant Idli pre-mixes as powder or batter are available in the market, they do not have the distinctive taste and aroma similar to the Idli prepared at home. Hence ready-to-eat (RTE) form of this food is in demand. Therefore, an attempt was made to prepare RTE Idli bearing similar taste as home-cooked Idli with an extended shelf-life of up to two months at an ambient temperature using Electron Beam Irradiation (EBI) at dosages 2.5 kGy, 5 kGy and 7.5 kGy and combination processing comprised of EBI dosage at 2.5 kGy and thermal treatment (80 °C for 20 min). The treated Idli's were microbiologically and sensorially evaluated at storage periods of zero day, 14 days, 30 days and 60 days. Idli's irradiated at 7.5 kGy and subjected to combination processing at 2.5 kGy and thermal treatment were shelf-stable for 60 days. 2.5 kGy and 5 kGy radiation dosages alone were not sufficient to preserve Idli samples for more than 14 days. Undesirable change in sensory properties of Idli was observed at an EBI dosage of 7.5 kGy. Sensory properties of combination processed Idli's were found to undergo minor change over the storage period. The present work suggests that lowest radiation dosage in combination with thermal treatment could be useful to achieve the extended shelf-life without considerably impairing the organoleptic quality of Ready-to-Eat Idli.
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.
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.
To establish effective working relationships with medical staff and community physicians, an IDS must adopt a strategic-planning approach that adequately incorporates physicians' needs and expectations. Research shows that most physicians considered the IDS's market position, the degree to which the IDS can offer physicians practice-enhancing capabilities, and physician involvement in IDS governance to be critical factors for the success of an IDS. By establishing a meaningful role for physicians in the organizational strategic-planning process, an IDS can significantly improve its market position and its relationships with physicians.
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.
LEE, JAE-CHUL; CHEN, BAI HUI; CHO, JEONG-HWI; KIM, IN HYE; AHN, JI HYEON; PARK, JOON HA; TAE, HYUN-JIN; CHO, GEUM-SIL; YAN, BING CHUN; KIM, DAE WON; HWANG, IN KOO; PARK, JINSEU; LEE, YUN LYUL; CHOI, SOO YOUNG; WON, MOO-HO
2015-01-01
Inhibitors of DNA-binding/differentiation (ID) proteins bind to basic helix-loop-helix (bHLH) transcription factors, including those that regulate differentiation and cell-cycle progression during development, and regulate gene transcription. However, little is known about the role of ID proteins in the brain under transient cerebral ischemic conditions. In the present study, we examined the effects of ischemia-reperfusion (I-R) injury on the immunoreactivity and protein levels of IDs 1–4 in the gerbil hippocampus proper Cornu Ammonis regions CA1–3 following 5 min of transient cerebral ischemia. Strong ID1 immunoreactivity was detected in the nuclei of pyramidal neurons in the hippocampal CA1–3 regions; immunoreactivity was significantly changed following I-R in the CA1 region, but not in the CA2/3 region. Five days following I-R, ID1 immunoreactivity was not detected in the CA1 pyramidal neurons. ID1 immunoreactivity was detected only in GABAergic interneurons in the ischemic CA1 region. Weak ID4 immunoreactivity was detected in non-pyramidal cells, and immunoreactivity was again only changed in the ischemic CA1 region. Five days following I-R, strong ID4 immunoreactivity was detected in non-pyramidal cells, which were identified as microglia, and not astrocytes, in the ischemic CA1 region. Furthermore, changes in the protein levels of ID1 and ID4 in the ischemic CA1 region studied by western blot were consistent with patterns of immunoreactivity. In summary, these results indicate that immunoreactivity and protein levels of ID1 and ID4 are distinctively altered following transient cerebral ischemia only in the CA1 region, and that the changes in ID1 and ID4 expression may relate to the ischemia-induced delayed neuronal death. PMID:25503067
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.
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.
Zhou, Peng; Robles-Murguia, Maricela; Mathew, Deepa; Duffield, Giles E.
2016-01-01
Inhibitor of DNA binding 2 (ID2) is a helix-loop-helix transcriptional repressor rhythmically expressed in many adult tissues. Our previous studies have demonstrated that Id2 null mice have sex-specific elevated glucose uptake in brown adipose tissue (BAT). Here we further explored the role of Id2 in the regulation of core body temperature over the circadian cycle and the impact of Id2 deficiency on genes involved in insulin signaling and adipogenesis in BAT. We discovered a reduced core body temperature in Id2−/− mice. Moreover, in Id2−/− BAT, 30 genes including Irs1, PPARs, and PGC-1s were identified as differentially expressed in a sex-specific pattern. These data provide valuable insights into the impact of Id2 deficiency on energy homeostasis of mice in a sex-specific manner. PMID:27144179
Ivanova, T S; Krupodorova, T A; Barshteyn, V Y; Artamonova, A B; Shlyakhovenko, V A
2014-06-01
The present status of investigations about the anticancer activity which is inherent to medicinal mushrooms, as well as their biomedical potential and future prospects are discussed. Mushroom products and extracts possess promising immunomodulating and anticancer effects, so the main biologically active substances of mushrooms responsible for immunomodulation and direct cytoto-xicity toward cancer cell lines (including rarely mentioned groups of anticancer mushroom proteins), and the mechanisms of their antitumor action were analyzed. The existing to date clinical trials of mushroom substances are mentioned. Mushroom anticancer extracts, obtained by the different solvents, are outlined. Modern approaches of cancer treatment with implication of mushroom products, including DNA vaccinotherapy with mushroom immunomodulatory adjuvants, creation of prodrugs with mushroom lectins that can recognize glycoconjugates on the cancer cell surface, development of nanovectors etc. are discussed. The future prospects of mushroom anticancer substances application, including chemical modification of polysaccharides and terpenoids, gene engineering of proteins, and implementation of vaccines are reviewed.
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.
Musselwhite, Laura W; Maciag, Karolina; Lankowski, Alex; Gretes, Michael C; Wellems, Thomas E; Tavera, Gloria; Goulding, Rebecca E; Guillen, Ethan
2012-01-01
Universities Allied for Essential Medicines organized its first Neglected Diseases and Innovation Symposium to address expanding roles of public sector research institutions in innovation in research and development of biomedical technologies for treatment of diseases, particularly neglected tropical diseases. Universities and other public research institutions are increasingly integrated into the pharmaceutical innovation system. Academic entities now routinely undertake robust high-throughput screening and medicinal chemistry research programs to identify lead compounds for small molecule drugs and novel drug targets. Furthermore, product development partnerships are emerging between academic institutions, non-profit entities, and biotechnology and pharmaceutical companies to create diagnostics, therapies, and vaccines for diseases of the poor. With not for profit mission statements, open access publishing standards, open source platforms for data sharing and collaboration, and a shift in focus to more translational research, universities and other public research institutions are well-placed to accelerate development of medical technologies, particularly for neglected tropical diseases.
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.
Summary Follicular helper T (Tfh) cells are specialized providers of T cell help to B cells, and are essential for germinal center formation, affinity maturation, and the development of most high affinity antibodies and memory B cells. Tfh cell differentiation is a multi-stage, multi-factorial process involving B cell lymphoma 6 (Bcl6) and other transcription factors. This article reviews understanding of Tfh cell biology, including their differentiation, migration, transcriptional regulation, and B cell help functions. Tfh cells are critical components of many protective immune responses against pathogens. As such, there is strong interest in harnessing Tfh cells to improve vaccination strategies. Tfh cells also have roles in a range of other diseases, particularly autoimmune diseases. Overall, there have been dramatic advances in this young field, but there is much to be learned about Tfh cell biology in the interest of applying that knowledge to biomedical needs. PMID:25367570
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
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…
Neumeier, William H; Guerra, Nichole; Thirumalai, Mohanraj; Geer, Betty; Ervin, David; Rimmer, James H
2017-10-23
Intellectual disability (ID) is characterized by limitations in intellectual functioning and adaptive behavior. Adults with ID exhibit higher rates of obesity and poorer health status compared to the general population. Continuity of care and barriers to health-related activities may contribute to the poorer health status observed in this population. To address this problem, a tailored weight management online health information and communication technology platform, known as POWERS forID , was developed and is being tested to determine if this delivery mechanism can improve weight maintenance/weight loss in adults with ID. Obese adults with mild-to-moderate ID (n = 70) are randomized to the POWERS forID intervention or control group for a 24-week trial. Each group undergoes an assessment that includes body weight, waist circumference, and percent body fat at baseline and at weeks 6, 12, and 24. Physical activity barriers, healthy eating barriers, food frequency, and psychosocial wellbeing are measured at baseline and at weeks 12 and 24. Blood lipids are assessed at baseline and 24 weeks. Participants randomized to POWERS forID receive access to the POWERS forID website and calls from a health coach (weekly during weeks 1-12, biweekly during weeks 13-24). The health coach employs motivational interviewing techniques adapted for individuals with ID to promote behavior change. Participants randomized to the control group receive standard clinical weight-loss care. Differences in weight, waist circumference, blood lipids, percent body fat, and psychosocial self-report will be assessed. Barriers and facilitators of implementation as well as perception of study outcomes will be conducted via qualitative analysis. POWERS forID is a novel information and communication technology platform designed to address health needs for adults with ID. This article describes the development and components of POWERS forID . The overall aim is to assess usability and feasibility of POWERS forID for promoting weight loss for obese adults with ID over the course of a 24-week randomized control trial. Clinicaltrials.gov, NCT03139760 . Registered on XXX.
Id (DNA binding and/or differentiation) proteins occur physiologically during ontogenesis and negatively regulate the activity of other helix-loop-helix (HLH) proteins. Id2 protein causes block of cells differentiation in the S phase of the cell cycle and regulates the activity of Rb protein. The role of Id2 protein in physiological cell cycle progression and in neuroblastoma (NBL) pathogenesis was proposed by Lasorella. The aim of the study was evaluation of Id2 expression and its prognostic significance in NBL cells coming from primary tumors and evaluation of its prognostic significance, and correlation of Id2 expression with known prognostic factors. Sixty patients with primary NBL treated from 1991 to 2005 were included in the analysis. We found 50 patients with high and 10 patients with low intensity of Id2 expression. The median percentage of NBL cells with Id2 expression was 88 %. We found no correlation between the number of NBL cells or the intensity of Id2 expression and OS and DFS. In patients with stage 4 NBL, almost all patients had high expression of Id2 and it was significantly more common than in other disease stages (p = 0,03). We found no correlation between Id2 expression and other known prognostic factor in NBL patients. We assume that Id2 is not prognostic factor. However, due to its abundant expression in most of NBL cells and its role in cell cycle, it may be potential therapeutic target. Exact knowledge of expression time may be helpful in explaining mechanisms of oncogenesis.
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
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.
Inhibitor of differentiation or DNA binding (Id1) is a member of the helix-loop-helix transcription factor family that is overexpressed in various types of cancer, including gastric carcinoma. Previous studies showed that Id1 is a prognostic marker in patients with gastric cancer. However, the role of Id1 in the proliferation of human gastric cancer cells has yet to be clarified. In the present study, we downregulated the Id1 gene in SGC-7901 gastric cancer cells by RNA interference, and we also constructed a recombinant plasmid-expressing Id1 to investigate its effects on the proliferation of SGC-7901 cells. Results showed that the downregulation of Id1 inhibited proliferation of SGC-7901 cells, while the upregulation of Id1 had no effect on SGC-7901 cell proliferation. The potential mechanism was also investigated. The changes of certain proteins associated with cell proliferation, apoptosis and the cell cycle were detected by western blotting. Furthermore, we demonstrated a positive correlation between Id1 and phospho-Akt expression in SGC-7901 cells. PMID:22245935
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.
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.
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.
Lee, Stephen C; Bhalerao, Khaustaub; Ferrari, Mauro
2004-05-01
Nanotechnology provides multifunctional agents for in vivo use that increasingly blur the distinction between pharmaceuticals and medical devices. Realization of such therapeutic nanodevices requires multidisciplinary effort that is difficult for individual device developers to sustain, and identification of appropriate collaborations outside ones own field can itself be challenging. Further, as in vivo nanodevices become increasingly complex, their design will increasingly demand systems level thinking. System engineering tools such as object-oriented analysis, object-oriented design (OOA/D) and unified modeling language (UML) are applicable to nanodevices built from biological components, help logically manage the knowledge needed to design them, and help identify useful collaborative relationships for device designers. We demonstrate the utility of these systems engineering tools by reverse engineering an existing molecular device (the bacmid molecular cloning system) using them, and illustrate how object-oriented approaches identify fungible components (objects) in nanodevices in a way that facilitates design of families of related devices, rather than single inventions. We also explore the utility of object-oriented approaches for design of another class of therapeutic nanodevices, vaccines. While they are useful for design of current nanodevices, the power of systems design tools for biomedical nanotechnology will become increasingly apparent as the complexity and sophistication of in vivo nanosystems increases. The nested, hierarchical nature of object-oriented approaches allows treatment of devices as objects in higher-order structures, and so will facilitate concatenation of multiple devices into higher-order, higher-function nanosystems.
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.
Earthquakes are among the most impressive geological processes with destructive effects on humans, nature and infrastructures. Secondary earthquake environmental effects (EEE) are induced by the ground shaking and are classified into ground cracks, slope movements, dust clouds, liquefactions, hydrological anomalies, tsunamis, trees shaking and jumping stones. Infectious diseases (ID) emerging during the post-earthquake period are considered as secondary earthquake effects on public health. This study involved an extensive and systematic literature review of 121 research publications related to the public health impact of 28 earthquakes from 1980 to 2015 with moment magnitude (Mw) from 6.1 to 9.2 and their secondary EEE including landslides, liquefaction and tsunamis generated in various tectonic environments (extensional, transform, compressional) around the world (21 events in Asia, 5 in America and one each in Oceania and Europe). The inclusion criteria were the literature type comprising journal articles and official reports, the natural disaster type including earthquakes and their secondary EEE (landslides, liquefaction, tsunamis), the population type including humans and the outcome measures characterized by disease incidence increase. The potential post-earthquake ID are classified into 14 groups including respiratory (detected after 15 of 28 earthquakes, 53.57%), water-borne (15, 53.57%), skin (8, 28.57%), vector-borne (8, 28.57%) wound-related (6, 21.43%), blood-borne (4, 14.29%), pulmonary (4, 14.29%), fecal-oral (3, 10.71%), food-borne (3, 10.71%), fungal (3, 10.71%), parasitic (3, 10.71%), eye (1, 3.57%), mite-borne (1, 3.57%) and soil-borne (1, 3.57%) infections. Based on age and genre data available for 15 earthquakes, the most vulnerable population groups are males, young children (age ≤ 10 years) and adults (age ≥ 65 years). Cholera, pneumonia and tetanus are the deadliest post-earthquake ID. The risk factors leading not only to disease emergence but also to disease incidence increase include (1) damage to infrastructures and health care systems that remained unfixed for a long time in the critical post-earthquake period, (2) aggravating weather conditions comprising immense and dramatic temperature changes, (3) prolonged physical exposure to large dust clouds generated by landslides and aspiration of contaminated tsunami water, (4) unfavorable conditions in overcrowded emergency shelters, (5) increased exposure to disease vectors population, (6) the weak immune system of elders, chronically ill individual and young children, (7) large percentage of illiteracy and population living below the national poverty line (insufficient personal hygiene), (8) poor education and training on disease prevention, (9) sanitary deficiencies, (10) lack of screening for blood-borne diseases before emergency surgeries, blood transfusions and intravascular drug use, (11) use of unsterilized medical equipment, (12) insufficient or low vaccination coverage and (13) close contact with the affected local population. In conclusion, our study referred to potential ID following strong, major and great earthquakes and their secondary EEE from 1980 to 2015. The establishment of a strong disaster preparedness plan following international guidelines and comprising adequate environmental and infrastructure planning and resilience of health facilities is fundamental for the enhancement of surveillance systems, the early detection of the emergence and spread of ID and their successful management.
Sharma, Bal Krishan; Kolhe, Ravindra; Black, Stephen M.; Keller, Jonathan R.; Mivechi, Nahid F.; Satyanarayana, Ande
2016-01-01
Reprograming of metabolism is one of the central hallmarks of cancer. The majority of cancer cells depend on high rates of glycolysis and glutaminolysis for their growth and survival. A number of oncogenes and tumor suppressors have been connected to the regulation of altered glucose and glutamine metabolism in cancer cells. For example, the oncogene c-Myc plays vital roles in cancer cell metabolic adaptation by directly regulating various genes that participate in aerobic glycolysis and glutaminolysis. Inhibitor of differentiation 1 (Id1) is a helix-loop-helix transcription factor that plays important roles in cell proliferation, differentiation, and cell fate determination. Overexpression of Id1 causes intestinal adenomas and thymic lymphomas in mice, suggesting that Id1 could function as an oncogene. Despite it being an oncogene, whether Id1 plays any prominent role in cancer cell metabolic reprograming is unknown. Here, we demonstrate that Id1 is strongly expressed in human and mouse liver tumors and in hepatocellular carcinoma (HCC) cell lines, whereas its expression is very low or undetectable in normal liver tissues. In HCC cells, Id1 expression is regulated by the MAPK/ERK pathway at the transcriptional level. Knockdown of Id1 suppressed aerobic glycolysis and glutaminolysis, suggesting that Id1 promotes a metabolic shift toward aerobic glycolysis. At the molecular level, Id1 mediates its metabolic effects by regulating the expression levels of c-Myc. Knockdown of Id1 resulted in down-regulation (∼75%) of c-Myc, whereas overexpression of Id1 strongly induced (3-fold) c-Myc levels. Interestingly, knockdown of c-Myc resulted in down-regulation (∼60%) of Id1, suggesting a positive feedback-loop regulatory mechanism between Id1 and c-Myc. Under anaerobic conditions, both Id1 and c-Myc are down-regulated (50–70%), and overexpression of oxygen-insensitive hypoxia-inducible factor 1α (Hif1α) or its downstream target Mxi1 resulted in a significant reduction of c-Myc and Id1 (∼70%), suggesting that Hif1α suppresses Id1 and c-Myc under anaerobic conditions via Mxi1. Together, our findings indicate a prominent novel role for Id1 in liver cancer cell metabolic adaptation.—Sharma, B. K., Kolhe, R., Black, S. M., Keller, J. R., Mivechi, N. F., Satyanarayana, A. Inhibitor of differentiation 1 transcription factor promotes metabolic reprogramming in hepatocellular carcinoma cells. PMID:26330493
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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.
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
Inhibitor of DNA binding (ID) proteins, including ID1-4, are transcriptional regulators involved in promoting cell proliferation and survival in various cell types. Although upregulation of Id proteins has been associated with a broad spectrum of tumors, recent studies have identified that ID3 plays a tumor suppressor role in the development of Burkitt’s lymphoma in humans and Hepatosplenic T cell lymphomas in mice. Here, we report rapid lymphoma development in Id2/Id3 double knockout (L-DKO) mice caused by unchecked expansion of either invariant Natural Killer T (iNKT) cells, or a unique subset of innate-like, CD1d-independent T cells. These populations started expansion in neonatal mice and, upon malignant transformation, caused fatality at age between 3–11 months. The malignant cells also gave rise to lymphomas upon transfer to Rag-deficient and wild-type hosts, reaffirming their inherent tumorigenic potential. Microarray analysis revealed a significantly modified program in these neonatal iNKT cells that ultimately led to their malignant transformation. The lymphoma cells demonstrated chromosome instability, along with upregulation of several different signaling pathways, including the cytokine-cytokine receptor interaction pathway, which can promote their expansion and migration. Dysregulation of genes with reported driver mutations and the NF-kB pathway were found to be shared between L-DKO lymphomas and human NKT tumors. Our work identifies a distinct premalignant state and multiple tumoriogenic pathways caused by loss function of ID2 and ID3. Thus, conditional deletion of Id2 and Id3 in developing T cells establishes a unique animal model for iNKT and relevant innate-like lymphomas. PMID:28258199
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
Rodríguez, José L.; Sandoval, Juan; Serviddio, Gaetano; Sastre, Juan; Morante, María; Perrelli, Maria-Giulia; Martínez-Chantar, María L.; Viña, José; Viña, Juan R.; Mato, José M.; Ávila, Matías A.; Franco, Luis; López-Rodas, Gerardo; Torres, Luis
2006-01-01
The Id (inhibitor of DNA binding or inhibitor of differentiation) helix–loop–helix proteins are involved in the regulation of cell growth, differentiation and cancer. The fact that the molecular mechanisms of liver regeneration are not completely understood prompted us to study the fate of Id2 in proliferating liver. Id2 increases in liver regeneration after partial hepatectomy, following the early induction of its gene. Co-immunoprecipitation shows that Id2 forms a complex with E2F4, p130 and mSin3A in quiescent liver and all these components are present at the c-myc promoter as shown using ChIP (chromatin immunoprecipitation). Activation of c-myc during hepatocyte priming (G0–G1 transition) correlates with the dissociation of Id2 and HDAC (histone deacetylase), albeit p130 remains bound at least until 6 h. Moreover, as the G0–G1 transition progresses, Id2 and HDAC again bind the c-myc promoter concomitantly with the repression of this gene. The time course of c-myc binding to the Id2 promoter, as determined by ChIP assays is compatible with a role of the oncoprotein as a transcriptional inducer of Id2 in liver regeneration. Immunohistochemical analysis shows that Id2 also increases in proliferating hepatocytes after bile duct ligation. In this case, the pattern of Id2 presence in the c-myc promoter parallels that found in regenerating liver. Our results may suggest a control role for Id2 in hepatocyte priming, through a p130 dissociation-independent regulation of c-myc. PMID:16776654
... 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...
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.
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
The present study examined the concurrent validity of the Hamburg Wechsler Intelligenztest für Kinder - IV (HAWIK-IV; Petermann & Petermann, 2010) and the Intelligence and Development Scales (IDS; Grob, Meyer & Hagmann-von Arx, 2009). HAWIK-IV and IDS were administered in counterbalanced order to N = 172 children aged 6 to 11 years. The study presents the descriptive statistics, correlations, and an exploratory factor analysis of the data. There is a high correlation between HAWIK-IV Full Scale IQ and IDS intelligence score (r = .83). HAWIK-IV indices showed moderate to high correlations with the cognitive scales of the IDS (Cognition, Language, Mathematics). Low to absent correlations were found between HAWIK-IV indices and the noncognitive scales of the IDS (Social-Emotional Competence, Psychomotor, Achievement Motivation). The factor structure can be interpreted meaningfully and allows integration of the IDS cognitive, language, and mathematical subtests into the four HAWIK-IV indices. The results show that HAWIK-IV and IDS test results can be related to each other.
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.
Foot-and-mouth disease virus (FMDV) infection is responsible for the heavy economic losses in stockbreeding each year. Because of the limited effectiveness of existing vaccines and antiviral drugs, the development of new strategies is needed. RNA interference (RNAi) is an effective means of suppressing virus replication in vitro. Here we demonstrate that treatment with recombinant, replication-defective human adenovirus type 5 (Ad5) expressing short-hairpin RNAs (shRNAs) directed against either structural protein 1D (Ad5-NT21) or polymerase 3D (Ad5-POL) of FMDV totally protects swine IBRS-2 cells from homologous FMDV infection, whereas only Ad5-POL inhibits heterologous FMDV replication. Moreover, delivery of these shRNAs significantly reduces the susceptibility of guinea pigs and swine to FMDV infection. Three of five guinea pigs inoculated with 10(6) PFU of Ad5-POL and challenged 24 h later with 50 50% infectious doses (ID50) of homologous virus were protected from the major clinical manifestation of disease: the appearance of vesicles on the feet. Two of three swine inoculated with an Ad5-NT21-Ad5-POL mixture containing 2 x 10(9) PFU each and challenged 24 h later with 100 ID50 of homologous virus were protected from the major clinical disease, but treatment with a higher dose of adenovirus mixture cannot promote protection of animals. The inhibition was rapid and specific because treatment with a control adenovirus construct (Ad5-LacZ) expressing Escherichia coli galactosidase-specific shRNA showed no marked antiviral activity. Our data highlight the in vivo potential of RNAi technology in the case of FMD.
Gyawali, Sudesh; Rathore, Devendra S; Kc, Bhuvan; Shankar, P Ravi
2013-01-03
Unsafe injection practices and injection overuse are widespread in developing countries harming the patient and inviting risks to the health care workers. In Nepal, there is a dearth of documented information about injection practices so the present study was carried out: a) to determine whether the selected government health facilities satisfy the conditions for safe injections in terms of staff training, availability of sterile injectable equipment and their proper disposal after use and b) to assess knowledge and attitudes of healthcare workers in these health care facilities with regard to injection safety. A descriptive cross-sectional mixed type (qualitative and quantitative) survey was carried out from 18th May to 16th June 2012. In-depth interviews with the in-charges were conducted using a semi-structured questionnaire. Observation of the health facilities using a structured observation tool was done. The data were analysed manually by summarizing, tabulating and presenting in various formats. The in-charges (eight males, two females) who participated in the study ranged in age from 30 to 50 years with a mean age of 37.8 years. Severe infection followed by pain was the most important cause for injection use with injection Gentamicin being most commonly prescribed. New single use (disposable) injections and auto-disable syringes were used to inject curative drugs and vaccines respectively. Sufficient safety boxes were also supplied to dispose the used syringe. All health care workers had received full course of Hepatitis B vaccine and were knowledgeable about at least one pathogen transmitted through unsafe injection practices. Injection safety management policy and waste disposal guideline was not available for viewing in any of the facilities. The office staff who disposed the bio-medical wastes did so without taking any safety measures. Moreover, none of these staff had received any formal training in waste management. Certain safe injection practices were noticed in the studied health care facilities but there remain a number of grey areas where unsafe practices still persists placing patient and health workers at risk of associated hazards. Training concentrating on injection safety, guidelines to dispose biomedical waste and monitoring of the activity is needed.
Background Unsafe injection practices and injection overuse are widespread in developing countries harming the patient and inviting risks to the health care workers. In Nepal, there is a dearth of documented information about injection practices so the present study was carried out: a) to determine whether the selected government health facilities satisfy the conditions for safe injections in terms of staff training, availability of sterile injectable equipment and their proper disposal after use and b) to assess knowledge and attitudes of healthcare workers in these health care facilities with regard to injection safety. Methodology A descriptive cross-sectional mixed type (qualitative and quantitative) survey was carried out from 18th May to 16th June 2012. In-depth interviews with the in-charges were conducted using a semi-structured questionnaire. Observation of the health facilities using a structured observation tool was done. The data were analysed manually by summarizing, tabulating and presenting in various formats. Results The in-charges (eight males, two females) who participated in the study ranged in age from 30 to 50 years with a mean age of 37.8 years. Severe infection followed by pain was the most important cause for injection use with injection Gentamicin being most commonly prescribed. New single use (disposable) injections and auto-disable syringes were used to inject curative drugs and vaccines respectively. Sufficient safety boxes were also supplied to dispose the used syringe. All health care workers had received full course of Hepatitis B vaccine and were knowledgeable about at least one pathogen transmitted through unsafe injection practices. Injection safety management policy and waste disposal guideline was not available for viewing in any of the facilities. The office staff who disposed the bio-medical wastes did so without taking any safety measures. Moreover, none of these staff had received any formal training in waste management. Conclusions Certain safe injection practices were noticed in the studied health care facilities but there remain a number of grey areas where unsafe practices still persists placing patient and health workers at risk of associated hazards. Training concentrating on injection safety, guidelines to dispose biomedical waste and monitoring of the activity is needed. PMID:23286907
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.
The transcription factor ID2 is an important repressor of neural differentiation strongly implicated in nervous system cancers. MicroRNAs (miRNAs) are increasingly involved in differentiation control and cancer development. Here we show that two miRNAs upregulated on differentiation of neuroblastoma cells – miR-9 and miR-103 – restrain ID2 expression by directly targeting the coding sequence and 3′ untranslated region of the ID2 encoding messenger RNA, respectively. Notably, the two miRNAs show an inverse correlation with ID2 during neuroblastoma cell differentiation induced by retinoic acid. Overexpression of miR-9 and miR-103 in neuroblastoma cells reduces proliferation and promotes differentiation, as it was shown to occur upon ID2 inhibition. Conversely, an ID2 mutant that cannot be targeted by either miRNA prevents retinoic acid-induced differentiation more efficient than wild-type ID2. These findings reveal a new regulatory module involving two microRNAs upregulated during neural differentiation that directly target expression of the key differentiation inhibitor ID2, suggesting that its alteration may be involved in neural cancer development. PMID:22848373
The transcription factor ID2 is an important repressor of neural differentiation strongly implicated in nervous system cancers. MicroRNAs (miRNAs) are increasingly involved in differentiation control and cancer development. Here we show that two miRNAs upregulated on differentiation of neuroblastoma cells--miR-9 and miR-103--restrain ID2 expression by directly targeting the coding sequence and 3' untranslated region of the ID2 encoding messenger RNA, respectively. Notably, the two miRNAs show an inverse correlation with ID2 during neuroblastoma cell differentiation induced by retinoic acid. Overexpression of miR-9 and miR-103 in neuroblastoma cells reduces proliferation and promotes differentiation, as it was shown to occur upon ID2 inhibition. Conversely, an ID2 mutant that cannot be targeted by either miRNA prevents retinoic acid-induced differentiation more efficient than wild-type ID2. These findings reveal a new regulatory module involving two microRNAs upregulated during neural differentiation that directly target expression of the key differentiation inhibitor ID2, suggesting that its alteration may be involved in neural cancer development.
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.
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.
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…
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
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.
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.
Zhou, Peng; Hummel, Alyssa D.; Pywell, Cameron M.; Dong, X. Charlie; Duffield, Giles E.
2014-01-01
Inhibitor of DNA binding 2 (ID2) is a helix-loop-helix transcriptional repressor rhythmically expressed in many adult tissues. Our previous studies have demonstrated that Id2 null mice have altered expression of circadian genes involved in lipid metabolism, altered circadian feeding behavior, and sex-specific enhancement of insulin sensitivity and elevated glucose uptake in skeletal muscle and brown adipose tissue. Here we further characterized the Id2−/− mouse metabolic phenotype in a sex-specific context and under low and high fat diets, and examined metabolic and endocrine parameters associated with lipid and glucose metabolism. Under the low-fat diet Id2−/− mice showed decreased weight gain, reduced gonadal fat mass, and a lower survival rate. Under the high-fat diet, body weight and gonadal fat gain of Id2−/− male mice was comparable to control mice and survival rate improved markedly. Furthermore, the high-fat diet treated Id2−/− male mice lost the enhanced glucose tolerance feature observed in the other Id2−/− groups, and there was a sex-specific difference in white adipose tissue storage of Id2−/− mice. Additionally, a distinct pattern of hepatic lipid accumulation was observed in Id2−/− males: low lipids on the low-fat diet and steatosis on the high-fat diet. In summary, these data provides valuable insights into the impact of Id2 deficiency on metabolic homeostasis of mice in a sex-specific manner. PMID:25108156
Many challenging engineering problems are regular, meaning solutions to one part of a problem can be reused to solve other parts. Evolutionary algorithms with indirect encoding perform better on regular problems because they reuse genomic information to create regular phenotypes. However, on problems that are mostly regular, but contain some irregularities, which describes most real-world problems, indirect encodings struggle to handle the irregularities, hurting performance. Direct encodings are better at producing irregular phenotypes, but cannot exploit regularity. An algorithm called HybrID combines the best of both: it first evolves with indirect encoding to exploit problem regularity, then switches to direct encoding to handle problem irregularity. While HybrID has been shown to outperform both indirect and direct encoding, its initial implementation required the manual specification of when to switch from indirect to direct encoding. In this paper, we test two new methods to improve HybrID by eliminating the need to manually specify this parameter. Auto-Switch-HybrID automatically switches from indirect to direct encoding when fitness stagnates. Offset-HybrID simultaneously evolves an indirect encoding with directly encoded offsets, eliminating the need to switch. We compare the original HybrID to these alternatives on three different problems with adjustable regularity. The results show that both Auto-Switch-HybrID and Offset-HybrID outperform the original HybrID on different types of problems, and thus offer more tools for researchers to solve challenging problems. The Offset-HybrID algorithm is particularly interesting because it suggests a path forward for automatically and simultaneously combining the best traits of indirect and direct encoding.
...-AB20 Children's Online Privacy Protection Rule Proposed Parental Consent Method; AssertID, Inc. Application for Approval of Parental Consent Method AGENCY: Federal Trade Commission (FTC or Commission... concerning the proposed parental consent method submitted by AssertID, Inc. (``AssertID'') under the...
. 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
December 1997 removal close-out report to document response activities in areas north of B-Street at the LCP Chemicals Superfund Site, GA. Region ID: 04 DocID: 10879193, DocDate: 12-01-1997 Region ID: 04 DocID: 10879193, DocDate: 12-01-1997
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.
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…
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
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.
SUMMARY We developed Split DamID (SpDamID), a protein complementation version of DamID, to mark genomic DNA bound in vivo by interacting or juxtapositioned transcription factors. Inactive halves of DAM (DNA Adenine Methyltransferase) were fused to protein pairs to be queried Interaction or proximity enabled DAM reconstitution and methylation of adenine in GATC. Inducible SpDamID was used to analyze Notch-mediated transcriptional activation. We demonstrate that Notch complexes label RBP sites broadly across the genome, and show that a subset of these complexes that recruit MAML and p300 undergo changes in chromatin accessibility in response to Notch signaling. SpDamID differentiates between monomeric and dimeric binding thereby allowing for identification of half-site motifs used by Notch dimers. Motif enrichment of Notch enhancers coupled with SpDamID reveals co-targeting of regulatory sequences by Notch and Runx1. SpDamID represents a sensitive and powerful tool that enables dynamic analysis of combinatorial protein-DNA transactions at a genome-wide level. PMID:26257285
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.
The first phase of the ESRF beamline ID23 to be constructed was ID23-1, a tunable MAD-capable beamline which opened to users in early 2004. The second phase of the beamline to be constructed is ID23-2, a monochromatic microfocus beamline dedicated to macromolecular crystallography experiments. Beamline ID23-2 makes use of well characterized optical elements: a single-bounce silicon (111) monochromator and two mirrors in Kirkpatrick–Baez geometry to focus the X-ray beam. A major design goal of the ID23-2 beamline is to provide a reliable, easy-to-use and routine microfocus beam. ID23-2 started operation in November 2005, as the first beamline dedicated to microfocus macromolecular crystallography. The beamline has taken the standard automated ESRF macromolecular crystallography environment (both hardware and software), allowing users of ID23-2 to be rapidly familiar with the microfocus environment. This paper describes the beamline design, the special considerations taken into account given the microfocus beam, and summarizes the results of the first years of the beamline operation. PMID:20029119
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
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
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.
This paper presents a research-based teaching-learning sequence (TLS) that focuses on the notion of interaction in teaching Newton's third law (N3 law) which is, as earlier studies have shown, a challenging topic for students to learn. The TLS made systematic use of a visual representation tool—an interaction diagram (ID)—highlighting interactions between objects and addressing the learning demand related to N3 law. This approach had been successful in enhancing students' understanding of N3 law in pilot studies conducted by teacher-researchers. However, it was unclear whether teachers, who have neither been involved with the research nor received intensive tutoring, could replicate the positive results in ordinary school settings. To address this question, we present an empirical study conducted in 10 Finnish upper secondary schools with students ( n = 261, aged 16) taking their mandatory physics course. The study design involved three groups: the heavy ID group (the TLS with seven to eight exercises on IDs), the light ID group (two to three exercises on IDs) and the no ID group (no exercises on IDs). The heavy and light ID groups answered eight ID questions, and all the students answered four questions on N3 law after teaching the force concept. The findings clearly suggest that systematic use of the IDs in teaching the force concept significantly fostered students' understanding of N3 law even with teachers who have no intensive tutoring or research background.
Many challenging engineering problems are regular, meaning solutions to one part of a problem can be reused to solve other parts. Evolutionary algorithms with indirect encoding perform better on regular problems because they reuse genomic information to create regular phenotypes. However, on problems that are mostly regular, but contain some irregularities, which describes most real-world problems, indirect encodings struggle to handle the irregularities, hurting performance. Direct encodings are better at producing irregular phenotypes, but cannot exploit regularity. An algorithm called HybrID combines the best of both: it first evolves with indirect encoding to exploit problem regularity, then switches to direct encoding to handle problem irregularity. While HybrID has been shown to outperform both indirect and direct encoding, its initial implementation required the manual specification of when to switch from indirect to direct encoding. In this paper, we test two new methods to improve HybrID by eliminating the need to manually specify this parameter. Auto-Switch-HybrID automatically switches from indirect to direct encoding when fitness stagnates. Offset-HybrID simultaneously evolves an indirect encoding with directly encoded offsets, eliminating the need to switch. We compare the original HybrID to these alternatives on three different problems with adjustable regularity. The results show that both Auto-Switch-HybrID and Offset-HybrID outperform the original HybrID on different types of problems, and thus offer more tools for researchers to solve challenging problems. The Offset-HybrID algorithm is particularly interesting because it suggests a path forward for automatically and simultaneously combining the best traits of indirect and direct encoding. PMID:28334002
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.
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
"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.
Olden, Matthias; Holle, Rolf; Heid, Iris M; Stark, Klaus
2016-09-15
Creating study identifiers and assigning them to study participants is an important feature in epidemiologic studies, ensuring the consistency and privacy of the study data. The numbering system for identifiers needs to be random within certain number constraints, to carry extensions coding for organizational information, or to contain multiple layers of numbers per participant to diversify data access. Available software can generate globally-unique identifiers, but identifier-creating tools meeting the special needs of epidemiological studies are lacking. We have thus set out to develop a software program to generate IDs for epidemiological or clinical studies. Our software IDGenerator creates unique identifiers that not only carry a random identifier for a study participant, but also support the creation of structured IDs, where organizational information is coded into the ID directly. This may include study center (for multicenter-studies), study track (for studies with diversified study programs), or study visit (baseline, follow-up, regularly repeated visits). Our software can be used to add a check digit to the ID to minimize data entry errors. It facilitates the generation of IDs in batches and the creation of layered IDs (personal data ID, study data ID, temporary ID, external data ID) to ensure a high standard of data privacy. The software is supported by a user-friendly graphic interface that enables the generation of IDs in both standard text and barcode 128B format. Our software IDGenerator can create identifiers meeting the specific needs for epidemiologic or clinical studies to facilitate study organization and data privacy. IDGenerator is freeware under the GNU General Public License version 3; a Windows port and the source code can be downloaded at the Open Science Framework website: https://osf.io/urs2g/ .
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.
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.
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
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/.
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
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.
Trivedi, M H; Rush, A J; Ibrahim, H M; Carmody, T J; Biggs, M M; Suppes, T; Crismon, M L; Shores-Wilson, K; Toprac, M G; Dennehy, E B; Witte, B; Kashner, T M
2004-01-01
The present study provides additional data on the psychometric properties of the 30-item Inventory of Depressive Symptomatology (IDS) and of the recently developed Quick Inventory of Depressive Symptomatology (QIDS), a brief 16-item symptom severity rating scale that was derived from the longer form. Both the IDS and QIDS are available in matched clinician-rated (IDS-C30; QIDS-C16) and self-report (IDS-SR30; QIDS-SR16) formats. The patient samples included 544 out-patients with major depressive disorder (MDD) and 402 out-patients with bipolar disorder (BD) drawn from 19 regionally and ethnicically diverse clinics as part of the Texas Medication Algorithm Project (TMAP). Psychometric analyses including sensitivity to change with treatment were conducted. Internal consistencies (Cronbach's alpha) ranged from 0.81 to 0.94 for all four scales (QIDS-C16, QIDS-SR16, IDS-C30 and IDS-SR30) in both MDD and BD patients. Sad mood, involvement, energy, concentration and self-outlook had the highest item-total correlations among patients with MDD and BD across all four scales. QIDS-SR16 and IDS-SR30 total scores were highly correlated among patients with MDD at exit (c = 0.83). QIDS-C16 and IDS-C30 total scores were also highly correlated among patients with MDD (c = 0.82) and patients with BD (c = 0.81). The IDS-SR30, IDS-C30, QIDS-SR16, and QIDS-C16 were equivalently sensitive to symptom change, indicating high concurrent validity for all four scales. High concurrent validity was also documented based on the SF-12 Mental Health Summary score for the population divided in quintiles based on their IDS or QIDS score. The QIDS-SR16 and QIDS-C16, as well as the longer 30-item versions, have highly acceptable psychometric properties and are treatment sensitive measures of symptom severity in depression.
The focus of the present study is the Brazilian response within science, technology and innovation to the targets formulated in the UNGASS document. An analysis was made of items 70-73 of the UNGASS Draft Declaration of Commitment on HIV/AIDS (2001), which defined science, technology and innovation targets relating to HIV/AIDS. The main topics listed in these items were put into operation in the form of keywords, in order to guide systematic searches within the standard biomedicine databases, also including the subdivisions of the Web of Science relating to natural and social sciences. The success of Brazilian research within the field of characterization and isolation of HIV-1 is undeniable. Phase II/III vaccine studies have been developed in Rio de Janeiro, Belo Horizonte and São Paulo. Empirical studies on the monitoring of primary resistance have been developed in specific populations, through the Brazilian HIV Resistance Monitoring Network. Within the field of monitoring secondary resistance, initiatives such as the National Genotyping Network have been highlighted. Two national systems--the Mortality Information System and the Notifiable Diseases Information System (Aids)--and some studies with wider coverage have given rise to work on trends within the epidemic. The production of high-quality generic medications and their free distribution to patients have been highlighted. Brazil has implemented a consistent and diversified response within the field of HIV/AIDS, with studies relating to the development of vaccines, new medications and monitoring of the epidemic.
Montañez, Maria Isabel; Ruiz-Sanchez, Antonio J; Perez-Inestrosa, Ezequiel
2010-08-01
We provide an overview of the application of the concepts of nanoscience and nanotechnology as a novel scientific approach to the area of nanomedicine related to the domain of the immune system. Particular emphasis will be paid to studies on drug allergy reactions. Several well defined chemical structures arranged in the dimension of the nanoscale are currently being studied for biomedical purposes. By interacting with the immune system, some of these show promising applications as vaccines, diagnostic tools and activators/effectors of the immune response. Even a brief listing of some key applications of nanostructured materials shows how broad and intense this area of nanomedicine is. As a result of the development of nanoscience and nanotechnology applied to medicine, new approaches can be envisioned for problems related to the modulation of the immune response, as well as in immunodiagnosis, and to design new tools to solve related medical challenges. Nanoparticles offer unique advantages with which to exploit new properties and for materials to play a major role in new diagnostic techniques and therapies. Fullerene-C60 and multivalent functionalized gold nanoparticles of various sizes have led to new tools and opened up new ways to study and interact with the immune system. Some of the most versatile nanostructures are dendrimers. In their interaction with the immune system they can naturally occurring macromolecules, taking advantage of the fact that dendrimers can be synthesized into nanosized structures. Their multivalence can be successfully exploited in vaccines and diagnostic tests for allergic reactions.
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.
Bouchaouch, Abdelali; Hassani, Fahd Derkaoui; Abboud, Hilal; Mukengeshay, Jeff Ntalaja; El Fatemi, Nizare; Gana, Rachid; El Maaqili, Moulay Rchid; El Abbadi, Najia; Bellakhdar, Fouad
2015-01-01
Les traumatismes de l’étage antérieur de la base du crâne représentent 15 à 20% des traumatismes crâniens en général. Ils menacent les structures neuro-encéphaliques sus jacentes et sont très souvent responsables de brèches ostéo-méningées exposant au risque infectieux. Notre travail a concerné 136 dossiers exploitables de traumatisme de l’étage antérieur de la base du crâne colligés sur une période de 10 ans entre janvier 2003 et décembre 2012. Le diagnostic a été suspecté devant les signes cliniques évocateurs (ecchymose péri-orbitaire, rhinorrhée…) et a été confirmé dans la plupart des cas par la TDM. Le traitement idéal est la fermeture chirurgicale de la brèche en association aux moyens médicaux (vaccination, anti-épileptiques, mesures de réanimation…) Le moment idéal de la réparation est au-delà de la 72ème heure après la diminution de l'oedème cérébral en cas d'absence d'une lésion intracrânienne nécessitant une intervention en urgence. Notre équipe ne pratiquant pas la voie endoscopique, l'abord frontal est souvent indiqué. Le pronostic dépend des lésions cérébrales associées et surtout de la présence d'une brèche dont le diagnostic et la réparation doivent être les plus rapides et les plus précis possibles. Ainsi toute rhinorrhée post-traumatique nécessite une exploration systématique, le timing idéal: c'est la disparition de l'oedème cérébral pour faciliter l'exploration, ceci est en général possible à partir de la 72ème heure sauf dans les cas associés à une autre lésion intra crânienne nécessitant une exploration en urgence. PMID:26327992
October 11, 2011 report, prepared for LCP site steering Committee by EPS, presents results of sediment and fish tissue samples. Region ID: 04 DocID: 10839615, DocDate: 10-11-2011. Region ID: 04 DocID: 10839615, DocDate: 10-11-2011
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.…
A laboratory study was undertaken to provide simplified procedures leading to the presumptive identification (I/D) of defined microorganisms on-board an orbiting spacecraft. Identifications were to be initiated by nonprofessional bacteriologists, (crew members) on a contingency basis only. Key objectives/constraints for this investigation were as follows:(1) I/D procedures based on limited, defined diagnostic tests, (2) testing oriented about ten selected microorganisms, (3) provide for definitive I/D key and procedures per selected organism, (4) define possible occurrences of false positives for the resulting I/D key by search of the appropriate literature, and (5) evaluation of the I/D key and procedure through a limited field trial on randomly selected subjects using the I/D key.
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
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.
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.
